THEARTANDSCIENCEOF

LOWCARBOHYDRATE

LIVING

ANEXPERTGUIDETOMAKINGTHELIFE-SAVINGBENEFITSOFCARBOHYDRATERESTRICTION

SUSTAINABLEANDENJOYABLE

JeffS.Volek,PhD,RDStephenD.Phinney,MD,PhD

withcontributionsby:EricKossoff,MD|JacquelineEberstein,RN|JimmyMoore

Copyright©2011BeyondObesity,LLCAllrightsreserved.

ISBN-13:978-0-9834907-0-8

E-BookISBN:978-0-98349-073-9

Visitusatwww.artandscienceoflowcarb.comtoorderadditionalcopies.

TABLEOFCONTENTS

Section1:IntroductionIntroductionChapter1:OverviewofLowCarbohydrateandKetogenicDiets

Section2:PerspectiveChapter2:LowCarbohydrateLessonsfromAboriginalCulturesChapter3:The“Modern”HistoryofCarbohydrateRestrictionChapter4:CommonConcernsataGlanceChapter5:DietaryCarbohydrates:ScientificandCultural

Perspectives

Section3:PhysiologyChapter6:BasicHumanEnergeticsandFuelPartitioningChapter7:InsulinResistanceChapter8:LipoproteinEffectsChapter9:EffectsofCarbohydrateRestrictiononFattyAcid

MetabolismChapter10:BodyCompositionandPhysicalPerformanceChapter11:PersonalizedNutritionChapter12:LowCarbohydrateResearchPitfalls

Section4:ClinicalApplicationsChapter13:ClinicalUseofVeryLowCalorieandLowCarbohydrate

Diets

Chapter14:MetabolicSyndromeChapter15:TreatingType-2DiabetesasCarbohydrateIntoleranceChapter16:TheImportanceofDietaryFatinLong-termMaintenanceChapter17:TheJoyofCooking(andEating)FatChapter18:TenClinicalPearls

Section5:GuestChaptersChapter19:KetogenicDietsinSeizureControlandNeurologic

DisordersBycontributingauthorEricKossoff,MDChapter20:RobertC.Atkins,MD–30YearsofClinicalPracticeBycontributingauthorJacquelineEberstein,RNChapter21:DearDoctor–APatient’sPerspectiveBycontributingauthorJimmyMoore

AcknowledgementsAbouttheAuthorsReferences

Section1

INTRODUCTION

INTRODUCTION

InterestingTimes

For those of us doing research on low carbohydrate diets, the lastdecade has given truth to the ancient Chinese curse: “may you live ininteresting times.” There has been a flood of scientific publications oneverything from clinical studies of carbohydrate-restricted diets tounderlyingmolecularmechanisms thatexplainhowandwhy theywork.Andinthepublicdomain,booksandarticleshavecriticallyexaminedthecurrent dogma that ‘carbohydrates are necessary and good, whereasdietaryfatsarebad’.

Meanwhile, our population just keeps on gaining and gaining: not justadults, but children as well – not just in the US, but elsewhere in thedevelopedanddevelopingworldaswell.Ofcourse,wearenotaloneinbeing concerned about this epidemic of obesity. All sincere doctors,dietitians,scientists,andpolicymakerswanttoturnthisprocessaround,butthereisasyetnocommonconsensusonwhattodoandhowtodoit.

There is a glimmer of hope, however. Just as we have seen theconsensus changeon dietary trans fats andmore recently on the highfructose content in our diet, we are beginning to seemovement awayfromdietshigh incarbohydrates–especiallyrefinedcarbohydratesandsimple sugars. But many of the mainstream experts still warn against‘going too far in theotherdirection’,stating that therearestill toomanyquestionsaboutthesafetyandefficacyoflowcarbohydratediets.Butisthis really true?Are there still toomany unanswered questions, or hasthisposition lost tractionwhenthefloodofrecentresearchistakenintoaccount?

This isan importantquestionthatwefeeluniquelyqualified toaddress.Collectively, the two of us have designed, conducted, and publishedseveral dozen studies of low carbohydrate diets. These results haveconsistently drawn us forward to do further research because of thepositiveoutcomeswehaveobserved.Wehavecounseledthousandsof

patientsonlowcarbohydratedietsandtrackedclinicaloutcomes.Andasevidenceofourpersonalconvictions,bothofushavechosentofollowalowcarbohydratelifestyle.

In short, we believe that the most important issues about lowcarbohydrate diets have now been resolved. But perhaps because weareaheadof theconsensuson this,we indeed findourselves ‘living ininteresting times’. Rather than being daunted by the intensity of thedialogueaboutlowcarbohydratediets,however,wearedelightedbythisprocess,anditisthisenergythathasmotivatedustowritethisbook.

Weasknotthatyouacceptourpositionpresentedinthisbookbecauseof our accumulated academic degrees or publications, but ratherbecauseouranalysisofabroadrangeofinformationmakessense.Asaplacetobegin, let’s lookatsomeoftheobviousdiscordstobefoundinthecaseformaintainingthecurrenthighcarbohydrate,lowfatparadigm.

FiveDiscords

First,the‘lowfatmessage’hasbeenpushedinthepopularmediaandinacademiaforthreedecades,whileinthissameperiodtheprevalenceofobesityintheUSpopulationhasgrowndramatically.

A‘lowfatdiet’–evenonerestrictedincalories–ishighincarbohydrate,whichdrivesupblood insulin levels. Insulin isahormonethatdrivesfatintostorage(i.e.,intofatcells)andstimulateshunger.Alowcarbohydratediet,ontheotherhand,allowsinsulinlevelstoremainlowandfatstorestobeburnedinthecontextofreducedhungerandcravings.

Dietarysaturatedfathasbeendemonizedinthemedia,textbooks,andinnational policy; whereas published scientific data shows no connectionbetweendietarysaturatedfatintakeandeithersaturatedfatlevelsinthebodyorthelongtermriskofheartdisease.

The strongest correlation between a major dietary nutrient and bloodlevelsofsaturatedfatiswithdietarycarbohydrate–notwithsaturatedfatintake! On average, the more carbohydrate you eat, the higher thecontentofsaturatedfatsinyourblood.

And fifth, at the same time that science is increasingly defining thevariabilityinourindividualresponsestodietandexercise,nutritionpolicymakerspersistinpreachingaone-size-fits-allmessage.Forexamplethenew Dietary Guidelines for Americans released January 31, 2011recommends everyone consume at least 45% of their calories fromcarbohydrate[3].Thisstandsinstarkcontrasttothefactthattheirunitaryedict actuallymatches the ‘metabolic fingerprint’ (i.e., the carbohydratetolerance)of less thanhalfof thepopulation.Someoneneeds tospeakup.Tantamounttopointingouttheking’swardrobefailure,wecan’tmakeforwardprogressbymoon-walkingbackwards.

TheUnmetNeed

We believe both history and science now dictate that it is time totranscend the myths and sound bites that dominate the discussion ofoptimum dietary fat and carbohydrate intakes.We need to get beyondthesimplisticideathatallhumanscanandshouldeatthesame‘perfectdiet’ across all phases of our life-cycle. Given the obvious metabolicdiversity among humans, we need to accept dietary diversity as animportant variable on achieving optimum health across the wholepopulation.

Thus the purpose of this book – scientific evidence now supportsinclusionofwellformulated lowcarbohydratediets in the listofsafeandsustainable dietary options to promote individual optimum health andwellbeing.Andthisiswherethe‘art’mustjointhe‘science’.Justbecauseyoudecidetostopeatingsugar,bread,potatoes,riceandpastadoesn’tmean thatyouhavea lowcarbohydratedietsuitable for long-termuse.Thatpathtoawellformulateddietismorecomplex.Infact,understandingthe‘howandwhy’ofthisformulationprocesstakesawholebook.

ThreeKeys

Safety.Betweenthetwoofus,wehavemorethan50yearsofresearchandclinicalpracticeexperiencewithlowcarbohydratediets,andbetweenuswehavepublishedafewhundredpeer-reviewedpapersonthetopic.Muchofthisefforthasbeendirectedatunderstandinghowtoformulatealowcarbohydratediet foroptimumsafetyand function.Wehavewritten

this book because we are confident that a wellformulated lowcarbohydrate diet offers improved long-term health and wellbeing topeoplewhosemetabolismstrugglestodealwithahighcarbohydrateload(akacarbohydrateintolerance).

Individualspecificity.Everyindividualhumanisunique,andthisvariabilityextends to howwe respond to the foodsweeat.Starting twodecadesagowithProfessorGeraldReaven’scourageousstandagainsttheuseofhigh carbohydrate diets in people with what we now call metabolicsyndrome[4],we have become increasingly aware that someof us are‘carbohydrate intolerant’. This concept of carbohydrate intolerance isincreasinglyunderstoodtobeamanifestationofinsulinresistance,andisassociatedwithhighblood triglycerides,highbloodpressure,and in itsmost severe form, type-2 diabetes. These subgroups in the populationshow dramatic clinical improvement when dietary carbohydrates arereduced,and thusdeserve tobeofferedaseparatepath fromthe ‘highcarb,lowfat’mantrapromotedbynationalpolicymakers.

Sustainability(GettingBeyond‘Casual’).It isthecommonexperienceofmanyindividualswhohavenaivelytriedalowcarbohydratediet,andalsoofresearcherswhohavestudiedcasuallyadministeredlowcarbohydratediets,thatnormalpeoplecan’tfollowthemforverylong.Butisitthelowcarbohydrate aspect that’s at fault here, or is it specifically the casualnature of these dietary efforts that predestines most normal people toforegothelongtermbenefitsofcarbohydraterestriction?Theanswer isthat making carbohydrate restriction sustainable is complex and takescarefuleffortandguidancetobesuccessful.Inthisbook,weidentifyandexplainmanycharacteristicsofa ‘wellformulated lowcarbohydratediet’suitableforlongtermuse.InChapter18,forexample,wesummarizejustthe key points in this process under ten headings. Thus this topic isclearlymoredeservingofabookthanasoundbite.

WhyaHealthCareProfessionalShouldBuythisBook

Carbohydrate restriction is commonly practiced but seldom taught.Perhapstheassumptionisthatanyonecanusecommonsensetofigureitout(i.e.,the‘casualapproach’).Alternatively,thosewhodeterminethecurriculumat our prestigious universities and professional schoolsmay

notbelievethatthistopicdeservesseriousacademicinterest.

Whateverthereason,thisbookrepresentsourbestefforttofillthegapininformationabout carbohydrate restriction for health careprofessionals.To this end, we have attempted to walk the tight-rope of ‘objectivelypromoting’ the case for carbohydrate restriction in individuals withunderlyinginsulinresistanceorcarbohydrateintolerance.

Critics will correctly state that our arguments in favor of carbohydraterestrictionseemone-sidedandsmackofadvocacy.Butweaskyou:whatis the proper response when three decades of debate aboutcarbohydraterestrictionhavebeenlargelyone-sidedanddrivenmorebycultural bias than science?Someone needs to stand up and representthealternateviewandthesciencethatsupportsit.

In this effort, we have attempted to speak directly to you, the reader,rather than employ the more sterile third-person voice. Citations havebeenheld toaminimumof thekeypublications ineachchapter (ratherthan the 50-100 citations per chapter we could easily conjure up). Tocoversomeareaswhereothersarebetterversed,wealsohaverecruitedthree individuals with unique experience to contribute chapters to thiseffort.

Wehaverecentlyco-authored“TheNewAtkinsforaNewYou”[5]which,while soundly based on science, ismore of a step-by-step, consumer-orientedguidetofollowingawellformulatedlowcarbohydratediet.Thiscurrent book is functionally consistent with ‘The New Atkins’, but wedelvedeeper intohow thedietworksandhow itcanbeusedclinically.Thusitismoretechnical,butbynomeansdoyouneedtobeamemberofMENSAtocomprehendourmessage.

The readership of this book is not necessarily limited to healthcareprofessionals. Anyone with serious curiosity about nutrition andmetabolism,oradesiretounderstandhowtraditionalfoodpracticescanbe used to improve health, will likely enjoy this book. Students andresearchers in the lifesciences(e.g.,biochemistry,physiology,nutrition,exercise science, physical therapy, athletic training, genetics, etc.)mayalsofindthisbookintriguing.

WhoUltimatelyStandstoBenefitfromthisBook?

If thepeople living in theUnitedStateswereapie, thosewhostand tobenefitfromrestrictingcarbohydratewouldbemorethanamodestslice.Currently, 2 in 3 adults qualify as overweight, and 1 in 3 is obese. Incertain ethnic groups (e.g., Hispanic and Mexican American men andBlack women) 4 in 5 are overweight. More than 1 in 3 adults havemetabolicsyndrome,1in4haveimpairedfastingglucose,andabout1in10have type-2diabetes.Many if notmost of thesepeoplehave somedegree of carbohydrate intolerance and therefore would derive directbenefitfromadietlowincarbohydrate.Intotal,thissliceofthepiecouldrepresentahundredmillionormorepeoplejustintheUS.

image

TheAmericanPie.Theunremittinghighprevalenceofobesity,metabolicsyndrome,anddiabetes–allconditionsthatcanbestbedescribedascarbohydrateintolerance-coupledwiththeverylimitedefficacyof traditional low fat diets,maybe the result offorcingasquarepeg intoa roundhole.Even ifyou thriveonalow fat diet now, carbohydrate intolerance is increasinglyprevalent as we age. Thus, over a lifetime, the majority of usmayfindthatwearebettersuitedtoalowcarbohydratediet.

Whodoesn’tstandtobenefitfromalowcarbohydratediet?Ifyouhappen

tobeamongtheapproximately1in4adultswhowillbeblessedwiththeabilitytothriveforalifetimeonalowfatdiet,consideryourselffortunate.Thedietwedescribeheremaynotbeappropriateforyoupersonally,butthat does not absolve you from understanding its benefits for yourpatients. In addition, those of uswho do remain thin and healthy on ahighcarbohydratedietstillpayfortheill-healthandlostproductivityofthemanywhoarepoorlyserved(literally)bythe‘highcarblowfat’message.Andwhileyoumaybemetabolicallyblessedinbeingabletotoleratelotsofcarbohydratenow,thatdoesn’tguaranteethatthiswillcontinueasyouage.Itjustmeansthatyoucurrentlyhavemoredietoptionsthanthoseofuswithcarbohydrateintolerance.

Weallstandtobenefit,bothnowandinthefuture,ifawellformulatedlowcarbohydrate diet becomes an accepted option in promoting healthacrossmanysubgroupsofourpopulation.Weoffer thisbook toyou inhopesthatthisinformationwillbroadentheoptionsavailabletoyouandyourpatientsinthemanagementofcarbohydrateintolerance.Mayweallwork together towards thatdaywhen,walkingdown thestreet,we findthatobesityisonceagainrareandnolongerthenorm.

JeffVolekStevePhinney

Chapter1

OVERVIEWOFLOWCARBOHYDRATEANDKETOGENICDIETS

HistoricalPerspective

Whoinventedthelowcarbohydratediet?WasitDr.RobertAtkins’weightlossrevolutionin1972?OrWilderandPeterman’santi-seizuredietattheMayoClinic in the 1920’s?Or perhapsBanting’s pamphlet inBritain in1863?

The answer: none of the above. But for sure, it was long, long beforethese recorded efforts to codify and monetize carbohydrate restriction.Thisdoesnot inanywaydiscount thecontributionsof thesecontrarianpioneers who attempted to steer us away from our sometimes fatalromancewithagriculturalcarbohydrates.Buttounderstandtheoriginsoflowcarbohydratemetabolismandtoappreciatehowdeeplyitisrootedinourbasichumanphysiology,weneedtogobackhundredsofthousandsofyears,ifnotamillionortwo.

Current evidence suggests that our human ancestors evolved in Africaandthenspreadacrosstheglobeinsuccessivewavesofmigration.Andwhile that original African ancestral group may have developed in atropicalenvironmentwherefruitandtuberscouldbeforagedyear-round,our ability as humans to migrate into barren or temperate regionsdependeduponourabilitytosurviveprolongedperiodsoffasting,andtoadapt to hunting and gathering of less carbohydraterich fare. Andeventually, this evoked tolerance of a low carbohydrate diet allowedsomehumans tobecomehighlyspecializedhuntersandherders, livingas mobile cultures in rhythm with the animals that fed them. Recentexamples of these low carbohydrate nomadic cultures were theMasaiherdsmen inCentralAfrica[6], theBisonPeople of theNorthAmericanGreatPlains[7],andtheInuitintheArctic[8].

But long before these last low carbohydrate cultures were finallysuppressedbytheagricultural imperative,muchoftheworld’spopulacesubsisted (if not thrived) on continuous or intermittent carbohydraterestriction. For example, agricultural carbohydrates such as wheat andryedidnotcomenorthoftheAlpsuntilbroughtbytheRomansafterthetimeofChrist.TheIrish,Scandinavians,andRussianshadnoagriculturalcarbohydrates suitable to their climate until the potato emigrated toEuropefromtheAndesinthe16thcenturyAD.Whatthismeansisthatmanyofourancestorshad littleexposure tohighproportionsofdietarycarbohydrate until 1-2 thousand years ago; and for many aboriginalcultures, their choice of a low carbohydrate lifestyle persisted towithinthelastfewhundredyears.

Now fast forward to the present. The United States is currently re-assessing a 3-decade, uncontrolled experiment inwhich carbohydrateswere laudedandfatsdemonized.Concurrentlywehavebecomeoneofthemostobesecountries in theworld.Andacross theglobe, tragically,indigenouspeopleswithhistorically lowcarbohydrate intakesnowhaveextremelyhighprevalenceratesofobesityandtype-2diabetes(e.g.,theGulfStatesintheMiddleEast,PacificIslanders,FirstNationsinCanada,andAustralianAborigines).

What these observations suggest is that for many humans, from anevolutionary perspective, a high carbohydrate diet is a metabolicchallengethatsomefinddifficultasearlyasadolescenceandmanyfailtomeetinthemiddleyearsoflife.Equallyapparentisthatthesenegativeeffects of a high carbohydrate intake can be forestalled or reduced byvigorous exercise, high intakes of micronutrients and/or fiber fromvegetables and fruit, avoidance of simple sugars, and constant energyrestriction.Formanyofuswithsevereobesity,metabolic syndrome,orovert type-2 diabetes, however, these ‘healthy lifestyle’ choices are notenough to fully counteract the negative effects of a substantialcontributionofcarbohydratetoourdailyenergyintake.

Thiscondition,inwhichacollectionofdiseasescharacterizedbyinsulinresistancearedrivenbyconsumptionofasinglenutrientclass,deservesto be identified as “carbohydrate intolerance”. And aswith other singlenutrient intolerances (e.g., lactose, gluten, fructose), the preferred

intervention is to reduce one’s dietary intake below the threshold levelthatproducessymptoms.

WhatDoes“LowCarbohydrate”Mean?

Therearetwowaystodefinethethresholdbelowwhichyouareeatinga“lowcarbohydrate”diet.Thefirstisdefinedbywhatyouasanindividualperceive–it isthatlevelofcarbohydrateintake(beit25gramsperdayor 125 grams per day) below which your signs and symptoms ofcarbohydrate intolerance resolve.Atoneendof thisexperiential range,someone with early signs of metabolic syndrome (e.g., high serumtriglyceridesand10extrapoundsaroundthemiddle)mightpermanentlybanishtheseharbingersofill-healthbyholdingtotaldietarycarbohydrateintakeintherangeof100-125gramsperday.

At theotherendof thisspectrummightbea type-2diabeticwho,ona“balanceddiet”providing300gramsperdayofcarbohydrate,requires2shotsof insulinplustwootheroraldrugstokeepfastingglucosevaluesevenmarginally controlledunder150mg/dl.For thisperson toachievean optimum initial response that allows reduction (and hopefullywithdrawal) of diabeticmedications, clinical experience has shown thatholding dietary carbohydrate at 20-to-25 grams per day is oftennecessary.Formany type-2diabetics, a fewweeksat this level allowsthemtoreduceorstopbothinsulinandoralmedicationwhileatthesametime achieving better overall glucose control. A few months later,following substantial weight loss, some individuals might be able toincrease daily carbohydrate intake above 50 grams per day and stillmaintainexcellentglucosecontrol,whereasothersmightneedtoremainbelow the 50 gram level to keep their type-2 diabetes in completeremission.

Ineithercase,whether it isbeingableto loseweightandkeepitoff,orputting a frank case of type-2 diabetes into remission, howmuch youchoosetolimityourdietarycarbohydrateintakeshouldbedrivenbyyourpersonal experience. As a result, the amount of carbohydrate that youdecide to eat might vary considerably depending on your individualmetabolicconditionandthelevelofbenefityouwishtoderive.

Defining‘NutritionalKetosis’

Thesecondwaytodefine‘lowcarbohydrate’isphysiologic–specificallythat level below which there is a fundamental shift in your body’s fuelhomeostasis (i.e., energy regulation) away from glucose as a primaryfuel. This shift is the adaptation of the body’s hormonal set and inter-organfuelexchangetoallowmostofyourdailyenergyneedstobemetby fat,eitherdirectlyas fattyacidsor indirectlybyketonebodiesmadefromfat.Thisprocess,whichisdiscussedmorefullyinChapter7,beginsfor most adults when total carbohydrate is restricted to less than 60gramsperdayalongwithamoderateintakeofprotein.Afterafewweeksatthislevel,theprimaryserum‘ketone’(betahydroxybutyrate,orB-OHB),rises above 0.5 millimolar (mM). At this ketone level, which is 10-foldhigher than that in someone with a daily intake of 300 grams ofcarbohydrate, the brain begins to derive a substantial portion of itsenergyneeds fromB-OHB, resulting ina commensurate reducedneedforglucose.

With further restriction of carbohydrate below 50 grams per day, theserumB-OHB rises in response to reduced insulin secretion.However,becausedietaryproteinpromptssomeinsulinrelease,andserumB-OHBitself stimulates insulin release by the pancreas (albeit subtly), adultseating 20 grams of carbohydrate and 75-150 grams per day of proteinrarely runserumB -OHB levelsabove3mM.This is incontrast to theresponse to total starvation (i.e.,nodietarycarbsorprotein)where theserumBOHBlevelsrunashighas5mM.

This10-fold rangeof serumketones, from0.5 to5mM, is yourbody’snormalphysiologicalresponsetovaryingdegreesofdietarycarbohydrateandproteinrestriction.Thisresponserangeiscalled‘nutritionalketosis’,and is associated with metabolic adaptations allowing your body tomaintainastablestateof inter-organ fuelhomeostasis.Thisprocess isdependent on an adequate, albeit minimal, ability of the pancreas toproduce insulin in response to dietary protein and serumketones, thusmaintainingserumB-OHB in the rangewhere it replacesmuchof yourbody’s (andyourbrain’s)need forglucosewithoutdistortingwholebodyacid-basebalance.

Nutritional ketosis is by definition a benign metabolic state that giveshuman metabolism the flexibility to deal with famine or major shifts inavailabledietaryfuels.Bycontrast,‘diabeticketoacidosis’isanunstableanddangerousconditionthatoccurswhenthereisinadequatepancreaticinsulin response to regulate serum B-OHB. This occurs only in type-1diabetics or in late stage type-2 diabetes with advanced pancreaticburnout. In this setting of deficient insulin, when exogenous insulin iswithheld,serumB-OHBlevelsreachthe15-25mMrange–5-to-10-foldhigherthanthelevelscharacteristicofnutritionalketosis.

Unfortunately, among the general public and even many health careprofessionals as well, these two distinct metabolic states tend to beconfusedoneforanother.Understandinghowdifferenttheyareiskeytobeing able to capture the many benefits of nutritional ketosis whileavoidingtherisksinthatverysmallminorityofthepopulationsubjecttodevelopingdiabetic ketoacidosis.To thisend,a full chapter later in thisbookisdevotedtotheclinicaluseofcarbohydraterestrictionindiabetes.

UtilityandSustainabilityofCarbohydrateRestriction

Upuntil150yearsago,theapparentmotivationforhumanstoeatalowcarbohydratedietwasbecausethatwaswhattheirregionalenvironmentprovided.Forexample,absentwildorchardsandfieldsofwavinggrain,the Inuithad littlechoiceother thanmeatand fat from thearctic tundraandthesea.However,somecultureswithlongexperienceandapparentchoice attempted to actively defend their low carbohydrate lifestyle.ExamplesofthisincludedtheBisonPeopleoftheNorthAmericanGreatPlains, who maintained their nomadic existence until the bison werevirtually exterminated, and the Masai of East Africa who still avoidedvegetable foods (against the vigorous advice of the British) into the1930s. Manifestly, for these cultures, not only were their lowcarbohydratedietarypracticessustainable–allowingthemtosurviveandreproduce for hundreds of generations under difficult environmentalconditions–theyregardedtheirdietofanimalproductsaspreferabletoanagriculturallifestyle,despitethelatterhavingbeenavailabletothem.

In the 1920s, carbohydrate restriction was employed in mainstreammedicalpracticeinthemanagementofdiabetesandinthetreatmentof

seizures. In both of these clinical situations, as there was no othereffective treatment, these dietary interventions were sustained byindividualpatients foryears.With theadventof insulin fordiabetesandanti-seizure drugs like diphenyl-hydantoin (Dilantin), these dietaryinterventions began to fall out of favor.However now that the practicallimitations and side effects of modern pharmaceutical therapy arebecomingrecognized,thewheelmaybeagainturning.

Oneoftheperceivedlimitationsofmodernlowcarbohydratedietsisthattheyhavebecomestigmatizedasextremeandthusnecessarilylimitedtotemporary use. Adding to this sense of transience, most popular dietbookspromotingcarbohydraterestrictionhaveeffectivelyonlydescribedan initialenergyrestrictedphase topromoteweight loss.Sowhatdoesthe reader do after 3months eating 1400 kcal/daywith a 30 lbweightloss?Nohealthyadultover5feettallachievesenergybalanceon1400kcal per day, so the transition from weight loss to long-term weightmaintenancenecessarilymeansaddingback food.Buthowmuch,andfromwhatfoods?Carbohydrates?Protein?Fat?

It is a primary hypothesis (if not principle) of this book that a lowcarbohydrate diet that is sustainable in the long term (e.g., for themanagementoftype-2diabetes,seizures,orsevereobesity)necessarilycontains an appropriate fat content in its weight maintenance phase.Thus, if a book promoting a low carb diet does not contain practicalinstructionandrecipespromoting the inclusionof fat in itsmaintenancediet,itisnotlikelytoresultinmuchlong-termsuccessamongitsreaders.Tothisend,laterchaptersinthisbookwilldescribethephysiologyoffuelpartitioning,clinicaluseoflowcarbohydrateandketogenicdiets,plustwofullchaptersandaweek’sworthofmenusaddressingthepracticalitiesofpreparingandconsumingamaintenancedietthatisrichinfat.

RecentandFutureResearch

Thelastdecadehasseenadramaticincreaseinthevolumeofresearchpublicationonthetopicofcarbohydraterestriction.Multiplerandomized,controlled trials (RCTs) have been performed comparing a variety ofotherdietstocarbohydraterestriction.Manyofthesehavedemonstratedclear advantages in favor of low carbohydrate and ketogenic diets.

However, the interpretation of these studies is sometimes clouded byreticence of authors or editors to give them due credit or by pitfalls inresearchmethodology.Theprosandconsofthisrecentbodyofresearchare addressed throughout this book. In addition, multiple contributingauthorsprovide their insightson topicspertinent to the rangeofeffectsandbenefitsofcarbohydraterestriction.

Section2

PERSPECTIVE

Chapter2

LOWCARBOHYDRATELESSONSFROMABORIGINALCULTURES

IntroductionandCaveat

Humanexperiencewithlowcarbohydratedietsbeganwhenthisplanet’sfirst primates chased down and killed some unfortunate but succulentanimaland thencouldnot findanynearbywild tubers toservewith themeat.Ratherthanstarve,theyprobablydecidedwithsomereluctancetoaccepttheindignityofamealconsistingofjustmeatandfat.Thateventlikely occurredwell over 2million years ago, afterwhichour ancestorsstumbledaboutinthedietarydarknessuntilthedevelopmentofmodernagriculture brought us a dependable supply of carbohydrates startingmaybe 8000 years ago. And in some remote corners of the earth, thearrival of agricultural carbohydrate has only occurred within the lastcentury.But for almost all of our ancestors, in the intervening 2millionyears,humanshadtofigureouthowtomakedowithjustmeatandfatastheirprimarysourcesofdietaryenergy.

Gettinga lowcarbohydratediet “right” isnotassimpleas justavoidingsugarsandstarches.Onehastodecidehowmuchandwhatsourcesofproteinandfatstoseekout.Thencomesdevelopingmethodstopreparethem and maybe even to store them. Along with enough energy andprotein, our intrepid ancestors also had to figure out how to get theirminimumrequirement formineralsandvitamins to reachadulthoodandreproduce.Given the obvious fact that at least some of them survivedthisgauntlet,therehadtohavebeenpocketsofpeoplewhofigureditallout. But maybe it’s not all that much of a surprise. After all, they hadaround2millionyearsoftrialanderrortodoso.

Practically speaking, what this means is that most of the importantprinciples of carbohydrate-restricted diets were discovered eons ago.

Unfortunately, those people holding this information were usually notliterate, so this dietary informationwasnever carved in stoneand thustendedtodiewiththem,andwiththeircultures.Equallyunfortunate,theoften literate people whose contact brought agricultural foods to theEarth’s last remaining hunting cultures were often less than accuratereportersofthepre-contactculturestheywereobserving.Thuswhatwedo‘know’ofthedietarypracticesofaboriginalhuntingpeopleswasseenthroughthe lensofculturalbias.Thisnecessitatesan importantcaveat:bewareofethnocentricinterpretationofaboriginalbehaviors.

Itisanormalhumantendencytointerpretthebehaviorofothersthroughthelensofourownculturalpractices.Nomadicpeople,forexample,areoften viewedasunsettledor uncivilizedbecause theydonot build andmaintainpermanenthousesorvillages.As fordietarypractices,peoplewho cannot imagine themselves living without copious dietarycarbohydrate (our daily bread) will tend to look for the hidden dietarycarbohydratesources,howeverimprobable,inthedietsofhunters.

Thatsaid,however,itisthehypothesisofthischapterthatnotallthatiswritten about the diets of hunters and nomadic shepherds is incorrect,and when assessed against a modern understanding of metabolism,muchof thebiasandmythologycanbepeeledaway, leavingasparsebutusefultruth.

The reason we should be motivated to undertake this effort is theinescapable conclusion that the dietary path down which industrializedcultures have wandered this last century is clearly not leading us tohealth and wellbeing. And to better understand where we should begoing, perhaps it might help to thoughtfully examine where we havebeen.

SeekingCredibleReporters

It is therefore useful to exercise caution when evaluating reports ofobservers, even scientifically trained ones, who regard their nomadicobjectsofstudyasculturallyinferior(orassavages,forthatmatter).Thebetterobserversare thosewho livedamong,ate the food,and traveledwiththehuntingorherdingculturestheywerestudying.Suchindividuals

included George Catlin among the Plains Indian[7], John Rae[9],Frederick Schwatka[10], and Vilhjalmur Stefansson among the Inuit[8],plusJohnOrrandJ.L.GilksamongtheMasai[6].

Alloftheseobserverscommentontheesteemthathuntingandherdingpeoplesheldforfat.Buffalohuntedinthefall,fattenedfromasummerofgrazing, were used by the Plains Indian to make pemmican (i.e., amixture of driedmeat and hot fat that cools to become a stable blockwhensealedinaraw-hidesack).Caribouweresimilarlyhuntedinthefallalongtheirmigrationroutesfromthetundrabacktotheforests,whentherapidly dropping temperature allowed the meat and fat to be storedfrozenincachesforwinteruse.AlongthePacificCoast,vastquantitiesofasmeltlikefish(calledtheoolichan)wereharvested,processed,andthe‘grease’ stored in cedar boxes for year-around use and for trade withinlandbands.

What is generally lacking, however, is accurate quantitative informationon the proportions of fat, protein, and carbohydrate eaten by theseaboriginalculturespriortoEuropeancontact.WedohaveOrrandGilksreport[6]ofthedailyfoodintakeofaMasaiwarrior-classmale:1.2kgofmeat, 2 liters of milk, and 50 ml of blood. But we don’t know the fatcontentsof themeatandmilk,whichcanvarygreatlyon thecutof themeat, thepreparationof the cattle before slaughter, and theamount ofcreamincludedinthemilk.

FindingCredibleDietaryQuantitation

Perhaps our best transducer of the pre-contact Inuit diet isStefanssonduringhisone-yearofcloselymonitoreddietaryintakewhileparticipatingin the Bellevue experiment (see sidebar).With both his reputation andwellbeing riding on the outcome of this experiment, it is a goodassumption thathewouldhaveearnestlyattempted to reproduce thosedietary practices of the Inuit which had previously sustained him for adecadeintheArctic.ThepublishedresultsofthisexperimenttellusthatStefanssonate15%ofhisdailyenergyasprotein,over80%asfat,andafewpercentascarbohydrate(fromglycogennaturallyfoundinthemeat)[11].

PuttingHisLifeontheLine:Stefansson’sInuitDietExperiment

In 1907, a Harvard-trained Canadian anthropologist went into theCanadianArctictostudytheInuitculture.Whetherbychanceordesign,he spent his first Arctic winter living among the native people of theregionwithoutanyexternalfoodsupply.Eightmonthslater,heemergedspeaking their language and empowered by the fact that he could livewellofftheavailablefoodoftheregion.

A decade later, Vilhjalmur Stefansson left the Arctic, having traveledwherenopersonofEuropeanoriginhadgonebefore,sometimesfortwoyears without any resupply. Upon his return to ‘civilization’, he wrotecopiouslyabouthisexperienceamong‘ThePeople’(whichiswhat“Inuit”meansintheirlanguage).

Unfortunately forStefansson, thedecadebetween1915and1925wastheeraofvitamindiscovery–theperiodinwhichscientificnutritionhititsstride. Suddenly, we had scientists to tell us what was good for us,replacinggrandmothersandculturalwisdom.Andscientistsnowsaidthatall humans needed fruit and vegetables to prevent deficiency diseaseslikescurvyandberiberi.

To the newly-minted nutritionists of the 1920s, Stefansson became theproverbial buck wearing a bulls-eye. To salvage his reputation, heconsented(alongwithanArcticexplorercolleague)toreproducehisInuitdietundercontinuousobservationinBellevueHospitalinNewYorkCity.Afterayear,heandhiscolleagueemergedhaleandhearty,muchtothedisappointmentofthescientistsincharge.

What Stefansson’s experience (and many other subsequent studies)demonstratedwasthatdietarycarbohydrateisnutritionallysuperfluousinthecontextofawellformulatedlowcarbohydratediet.

Furthermore, the fact that aboriginal pemmican (not the condimentversion loadedwith nuts and berries to suit European tastes) providedabout 75% of its energy from fat necessarily leads us away from the

commonmisconceptionthathunters’dietswerehighinprotein.EventheMasaidietarydataprovidedbyOrrandGilks(ifweusemodernmeatandmilk composition data) suggest that they ate about 30% of energy asproteinand70%asfat.Thuswehavearangefortheproportionoffatinculturallyevolvedhuntingandherdingdietsfrom70%tomorethan80%ofdailyenergyintake.

There are, of course, extensive published data that dispute theseproportions.Analysesoffoodwastefromcavefloorsandvillagemiddens(mounds of discarded household waste) often suggests higher proteinintakes, leadingsometocontendthata ‘typicalhunter-gatherer’ate40-50%ofhisenergyasprotein,20%ascarbohydrates,andonly40%orsoas fat. However there are a number of problems with getting goodquantitativeinformationbythismethod.Forexample,itdoesnotallowusto knowwhich parts of the foodwere treasured, which discarded, andwhatpartswerefedtothedogs.

AmongtheInuit,whenasealorcaribouwaskilled,thefatwassavedforhumanconsumption(orlampfuel)andtheleanerpartsweregiventothedogs(oranygullible‘whiteguys’intheparty).Farthertothesouth,whenaspringbuffalo (i.e.,one thathadyet to rebuildbody fat reservesafterthewinter)was killedon theGreatPlains, thehumansate the tongue,liver,andmarrow.These tissues tended to retain their fat contentevenduringperiodsofprivation.The leanmeatwaseitherdried(toserveasan emergency food source) or fed to the dogs. This differentialpartitioning of the kill actually makes a lot of sense, as a dog’smetabolismismuchmoretolerantofahighproteinintakethanisthatofahuman.Buthowthiswasdoneinaquantitativesensecannotbedivinedby examining animal bones and sea shells in village trash heaps (i.e.,‘middens’). So how does one say in Latin “beware of garbage dumpscience”?

Another limitation of studying these refuse middens is that they onlyoccuradjacenttolongtermsitesofhabitation,suchastownsorvillages.However, some of the most highly evolved hunting societies werenomadic. If you spend most of your year on the prairie following themigrationof thebuffalo,youarenotgoingtospendenoughtimeinonesite to create amidden. And if youmanufacture pemmican atmultiple

sites along your migration path and return with it every year to aprotectedwintercamp,thennothingyoudiscardinanadjacentdumpwillinformthemoderninvestigatorthatmuchofyourdietconsistedoffatthatwasharvestedelsewherebeforecomingintothatcamp.

Similar concerns would apply to shell middens found on the BritishColumbia coast and elsewhere. These imply a high intake of shellfishprotein. However if fresh shellfish harvested in the fall and winter aredipped in oolichan grease transported from a distant spring oolichancamp,thatcomponentofthedietwouldnotbeappreciatedbyexaminingthemiddenatthewintercamp.Sohereagain,standardanthropologicaltechniques used to analyze the composition of aboriginal hunting andfishingdietsmaymisleadusastothediet’sfatcontent,particularlyiftheinvestigator comes to the topic with the preconception that such dietswerehighinprotein.

TypeofFatConsumed

There is copious evidence that established hunting societies wereselective of the types of fat that they acquired and ate. These choicesseemtohavebeenmadeforanumberofreasons,includingtheshelf-lifeofspecificfats(i.e.,storability)aswellasthenutritionalpropertiesofthedifferent types of fat available. In the same way that herding societiesprocessed milk to produce butter and cheese for long-term storage,hunters developed methods to process and store fats to tide themthroughleanperiodsinthehuntingcycle.

PemmicanwasastapleofthebisonpeoplelivingontheGreatPlainsofNorthAmerica.FromTexas to theCanadianPrairieProvinces, teepeeswereerectednexttoakill,thefatcutawayandsavedasthemeatwasdried in the sun or over a slow fire. A few days later, as their dogsconsumed the last unwanted bits of cartilage and sinew, these peoplestruck camp and departed with full stomachs and 100-200 pounds ofreservefood.Atthosetimeswhenafreshkillevadedthem,anindividualcould remain healthy and happy on a poundof pemmicanper day.Sowhenhuntingwasgoodand thebuffalo fat, familiescouldprocessandtransportwiththemacoupleofmonths’foodsupply.

Whilepemmicanwasobviouslyproducedonthebasisofavailability,thepriorityof itsconsumptionwasbasedupon itsphysicalproperties.Latesummerandfallpemmicanwasricherinsaturatedfats,makingitfirmerand thus was more resistant to melting and rancidity. This pemmicancouldbeheldinreserveforayearortwowithoutgoingbad.Incontrast,winterpemmican,madewithbodyfatthatwasricherinpolyunsaturates,tendedtobe ‘softer’andwasmorepronetorancidity.Sothese lotsgotconsumedsoonerratherthanlater.

ItwasthissummerpemmicanthatbecameastandardtradeitemoftheupperMidwestinthe18thand19thcenturiesastheCanadianNorthwestandHudson’sBayCompaniescametodominate theregional fur trade.Pemmican fueled the transport of furs out of the Canadian interior infreightcanoes,paddledbyvoyageurswhohadnotimetostopandhuntastheypushedatotalof3000milesuptheSt.LawrenceRiverandGreatLakesandbackinasingleseason.ButlongbeforetheEuropeanscame,archeological evidence tells us that the aboriginal people of the GreatPlains were already trading pemmican to their distant neighbors forpipestone,tobacco,flint,beaver,ermine,andevenseashells.

But the fatmostvaluedandmostextensively traded inaboriginalNorthAmericawasextractedfromanobscurelittlefishthatappearedforjustaweekalong theNorthPacificcoasteveryyear inMarch (until recently).FromtheKlamathRiverinNorthernCaliforniatotheAleutians,aniconofthe aboriginal people in the region was the oolichan (aka eulachon orcandlefish).ThislittleforagerofthePacificcameintoinletsandestuariesevery spring in vast numbers, where for 10 millennia the aboriginalpeoplewouldgatherinanticipationofitsreturn.

There were three major sources of fish fat available to the aboriginaleverymaninthisregion:salmon,eel,andoolichan.Huntinglargergamelikewhale,sealion,andsealrequiredaccesstotheseaandtheuseofsea-goingcanoes.Somebutnotallcoastalpeopleshadthetechnologytoconstructtheselargeboats.Butifyouwereshore-bound,thesalmon,eel, andparticularly theoolichancame to you–dependably, yearafteryear,centuryaftercentury.Dependabilityyoucouldbuildacultureon.

Theoolichanisupto20%fatbyweight.Whenyouhangitouttodry, it

becomesadrystickthatyoucanlightlikeacandleinyourwinterlodgeso you can see in the dark – thus its name ‘candlefish’. But moreimportantly, a ton of fresh fish harvested in March yields up to 400poundsof fatyoucanextract,store incedarboxes,andeat throughouttheyear.

Why process and store oolichan grease? Because not only was itavailable – itwas unique!Unlike the oil from seal,whale, and salmon,oolichanfatisverylowinpolyunsaturates(bothomega-3andomega-6)[12].Itsprimaryfattyacidsaremonounsaturated,muchlikeoliveoil.Thatplus its content of saturated fats makes it a semi-solid at ‘roomtemperature’,so itwasmuchmoreeasilystoredand transported in thebent-woodcedarboxescraftedforthispurposebylocalartisans.

Archeological evidence indicates that oolichan ‘grease’ was producedalong the North Pacific coast by the ton, much of which was carriedinlandfortradingpurposesalongestablished‘greasetrails’.Inexchange,thecoastalpeoplegotbeaverpelts,flint,copper,anddriedmoosemeatfrom inlandsources.Someof thesegrease trailsextendedhundredsofmilesintotheinterior,andtheywereusedtotransportthisuniquedietarystapleinlandforthousandsofyears.

Sowhymight thisbe?Whywait around for a school of little fishwhenharpooningasinglewhaleorafewsealionsgivesyouthesameamountof fat?Theanswer is found in lipidchemistry– themoredoublebondsyouhave inagivenamountof fat, thesooner itgoes rancid.Rancidityoccurswhenoxygenmoleculesareaddedtothefat,changingthetasteanddestroyingitsnutritionalvalue.Thehumannoseidentifiesrancidfatasoffensive.Andseal,whale,andmost fishoilsgorancidwithina fewweeks unless refrigerated or stored in airtight containers, whereasoolichangrease(likeoliveoil)canbestored forayearormorewithoutgoingrancid.

WhichCameFirst?OolichanGreaseorOliveOil.

InarecentconversationwithBillMoore,alocalfishermanoftheNiska’aBand inGreenville (Laxgalts’ap),BritishColumbia,oneofussuggested

that oolichan grease is like olive oil from the sea. Bill thought for amomentandthenresponded:“wehavebeenharvestingtheoolichanfor9000 years, which is a lot longer than people have grown olives; somaybeweshouldthinkofoliveoilasoolichangreasefromtheland.”

Butthere’sanotherreasonwhyoolichangreasewaswildlypopularinthepre-contact Pacific Northwest. Again, this can be explained in part bysimple chemistry. The human body stores fat for reserve energy tosustainitselfifthereisnothingelsetoeat,andourbodiesseemtofavorthe storage of monounsaturates over other classes of fatty acids.Monounsaturates,alongwithsaturates,appeartobewhatourcellswanttoburnwhentheyareadaptedtoburningmostlyfat.Oolichangreaseisrich inmonounsaturates,andthus ismore likehumanfat thananythingelse in the region. Thus oolichan grease appears to have an ideal fatcomposition for humans who consume a diet appropriately rich in fat.Somehow,without thebenefitofmodernchemistryornutritionists totellthemwhattodo,adiversecollectionofpeoplesinhabiting3000milesofthe Pacific coastline of North America discovered this, and built theirculturesandaregionaltradeeconomyaroundthisonesourceoffat.

Salt

Whole books have been written about the history of salt. Wars werefought over access to salt. Roman soldiers were often paid with ameasure of salt, hence the origin of the Englishword ‘salary’. Huntersandtheirprey,herdersandtheircattle,allshapedtheiractionsandhabitsaround access to salt. The reason, of course, is that salt (sodium) isnecessaryforlife.

Humansdidnotneedtoknowchemistrytounderstandthevalueofsalt.Salt deprivation leads to lightheadedness, fatigue, headache, andmalaise.Aboriginalculturescould figureout that if theydrank fromonespring, they began to feel lousy, but if they drank from that other one,they’d feelOK. The Inuit knewwhich ice tomelt forwater to boil theirmeat.Seaicelosesitssaltcontentwithage.Freshicehadtoomuchsalt,freshsnowhadnone,whereasolderseaicewasjustright.

Inland hunters followed their prey to salt licks and salt springs. Thesewaterswereprizedforcooking,andsomecultures learnedtodry thesewaterstomakedrysalt.Buttheuniversaldependablesourceofsalt forinland hunters and herders alike was blood. Blood was collected fromfreshlykilledanimalsusingtheemptiedstomachasacontainer,whetherfrom a bison on the Great Plains or from caribou or muskox on thetundra.Aliterofwholebloodcontainsabout2gramsofsodium,so500mlperdaywouldwardoffacutesymptomsofsaltdepletion.

Among theMasai living in hot inlandKenya, the consumption of bloodwas a staple of their culture (along with meat and milk). Even in the1920’s,longafterBritishtradehadprovidedthemaccesstodrysalt,theMasaistillbledtheircattle toprovideeachhunterwitha token50mlofblood per day[6]. Given another century of perspective, perhaps theperjorative phrase misrepresenting many aboriginal cultures as‘bloodthirsty savages’ might better be replaced by the phrase‘bloodthirstysavants’.

Today we ‘know’ that too much salt is bad for us, so why this longdiscussionofadiscreditednutrient?Theshortansweristhattheamountofcarbohydrateinourdietchangesourneedforsalt.Highcarbohydratedietsmake the kidneys retain salt, whereas a low carbohydrate intakeincreases sodium excretion by the kidney (called ‘the natriuresis offasting’). Hunting cultures seemed to understand this, and thus theirhighlyevolvedpracticesoffindingsodiumandconsumingenoughofittomaintainhealthandwellbeing.

Summary

Thelastfewdecadeshaveyieldedalotofscientificknowledgeaboutlowcarbohydrate diets, but in the few thousand millennia preceding thedevelopment of modern science, our hunting and herding ancestorssolved the practical problems needed to live and function well with aminimal carbohydrate intake. They didn’t need to know how it worked,just that it did. Successful dietary practices were integrated into theirculturesandpassedalongacrossgenerations.

But as these traditional cultures were overwhelmed and replaced by

agriculture, much of this hard won knowledge has been lost. This isunfortunate,giventhepotentialvaluethatlowcarbohydratedietsofferus,particularly in the management of diseases associated with insulinresistance. So let us summarize three lessons plucked from a few ofthesecultures.

1.First, awell formulated lowcarbohydratediet ismoderate inprotein and higher in fat. People attempting to follow a lowcarbohydratedietthatisalsolowinfatwillfinditunpleasantifnotunhealthyanddifficult tosustain.Aboriginalculturesknewthatthebodyprefersfatoverproteinasfuel.

2.Second,thetypeoffateatenwhenmostofyourenergycomesfrom fat is important. If you are a hunter getting 70-80% of yourenergy fromfat,yourdietary fatcompositionneeds tobedifferentfrom what you would consume if you were a subsistence farmereatingmostly carbohydrateswith just 15% of your energy as fat.Whenfatisusedforfuel,thebodyprefersthatthemajorityofitbeprovided as monounsaturates and saturates. On a lowcarbohydrate diet appropriately rich in fat, even if only a smallproportion of your fat is polyunsaturated, this small fraction timesthetotalamountwillstillprovideenoughgramsoftheessentialfattyacids.Because they function likevitamins rather than fuel, for theessential fatty acids, it’s all about dose, not percent. And for theomega-6 fats in particular, more is not necessarily better. (SeeChapter 9, Effects of Carbohydrate Restriction on Fatty AcidMetabolism)

3.Third,thebody’smetabolismofsalt isuniquelydifferentwhenoneisadaptedtoalowcarbohydratediet.Saltandwateraremoreefficientlyexcreted,which isagoodthingas longasyoumaintainan adequateminimum sodium intake. Ignore this lesson and youarelikelytosufferthecompletelyavoidableproblemsofheadache,fatigue,weakness,andconstipation–maladiesthatanyInuithealer

wouldhavepromptlyresolvedbygivingyouabowlofbloodsoup,ormeatbrothmadewithseaiceoftheproperage.

Chapter3

THE“MODERN”HISTORYOFCARBOHYDRATERESTRICTION

Introduction

Intherealmofpracticalnutrition,bywhichwemeanwhatpeopleactuallyeat day in and day out, there is little new in the world. The spate ofclinicalstudiesinthelast10yearscomparingtheeffectsoflowfatversuslow carbohydrate diets on body weight and blood lipids merely echomuchof theworkof scientists spanning the last twocenturies.This, incombinationwiththeempiricalexperienceofaboriginalculturesthatlivedbyhuntingorherding(asdiscussedintheprecedingchapter),offersusarich background upon which to judge the current turmoil surroundingdietarycarbohydrate.

Stepping back a bit from the current fray, the fact that there is turmoilsurrounding the relative roles of dietary fats and carbohydrates is itselfrather surprising. After all, modern organic chemistry cut its teeth onnutrientcomposition(alongwithdyesandpetrochemicals)startinginthemid1800s.Now,oneandahalfcenturieslater,weshouldhaveuniversalagreementonthedefinitiveinformationtellinguswhatisbestforhumanstoeat.Forexample,howcould thecarbohydrate-fatcontroversynotberesolved after we paid $700 million to perform the Women’s HealthInitiative(anassessmentofbothalowfatdietandhormonereplacement)on50,000womencompletedin2006?

The explanation for the ongoing carbohydrate-fat controversy isfascinatingly complex, and not surprisingly, it probably hasmore to dowithpoliticsandegosthanwithscienceperse.Atthecruxofourcurrentdiet dilemma is the 1977 McGovern Committee’s publicationDietaryGoals for theUnited States. This document, primarily produced by agroup of lawyers and journalists serving on McGovern staff, was

influencedmore by personal opinion than by the technical expertise inthefield.WhilerevisedguidelineswerepublishedbytheUSDAin1980,theystillexhortedAmericansto:“AvoidTooMuchFat,SaturatedFat,andCholesterol”.

Inresponsetothisless-than-scientifically-rigorousprocess,inthatsameyeartheFoodandNutritionBoardoftheNationalAcademyofSciencesreleased a competing document Toward Healthful Diets that avoidedrecommendations on fat and cholesterol intakes, focusing instead onmaintaining a healthy bodyweight.Rather than beingwelcomed into ameaningfuldiscussion,theFoodandNutritionBoard’schairpersonatthetime,Dr.PhilipHandler,wasvigorouslypressuredtotoethepartyline.Inan eloquently understated response, giving the following testimonybefore a congressional committee in 1980, Dr Handler did…and thencourageouslydidnot…acquiesce:

Howevertenuousthelinkage,howeverdisappointingthevariousintervention trials, it still seems prudent to propose to theAmerican public that we not onlymaintain reasonable weightsfor our height, body structure and age, but also reduce ourdietaryfat intakessignificantly,andkeepcholesterol intaketoaminimum.And,conceivably,youmightconcludethatitisproperforthefederalgovernmenttosorecommend.

On theotherhand,youmay insteadargue:What righthas thefederal government to propose that the American peopleconduct a vast nutritional experiment, with themselves assubjects,onthestrengthofsovery littleevidencethat itwilldothemanygood?

Mr. Chairman, resolution of this dilemma turns on a valuejudgment.Thedilemmasoposedisnotascientificquestion;itisa question of ethics, morals, politics. Those who argue eitherposition strongly are expressing their values; they are not

makingscientificjudgments.

Now,with thethree interveningdecades lendingacuity toourhindsight,Dr.Handler’scautionarypositionappearstohavebeenpreciselycorrect.Understandinghowheandhisfellowscientistscametobeignored,andhow as a result our population has developedmore obesity, diabetes,andmanyformsofcanceroverthelast30years,isanimportantlessonthatwouldserveuswelltostudy.

Oneoftheclearervoicesintherecentdialogueaboutlowcarbohydratediets is that of Gary Taubes. A renowned (and some might say,courageous)sciencewriter,Taubesweighed inon the topicwithaNewYorkTimesMagazinearticleentitled“WhatIfIt’sBeenABigFatLie?”inJune 2002. Taubes has subsequently presented in depth analyses ofthese dietary controversies in two books - Good Calories, BadCalories[13] andWhyWeGet Fat [14].We highly recommend readingthesedefinitiveandcarefully referencedbooks for the fullstory,but thenextfewpageswilltouchonsomekeypointspresentedbyTaubesinhischronicleofthedietarycarbohydrate-fatcontroversy

Banting’sLetteronCorpulence

In 1862, a retired British undertaker named William Banting wasstrugglingtocontainhisweight.AlloftheusualnostrumsoftheVictorianmedicalestablishment–exercise,calorie restriction,purgatives– failedtowork.

Asanaside,itisinterestinghowlittlehaschangedsincethemid-1800’s,Mostdoctorsstillprescribeexerciseandcalorierestriction,andthemostpopular drug in use (Orlistat, aka Xenocal or Alli) acts by blockingintestinalfatabsorption(i.e.,it’sapurgative).

Eventually he consulted a surgeon named William Harvey who hadstudiedinParis.

AtthattimeontheContinenttherewasinterestindietslimitedinsugars

andstarches,soHarveyprescribedsuchadietforWilliamBanting.

Within a year, Banting had lost 50 pounds while suffering none of theunpleasant side effects of his other weight loss attempts. He was sopleasedwithhissuccessonHarvey’sdiet thathepublisheda16-pagepamphletdescribingthisdietanditseffects.ItsoldwellnotonlyinBritainbut in the US as well, and it was also translated into multiple otherlanguages.Withinafewyears,‘tobant’becameaverbsynonymouswithdieting.

The diet Harvey prescribed for Banting consisted of meat, fish, andpoultry,nolimitationonanimalanddairyfats,smallportionsoflowsugarfruits, and even a few bits of toast. Otherwise no sugars, sweets, orstarcheswereallowed.Beer,which is rich in carbs,was forbidden, butwine and distilled spiritswere allowed if not encouraged. In addition toinitiallyacknowledgingHarvey, latereditionsofBanting’spamphletalsoacknowledged the work of the French physicians who had influencedHarvey.

Thus thedietpromotedbyBantingwasnot inventedby thisundertakeroutof thinairbut ratherhad its roots in themainstreammedicineof itsday.However, itsrapidrise topopularusecausedconcernsamongthemoreconservativemedical leadersoftheday,whospokeoutagainstit,atfirstclaimingthatitofferednothingnewandthenwarning(withoutanyscientificevidence)thatitcouldbedangerous.Thepublicwasobviouslynot convinced by this pushback, however, as theBanting regimen andsimilar diets remained popular well into the 20th century, and it hadsupport fromsomein themedicalcommunityaswell.SirWilliamOsler,the renowned Johns Hopkins physician and one of the fathers ofmainstream medicine in the US, commented favorably on Banting’sregimen in his iconic textbook The Principles and Practice ofMedicinein1892.

TheEisenhowerOpportunity

In 1955, President Dwight Eisenhower suffered a heart attack, afterwhich his next 4 years in office were spent under an intense mediaspotlight. Despite having a completely normal serum cholesterol level

andnormalbodyweightat thetimeofhismyocardial infarction,hewasconvincedbyhismedicaladvisorsthathehadtoreducehisintakeoffatand cholesterol. Soldiers, even generals like Eisenhower, are used totaking orders, so he did as he was told. In response, to everyone’sdismay,bothhisweightandbloodcholesterol levelwentup rather thandown. So he redoubled his dietary restrictions and obsessed over hisbloodtestresults.Itwasaclassiccaseof‘doingbetterbutfeelingworse’.

But thatdidn’t stop thepublichealthexpertsof the time, likeProfessorAncelKeysoftheUniversityofMinnesota,fromtakingthisopportunitytopromotealowfat,lowcholesteroldietforthewholenation.Therationalewas that the United States was suffering from an epidemic of heartdisease(whichwasanythingbutaprovenfact),andsomethinghadtobedone to contain it. And since animal fats contained cholesterol, andarterial plaques contained cholesterol, connecting these dots was aneasystorytosell.

Meanwhile the research community set about trying to pour solidconcrete under this dietary house of cards. In the 1970s, twomassivestudieswerestartedonmenwithhighbloodcholesterollevels.Thefirst,calledtheMultipleRiskFactorInterventionTrial(MRFIT)usedaverylowfat diet, exercise, blood pressure control and smoking cessation to tryandreduceheartattackrisk[15].Thesecond,theLipidResearchClinics(LRC)study,testedthecombinationofalowfatdietplusthecholesterolloweringdrugcholestyramine[16].

Closetoadecadelater,theresultsofthesestudiesweretallied.FortheMRFIT subjects who did everything they were told, there was aslightincreaseinthedeathratecomparedtothoseintheplacebogroupwho did nothing at all. In the LRC study, the cholesterol lowering drugslightly reduced the number of heart attacks compared to the placebogroup, but overall mortality in the two groups was not significantlydifferent. Specifically, out of 1800 men in each group, 68 died in thetreatmentgroupand71intheplacebogroup.

IgnoringthefactthattheMRFITstudygottheoppositeresultfromwhatthey had predicted, and that the effect of the LRC study on overallmortality was insignificant, the advocates of the dietary fat/cholesterol

hypothesissettoworksellingtheUnitedStatesGovernmentandpeopleontheideathateatinglessfatandcholesterolwasgoodfortheirhealth.Andintheprocess,cautionaryvoicessuchasDr.PhilipHandler(quotedabove)weresteam-rolledbyavocalgroupofanti-fatadvocates.

As forPresidentEisenhower, in the13yearsafterhis firstheartattack,he followed his doctor’s orders with military precision. Despite stickingclosely to a very low fat, high carbohydrate diet, he suffered frompersistentdigestiveproblemsand6moreheartattacks,thelastofwhichkilledhimin1969.

RobertC.Atkins:aRevolutionBuiltuponHistoricalRock

Intheearly1960s,Dr.RobertC.Atkins,acardiologisttrainedatCornellMedical College and practicing in NewYork City, put himself on a lowcarbohydratedietandeasilylostweightthathepreviouslyhadstruggledto lose. Recommending this diet to others, he observed that they tooweresuccessfulatlosing.Soonhehadbuiltasizeableclinicalpracticeinwhich he refined the use of dietary carbohydrate restriction as atherapeutictool.

In retrospect,Dr.Atkins’ timingcouldhavebeenbetter.The1970swasprobably not the best time to be extolling the virtues of very lowcarbohydratediets.That’sbecause themainstreamnutritionconsensusled by Dr. Frederick Stare at Harvard and Dr. Theodore Van Itallie atColumbia increasinglyportrayed lowcarbohydratedietsasdangerouslyhigh in fat.Todoso, theyneeded to ignoreconsiderablecontemporaryworkbyDr.JohnYudkinofQueen’sCollegeinLondonandDr.CharlotteYoung at Cornell (whose research possibly influenced Dr. Atkins, whowas trained at Cornell). These and other respected scientists haddemonstrated safe and rapid weight loss with reduced hunger byprescribinglowcarbohydratedietsunrestrictedinfat.ButlikeDr.Handler,thesescientificallycrediblevoiceswerenomatchforDrs.StareandVanItallie.Theytooweresteam-rolledorignored.

Giventhishostileacademicclimate,beinginprivatepracticewasclearlyanasset forDr.Atkins.Unlikeuniversity facultywhoneedtogetgrantsfundedandpaperspublished,Atkinswasnotdependentuponconsensus

committees(thepeer-reviewsystemusedbytheNIH)forresearchgrantsoronjournaleditorswhodecidedwhichpaperstoacceptorreject.Asaresult,hewaslessinhibitedthanhisacademiccontemporariesandthuslesspronetobeingsteam-rolled.And,althoughDr.Atkinswasbrandedaheretic and quack by his contemporary medical peers, his booksnonethelessreachedmillions.

In1972,hepublishedDr.AtkinsDietRevolution[17].Init,heleveragedhis decade of clinical experience with the low carbohydrate diet –valuableclinicalexperience thatmanyofhiscriticshadnoneof.Atkinsassertedthatonecouldloseweightonhisdietwithouthunger,thatbloodlipids and especially triglycerides improved despite an appropriate fatintake,andthat‘balanceddiets’didnotworkbecausetheyfailedtodealwith the underlying disturbance in carbohydrate metabolism commonlyseeninobeseindividuals.

Thisbooksoldhalfamillioncopiesinitsfirst6months,andthereactionwasasdramaticasitwaspredictable.Harvard’sFredStarewrote:“Anybookthatrecommendsunlimitedamountsofmeat,butter,andeggs,asthis does, in my opinion is dangerous. The author who makes thesuggestionisguiltyofmalpractice.”Columbia’sTedVanItalliedenouncedthe Atkins Diet in an editorial in JAMA in 1973[18], declaring it full of“gross inaccuracies”. In response, testifyingbeforeSenatorMcGovern’sSelectCommittee,Dr.Atkinscounteredwith:

“It is incredible that in 20th-century America a conscientiousphysician should have his hard-won professional reputationplaced on the line for daring to suggest that an obesity victimmightachievesomereliefbycuttingoutsugarsandstarches.”

Withthatexchange,thebattlelinesweredrawn,andthepolemicsplayedoutoverthenextthreedecadesuntilDr.Atkins’deathfromaheadinjurycausedbyafall.Inthatperiod,Dr.Atkinssoldtensofmillionsofcopiesof his books, while his critics steadfastly defended the superiority ofdietary carbohydrate over fat. In the meantime, serious scientists

interested in the objective evaluation of carbohydrate restricted dietsfound the NIH and other granting agencies hostile to their researchapplications.Asaresult,littlemeaningfulresearchwasdonetoaddressthe important questions about the safety and efficacy of carbohydraterestriction, and that which was done got shunted into obscurity. (Forexamplesofthis,seeChapter12).

AtkinsWasNotTheOnlyOne

The series of books by Dr. Robert Atkins was not the only voice insupport of low carbohydrate diets. There have beenmany other bookspublishedonthetopic,somebadandsomegood.Amongthelatter,werecommend looking at the “Protein Power” books by Drs.Michael andMary Dan Eades[1], and also the work of Dr. Richard K. Bernstein[2]advocating the use of carbohydrate restriction in type 1 diabetics (thelatterunderclosemedicalsupervision).

SenatorMcGovern’sDietaryGuidelines

The official expression of the low fat diet hypothesis was SenatorMcGovern’sSenateSelectCommitteementionedabove.Between1976and 1980, this group set the agenda for who would testify and whatwould be decided vis-a-vis national dietary guidelines. Theworkings ofthis committee are discussed in detail in Good Calories, BadCalories[13].Butitwasclearfromthebeginningthattheoutcomewouldbeinfavorofreduceddietaryfatandcholesterolindependentofwhatthescienceshowed.

Unfortunately,thisbureaucraticintransigenceinthefaceofdatahasnotslackened. After their initial goals and guidelines between 1977 and1980, the results of the MRFIT and LRC studies came in and weresummarily ignored.Starting fromDr.Handler’s position in 1980 “Thosewhoargueeitherpositionstronglyareexpressing theirvalues; theyarenotmakingscientificjudgments”,theMRFITstudygaveanegativeresultand the LRC study came out statistically even. Nonetheless, the

advocacyforalowfat,lowcholesterolnationalpolicylumberedforward.

Why?By themid1980s,whathadchangedwas thatnowtheacademicmainstream decided that there was more butter (or maybe ‘low fatspread’better fits theanalogy)onthe ‘conformitysideof thebread’.Noone within the academic community with Dr. Handler’s courage andstaturechosetostanduptoquestiontheking’swardrobe.ButbecausetheMRFITandLRCstudieshad‘failed’,andalsobecausebothoftheselargestudieshad failed to includedwomenassubjects, itwasdecidedthatanewstudyshouldbedonetodemonstratethebenefitsofalowfat,highcarbohydratedietinwomen.

TheWomen’sHealthInitiative(WHI)

The ultimate, and also the most expensive, test of the low fat heartdiseasehypothesiswastheWHIlaunchedin1991.Thismassivestudyof50,000womentriedtosimultaneouslyaddressanumberofhealthissuesinwomen,including(butnotlimitedto)thepurportedbenefitsofalowfatdiet.Theparticipantswererandomizedtovarioustreatments,includingagroupthatwasaggressivelycounseledtoreducetheirdietaryfatto20%of daily energy intake (which implies a goal of at least 65% of energyfromcarbohydrate).

After 8 years, when theWHI investigators tallied the data, this low fatgroupwas found to have no reduction in heart disease, stroke, breastcancer,orcoloncancercomparedtothegroupthatstayedontheirusualdiet(about37%fat).Simplyput,avigorouslypromotedlowfatdietrichincomplexcarbohydrates, fruitsandvegetablesdidn’t seem tobeall thathealthful after all. Rather than admit that their carefully defendedparadigmmightbeflawed,thestudy’sproponentssetaboutparsingthedatatoexplainwhytheirpoliticallyordained“healthydiet”didn’twork inthiscase.

Nor did they adequately address criticism of their protocol design thathadbeenopenlyexpressedfromtheoutsetofthestudy.Crediblecriticshadpreviouslynoted that theWHIstudydesignwasstronglybiased infavorof their lowfatdiet[13].Thusthe lackofapositiveresult isall themore surprising, implying that telling women to reduce dietary fat may

haveharmedtheirhealth.

TheFoodandNutritionBoard2010

Now it is almost a decade after theWHI results have been tallied anddigested, and we’ve seen many new studies published pertaining tocarbohydrate-restricteddiets.Sowe’remakingprogress,right?Well,notifwelookattherecent(June2010)reportoftheUSDietaryGuidelinesAdvisory Committee (DGAC). This group of 13 nutrition experts(appointedbytheFoodandNutritionBoard–thegroupformerlychairedby Dr. Handler, who had advised caution about the original low fatguidelines) is tasked with recommending nutrient intakes for the USpopulation.Onthetopicofdietarycarbohydrateintake,theyadvisedtheUSDA to define the minimum human requirement for dietarycarbohydrate at 130 grams per day. And in their conclusions on lowcarbohydratediets,theDGACstates[19]:

“Diets that are less than 45% carbohydrate ormore than 35%protein are difficult to adhere to, are not more effective thanother calorie-controlled diets for weight loss and weightmaintenance, andmay pose health risk, and are therefore notrecommendedforweightlossormaintenance.”

InotherwordstheDGACreportistellingALLAmericanstoconsumeatleast 45% of their calories as carbohydrate, that there is no benefit toconsuminglessthanthisamount,andthatinfactitmaybedangeroustodo so. Let’s lookat specific statements by this committeepertaining tocarbohydrate.

•Carbohydrates(sugarsandstarches)provideenergytocellsinthe body, particularly the brain, which is a carbohydrate-dependentorgan.(italicsadded)

•AnEstimatedAverageRequirement(EAR)forcarbohydrateis

established based on the average amount of glucose utilizedbythebrain.

•TheRecommendedDietaryAllowance(RDA)forcarbohydrateissetat130g/dforadultsandchildren.

WhatisremarkabletothoseofuswithexpertiseinhumanmetabolismistheDGAC’sstatementthatthehumanbrainiscarbohydratedependent,thereby mandating a high intake of dietary carbohydrate. Interestingly,thiswaswrittennotbylawyersandjournalistsliketheoriginalMcGovernCommitteereport,butbyacommitteeofphysiciansandPhDscientists.Theyshouldknowbetter.

Infact,thehumanbrainisacarbohydrate-dependentorganONLYifoneroutinely eats a lot of anti-ketogenic nutrients such as sugars andconcentratedcarbohydrates.Whendietarycarbohydratesareheldto50gramsorlessperday,humansundergoaprocesscalledketoadapation,causingthelivertomakeandreleaseketonesintothebloodstream.Aftera few weeks of the ketoadaptation process, serum ketones increaseseveralfold,reaching1-3millimolar(mM).

Above 1 mM ketones, more than half of the brain’s fuel comes fromketones.Therestofthebrain’sfuelmustindeedcomefromglucose,butthis amount (usually less than 50 grams per day) is easily producedendogenouslybytheliverfrom‘metabolicleft-overs’viaaprocesscalledgluconeogenesis. Thus, the brain uses glucose in varying amountsdepending upon the availability of ketones. The manifest ability of thebody to supply the brain with fuel independent of dietary carbohydrateintake clearly contradicts this committee’s assertion that the brain is acarbohydrate-dependent organ. Simply put, this is a classic case of afalsepremiseleadingtoafalseconclusion.

The DGAC’s second statement, that low carbohydrate diets “may bedangerous” was referenced to two published epidemiological studiesfromEurope[20,21].However thecommitteememberswerealso likelyaware of a similar study done in the United States and about to bepublishedbyHarvard researchers[22]. This recent report evaluated thereported food intakes from the Nurses Health Study and Health

ProfessionalsFollowupStudy,whichlookedathealthoutcomesover20-26 years. Dividing the subjects into subgroups based upon reporteddietarycarbohydrateintakes,theHarvardresearchersfoundaslightbutstatisticallysignificant increaseinmortality(~20%) inthegroupwiththelowestintakeofcarbs.

Basedonthesedata,thisinfluentialgroupofauthorsdeclaredmostlowcarbohydrate diets, particularly those containing animal products, asprobably unsafe. Interestingly, the lowest carbohydrate intake group intheHarvardstudycohortreportedtheyconsumed37%ofdietaryenergyas carbs, which translates into 185 grams per day for a personconsuming 2000Calories per day.Obviously this level of carbohydrateintake is well above the level of restriction shown to facilitate fatmobilizationassociatedwithnutritionalketosis.

Thus virtually no onewithin these study groupswas ketoadapted, andthis report has little relevance to the degree of carbohydrate restrictionaddressed in thisbook.Asanaside, it iscurious tonote that this “low”levelofcarbohydrateintakethatisdeemedtobeunsafe(185gramsperday)iswellabovetheminimumintake(130gramsperday)regardedbythe Dietary Guidelines Advisory Committee to be at the lower limit ofsafety.

However, the most powerful argument against accepting this cautionabout low carbohydrate diets expressed by theHarvard researchers isthe fact that it was this same analytical technique, some of the sameauthors,andoneof these twostudycohorts (theNursesHealthStudy)that led us down the flawed path of prescribing hormone replacementtherapy(HRT)topreventheartdiseasebackinthe1990s.Onlyaftertheprospective, randomizedWomen’s Health Initiative datawere analyzeddidwe(and they)discover thatHRTactuallycausesheartattacks (andsome forms of cancer) rather than prevents them. So after it wasdemonstrated to yield incorrect results then, it is fascinating that thesesameauthorsnowtrotoutthesame‘dead-on-arrival’analyticalmethodinanattempttodiscreditlowcarbohydratediets.

Some of the members of the Dietary Guidelines Advisory Committeeknowandunderstandthesefacts.Sowhydidtheycavetotheconsensus

andputtheirnamesonthecommittee’sflawedreport?Theanswerisnothard to guess. First, the committee was not chosen at random fromamong the hundreds of qualified scientists available to serve. It wasselected to include individualsknown to functionwellonacommittee–iconoclastsneednotapply.Second,thecommitteemembershipincludesa number of senior leaders in the field with considerable de factoinfluenceoverwhogetspaperspublishedandgrantsfunded–individualswhomsomeoneabitlessseniorinthefieldwouldnotwanttocross.

Summary

“Thosewhodon’tknowhistoryaredestinedtorepeatit.”–EdmundBurke(1729-1797),BritishStatesmanandPhilosopher

One might argue about whether or not we should ‘repeat history’ byadopting lessons learned fromour huntingandherdingancestors,whopracticed carbohydrate restriction for hundreds of thousands of years.However,fewwouldarguethatrecentnutritionhistory(1970topresent),withunprecedentedincreasesinobesityanddiabetes,hasbeengoodforus.Nonetheless,thereareimportantlessons–albeitnegativeones–tobegleanedfromthisrecentpainfulexperience.

Upuntilthe1970s,weseemedtobeonapathtoobjectivelyevaluatethebenefits and risks of therapeutic carbohydrate restriction. Duemore topoliticsthanscience,theviewsofAncelKeysgainedascendency,dietaryfat was deemed toxic, and carbohydrates were promoted. As the foodindustry built a supporting infrastructure to produce andmarket low fatfoods, understandably the resistance to change became all that muchstronger.

AgainstthisfortressbuiltonsandstoodlowcarbohydrateiconoclastslikeRobertAtkins,MikeandMaryDanEades,andRichardK.Bernstein.Butnowthesandunder the fortress isslowlybeingerodedaway, thanks innosmallparttotheincisiveanalysisofGaryTaubes[13,14].Timewilltellhow soon it will fall, allowing carbohydrate restriction to be fairly andobjectively evaluated. When that occurs, be it in two years or ten,carbohydraterestrictionmayfinallyachieveacceptanceasatherapeutictoolinwesternmedicine.

Chapter4

COMMONCONCERNSATAGLANCE

We hope you feel comfortable with this historical perspective of lowcarbohydrate diets. However, in all likelihood you will hear strongreservations from others about adopting this lifestyle for yourself orprescribingittoyourpatients/clients.Atthispointinthebook,wethoughtit would be helpful to briefly address common issues that people raiseaboutcarbohydraterestricteddiets.Thesewillbeaddressed indetail infollowingchapters.

1.It’sMostlyWaterandMuscle

Issue: Yeah, you lose pounds faster on low carb, but it’s mostlywaterandmuscleratherthanbodyfat.

Response:Thesurvivalofthismythoverthelast30yearsissoamazingthatwedevotepartofChapter12(LowCarbohydrateResearchPitfalls)to a discussion of why this has occurred. In short, there is nowoverwhelmingevidencethatnotonlydogroupsofpeoplerandomizedtoa lowcarbdiet losemoreweight thanonhigher carb intakes,but theyalsolosemorebodyfat.Themythofwaterandmusclelosscamefrombrief studies (a fewweeksor less) in peoplewhonever completed theadaptationphaseofthelowcarbdiet,inwhichthereisoftensubstantialwaterlossbecauseofthediureticeffectsofthediet.Ifyoulose5poundsoffatand5poundsofwater inthefirst2weeks,yes,halfofyour initialweightlosswasnotfromfat.Butifyouthenstayonthedietfor18moreweeks, losing two-and-a-halfpoundsof fatperweek (butkeepingallofyourmuscle), after 20 weeks you’ve lost 55 pounds, 50 of which wasbodyfat.Howtogetthisresult,losingalmostallfatandretainingorevenincreasingyourstrengthandwellbeing,isexplainedasthesumofmanyfactorswhich togetherwedefineas ‘awellformulated lowcarbdiet’.Tofullyunderstandhow todo thisandwhy,you’llneed to read the restofthisbook.

2.CarbsareCritical

Issue: We need carbohydrate for energy, especially when weexercise.

Response:Yes,carbsdoprovideonesourceofenergyforyourmusclesand brain, but both of these organs have completely adequatealternatives derived from dietary fat. And here’s the key fact in thisdiscussion:ahighcarbohydratedietblocksyourability toemploy fat tofuelyourbrain,and tosomedegree,yourmusclesaswell.Asnoted inthe next chapter, there is no other reason we have to includecarbohydratesinthediet,whichisanotherwayofsayingcarbohydratesarenotanessentialdietarynutrient.However,justbecausecarbsarenotessentialfromadietaryperspectiveisnotreasonenoughtorestrictthem.The real question is whether limiting carbs will adversely affect yourability to exercise. The answer is a definitive NO. When carbs arerestricted to the point of inducing nutritional ketosis, the body has aremarkable capacity to transition to burning fat, even during exercise.Thirtyyearsago,Dr.Phinneydidastudyshowingthatfatsuppliedalmostalloftheenergyusedbyhighcalibercyclistsaftertheyhadadaptedtoaketogenic diet (see Chapter 10, Body Composition and PhysicalPerformance;alsoRef[23]).Theseguyshadnoproblemperforminghighlevelexercisewithvery littledietarycarbohydrate.Sodon’tbuy into theclevermarketingbymanufacturerspromotingallthosesugarysportsandenergydrinks.Therealityisthatyoucanexercisejustfinewithoutthemwhen you have experienced the ketoadaption that comes after severalweeksofaverylowcarbohydratediet.

3.FearofFat

Issue: My doctor or dietitian agrees that a low carbohydrate dietmighthelpme loseweight, but s/he’sconcernedabout eating toomuchfatlongterm.

Response:Thisisacaseofgoodnews/badnews.Yourhealthcareteamappears to be supportive of a low carbohydrate diet. That’s the goodnews.Thebadnewsisthattheystillviewfatasharmfulunderalldietaryconditions. However, when you are ketoadapted, fat becomes your

body’s favorite fuel.But if you simultaneously restrict carbohydrateandalso fat, the only other source of energy left to put on your plate isprotein, and excessive consumption of protein is not a good idea. Sologicallyfathastobepartofaproperlyformulatedlowcarbohydratediet.Particularly after you transition toweightmaintenance,when your dailyenergy intake needs to equal your daily expenditure, consumingadequatefatbecomesessential.Simplyput,akeymessageinthisbookisthatfatisyourfriendwhenyouareonalowcarbohydratediet.

4.KetoneConfusion

Issue:Lowcarbohydratedietscannotbegoodformebecauseasasideeffectmybodymakestoxicketones.

Response:Verylowcarbohydratedietsdoindeedincreaseproductionofketonesasaresultofacceleratedratesoffatbreakdownanddeliveryoffattyacids to the liver.This isperfectlynaturaland in fact representsarather clever and vital adaptation in fuel partitioning when yourcarbohydrate intake is low.Whencarbohydrate isrestrictedto lessthan50 grams per day, fat breakdown is increased markedly, and bloodketones increasemoderately. This state of nutritional ketosis results inketone levels way below those characteristic of uncontrolled type-1diabetes.Thisgreaterthan10-folddifferencebetweennutritionalketosisanddiabeticketoacidosis (discussed inChapter1) is like thedifferencebetweenagentlerainandatorrentialdownpour.Afteraweekortwoofthismoderate increase in ketone production,many of the cells in yourbody switch from using glucose to ketones for their primary fuel. Thisprocessofketoadaptationisapowerfulmetabolicstatebecauseitmeansyour cells have a sustained fuel supply thanks to a steady release ofenergyfrombodyfat!

5.BanishtheSaturatedFatDemon

Issue:Maybeanappropriatefatdietisn’tnecessarilybad,butIstillhavetoavoidallthosedangeroussaturatedfats.

Response:IF‘youarewhatyoueat’,andIFsaturatedfatsfromthediethad been proven to cause death and destruction, then thismight be a

validconcern.Let’stakeaquicklookateachoneinturn.Wehavedonebothhumanandanimalstudiesexaminingtheamountsofsaturatedfatsinbloodandtissuesamplesafteralowfat,highcarbohydratedietversusa low carbohydrate diet containing appropriate fat. In both cases, thefatcontainingdietprovidedaboutthreetimesasmuchsaturatedfat.Andyet,wesawno increase insaturated fat levels ineitherbloodor tissuesamples. In fact, inpeoplewithmetabolicsyndrome, theappropriatefat,low carb diet actually decreased their blood levels of saturated fat,whereas the low fat diet subjects saw no decrease in blood saturates.This paradox – eating a saturate-rich diet makes your blood levels ofsaturates go down – occurs because ketoadapted people dramaticallyincreasetheratethattheirbodiesburnsaturatedfat.Whenyoucutbackoncarbohydratestothepointthatfatsgetburnedfirst,thesaturatedfatsgotothefrontoftheline,andifyouburnthemupforenergybeforetheycanaccumulate,howaretheygoingtoharmyou?

In response to thesecond ‘IF’, scientistshavebegun to takea secondlookatthe50-yearoldideathatdietarysaturatedfatsareharmful.Yes,ithasbeenshown thatsaturated fats inanimalorhumandietscan raiseblood cholesterol under some circumstances. However, we now knowthat some forms of blood cholesterol are either not harmful or evenprotective (like HDL cholesterol), and a wellformulated low carb dietcontaininga fairamountofsaturated fathasbeenshownrepeatedly toraise blood levels of this ‘good cholesterol’. Moreover, three studiespublished in the last year have examined carefully collected dietaryrecords of huge populations who were followed for decades. In all ofthreeoftheserecentstudies,therewasnoconnectionbetweensaturatedfatintakeandeitherthefrequencyofheartattackordeath[24-26].

Ifitdoesn’taccumulatewhenyoueatit,andeatingithasn’tbeenshowntoactuallyharmyou,where’sthedemoninsaturatedfat?

6.FeelingFaint

Issue:I’mhappylosingweightwithalowcarbohydratediet,butI’malwaystired,getlightheadedwhenIstandup,andifIexerciseformorethan10minutesIfeellikeI’mgoingtopassout.

Response:Congratulationsonyourweightlosssuccess,andwithjustasmall adjustment to your diet, you can say goodbye to yourweaknessandfatigue.Thesolutionissalt…abitmoresalttobespecific.Thismaysound likewe’recrazywhenmanyexpertsarguethatweshouldalleatlesssalt,howeverthesearethesameexpertswhotellusthateatinglotsof carbohydrates and sugar isOK. But what they don’t tell you is thatyour body functions very differently when you are ketoadapted. Whenyou restrictcarbs foraweekor two,yourkidneysswitch fromretainingsalttorapidlyexcretingit,alongwithafairamountofstoredwater.Thissalt andwater lossexplainswhymanypeopleexperience rapidweightlossinthefirstcoupleofweeksonalowcarbohydratediet.

Riddingyourbodyofthisexcesssaltandwaterisagoodthing,butonlyuptoapoint.Afterthat,ifyoudon’treplacesomeoftheongoingsodiumexcretion,theassociatedwaterlosscancompromiseyourcirculationTheendresultislightheadednesswhenyoustandupquicklyorfatigueifyouexercise enough to get ‘warmed up’. Other common side effects ofcarbohydraterestriction thatgoawaywithapinchofaddedsalt includeheadacheandconstipation;andoverthelongtermitalsohelpsthebodymaintain its muscles. The best solution is to include 1 or 2 cups ofbouillon or broth in your daily schedule. This adds only 1-2 grams ofsodium to your daily intake, and your ketoadaptedmetabolism insuresthat you pass it right on throughwithin amatter of hours (allaying anyfearsyoumighthaveofsaltbuildupinyoursystem).Thisrapidclearancealsomeans that on days that you exercise, take one dose of broth orbouillonwithinthehourbeforeyoustart.

7.ShortvsSustainedWeightLoss

Issue:Iamreadytotryalowcarbohydratedietforweightloss,butonceI’vereachedmygoalmydietitiantellsmeIneedtoswitchtoadietwithlotsofwholegrainsandotherhealthycarbohydrates.

Response:Unfortunately,all too frequentlypeople loseweightona lowcarbohydratedietandthenpromptlyregainitallback.Why?Acommonreasonistheyfailedtoviewalowcarbohydratedietasalifestyle.Ifyourespondreallywelltoalowcarbohydratedietasaweightlosstool,partofthereasonisyourwillpower,buttheotherreasonisthatyourbodyis

probably not good at processing carbohydrates. For most people, thisdifficultymetabolizingcarbohydratesdoesnotgoawayevenafteryou’velostsomeweight.Soafterlosing15or150pounds,ifyoutransitionbacktoadietwith toomuchcarbohydrate,youwill likely regainmuchof theweight,evenifthecarbsyoueataretheapparent‘healthy’ones.Yes,itispossiblethatyoumightbeabletoaddsomecarbsbackintoyourdietonceyouhavereachedyourgoalweight,butbeverycautious.Listentoyourbodyasmuch ifnotmore thanyou listen toyourdietitian.Addingbacktoomuchcarbohydratecanputyouonaslipperyslopebacktoyourformerweight.Toprepareyourself for long termsuccess, fromtheverystart you need to view your low carbohydrate diet as a permanentlifestyle,notjustatemporaryweightlosstool.

8.ModerationMadness

Issue: Restricting an entire macronutrient class seems extreme –especiallycarbohydrateswhichareknowntogiveusquickenergy.Weshouldbeencouragingmoderationinallfoodsandabalanceddiet.

Response:Thisisoneofthemorecommoncommentswehear.Afterall,howcanyouargueagainstquickenergy,moderationandbalance?Theanswerdependstosomedegreeonpreconceptionsaroundthemeaningofmoderationandwhatyouconsider‘good’nutrition.Ifconsuminglotsofcarbohydrate provided someessential nutrient thatwould otherwise belacking,thenwemightagreethatalowcarbohydratedietisunbalancedor even extreme.But that’s clearly not the case. Think of it thisway –what if you lived inCaliforniaandplannedavacation inHawaii.Wouldyou believe someone who told you going that far was ‘extreme’, andtherefore you ought to try flying just half way there instead? In thisanalogy, practicing this formofmoderationwould land you in seriouslydeepwater.‘Moderation’and‘balanced’aremeaninglesstermswhenweare talking about ‘islands of safety’. And if your body is carbohydrateintolerant,eatingalowcarbohydratedietisyourislandofdietarysafety.Shouldapersonwithgluten intoleranceconsumemoderateamountsofgluten so they can have a balanced diet? Of course not. Then whyshould a person with carbohydrate intolerance consume moderate

amounts of carbs tomeet somearbitrary criterion of a ‘balanced’ diet?From the point of view of essential nutrients and adequate energy topower your body, a low carbohydrate diet is ‘balanced’. Yes, this doesmeanthatcarbohydratesasanonessentialnutrientclassarerestricted,butyoucanstill getallof theessentialnutrientsandenergyyourbodyneedsbyselectingfromabroadarrayofnaturallowcarbohydratefoods.

9.MissingMicronutrients

Issue: You can’t get all the vitamins and minerals you need forhealthonalowcarbohydratediet.

Response: If you choose from a variety of naturally low carbohydratefoods(e.g.,eggs,fish,meats,poultry,nuts,seeds,berries,cheese,oliveand canola oils, cream, butter, and a vast array of vegetables) you’llautomatically achieve adequate intake of all the essential vitamins andminerals.ButwheredoyougetyourvitaminCifyoucan’tdrinkorangejuice? How about Brussels sprouts, peppers, cauliflower, kale, andbroccoli?AllareexcellentsourcesofvitaminC.Also,halfacupofberriesperdaycanprovidequiteabitofvitaminC.Forexample,there’s42mgofvitaminC–halfofthedailyrecommendedintake–(andonly5gramsofcarbs)inhalfacupoffreshstrawberries.

10.BrittleBonesandKidneyCrisis

Issue: I have heard that diets like Atkins which are low incarbohydrate andhigh inproteinmaycausemybones toweakenandmykidneystofail.

Response:Firstofall,awellformulatedlowcarbohydratedietlikeAtkinsisnotreallythathighinprotein.Werecommendproteinbetween1.5and2.0 grams per kilogram reference body weight (0.7 to 0.9 grams perpound referenceweight).This translates tobetween90and150gramsperdayforarangeofadults,whichisaboutwhattheaverageadultintheUS is already eating. This level is well tolerated and is not associatedwithadverseeffectsonbone,kidneyorotherhealthindictors.Thereasonthatprotein intakeshigher than theminimumrecommended (0.8gramsper kilogram) were thought to negatively impact bone is because they

causeasmallbutmeasureableincreaseinurinarycalciumexcretion.Onthesurface,thiscouldindicateahigherriskforbonelossovertimeanddevelopment of osteoporosis. However, we now know that increasingdietary protein above the minimum also causes greater intestinalabsorptionofdietarycalcium,whichbalancestheslightlygreatercalciumloss in the urine. In fact, recent research suggests that diets higher inproteinareassociatedwithhealthierbonesaspeopleage.

Similar to the situation with bone health, the concern about kidneyproblems stems fromabelief that highprotein diets contribute to renaldisease. This belief is based on studies of restricting protein in peoplewhoalreadyhaveseverelydamagedkidneys.However,thereisnodatalinking the moderate protein intake range listed above to damage inpeople with normal kidney function. In technical terms, despite someevidence that higher protein intakes can increase glomerular filtrationrate,theevidencelinkingthisnormalphysiologicresponsetoprogressivelossofkidneyfunctioninhealthypeopleiscompletelylacking.

Chapter5

DIETARYCARBOHYDRATES:SCIENTIFICANDCULTURALPERSPECTIVES

Introduction

Asthepreviouschapterindicates,weareusedtorespondingtothelitanyof concerns thatare raisedabout lowcarbohydratediets.Typically, ourresponses to these questions involve a short answer and a publishedreferenceor two.(Well,maybesomeofStevePhinney’sanswersareabit more extensive…) The typical result of these interactions is thatpeoplearesurprisedandimpressedbythequalityofsciencesupportinglowcarbohydratenutrition.

However,oneparticularlystubbornissuethatstilltroublesagoodnumberof people can be encapsulated as a fundamental belief thatvery lowcarbohydrate diets are not balanced. And few would argue that anunbalanced diet is healthy. In essence, this is a case where a diet issabotagedsimplybyhowitscriticsframeitconceptually.Nomatterthatourresponsemighthaveanexcellentbasisofscientificsupport,ifweletthelowcarbdietbeframedas‘unbalanced’,it’sgameover.

How do we respond to professional colleagues and family/friends whohavesuchamind-set?Whilethisissuewasaddressedbrieflyas‘Point8’in theprecedingchapter, it iscomplexenough thatwe feel theneed todevote this chapter to addressing it more fully. There are a couple ofimportantpoints thatdeservecarefuldiscussion,andthesearerelevanttoyourdecisionwhetherornottoremainonthefenceaboutthesafetyandefficacyoflowcarbohydratediets.

DefiningaBalancedDiet

We like topromotemoderationandabalanced lifestyle formanygood

reasons. We can all agree that balancing competing factors like workdemandswithqualityfamilytime,orphysicalexercisewithrelaxation, isdesirable. But when we carry that over to diet, ‘balance’ is too oftenarbitrarily translated into eating relatively equal proportions ofmacronutrientsfromavarietyoffoods.

Whereasthismayworkformanypeople,wehavetriedtomakethecasein this book that a subset of people (particularly those with insulinresistance) manifest themselves as having varying degrees ofcarbohydrate intolerance. Within this subgroup, some may remainhealthyandfunctionalbyconsuming100gramsperdayofcarbohydrate,whereas others need to restrict this macronutrient down to 30 or 40grams per day to avoid overt diabetes, obesity, or hypertension. Soshould thesame ‘balanceddiet’ in respect tocarbohydrate,proteinandfat be recommended to these individuals as the rest of the generalpopulation?

Unfortunately, that judgmentmaydependonone’spreconceivednotionofa‘balanceddiet’.Wedon’tbatatherapeuticeyelashwhenwerestrictglutenifapersonhasCeliacdisease,orrestrictlactose(milksugar)inapersonwithlactoseintolerance.Alsoconsidertheperspectiveofourpre-agricultural ancestors who consumed relatively little carbohydrate forhundreds of thousands of years before modern agriculture practicesbecame dominant. And even into relatively modern times, the highlyevolvedhuntingculturesoftheInuitandNorthAmericanBisonPeopleortheherdingcultureoftheMasaioffertestimonytotheabilityofhumanstothriveinthevirtualabsenceofconcentrateddietarycarbohydrates.

From the perspective of an Inuit or Lakota grandmother, our currentagribusinessdietwouldappeartobeanythingbut‘balanced’.Balanceisarelativeterm,anditsantithesis,‘unbalanced’,isclearlydefinedbyone’sculturalbaseline.So let’s try to takeoffourculturalblindersand lookatthesourcesofthisconceptthatasubstantialpercentageofcarbohydrate(beit30%or60%)isanobligatecomponentofa‘balanceddiet’.

CarbohydrateasanEssentialNutrientClass

A root concept of dietary need is ‘essentiality’. If no single component

withinamacronutrientclassisessentialtohumanwellbeingorfunction,thenitishardtoargueinfavorofaneedforthatmacronutrient.Andifwetake that macronutrient away from the diets of individuals or wholecultures and they continue to thrive for a year or for millennia, caseclosed.Agreed?

In the last century, nutrition science defined nine amino acids (leucine,isoleucine, valine, threonine, tryptophan, phenylalanine, tyrosine,histidine,andmaybecysteine)asessential.Specifically,thatmeansthattheymustbesuppliedby thedietbecausetheycannotbeproducedbythe body in adequate amounts to meet metabolic need for proteinsynthesis.Withouttheseessentialaminoacidsoveramatterofweeksormonths, protein metabolism is impaired and disease and dysfunctionensue.

Similarly,between1929and1978, twoessential fattyacid families (theomega-6 and omega-3 classes)were defined. If these polyunsaturatedfatsarenotsufficientinthedietovermonths(omega-6)oroverdecades(omega-3), then overt disease and dysfunction occur. Omega-6deficiency causes skin rash, growth stunting and sterility. Omega-3deficiency causes heart disease (and possibly dementia) in the firstgeneration, plus impairedneurological/visual/intellectual development inthesecondgeneration.

But where is the evidence for essentiality for any single molecule orstructural class within dietary carbohydrates. What are the signs andsymptomscharacteristicofcarbohydratedeficiency?Fatigue?No,notifamodicum of sodium and a modest period of adaptation are allowed.Growth impairment? No, the pre-contact Osage, and Kiowa in NorthAmerica and the Masai in Africa were giants by modern standards.Impaired intellectual development? Well, the people of the PacificNorthwest were living in large wooden houses and processing andstoringoolichangreasemillennia before thedevelopment of oliveoil intheEasternMediterranean.

So what are the textbook characteristics of dietary carbohydratedeficiency?Yes,weagreethatmaintaininganormalbloodglucoselevelis essential for human wellbeing. But the key question is: how is that

linked to dietary carbohydrate intake? The spoilers here for thoseclaimingtheessentialityofdietarycarbsaretheterms‘gluconeogenesis’and‘adaptation’,whichallowustomaintainnormalbloodglucoselevelswithoutdietarycarbohydrate.

Gluconeogenesis is the combination of pathways through which ourmetabolismcollectsandrevisesthecarbonskeletonsofaminoacids,theglycerolbackbonesfromtriglycerides,andevenlacticacidtomakenewglucosetofeedthosefewtissues(likethelensoftheeyeandredbloodcells)thatcan’tburneitherfatorketones.

Adaptationistheprocessthroughwhichwholeorgansinthebodyforgoglucose(frommuscletobrain)andswitchtoburningmostly fat for fuel.The combination of gluconeogenesis and adaptation together is whatallowedagroupofbikeracersstudiedbyStevePhinneytoeatnovisiblecarbohydrate for 4 weeks and still show up and perform well in theirsecond exercise test[23]. But in light of Stefansson’s do-or-dieperformance in the 1928 Bellevue Study (Chapter 2), this was no bigsurprise.

Sowhatdoesthismean?Itmeansthatweshouldnotconfuseourbody’sability tomaintainanormalbloodglucosewithourdietarycarbohydrateintake. When humans are adapted to a low carbohydrate diet, bloodsugar levelsandone’scarbohydrate intakearecompletely independentof one another. In fact, ketoadapted humans maintain better glucoselevelsacrossfeeding,fasting,andextremesofexercisethanwhenfedalowfat,highcarbohydratediet[23,27].

Howaboutsportsperformance?Don’tathletesperformbetterwhengivenahighcarbohydratediet?Thatwastheacceptedparadigm20-30yearsago,butithasnotstoodthetestoftimeformanyendurancesports.Evensome weight lifters and other strength/power athletes are now trainingand performing on carbohydrate restricted diets. This works to theirbenefitinpartbecauseofanabilitytomaintainalowerbodyfatcontentwithoutlosingmusclesizeandfunctionandalsoanimprovedperceptionof ‘recovery’ between workouts. But here is the key question. Even ifsomeonecanrunamileabitfasteronahighcarbohydratedietthanononerestrictedincarbohydrates,isthisevidencefordietaryessentiality?If

thatwere true, then both caffeine and ephedra (both ofwhich improveperformance)couldalsobeclassedasessentialnutrients.

CarbohydrateasaCultural(ifnotReligious)Imperative

Christianity arose in a region where wheat was the staff of life. EveryChristianrecognizesthephrase“giveusthisday,ourdailybread”.Thisveryquicklybecomesthin iceforascientistwhenthere isnoemotionaldaylight between dietary carbohydrate and our instinctive (or religious)senseofwellbeing,andthusourveryexistence.Itisareligioustenetandthusdefiesbeingquestioned.

Thepointhereisthatthereisaveryblurrylinebetweenourrationalandemotional attraction to dietary carbohydrates. Specifically, do we asscientistsrationallyexaminethepossibilitythatourintellectualconstructsofdietaryessentialityshadowourreligiousbeliefs?Perhapsrarely.Doesitaffectourthinkingandactions?Almostcertainly.

But is this zeal to promote dietary carbohydrate purely a function ofChristianityorreligioningeneral?Obviouslynot.Asagriculturebecameadominantforcearoundtheglobe,themajorityofthoseearlyfarmerswerenotyetabletoreadorcount.That left thedecisionofwhentosowandwhentoharvestinthehandsofthelearnedclassinanysociety,betheychiefs,priestsorshamans.Thisempowereda leadershipclass inmostagrarian societies, and they appropriately recognized that the origin oftheirpoweremanatedfromagriculturalcarbohydrates.

NowfastforwardtothepresentinNorthAmerica.Whorulesourthinkingabout dietary principles? Is it the academic nutrition community (aka,scientists)? Doctors? Dietitians? Agribusiness? The US Department ofAgriculture?Oprah?Wedon’thaveadefinitiveanswer to thisquestion.Butifwelookobjectivelyatwherethemoneyandpowerlie,thereislittledoubtthatculture,religion,industry,andgovernmentarecomplicitinthesubjectivedecisiontodiscount thesciencesupporting lowcarbohydratediets.

Whenwethinkaboutitinthislight,the‘HailMary’tacticofclaimingthatlowcarbohydratedietsareimbalancedislinguisticallyspoton!

LowCarbohydrateDietsareExtreme

Thebeliefthatalowcarbohydratedietisunbalancedisoftenexpressedanotherway–it’slabeled‘extreme’.Becauseit isviewedasextremeintherestrictionofamacronutrientwehappentocherishasaculturalicon,thereisananalogousperceptionthatthedietisunpalatableanddifficulttoadheretoovertime.Infact,manybelievethemainreasonforweightlosssuccesswithcarbohydraterestrictionisbecauseofthemonotonyofthe diet. The views that consuming a low carbohydrate diet takesSpartan-like discipline, or that food choices are severely limited, aresomeofthemostcommonlyclaimeddeterrentstotheiruse.

Thatalowcarbohydratedietmustbedraconian,lackingbothpalatabilityand theability toelicitpleasurecouldnotbe further from the truth.Theactualexperienceofmostpeoplewhochoosetofollowawellformulatedlowcarbohydratediet is that it ishighlysatisfying.Infact, theeasewithwhich one’s hunger is satisfied while eating copious amounts ofvegetablesanddeliciousfatcontainingfoods(knowingthat this fat flowsdirectlytocellsforenergyratherthanstorage)soundprettyempowering–andthat’showmanypeopledescribeit.

And for those who happen to have even a small degree of culinarycuriosity, there are almost infinite combinations of naturally lowcarbohydrateingredientsthatcanbeincorporatedintodelectablemeals.So far from being simply bacon and eggs at everymeal, the ability toexperiment with a wide variety of ingredients can be an incrediblyenjoyableaspecttothelowcarbohydrateexperience(seesidebar).Consider thismenu for a dinner the authors sharedwhile writingthisbook

NewYorkstripsteakgrilledwithanItalianherbrub

Mushroomssautéedinoliveoilandgarlic

Garden-freshgreenbeans,steamedandbuttered

Caprese salad (heirloom tomato, freshmozzarella, basil leaves, and ahoney-basil-roastedgarlicvinaigrette)

Home-mademaplewalnuticecream

Total carbohydrate for the meal: 25 grams. Total Calories: 1000-1200(see Chapter 17 for more examples of the succulent variety in theauthors’diets)

Summary

What should you thinkwhen you hear consensus experts discount lowcarbohydratedietsas‘unbalanced’?Whatshouldyouthinkwhendoctorsordietitiansstatethathumansneedtoeatalotofcarbohydrates?Pleasedon’t think ‘conspiracy’. We firmly believe that our colleagues don’tsecretlymeet and decide how they are going to present a united frontagainstalowcarbohydratedietinsurgency.Wedoubttheyeventhinkofusasinsurgent.Theyjustthinkofusas‘wrong’,where‘wrong’isbasedmoreontheirculturalandreligiousidentitythanonscience.

These are powerful forces that shape what we think and what we arewilling to question. But both history and modern science tell us that,ratherthanbeingphysiologicallyrequiredfornormalmetabolism,dietarycarbohydrates are an optional macronutrient for humans. Blood sugarlevels are well maintained in the ketoadapted individual, even acrossintense exercise. There is no textbook entity or clinical conditioncharacteristicofdietarycarbohydratedeficiency.

Asyoureadoninthisbook,youmightcometoviewthedecisiontoeataloworhighcarbohydratedietasasimpletrade-off.Ifyouhaveunderlyinginsulinresistance,doyouwanttoeatcarbsandstruggleunsuccessfullywith your weight, or forego them and be thinner? If you have type-2diabetes,doyouwanttohavea“balanceddiet”ordoyouwanttocomeoff your pills and insulin while putting your diabetes into remission byadoptingawellformulatedlowcarbohydratediet?Formanypeople,thesebenefits make it worth the effort to set aside a cultural dietary icon infavorofbetterhealthandwellbeing.

Section3

PHYSIOLOGY

Chapter6

BASICHUMANENERGETICSANDFUELPARTITIONING

Introduction

To appreciate how human energy metabolism adapts when dietarycarbohydrates are reduced, it helps to have a basic understanding ofwhat fuelsweburnandwhereweburn them.This topic is labeled ‘fuelpartitioning’becausedifferentcellsanddifferentorgansinourbodiesuseand store different fuels. The focus here is not on biochemistry (i.e.,enzymesandpathways),butonthephysiologyofhumanfueluse–howthebody’sorgansacquirethefueltheyneedtofunctionfromeitherfoodorfromstoredenergyreserves.

For this purpose, you need to know a bit about energy units (seesidebar), and the tools we use to assess human energy use. Theadvanced reader may be tempted to skim through this chapter, as itprovidesbasicinformationtoallowarangeofreaderstofullyappreciatethecomplexityandadaptabilityofhumanenergymetabolism.However,theconceptofketoadaptation,thekeytounderstandingfuelpartitioningduring carbohydrate restriction, is explained herein and is best notneglected.“Calories”

When we use the term “calorie” in reference to human energetics, wereallymeana“Calorie”,whichisthesameasakilocalorie.Incorrectuse,a“calorie”withalowercase“c”istheamountofenergyneededtoraise1 cc of water by one degree Centigrade. Thus a kilocalorie (kcal) willraisealiterofwaterby1°C.

Clinical Example. So how does this apply to human energetics? This

makessensewhenyouthinkaboutthecommonpracticeof“warmingup”whenexercising.Aleanperson’sbodycontainsbetween50and80kgof“stuff” (i.e.,50-80 liters,mostofwhich iswater, seeBodyComposition,below)thatneedstobeheatedup.Soifyoustartexercisingataratethatexpends say 400 Calories per hour, you will have burned about 100Caloriesin15minutes.Sincemostofthefuelweburnendsupasheat,that means in 15 minutes you would have generated enough heat tobringyour temperatureupbetween1-2°C– fromnormal37°C toabout38.5°C.Thus,atthatpointinanexercisesession,youare“warmedup”–literally. After that, since 38.5°C is the human fever threshold, anyadditional heat generated by exercisemust be dissipated by radiation,convection, or evaporation of sweat to avoid developing a high fever,heatprostration,orheatstroke.

CarbohydrateMetabolism

Mostcarbohydratesprovideabout4Caloriespergramin theirpuredryform.However,mostpreparedcarbohydratefoods(freshbread,cookedrice/pasta/potato, juices) contain more water than carbohydrate, which“dilutes” out the calorie count somewhat. Thus 100 grams of mashedpotatoescontainsonly100Caloriesorso(beforeyouaddthebutterorgravy!).Granulatedsugar,on theotherhand, ispuredrycarbohydrate,so the 4 grams in a level teaspoon provides 16Calories.Once eaten,mostcarbohydratesaredigestedand turned intoglucose,which isalsowhatwecommonlycallbloodsugar.Theonemajorexceptiontothisruleisfructose,whichmetabolicallycannotbemadedirectlyintoglucose(seesidebar).Fructose–asugarthatpartitionslikefat

Most of the fructose we eat, whether as sucrose (table sugar), highfructosecornsweetener,orinnaturalfruitsandfruitjuicegetsmadeintofat by our liver. This is because our body can’t convert fructose toglucose,andthefirststepincellularfructosemetabolismdivertsitawayfromtheprimarypathwayofglucosemetabolism(theMyerhoff-Embden

pathway).Thusthesetwo6-carbonsugars,fructoseandglucose,followseparatemetabolicpaths.Inthecaseoffructose,itiscleavedintotwo3-carbon fragments, both of which primarily contribute to fat production(lipogenesis)intheliver.

TwistedLogic?Mostenergydrinksandsportsbeveragesusesucroseorhighfructosecornsweetenerastheirprimaryenergysource.Giventhattheaverageexhaustedathletestillhastensofthousandsoffatcaloriesinbodyenergyreservesbutisrunningoutofcarbohydrate(glycogen),whywouldonewanttoaddasugarthatcannotbeusedforquickenergy,withmostofiteventuallyendingupasfat?

Atanypoint intimeinahealthynon-diabetic individual, thereare justacouple of “teaspoons” of free glucose (about 40 Calories worth) in thebody’s circulation (i.e., the bloodstream). This means that when youdigest and absorb a cup ofmashed potatoes or rice,most of the 200Caloriesofglucoseenteringthebloodstreamwhenitgetsdigestedhastoberapidlyclearedtosomeplaceelsetokeepbloodsugar in thenormalrange. If it weren’t, blood sugar would rise to more than twice normalwithin 2 hrs after ameal, and you’d have an instant case of diabetes.Both types of diabetes are diseases caused by the body’s inability todispose of glucose entering the bloodstream. It comes in two generalvarieties– type-1 ifyourbodycan’tmake insulin,and type-2 ifyoucanmake insulinbutyourcells tend to ignore the insulinsignal (aka insulinresistance). These diseases and their response to carbohydraterestrictionarediscussedinChapter15.

So where does glucose go when it leaves the bloodstream? Normallymuchofitgetstakenupintomuscleandburnedimmediatelyorstoredaslittle starchlike granules (glycogen) in the cells for later use. Your liveralso stores some glucose as glycogen, which it then releases to keepblood sugar normal overnight or during prolonged exercise. And someingestedglucose isused “realtime”byyourbrain tokeep the lightson.Butanadultatrestburnsatmost50kcalofglucoseperhour,soatleasthalfof thatcupofmashedpotatoeshas tobepromptly tuckedaway instorage,preferablyasglycogen.

If you have insulin resistance, your rate of glycogen synthesis inresponsetoeatingcarbohydratesisconsiderablyimpaired.Evenifyou’readeptatstoringcarbs,there’sonlysomuchglycogenthatyourmusclesandlivercanstore–somewherebetween1000and2000Caloriesinanadult, dependingonhowbig yourmusclesareandyour trainingstatus(exercisetrainingcanincreasetheamountofstoredglycogen).Sowhathappens when you eatmore carbs than you can burn right away andyourglycogenreservesarealreadyfull?Ratherthanletyourbloodsugarskyrocketup todiabetic levels, your liver, and to somedegreeyour fatcells, go to work turning that extra glucose into fat – a process calledlipogenesis.Oncethatglucose(orfructose)ismadeintofat,thereisnoway back – humans can’t make fat back into blood sugar – solipogenesis is a metabolic one-way street, ending in what for manypeoplebecomesacrowdedparkinglot(yourfatcells).

ProteinMetabolism

Proteinconsistsoflongchainsmadeof20differentaminoacidsthatthebodyusestobuildandmaintainstructuresliketendons,ligaments,bone,skin,hairandnails,plusorganslikemuscles,kidneys,liver,intestine,andlungs. Amino acids are also used to make enzymes and membrane-bound receptors and transporters that move specific molecules (likeglucose) inandoutofcells.Andsomehormonesareproteins– insulin,for example, is a 51-amino acid protein chain that stimulates glucoseuptake bymuscle and fat, without which that cup of mashed potatoeswouldbeacutelytoxic.

Allofthebody’sproteins,whetherinblood,muscle,brain,orbone,areinacontinuousstateofturnover.Thisisbecauseproteincontainingtissuesare constantly being repaired or renewed, so your body needs aconsistent source of protein to maintain itself. If you don’t get enoughproteinforaday,aweekoramonth,yourbodywillallownetbreakdownofsometissuesinordertorecycletheaminoacidsitneedstokeepvitalstructuresuptopar.Andifyouaregrowingtallerorbuildingmuscle,thisfurtherincreasesyourneedsomewhatabovetheminimumproteinintakerequiredformaintenance.

Currentguidelinesrecommend0.8grams/dayofproteinperkilogramof

bodyweightforadults,withmoreforchildren,adolescents,andpregnantwomen.MostpeopleintheUSgetmuchmorethanthisunlesstheyareveganorvegetariansormakereally lousyfoodchoices.Sobeyondthisminimum, the key questions about protein are: 1) is the minimumrecommendedintakeoptimum;ifnot,howmuchis?And2)howmuchistoomuch?

Thequestionofdefininganoptimumproteindosedoesnothaveasimpleanswer.Inadditiontogrowthinchildhoodandpregnancy,multiplefactorssignificantly alter your daily protein need. Important variables thatincrease an individual’s protein need include energy restriction (i.e.,weight lossdieting), inflammationor illness,andrecoveryof lean tissueafteraperiodofloss(suchasfollowingstarvation,famine,orprolongedillness).

Anotherfactorknowntoinfluencesourbody’sneedforproteinisthemixof carbohydrate and fat that provides most of the energy in our diet.However, the magnitude of this factor is very dependent on timing. Inshorttermstudies,takingawaydietarycarbohydrateandreplacingitwithfatreducesourbody’sefficiencyinusingprotein.Putanotherway,whenyou first take away dietary carbs, you need more protein to maintainmuscle and other protein-containing tissues. But when you observe ahumanoveranumberofweeksofadaptationtoalowcarbohydratediet,mostof this initial inefficiency inproteinusegoesaway[27].Thus,onceyouareketoadapted,yourbody’sneedforproteinisn’tmuchhigherthanduringa‘balanceddiet’.Thisisakeyfact inourunderstandingthat lowcarbohydratedietsused in the long termdonotneed tobeparticularlyhighinprotein.

Alltheproteinweeat(withtheexceptionofstuffthatisrubbedorcutoff,like skin, hair, and nails) eventually gets burned for energy, yielding 4Calories per gram. And you can’t “push” your body to buildmuscle byeatingextraprotein–muscleisbuiltupunderthestimulusofexercise(orillicit pharmaceuticals) as long as adequate protein is available at thetime. No one has ever shown that more than 1.5 gram/kg improveshumanproteinsynthesis(whichtranslates to~100gram/dayfora5’10”male,aboutwhat theaverageUSomnivoreeatsdaily(100gram=400kcal = 15% of 2700 kcal). That said, however, generations of power

athleteshavemadetheempiricobservationthattheytrainandcompetebetteronproportionatelyhigherproteinintakes(e.g.,1.5to2.5gramsperkg).

Asforhowmuchistoomuchprotein, thisagainhasnotbeenpreciselydefined.Asageneralrule,intheshortterm,peoplestarttofeel“unwell“ifthey routinelyeatmore than30%of theirdailyenergyneedasprotein.Eventhoughlowcarbohydratedietsareoftencasuallyidentifiedashighprotein,thetruthismostmaynotactuallybethathigh.Onefactordrivingthis misunderstanding is that “protein foods” like bacon, eggs, friedchicken, tuna salad, hamburger, and even lean steak typically containmore fat calories than protein calories. So in fact, “high protein” dietsconsistingofcommonfoodstendtobehigherinfatthanprotein.

Second,whensomeonegoesontheAtkinsoranotherlowcarbohydratediet,theyusuallyloseweight,right?Muchofthatweightlosscomesfrombodyfat,whichtypicallyprovidesthebodyuptohalfitsdailyenergyfrom“inside”(i.e.,endogenousstores)duringtheinitialweightlossphase.Soif someone iseating1400kcal/dayconsistingof relatively lean “proteinfoods”thatarehalfprotein(700kcal)butburns2800kcalperday,his/herdietary protein intake is actually supplying only 25% of their total dailyenergyneed,fallingwellbelowtheempiric30%ceilingnotedabove.Buttothecasualobserverwhoisignoringthecontributionofbodyfatstores,theactualfoodbeingconsumedappearstobehighinprotein

Theother important implicationof this is thatwhenapersonmakesthetransitionfromweightlosstoweightmaintenanceonalowcarbohydratediet, total energy intake must increase. Carbohydrate necessarilyremainsasmallfractionofone’sdietaryenergysupplyinordertoremainin a ketoadapted state and avoid the side effects of carbohydrateintolerance.Therefore,theproportionoffattoproteininthedietneedstobe increased to avoid overeating protein. This important issue will bediscussedinmoredetailinChapter16.ProteinandKidneyFunction–LessonsfromKidneyDonors

In the past 50 years, tens of thousands of individualswith two healthykidneys have donated one of them to save another’s life. As a result,

therearecurrentlyabout100,000peopleintheUSwithonlyonekidney,with some of them surviving this way since the 1970s. None of thesepeopleareadvisedtoeat lessprotein,eventhoughtheyhaveonlyhalfasmuchkidneyfunction.Whatthiseffectivelydoesisdoubletheirproteinintakerelativetokidneyfunction.Yes,theremainingkidneydoesgetabitbigger,butitdoesn’tcomeclosetodoublinginsize.

Recently, within this population, only 65 have developed kidney failureand needed a transplant of their own over an approximately 3-yearperiod.Thisisabouthalftheaveragerateofkidneyfailureinthegeneralpopulation.Andhere’sthekicker–mostofthesepeoplegaveakidneytoa relative who needed one, and the most common causes of kidneyfailure run in families. Based on that, we’d expect the donors to havemorecasesofkidneyfailurethanthegeneralpopulation.Thisisahead-scratcher,butclearlythisindicatesthatdietaryproteinisnotabigkillerofkidneys.

Thatsaid,dietaryprotein restriction isa recognized factor inpreservingresidual glomerular function in individualswithadvancedkidney failure,but the value of extremely low protein diets in this situation remains atopic of ongoing debate. However, the extrapolation of this extremeclinical example to the presumption that dietary protein in the rangesdiscussed above is a primary cause of renal disease is completelyunfounded.

EnergyinFoods–Fat

Most fats we get from foods are triglycerides, consisting of a glycerol“backbone”with 3 fatty acidmolecules attached.Anadditional class ofdietary fat, coming from the membranes of plants and animal, isphospholipids, which tend to be higher in essential fatty acids. Bothtriglyceridesandphospholipidscanbemetabolized(burned) forenergy,andtheyprovideabout9Caloriespergram.Andbecausemanydietaryfatsandoilscontainlittleornowater,fattyfoodstendtobeprettyenergydense(e.g.,acupofbutter,oliveoil,orlardcontains1600-1800kcal).

Becausefatsdonotdissolveinwater,theyarecarriedinthebloodstream

as triglyceride droplets surrounded by emulsifying molecules likephospholipids, cholesterol, and proteins. These particles are calledlipoproteins,andtheyaresubjecttomuchloathingbecausetheycontaincholesterol. In reality, these lipoproteins are like trucks loaded withenergy traveling about in the bloodstream delivering fuel to cells. Alllipoproteins contain cholesterol, and their cholesterol contents may belabeled “bad” or “good” depending on where these lipoproteins areformed and where they tend to end up. It is a simple butunderappreciated fact that without cholesterol, there could be nolipoproteins, and we’d be hard pressed for an alternative method todistribute fats and fat soluble nutrients to our cells for structure andenergy.

Atanyonepointintimeinahealthyperson,thereismoreenergyasfatinthecirculationthanasglucose,anditsexchangeinandoutofstoragein fat cells and in the liver is every bit as dynamic and important as isglucose.Inanothersimilaritytoglucose,fatisalsotakenupbymusclesfor both immediate use as well as for storage. Fat storage droplets inmuscle serve as reserve fuel to support exercise (just like glycogen),droppingtolowlevelsafterprolongedexerciseandbuildingbackupoverthenextdayortwoofrecovery.

In addition to their role as the body’s primary fuel sourcewhen insulinlevelsare restrained,dietary fatsalsocontain two ‘families’ofessentialfatty acids. Identified by their uniquely positioned double (unsaturated)bonds called omega-3 and omega-6, these two classes of fatty acidsserveawidevarietyofstructuralandsignalingfunctionsthroughout thebody.Andbecausetheiruniquestructurescannotbecreatedbyhumanmetabolism,thesetwoclassesofessentialfatsmustbeconsumedfromdietary sources. The metabolism of these essential fatty acids isprofoundly changed in the context of carbohydrate restriction, and theimplicationsofthisforintakeguidelineswillbediscussedinChapter9.

BodyCompositionandEnergyContent

Peopleobviouslyvary tremendously inheightandweight.However,notsoobviousisthefactthattwoindividualsofthesameheightandweightcan vary a great deal in “body composition”. Becausewe humans can

onlystoreasmallamountof carbohydrateasglycogen (amaximumof500grams inawell-trained,muscularmale,which is0.6%ofan80kgbody),thebiggestvariationsinbodycompositionbetweenindividualsareintherelativeproportionsofleantissueandfat.

Healthynormalmencanhaveup to20%body fat,whereas thisupperlimitforwomenis28%.Thelowerlimitsforhealthfulpercentbodyfatareless clear, in part becausegetting to a very lowvalueby starvationasopposedtoexercisemightsignificantlyaffectone’swellbeing.Thatsaid,itisnotunusualtofindhighlytrainedmaleswithlessthan10%bodyfat(andsimilarlyunder15% in femaleathletes).Therefore it ispossible tohavetwo5’10”guysweighing170pounds,onewith17poundsofbodyfatandtheotherwith34pounds,withbothqualifyingasnormal.

The other variable with body fat is where it is located. Fat carried“centrally” (i.e.,aroundthemiddle,andparticularlywithin theabdominalcavity) isassociatedwithgreater risk fordevelopingdiabetesandheartdisease than fat carried below the waist. Therefore, risk calculationsbasedjustonheightandweight,andeventhosethatattempttomeasuretotal body fat, provide less than optimum information for an individualconcerned about her/his health. In this context, a simple waistcircumferencesometimesoffersbetter informationonhealth risk thanatotalbodyfatdeterminationbyaspace-ageinstrument.

The importance of where one carries body fat is interesting from anevolutionaryperspectivebecausetheapparentroleofbodyfat istotideusthroughleantimes,likefamineorseasonalfoodshortage.Whenyoulookatpicturesofpeoplewhohaveexperiencedafamine,neitherbelliesnorbuttsarepreserved,whichmeansbothgetmobilizedwhenthebodyneedsfuel.Butbarringtotalstarvation,adietortreatmentthatfavorsthelossofabdominalfatwouldbedesirable.

Which brings us to the question: how much energy reserve does ahealthypersoncarry,andhowlongwillitlastifthere’snofood?Solet’stakeahypothetical5’6”,132pound(60kg)womanwith25%bodyfatsetadriftinalifeboatwithplentyofwaterandnofood.Her15kgofadiposetissue is about 85% by weight triglyceride, so she has about 115,000Caloriesoffatreserves.Shecanalsoburnabouthalfofherbodyprotein

content(10,000kcalofher20,000total)beforeshedies.Sittingquietlyintheboat(i.e.,notrowing)she’llstartoutburningabout2000Caloriesperday.Thisimpliesthatshe’dlastabout62days.

Butnotso fast–abunchofother thingshappenwhenahumanstopseating.Remember thatprotein isconstantly turningover throughout thebody,andifthere’snoreplacementdietaryproteincomingin,leantissueisbrokendownandlost.Thebadnewsisthatourhypotheticalsubjectintheboatgetsweaker,butthereare2piecesofgoodnews.First,overaweekortwo,thebodyadaptstogetbywithlessproteinbreakdown(i.e.,ketoadaptation),sotherateoflossofleantissue(i.e.,muscle)slowsastheweeksgoby.

Second, our resting metabolism can adjust itself in response tostarvation, going down 10-15% in the first few weeks, and then goingdown further as more and more muscle is lost. Net/net: our hardyhypotheticalheroinewilllastsomewherebetween75and90daysinherlifeboat. The bad news for guys is that becausewe typically start withaboutthesameorlessamountofbodyfatandmoremuscle(translation,higher restingmetabolism), our down-hill slope is steeper and the little“X” at the end of the curve typically comes at about 60 days. Newtonmight have said something like “For every advantage, there’s adisadvantage.”Take-homemessage:whetheryou’reaguyoragal,takesomefoodwithyouinthelifeboatifyou’realongwayfromland.

WhatYourOrgansBurn

Here’saquestionforyou–doallcellsandorgansinyourbodyusethesame fuels? Specifically; if your diet consists of 20% protein, 30% fat,and 50% carbs, do all cells throughout the body use this identical fuelmix?Theanswer,ofcourse,is“no”(becauseifitwere“yes”,whywouldwebeaskingthisquestion?)

Somecellsprefer fats for fuel, otherspreferglucose,andsomearesospecializedthattheyprefer justoneparticularaminoacid.Sonomatterwhat you eat, it seems that some types of cells would feel deprivedunless the body had away to divvy up energy sources among organsand cells and also had alternatives when necessary. As a result, the

inter-organ exchangeof fuel is both complex and dynamic.Here are afewsimpletastesofthecomplexityandeleganceofthissystem.

Muscle:Whenwe saymuscle,we typicallymean the things thatmoveour arms and legs, technically called skeletal muscles (which differ informandfunctionfromthecardiacmuscleinourheartandalsofromthethird type of muscle (smooth) that lines blood vessels and ourgastrointestinal tract).At rest, skeletalmusclesprefer fat for fuel, usingglucoseonlywhen insulin levelsarehighandbloodsugarneedssomeplace to go. During sustained exercise, fat is still the preferred fuel atintensities up to 50-60% of that muscle’s maximum continuous effort.Above 60% of maximum effort, glucose (or stored glycogen)progressively assumes a dominant role, although this dominance isattenuated when individuals are given a few weeks to adapt to a lowcarbohydratediet[23, 27].Alsoat thesehigher intensities, someof thisglucose is not completely metabolized but is partially broken down tolactateandreleasedbackintothebloodstreamratherthanbeingoxidizedinmusclemitochondriaallthewaytoCO2andwater.Bycontrast,duringresistanceexercise (veryhigh intensity,briefduration),mostof the fueluseconsistsofglucosemadeintolactate.

Buthere’stheinterestingpart.Lactatehasabadreputationasacauseofmuscle fatigue and pain. This is a classic case of guilt by association.Duringtransition fromrest to intenseexercise, the increasedproductionoflacticacidrapidlydisassociatesintolactateandhydrogenion.Itistheaccumulation of hydrogen ion, not lactate per se, that contributes tofatigueduetoacidosis.Lactatehasamuchmoreinterestingandpositiveroletoplayinthehumanbody.Muchofthelactatereleasedfrommuscleduringexercisegetstakenupbytheliverandmadebackintoglucose(aprocesscalledgluconeogenesis)andsentbackto themuscleswhere itcanbemadeintolactateagain.Andbecausetheliverusesmostlyfattopower gluconeogenesis, this shuttle of glucose out from the liver andlactateback(calledtheCoricycle)actuallyendsuppoweringresistanceexercisefromenergyreleasedbyfatoxidationintheliver.

Heart: The predominant fuel preferred by your heartwhen you are notexercising is fat. The heart rarely uses much glucose, with the onlyexceptionbeingduringaheartattackwhenavessel ispluggedandthe

oxygensupplytothatpartofthemuscleiscutofforseverelyreduced.Inthat case, the small amount of glycogen in heart muscle is usedanaerobically tomake lactate.Andhere’sonemorebitofheresyaboutlactate.Duringexercise,ahealthyandwell-perfusedheartactuallytakesuplactatefromthecirculationandburnsit toCO2andwater.Lactate ispreferred by heart muscle cells over glucose, and during enduranceexercise, lactate can provide as much as 50% of your heart’s energyneed[28].

Liver: The liver does awhole lot of important things for the rest of thebody, such asmaking, storing, and releasing glucosewhen necessary,makingketoneswhencarbohydrate intake is restricted formore thanafew days, collecting and secreting fats and lipids as lipoproteins, andmakingandsecretinganumberofimportantbloodproteins.Asaresult,theliverusesalotofenergyforanorganitssize,andmostoftheenergyitusescomesfromfat.Thelivercangetthefatitneedsfromcirculatingfattyacids released from fatcells, fromremnant lipoproteins it removesfromthecirculation,orbymakingfatfromcarbohydrates(lipogenesis).

Brain: The brain is the spoiled child of the organ family. It can burnglucose or ketones (or a combination of the two) and it can’t burn fat.Thisisinterestingbecausethebrainitselfcontainsalotoffattyacidsinall its membranes andmyelin (although little or none as triglycerides),andthemanytypesofbraincellsallcontainmitochondriathatshouldbecapableofoxidizingfattyacids.Anothersurpriseaboutthebrain ishowmuch energy it consumes each day (600 kcal) despiteweighing just 3pounds.Thisismorethan10-timestheaverageenergyuseperpoundoftherestofthebody,whichexplainswhythebrainhassuchalargebloodsupply(toprovidefuelandoxygenandalsotokeepitcool).

Theotherimportantfactaboutthebrain’sfuelsupplyisthatitcontainsnoreservesupplyofglycogen,andbecauseitcan’tburnfat,itisabsolutelydependent upon a minute-by-minute blood supply containing both fuelandoxygentomeetitsneeds.Thisiswhyevenatransientdropinbloodsugar causes an intense physiological response (increased heart rate,shaking, anxiety, and intense hunger/cravings). And if blood sugarsuddenly drops to less than half of the lower limit of normal, it causescoma. The shaking, anxiety, and fast heart rate that occurwhen blood

glucoselevelsfallareduetoadramatic increaseinadrenergicnervoussystem activity (release of noradrenaline from nerve endings) andadrenaline from the adrenal glands. Among other effects, this acuteresponse to hypoglycemia stimulates two processes in liver: thebreakdown of any glycogen present and formation of glucose fromanythingavailable(lactateoraminoacidsfromprotein).

Understanding this combinationof factshelpsexplainwhy rapidweightlossdiets,especiallythoseemphasizingcarbohydrates,canbetoughtofollow.Ifforexampleyoudecidetoeat1200kcalperday,composedof25%protein(75grams),25%fat,and50%carbohydrate,yourdailycarbintaketotalsjust600kcal.That’smorethanenoughtopreventyourliverfrommakingketones,butit’sjustbarelyenoughtofeedyourbrain.But,yousay,your livercanalsomakeglucose fromsomeof theproteinviagluconeogenesis,whichiscorrect,butthattotalslessthan50grams(200kcal) per day. Still, this 1200 kcal diet should support your brain’s fuelneedsjustfine.

Butwhathappens ifyoudecide togo jog5miles in50minutes (whichconsumes100kcalpermile).Evenatthisrelativelyslowpaceof6milesperhour, abouthalf of yourmuscle fuel usewill come fromglucoseorglycogen, so you burn about 250 kcal of carbohydrate fuel. In thisscenario, inthe24-hoursthatincludesthisexercise,the600+250kcalofglucoseuseexceed the600+200kcalavailablesupply.Typically inthissetting,peoplestart to feel lousy (see “bonking”below).Yourbodycan make up the difference by drawing down its limited glycogenreserves or by the net breakdown of some muscle to increase livergluconeogenesis. But if you stick to the diet and continue the dailyexercise,something’sgottogive.Andwhattypicallyhappensisthatyourinstincts(onlyamasochistlikestofeelbaddayafterday)gettheupperhand over your best intentions, prompting you to either eat more orexerciseless.

In this situation, itwouldbeconvenient if this fuel conundrumcouldbesolvedbyyour livermakingsomeketones frombody fat tohelp fill thegap in the brain’s fuel supply. However, this appears to be a flaw inhumandesignbecauseliverketoneproductiondoesnotkickinuntildailycarbohydrate intake isconsistentlyatorunder50grams(200kcal)per

dayforanumberofdays.Thusthereappearstobeafunctionalgap inthe body’s fuel homeostasis when dietary carbohydrate intake isconsistentlysomewherebetween600and200kcalperday.

So let’s consider an alternative diet, say 1200 kcal consisting of 30%protein,15%carbs(i.e.,180kcalor45grams),and55%fat.Afteraweekortwoofgettingadapted(duringwhichyoumayexperiencesomeofthefuellimitationsymptomsdiscussedabove),yourserumketonesriseupintherange(1-2millimolar)wheretheymeetatleasthalfofthebrain’sfuelsupply.Nowifyougoforthat5milerun,almostallofyourbody’smusclefuel comes from fat, leaving your dietary carb intake plusgluconeogenesis fromprotein tomeet theminor fractionof yourbrain’senergyneednotprovidedfromketones.And,ohyes,afteryourrunwhileon the low carb diet, your ketone levels actually go up a bit (notdangerouslyso),furtherimprovingfuelflowtoyourbrain.

So what does this mean for the rest of us who are not compulsiverunners?Well,thisillustratesthattheketoadaptedstateallowsyourbodymore flexibility in meeting its critical organ energy needs than a‘balanced’ but energy-restricted diet. And in particular, this alsomeansthatyourbrain isa “carbohydratedependentorgan” (asclaimedby theUSDA Dietary Guidelines Advisory Committee as noted in Chapter 3)ONLYwhenyouareeatingahighcarbohydratediet.Whencarbohydrateisrestrictedasintheexampleabove,yourbody’sappropriateproductionof ketones frees the brain from this supposed state of ‘carbohydratedependency’.Andbecauseexercise stimulates ketoneproduction, yourbrain’s fuelsupply isbettersupportedduringandafter intenseexercisewhenonalowcarbohydratedietthanwhenyourcarbohydrateintakeishigh(seebelow).

Bonking(aka“HittingtheWall”)

Most endurance athletes know and fear a sudden loss in performancethat typicallyoccursanhourormore intoahigh intensityperformance.Runnerscallthis“hittingthewall”andbicyclistscallit“bonking”.Ineithercase,whattheathletedescribesisacommonandreproducibleseriesofevents. First, nomatterwhat else is going on around you, there is thesuddenonsetof food fantasies(intrusive thoughtsof food).Next,within

5-10minutescomechillsandshakes(theadrenaline release). Ifat thispoint you do not immediately stop and eat, the bottom falls out ofperformancecapacityandyoufeelprofoundlydepressed.Thisiswhyweoccasionally see the highly trained runner walking the last mile of amarathon in tears. It’s not just sadness fromnotwinning – the bonkedindividual’sbrainhasliterallycometothebitterendofitsfuelsupply.

Onceyouknowwhattolookfor,bonkingisnotlimitedtojustcompetitionathletes.As impliedabove,peopleonenergyrestricted, ‘balanced’(i.e.,nonketogenic) diets are quite prone to hitting the wall. And this is notlimited to people doing intense exercise while on a diet.What do youthinkmighthappentoyouontheabove1200kcal50%carbdiet ifyouhave an egg, one slice of toast (70 kcal), and unsweetened coffee forbreakfast, and then a green salad and diet soda for lunch (i.e., saving500 kcal of your allotted dietary carbohydrates for supper). At 3 in theafternoon, even if youhavebeen sitting quietly at a desk, it is now20hours since your last substantialmeal.What’s yourbrain lookingat forfuel?Nada.

Butbecausethisishappeningwhenyourenergyexpenditureis80kcal/hr (not 800 kcal/hr for the competing athlete), the whole process issloweddown. First the intrusive thoughts of foodmay last for an hour,thenyouranxietyandshakescomeongraduallyoverthenexthalfhour.Inthissetting,onlythemoststalwartpersonholdsoutagainsttheurgetoeat. If you talk to people who’ve been on a rigid ‘balanced’ diet (orperhapsrememberyourownexperience),thisisnotatallanuncommonevent. But if the same person restricts carbohydrate to less than 50gramsperdayforaweekortwo,raisingketonesabove1mM,bonkingdisappears–whethertherapidonsetversionduringexerciseortheslowversionat3intheafternoon.

Andafinalnoteaboutindividualvariationandbonking.Ideallyeveryoneon a weight loss diet would not make any carbohydrate into fat (theprocessoflipogenesisdescribedearlier).Itstandstoreasonthatnoneofthe limitedandpreciouscarbohydrate intakeneeded to feedyourbrainwouldbe“wasted”thisway.However,themultiplegenesthatcontrolthisprocess havemany known variants (aka polymorphisms) and thus aresubjecttoindividualvariabilityinresponsetonutritionalsignals.

The current scientific consensus is that lipogenesis in humans isinconsequential unless they are being overfed with masses ofcarbohydrate.Andcertainlylipogenesisshouldbeshutdownduringanyweightlossdietwhenenergyintakeisrestricted.Howeverwhenwe(DrsPhinney and Volek) looked for specific fatty acids produced bylipogenesis in people on low and high carb weight loss and weightmaintenance diets with similar total energy contents, we saw bigdifferences,notonlybetweenthediets,butalsobetween individualsonthe same diet[29, 30]. This implies that there is considerable inter-individualvariation in thedegreetowhichenergyrestrictionsuppresseslipogenesis. And if you are the unlucky person who still “leaks” somecarbohydrate into the lipogenesis pathway during an energy-restricted‘balanced’diet,your toleranceandhencesuccessona“balanced”highcarbweight loss dietwill be impaired. This process, and themetabolicadvantage associated with being ketoadapted, is further explained inChapters9and11.

For the record, the idea that lipogenesis is of any physiologicalimportanceduringaweightlossdietisatbesta“contrarian”position.Andone might reasonably ask if any of the lipogenic enzymes have beenidentifiedas“obesitygenes”.But theeasily identifiedobesitygenesarethose thathaveastronganddirecteffecton food intake.However, thelipogenic pathway has a number of genes that make a number ofenzymes,andasinglegeneeffecton food intakewill besubtleexceptunderspecificdietarycircumstances.Thusanyoneofthemisunlikelytostand out as an obesity gene using current methods of study, but incombinationtheymaystillhaveasignificanteffect.Energy, Oxygen Consumption, and Respiratory Quotient (RER orRQ)

Atanumberofpoints in this text,we talkabout ratesofhumanenergyuseandthemixoffuelsbeingburned.Itishelpfultounderstandhowthisis measured, particularly if you want to read and be able to critiqueongoingresearchonhumanenergymetabolism.

Themostdirectmethodistomeasurehumanheatproduction.Thishas

beendoneforoveracentury,buteventhemostmoderntechniquesarecumbersome,andtheysaynothingabout themixof fuelsbeingburned(justtotalkcal).

The most common current method is to measure a person’s oxygenconsumption, and along with this, CO2 production as well. Becausecarbohydrates, fats, and the carbon backbones of amino acids are allburned to CO2 and water via the consumption of oxygen, this indirectmethod(calledindirectcalorimetry)effectivelymeasuresaperson’stotalenergyconsumption.

Inaddition,theratiosofCO2producedrelativetooxygenconsumedaredifferent for these three major nutrients. This ratio, the volume ofCO2 output divided by oxygen intake (VCO2/VO2) is 1.0 forcarbohydrates,0.70forfat(triglyceride),andabout0.85forprotein.Thisratioiscalledtherespiratoryquotient(ifcorrectedforproteinoxidation)orrespiratoryexchangeratioifwejustusetherawnumber,ignoringproteinmetabolism. But because protein burns at 0.85, right in the middle,correctingforittendstochangetheresultslittleifatall.Thusyou’lloftenseeRQandRERusedinterchangeably.

Auseful ruleof thumb to remember is thata literofoxygenconsumedproduces about 5 kcal ofmetabolic energy. So a person sitting quietlyreading this chapter with an energy expenditure of 1 kcal/min isconsumingabout200ccofelementaloxygenperminute(1 liter÷5). Ifhe or she had a bagel and orange juice for breakfast,most fuel beingburnedisglucose,sotheRQwouldbe~1andCO2productionwouldbeabout thesame–200cc/min.However, if thatpersonwere followingavery low carbohydrate ketogenic diet, O2 consumption would be thesamebutCO2productionwouldbealotless,about140cc/min(i.e.,anRQof0.70isindicativeofvirtuallypurefatoxidation).Weight,WeightVariation,andBMI

Theothersetofassessmenttoolsdeservingofcommentarethoseusedtodetermineweightandbodycomposition.Althoughmodernscalesaregenerallyconsistentandevenprettyaccurate,theysufferfromnotbeing

able to differentiate water from muscle from fat. This is particularlyimportantfortheindividualtryingtocharther/hiscourseonaweightlossdietbecausehumansdonotregulatetheirbodywatercontentprecisely.Soifa70kgadulttypicallycontainsanaverageof42litersofwater,overthe course of a day that person’s body does not care if it contains 41litersasopposedto43litersofwater.Above43liters,thekidneysspeedtheir functionandclear theexcess fluid,whereasbelow41 liters, thirstpromptsustoincreaseourwaterintake.Theresultisthatmostpeople’sweight varies randomlyacrossa rangeequivalent to2 litersofwater–about4pounds.

Whenhumans cut back in calories, they tend to loseweight quickly atfirst.Someofthisiswaterweightduetoreducedglycogenreserves(thebodystores3-4gramsofwateralongwitheachgramofglycogen).Butthenifallsubsequentweightlosscomesfromfat,anda500kcalperdaydeficit results in a pound per week rate of loss (assuming a pound ofadipose tissue contains 3500 kcal), this weight variability within a 4poundrangecanleadtoagreatdealoffrustrationandmisunderstandingfor the individual. This 4 pound range in weight variability couldcompletelymaskfourweeksofexcellentdietadherenceat1poundperweek of body fat loss. And any clinician who has worked with dietingsubjects has seen individuals who are clearly sticking to much morestringentdietsplateau forup to2weeksand thenabruptlyshowa5 lbweightloss.Obviously,thiscanbeexplainedbytheunpredictableshiftsin body water content. Bottom line: the standard scale is a lousyshorttermtoolformonitoringyourdietprogress(orsomebodyelse’sdietadherence).

Arelativelyrecenttoolisthescaleordevicethatmeasuresweightaswellas theperson’selectrical impedance. It is tempting to think thatwecanbeaccuratelyinformedabouttotalweightandtotalbodyfatcontentinasinglemeasure.Whilethesedevicesareusefulforassessingchangesinthe average body composition when a large group of subjects arestudied, the repetition variability for a given subject under differingconditionsof temperature,hydration,andevenemotionalstressmakeitquestionableforindividualsasaclinicaltool.

Summary

Adults can vary tremendously in body composition, ranging from 5%body fat at oneextreme to50%at theother. Leanbodymass (proteincontaining tissue)alsovarieswithheight,gender,andphysical training,butnotacrossaswideaspectrumasbodyfat.

Comparedtofatandprotein,anadult’scarbohydratereservesareminor(rangingfromafewhundredto2000kcalatmost)anddon’tchangethatmuch except after extremes of exercise or food intake. When dietarycarbohydrate is restricted, tissue glycogen levels decline but do not goextremely lowdue tocompensatoryshifts inwholebody fueluseawayfromglucosetowardsfattyacidsandketones.

This adaptation to carbohydrate restriction is facilitated by sharplyreduced insulin levels and takes a fewweeks to be fully implemented.Onceketoadapted,thebodycanmaintainitsleantissuecompositiononamoderateproteinintakeandsustainprolongedphysicalexertionusingfatasitspredominantenergysupply.

Chapter7

INSULINRESISTANCE

Introduction

Perhapsthemostimportantphysiologicstepforwardinlowcarbohydratedietresearchwillcomewhenweunderstandtheintimatedetailsofhowinsulinworksinthehumanbodyandhow/whynormalinsulinactiongoesawryinsomeindividuals.Yes,that’sright–wearetalkingaboutafutureeventhere.

WhenDr.FrederickBanting(adifferentBanting,nottheundertakerwhowrote the diet pamphlet) discovered insulin in 1922, for which he wasawardedaNobelPrizeoneyearlater,mostpeoplewouldhaveguessedthatwe’dhave figuredouthow insulinworkswithina fewdecades.Soyes, we do know that insulin binds to a receptor at the muscle cellsurface,allowingglucosetobetransportedacrossthecellmembranetobeused for energyor to replacedepletedglycogen levels.Without theactionofthoseglucosetransportersbeingturnedonbyinsulin,glucoseisstuck floating around in the fluid outside of our cells. And in fat cells,stimulating the same receptor shuts off fat release and promotes fattyaciduptake,triglyceridesynthesis,andfatstorage.

But a big speed-bump in our understanding of how insulin worksoccurred in the 1930s, when scientists began observing that somepeoplewithhighbloodinsulinlevelsseemedtobeoblivioustoitssignal.Thus was born the concept of insulin resistance, broadly defined as adiminished ability of insulin to exert its normal biologic effect on a cell.Andtoday,morethan7decadeslater,westilldon’tfullyunderstandthemechanismof insulin resistance–whysomepeoples’musclecells justseemtothumbtheirnosesatthatbigdoghormonediscoveredwaybackin1922.

Itisnotthatwe’vefailedinthistaskforalackoftrying.Asofthiswriting,

a PubMed search on “insulin resistance” yields 57,905 citations.Hundreds of auspicious careers have been built upon the quest tounderstandthemechanismofinsulinresistance.

So why is this important? And why waste lots of paper on a chapterwhose conclusion hasn’t been written yet? For one, there are severalhundredmillionpeopleintheworldwiththiscondition.Insulinresistanceoccurs on a continuum, so it’s a little difficult to pin down the exactprevalence,butconservativeestimatesarethatabout1in4adultsintheU.S. are insulin resistant. As with most prevalent metabolic diseases,drug companies have feverishly worked to develop pills to target theproblem,butevensomeofthenewerones(e.g.,thethiazolidinediones)asaclassarerunningintosafetyproblems.

Theprimaryreasonwehaveanentirechapteraboutinsulinresistanceisthat wellformulated low carbohydrate diets consistently make it better.Thisbenefit isn’t limited to just theearlyphaseofa lowcarbdietwhenenergy intake is reduced. The improved insulin sensitivity persists formonths and years into carbohydrate restriction when weight loss hasceasedandmostofanindividual’sdietaryenergyiscomingfromfat.Butifyouasktheaverageconsensusexpertwhatincreasingdietaryfatdoestoinsulinsensitivity,s/he’lltellyouitgetsworse.

Wait a minute, you say. You tell me that low carb diets make insulinresistancegetbetter,but thenyou tellme theexpertssay thathigh fatdietsmakeitworse.Howdoesthismakesense?Areyouguysprescient,orareyoujustonemoresetofcharlatanssellingsnakeoil?

Answer:wearescientiststryingtofigureouthowthehumanbodyworks.Andsciencecan’tadvance ifwearen’t readyto testoutnewideasandpromptly accept those that are proven towork. But part of the answermaylieinthefactthatmostconsensusexpertsconsidera“highfatdiet”to be onewith 45-60%of energy as fat,whereasweuse this term fordietsproviding65-85%asfat.Withinourrange,awellformulateddiet isalmostalwaysketogenic,butnotsointheirs.ThisbringsusbacktoouranalogyofthatuncertainvacationertakingaflighthalfwayfromCaliforniatoHawaii rather than committing to thewhole trip.Drifting in a lifeboathalfwaythere isnothing likebaskingonthebeachatWaikiki.Thusthat

vast body of published research using “high fat diets” in the 45-60%rangeforfatintaketellsusnothingaboutwhathappensduringnutritionalketosis.Formoreonthistopic,seeChapter12.

TheBiologyofInsulinResistanceRemainsUnknown

The insulin receptor was discovered in 1969, but its 3-dimensionalstructurewasnotdescribeduntil2006.Downstreamofthatreceptorareany number of intracellular structural pieces – like multiple rows ofdominoslinedupandreadytotopplewheninsulinbindstotheoutsideofthecell.Manyof theseobjects (madeofproteinsandcodedbygenes)havebeenoptimisticallypromotedasthecauseofinsulinresistance,buttonoavail.Noneofthemalonecanfullyexplainthephenomenonofthebodyignoringinsulin’ssignal.

Part of this problem lies with how we do ‘science’. The paradigm of‘modernscience’ is thatwe isolateeach individual factorandstudy it inisolation.Thisisthe‘reductionist’approachtodiscoveringscientifictruth.This is straight forward and relatively easy to do, so lots of scientistsswearbyit.Butwhatifaclinicalproblemlikeinsulinresistanceisnotduetoasingledomino,butratheranumberofdysfunctionalproteinsorotherstructuralmaterialsincombination?

Theanswer – the reductionist approach can’t deliver ananswer in thissituation.Ifmultiplestepsinapathway,workinginvaryingcombinations,eventually compromise thatpathway’saction, the reductionistparadigmfails. But if one takes a more holistic or cosmopolitan approach toassessing the problem, the cause of the problem might be betterappreciated.Therestofthischapterwillofferwhatwethinkisacrediblescenario that explainswhyandhow insulin resistancegets better onalowcarbohydratediet.

CarbohydrateIncreasesInsulin

The primary stimulator of insulin release from the pancreas is dietarycarbohydrate. Incontrast,anequalamountofdietaryenergyas fathasvirtually no effect on insulin levels. This may be obvious for educatedindividuals trained in nutrition andmedicine, but it’sworth emphasizing

because it provides a theoretical construct for why a low carbohydratedietworkswell inpeoplewith insulin resistance. Ifyouconsumeahighcarbohydrate diet, particularly onewith a lot of rapidly digested sugarsandrefinedstarches,yourbodyhasanincreaseddependencyoninsulintomaintainnormalmetabolichomeostasis.

Specifically, the insulin released after a high carbohydrate meal isnecessary to simultaneously inhibit glucose output from the liver andpromoteglucoseuptakebyskeletalmuscle.Failureofinsulintoperformeither of these tasks, such as occurs in insulin resistance, will lead toelevated blood sugar (hyperglycemia). What this means is that whencarbohydrateintakeishighitputsanincreasedpressureoninsulintodoits job effectively. If you’re insulin sensitive, great - you can probablytolerate lots of carbohydrate and not run into metabolic problems.However, if insulin is struggling to perform its duties, increasedconsumptionofcarbohydratejustexacerbatesanalreadybrokensystem.

Alowcarbohydratedietswitchesthebody’sfuelusetoprimarilyfat.Withthat switch turned on, there’s less need to regulate hepatic glucoseoutput and markedly reduced surges in insulin release and glucoseuptake.Thus,alowcarbohydratedietallowslessdependenceoninsulinto maintain metabolic health. Stated another way, if we view insulinresistanceasaconditionofcarbohydrateintolerance,dealingwithdietarycarbs becomes a burden, and reducing this burden allows the body tofunctionmorenormally.

HowisInsulinResistanceMeasured?

Thereareanumberofmethodsusedtoassessthebody’sresponsetoinsulin,butthedefinitivemethodiscalledaninsulinclamp.Thisinvolvesinsertingmultiple intravenous lines into theperson, infusing insulinataconstantrate,andthenmeasuringhowmuchglucosehastobeinfusedtokeeptheperson’sbloodsugarconstantwithinthenormalrange.Thefasteroneneedsto infuseglucose, themoresensitive thatperson is tothefixeddoseof insulinbeing infused.Theproblemwiththismethod isthat it iscomplex,time-consuming, invasive,andputsthepersonatriskoflowbloodsugar(hypoglycemia)ifenoughsugarisn’tpromptlyinfusedwhen needed to counteract the insulin. It is also just a measure of

insulin’s effects on glucose metabolism. Insulin also has an array ofeffectsinothertissues(seeChapter14).

Amuchsimplermethodistosimultaneouslymeasurebloodglucoseandbloodinsulinlevelsandthenestimateinsulinsensitivityusinganequationbaseduponinsulinclampdata.Forexample,oneofthefirstmethodstoestimateinsulinresistancepublishedin1985wascalledthehomeostaticmodelassessment(HOMA)[31].Itiscalculatedastheproductoffastingbloodglucosexfastbloodinsulindividedby22.5.Highervaluesindicateinsulin resistance and lower values insulin sensitivity. Although thesecalculations of insulin sensitivity (or resistance) are just estimates, inmostcasestheircorrelationwiththeclampdataisreasonablygood(e.g.,r=0.8). While this leaves a degree of uncertainty when testing anindividual, itprovidesamuchmorerobustmeasurewhenassessingtheresponseofagroupofsubjectstoachangeindiet.

InsulinResistanceisaHallmarkofMetabolicSyndromeandType-2Diabetes

Whendiabeteswasfirstcharacterizedasadiseaseacoupleofcenturiesago, thediagnosiswasbasedon theappearanceofsugar in theurine.Thisoccursonlywhenthebloodsugarlevelgetssohighthatthekidneyscan’trecoverallofthefilteredglucose,lettingsomeofitescapeintotheurine.Thendoctorsstartedmeasuringsugarlevelsintheblood,allowingearlierdiagnosis.Butonlywhen the firstbio-assaysof insulin (followedbymodernradioimmunoassayorRIA)cameavailablecouldthevariableresponseofthebodytoinsulinbeassessed.

An interesting historical note is that the publication of the first RIA ofplasma insulin by Drs. Solomon Berson and Rosalyn Yalow in 1960marked a revolution in biology and medicine eventually leading to aNobelPrize in1977.Theydistinguished twogeneral typesofdiabetes:oneaninsulindeficientstateandtheotherassociatedwithoverproductionofinsulin.

Of the twogeneral formsof diabetes, the clinicallymoredramatic formoccurs when the pancreas fails to make insulin. Originally calledchildhood onset diabetes (because it was seen most commonly in

children), thispredominantlyauto-immunedisorder isnowcalled type-1diabetes.Thesepatientsneedinsulin injectionsnot just tocontrolbloodglucose levels, but also to regulate the release of fats from fat cells.Whenfatcellsreleasefattyacidstoorapidly,ketoneproductionbecomesimbalancedandthisleadstodiabeticketoacidosis.Thusketoacidosisischaracteristicoftype-1diabetes,oroflate-stagetype-2diabetesthathasprogressed to the point that the pancreas can no longer produce theminimal amount of insulin required to limit fatty acid release from thebody’sfatcells.

Bycontrast, inmost type-2diabetics, thepancreasproducesmorethannormalamountsof insulinbecause themusclecells (whichaccount formost of our bodies’ insulin-stimulated glucose clearance) havebecomeresistant to its signal. Typically, type-2 diabetics don’t develop diabeticketoacidosis, perhaps because their fat cells retain some of theirresponsetoinsulin.Thisinturnhelpsexplainwhymosttype-2diabeticsare overweight or obese, because their fat cells are constantlymaintainedinstoragemodebytheirhighlevelsofinsulin.

But insulin resistance does not develop suddenly, making yesterday’snormalpersonintotoday’stype-2diabetic.Itisaslowandusuallysilentprocessoccurringoveryearsordecades.Asinsulinresistancedevelops,a number of physical and biochemical changes occur. The liver turnsmorebloodsugar intofat,soserumtriglyceridesgoup.Fatcellsspendmoretimeinstoragemode,soweightgainoccurs,particularlyaroundthecenter of the body, including inside the abdomen. Blood pressure alsotendstoriseabovenormal,andgood(HDL)cholesterollevelsgodown.This combination of signs has been labeled ‘metabolic syndrome’, andsome doctors call it pre-diabetes because a high proportion of peoplewith 3 or more of these signs eventually develop full-blown type-2diabetes.Formoreonmetabolicsyndrome,seeChapter14.

Even before the signs of metabolic syndrome occur, the cleverdoctor/detective can spot clues of impending diabetes. Before bloodglucose and insulin start to rise; before serum triglycerides go up andHDL cholesterol goes down; before waistlines start to expand; twobiomarkersof imminent troublehavebeendiscovered.The first,a fattyacidcalledpalmitoleicacid(POA),startstoriseinbloodlipids,anditisa

signof increasedconversionofcarbohydrate into fat.POAisdiscussedindetailinChapter9andalsoinChapter11.Atthispoint,sufficeittosaythatanelevatedlevelofPOAinthebloodisanearlysignthatone’sbodyis struggling to handle whatever dose of carbohydrate is beingconsumed.

Thesecondearlyharbingerofmetabolicsyndromeand type-2diabetesis a locus of factors that we lump together under the heading‘inflammation’.Inflammationispartofwhatwesometimescall‘immunity’or‘hostdefense’.Itisthatcomplexmixoffunctionsthatourbodiesusetodefend against foreign substances and infections, and also how itstimulates thehealingprocessafter injury.Wewant inflammation levelstosurgequicklywhenthereisathreat,andretreat justasquicklywhenthethreatispast.

About 20 years ago, it was noted that people with persistently highbiomarkersofinflammation(e.g.,CRPandIL-6)wereatincreasedriskofheart attack[32, 33]. And then ten years ago this observation wasextended to type-2 diabetes as well. This perspective has led us toregardinflammationasapotentialunderlyingcauseofinsulinresistanceandtype-2diabetes[34,35].Further,wenowhaveevidencethat insulinisassociatedwithinflammation[36,37],settingupaviciouscyclefueledbyrepeatedingestionofinsulininducingcarbohydrates.

Sincetheprimaryfactorthatdrivesseruminsulinisdietarycarbohydrate,this in turn raises the controversial possibility that dietary carbohydrateintake drives both inflammation and high blood insulin levels, both ofwhich in turn promote insulin resistance. Does it work this way ineverybody?Ofcoursenot,becauseweknowthattheotherkeyvariableisgenetics.Butwehavejustbeguntoscratchthesurfaceofwhichgenes(or gene combinations) predispose people to become ‘carbohydrateintolerant’.

Dietary Carbohydrate and Its Insulin Response as Stressors ofOxidativeMetabolism

Thisisgettingprettyesoteric,sowe’llkeepthissectionshort.Thatsaid,however, there are some pretty interesting dots to connect here.

Inflammationcausesourcells(specificallyourmitochondria)toincreaseproductionofmoleculescalled ‘freeradicals’.Freeradicalsare likeminiroadsidebombsthatinterferewithnormalcellularfunctions.Soherearethedotswethinkcanbeconnected:1)dietarycarbohydrateraisesseruminsulin; 2) insulin promotes inflammation in susceptible people; 3)inflammation increases cellular free radical generation; 4) free radicalsattackanyconvenientnearbytarget;5)idealtargetsforfreeradicalsaremembranepolyunsaturated fats; 6)membranepolyunsaturated fatsareimportantdeterminantsofcellularfunctionsuchasinsulinsensitivity.

MembranePolyunsaturatedFattyAcidsandInsulinSensitivity

In 1993, the New England Journal of Medicine published a studydemonstrating that highly unsaturated fatty acids (HUFA; e.g.,arachidonate and docosahexaenoate [DHA]) in muscle membranephospholipids are tightly correlated with insulin sensitivity[38].Specifically, thismeans that themore of theseHUFAs there are in themuscle membrane, the more insulin sensitive the muscle. Thisobservation subsequently has been corroborated and extended bymultiple other studies. For example the significant correlation betweenmuscle HUFA and insulin sensitivity was shown to be specific to thephosphatidylcholinephospholipidswhichpredominateontheouter layerofthemusclemembrane[39].Thisisinterestingfromtheperspectivethatit implies a role for the background fatty acid composition of themembrane per se, rather than the protein components inserted into it(likeinsulinreceptorsorglucosetransporters).Inotherwords,figurativelyspeaking,whatthe‘fabric’ofthewallitselfismadeofisveryimportantforglucose transport – it’s not just about the number of switches (i.e.receptorsandtransporters)insertedinthewall.

HowtheseHUFAsgetintomusclemembranesisaverycomplexprocessinvolvingbothdietcompositionandmetabolismof thevariousessentialfatsaftertheyareeaten.ThisprocessisdiscussedindetailinChapter9.For the purposes of this chapter, both dietary intakes of either theessential fatty acid precursors or their final products are important.However, there is increasing evidence that some individuals haveimpairedabilitytoconvertessentialfattyacidprecursorsintoHUFA[40].

Asa rule,HUFAareabit lessprone tobeburned for fuel thanshorterfattyacids,soonaveragethebodytendstohangontothem.Butthereisanotherwaythattheycanbedestroyedbesidesbeingbeta-oxidized(i.e.,burned for energy). As mentioned above, HUFA have lots of doublebonds,andthismakesthemverysusceptibletodamagebyoxygenfreeradicals(alsocalledreactiveoxygenspeciesorROS).Thepotentialroleof oxidative stress degrading membrane HUFA and thus promotinginsulinresistancehasyettobefullyexplored,butitmaybeveryrelevanttothischapter.Here’swhy.

LowCarbohydrateDietsandMembraneHUFA

Twenty years ago,wepublished a couple of studies showing that verylow calorie ketogenic diets raised the HUFA content in serumphospholipids(thebuildingblocksformembranes)[41,42].Thesubjectsforthesestudiesstartedoutprettyheavyandlostalotofweightoveranumber of months. But after the weight loss diet was over, they wentbacktoconsumingmorecarbohydrate,andtheirHUFAlevelswentbackdown.Thisoccurredinspiteofthemajorweightloss,soit lookedmorelikeadieteffectthananobesityeffectperse.

Recently,wehaveperformed twomore studies, one inpeopleafter 12weeksonalowcarbohydrate,highfatdietthatcausedamodestweightloss[29],andthesecondonpeoplefedalowcarbohydrate,highfatdietwith sufficient calories to hold their weight stable[30]. In both cases,serum phospholipid HUFA went up when dietary carbohydrate wasrestricted.Andalsoinbothcases,thepatternoffattyacidsintheblooddidnotindicatethattheirmetabolismwasmakingmoreoftheHUFA–ifanything, it indicated that they were making less as evidenced byconsistentandmarkedreductionsinthemetabolicintermediatesintheirbiosyntheticpathway.

Inthefirststudy,thesubjectswereselectedbecausetheyhadmetabolicsyndrome,soasagroup,theyhadunderlinginsulinresistance.After12weeksofthelowcarbdiet,theirinsulinresistanceimprovedby55%,andthis occurred at the same time as their blood HUFA levels wereincreasing.Thisobservationdoesnotprove that the risingHUFA levelswereadirectcauseoftheimprovedinsulinsensitivity,butthisiscertainly

consistentwiththeobservationsofBorkmanetal[38].

LowCarbDietsReduceInflammation

Intheabovestudyofpeoplewithmetabolicsyndrome[29],wealsodidapanelof tests forbiomarkersof inflammation.Anddespite the relativelysmall size of the study group and the notorious variability of thesebiomarkers,everyoneofthe16indicatorsofinflammationwentdowninthe group on the low carbohydrate diet. Although some of thesereductionswerenotstatisticallysignificantwhenassessedseparately,theimportant observation is that they all went down. For that to happenpurelybychance,it’slikeflippingacoinandgettingheads16timesinarow(whichhasaprobabilityofhappeningoncein65,000tries).

More importantly, that study also included a randomized comparisongroupgivenalowfat,highcarbohydrateweightlossdiet,andcomparedto their results, the low carbohydrate group had significantly greaterreductions in6of the16 inflammatorymarkers. Incontrast,noneof themarkersweresignificantlylowerinthelowfatcomparedtothelowcarbgroup. In simple terms, what thismeans is that both energy restricteddietstendedtoreduceinflammationinpeoplewithmetabolicsyndrome,but that this effect was significantly greater with the low carbohydratediet.

Theseresultsareconsistentwithotherpublishedstudiescomparinglowcarbtolowfatdiets.Notalllowcarbdietstudieshaveshownsignificantreductions inbiomarkers likeCRPor IL-6,butmanyhave.Wesuspectthe variable results seen in other studies may be due to bothquestionablecompliancewiththeassigneddiet,plusthedietsnotbeinglowenoughincarbohydratetoachievetheseanti-inflammatoryeffects.

InsulinResistanceandDietSuccess

In2007,Gardneretalpublishedarandomized,controlledtrialcalledtheA-to-Z Study involving 4 diets lasting a year given to groups of obesewomen[43].Atoneendofthisdietspectrumwasthe‘Ornishdiet’whichisveryhigh incomplexcarbsandvery low in fat.At theotherendwasthe ‘Atkinsdiet’ (i.e., lowcarbohydrate).After 6months, thewomenon

Atkinshad lostsignificantlymoreweight,butafter12monthstheywerestill lowerbutnotsignificantlyso. Interestingly,bloodpressureandHDLcholesterolweresignificantlybetteronlowcarbohydratethananyoftheother diets, and this beneficial effect remained significant out to 12months.

After publishing this initial paper in JAMA, Dr. Gardner went back andexamined his data based upon the subjects’ insulin levels before theystarted dieting.When the women on each diet were divided into threesubgroups(tertiles)basedonbaselineinsulinresistance,theresultswerestriking.Inthelowcarbohydratedietgroup,weightlosswassimilarinthemost insulin sensitive (11.7 lbs) and insulin resistant (11.9 lbs)women.Howeverweightlosswiththehighcarbohydrate(Ornish)dietwasmuchgreaterintheinsulinsensitive(9.0lbs)thantheinsulinresistant(3.3lbs)women.

Thus the most insulin sensitive subgroups of women experienced asimilarweightlosswhenassigneddietseitherhigh(9.0lbs)orlow(11.7lbs)incarbohydrateIncontrast,thesubgroupsthatwereinsulinresistantfaredverypoorlywhenassignedadiethighincarbohydrate(3.3lbslost)compared to a low carbohydrate diet (11.9 lbs). Specifically, thosewomenwithinsulinresistancelostalmost4-timesasmuchweightwhendietarycarbohydrateswererestricted[44].

Simply put, insulin resistance strongly influences how we respond todifferent diets. This validates the concept that insulin resistance isessentiallyanexpressionofcarbohydrateintolerance.Dr.Gardner’sdataclearlydemonstratesthatratherthanforcinganinsulinresistantbodytodeal with a macronutrient it can’t handle well, this condition is besttreatedwithadietthatlimitscarbohydrate.

Why Do Many Experts Believe that High Fat Diets Cause InsulinResistance?

Therearetwogeneralexplanationsforcontrarydataonthispoint.Theyare 1) the definition of ‘high fat’, and 2) the duration of the diet beingtested.

The definition of a high fat diet in the scientific literature is remarkablybroad.Given the current demonizationof dietary fat, anydiet providingmorethan35%ofenergyasfatistypicallycalled‘highfat’.Furthermore,most studies of humans fed ‘high fat diets’ go no higher than 60% ofenergyas fat,whichmeans that thesesubjectsarestill gettingat least20-25% of their energy from carbohydrates. This is because theinvestigators either don’t think the subject can tolerate a lowercarbohydrate intake, or they don’t think going lower on the dietarycarbohydrates is safe. Of course, starting with Stefansson’s Bellevueexperiment,we’veknown for80years thatneitherof thesepositions isvalid.

What we do know is that, pretty consistently, as dietary fat percent isincreasedfrom30%to60%inanimalsandinhumans,insulinsensitivitydoes getworse.But once above 60%of energy as fat,which typicallytranslates to less than 20%of energy as carbohydrates (assuming 15-20%fromprotein),insulinresistanceturnsaroundandstartstoimprove.Sowhat’shappenedisthatthemainstreamconsensusdidstudiesofupto60%fat,sawwhatlookedlikeastraightline,andthenjustassumeditkeptongoinginabaddirection.Inaword,theyextrapolatedthemselvestoafalseconclusion.

Butifyoulookatwelldonestudiesathigherfatintakes,thisextrapolationdoesn’t stand the ‘red-face test’.Forexample, inDr.GuentherBoden’sstudy of type-2 diabetics, when they cut dietary carbohydrates to 20gramsperdayforjust2weeks,therewasadramaticreductionininsulinresistance as measured by the insulin clamp technique[45]. Similarly,insulin sensitivity was dramatically improved in Dr. Forsythe’s subjectswithmetabolicsyndromeassignedtothelowcarbdiet[29].

Theothervariable thatcanmisleadus to think thathigh fatdietsmakeinsulinresistanceworseisthedurationoftimeonthediet.Itisacommontheme throughout this book that it takes humans at least 2 weeks toadapt to a lowcarbohydratediet.Giving creditwhere credit is due,wecall this the ‘Schwatka imperative’.So if you readaboutastudywheresubjectswereonthetestdietforonlyafewdays(orsometimesjustonemeal!), disregard it. Whether the parameter you are interested in isexerciseperformance,disposalofsaturatedfats,orinsulinresistance,it

takes at least 2 weeks of adaptation before human metabolismaccuratelyreflectsthetruelong-termeffectsofthediet.

Thusahigh-fatdietisnotahigh-fatdietisnotahighfatdiet–thatistosaywhenyoureadorhearsomeonetalkabouthighfatdietsbesuretoqualify the level of carbohydrate and the period of adaptation, both ofwhichhaveimportanteffectsontheoutcome.

Summary

Westartedthischapterbytellingyouthattheunderlyingcauseofinsulinresistance is unknown, and we finished by pointing out that lowcarbohydrate diets make insulin resistance better, and that insulinresistant individuals achieve more weight loss on a low carb dietcomparedtoaverylowfatdiet.Clearlyagreatdealofsciencestillneedstobedonetoexplaintheseobservations.

Thatsaid,wehavealsoconnectedsomeveryinterestingdotsthatseemto be leading us in a consistent direction. Inflammation predicts thesubsequent development of metabolic syndrome and type-2 diabetes,and inflammation is the biologic enemy of the highly unsaturated fattyacids found in cell membranes. Reduced levels of these membraneHUFAs are associated with insulin resistance, and a low carbohydratediet simultaneously corrects the membrane HUFA deficit, improvesinsulinsensitivity,andreducesthebody’slevelofinflammation.

Does this prove that insulin resistance is caused bymembrane HUFAdegradation as a result of inflammation and oxidative stress? Notnecessarily,howeveritcertainlymakesforastronghypothesis.Butinthemeantime,giventhepotentbenefitofawellformulatedlowcarbohydratediet insomeonewith insulin resistance,plus itsverypositiveeffectsonblood lipids and fatty acids (described in the next 2 chapters), thispowerful tool should not be discounted based upon ill-foundedpresumption,culturalbias,orextrapolateddata.

Chapter8

LIPOPROTEINEFFECTS

Introduction

Ifyourbloodregistersahighlevelofcholesterol,that’sasurefirewaytoputmanyphysiciansintoDEFCONmode,i.e.,racingfortheirprescriptionpads. In the last decade, however, we have learned that there’smuchmoretothehearthealthpicturethantotalcholesterol.Andgiventhatthisnewperspectivefundamentallychangesourperspectiveonthepowerofdietaryinterventionstoreduceheartdisease,thischapterwillattempttoexplainthiscomplexpicturewithouttheusualover-simplification.

Themajorityofcholesterolcirculates inourbloodstreamas ‘lowdensitylipoprotein cholesterol’ (LDL-C),making it the prime target of drug andlifestylestrategiestopreventheartdisease.Whilethewidespreaduseofstatins (a class of drugs used to lower cholesterol by inhibiting itsproduction) has shown a certain degree of success in reducingcardiovascular risk, there is considerable uncertainty that cholesterolloweringperseistheprimarysourceofthisbenefit.Ithasbeenarguedthat other mechanisms independent of reducing LDL-C (e.g., anti-inflammatory effects) may account for much of the clinical efficacy ofstatin drugs[46]. And yet, despite this causal uncertainty, the proposedlink between blood cholesterol and heart disease has been the drivingforce behind dietary recommendations to restrict cholesterol andsaturatedfat.

But there’smore to this iceberg than itsobvious tip.Takenasawhole,dietary strategies to lower LDL-C have consistently failed to impactincidenceofheartdisease.Granted reducingcholesterol levels throughdietmaybeaneffectivestrategy forasubsetof thepopulation,a largenumberofpeoplegetnoreductionincardiovascularriskwhentheylowertheircholesterol.Ifyouhappentobesuchaperson,adietaimedattheLDL-C bull’s eye not only misses the mark, it’s actually aimed at the

wrongtargetaltogether.

LDLSupremacy

As thename implies, lipoproteins are spherical particles that consist ofvarying amounts of lipids (fat substances like cholesterol, triglycerides,phospholipids)andproteins.The lipidsolublepartsarepackagedinthecore,whereasthewater-solublecomponentsfacetheperiphery,therebyallowing lipoproteins to travel through the aqueous serum of thebloodstream delivering lipid cargo to and from cells. In simple terms,LDL-C(anditsprecursorvery-lowdensity-lipoproteincholesterol)deliverscholesterol and other lipid substances from the liver to other organsthroughout the body, whereas high-density lipoprotein (HDL-C) carrieslipids in the opposite direction back to the liver for disposal. ToomuchcholesterolcirculatingasLDL-Cmayleadtoaccumulationofcholesterolinthearterialwall,plaqueformation,andarterialdisease.

The assumed links between high blood cholesterol and heart diseaseand the cholesterol-raising effects of saturated fat gained momentumbetween1950and1970andhasbeentheimpetusbehinddietarypolicyfornearlyfourdecades.However,asexplainedbyGaryTaubesinGoodCalories,BadCalories[13], rather than growing stronger as newdatahas accumulated over the last 40 years, the diet-heart hypothesis stillstands on shaky ground. Much to the chagrin of the medicalestablishment and the rest of the herd defending the nutritionalconsensus,agrowingbodyofliteraturelinkinglowcarbohydratedietstoimproved lipid patterns has reached a critical mass. From a scientificperspective, the results are compelling. Nonetheless, the politicalsituationremainsthatifyoudaretopresentanalternativeviewopposingthetenetsofthemainstreamdiet-hearthypothesis,chancesareyou’llbebrandedaheretic.

Butbeforewegettothegoodstuff,weneedtodealwiththe800poundgorillaintheroom.

LDLResponsetoaLowCarbohydrateDiet

Plasma LDL-C responses to low carbohydrate diets can be variable in

magnitudeanddirection.Inwellcontrolledexperiments,theserumLDL-C level in response to a very low carbohydrate diet may increase,decreaseorstay thesame. Inside-by-sidecomparison to low fatdiets,LDL-C levels are usually higher in response to low carbohydratediets[47].Thisisoneofthefavoritetalkingpointsoflowcarbohydratedietcritics.

Themoreimportantquestionisshouldyoubeconcernedifyouareoneof the people who show an increase in LDL-C on a low carbohydratediet?Dependingwho you direct the question to, the answermay vary.Position statements and mainstream clinical guidelines recommendaction steps if your serum LDL-C level is above 100mg/dL. Formostphysicians,thatusuallymeansgivinglipservicetolifestylechangeslikediet andexercise, followedpromptlybyaprescription for a statindrug.But let’s takeaminuteandpeeloffa fewmore layersof theonionandconsider the more balanced perspective of LDL-C offered by theresearchofthelastdecade.

First, thepresumedcausal linkbetween‘total’LDL-Candheartdiseaseis tenuous. Cholesterol reductions induced by statin drugs may beassociatedwith reducedcardiovascular risk,butwhen it’sa low-fatdietthat lowersLDC-C,and it’s compared toahigher fatdiet, guesswhichdid a better job at lowering the REAL incidence of heart disease? In1994, theLyonDietHeartStudy [48]was terminatedprematurelyat27months due to a dramatic decrease in mortality in the group thatconsumeda40%fatMediterranean-typedietcompared toagroup thatwas prescribed the American Heart Association’s ‘prudent diet’. Thisdramatic difference in heart disease and overall mortality occurreddespitethefactthattherewerenodifferencesinthetwogroups’LDL-Cresponses to thediets.Evenmoreconvincing is the recent report fromtheWomen’s Health Initiative[49] showing that dietary fat restriction inthese postmenopausal women reduced LDL-C but had no effect oncardiovasculardisease(CVD)outcomes(heartattack,stroke,andoverallmortality)after8years.

Second, unless your serum LDL level was determined by the morelaboriousdirectassessmentmethod(chancesaretheywerenot),thereispotentiallyahighdegreeoferrorintheestimationofLDL-C(seesidebar

-CanYouTrustYourLDL-CNumbers?).

Third, it is now well accepted that what we call LDL-C is, in fact, acomplexmixture of lipoproteins consisting of particles varying across arange of sizes. Smaller LDL particles are more atherogenic (i.e.,dangerous) than larger ones. And here’s a key fact pertinent to thisdiscussion:lowcarbohydratedietsconsistentlyandsignificantlyincreaseLDL particle size irrespective of the response in LDL-C concentration.Compelling data now indicate that having more small LDL particles isassociatedwithincreasedriskforheartdisease[50].

Fourth, there is a good reason serum LDL-Cmay transiently increaseduringtherapidweightlossphaseofalowcarbohydratedietandithasnothingtodowiththetypicalatherogenictheoryofLDL-C(seeChapter13).

Circling back to the question, should you be concerned if your LDL-Cdoesnotgodown(orevenrisesslightly)onalowcarbohydratediet?Inthebigpicture,andparticularlyso forpeoplewithmetabolicsyndrome,LDL-C ismore smoke than fire. A small tomoderate increase in one’stotalLDL-Cisnotworrisomeifotherlipidandinflammatorymarkersaredramatically improved in response to reducing dietary carbs. If, forexample,yourserumtriglycerideswentwaydownonalowcarbohydratediet (which they almost always do) then chances are you have alsodecreased the smallermoredangerousLDLparticleseven if your totalLDL-Cconcentration increased.Andaswenote in thenext fewpages,another concurrent response to a low carbohydrate diet is increasedHDL-C,whichisapotentfactorassociatedwithreducedCVDrisk.CanYouTrustYourLDL-CNumbers?

The most common way LDL-C is determined is to estimate itsconcentrationusinga formuladerived fromdirectmeasurementof totalcholesterol, HDL-C, and triglycerides. The equation was developed in1972 by William Friedewald and colleagues[51] and continues to beroutinelyusedinclinicalassessmentofcardiovascularriskandresearchstudies, including those involving low carbohydrate diets. LDL-C iscalculatedastotalcholesterolminusthesumofHDL-CandVLDL-C.

LDL-C=TotalCholesterol–[HDL-C+(Triglycerides/5)]

A major assumption is that the ratio of triglyceride to cholesterol isconstant.VLDLisestimatedasequaltotriglycerides(mg/dL)dividedby5.Thispresumed5:1ratioisnotconstant,andtheerrorsfromthisLDL-Ccalculation are significant[52]. In the original 1972 paper, theseresearchers noted that the calculation of LDL-C was inaccurate whenchylomicronswerepresentortriglycerideswereabove400mg/dL.Theseessential limitations under conditions of high plasma triglycerides arewidely recognized today. Less appreciated are the potential errorsassociated with low plasma triglycerides, a condition that is highlyrelevantwheninterpretingtheLDL-Cresponsetolowcarbohydratedietssincetheyoftenresultinmarkedreductionsintriglycerides.

For example, a published case report describes a man with plasmatriglycerides of 55mg/dL who had an estimated LDL-C of 172mg/ dLusing the traditional Freidewald equation. But when measured by twoseparatedirectmethods,hisactualLDL-Cprovedtobe126mg/dL(thiswasalsosubstantiatedbyanormalapoBlevel)[53].Inaformalstudyof115volunteerswithplasmatriglycerideslessthan100mg/dL,useoftheFriedewaldformularesultedinastatisticallysignificantoverestimationofLDL-Cbyanaverageof12mg/dL[54].

How does this play out if you are on a low carbohydrate diet? Let’sassumethata lowcarbohydratedietcausesareductionof triglyceridesfrom200to75mg/dLwithnochangeintotalandHDLcholesterol.Asaresult, the calculated LDL-C from the Friedewald equation wouldnecessarily increase from 100 to 125 mg/dL. How much of this 25%increaseisrealandhowmuchartifact?ThatcanonlybedeterminedbyadirectassessmentofLDL-C,whichmostphysiciansdonotbothertodo.

TC HDL-C TG LDL-C

(calculated)LDL

(actual)

BeforeLowCarb 200 60 200 100 ??

Diet

AfterLowCarbDiet

200 60 75 125 ??

LDL-C:QualityOverQuantity

Most people nowhave the ‘LDL-C is bad andHDL-C is good’ conceptdownpat.Butthereismoretothestory.ItiswellestablishedthatnotallLDL particles are created equal. Moreover, certain types of LDL havebeen shown to correlate with abnormal lipid profiles and promoteatherosclerosis. As noted previously, the larger more buoyant LDLparticlesarelessharmfulthansmallerones.SmallLDLparticlesresideinthecirculationlonger,havegreatersusceptibilitytooxidativedamagebyfreeradicals,andmoreeasilypenetrate thearterialwall,contributing toatherosclerosis. Nomatter what your total LDL-C concentration, if youhaverelativelymoresmallparticles(referredtoasPatternB)itputsyouat a severalfold higher risk for heart disease compared to people withlargerLDLparticles(PatternA)[49].Andonceagain,thisisindependentofyourLDL-Cconcentration.

Howcanyoutell ifyou’repatternAorB,andhowmanysmallparticlesyouhavefloatingaround?Thisisnotasimpletestforyourdoctortodo,soit’snotroutinelyorderedbyphysicians,andthusitdoesn’tshowuponstandard lipid panels. The most common analytical methods use aprocess called gel electrophoresis, but new techniques are availablebased on nuclear magnetic resonance (LipoProfile Test fromLipoScience) and ultracentrifugation (VAP Cholesterol Test fromAtherotech).

In themean time, the ratioofyour triglyceride toHDL-C(TG/HDL-C) isaneffectivesurrogateforLDLparticlesize.ValuesofTG/HDL-Cover3.5indicate thatyouprobablyhavepatternBwithapredominanceofsmall

LDLparticles,andaratio thishigh indicates there’sagoodchanceyoumayalsohaveinsulinresistance[55].

StatinsandLowCarbohydrateDiets

Manyphysicians immediately turn tostatins ifapatient’sLDL-C level isabove standard guidelines, but the decision to begin lipid loweringtherapy deserves serious thought. Without question statins markedlylowerLDL-Cbuttheimpactondecreasingcoronaryeventsis lessclearcut.For instance, theoriginalLipidsResearchClinics(LRC)cholesterolloweringstudywithbindingresin(cholestyramine)reducedthenumberofheartattacksbutnotoverallmortality[16].Andarecentstudywithastatin(theJUPITERStudy)indicatesthatmuchofthebenefitwiththisclassofdrug is due to reduced inflammation rather than reduced LDL-C[46].Therefore,ifadietcouldreduceyourlevelofinflammation(discussedinChapter14),perhapsthere’slessneedforthedrug.

So in the big picture, the potential benefit of a statin drugneeds to beweighed against the risk of side effects and cost of medication. Thenumberofpeoplewhoexperienceadversesideeffects isnot trivial, themostcommonbeingfatigueandmusclepain,andmorerecentlythereisconcern with cognitive impairment and increased risk of diabetes.Furthermore, whether or not you make a personal or professionaldecisiontobeginstatintherapy,therearestilluniquebenefitsassociatedwith a low carbohydratediet (see sidebar –RestrictingCarbohydrateshasBenefitsBeyondStatins).RestrictingCarbohydrateshasBenefitsBeyondStatins

Statin therapy effectively lowers LDL-C, but if a patient presents withother risk factors the typical course of action is to prescribe additionaldrugs.Inthecaseofatherogenicdyslipidemia,combiningastatinwithafibrate and/or nicotinic acid is common. While this poly-pharmacyapproach can be effective in reducing lipid biomarkers, there is anincreased cost and greater likelihood of side effects withmultiple druguse.Importantly,incontrasttotheeffectofalowcarbohydratediet,noneofthelipidloweringdrugsareeffectiveatreliablyincreasingLDLparticle

size. Since a low carbohydrate diet does increase LDL-C size, itrepresents a fully rational approach to the management of Pattern Bdyslipidemia.Inaresearchstudythatiscurrentlypendingpublication,weexaminedtheeffectofimplementingalowcarbohydratedietonLDLsizeand other features of metabolic syndrome in previously hyperlipidemicmenandpostmenopausalwomenwhohadachievedaloweredLDL-Cbystatin treatment. After 6 weeks the low carbohydrate diet resulted insignificant improvements in a number of markers while maintainingpreviously reduced levels of LDL-C. LDL particle size was significantlyincreased as measured by two separate methods (gel electrophoresisand vertical auto profile ultracentrifugation). Additionally, there weresignificant improvements in plasma triglycerides (reduced by 36%),insulinsensitivity (increasedby25%),systolic (-5%)anddiastolic (-6%)bloodpressure,andbloodflowintheforearm.Insummary,atherogenicdyslipidemia and other metabolic syndrome markers are prevalent instatin users despite wellcontrolled LDL-C and the anti-inflammatoryeffectsof thisdrugclass.Thus theadditionofavery lowcarbohydratediet in combination with statin therapy can significantly improve insulinsensitivity,LDLquality,andotherfeaturesofmetabolicsyndrome.

Insummary, ifLDL-C isyoursole intended target,a low fatdietand/orcholesterol-lowering drugs appear tomake sense. But there is enoughdoubttoquestionwhetherLDL-Cisthebesttargetforeveryone.Ifyourtarget encompasses a broader range of potent biomarkers liketriglycerides,HDL-C,LDLparticlesize,insulinresistance,orinflammatorymarkers, then using a low fat/high-carbohydrate diet is equivalent todancing on the edge of amine field, whereas a low carbohydrate dietimprovesallthesebloodborneriskmarkers[56].

TriglycerideasaTarget

ThereductionistfocusontotalLDL-Castheonlyvalidtherapeutictargethasdistractedusfromthemountingevidencethatotherbiomarkersmaybebetterpredictorsofrisk,especiallyifyou(oryourpatient)haveinsulinresistance.IfLDL-Cisnotthemostrelevanttargetformanypeople,whatis? Many studies have reported that an elevated fasting plasma

triglyceride level is an independent risk factor for heart disease. If youhavehightriglyceridesafteranovernightfast,thereisagoodchanceyoualsohaveelevatedpostprandial lipemia(anexaggeratedandprolongedincreaseinplasmatriglyceridesafterameal).

Abnormal postprandial lipemia is the driving force behind thedyslipidemia of the atherogenic lipoprotein phenotype (ALP). ALP is aterm frequently used to describe a clustering of pro-atherogeniclipoprotein abnormalities including moderately increased fastingtriglycerides (150 to 500 mg/dL), exaggerated postprandial lipemia,decreased HDL-C (<40 mg/dL), and a predominance of atherogenicsmalldenseLDLparticles(patternB).

These lipid disorders have also been referred to as the ‘lipid triad’ or‘atherogenicdyslipidemia’.TheprevalenceofALPvariesdependingonthecriteriaused(i.e.,triglyceride,HDLlevel,orLDLsize).WhendefinedaspeakLDLparticlediameter<25.5nm,ALPhasbeenestimatedataprevalenceof30-35%inmiddle-agedmenintheUnitedStates.Sowhatmakeshavinghighpostprandialtriglyceridesharmful?Increasedhepatictriglycerideproductionprecipitates formationofhighlyatherogenicsmallLDLparticlesandareductioninHDLcholesterol,allofwhichindicateacausalroleforelevatedtriglyceridesinthepathogenesisandprogressionofheartdisease.

CarbohydrateistheMajorDriverofPlasmaTriglycerides

Anincreaseinfastingtriglyceridelevelsisanearlysignalthatyourbodyisstrugglingtometabolizecarbohydrate.Thereforetheweaponofchoiceformanagingelevatedtriglyceridelevelsiscarbohydraterestriction.Whyrestrictcarbsandnotfat?Mostpeoplehaveatotalofabout20grams(alittle more than 1 tablespoon) of extracellular glucose – 10 gramscirculatingintheirbloodandanother10gramsdiffusedintoextracellularfluid.Asinglemealfroma‘balanceddiet’caneasilycontainwellover100gramscarbohydrate,necessitatingamechanismtorapidlydisposeoftheincomingcarbohydrateinordertomaintainnormalbloodglucose.Intheresting statemuch of this glucose should be converted to glycogen inskeletal muscle and liver. However, these organs have a maximumstoragecapacityofabout400and100grams,respectively.

Inadditiontothis limitedcapacitytostorecarbohydrateinthebody,themetabolic conversion of glucose to glycogen (glycogen synthesis) isrelativelyslow,andinparticularitismarkedlyimpairedinindividualswithinsulin resistance.How thendoesapersonwith insulin resistancedealwith a high carbohydratemeal?Whereas the conversion of glucose toglycogen is self-limiting, there is an almost infinite capacity to convertcarbohydrate to fat (aka, de novo lipogenesis). The fatty acids derivedfrom carbohydrate-induced hepatic de novo lipogenesis are made intotriglycerides, packaged into large VLDL particles, which are thenreleasedintothecirculation,contributingtoelevatedplasmatriglycerides.Alternatively, if they are not released from the liver, these triglyceridescanbuilduptocausefattyliver(hepaticsteatosis).

CarbohydrateistheMajorDriverofLDLParticleSize

The formationof LDLparticles of varying sizes is intimately linkedwithtriglyceride metabolism in the liver. When viewed through metabolicbinoculars, it comes as no surprise that dietary carbohydrate has apredictableeffectonLDLsize.DietarycarbohydraterestrictionincreasestheprevalenceoflargerLDLparticles,whereaslowfat/highcarbohydratediets have the opposite (and overtly harmful) effect. This inverserelationship between dietary carbohydrate content and LDL size isevidentoverawide rangeof carbohydrate intakes[57],and it canhavequitedramatic(i.e.,positive)effectsatverylowcarbohydrateintakes[56].Aspeoplemovedownthecarbohydrateladder,moreandmoreofthemconverttheirserumlipidsfrompatternBtoPatternAandthusdecreasetheircardiovascularrisk.Andmovingupthecarbohydratecontinuumhasthe opposite effect. In carefully controlled feeding studies, low fat/high-carbohydratedietsdecreaseLDLparticlesize,causingsomeindividualstoshiftfrompatternAtopatternB[58,59].

TheTriglycerideSaturatedFatConnection

Anadditionalhighlyrelevantaspectofplasmatriglycerideisitsfattyacidcomposition.Bloodtriglyceridescontainingsaturatedfattyacidsaremorehighly correlated with insulin resistance than ones containing essentialfattyacids[60]. Inaddition,anumberofprospectiveandcase-controlled

studiesassociatehigherproportionsofsaturatedfatsinbloodlipidswithincreased coronary disease risk[61-63]. How does one come to havemoresaturatedfatintheirbloodlipids?Ifyousubscribetothesimplisticconcept that youarewhat youeat, then youmight believe that dietarysaturatedfatsaretoblameforinsulinresistanceandcoronarydisease.

However association does not prove causality. The alternativeexplanationisthataninsulinresistantliverreadilyconvertscarbohydratetofat(denovolipogenesis),andthemainproductofthispathwayisthesaturated fat palmitic acid (16:0). When stressed by excess dietarycarbohydrate, the liver secretes highly saturated triglyceride-rich VLDLparticles.Onceinthecirculation,theselargeVLDLarereadilyconvertedtosmallatherogenicLDLparticles.Havinga lotofsaturated fat inyourtriglycerides, therefore has little to do with your dietary saturated fatintake,butratherhowmuchcarbohydrateyoueatandhoweffectively(orineffectively)yourbodyprocessesit(seesidebarandalsoChapter9).DietaryCarbohydrate:SaturatedFat’sEvilTwin

Saturated fat in thedietgetsblamedfora lotofbad things. It turnsoutmost of the harmful effects attributed to dietary saturated fat (e.g.,increased heart disease, insulin resistance, vascular dysfunction, etc.)are unsubstantiated. The truth is that saturated fats only becomeproblematicwhentheyaccumulate.Andtheguiltypartyforsaturatedfataccumulation,inmostcases,isdietarycarbohydrate.

Yes;dietaryintakeofcarbohydrate-notsaturatedfat-isthemajordriverof plasma levels of saturated fat. Counter-intuitively, prior studies havereported lower plasma levels of saturated fat in response to diets thatcontained 2-3 fold greater intake of saturated fat but were lower incarbohydrate[29, 64, 65]. Even in controlled feeding studies in weightstable individuals (which necessitates a high intake of dietary fat), lowcarbohydratedietsdecreaseplasmasaturatedfatlevels[30].

Acautiousreadermightsuggestthatthesaturatedfatsarenotshowingup inour testsbecause theyare leaving thebloodandaccumulating intissuetriglycerides.Butwehavedonethisexperimentinmiceadaptedtoa low carbohydrate diet, and despite eating almost 3-times as much

saturated fatas thecontrolmice for8weeks, tissue levelsofsaturatesare the sameor lower in the lowcarbmice.Howcan thisbe?Clearly,humansandmiceadaptedtoalowcarbohydratedietbybecomingveryadeptatusingsaturated fatsas thepreferred fuel inmusclesand liver.Thus,fromthebody’sperspective,alowcarbohydratedietreducesbothbloodandtissuesaturatedfat levels irrespectiveofdietarysaturatedfatintake.

ImportanceofRaisingHDL-C

HDL-Cisoneofthebestbiomarkersoflongtermcardiovascularhealth.Unfortunately fordrugcompanies,however, it isa therapeutic target forwhich existing drugs have little efficacy. Low levels indicate significantcardiovascular risk independent of LDL-C. The importance of HDL-Cderives from its well established role as a scavenger of excessunesterifiedcholesterol from lipoproteinsand tissues requiring transportbacktotheliver(i.e.,reversecholesteroltransport).

HDL-C also increases bioavailability of nitric oxide (important to theregulationofvascularfunctionandbloodpressure)andhasantioxidant,anti-inflammatory,anti-thrombotic,andanti-apoptoticeffects,allofwhichcontributetoitsantiatherogenicproperties.Almostasconsistentastheirtriglyceride-loweringeffects, lowcarbohydratedietsincreaseHDL-C[47].The increase in HDL-C may not occur as quickly as the decrease intriglyceride,butbasedonempiricalevidenceandtheresultsofarecent2year diet study[66], this slowly developingHDL-C boost appears to beveryresilient.Anotablefeatureofthisstudywasthegradualincreaseincarbohydratesoverthe2yearinterventionwhichinthiscaseresultedina concomitant loss of the triglyceride-lowering benefit but a persistentbenefitinHDL-C.

Diet

DietIntervention

3mo 6mo 12mo

24mo

ChangeTriglyceride

LowCarb -35% -35% -28% -11%

LowFat -15% -20% -14% -12%

ChangeHDL-C

LowCarb 5% 13% 17% 17%

LowFat -1% 2% 9% 10%

Summaryoflipidresponses(percentchangefrombaseline[66]).

TheTriglyceride/HDLRatioasaCorrelatetoInsulinResistance

Inthesearchforlipoproteinmarkersthatcorrelatewithinsulinresistanceandpredisposition toCVD, recent researchhas focusedon the ratiooftriglyceride/HDL-C.Studiesindicatethetriglyceride/HDL-Cratioishighlyassociated with insulin resistance[55]. Simply put, the higher yourtriglycerides and/or the lower your HDL-C, the greater your degree ofinsulin resistance. This association was stronger than any other lipidparameterandwasequaltothatofthemoreconventionalmethodsusingfastingglucoseandinsulinsuchastheHomeostasisModelAssessmentof Insulin Resistance (HOMA-IR) and Quantitative Insulin SensitivityCheckIndex(QUICKI).TheratioiscomparabletotheATPIIIcriteriaformetabolic syndrome in predicting insulin resistance and even better inprediction of the LDLPatternB phenotype in two separate populationswhowereondifferentdiets.ATG/HDLratio33.5hasbeensuggestedasa cutoff for identifying the insulinresistant patient most at risk forcardiovasculardisease[55].

Summary

Thesyllogistic logic thatreducingdietarysaturatedfat intakedecreasesLDL-Cconcentration,which in turndecreasesheartdisease,hascomeunder severe scrutiny.There is a growing recognition that replacing fatwith carbohydrate has untoward negative effects on non-LDL lipidparameters, such as serum TG and HDL-C. We have examined thestrengthsandlimitationsofLDL-CwithitsPatternAandBvariants,HDL-C,and triglyceridesasbiomarkersof risk, andpointedout thedifferingeffects of low fat and low carbohydrate diets on each. The triglyceride/HDL ratio provides a broader assessment of risk, and its relationshipwithinsulinresistancemakesitfarsuperiortoLDL-C.

And how best to improve your triglyceride/HDL ratio? The strikingreductions inplasma triglyceridesandconsistent increases inHDL-C inresponsetolowcarbohydratedietsareunparalleledbyanyotherlifestyleintervention,orevendrug treatment,and therefore represents themostpowerful method to improve this ratio. These lipid parameters may bemore important targets as they reflect how efficiently the body isprocessingdietarycarbohydrateandthelevelof insulinresistance.ThisisdescribedingreaterdepthinChapter14.

Post-Script:TriglycerideMetabolismPrimer

Chemically, a triglyceride is composed of 3 molecules of fatty acidsbound to a glycerol backbone. Triglyceride is the major type of fatingested and stored in the body. Food containing triglycerides aredigested primarily in the small intestine and then re-esterified back totriglycerides and packaged into chylomicrons within intestinal cells.Chylomicronsenterthecirculationviathelymphaticsystem.Triglyceridesarealsomadeintheliverandpackagedintolipoproteinscalledverylowdensity lipoproteins (VLDL) that are released into the plasma.Chylomicrons and VLDL therefore constitute the triglyceride-richlipoproteins. The liver synthesizes apo-B-100 which associates withVLDL,whereasthe intestinesynthesizesanabbreviatedversionapo-B-48 that associateswith chylomicrons. The triglycerides in chylomicronsand VLDL are hydrolyzed by lipoprotein lipase (LPL) located in thecapillarywallsof various tissues,primarily skeletalmuscleandadiposetissue. The primary functions of LPL are to clear triglycerides from the

circulationandaugment thesupplyof free fattyacids tovarious tissuessuchasskeletalmuscle,adiposetissues,andheartforeitherstorageoroxidation. Both chylomicrons and VLDL contain apo-C-II, which isrequiredasacofactorforLPLactivity.Afternearlycompletehydrolysisofthetriglycerides,theremainingportionisreferredtoasachylomicronorVLDL remnant. These remnant lipoproteins are relatively rich incholesterol and cholesteryl esters and retain their apo-E and apo-Bproteins,howeverapo-Cistransferredtonascent(newlyformed)HDL-C.UptakeofchylomicronandVLDLremnantlipoproteinsoccursviaspecificreceptors on the liver which recognize apo-E and apo-B-100 proteins,respectively. Chylomicron remnants are taken up directly by the apo-Ereceptor,whereasVLDLremnantsarefirstconvertedintoanintermediatedensitylipoprotein(IDL),whichinturnmaybeeitherconvertedintoLDLorbetakenupbytheliverviatheapo-B-100/Ereceptor.

Chapter9

EFFECTSOFCARBOHYDRATERESTRICTIONONFATTYACIDMETABOLISM

Introduction

Partofthehumanbody’sadaptationtocarbohydraterestrictioninvolvesfundamental changes in how it metabolizes fatty acids. Of course itmakessensethatstoppingmostofyourdietarycarbohydrateintakewillforcethebodytospeedupitsrateoftotalfatoxidation.Butthere’smuchmoretothisstorythanthat.

Notonlydoestotalfatoxidationincrease,butthebody’srateofsaturatedfat oxidation accelerates more than other types of fatty acids, drivingdown levels of saturated fat in the blood. Also, the body literally stopsmakingfatoutofcarbohydrate(i.e.,denovolipogenesis),muchofwhichendsupassaturatedfatsintheblood.Understandingthatthishappensandwhyopensanimportantdoortoourunderstandingofhowahighfatdiet,evenonecontainingalotofsaturatedfat,canstillbehealthy.

Butperhapsequally(ifnotmore)importantisthedramaticchangeinhowour bodies handle polyunsaturated fats when we cut back oncarbohydrate intake. Polyunsaturates are obligate components ofphospholipids,whichinturnareneededtoconstructthemembranesthatencloseourcellsandregulatecellularfunctions.Gettingtherightamountof polyunsaturated fats into membranes is critical for life-definingprocessessuchasglucose transport (i.e., insulinsensitivity),controllinginflammation, salt excretion, blood pressure control, egg release fromovarianfollicles,andspermmotility.

DisposingofaMyth

We’veallheardthesaying“youarewhatyoueat”.Mothersandspouses

love to tell us this when we are eating something ‘bad’. Unfortunately,within the realms of dietetics andmedicine, this oft-repeated aphorismhas become synonymous with the truth. Why is this unfortunate?Becauseit’snottrue.

A typical lean,healthyhumaneats ten timesasmanycaloriesperyearass/hehasinbodyenergystores.Sooveradecade,thattranslatestoabout 99% of what we eat getting burned. And at many levels in theprocessesofdigestion,absorption,transport,storage,andoxidation,thebodyhasachoiceofwhatitsavesandwhatitburns.

So the trueaphorism is “youareonly that verysmall fraction that yourbodychoosestosavefromwhatyoueat”.

Whichmeans you caneatTwinkieswithout becomingone, or eat beefwithoutgrowinghorns.

Getting back to the topic of fatmetabolism, thismeans that your bodyhasaremarkableabilitytoselectwhatitwantstokeepwhileburningofftherest.Italsomeansthatyoucanselectivelystorespecificfattyacidsinspecificplaces.Thusthemixoffatsfoundinmembranephospholipidsisdramaticallydifferentfromthatfoundinthetriglyceridesstoredinadiposetissue.Andeventhemixoffattyacidsinouradiposetissuetriglyceridesvaries fromsite tosite.Forexample, the fatcomposition inyour legs isdifferentfromthemixfoundaroundyourabdomen[67].Sothenexttimeyouhearsomeoneargueapointbystating “youarewhatyoueat”,besuretotreatthatperson’sopinionwithahealthydoseofskepticism.

DisposingofSaturatedFats

Thereare three thingswecandowith saturated fatsobtained from,orproducedasa resultof,ourdiet:burn them,store them,ormake themintosomethingelse (e.g.,amonounsaturate). Insulin,whichgoesup inthe blood when we eat carbohydrates, turns off fat oxidation andstimulates fat storage. Andwhenwe stop eating lots of carbs and ourinsulin levels fall, the opposite happens; fats come out of storage andbecomethebody’sprimaryfuel.

Butwhathappensifyoueatmoretotalgramsofsaturatedfatwhenyou

stopeatingallthosecarbohydratecalories?Thiscomesdowntoanissueof balance.Which sidewins - the increased intakeof saturated fats ortheirincreasedoxidationintheketoadaptedindividual?Theanswerisnotobviousbecausewenowknowthatourmetabolismhasthecapabilitytodifferentiatebetween typesof fatbasedonchain lengthandnumberofdoublebonds.

Toanswerthisquestion,wetookbloodsamplesfromtwentypeopleafter12weeksonalowcarbohydratedietandanothertwentywhohadbeenfollowingalowfat,highcarbweightlossdiet[29].Intheserumfrombothgroups, we measured both total triglyceride and its specific fatty acidcomposition.Butbeforewetellyouwhatwefound,wealsoneedtotellyouthat thesaturatedfat intakeof the lowfatdietgroupwas12gramsperday,whilethelowcarbohydrategroupwaseating36gramsperday–threetimesasmuch.

Intheserumsamplesdoneatbaselineandagainafter12weeks,serumtriglyceridesinthelowfatgroupwentfrom187to151mgper100ml,atidy19%reduction.Butinthelowcarbgroup,thebeforeandaftervalueswere211and104,awhopping51%fall.Bothvisually(justlookingatthenumbers) and statistically, the low carbohydrate group had a muchgreater(better)reductioninserumtriglycerides.

But what about the fatty acids contained in this serum fraction? As aproportionofthetotal,thelowcarbgrouphad33%saturatesatbaselineand 29%after 12weeks,whereas the low fat group started at 30 andendedat29%.Soafter12weeksofdieting, theproportionofsaturatedfats in thebloodtriglycerideswasthesameforbothgroupsdespite thefact that the lowcarbgroupwaseating three timesasmanygramsperdayofsaturatedfatintheirdiet.

But there’s more. Because the low carb group ended up with bloodtriglyceridesof104mgper100mlcomparedtothelowfatgroup’s151,they actually had about 30% less total triglycerides circulating in theirserum. So although the two groups had similar relative proportions ofsaturates,thismeansthattheabsoluteserumcontentofsaturatesinthelowcarbgroupwas30%lower than the lowfatdietgroup.Sowhatwefound, inanutshell, is thatdespiteahigher intakeof saturated fat, the

proportionate blood level of saturated fats did not increase, and theirabsolutelevelsfelldramaticallywiththelowcarbohydratediet.

Now, it’s fair to ask, what about other parts of the body like the liver,muscles,and fat cells.Maybeall that saturated fat from thediet is justgetting tuckedawayanddoingbad thingssomewhereother than in theblood.Well,thatisn’tlikelygiventhelowinsulinlevelsassociatedwithalowcarbohydrate intake.But to check this issue in agroupof subjectsthat were willing to let us take pieces of their muscle, liver, and fat toexamine,weputsomemiceonthesetwodiets.

After8weeks,duringwhichthelowcarbmiceatetwoandahalftimesasmuch saturated fat, in 4 tissues examined, the triglyceride content ofsaturated fats was either the same (soleus muscle and liver) orsignificantlyreduced(gastrocnemiusmuscleandadiposetissue[akafatcells])inthelowcarbgroupcomparedtothelowfatgroup.

Thebottomlineonthispointisthatwhenourmetabolismadaptstoalowcarbohydrate diet, saturated fats becomea preferred fuel for the body,andtheirlevelsinbloodandtissuetriglyceridepoolsactuallydrop.Therearecurrentlyvalidquestionsbeingraisedaboutwhetherdietarysaturatedfat intake represents any health risk at all, even in people who eatmodetareamountsofdietarycarbohydrate.Butclearly,inthecontextofaketoadaptedindividualfollowingalowcarbohydratediet,wheresaturatedfatdisposalisacceleratedcausingbloodlevelstodrop,thereisnobasistobeconcernedabouttheirinclusioninthefoodswechoosetoeat.

MakingFatfromCarbohydrate-ThePOAStory

We humans have all of the cellular machinery needed to makecarbohydrates into fat,concentratedmostly in liverandfatcells.But forthe past 2 decades, the consensus experts have dictated that thisbecomes important in humans only when one’s intake of carbohydratecalories exceeds the body’s total rate of energy use. This position issupportedbyagreatdealofscientificdata,but itstandsuponly ifonemakesalotofassumptions.Oneofthoseassumptionsisthatmostofthefatmadebyourcellsremainsasthesaturatedfatpalmitate(16carbonswithnodoublebonds).Butwebelievethatassumptionisnotcorrect,and

here’swhy.

Fifteenyearsago,wedidastudyatUCDaviswherewefedagroupofwomenalltheirfoodfor4months.Forthatwholetime,eachpersonwasfed just enough total calories to keep her weight stable. But whatchangedoverthose4monthswasthatweprogressivelyreducedtheirfatintakefrom31%to25%,andthento15%.Ateachstep,whenwetookaway fat calories, we added an equal amount of carbohydrate whileholdingproteinintakeconstant.

And to keep the diet as healthy as possible, the added carbohydrateswere in the form of complex starches and grains, keeping total sugarintake as low as possible. In spite of this, serum triglycerides roseprogressively as the fat was removed from the diet[68]. And when welooked at the blood fatty acids, the proportion of palmitate and totalsaturates were significantly increased. But the biggest proportionatechange in any of the serum fatty acids was a monounsaturated 16-carbon fatty acid called palmitoleic acid (POA, technical abbreviation16:1w7[see Figure 2 Page 117]). Among fatty acids attached tocholesterol in the serum (called cholesteryl esters, orCE),POAalmostdoubledasdietaryfatwasreducedfrom31%to15%.

POA is what the body makes from palmitate using the enzyme SCD1(explained in post-script at end of chapter), and POA was clearlyidentified as amajor product of human lipogenesis in 1998[69]. In thatstudy,thesubjectswerefedmassivedosesofcarbohydrates.Butinourstudy at UC Davis, the subjects weren’t being overfed, so based onprevailingassumptionsaboutlipogenesis,theyweren’t“supposed”tobemakingmuchoftheirdietarycarbohydrateintofat.Butourtestsubjects,at a stable weight, did have progressively increased serum POA asdietaryfatwasreplacedbycarbohydrate.Andtobesurethiswasn’tjusthappening in the blood; we also took small bits of body fat using aneedle, and we found POA accumulating in their adipose tissuetriglyceridesaswell.

But what was most interesting about POA in these subjects was howmuchtheydifferedonefromanother.Afteramonthonthe31%fatdietwheneveryonehad beeneating exactly the same food, the serumCE

POA ranged from 2% to 6%. Threemonths later, after 6weeks eating15%fat,serumPOAnowrangedfrom3%to10%.Ofthe28subjectsinthestudy,twohadnochangeintheirCEPOAastheyatemoreandmorecarbohydrate in place of fat, but among the other 26, all of their POAvalueswentup.Andtheyseemedtodoitinparallel–thosewhostartedlow went upmodestly, whereas those who started high went upmorerapidly.Thisimpliesthatthereisalotofdiversityamonghealthyhumansin howmuch POA theymake (and perhaps total conversion of dietarycarbstofat)understandardizeddietaryconditions.AnditalsoindicatesthatwecanusePOAasabiomarkerforlipogenesis.

ThisconceptofPOAasabiomarkerofcarbconversiontofatwasfurtherreinforcedwhenwelookedatPOAinthesubjectsfromourrecentstudyof people put on a low carb diet for 12 weeks[29]. In addition to thesaturated fat data noted earlier in this chapter,we also looked atPOAlevels in their serum CE fraction. In this case, our baseline data wasobtained when they were eating 36% of their energy as fat, and thesecondsamplecameaftereating59%fromfat.Thesesamples,plusthehigh carb feeding study mentioned above, are presented together inFigure1.ThisshowsagainthattherewasmorediversityinPOAbetweensubjectsat36%thanat59%dietary fat,and that thegroupasawholecamedowndramaticallyatthehigherfatintake.

image

Figure1.Cholesterylesterpalmitoleicacid(akaCEPOA).Proportionexpressedaswt%versus%dietaryfatfromtwostudycohorts.

So what do we know about POA, and is it really important enough tojustifystruggling throughall thisdetail?Well, ithasbeenobserved thatserumPOApredicts thesubsequentdevelopmentof type-2diabetes. Intwopublishedstudies,peoplewithoutanyincreaseinbloodsugarlevelsbutincreasedPOAareathighriskofbecomingdiabeticlateron[70,71].Theconsensusexpertsdon’tseemtoknowwhythishappens,but fromour research perspective, it looks like increasedPOA levels are a signthat thebody ishavingdifficultygettingglucose intomusclecells tobeburned.Asanalternative,glucoseisdivertedtofatproductionintheliverjust to get rid of it, and this starts happening long before blood sugarlevelsrise.

Butsteppingbackjustabit,POAfunctionsabitlikeGalileo’stelescope.Ashewatched themoonsof Jupitergoaround thatbigplanet,Galileorealizedthat theEarthand itsmoonweresimilarlyrevolvingaroundthesun. So what’s the ‘eureka moment’ that comes from looking at POAlevels?Ifsomeapparentlyhealthypeopleeatingmorethan20%oftheirenergy from carbs make a lot of POA, and this increases as thecarbohydratedoseincreases,thenwho’sthe‘perp’inthiscrime?Hello?It’sallaboutthecarbs!

Aswenotedabove,POApredictsinsulinresistanceandtype2diabetes.Reducing carbohydrate reduces serumPOA levels. Peoplewith type 2diabeteswhorestrictcarbsgetbetterorevengointocompleteremission.But two individualsat thesame levelofcarb intakecandiffergreatly inhowmuchPOAtheymake,so itstandstoreasonthatdietsneedtobeadjustedtothetolerancesofeach individual.Forgetabout the ideathat“onedietisperfectforeveryone”.ThisissueisdiscussedingreaterdetailinChapter11.

Bottomline:POAisasensitive(andpowerful)biomarkerofcarbohydrateintolerance. Long before classic signs of diabetes (high blood sugar,elevated hemoglobin A1c) develop, POA goes up. This is a tool that

couldtelltheclinicianwhoisatriskwellbeforeotherindicators.Andoncethesepeopleareidentified,POAmightbeusedtoguideeachindividualto the right level of carbohydrate restriction to keep this problem inremission. Unfortunately POA is still a research test that is notstandardizedandavailabletoclinicalpractitioners,butwehopethistestwillbemadeavailableinthenearfuture.

The Polyunsaturated Fatty Acid Response to CarbohydrateRestriction

Most serious scientists avoid the topic of polyunsaturated fatty acid(PUFA)metabolismlikeaplague.Why?Becauseit’satangleofobscurenamesandsymbols,parallelmetabolicpathways,andpositionalisomerswithconflicting functions.Andbesides, therearesomanyof them! Inasingle serum fraction,we typically identifyabout20different fattyacidswith two or more double bonds (the definition of a polyunsaturate)belonging to 3 different metabolically distinct families (for details, seepost-scriptbelow).

Soagain,itisfairtoask,what’stheupsideofopeningthismetaboliccanof worms? The answer, simply, is that the dramatic changes in PUFAassociatedwithadaptingtoalowcarbohydratedietcanhelpexplaintheunderlyingphysiologyofitsbenefits.

First,we’llofferyouanoverviewofwhythatmightbe.Thenwe’lltellyouhowwestumbledintothisunderstandingoverthelast20years.

Point 1. Low carbohydrate diets cause the physiologically importantendproductsofessentialfattyacid(EFA)metabolisminmembranestogoup sharply[29, 41, 42]. EFA endproducts in muscle membranes arepositively correlated with insulin sensitivity[38]. Thus these membranecomposition changes can explain the improved insulin sensitivity thatoccurs when an insulin resistant individual adopts a low carbohydratediet.

Point 2. Increased EFA endproducts in liver membranes shut downexpression of the enzymes that drive lipogenesis[72]. The consensusexperts assume that human lipogenesis is inconsequential, however,

they see no reason to explain how it stops when dietary carbs arereduced. But from the perspective offered by POA, something clearlyputs the brakes on lipogenesis when a person transitions to a lowcarbohydrate diet, and our observation of increased EFA endproductsoffersanelegantmechanism.Inaddition,thishelpsexplainthedramaticreductioninserumtriglyceridesthatweseeinindividualswithmetabolicsyndromewhogoonalowcarbohydratediet.

Point 3. A simple explanation for increasedEFA endproductsmight bethatthebodymakesmoreofthemonalowcarbdiet.Butunfortunatelyitisn’t that simple. All of the data (levels ofmetabolic intermediates andenzymeactivities)pointintheoppositedirection–thatproductionofEFAendproductsgoesdown!Soiftheygoupwithoutmorebeingmade,thisindicatesthatthebodymustbedestroyingthemmoreslowly.Andsincethearch-enemyofPUFAisagroupofmoleculeswecallfree-radicals(ormore precisely, reactive oxygen species – ROS), perhaps the rate ofROS generation is reduced when dietary carbohydrates are restricted.Themainstreamconsensusstill regards thisasan ‘outside thebox’ (orshouldwesay“radical”)fantasy,butitisalsoconsistentwithourmultipleobservations thatahostofbiomarkersof inflammation(known inducersofROSgeneration)godownwhenalowcarbdietisadopted[29].

Sothereyouhaveit.It’sreallykindofelegant.Inflammationdrivenbytheforcedmetabolism of carbohydrate drives up the production ofROS inmitochondria.ROSdamagemembraneEFAendproducts,whichatsomepointcan’tbereplacedfastenough.TheresultantreductioninmembraneEFA endproducts unleashes the genes (e.g. fatty acid synthase) thatcontrol liver lipogenesis, and at the same time the loss of membraneHUFA causes increased insulin resistance inmuscles. Insulin resistantmusclestakeuplessglucose,resultinginmoreofitbeingdivertedtotheliverfor lipogenesis.TakeawaythehighlevelsofROSandmembranessuffer less damage, their content of EFA endproducts rises, and bothdyslipidemia and insulin resistance improve. The trigger for this set ofmetabolic dominos – the switch that controls this process – is dietarycarbohydrate.

Summary

Clearlythereismuchmoretodietaryfatsandhealththaniscontainedinsimplisticedictslike“saturatedfatsarebadforyou”.Wehaveshownyouthat our bodies respond to saturated fats very differently whenwe areketoadapted,suchthattheyarerapidlyburnedforfuelratherthanbeingstored.Bycontrast,peopleeatinghigherlevelsofdietarycarbohydrates,even when they are not overeating total calories, have higher bloodlevels of saturated fats. As illustrated by the elevated levels of POAassociated with higher proportions of dietary carbohydrate, someindividualsareparticularlypronetodisposeofdietarycarbohydratesvialipogenesis,whichcreatesalotofsaturatedfattyacidsaswellasPOA.

The other new and important insight into the fatty acid response tocarbohydrate restriction comes from examining the changes in EFAendproductsinphospholipids.Ketoadaptationresultsinmarkedchangesinhowourbodiesareabletoconstructandmaintainoptimummembranecomposition,andthisappearstobedueto lessproductionofROSandinflammatorymediators. There ismuchmore for us to learn about thisprocess, but at the very least, this observation helps explain theimprovement in insulin sensitivity that occurs when you becomeketoadapted.

Postscript: Details of Fatty Acid Nomenclature and MetabolicPathways

Thissectionisincludedhereforthereaderwhowantsmoredetailaboutthenamesandmetabolicrelationshipsamongthevarioustypes(classes)of fattyacids. Ifyouhaven’t takenchemistryorbiochemistry in thepast(orifyoudidn’tenjoyit),youmightdecidetoskipthissectionandmoveontothenextchapter.Butformanyreaders,workingthroughthissectionwill facilitate your understanding of a number of pointswemakeaboutfatsandfattyacidmetabolismelsewhereinthisbook.

Fatty acids are generally classed by the length of the carbon chain –‘short’(2,3,or4),‘medium’(6to12)and‘long’(14ormore)–andbythenumberofdoublebondswithinthatchain.Saturatedfatshavenodoublebonds,monounsaturateshaveonedoublebondinthecarbonchain,andpolyunsaturateshavetwoormoredoublebonds.

Short-chain fatty acids are commonly consumed in the diet, such asaceticacid (2-carbons) in vinegarand lacticacid (3 carbons) in yogurt,buttermilk, natural cheeseand some fermented vegetableproducts likesaukraut and kimchi. In addition, the ‘ketones’ made in our liver –betahydroxybutyrateandacetoacetate–are4carbonfattyacidswhich,like lactate, have an extra oxygen attached to the carbon chain. All ofthese, whether consumed in the diet or produced metabolically, arerapidlyoxidizedasfuelbyavarietyoftissuesasdescribedinChapter6.

Medium-chainfattyacidsarefoundindairyfats(milk,butterandcream)andinsome‘tropicaloils’ likepalmoil.Thesefattyacids,withtheslightexceptionof12-carbonlaurate,arenotincorporatedintotriglyceridesandstored in thebody.Onceeaten, theymustbepromptlyoxidized for fuelby mitochondria. Unlike long-chain fatty acids that require assistancefrom mitochondrial membrane proteins to get into the mitochondrialmatrix, medium-chain fatty acids bypass this regulatory step. If weconsumemoremedium-chainfatsthancanbeburnedinashortperiodoftime, our liver converts the excess into ketones, which in turn can beburnedbyawiderrangeoforgans(e.g.,thebrain).

Long-chain fatty acids consumed in the diet can be either oxidized(burned for energy) or stored as triglycerides. As a general rule, thelonger thecarbonchain, themore likelyafattyacid is tobestored.Butthisisnotuniformlytrue,becauseanunsaturatedfattyacidwithadoublebond close to the ‘omega-end’ (the opposite end of the chain from theterminal‘COOH’carboxylicacidmoiety)ismorelikelytobeoxidizedthana chain of equal length with any double bonds farther away from theomega-end[73].Thusomega-3fattyacids,whicharesonamedbecausetheyhaveadoublebondthatisjust3carbonsfromtheomega-end,aremorereadilyoxidizedforfuelthananalogousomega-6oromega-9fattyacids. These differingmetabolic preferences for oxidation over storagehelpexplainwhy thecompositionofourbody fatstoresdiffers fromthecompositionofthefatsinourdiet(i.e.,whywearen’twhatweeat).

Amongthepolyunsaturatedfattyacids,therearetwosubgroupsthatareessential for human wellbeing and function. These consist of twoseparate families each ranging in chain length from 18 to 22 carbons.The omega-6 family, all having a double bond 6-carbons in from the

omega-end, starts with its 18-carbon precursor linoleate (18:2ω6) andcanbeelongatedanddesaturatedtoaseriesofproductswhichallretainthe original omega-6 double bond. For the most part in humanmetabolism,thisprocessstopswitharachidonate(20:4ω6).ThisseriesofstepsisdepictedverticallyontheleftsideoftheFigure2.Notealsothatthis numerical shorthand consists of the number of carbons (e.g., forarachidonate20),followingthecolonisthenumberofdoublebonds(4),and the ω6 indicates the distance from the first double bond to theomega-end.Alladditionaldoublebondsoccurat3-carbonintervals.

These same enzymes that process omega-6 fatty acids also elongateanddesaturatetheomega-3precursoralpha-linolenate(18:3ω3–nottobe confused with linoleate – which is why the numerical ‘omega’shorthand is better). However rather than stopping with the omega-3productEPA (20:5ω3)which is analogous to arachidonate,most of theomega-3productfoundinhumantissuesisdocosahexaenoate(22:6ω3,or DHA for short). Even people who eat a lot of fish or fish oilsupplements,whichcontainlotsofEPA,stillhavemoreDHAthanEPAintheir cell membranes. Thus this pathway with its various FADS andelongase enzymes actively processeswhatwe eat to try andmaintainthe optimum collection of ‘essential fatty acid end products’ likearachidonateandDHAinourcellmembranes.

image

Figure 2. Enzymatic metabolism of essential (omega-6 and omega-3)and nonessential fatty acid families. SCD-1, steroyl-CoA-desaturase,addsadoublebond9-carbonsinfromtheacidendofthecarbonchain.FADS2, fatty acid desaturase-2, addsadoublebond6-carbons in fromtheacidend.FADS1addsadoublebond5-carbonsinfromtheacidend.Elongaseaddstwocarbonstothechainattheacidend.Becauseallofthese enzymes work at the acid end, an omega-3 or omega-6 doublebonddoesnotchangeinrelationtotheomega-endwhentheseadditionsare made at the other end of the chain. Thus an omega-3 fatty acidremainsanomega-3fatuntil itgetsburnedforfuel,andthesamegoesfor the omega-6 family. Metabolically, they cannot be inter-converted(whichiswhytherearenohorizontalarrowsontheleftsideofthisfigure.SCD-1, on the other hand, can add a double bond to a saturated fat,making either an omega-9 monounsaturate (oleate, 18:1ω9) if startingwith18:0,orpalmitoleate(POA,16:1ω7)whenstartingfrom16:0.

Animportantpointthatwetouchonanumberoftimesinthisbookisthatwhen a person switches from a high carb diet to one low enough incarbohydratethatthebodystartsmakingketones(usuallyatorunder50gramsperdayoftotalcarbs),thebody’seconomyofessentialfattyacidschanges dramatically. This is seen as a rise in both arachidonate andDHA in serum phospholipids,while at the same time, the levels of theintermediateproducts(thefattyacidshalfwaybetweenprecursorandendproduct(like20:3ω6intheomega-6pathway)gowaydown.Thisisabitvexingtosaytheleast,becauseif thebodywascrankingout lotsmoreend products through this pathway, onewould expect the levels of theintermediatestogoupintheprocess.

Theorganthatismostactiveinthismetabolismofessentialfattyacidsisthe liver,which ishard togetsamples from inhumans.But in researchthatiscurrentlypendingpublication,whenweputmiceonalowcarbdietforamonthortwoandthenmeasuredthelevelsofFADS1andFADS2intheir livers, it was reduced by 50%. But in these same animals,membrane levels of the end product fatty acids were increased andintermediatesdecreased,similartowhatwesawinhumans.

Putting this all together, along with our observation showing reducedinflammation with a low carb diet, we have to conclude that thesemembrane changes and reduced FADS enzyme levels indicate thatmuch less of the endproducts are getting destroyed.And although thishasyet tobeconclusivelyproven, themost likelyculprit in thiscaseofmembranevandalismisROS(akafreeradical)productionthatisdirectlylinkedtodietarycarbohydrateintake.

Chapter10

BODYCOMPOSITIONANDPHYSICALPERFORMANCE

Introduction

Whenindividualsembarkonaprogramtoloseweight,theimplicitgoalistoshedunwantedbody fat.Rarelydopeoplesetoutwith the intendedpurposetolosemuscle.Thisseemsobvious,buttheimportanceofbodycompositionisoftenovershadowedbythepromptfeedbackandpowerfulconnection people have with their scale weight. There are alsowidespreadmisconceptionsabouttheimportanceofdietarycarbohydrateinaffectingchangesinbodycompositionandexerciseperformance.Thischapterwillshedsomelightontheseissuesbyprovidinginsightintotheremarkable capacity for humans to adapt to carbohydrate restriction,allowingforcompletesparingofleantissueandmaintenanceofphysicalperformanceinspiteofsignificantwithdrawalofcarbohydrateandmajorcumulativeweightloss.

WhyBodyCompositionisImportant

Simplyput,bodycompositionreferstothebody’srelativeproportionsorabsolute contents of fat mass and lean tissue. Ideally a weight lossprogramwillmaximizefatlossandminimizemuscleloss.Why?Foronereason, in today’s culture we tend to view too much body fat asunappealing, whereas a low body fat revealing well toned muscles isseen as being fit and attractive. Beyond aesthetic reasons, the healthbenefitsthataccompanysignificantweightlossarelinkedwithreductionsinbodyfat,notmuscle. Inaddition, there isagrowingappreciationthatincreased muscle mass contributes to metabolic health. More muscletranslates to greater tissue volume to take up blood glucose andmoremitochondriathatcanburnfat.Thathelpsfendoffinsulinresistanceanddiabetes.Finally, lossofmusclewill haveanegativeeffectonphysical

performanceandactivitiesofdaily livingbydecreasingstrength,power,andendurance.

In reference to this last point on physical performance, it is interestingthat the last threedecadesofnationaldietaryguidelinesespousing thehealth benefits of a low fat/high carbohydrate diet have occurred inparallelwiththedogmaticsupportofsportsnutritionistsforcarbohydrateloading.Theoriginsofthesehighcarbohydraterecommendationsforthegeneral population andathletesmaybe coincidental, but over the timetheyhavetendedtoreinforceeachother’sposition.

WeightLossandBodyComposition

Howdoesatypicalweight lossprogramimpactfatmassandleanbodymass?Thisdependsonmanyvariables,including(butnotlimitedto)thelevelofcaloriesandproteincontent,adequacyofconcurrentmineralandvitamin intakes, and perhaps dietary carbohydrate content. In addition,theinitialactivitylevelandleanbodymasscontentoftheindividual,plustype and amount of activity during a diet program, will be importantfactorsindeterminingthenetcompositionofthelostweight.

Mostbodycompositionassessmentmethodscalculatetheproportionsoffatmassandleanbodymassfromestimatesofbodydensity,whicharein turn derived from either assessment of body volume (density =mass/volume) or regression equations. This works because muscle ismoredense(itsinksinwater)whereasfatfloats.Sooncebodydensityisdetermined, it is then converted to a percent body fat (usingequationsdevelopedbySiriorBrozek–seepost-script),whichisusedtocalculatefatmassandleanbodymass.

These‘two-compartmentmodels’basedonbodydensitydonotaddressthe multi-component nature of lean body mass (perhaps better callednonfat tissue), which includes other non-fat substances like water,minerals, connective tissues, and bone. In contrast, dual-energy X-rayabsorptiometry (DXA) partitions out bone from the lean body masscompartmentandthusprovidesa3-compartmentmodel--fatmasssofttissue,leanbodymasssofttissue,andbone(seepost-script).

Thisdirectmeasureofbonemineralcontentisclinicallyusefulinitsownright, but because bone is very dense, including it in the calculationimproves the accuracy of body fat content as well. However there isanother important variable that none of these techniques address. Anyfluctuations inwatercontent(e.g., reduction inextra-vascularvolumeorintracellular glycogen-associated water) would be interpreted asdecreased lean body mass because common body compositionassessmentmethodstreatwateras leantissue.This is important in thecontext of carbohydrate-restricted diets because they typically reducemuscle glycogen (and its associated water) by more than half andbecausetheirnatriureticeffectsonthekidneycanmarkedlyreducetotalbodywatercontent.

Onaverage,a10kgweightlossbyconventionallow-fatdietingalonewillresult in about three-fourths of the loss from fat mass (i.e., tissuetriglyceride)[74]. There are a number of reasons why this is notautomatically100%;firstbecauseadiposetissueitselfisonlyabout85%fat,andalsobecauseenergyrestrictionmakesthebodylessefficientinitsuseofdietaryprotein, raising thedoseneededtooptimallypreserveexisting lean tissue. A third factor is that severely obese individuals,particularlymales,accumulateextramuscle that isneeded tocarry theextraweight, and this is lost with the excessweight unless purposefulexerciseisaddedtomaintainmusclemass.

An even greater loss in lean bodymassmay be expectedwithweightloss approaches that contain inadequate dietary protein, minerals, orboth.Combine thiswith a short term study thatmobilizes considerablebody water, and the effects of carbohydrate restriction on bodycompositioncanbeconjuredtoappearquitenegative(seeChapter12).Therefore, itmakes intuitive sense that inaddition to themacronutrientmakeup of the diet, both duration of a study and the diet associatedmineralcontentcouldimpactresponsesinbodycomposition.

DietaryMacronutrientDistributionAffectsBodyComposition

Addressingtheissueofmacronutrientcompositionofweightlossdietsonbody composition responses, Krieger et al.[75] concluded from theiranalysis of 87 published weight loss studies that diets lower in

carbohydratewere associatedwith greater fat loss, and also that dietsproviding more than the bare minimum of protein resulted in betterpreservation of lean body mass. These effects were independent ofenergyintakeandparticipationinexercise.Translation:it’snotjustabouteatinglessfood.Thetypeofmacronutrientsconsumedhasanimportanteffectonbodycomposition(andmanyothermetaboliceffects)too.

VeryLowCarbohydrateDietsandBodyComposition

Despite considerable published evidence to the contrary, there is acommonbeliefthatbothmusclelossandimpairedphysicalperformanceareexpectedtooccurwhenindividualssignificantlyreducecarbohydrateintake.Asthelogicgoes,inthefaceofreducedcarbohydrateintake,thebody resorts tocatabolizingproteinstores forenergy.Ofcourse,aswehave longsincedemonstrated (anddiscussed inChapter6), this isnottrueifanadequateperiodofketoadaptation(atleast2ormoreweeks)isallowed[23,27,76].

Let’sbrieflyreviewtheexperimentalevidence.Althoughresultsvary,onthewhole studiesexaminingbody composition in response to very lowcarbohydratedietsdonotraiseanyconcernsaboutanexaggeratedlossof lean tissue. In fact, properly formulated ketogenic diets have aremarkablecapacitytoprotectmuscleandexerciseperformanceduringperiodsofcaloricrestriction.

In a small butwell controlled studypublished in 1971,Younget al.[77]examined the effects of a hypocaloric, very low carbohydrate diet onbody composition and nitrogen balance in young overweight men. Allfoodswerepreparedandprovidedtosubjectsovera9weekweightlossperiod.Thedietseachcontained1800kcal,115gprotein,5gsodium,andbetween30and60gcarbohydrateperday.Compliancewashighasevidenced by the presence of urine ketones (discussed inChapter 13)and consistent weight loss (range 12-18 kg over 9 wk). Notably, bodycomposition determined from underwater weighing indicated nearly alltheweight losswasattributed to reductions in fatmass.Therewasnetnitrogen (i.e.,protein) lossduring the firstweekofweight reductionbutthereaftersubjectswereinbalanceorretainingnitrogen.

Over a decade later, Hoffer et al.[78] severely restricted energy intake(500kcal/day) inoverweightwomen forup to8weeks.Thegroupwhoconsumed a low calorie diet with adequate protein (85 g/day) plusminerals and vitamins (including sodium >5 g/day) but devoid ofcarbohydrate remained in positive nitrogen balance. In contrast, thosesubjectsfedalowerproteinintake(45gproteinand45gcarbohydrate)but identical total calorieswere in negativeprotein balance.Thusevenunder severe caloric restriction, there is a remarkable capacity topreserveleantissueonalowcarbohydratedietwhenadequateprotein,vitamins,andminerals(includingsodium)areprovided.

Phinneyetal.[27]examinedmetabolicadaptations toaneucaloric (i.e.,energymaintenance)verylowcarbohydrateketogenicdietovera4weekperiod inhighly trainedmen(bicycleracers).Thedietconsistedof1.75g/kg protein, <10 g carbohydrate, >80% of energy as fat and wassupplemented with minerals including 5 g sodium. Meticulousmeasurementsofnitrogenbalance,includingcomplete24hoururineandstoolcollections,wereobtaineddaily.Undertheseconditionsofconstantenergy and nitrogen intake, the transition from a high carbohydrate toketogenicdietresultedinatransientlossofnitrogenduringthefirstfewdays.However,thesubjectsthenrapidlyreturnedtopositivebalancebytheendof the firstweek,where it remained for theremaining3weeks.Thus,overthe4weeksoftheketogenicdiet,therewasanaveragegainof approximately 1 pound of lean bodymass in highly trained subjectswhocontinued(butdidnotincrease)theirtrainingregimen.

Thismaintenanceofnitrogenbalancewasconfirmedbymeasurementsof whole body 40K counting (a direct measure of total body potassiumcontent,which is tightlycorrelatedwith leanbodymass),whichshowedno significant net change after the ketogenic diet. The proportion ofnaturally-occurringradioactive40Kinhumantissuesissmallbutconstantanddistributesalmostentirelywithintheintracellularcompartmentoffat-freemass.Thus, itprovidescorroboratingevidencealongwithnitrogenbalance that ketogenic diets with adequate protein and mineral intakeneednotresultinleantissuelossinphysicallyactivemen.

Volekreportedthatnormal-weightmenwhoswitchedfromtheirhabitualdiet (48% carbohydrate) to a ketogenic diet (12% carbohydrate) for 6

weekssignificantlydecreasedfatmass(-3.4kg)andincreasedleanbodymass (1.1 kg)[79]. There was a significant decrease in serum insulin(-34%)andsimple regression indicated that70%of thevariability in fatlossontheketogenicdietwasexplainedbythedecreaseinseruminsulinconcentrations. Ina follow-upstudy inoverweightmenandwomen[80],Volekshowedthatahypocaloricverylowcarbohydratedietresultedin2-fold greater wholebody fat loss than a low fat diet with a similarprescribedenergyintake.

Anovel and potentially clinically significant finding of this second studywas that trunk fatmasscomprised lessof the total remaining fatmassafter the low carbohydrate diet, indicating a preferential loss of fat in aregion that carries a greater health risk. Specifically, this study was acrossoverdesign,inwhichsubjectsweregivenbothdietsinrandomizedorder,sobodycompositionchangesweredeterminedineachsubjectonboth diets. Fat loss in the trunk region was greater during the lowcarbohydratedietin12of15menand12of13women.

In subjects with metabolic syndrome, Volek recently showed that thedecreaseinwholebodyfatmassfromDXAwas1.5-foldgreaterafter12weeksofa lowcarbohydrate thana low fatdiet (5.7 kgvs3.7 kg)[56].The decrease in abdominal fat was 1.6-fold greater after the lowcarbohydratethanthelowfatdiet(-828gvs-506g).

The various mechanisms regulating composition of weight loss anddistributionof fat lossduring lowcarbohydratedietsremainunclear,butin largepart canbeattributed to factors regulatingmetabolic control offuelpartitioning.Wehaveshownreliabledecreasesin insulinandleptininsubjects restrictingcarbohydrate. Insulin is thepredominanthormonethat inhibits lipolysis,and thiseffectoccursevenat the lowerendof itsnormal physiologic range. Thismeans even small reductions in insulinmayhaveapermissiveroleinfatmobilizationonalowcarbohydratediet.

ImportanceofResistanceTrainingforBuildingMuscle

Resistancetrainingdoesnotaffectfatlosstoagreatextentindependentof diet. However, muscular overload induced by resistance exercisecreatesananabolicstimulusforskeletalmusclefiberhypertrophy.Many

studieshavebeenconductedinthecontextoflowfatdietsandgenerallyindicatethatresistanceexercise(2-3days/week)canpreserveleanbodymass during weight loss. Volek and Kraemer et al.[81] showed thatoverweightmenwhoconsumedalow-calorie,highfiber,lowfatdietandremainedsedentarylost9.6kgofweightin12weeks.Twoothergroupsconsumed the same diet but added either endurance training (3days/week working up to 50min per session) or a combination of thesame endurance training with progressive resistance training (3days/weekfor30-40minpersession).Allgroupsshowedsimilarweightlosses.However,exercisedidimpactthecompositionofweightloss(seetable).Thisstudydemonstratedonaveragethatexerciseisnotarobuststimulusforweightloss.Butthecombinationofdietaryenergyrestrictionwith resistance training resulted in better maintenance of lean tissueduringweightloss.

GroupsbyDietandTrainingType

BodyComp(DXA)

DietDiet+

Endurance

Diet+

Endurance+

Resistance

WeightLoss(kg)

-9.6 -9.0 -9.9

%LossasFat 69 78 97

%LossasLean 31 22 3

LowCarbohydrateDietsandResistanceTraining

Resistance training is a potent stimulus to increase muscle mass andstrength,andthusthereisgoodreasontoconsiderweighttrainingasanadjunct to a low carbohydrate diet for improving body composition andfunctional capacity.Themetabolicdemandsof resistanceexercisevarydependingon the totalworkvolumeand therestperiodsbetweensets,which can impact one’s ability to tolerate different workouts on a lowcarbohydratediets.Althoughexperimentalevidenceisscarce,itappearsmost conventional types of resistance training are tolerated very wellafteradaptationtoalowcarbohydratediet.

Jabekk et al.[82] studied untrained overweight women between 20-40yearsofage,allofwhomparticipatedina10weeksupervisedresistancetraining program (2 workouts per week). Subjects were randomlyassigned to either a hypocaloric low carbohydrate diet or to continueconsumingtheirhabitualdiet.Thelowcarbohydratedietconsistedof23gcarbohydrate/day (6%ofenergy)and95g/dayprotein (22%energy).Weightlosswas5.6kginthelowcarbohydrategroup,whichwasentirelyattributed to fat loss.Thus,a lowcarbohydratediet incombinationwithresistance training resulted in significant fat loss and completepreservationofleanbodymass.

Onlyafewstudieshavedirectlycompareddietsvaryinginmacronutrientdistributioninsubjectsengagedinanexercisetrainingprogram.Althoughnot a very low carbohydrate diet, Layman et al.[83] reported that amoderate restriction in carbohydrate with protein intake at 1.6 g/ kg(38:30:32;energy%ascarb:protein:fat) resulted inmore favorablebodycomposition changes thana low fat dietwith protein intakeat 0.8 g/kg(61:18:26; %carb:protein:fat) in middle-aged, overweight women. Allgroupssignificantlydecreasedtheirtotalcaloricintakeby~600kcal/day.After16weeks,themoderatecarbohydratedietgroupwithhigherproteinlostapproximately2.0kgmorebodyweight than the low fatdietgroup(9.3vs.7.3kg).Theadditionofanexerciseprogram(5day/weekwalkingand 2 day/week resistance training) to themoderate carbohydrate dietproducedanadditiveeffectbyhelpingtopreserve leantissuewhilestill

allowingforbetterfatloss.

Volekperformedasimilarexperiment inoverweight/obesemenbut thistimethedietswereinfactlowincarbohydrateandtheresistancetrainingprogramwasmoreintense[84].Menwererandomizedeithertoalowfatdietgroupthatrestrictedfattolessthan25%ofenergyortoaverylowcarbohydrateketogenicdietgroup that restrictedcarbohydrate to~12%energy.Bothgroupsalsoparticipatedinaresistancetrainingprogram(3days/week).BodycompositionwasassessedusingDXAbeforeandafterthe 12 week program. The results were compared to non-training dietonlygroups.Asexpected,thelowcarbohydratedietgrouplostmorefat,which was associated with greater decreases in insulin. Resistancetraining, independent of diet, resulted in increased lean body masswithout compromising fat loss in both diet groups. The most dramaticreductioninpercentbodyfatwasinthelowcarbohydratedietresistancetraininggroup(-5.3%),followedbylowfatresistancetraining(-3.5%),lowcarbohydrate diet only (-3.4%), and low fat diet only (-2.0%) groups.These data show for the first time that resistance training is a potentstimulustoprotectleanbodymassinmenconsumingalowcarbohydrateketogenicdietwhilestillallowingforsignificantlygreaterfatloss.

WhenourworkiscomparedtothefindingsofLayman,asimilarpatternand magnitude of change in body weight are seen across the fourgroups. The low carbohydrate diet groups lost more body fat,independent of training, whereas resistance training had a favorableeffectonleanbodymassindependentofdiet.Thecombinationofalowcarbohydrate diet and resistance training appears to be additive in thesense that it maximizes fat loss while preserving/increasing lean bodymassandtherebyresults in thegreatestreductions inpercentbodyfat.Ofnote,noneofthesubjectsintheketogenicdietplusresistancetraininggroup dropped out of the study, nor did they have any problemscompleting thehigh intensityworkouts.Asexpectedwithaprogressiveresistancetrainingprograminpreviouslynon-resistancetrainedsubjects,theyallshowedmarked increases inmaximalstrength.Thus,despiteadecreaseincarbohydrateavailability,adaptationtoawellformulatedverylow carbohydrate diet allowed individuals to participate in and benefitfromahighintensitystrengthtrainingprogram.

EndurancePerformance

Aswithresistanceexercise,thedependenceofenduranceperformanceon muscle glycogen has been substantially overemphasized. StartingwiththeclassicstudiesofChristensenandHansen[85]beforeWorldWarII, a string of shortterm studies have been published demonstratinglongerenduranceexercisetimeswithhighcarbohydratedietscomparedto lowcarbohydratediets[86].Anystudyof less than14daysduration,however,doesnotallowadequatetimeforketoadaptation,anditsresultsareuselessinassessingtheeffectsofasustainedlowcarbohydratediet.Thus,whenmorerecentstudiesusing longerperiodsofdietadaptationtoa lowcarbohydrate intakeweredone, theapparent advantagesof ahighcarbohydratedietwerenotobserved[23,76].

Intheselongerdurationstudies,whencarbohydratewaskeptlow,withorwithout energy restriction, we observed no loss of peak aerobic power(VO2max) or peak muscle strength[87]. This clearly demonstrates thatdietary carbohydrate is not an obligate nutrient for the long termmaintenance of muscle health and function. This observation is alsoconsistentwiththeabilityofawellformulatedcarbohydraterestricteddiettopreserveleanbodymassasreportedabove.

Summary

As discussed elsewhere in this book, the adequate intake of mineralsproperlyadjustedtotheneedsofcarbohydraterestrictionisessential tolongtermhealthandfunction.Whentheseconditionsaremet,andwhenadequate(butnotexcessive)proteinisprovided,bodymassandphysicalperformancecanbeeffectivelymaintaineddespitesubstantialrestrictionof dietary carbohydrate. In the clinical setting, this means that bothendurance and resistance exercise are important factors that can beutilized in conjunction with carbohydrate restricted diets to optimizechangesinbodycompositionandwellbeing.

Post-Script:CommonBodyCompositionMethods

BMI–Bodymass index iscalculatedasweight inkilogramsdividedbyheight inmeterssquared.Valuesmorethan25areusedasacutoff for

being overweight and more than 30 as obese. It’s easy and cheap tomeasure,explainingwhyit’swidelyused.ButBMIcanoverestimatebodyfatnessinpeoplewithalotofmuscleandlargeframes.

UWW–Underwater weighing is based on Archimedes Principle. BodyDensity=BodyMass/BodyVolume.Ifanobjectweighs75kginairand3kginwater,thenthelossofweightinwaterisequaltotheweightofthevolumeofdisplacedwater(i.e.,72kg=72L=72,000cc.Densityisusedto calculate percent body fat (see below). UWW is considered veryaccurate,but it is tediousandmoderatelyuncomfortable for thesubjectand limited to university laboratories. Error associatedwith air in lungscanbesignificant.

AirPlethysmography–AlsoknownasBodPod.Fundamentallythesameas underwater weighing but uses air instead of water. Measures thevolume of air a person’s body displaceswhile sitting inside a chamberrather than measuring how much water their body displaces whendunkedinatank.SamelimitationsasUWW.

DXA–dual-energyX-rayabsorptiometry.Becomingpreferredmethodtoassessbodycomposition.Estimatessoft tissue(fatand lean)andbonemass.Usesaconstantpotentialx-raysourcetoachieveabeamofdualenergyradiation.X-rayspassingthroughthebodyareattenuated,whichis a function of tissue composition. Advantages include quick, reliableandaccurate, non-invasive andminimal inconvenience, 3 compartmentmodel, and allows regional analyses of body segments. Maindisadvantagesarehighcostandsmalltabledimensions.Assumessameamount of fat over bone as over neighboring bone free tissue andconstanthydrationandelectrolytecontentofleansofttissue.

Skinfold – Based on the relationship between the fat located directlybeneath the skin (subcutaneous fat) and internal fat, andbodydensity.Calipersareusedtomeasurethethicknessofadoublelayerofskinandsubcutaneousfattissue.Commonsitesincludetriceps,abdominal,thigh,suprailiac,subscapular,chest,andmidaxiallary.Sumofskinfoldsisusedinamathematicalequationtopredicteitherbodydensityorpercent fat.Equationsmustbepopulationspecific(i.e.,similarage,gender,stateoftraining, fatness, race) in order to be accurate. Accuracy is also highly

dependentontheskillofthepersonperformingthetest.ComputingPercentBodyFat(SiriEquation):%Fat=(495/Density)–

450

AssumesdensityFatTissue=0.90g/ccanddensityLeanTissue=1.10g/cc

Assumptions:Densitiesoffatandleantissuesremainconstantevenwithlarge individual variations in total body fat; lean tissue components ofbone and muscle are essentially the same density among differentindividuals, but this has been questioned in certain ethnic groups,growingchildren,andagingadults.Baseduponthechemicalanalysisofasmallnumberofhumancorpses,noneofwhomwereobese[88].

Chapter11

PERSONALIZEDNUTRITION

Introduction

When we are introduced to people as ‘nutritionists’, we’re inevitablyasked…what should I eat? Our usual answer…it depends. And if theconversationcontinuesandwegetaroundtotellingthemourresearchisfocusedonverylowcarbohydratediets,thequestionalmostalwayspopsup…howmuchshouldIrestrictmycarbohydrate?Again,ouranswer…itdepends? These answers are certainly concise, and also scientificallytrue, but they really beg the logical follow up question…depends onwhat?That’swhere theconversationstarts togetcomplicated,butalsoreally fascinating, because it cuts right to the heart of personalizednutrition.

The last few years have brought incredible progress in genetics,particularlytomethodsformeasuringDNAandclinicalbiomarkers.Alongwiththesescientificandanalyticaladvancementshascomethepromiseof personalized approaches to lifestyle. The recognition that twoindividuals respond differently to the same diet and therefore requireunique combinations of nutrients for optimal health is oddly juxtaposedwithlongstandingnationaldietaryguidelinesthatpromoteaonesizefitsall approach. Along these lines, papers encouraging dietitians to studygenetics in preparation for personalized nutrition are publishedsimultaneouslywithonescondemninganydietoutsidenarrowguidelines.We’re optimistic that this dichotomy between hedging for the future ofpersonalized nutrition coupled with an unwillingness to break fromtraditionistemporary,althoughwedarenotdefinetemporary.

Despite some reluctance on the part of many dietitians, doctors, andpolicy makers to break from cookie cutter diet treatments, manyentrepreneursareattemptingtocapitalizeonthepromiseofpersonalizednutrition. There is no shortage of companies that will gladly accept a

smallcheekswabwithafairamountofcashandinreturnprovideyouacustomizeddietandsupplementplan.Aretheresultsbasedonscientificresearch?Andmoreimportant,aretheyhelpful?Thetruthisit’shardtotell.We’re far fromhavingpreciselydefinedgenetic testing forpersonaldietprescription.Theprudentadvicefornowistohaveahealthydoseofskepticism.

The aim of this chapter is to provide some technical background andframe some of the relevant issues and challenges that need to beaddressed in moving toward a more personalized approach to diet,especiallyasitpertainstocarbohydrateintake.Inthisregard,theremaybe some novel signs that can be used to dial in on your level ofcarbohydratetolerance.

DietandVariability

We readily accept the idea that people differ in appearance, intellect,physical performance,preferences formusic, art, sports, andof coursefood.Therefore,theneedtocustomizedietsshouldcomeasnosurprise.Butwhat is theevidence?Someof thebestproof showing thegeneticcontribution to the variability in weight loss comes from studies inmonozygotic ‘genetically identical’ twins. Drs. Claude Bouchard andAngelo Tremblay conducted two such experiments in the 1990s thatexamined the variability in changes in body weight in response tonegativeandpositiveenergybalanceinrelationtogenetics[89].

Inthepositiveenergybalanceexperiment,twinswereoverfed1000kcal/day (6 days out of 7) for 100 days. There was a wide discrepancy inweight gain ranging from about 9 to 30 pounds between the differentpairs of twins, but weight gain within each twin pair was quite similar.Specifically,thebetweentwinvarianceinweightgainwasthreetimesthevariance within pairs. When looking at gains in upper body fat orabdominalvisceral fat, thebetween twinvariancewassix timesgreaterthanwithinpairs.

Inthenegativeenergybalanceexperiment, twinsexercisedtwiceaday(9 days out of 10) for 93 days, while each individual’s dietary energyintake was held at their sedentary maintenance energy level. This

createdadailydeficitof624kcal/dayforeveryoneinthestudy.Similartothe weight gain findings, there was a surprisingly wide discrepancy inweightlossamongthedifferentpairsoftwinrangingfrom2to18pounds,while weight loss within twins was again very similar. These wellcontrolled prospective twin studies demonstrate a remarkable level ofvariabilityinweightandfatlossbetweentwinpairs.Incontrast,themuchsmallervariance inchanges inweight,especially fatmass,within twinsprovides convincing evidence for the role of genetic factors indetermining howour bodies respond to both energy deficit and energysurplus.

Aroleforgenetics inotherbiologicresponsescanbeinferredfromwellcontrolledstudieswherethesamenutrientcompositionisfedtosubjects.In a recent very low carbohydrate feeding experiment in men weobserved a wide range of responses in some variables (e.g., LDL-C),whereas other variables showed a considerably lower variance (e.g.,triglycerides,HDL-C).ForexampletheaverageLDL-Cresponsewas+6mg/dL,butwhen lookingat individual responsesonesubject increased53mg/dLwhereasanotherdecreased41mg/dLdespiteconsuming thesamediet[30]!What thismeans is thatgeneshaveamajor role inhowyourespondtodietandexercise. It ispossible, forexample, that ifyouexercisevigorouslyyoumayseeverylittlebenefitintermsofweightloss,but you may be programmed to be responsive to other stimuli likecarbohydraterestriction.

NutrigeneticsandNutrigenomics

Two recently coined terms that come up when studying the interplaybetweendietandgenesare‘nutrigenetics’and‘nutrigenomics’.Theyareintimately related,at timesoverlapping, concepts that sharea commongoalofelucidatingthewaydietandgenesinteracttoimpactsusceptibilityto disease. Both are directed at understanding how genetic variationexplainsdifferencesinthedietaryresponsesofindividuals.Forexample,supposethatyouandyourco-workeragreetoeattheexactsamedietforone month. Results of laboratory work indicate your co-worker’scholesterol increased while yours decreased. A nutrigenetic approachwould look at just a few gene candidates (‘suspects’) and aim to

determine thegeneticdifferencesbetweenyouandyourco-workerandhow those genetic variations (alleles) relate to your distinct cholesterolresponses.

Nutrigenomics,ontheotherhandisconcernedwithdiscovery…it looksat many genes at once. A nutrigenomics approach might involveextractingasmallpieceofadipose tissue fromyouandyourco-workerbeforeandafteryour1-monthdiettomeasuretheactivityofanarrayofhundreds of genes to see which ones were responsive to the diet.Sometimes thegeneproducts (proteins,metabolites)aremeasured,sonutrigenomics is tightly linked with ‘proteomics’ and ‘metabolomics’. Inshortnutrigeneticsanalyzeshowgeneticvariationamongpeopleallowsthem to respond differently to the same diet or the same supplement,whereas nutrigenomics refers to how nutrients alter gene expression.Sometimes distinguishing between the two is not clear-cut and someexpertsprefertouseacatchalltermlikenutritionalgenomicstodescribeanyeffortthatprobestherelationshipsbetweengenesanddiet.

ComplexityofNutritionalSignals

Nutrients are broadly classified into 4 macronutrient categories(carbohydrate,fat,protein,alcohol)thatprovideenergy.Wealsoneedaregular source of several essential micronutrients (vitamins, minerals)that our body cannot make and we therefore must obtain from food.There are also a host of other nonessential chemicals in food broadlyreferred to as phytonutrients that can elicit important effects onmetabolismandhealth.Thereforewhenweeat typicalmealsconsistingofmultiple foods, thebodymustprocesspotentiallyahundredormoredifferentchemicalsignals.

These nutrient signals in turn induce robust hormonal responses thatfurther impact regulatory control over a broad range of physiologicprocesses,andtheseresponsescandiffergreatlydependingonboththemacronutrientandmicronutrientcompositionsofthediet.Moreover,thereareimportantinteractiveeffectsthatchangethewaythebodyprocessesnutrients.Forexample,ironishandledverydifferentlybythebodywhenconsumedwithvitaminC,andsaturatedfatintakehasavariableeffectinthebodydependingonhowmuchcarbohydrateisconsumedalongwith

it. And finally, when you add other variables like dosage and timing ofingestion that can also change the signal dynamics, the vastpermutationsofnutrientsignalsimpactingphysiologicoutcomesbecomeanextraordinarilycomplexsystemtostudy.

ComplexityoftheGenome

Thegenomeconsistsofover3billionbasepairsmadeupoflongchainsof adenine, guanine, cytosine and thymine on the 23 chromosomes.Humanshaveabout 21,000genes, eachencoding a protein, scatteredaround the genome. The length of DNA that contains a typical geneextendsabout50,000basepairs,ofwhichonlya fraction, say1,000—actually encode the protein sequence. This means the majority of thegenome(~98%)consistsofexpansesofDNAwhosefunction(s)remainunknown.Thisissometimescalled‘junk’DNA.Interestingly,functionsarebeing found for some of this junk. For example some noncoding DNAsequencesaregenetic “switches” that regulatewhenandwheregenesareexpressed.Oneexpertestimatesthat5%ofthenoncodingDNAhasafunction.SowhetheraDNAvariantisfoundinageneorinanoncodingexpanse of DNA, it may have meaning for some yet unknown dietaryresponse.

Anyoneperson’sDNAisabout99-99.5%identicaltoanyotherperson’sDNA. There are two major causes of person-to-person geneticdifferences.Themajorcauseisnamedcopynumbervariants.ThesearemanydifferentplacesintheDNAwherethenumberofcopiesofagenecanvaryfromonetomanyhundreds.For instance,onaverage,peoplefromcultures thathistoricallyhavehighstarchdiets (suchasJapaneseand European Americans) have more copies of the gene salivaryamylase than people from cultures that historically eat low starch diets(such as Mbuti and Yakut)[90]. Amylase is involved in digestingcarbohydrates.More copies of the salivary amylase gene is correlatedwithmoreenzymaticactivity.Manybutnotallgenesexhibitcopynumbervariation in humans. Some of these copy variants show evidence ofadaptations that tookplaceoveramillionyearsago,whileothersshowevidenceforselectionbydietonlyinthelastfewthousandyears.

Thesecondmostabundantsourceofperson-to-personvariationinDNA

consistsofsinglenucleotidepolymorphisms(SNPs).ASNPisaplaceintheDNAwhereoneofthefournucleotideshasbeenreplacedbyanother.TheseSNPsmay change the function or amount of any of our 21,000proteins. So far, scientists have identified about 20 million SNPs butmanymoreexist.Overallanytwopeopledifferforabout3millionSNPs,which is about 0.1% of their total DNA. As an example, SNPs in theLactasegeneareresponsible for thepersistenceofLactaseexpressioninadultswhichallows foradults todrinkmilk– lactose tolerance.Mostcultures that kept milk producing animals, such as cows, camels, andgoats independently evolved different SNPs in the Lactase gene thatallow for lactose tolerance. The task of finding which SNPs and copynumber variants are important in respect to nutritional genomics willcertainlybechallenging.Althoughtheeffectsofa0.5-1%differencemayseemsmall,theoveralleffectsonphysiologycanbelarge.Forexamplesomeof thepolymorphisms ingenesthatcodeforenzymes involved incarbohydrate digestion (i.e., amylase and lactase) are the result ofselectionactingonhumanpopulationseatingvaryingamountsofstarchandlactose.

PersonalizedNutrition–WheretoStart?

It seems reasonable to target nutrients that represent dietary triggerscapable of pushing someone from susceptibility to disease. Since theyare consumed in larger quantities, it makes sense that macronutrientswouldexertsomeofthemostpowerfulsignals.

WhyWeRespondMoreAcutelytoCarbohydratethantoFatIntake

Depending on dose and timing of dietary carbohydrate, blood glucosecan exhibit large and rapid excursions. However failure tomaintain anadequate supply of glucose can have dire consequences; thus ourbodiesardentlydefendedaminimumbloodglucose level.Fallingbelowthis minimum (in the absence of blood ketones) triggers promptphysiologicalresponsestomaintainglucoselevelsnecessaryforbrain.Incontradistinction, blood fat levels (either as triglycerides or free fattyacids) are neither sensed normonitored to the same degree or in thesamewayasglucose.Theneedtosensefattyacidlevelsisnotasvital

forminute-tominutefunctioning.

There are a number of reasons why defining an individualizedcarbohydratelevelisalogicaltarget.First,thepotentialrangeofhumandietary carbohydrate intake is remarkably broad. At one extreme,becauseitisnotactuallyessentialinthehumandiet,intakecanbeverylow. At the other extreme, most healthy humans can tolerate carbs inrelatively large quantities for extended periods without toxicity. Thus,there is a wide range of intakes that can be compatible with health.Second, the consumption of carbohydrates trigger potent downstreamregulatory elements that induce a unique metabolic state orchestratedthroughseveralkeytranscriptionfactors.

HumanAdaptabilityandCarbohydrate

As humans we share a common physiology in the way cells, tissues,organsandsystemsareputtogetherandrespondtostimuli.Alongtheselines one of the most impressive aspects of human physiology is theability to adapt to varying nutritional input. Take an average personhabitually consuming over half her/his calories from carbohydrate andthenabruptlydeprivethatpersonofthisnutrient.Perhaps‘thatperson’isyou. Over the course of a week or two you will observe a robust andcoordinatedsetofadaptationsgointomotionthatresultsinnearlyperfectmetaboliccontrol.Thisadaptability toachangingdietary input isoneofthemarvelsofthehumanbody,butthisvariabilityisalsooneoftheleastappreciated aspects of nutritional science.Not everyone has the same‘skill’inadaptingtodietarychange.

Does everyone respond to reducing dietary carbohydrate in a uniformmanner?Inotherwordsistherevariabilityinthewaypeoplerespondtoremoving the majority of carbohydrate from their diet? While the timerequiredforadaptationmayvary,anditcertainlytakesatleast2weeks,theendresultof thisadaptation is thesame.Starvationexperimentsorstudiesthatseverelyrestricteddietarycarbohydrateindicateaconsistentshift inmetabolic fuel partitioningwith little variability. Typically, nobodydiesoreven losesconsciousness.Youcould interpret that tomeanweare hardwired to respond to carbohydrate restriction in a reliable and‘healthy’manner.

But what if we ask the corollary question; does everyone respond toincreasingcarbohydrateinaconsistentmanner?Inthiscase,theresultsarelikelynotaspredictable.Somepeoplecantoleratemoderatetohighlevelsofcarbohydratewithoutsignsorsymptomsofmetabolicdistress.However, others will struggle to maintain health (e.g., normal bloodglucoseandlipids)underanincreasing‘carbohydratechallenge’.Fromagenetic perspective, this means the ability to thrive under a lowcarbohydrate diet is highly conserved,whereas the ability to tolerate ahighercarbohydrateintakeislessso.

Whatdoesthistellusintermsofpersonalizednutrition?Onecouldtakethepositionthatalowcarbohydrateintakeisthe‘normal’metabolicstateassociatedwithhealth.This isconsistentwiththeviewthat themajorityof human evolution occurred in the backdrop of a low carbohydrateintake. The ability to tolerate more dietary carbohydrate is clearly aproblemformany.Considertherecentuncontrolledexperimentinwhichapproximately 200 million adults in the United States have beenencouragedtoconsumehigherlevelsofdietarycarbohydrateinplaceoffat. In the same time frame, more than half of us have ended upoverweightorobese.Theresultsfromthisnationallevelexperiencepointus to the logical conclusion that the ability to remain healthy withincreasinglevelsofcarbohydrateislimitedtoasubsetofthepopulation.Therefore determining who those people are and what characteristicsgivethemtheabilitytoconsumecarbohydratewithoutuntowardeffectsisamajorquestionthatcanandshouldbeaddressed.

Wehavealreadyexplainedthat insulinresistance,metabolicsyndrome,andtype2diabetesareallmanifestationsofcarbohydrateintolerance.Inotherwords, ifyouhaveoneof theseconditionsyouaresensitive(inanegativecontext)totheeffectsofcarbohydrate.Towhatextentthisisareflectionofgenetic variation remainsunclear.However, inouropinion,findinganobjectivemeanstodefinetheoptimalcarbohydrateintakeforan individual represents ‘low hanging fruit’ in our quest to developnutritionalgenomicsandpersonalizednutrition.

HowMuchDoesGenotypeMatter?

Howmuchofthevariabilityinagivenphenotypelikebodyweightorbody

mass index is attributed to genotype? Although there is some debatedependingonthespecificstudyandmethodologicalapproach,geneticsprobablyaccountsfor50-80%ofthevariability inBMI.Thehardtruthisthat finding the specific genes responsible has been a disappointment.The contribution of any given individual SNP variant to weight loss isrelatively small. When multiple SNPs are combined, it is possible toharness the informationandexplain the totalgeneticcontribution to thevariabilityindietresponse.Complexdiseasesliketype2diabetesarenotduetoasinglegene,theyarepolygenetic(i.e.,diseasesthatdependonthe simultaneous presence of several genes). Studies that havemeasuredmillionsofgenesinlargecohortshavediscoveredatotalof38SNPs associatedwith type 2 diabetes[91]. These genetic variants onlyexplain about 10% of type 2 diabetes heritability meaning there stillremainseveralwehavenotyetdiscovered.ItislikelythatalltheknownSNPswill need to be includedand statisticallymanipulated to begin toaccountforthetotalcontributionofgeneticsanddevelopusefultoolsforclinical prediction. This has not been done yet in large numbers ofsubjectseatingwidelydifferentcarbohydrate intakesoranydiet for thatmatter.

PersonalizingDiet,BeyondGenetics

When considering the reasons for variability in response to diet,undoubtedlygeneticsplaysarole,butcanyoupersonalizeyourdietwithnon-geneticmarkers?Asdiscussed inChapter7,a randomizedclinicaltrial(the‘AtoZStudy’)comparingweightlossresponsestodietslowandhighincarbohydrateindicatedthatthelevelofinsulinresistancewasanimportantdeterminantofsuccess. In the initialpublication[43],afteroneyearwomenassignedthelowcarbohydratedietlostmorethantwicetheweight (10.6 lbs) thanwomenassigned thehighcarbohydratediet (4.8lbs). These data are consistent withmultiple recent studies comparinghighcarbohydratetolowcarbohydratedietsforweightloss.

However in a follow up analysis of the original study data (which hasbeenpublishedonly inabstract form)[44],whenwomenassignedtothehighcarbohydrateandlowcarbohydrategroupsweredividedintotertilesbased on baseline insulin levels as amarker of insulin resistance, the

resultswerestriking.Inthelowcarbohydratedietgroup,weightlosswassimilar in themost insulinsensitive (11.7 lbs)and insulin resistant (11.9lbs) tertiles. However weight loss with the high carbohydrate diet wassignificantly greater in the insulin sensitive (9.0 lbs) than in the insulinresistant (3.3 lbs) tertiles. Thus insulin-sensitive women experienced asimilar success independent of which diet theywere assigned, but themore insulinresistantwomenfaredpoorlywhenassignedadiethigh incarbohydratecomparedtoalowcarbohydratediet.

This is consistent with the concept that insulin resistance is amanifestation of carbohydrate intolerance, and demonstrates thiscondition is best treatedwith a diet that limits carbohydrate.Moreover,this is the first human study to demonstrate that a clinical biomarker(insulinresistance)canbeusedtosegregateweightlossresponsestoaspecificdiet.Whilethissegregationofindividualstowardsadietthatwillbest suit them for weight loss is helpful, it does not inform thoseindividualsifandhowmuchtorestrictcarbohydratetooptimizechancesforlong-termweightmaintenance.

MarkersofCarbohydrateIntoleranceBeyondInsulin

If you have carbohydrate intolerance, metabolically this translates to apropensitytodivertdietarycarbohydrateawayfromskeletalmuscleandtowardstheliver.Andifliverglycogenstoresarefull,asignificantportionofyouradditionaldietarycarbohydrateswillbeconvertedtofat.Outsideof elevated serum triglycerides and an increase in liver triglyceridecontent (steatosis), a person cannot see, feel or otherwise detect thisstealthlike conversion of carbohydrate to fat until a lot of damage hasbeendone.Itwouldbehelpfultoidentifyanearlysignalofthisinsidiousdiversionofcarbohydrateintofat.

In thiscase,geneticanalysis isnotyetpossiblebecausenotenough isknown.Whenandifgeneticscanbeusedtopredictpropensitytoconvertcarbohydrates into fat is unknown. If you are consuming too manycarbohydrates, it is helpful to have an objectivemeasure on how yourbodyishandlingthedigestedsugarforlong-termsuccess.Overthelongterm, exceeding your carbohydrate tolerance is associatedwith slowedweight lossorevenweightgain,soyoumightusethescaleorperhaps

various body circumferencemeasures (e.g., waist, hip). Failure to seedownward trends in thesemeasures isasignyouhaveexceededyourlevelofcarbohydratetolerance.

However, itcantakeweeksorevenmonthstoaccuratelydetect lackofprogress. That’s a lot of valuable time wasted. If you obtained bloodwork,certainclinicalmarkerswillincreasewhentoomanycarbohydratesare being ingested. Most notable will be an increase in triglycerides.While this can serve as a reasonable gauge as to whether you haveexceeded your carbohydrate limit, values do vary fromday to day andthere is the expense and inconvenience of having to have your blooddrawnandanalyzedonarepeatedbasis.

SerumTriglycerideLevelvsComposition

Triglyceridelevelsinplasmaareafunctionofhowfasttheyareenteringthebloodstreamcomparedtohowquicklytheyarebeingremoved.Afteranypreviousmealhasbeendigestedandabsorbed, theonlysourceofnewtriglycerideinthecirculationistheliver,whichsecretesVLDLmadefrom free fatty acids, other lipoprotein remnants, or fatty acids newlymade from glucose (i.e., lipogenesis). Given this complex balance offactors, itwouldbeverydesirabletohaveaspecificbiomarkerofnewlymadefattoquantitatethedegreeonongoinglipogenesis.

Asdiscussed inChapter9,palmitoleicacid (POA)caneffectivelyservethisrole,asitsonlysignificantdietarysourcesaremacadamianutsandavocados.Thispotential biomarkerof carbohydrate intolerancehas theadvantage over SNPs in that POA changes in response to one’s diet.Thus it has the capability to assist the individual in finding the correctlevel of dietary carbohydrate intake to avoid substantial conversion ofcarbohydratetofat,andthustailorone’sdiettothatlevelofcarbohydratethancanbeefficientlymetabolized.AnobviousadvantageofmeasuringPOAis that itsproductionbythe liver isdeterminedbythedownstreamsumofmanyfactorsthatdetermineinter-organglucoseexchange.Thusit is one measure influenced by many physiologic and genetic inputs,givingitanadvantageovermeasuringafewSNPsinthisoverallpathwayandtryingtoassesstheircombinedeffect.

Summary

There is a strong biologically based argument for tailoring diets toindividuals.Effectsofdifferenttypesandamountsoffoodonhealthandweight vary widely between individuals. Although these generalobservations reflect reproducible peer reviewed science, specificrecommendations for individuals based onDNA analysis are not readyfor prime time – despite the commercial availability of nutrigenomicanalyses.

Developing the tools for DNA based nutritional recommendations is averyactiveareaof research.Thechallenge is todemystify theprocessand unravel the intricacies of how people respond to food so thatknowledgecanbetranslatedintoroutineclinicalmanagementofpatientcare.Overthenextdecade,personalizednutritioncanbeexpectedtohitthenutritionfieldlikeatsunami–besttobeaheadofthewave.

Chapter12

LOWCARBOHYDRATERESEARCHPITFALLS

Introduction

Whenaresearchpaper ispublished inapeer-reviewed journal,weareconditionedtothinkofitasanobservationthatprobablycanbebelievedastrueuntilitiseitherconfirmedorrefutedbysubsequentresearch.Youobserve something new and report it. Your observation is subjected toscrutiny and it either holds up or not. If it does, you get credit for thediscovery.Thisisplainvanillascience.

Butintherealworld,whenaresearchpaperispublishedthatreinforcesa concept that we very much want to believe, ‘we’ – the mainstreamconsensus–treatitasdogma.Afterall,ifwewanttobelievethatafewthousand years of agricultural exposure has irrevocably shifted ourgenetic makeup away from a couple of million years of evolutionarypressuregeneratedbyourhuntingancestors,what’stostopus?

If this sounds overly cynical to you the reader, please accept ourapologies. But if you have ever tried to argue the case for data overdogma,perhapsthissoundsfamiliar.

But let’s frame it another way. Every year or so, there’s a high profilecase in which a scientist fabricates data to generate a high profilepublication. This is clear scientific malfeasance. Fame, fortune, andfederal grants ride on high profile publications. Some of these peopleforfeittheirresearchcareers,andsomegotojail.

But what rarely makes the news is the much more common situationwhereascientistdesignsastudywithaparticularresultinmind.Saythatyourpreliminarydatatellyouthatyou’llprobablyseetheresultyouwantafter1weekor2weeks,butthatresultwouldn’tbelikelytopersistifyoucontinuefor4or6weeks.Isitwrongtodojusta2weekstudy?

Anothersurprisinglycommonsituation is thatascientistchoosesnot topublish‘embarrassingdata’,ordecidestopresentitinawaythatavoidsthe reader drawing the logical (but embarrassing) conclusion. But isn’tthere a peer-review ‘checks and balances’ system in place to ensureproper scientific methods and that logical conclusions are made? Yes,ideallythisistrue,buttherealityisthatthepeer-reviewsystemisfarfromperfect, and in particular tends to favor findings in line with theconsensus.Moreoftenthannot,editorsandanonymousexpertschosento review thepapergive their uncritical acceptance rather thangrapplewiththeuncomfortabledata.Onoccasionanastutereviewermaycall-outthe scientist with the comment “your data do not support yourconclusions”,butthisismoreofararitythanthenorm.

Whatwouldmotivateascientisttotakeachancethats/hemightgetsuchfeedback.

Canweallsay‘peer-pressure’?Howabout‘calculatedrisk’?

WhatWePublish,AndWhatWeCite

Science, in general, and the nutritional sciences in particular, havebecomehighlyconformist.Smartscientistsgototheirscientificmeetings,listentothediscussion,andcometounderstandwhatisacceptableandwhatisnot.Thosewhoignorethisreadilyavailableinformationdosoattheir own risk. Non-conformists tend to have trouble getting paperspublishedandresearchgrantsfunded.

Thesecond levelofcontrolover the ‘impact’ofwhat ispublished is thenumber of times a peer-reviewed publication is cited in subsequentpublishedpapers.Ifyourpapergetscitedbyanotherscientist,it’susuallyasignofacceptanceoresteem.Ifyouwantyourcareertoadvance,youneed your peers to cite your publishedpapers.Themore ‘impact’ (i.e.,citations)yourpapershave,thebetteryourreputationasascientist.Andcitations are a very subjective behavior. If your peers like your paper’sconclusions, it will get citedmuchmore than if your conclusions forcethemtochangetheirperspectiveonatopic.

Herearethreeclassicexamplesfromthelowcarbohydratedietliterature.

TheYangandVanItallieStudy

In 1976,Dr. TheodoreVan Itallie (yes, the sameonewhoaccusedDr.Atkinsof“grossinaccuracies”in1973[16])andhisjuniorcolleaguefromColumbiaUniversitypublishedapaperinthehighlyrespectedJournalofClinical Investigation. It was entitled “Composition ofweight lost duringshort term weight reduction”[92]. Drs. Yang and Van Itallie gaveextremelyobesemalesubjectseitherarelativelylowprotein(50g/d)dietcontaining90g/dofcarbohydrate,orthesameproteinwithlowcarb(10g/d)for10dayseachinacrossoverstudy.Thefatcontentsofthesetwoliquiddietswereadjustedso thatbothdietsdelivered800Caloriesperday,andthesodium(1.3g/d)andpotassiumcontents(2.4g/d)werealsoidenticalacrossthetwodiets.Usingthebesttechniquesofthetime,theinvestigators measured total weight loss and the composition of thatweightlossacrosseach10-dayperiod.

The reported rates of weight loss for the subjectswere: high carb diet0.28kgperday,lowcarb0.47kgperday.Theratesofnitrogen(i.e.,leantissue)losswere:highcarbdiet1.6g/d,lowcarbdiet2.9g/d.Thesetworatesof lean tissue lossdidnotdiffersignificantly,andsinceagramofnitrogen is theamount inanounceof lean tissue,even thecumulativedifferenceover10days (i.e., less thanapoundof lean tissue)wasnotphysiologically significant. Fat losses during the two diet periods weresimilar(notsurprisingasdietaryenergyintakeswereidentical),andthusthe differences in weight loss were due tomuch greater loss of waterduringthelowcarbohydratediet.

Intheirdiscussion,theauthorsnotedthatthemorerapidweightlosswiththe lowcarbohydratedietwasduetowater loss,accountingfor61%ofthe total. They also commented on the “slightly greater” loss of leantissue during the low carbohydrate diet, even though this was not astatistically significant difference between the two diets (and thusscientificallyinaccurate).Interestingly,theauthorsendedtheirdiscussionwith the acknowledgement that data from a shortterm study such astheirs might not predict the human response to a longer period ofcarbohydrateandenergyrestriction.

As of this writing, this paper has been cited 116 times in the peer-

reviewed literature. The most common reason for its being cited is toemphasize (incorrectly) that most of the weight loss with a lowcarbohydratedietisduetowaterloss,whileothersmakereferencetothegreater(sic)rateofleantissueloss.Andingeneraldiscussionaboutlowcarbohydratediets,thisflawedconclusionisfamouslyofferedasproofofthefutilityofcarbohydraterestriction.

Now,forcomparison,let’scontrasttheresponsetothisstudywiththattoanothersimilarstudypublished8yearslaterin1984.Entitled‘Metaboliceffectsofverylowcalorieweightreductiondiets’,thisstudywasdonebyDr.HofferandcolleaguesatMITandHarvard,andwasalsopublishedinthe Journal of Clinical Investigation[78]. So, similarly prestigiousinstitutions and the sameexcellent journal.HoweverDr.Hoffer’s paperhasonlybeencited77 times–one third lessoften than theVan Italliestudy.Whymightthisbe?

Perhaps it isbecauseDr.Hofferstudiedmoderatelyoverweightwomengivenlowandhighcarbohydratedietsofabout700Caloriesperdayfor6-8 weeks and found no difference in their rates of weight loss. Butprovocatively, what he also found was that his low carbohydrate diet(providing amore effective protein level for dieting subjects – 1.5 g/kgreference weight per day) resulted in significantlybetter preservation ofleantissueandphysicalperformancecomparedto thesamenumberofcalories as a mixture of protein (0.8 g/kg – the current DRI) pluscarbohydrate.

Inessence,whatDr.Hoffer’sstudydemonstratedwasthatinthecontextof energy restriction, protein is more effective at preserving lean bodymassthananequalnumberofcaloriesascarbohydrate.Butthiswasnotwhatthemainstreamnutritionconsensuswantedtohear,somostofthe‘experts’ tried to ignore this wellcontrolled study done under conditionsmuchmorerelevanttotherealworldofweightlossdietsthanVanItallie’sshorttermstudyofhislowprotein,highfatdiet.

TherewereotherveryimportantlessonstobegleanedfromDr.Hoffer’sstudy. At the time of both his andDr. Van Itallie’s studies, it had beenknown for decades that both total starvation and severe carbohydraterestriction increase excretion of sodium by the kidneys. Known

technicallyas‘thenatriuresisoffasting’,therewasactiveresearchbeingdone in that period to elucidate the physiological mechanism of thisphenomenon. InDr.Van Itallie’s study, he gave his subjects 1.3 g/d ofsodium, and those on the low carb diet lost a lot of body water(presumablydue to thenatriuresiseffect). It isalsovery likely that theywere constantly lightheaded, dizzy, and easily fatigued given thiscombinationofalowcarbohydratedietandaverylowsodiumintake.Incontrast,Dr.Hoffer’ssubjectsweregiven5gramsofsodiumperday,andthere was: a) no difference in water weight loss between his two dietgroups,andb)hislowcarbsubjectshadnoheadache,nodizziness,andtheirenduranceperformance(assessedinaseparateconcurrentstudy)wasasgoodorbetterthanthesubjectsgiventhemixeddiet.

Now,youmightask, isn’t it tantamount tosubjectabuse togive them5gramsof sodiumper day?Wasn’t that harmful?The simple answer is,no.Thereason:allcarbohydrate-restricteddiets,evenonesproviding50-60 grams of carbohydrate likeDr.Hoffer’smixed diet, are natriuretic –they make the kidneys dump sodium. Now, if you are bloated,edematous,orhypertensive,‘dumpingsodium’isagoodthing.Butifyoudo not (or no longer) have these fluid-excess symptoms, then over-excretion of sodium results in the above list of symptoms. And moreworrisome,itcanhavenegativehealtheffectsaswell.

Sodiumisthepositivelychargedionthatthebodyusesinitscirculatingfluid (serum and extracellular fluid) to balance the concentration ofpositive charges from potassium that is concentrated inside cells. Themembrane enzyme sodium-potassium ATPase is the ion pump thatkeepsbothofthesecationsseparatedandintherightplace.Fornerves,muscles, andother cellular functions towork right, neither of these ionconcentrations can deviate much from that of the other. With severesodiumrestriction(like1.3gramsperday,combinedwith thenatriureticeffectsofcarbohydraterestriction),thebodyrespondsfirstbymobilizinganyexcessextracellularfluid(whichiswhybloatingdisappears)andthenby contracting its circulating volume. It is this contracted circulatingvolumethatcausesdizziness,headache,andeaseoffatigue.

At some point, when confronted with this low sodium intake pluscarbohydrate restriction, most people’s defense mechanisms can’t

maintainnormalmineralbalances.Sothebody’snextlevelofdefenseisfor theadrenalglandtosecretethehormonealdosterone,whichmakeskidneytubularcellsexcretepotassiuminordertoconservesodium.Thatis,thebodywastessomeofitsintracellularpotassiuminordertoclingtowhatever sodium it can. However unless there is copious potassiumcoming in from thediet, this excessurinary potassiumcomes from thebody’spotassiumpoolinsidecells.Twothingsthenhappen.First,nerveandmuscle cells don’t work well, leading to cardiac dysrhythmias andmusclecramps.Second,becausepotassiumisanobligatecomponentofleantissue,thebodystartslosingmuscleevenifthere’splentyofproteininthediet.

Clearly none of these effects of sodium restriction are desirable,particularlywhenone is trying to losebody fatwhile retainingasmuchlean tissue as possible. Luckily, if in the context of a low carbohydratedietyougivethesubject/patientatotalof5gramsofsodiumperday(forexample2-3gramsontheirfoodand2gramsasbroth/bouillon),noneofthese bad things happen. And what about blood pressure? Typically,duringadietprovidinglessthan50gramsofcarbohydrateand5gramsperdayofsodium,bloodpressurestaysinthelownormalrange,eveninformerly hypertensive subjects just recently off their anti-hypertensivemedication.

So, were there any negative side effects of Van Itallie’s low carb, lowsodiumdietonhisresearchsubjects?Luckily,apparentlynothingmajor,but the 10-day study period was short enough that major cumulativeeffectswereunlikely.Thusitsprimarynegativeeffectwastogivefueltocriticsoflowcarbohydratediets,someofwhomtothisdaystillclaimthatthisstudyshowsthatmostoftheweightlostonalowcarbohydratedietiswater.Andthisviewpersistsinspiteofthemanysubsequentlonger-termstudies(likeDr.Hoffer’swithadequatesodium,potassium,andprotein)that demonstrate that evenwithout added resistance training, from 70-90%ofone’sweightlosscomesfromadiposetriglyceride.

TheYaleTurkeyStudy

Thisisanamazing(andcompletelytrue)tale.

In 1980, the prestigiousNewEngland Journal ofMedicine published astudybyDr.Felig’sgroupatYale,inwhichtheycompareda400Calorie“protein diet” to a 400 Calorie diet consisting of half protein and halfcarbohydrate[93]. The protein source used in both diets was boiledturkey, thecarbohydratesourcewasgrape juice,and thedietdurationsvaried from 3-5 weeks. Across the duration of the diets, whole bodyprotein losses were modest and not significantly different, but thesubjects on the protein diet lost a lot more sodiumwhile appearing togain a substantial amount of potassium. They also reported low bloodpressure in the protein diet subjects, along with reduced plasmanorepinephrine levels. The authors concluded that the protein (i.e., lowcarbohydrate) diet interfered with the adrenergic nervous system andnormalbloodpressurecontrol.Thisindictmentoflowcarbohydratedietshasbeencited145timesinthepeer-reviewedliterature.

Withinafewdaysofitspublication,anumberoflettersweresubmittedtothejournalprotestingthemethodsusedbytheauthorsofthisstudy.Butalthough the paper was published in February, the letters were notpublished until 5 months later. In their responses to these letters, theoriginalauthorswereallowedbytheeditor(apersonalfriendofDr.Felig,andthelatteralsoservedontheJournal’seditorialboard)todiscountthestatedconcernswithoutactuallyansweringthem.

So,whatwassobadaboutthispaper?Well,firsttherewastheproblemofgivingavery lowcarbohydratediet,knowntoelicit the ‘natriuresisoffasting’ without giving enough sodium to prevent overt and dangeroussymptoms. The authors claimed that they held sodium intake low andconstantacrossthetwodietsinordertobeabletopreciselymeasurethebalanceofintakeversusoutput.

Second (and most fascinating), although they had a number ofexperienced research physicians on their team, theymade an obviousproceduralerror inperforming thestudy.Asnotedabove, for their soledietaryproteintheyused‘boiledturkey’,whichtheychosebecausetheywanted to have a uniform source of protein so they could preciselymeasureeachsubject’sdailyintake.This,whenbalancedagainsturinarynitrogenexcretion (theprimarymeasureofproteinbreakdown),allowedthemtodetermineifthesubjectshadanetretentionorlossofprotein.

Butherewastheirproblem.Ratherthanmeasurehowmuchproteinwasintheboiledturkey,theyusedtheprotein(andpotassium)valuesforrawturkeyfromastandardhandbookoffoodcomposition.Theirrationalefordoing thiswas that theyonlyboiledslicesof turkeybreast forabout30minutestosoftenthem,soassumedthatlossesofproteinandpotassiumintothebrothwerenegligible.

For an experienced nutritionist, however, it was obvious from the datapublished in their paper that such losses were not negligible. Why?Becauseinwholebodybalancestudieslikethisonelastingforaperiodofweeks, when the body loses nitrogen, it also loses potassium. This isbecause leantissuecontainsa lotofpotassium,sochanges inoneareusually highly correlated with changes in the other. This is one of thebasic tenants ofmammalianmetabolism.But inDr. Felig’s subjects ontheproteindiet,theyappearedtoaverageabout2ouncesofleantissueloss per day, but ‘gained’ a lot of potassium over the same period.Because potassium and nitrogen contents of the body generally tracktogether,thisshouldhavebeenahugeredflagforboththeauthorsandthe reviewers of this paper, but itwas ignored by both. This paper gotpublished and has been cited over a hundred times, despite having ahugemethodologicalflawanddrawingthewrongconclusions.

Here’swhathappened,andhowwefigureditoutwithinacoupleofdaysof its publication. Aboriginal hunters (or more likely their wives andmothers-in-law)haveknownfromtimeimmemorial that ifyouboilmeat,youmustdrinkthebrothtostaywell.Butbackinthewinterof1980,wehad to re-invent this wheel. Simple physiology dictates that when ananimaliskilled,withinlessthanaminute,ATPinthemusclesisdepletedand sodium-potassiumATPase ceases to function.Thatmeans that bythe time any meat reaches a cooking pot, lots of the intracellularpotassiumhasleakedthroughmembranesandequilibratedwiththefluidoutsideofcells.Sowhenmeatisboiled,particularlyifitisslicedintohalf-inchthickslices,lotsofthepotassiumitcontainsleaksoutintothebroth.

Toconfirmthis,wetookfreshturkeybreast,sliceditone-half inchthick,andboileditindistilledwater(onepoundofmeatinaquartofwater)forexactly30minutes.Thenwe(bywhichImeanMarieMarcucci,theheadtechnician in theGCRCLabatMIT) analyzed the broth for potassium,

comparing this result to the handbook value for potassium in turkeybreast.Whatwefoundwasthat45%ofthepotassiuminthemeatcameout into the broth. This means that if you want to consume all of thepotassiumthatwasinthemeat,you’dhavetodrinkthebroth.TheOsagedid it, the Inuitdid it,but theseYalescientistsdidn’t.Ormoreprecisely,theydidn’thavetheirresearchsubjectsdoit.

Sohowdoesthisexplaintheanomalyinthisstudy’sresults?Let’suseasimple financialanalogy.Youdosomething thatearnsyou$100.Everydayyoudoit,andafter30daysyouassumeyou’veearned$3000.Butyou forget that you have to pay 45% tax on your income (done byautomaticmonthlydeductionsfromyouraccount).Meanwhile,everydayyouspend$60forhousing,food,andwhatever.Attheendofthemonth,you thinkyouhave$1200 left,butwhenyoucheckyourbankaccount,youdiscoveryouare$150inthehole!

So in effect the Yale scientists credited each subject with 100mEq ofpotassiumintakewhentheyonlygot55.Iftheirurinecontained70mEq,theyassumedthattheother30mEqwereretained,andthat’swhattheyreported.But in reality,with 70mEq coming out for every 55 going in,eachsubjectwas losing15mEqofpotassium frombodystores,drivenbyaldosteronebecausetheywerebeingsodiumrestricted.Andbecausehaving adequate potassium in muscle is an obligate requirement tomaintain muscle protein synthesis, this potassium deficit drovemuscleproteinbreakdowndespiteanapparentlyadequatedietaryproteinintake.

That was 1980. They published a study with a blatant methodologicalerrorthatdistortedtheirresults,wepointeditout,buttheywereallowedtoskate.Sowhatharmwasdone,andwhymakesuchabigdealoutofit30 years later?Theshort answer is that a studywasdonebyagroupwithknownhostilitytolowcarbohydratediets(e.g.,seeDr.Felig’shostileeditorials inNEJM in1978[94]and1984[95]).Theygot theanswer thatthey wanted (but not supported by their data), and the untruth that itpromotedpersiststoday.

Andwhydredgeallthisoldhistoryupnow?

Ifwecan’trecognizeourpasterrors,howdoweprogress?

CarbohydrateLoading

A beloved mainstay of sports nutrition is the concept that a highcarbohydrate intake is required to support high intensity performance.Andtheequallyfondlyheldcorollaryofthisisthatlowcarbohydratedietsimpair one’s capacity for exercise. And of course, there are copiousstudiesthatsupporttheseviews.

The classic study leading to the practice of carbohydrate loading wasdoneby twoDanishscientists,ChristensenandHansen,andpublishedin 1939[85]. Theygave trainedathletes oneof threediets,mixed, highfat,orhighcarbohydrateforperiodsof7dayseachbeforehavingthemride toexhaustionona stationarybicycle.Their observationwasprettystraightforward:themorecarbohydrateinthediet,thelongerthesubjectcouldpedal.

This concept was picked up in the 1960s by a team of Swedishscientists[86], one of whom (Dr. Jonas Bergstrom) had developed aneedle that allowed muscle biopsies to be obtained without surgery.Using this needle, theywereable to showadirect correlationbetweenthe amount of glycogen in a muscle and the duration of exercise thatmusclecouldsustain.Theirdatawereclearandunequivocal,andmanysimilarstudiesdonebyothershaveconfirmedtheirfindings.

But there is justoneminor issuewith thiswholebodyof research; inaword,duration.ChristensenandHansenused7daydiets,Bergstrom’sgroupused7-10days,andmanyothersusedperiodsofdietadaptationasshortas4days.WhenaSwedishcolleagueofthisgroupwasaskedwhytheydidn’tuselongerperiodsofadaptationtothelowcarbohydrate,high fatdiet,he replied that theycouldn’tgetathletes toeat thatmuchprotein for any longer period. It seems that their idea of a lowcarbohydratedietwastofeedtheirsubjectslotsofleansteak!

This is an interesting twist, given the long and successful history ofScandinavianexplorers in theArctic. In 1885-6,Nansenand Johansenleft theresearchshipFramandmadeanattemptat reaching theNorthPole[96]. On their return, they came ashore on an uninhabited islandnorthofRussiawhere theywerestranded forayear livingonsealandpolarbear.Andduringhis first transitof theNorthwestPassage,Roald

Amundsenspent twoyears livingamongtheInuitonKingWilliamLand(nowcalledNunavut).ThustheScandinavianswerewellacquaintedwiththedietsofPolarcultures.Butthesewerebothsituationsdictatedbytheneedforsurvival.NoonewouldeatanInuitdietbychoice,right?

Well,hereareafewnamestochewon:JohnRae,FrederickSchwatka,and Vilhjalmur Stefansson. All of them traveled thousands of milesthroughtheArcticbetween1840and1920employingtheclothing,tools,anddietoftheInuit.Consumingadietthatwasmostlyfatandmoderatein protein, clearly the lack of dietary carbohydrate didn’t seem to holdthemback.Andinaparticularlytellingpassagefromhisdiary,SchwatkanotedthatittookhimbetweentwoandthreeweekstoadapttotheInuitdiet,“afterwhichprolongedsledgejourneysarepossible”.

These observations suggest that the ‘Achilles heel’ of thecarbohydrateloadingstudiesistheirshortduration(asinnotenoughtimeallowedforadaptation),andperhapscompoundedbyallowingtheirfearoffattodrivethemtotrytoeattoomuchprotein.Totestthisconcept,wedidapairofstudiesafewdecadesago[23,76].

Thefirststudyinvolvedsixsubjectsgivenaverylowenergy(about700Calories per day) meat diet for 6 weeks, during which the averagesubjectlost25pounds,whichmeansthatmostoftheirdailyenergycamefrom body fat stores. Everybody was given supplements of sodium (3gramsperday),potassium,andamultivitamin.Beforethediet,afteroneweek,andafter6weeks,eachsubjectwalkeduphillonatreadmilluntilexhaustion.Theaveragetimesonthetreadmillwere:168min,130min,and269min.Clearlyoneweekdidnotallowenoughtimeforthesubjectstoadapttothelowcarbohydratediet,andtheirexercisetimesdecreased.After6weeks,however,therewasamajorreboundinperformance.Butbeforegettingtooexcitedbythishugeincrease,weneedtopointoutthatdespitehavingeachsubjectcarryabackpackthatbroughtthembacktotheir starting weight, both their pulse rate and measured oxygenconsumptionindicatedthattheyweredoinglessworkatthesameangleand speed on the treadmill during that final test. But that problemnotwithstanding,thesesubjectsobviouslywerenotincapacitatedbytheir6weeksonaverylowcarbohydrateintake.

Toovercomethisissueofimprovedefficiencywithweightloss,andtogetamoreprecisemeasureoftheeffectsofdietarycarbohydratealone,wedida secondstudy.This timewe recruited5bicycle racers– leanandhighlytrainedyoungmen.Becausetheyhadlittleifanyextrabodyfattolose,wefedthemamoderateprotein(15%ofenergy)andveryhighfatdiet (>80% of energy) patterned after what Stefansson ate in BellevueHospital in 1928. However because we were not interested in issuesrelatedtovitaminsandminerals,wealsogavethem5gramsperdayofsodium,1gramofpotassium,calciumandmagnesiumsupplements,andavitaminpill.Andnoneofthemeatwasboiled!

Atbaseline,theaveragesubjecthadapeakaerobicpowerof5.1litersofoxygenperminuteandrodethestationarybikeat60%ofthisvaluefor147minutes.Thistranslatesintoaveryimpressive900Caloriesperhourfor twoandahalfhours (withonlywaterallowedduring the ride).AfterfourweeksontheInuitdiet,theirpeakaerobicpowerwasunchangedat5.0 liters perminute, and their duration at the samepower outputwas151 minutes (again no significant change from the high carb baselinevalues).Whatdidchangedramaticallywasmuscleglycogen.Comparedtobaseline, theystarted thesecond ridewithonlyhalfasmuchof it intheirthighmuscles,andtheyonlyusedaquarterasmuchtodothesameamountofwork.Wealsomeasuredtheirbodies’useofbloodsugarandtotal carbohydrate oxidation, and both of these were also dramaticallyreduced.

Whatdidthisprove?Well,ifyou’reacynic,youcouldsaythat100yearslaterwe justprovedFrederickSchwatka right.Butwealsoproved that,giventherightamountofproteinandmineralsplusenoughtime(inthiscase, 4 weeks) for the human body to adapt, there is not a directcorrelation between muscle glycogen content and work performance.However, this correlation between muscle glycogen content andperformance is the key principal of the carbohydrateloading construct,and our study demonstrated that it is only valid in the context of shortterm changes in diet. Thus, although the oft bandied truism that lowcarbohydratedietsnecessarilyimpairphysicalperformanceremainsaliveinthemindsofthosewhowanttobelieveit,inrealityitnolongerhasabasisinscientificfact.

Summary

Philosophers have been debating the meaning of scientific truth forthousandsofyears,andthischapterhasn’tmovedthatboulderveryfarupthehill.Also,nothingwehavepresentedhererepresentsfraud.Whatwehavepresentedarethecontrastingfatesofresearchdatapertainingto low carbohydrate diets, and how this plays out in the context of amainstream nutrition consensus that remains strongly biased againstcarbohydraterestriction.

Allof thestudiesmentionedabovewerepublishedmore than25yearsago, and in readily accessible and respected journals.Sowhatwearenot dealing with is the Warren & Marshall syndrome* – that 10 yearwindow of hoping uncomfortable data will go away has long sinceexpired.Howeverwehopethatwehaveprovidedyouwithsomecriticalinsight into how data is pitched by the medical media, and how thethoughtfulreadercanoftenfindthetruthbetweenthelines.

Wealsohope that the issueswehavediscussedherebringabitmoreclarity to futureresearch.Forexample,defininga lowcarbohydratedietas one under 100 grams per day of carbohydrate or less than 15%ofdaily energy intake would help, as would differentiating betweenketogenic and nonketogenic diets. Similarly, recognition that dietsbetween40-60%ofenergyas fatare fundamentally (andmetabolically)different from those providing 70-80% as fat, and thus lumping themtogetherunderthesingleheading“high-fat”ismisleading.Andfinally,theongoingspateofshorttermstudiespurportingtorepresentthelong-termeffectsofcarbohydraterestrictiondoesadisservicetothescienceofthisfield (e.g., a recent 5-day studybyHollowayet al.[97]).Avoiding thesepitfallswouldgoalongwayinresolvingmuchoftheconfusionaboutlowcarbohydrate diets, and this clarity would serve the interests of thosepatientswhostandtobenefitfromtheiruse.

*seesidebarinChapter14,MetabolicSyndromechapter,page177

Section4

CLINICALAPPLICATIONS

Chapter13

CLINICALUSEOFCARBOHYDRATERESTRICTION:VERYLOWCALORIEANDLOW

CARBOHYDRATEDIETS

Introduction

Theevolution of carbohydrate restriction as a clinical tool over the lastcenturyhasbeenessentiallyasearchforsustainability.Inthefirsthalfofthe 1900s, the beneficial effects of total (or sub-total) starvation onconditions ranging from diabetes to epilepsy were observed. However,the negative effects of starvation on lean body mass and functionnecessarily curtails its use beyond brief periods. The exception to thispattern was the very high fat ketogenic diet developed by Wilder andPeterman for pediatric seizures, but this was considered by mostpractitioners to be too severe, and thus (perhaps inappropriately)supersededbydrugs.

The1970sbroughtusverylowcaloriediets(VLCD;akaproteinsparingmodifiedfasting)comprisedofeithercommonfoodsorpreparednutrientformulations. Most were used under medical supervision, includingmonitoringandprovisionofsupplements.Anexceptiontothispracticeofclinicalmonitoringandappropriatesupplementsledtothe“LiquidProteinDiet” scandal – a problem of inadequate formulation and inadequatemedical monitoring[98]. Typically providing between 300 and 800Calories per day, VLCDs allowed severely obese patients to achieverapidandmajorweightloss.Butoncetheweightlosswasachieved,thestate of nutritional ketosis induced by the carbohydrate restriction wasrelinquished (because most people then returned to a “balanced”maintenancediet),alongwithmanyofitsassociatedmetabolicbenefits.

ParallelintimetothepopularityofVLCDs,Dr.RobertAtkinspromotedaless energy-restricted approach to a ketogenic diet. His focus was on

keeping carbohydrate intake low enough to induce ketosis, but not toseverely limit (or even count) calories. To achieve this, he advisedindividuals to eat protein and fat to satiety while keeping dietarycarbohydrates lowenoughtomaintainpositiveurineketones. Itwashisview that this diet, including vegetables, limited fruit, and vitaminsupplements,couldbefollowedbytheindividualoutpatientwithoutclosemedical supervision unless there was a pre-existing complicatingcondition likediabetesorhypertension.Formostpatients,however, theAtkinsdiettendedtobeonlyatemporarysojournintonutritionalketosis,whetherforwantofsweetsorwantofapprobationfromtheirfriendsanddoctor.

However, in these parallel few decades of the VLCD and Atkins diet,hundreds of studies were done, and we learned a great deal aboutcarbohydrate restriction. Among these lessons are many which cancontributetothesafeandsustainableuseofcarbohydraterestricteddietsgoingforward.

CountingCaloriesvsCarbs

ItwasDr.Atkins’contentionthatwhenmostcarbohydratewasremovedfromthediet,heavypeople loseweightmoreeffectively thanbyclassicbalanced calorie restriction. The mechanism was (and remains) hotlydebated.Claimsofreducedmetabolicefficiencyduringnutritionalketosisremainunproven.Amongotherpointsagainst this is thefact thatStevePhinney’s bike racers produced the samepower output in testing on astationarybikeusingthesameoxygenconsumptionafteradaptingtotheInuitdietcomparedtotheirtestonahighcarbdiet[23],leavinglittleroomformetabolicinefficiencyinthisgroupofsubjects.

But this argument over the mechanism of weight loss is an academicstraw-man. In study after study, over the first 3-6 months, peoplerandomizedtoalowcarbdieteatentosatietylosemoreweightandmorebody fat than those assigned to a low fat, calorie restricted diet. Acrediblemechanismtoexplainthisisnothardtofind–carbohydratesinourdietmayofferashorttermsenseof increasedenergy,buttheyofferlittleinthewayoffunctionalsatiety.

ThebestexampleofthiseffectwasreportedbyDr.GuentherBoden[45]inaninpatientstudyofobesetype-2diabetics.Afteraweekofeatingabalanceddiettosatiety,thesubjectsweregivenalowcarbohydratedietconsistingofmostof thesamefoods,withtheexceptionthat theywereaskedtolimittheirtotaldailycarbohydrateintaketo20grams.Overthenext two weeks, their spontaneous nutrient intakes were carefullymeasured. Interestingly, the subject’s average daily energy intakedroppedfrom3100to2100Calories,andthiswasallduetothe‘missing’carbs.Despitehavingthechoicetoeatmore,theproteinandfatintakesof these subjects remained relatively constant. And despite this 1000Calorie per day deficit, their reported hunger, satisfaction, and energylevels did not changeappreciably.What did changewas their diabetescontrol–dramaticallyforthebetter.Formoreonthistopic,seeChapter15.

Butthisstudywasjust2weekslong.Whathappensinthelongerterm?Well,theprocessoffullmetabolicadaptationtoalowcarbohydratediettakes up to 6 weeks, so for the first few months, we would expectwellbeingandfunctiontogetbetter.Butaftermanymonthsandamajordegreeofweightloss,itisanormalresponseofthehumanbodytotrytolimit its losses. This is typically achieved by eatingmore, but what? Ifdietarycarbohydrateintoleranceledtothechoiceofalowcarbohydratediet at the outset, why lift that restriction? In particular, why add backcalories that promote fat storage but do not provide functional satiety?Acceptingthatproteinisgoodforusonlyinmoderation,theanswerisfat(seeChapters2and16).Howmuchfatshouldyouaddasyouapproachweightmaintenance?Thesimpleanswer:“letsatietyrule”.

Ketones–ToMeasureorNot

As noted in Chapter 1, nutritional ketosis is defined by serum ketonesranging from 0.5 up to 5 mM, depending on the amounts of dietarycarbohydrate and protein consumed. In most people, the combinedintakeof100gramsofcarbohydrateand100gramsofproteinwilldriveserumketoneswellbelow0.5mM.Whilethereisnothingmagicalabouthaving circulating ketones above this threshold level, it does have thepracticalvalueofprovidingthebrainwithavirtually limitless,fat-derived

fuel source. This alternative fuel is eminently more sustainable,particularlyintheinsulinresistantorcarbohydrateintolerantindividual.

Within a few days of starting on carbohydrate restriction, most peoplebeginexcretingketonesintheirurine.Thisoccursbeforeserumketoneshaverisentotheirstableadaptedlevelbecauseun-adaptedrenaltubulesactively secrete betahydroxybutyrate and acetoacetate into the urine.This is thesamepathway that clearsotherorganicacids likeuricacid,vitaminC,andpenicillinfromtheserum.

Meanwhile, the body is undergoing a complex set of adaptations inketonemetabolism[99].Betahydroxybutyrateandacetoacetatearemadein the liver in about equal proportions, and both are initially promptlyoxidizedbymuscle.Butoveramatterofweeks,themusclesstopusingthese ketones for fuel. Instead, muscle cells take up acetoacetate,reduce it tobetahydroxybutyrate, and return it back into the circulation.Thus after a few weeks, the predominant form in the circulation isbetahydroxybutyrate,whichalsohappens tobe theketonepreferredbybraincells(asanaside,thestripsthattestforketonesintheurinedetectthepresenceofacetoacetate,notbetahydroxybutyrate).Theresultofthisprocessof ketoadaptation isanelegantly choreographedshuttleof fuelfromfatcellstolivertomuscletobrain.

Inthekidney,thisprocessofketoadaptationisalsocomplex.Overtime,urineketoneexcretiondropsoff,perhapstoconserveavaluableenergysubstrate(althoughurineketoneexcretionneveramounts toverymanywastedcalories).Thisdecline inurineketoneshappensover thesametime-course that renal uric acid clearance returns to normal (discussedbelow) and thus may represent an adaptation in kidney organic acidmetabolisminresponsetosustainedcarbohydraterestriction.

Thesetemporalchangesinhowthekidneyshandleketonesmakeurineketonetestingaratheruncertain ifnotundependablewayofmonitoringdietary response/adherence. Testing serum for betahydroxybutyrate ismuch more accurate but requires drawing blood, and it is expensivebecauseitisnotaroutinetestthatdoctorsnormallyorder.

A non-invasive alternative is tomeasure breath acetone concentration.Acetone is produced by the spontaneous (i.e., non-enzymatic)

breakdownofacetoacetate.Becauseit isvolatile,acetonecomesoutinexpiredair,anditscontentislinearlycorrelatedwithbloodketonelevels.Anumberofbusinesseshavedevelopedprototypehandhelddevicestomeasurebreathacetone,butatthetimeofthiswriting,nothingpracticalisonthemarket.

Butwhatevertestisused,thekeyquestioniswhydoit?Manypeopleareable to initiateand followa lowcarbohydratediet just finewithoutevermeasuring ketones. Others, however, find an objective measure ofnutritional ketosis to be reassuring. In some clinical settings, ketonetesting is used as a measure of ‘diet compliance’. While this may beusefulintheshorttermtokeeppatientsontrackinastrictlyregimenteddietaryprogram,itbegsthequestionofhowthatindividual’sdietwillbemanaged long term. For this purpose, the handheld breath acetonemonitorsunderdevelopmentholdsomepromiseasaguidance toolputinto the hands of the individual striving to find the right level ofcarbohydrateintakeforlong-termmaintenance.

Biochemicalchanges(uricacid,acid/base,electrolytes,cholesterolmobilization)

There are often dramatic but wholly predictable changes that occur inblood chemistry values upon initiation of a low carbohydrate diet.As aresult,andalsodue to thevery limited food intakesofpeople followingverylowcaloriediets,mostclinicsusingthemdoroutinebloodtestsoverthe first few months of dieting. Because of the greater intake ofvegetablesandtotalenergy,alessrestrictedlowcarbohydratedietsuchasAtkinsraisesfewerconcernsinanotherwisehealthypatient.Thusthechoiceoflaboratorymonitoringinthisinstanceislefttoone’sphysician,whoshouldalwaysbeconsultedbythepatientbeforestartinganyweightlossregimen.

Early on in theVLCDera, hypokalemia (lowbloodpotassium)wasnotuncommon,butoncewelearnedtosupplyamodicumofsodiumtoavoidaldosterone-induced potassium wasting, this became a rare finding(limited usually to individuals with the concurrent use of diuretics).However,persistenthypokalemiaunresponsivetosodiumandpotassiumreplacement can be a sign of underlying magnesium depletion[100].

Since serum magnesium is poorly correlated with intracellularmagnesium,thebest‘test’formagnesiumdepletionisa20-daycourseoforal replacement (see Chapter 18) as long as the patient has normalrenalfunction.

Averypredictablechangeinserumchemistryisasharpriseinuricacidconcentration in the first week or two of carbohydrate restriction. Asnotedabove,this isduetocompetitionbetweencirculatingketonesanduricacidforrenaltubularexcretion.Putanotherway,uricacidrisesinthebloodnotbecausethebodyismakingmoreofitbutbecausethekidneystemporarilyclearlessofit.Thusthebloodlevelneedstoriseinorderforthesameamountofittobeclearedbythekidney(becauseketonesare‘getting in the way’). Subsequent to this abrupt early rise in uric acid,within 4-6weeks the level then falls back to or below its pre-diet levelevenifthedietarycarbohydraterestrictionandketonemiacontinue.Thisispartofthebody’songoingadaptationtonutritionalketosis.

Inthevastmajorityofpatients,thisriseinserumuricacidiscompletelybenign and requires no intervention. In the minority of individualspredisposed to gout, however, wide swings in uric acid can trigger anattack.Andthisgoesbothways–eithertheabruptrisewithdietinitiationortheanalogousabruptfalliftheketonemiaisreversedbybreakingthecarbohydraterestrictioninthefirstfewweeks,canactasatrigger.Mostpeoplewith the genetic predisposition to gout know it long before theyconsider a low carbohydrate diet, so either preventative medication orpromptinterventionatthefirstsymptomscanusuallypre-emptanattack.Also,becauseitistherapidchangeinuricacidthatistheprimarytrigger,onceonacarbohydraterestricteddiet, thepatientwithahistoryofgoutshouldbecounseledtoavoidfrequentcyclinginandoutofcarbohydraterestriction(i.e.,avoid‘goingonandoffthediet’).

There is a persistent myth that nutritional ketosis results in clinicallysignificantacidosis,despiteoverwhelmingevidencetothecontrary.Yes,the modest rise in serum ketones will shift serum chemistries a bittowardstheacidend,butbloodpHandserumbicarbonatevaluesalmostalwaysremainwellwithinthenormalrange.Andthedegreeofthisshiftin pH is considerably less than that seen with just 5-7 days of totalfasting,which ispartofnormalhumanphysiology.Putanotherway, the

buffering capacity of otherwise healthy humans is able to compensateacross the full range of nutritional ketosis without any significantmetabolic disturbance. Thus acid/base status does not need to bemonitored during carbohydrate restriction in otherwise healthyindividuals. In type-2 diabetics, however, if there is any question of anindividual’s insulin reserve (e.g., low serum insulin in the context ofelevatedbloodglucose),monitoringofserumketonemiaandbicarbonatelevelsshouldbecarefullyconsidered.

There is one anomaly in clinical testing that physicians and patientsshouldbeawareof:a transient rise in serum totalandLDLcholesterolthatcanoccurwithmajorweightloss.Wereportedthisin1991[101],andour research revealed the cause. It turns out that along with thetriglyceride stored in adipose tissue, our fat cells also contains a smallamount of dissolved cholesterol. After about 30 pounds ofweight loss,the shrinkage of these cellular fat droplets proceeds to the point thatsomeofthischolesterolhastobereleasedintotheserum.Theamountof cholesterol involved is 100-200 mg per day in someone losing 2poundsofadiposetissueperweek.Interestingly,althoughthisrepresents‘reverse transport’ back to the liver, this cholesterol rise appears in theLDL fraction.Butonceaperson’sweight lossceases, thisexpulsionofcholesterol stored in adipose tissue stops and serum LDL cholesterolreturnstoitsnewpost-weight-lossbaseline.

So ifyouoryourpatientexperiencea rise inserumLDLcholesterolasthescalepasses30ormorepoundsofweightloss,don’tpanic.Thisisasignthatyourbodyisdumpingpreviouslyaccumulatedcholesterol.Sincethis situation typically lasts only a month or two, whereas it takesdecadesofelevatedLDLcholesteroltocausebloodvesseldamage,theprobability of any clinical risk is very small.Wait until your weight hasstabilizedinmaintenanceforamonthortwoandthentestyourLDLlevelagaintobesureithascomebackdown.

DietaryFatandGallbladderHealth

Although this transient rise in LDL cholesterol duringmajorweight lossmaylookworrisomeatfirst,itisatransientanomalyassociatedwiththebody’s dumping cholesterol that had slowly accumulated in excess

adiposetissue.Thepathofthischolesteroloutofthebodyisasfollows:it is taken up by the liver, secreted into bile which is stored in thegallbladderandthenexcretedviathegastrointestinaltract.

On its face, the100-200mg/day rateof clearancedoesnot sound likemuch.Afterall,wetypicallyeatmorethan300mgofdietarycholesterolperday.Butmostof thecholesterolweeatnevergetsabsorbed,soanadded 100-200 mg/day transiting the gall bladder is actually a fairamount.Ifsomeonewhohasalreadylost30pounds(thustriggeringthiseffluxofcholesterol)proceedstoloseanother30poundsover3months,thataddsupto10-20gramsofstoredcholesterolthebodyhastogetridof.

Is this a problem? Well, not as long as the gallbladder gets regularsignalstocontract,comingintheformofcholecystokininreleasedbytheuppersmallbowelinresponsetodietaryfat.However,ifdietaryfatintakeislow(under30gramsperday)duringrapidweightloss,thegallbladderdoesn’t get the signal to empty itself, and this cholesterol can build upandincreasetheriskofgallstoneformation.BackintheVLCDera,someof thecommercial formuladietswerevery low in fat,and theirusewasassociated with a surprisingly high rate of gallstone formation[102].However, if ameat/fish/poultry VLCD containing the associated naturalfatswasused,or30ormoregramsoffatwasaddedtoaliquidformula,newgallstoneformationwasrarelyaproblem.

Addonemore item to the list of benefits of dietary fat. It protects yourgallbladderfromgallstonesduringmajorweightloss.

LevelofMedicalMonitoring

All individuals considering a low carbohydrate diet should consult theirphysicianbeforestarting.Butunlesstherearesignificantabnormalitiesincardiac, liver,kidney,orendocrinefunctions, frequentclinicalmonitoringmaynotbenecessaryasthedietproceeds.Clearly,medicationsforhighblood pressure, fluid retention, glucose control, and dyslipidemia willneedtobeadjusted(usuallythismeanswithdrawnordecreased)asthedietproceeds–oftensoonerratherthanlater.

YouToo,Doctor!

Weknowofmorethanonephysicianwhohasheardusgiveatalkandthen launched themselves into a carbohydrate restricted diet. Typicallywefindoutaboutitinthefollowingtypeofconversation.

Them: “I love theweight loss on your diet, and I’ve been able to takemyself off my (blood pressure and/or diabetes) medications, but howcomeIfeelsolousy?”

Us:“Haveyoureadourbook?Areyoudrinkingbrothregularly?”

Them:“Book?Broth?”

Having read this far, youknowwhy theseare important foryourhealthand wellbeing. And when you’ve finished the last chapter, you will bebetterequippedthanmostofyourcolleaguestomanagepeoplewiththispowerful clinical tool. But particularly if you are on medication for aweight-related condition, you need a physician (other than yourmirror)monitoringyourprogress.Ifyourpersonalphysicianisn’texperiencedinthe use of low carbohydrate diets, Jimmy Moore (Chapter 21) has aservicetohelpyoufindonewhois,oryoucanjustgiveyourphysicianacopyofthisbook.

RoleofClinicalSupport

Independentofmedicalmonitoringofone’s lowcarbohydratediet, thereis an additional role for ongoing clinical support. Multiple studies withdietsacrossawiderangeofmacronutrientcompositionshaveshownthaton average the amount of weight loss is positively correlated with thenumberof visits toasupportgroupor clinic.Thisobservationhelpsusunderstand thewidevariations in theamountsofweight loss instudiesusing the same diets. But there is one important caveat – the supportprovided needs to be appropriate in content to the diet in question. Ifpatientsonalowcarbohydratedietattendanutritioneducationgroupinwhichtheyaretaughtthathighfatdietsandsaturatedfatsarebad,thenet effect on that person’s weight loss and wellbeing is likely to be

negative.

ListofIndicationsforLowCarbohydrateDieting

Inadditiontoitssuperiorperformanceinachievingweightloss,thereareahostofconditionsthatrespondbettertocarbohydraterestrictionthantootherdiet or lifestylemeasures.Althoughmanyof theseconditionsareassociatedwithinsulinresistance,someotherssuchassleepapneaandseizuresarenot.

insulinresistance/metabolicsyndrometype-2diabeteshypertensionpolycysticovarysyndrome(PCOS)gastroesophagealrefluxdisease(GERD)sleepapneamedication-resistantseizures

Summary

Weight loss induced by a wellformulated very low calorie diet can bedramatic, but VLCDs require closer medical supervision than acarbohydraterestricteddietprovidingmoreenergyandabroaderrangeof foods such as the Atkins Diet. Furthermore, the question of how totransition from a VLCD into a sustainable weight maintenance dietremainsan issue,whereas it isamorenatural transition from theearlyphasesofAtkins toa lowcarbohydratemaintenanceenergy intake.Thisis achieved by the simple expedient of maintaining the appropriatedegreeofcarbohydraterestrictionandaddingmorefat.

Thebeneficialeffectsassociatedwithnutritionalketosismakethisclassofdietsadvantageousinthetreatmentofanumberofclinicalconditions.However, the often dramatic improvements in blood glucose control,bloodpressure,and fluid retention requirepromptadjustments insomemedications.Therefore,asthecomplexityoftheseassociatedconditionsisincreased,closermedicalattentionandmonitoringmayberequired.

Chapter14

METABOLICSYNDROME

Introduction

A chapter on metabolic syndrome might best be told as a “whodunit”detective story. The victims: approximately 64million or 34% of adultswithmetabolicsyndromeintheUnitedStates[103].Theperpetrator(s)ofthecrime:acastofallegedsuspectshavebeenidentified.Likeanygoodmystery, a web of deception has been artfully cast to cloak the realculprit. For a while at least, the wrong suspect has been put in jail. Ifyou’re clever though, maybe you’ve already deduced the truly guiltyparty.But ifnot, inthischapterwe’ll layoutthekeycluestothepuzzle.And once deprived of his cloak, the villain, awell known player at themetabolictable,willbeinescapablyrevealed.

ConnectingtheDots–SolvingtheCrime

met·a·bol·ic (adjective) \\me-t-bä-lik\ - of, relating to, or basedonmetabolism.

syn·drome(noun) \sin-drimagem\ - a group of signs and symptoms thatoccur together and characterize a particular abnormality orcondition.

As the definitions imply, metabolic syndrome describes a collection of

metabolic abnormalities. These derangements in combination are aharbinger of type 2 diabetes and cardiovascular disease. With anycollectionofsymptoms,agoodscientificdetectiveaskswhetherthereisacommoncause.Inthecaseofmetabolicsyndromethecommonthreadlinking an ever growing constellation of abnormalities is insulinresistance. Insulin resistance is defined as a diminished response to agivenconcentrationofinsulin.Whileinsulinresistancemaybedoingthedirtyworkat thecellular level, theringleaderof themetabolicsyndromecrime syndicate is dietary carbohydrate. Since the inability to properlymetabolizedietarycarbohydrateisthedirectresultwheninsulinactionisimpaired, froma functional perspective, insulin resistance canbemoreaccurately described as carbohydrate intolerance.When viewed in thiscontext,carbohydraterestrictionisafullyrationalapproachtotreatingthediverse factors that congregate in metabolic syndrome. Restrictingcarbohydrate is akin to arresting the crime boss – once you put thecorrectperpetratorinjail,everythingelsefallsintoplace.

Syndrome X, Insulin Resistance Syndrome, and MetabolicSyndrome

Dr.GeraldReavenisgenerallycreditedwithmakingtheobservationthatindividuals with insulin resistance (as evidenced by hyperinsulinemia)showedcommonmetabolicdisturbancesthatsignificantlyincreasedtheirriskofcardiovasculardisease.In1988hetermedthislocusofsymptoms‘syndrome X’[4]. Later he used the term ‘insulin resistance syndrome’,whichmore accurately reflected the underlyingmetabolic problem.Therelatedterm‘metabolicsyndrome’wasintroducedbytheAdultTreatmentPanelIII(ATPIII)oftheNationalCholesterolEducationProgram.Reavenviewedthemetabolicsyndromeasadiagnostictooltoidentifypeopleatincreased cardiovascular disease (CVD) riskbasedon thepresenceofspecificcriteria(seesidebar).Regardlessofthetermused,thepresenceofinsulinresistanceisacceptedastheunderlyingphysiologicconstruct.Interestingly,Reavenrecognizedthatthefavoreddietofthetime–alowfat/high carbohydrate diet –would exacerbate the syndrome. Thiswasself-evidentfromthetitleofhis1997reviewpaper[104]entitled“Dohighcarbohydrate diets prevent the development or attenuate themanifestations (or both) of syndromeX? A viewpoint strongly against”.

Reavenwascognizantthat“…lowfat/highcarbohydratedietsshouldbeavoided in the treatment of syndrome X.”, but few took heed of suchwarnings amidst the tsunami-like forces advocating in favor of fatrestriction.MetabolicSyndromeDefined[105]

You have metabolic syndrome if at least three of the following arepresent:

•Waistcircumference:

40inches(men)or

35inches(women)

•Fastingtriglycerides:

150mg/dL

•HDL-C:<40mg/dL(men)or<50mg/dL(women)

•Bloodpressure:

130/85mmHgoruseofhypertensivemedication

•Fastingglucose:

100mg/dLoruseofhyperglycemiamedication

CompetingParadigms

Now that two decades have passed, why has carbohydrate restrictionbeen ignored as an optional (if not preferred) treatment for metabolicsyndrome? There are probably many reasons, but the 3-decadeobsession with the diet-heart hypothesis, which focuses on reducing

elevated LDL cholesterol (LDL-C), stands out. Note in the above tablethatLDL-Cisnotafactor inthediagnosisofmetabolicsyndrome.Thusdietary changes targeted at lowering LDL-C are different from thoseaimedatdecreasinginsulinresistance.Fromatreatmentperspective,thediet-heart paradigm and metabolic syndrome represent separateabnormalitiesthatincreaseCVDrisk.

Butat itsheart,ourmedical researchestablishment is reductionist. It isclear that the authors of official dietary guidelines prefer to promote asimpleunifiedmessageratherthanexplainingtothepublicthatthereisalogicalchoiceoftreatmentoptionsdependingontheunderlyingcauseofincreasedCVD risk. Thus the fact that dietary fat restriction is not thepreferred diet therapy formetabolic syndromehasn’t sat verywellwiththemainstreammedicalconsensus.Assuch,alternativeapproacheslikelowcarbohydratedietsare ignoredorcondemned,despite the fact thattheir efficacy and safety are based on solid biochemical andmetabolicgrounds,supportedbybothscientificstudiesandclinicalexperience.

CarbohydrateRestriction–TheElephantintheRoom

Over the last 20 years there have been tens-of-thousands of studies,review papers, and international scientific conferences focused onmetabolic syndrome.How often can thewords carbohydrate restrictionbe found in the thousands of peer-reviewed papers on metabolicsyndrome?Howoftenarethesewordsutteredbyresearchers/cliniciansatseminarsaboutinnovativetreatmentoptionsformetabolicsyndrome?Truthfully?Hardlyever!

This situation is so bizarre youmight think copy editors are trained toremove these words from manuscripts and speakers forced to signcontracts to avoid mentioning low and carbohydrate in the samesentence. How did this level of cognitive dissonance become sopervasive across the medical field? And what compels otherwisereasonable healthcare professionals to ignore a potent tool for treatingmetabolic syndrome; opting instead for ineffective treatments based onlowfatdietsplusunprovendrugcombinations?

Theexplanationofthisdisconnectbetweendataandconsensusthinking

ismorebehavioralthanbaseduponclinicalscience.Clearlytheresearchsupporting low carbohydrate diets induces anxiety in many healthprofessionals, who respond with various rationalizations to support thestatus quo. However, we also need to recognize that changes in themedical consensus rarely occur as an “AhaMoment”.More commonly,change in response to scientific discovery is a long drawnout processthatplaysoutinslowmotionoveradecadeormore(seesidebarbelow).A Classic Example of Resistance to Change: Peptic Ulcers andHelicobacterpylori

ArecentexamplesymbolicoftheresistancetochangingmedicaldogmaisthetreatmentforupperGI(stomachandduodenal)ulcers.

Between 1984 and 1989, two Australian scientists (Drs. Warren andMarshall)published5papersintopqualityjournalsthatprovedbeyondadoubtthatabacterial infection(ratherthantoomuchacid)causedmostulcersinthestomachandduodenum.Afterthat,yearafteryear,doctorsstilltreatedulcerpatientswiththesameoldineffectivedietsandantaciddrugs;andinseverecases,withmajorsurgery.In1988,frustratedbyhisinability to convince other scientists of his discovery,Dr.Marshall eveninfected himself with this bacterium and promptly developed a case ofacutegastritis.Finally,about1995,themedicalconsensus‘flipped’,andthe hot new treatment for ulcers became an antibiotic cocktail toeradicateHelicobacterpylori.Tenyearsafter that, in2005,Drs.WarrenandMarshallwereawardedtheNobelPrize.

Is this justacaseof ‘Mondaymorningquarterbacking’?Were the initialresults ofWarren andMarshall fuzzy or inadequately described?Weretheirresultshardtoconfirm?Ifyou’veevertriedtotellyourdoctoraboutsomethingnew,perhapsyoumightnotbesurprisedthattheanswerstoallthreequestionsareno,no,andno.

After their initial publications, it would have taken less than a year foranotherresearchgrouptoreproducetheirresultsandpublishthem.Afterall, the typical antibiotic cure only lasts 2 weeks, and healing beginswithinafewdays.Soatthevery latest,confirmationof theirhypothesisshould have been published by 1990 and the treatment paradigm

changed.Instead,theideathatbacteriacouldgrowandcauseproblemsintheacidenvironmentofthestomachwasdiscountedout-of-hand,ifnotridiculed, by the experts. Why? Perhaps people regarded as expertsbecomeusedtodoingsomethingonewayfordecadesanddon’t liketoadmit that another way might be better. And because this is not anisolated phenomenon, forwant of a better term, let’s call this systemicreticence to accepting obvious change ‘the Warren & MarshallSyndrome’.

InsulinResistanceSyndrome

In simple terms insulin resistance is a state in which a givenconcentrationof insulinproducesa less thanexpectedbiologicaleffect.However,akeycharacteristicofmetabolicsyndrome is that theclinicalexpressionof insulinresistance isvariable,manifesting itself indifferentways. This is a reflection of the multiple roles played by insulinthroughoutthebody.Dependingonwhere(e.g.,skeletalmuscle,liver,fatcells, etc.) and how much insulin resistance is present, the metabolicsigns can vary widely between individuals and even within a givenindividual as the ability of various cells to respond properly to insulindeteriorates or improves.Moreover within any given cell theremay bepath-specific defects. That is, some insulin signaling pathwaysmay bepartially or fully resistant while others remain unaffected. Insulinresistancecanthereforebeahighlydynamicstateproducingaspectrumofphenotypes.Thishelpsexplainwhymetabolicsyndromeisdiagnosedby3ormoreoutof5parameters,ratherthanbyasingletestyieldingasingle number.A brief reviewof insulin action and insulin resistance invarious tissues is helpful to understand this range ofmarkers that canpresentinmetabolicsyndrome.

What Causes Elevated Blood Glucose: Insulin Resistance inSkeletalMuscleorLiver?

Whydidyourbathoverflow-was itbecauseyouforgot toturnoffthefaucet,orwasthedrainclogged?

CloggedDrainTheory: Insulinbindingto itsreceptoronskeletalmuscleinduces a signaling cascade that results in translocation of intracellularglucose transporters (GLUT 4) to the sarcolemma (muscle cellmembrane)and increasedglucoseuptake. Insulin resistance inmuscletherefore results indecreasedglucoseuptake.Akeydefectappears tobeanimpairedabilityof insulintosignalglucosetransporters inmuscleresultinginsignificantlydecreasedratesofglucoseuptakeandglycogensynthesis. The derangements in insulin-stimulated glucose uptakemayresult fromaccumulationof intramuscular fatwhichhasbeenshown toinhibit activation of upstream elements in the insulin signalingcascade[106]. In this scenario, the insulin resistant muscle fails toincreaseglucoseuptakeresultinginaccumulationofglucoseinthebloodstream.

Open Faucet Theory: An equally convincing case can be made fordefectsinhepaticinsulinactionasthedrivingforceunderlyinghighbloodglucose[107].Theopenfaucettheorypositsthattheinabilitytosuppresshepatic glucose output is the conductor of a poorly regulated glucosemetabolism orchestra. In the fasting state, the liver is primarilyresponsible for secreting glucose to maintain a normal level thecirculation. In the liver, insulin acts to inhibit glycogen breakdown andnewglucoseproduction, thussuppressingglucoseoutput. In the insulinresistant liver there is an inability to suppress hepatic glucose outputresulting in increasedreleaseofglucoseintothecirculation,evenwhenit’snotneeded.Asacompensatorymechanism,glucoseuptakeby theprimary cells responsible for clearing glucose in the fasted state (e.g.,brain, lean tissues,adipocytes, redbloodcells)maybenormalorevenincreased.

Eitherway,whetheryouhaveacloggeddrain(impairedglucoseuptake)orawideopenspigot(increasedhepaticglucoseoutput),theoverflowofglucose (water) makes for a metabolic mess. In the fasted state theprimarysourceofglucoseentering thebloodcomes from the liver.Theothermajor source of blood glucose is dietary carbohydrate. However,absorption of glucose from the intestines into the blood can be easilycontrolled by adjusting one’s intake of carbohydrate. If the insulin

resistant liver is already struggling to suppress its glucose output,providinganadditionaldietarysourceofglucoseiscompletelyirrational–thinkofaiminga firehose into youralreadyoverflowingbathtub.Sinceprogression to diabetes with life-threatening complications is onepossibleoutcome,amoredangerousanalogy thananoverflowingbathmightbeinorder.Managingthemetabolicmayheminsomeonewithinsulinresistancebyincreasingdietarycarbohydrateislikeusingaflame-throwertofightahousefire.

InsulinResistanceinAdipocytes

Adipocyteshaveahugecapacity forexpansion(notonlycaneachonecanget bigger –we canalsomakemoreof them), and this excessivestorage of adipose triglyceride is the basis for defining obesity. In noothertimeinhistoryhastheadipocyte’scapacityforexpansionbeensochallenged.Theprimaryfunctionofadiposetissueistostockpilesurplusfuelastriglyceridesinlipiddropletsandreleasethatstoredenergyintheformoffreefattyacids.However,withinthelast15yearstherehasbeenanexplosionofscientificpapersrevealingthatadipocytesdomuchmorethansimplystoreandreleasefat.Inaddition,theyproduceawidearrayof hormonelike substances called adipokines. These hormones aresecreted into the circulation, exerting important effects on a host ofphysiologic processes (e.g., carbohydrate and fat metabolism, foodintake, vascular and immune function, etc.). A key event was thediscoveryin1994thatfatcellsmakethehormoneleptin.Thisusheredina new era in which the adipocyte is now viewed as a full-fledgedendocrine cell. In addition to leptin, a host of additional adipokinesproducedinfatcellshavebeendiscoveredandshowntoplayimportantrolesinthedevelopmentofinsulinresistance.

Itishelpfultotakeastepbackandaskwhatgoeswronginobesityandmetabolicsyndromefromtheperspectiveoftheadipocyte.Expansionofadipose tissue does not happen spontaneously – it is in response tonutrientoverload.Interestingly,despitenutrientexcessandanexpandingwaistline, not all overweight people develop insulin resistance andmetabolic syndrome. But two important things happen in those peoplewho do. First, there appears to be a failure of adipose to fullyaccommodatethesurplusfattyacidsseekingahome,leadingtoectopic

fataccumulationinotherorganssuchasmuscleandliver.Second,thereare qualitative and/or quantitative changes in adipokine production,leading to changes in systemic insulin resistance. Let’s briefly discusseachofthesephenomena.

Fat accumulation in non-adipose tissues is largely due to insulinresistance in adipocytes. Insulin is the most important inhibitor oflipolysis,whichisthehydrolysisoftriglyceridestoreleasefattyacidsintothecirculation. Itseffectsare immediateandexquisitelysensitivewithinthephysiologicrangeofplasmainsulin levels.Theresultantchanges inplasma fattyacid levelsassociatedwith lowandhigh insulin levelscanvaryovera10-foldrange.Insulinresistanceintheadipocyteresultsinanunregulated release of fatty acids that are subsequently taken up byother tissues and stored. An increase inmuscle and liver fat is a wellestablished feature of obese individuals with insulin resistance.Interestinglyhighly trainedathleteswithhigh levelsof insulin sensitivityalsopackmorefatintheirmuscles(seesidebar–MuscleTriglyceridesandInsulinResistanceParadox).Andforthereaderwholikestechnicaldetail, increased fatty acid derivatives in muscle and liver have beenshown to increasekinases thatphosphorylate IRS-1onserine residuesthereby inactivating this important upstream element in the insulinsignaling cascade. This impaired insulin signaling leads to decreasedGLUT4 translocationandreducedmuscleglucoseuptake,settingupavicious cycle that causes both greater fat production (lipogenesis) andinsulinresistance.MuscleTriglyceridesandInsulinResistanceParadox

A highly trained athlete and an obese (untrained) individual both havehigher thannormalplasma fattyacidsandmuscle triglycerides, yet theformer has high insulin sensitivity while the latter is insulin resistant.Therein lies the paradox. If you delve into the exercise physiologyliteratureyouwillquicklylearnthatoneoftheclassictrainingadaptationsis a shift to a greater proportion of fuel derived from fat during activity.The source of that fat may be derived from circulating fatty acids ormuscle triglycerides. Thus, it makes sense that athletes would rev uptheirmetabolicmachinerytomobilizefattyacidsfromadiposetissueand

increase local storage of triglyceride inmuscle. In contradistinction theincreaseinplasmafattyacidsinobesityisduetoimpairedinsulininducedinhibition of lipolysis (i.e., adipocyte insulin resistance). The increasedrelease of fatty acids are taken up and deposited inmuscle and othertissues.Doincreasedmuscletriglyceridescauseinsulinresistanceintheobesepersonbutnot in theathlete?Or is insulin resistancecausedbysomethingelseandthefatbuildupinuntrainedmusclejustasymptomofthe problem (aka, an epi-phenomenon)? These questions serve toemphasize an important point. Although insulin resistance has been arecognizedproblem formore than50years, itsunderlyingcause isstillnotfullyunderstoodatthemolecularlevel.

Thusthisparadox.But therearesomerecentobservationsthatgiveushope of solving it. For one there is a significant difference in the fluxthrough the muscle triglyceride pool. Athletes repeatedly break downtriglycerides during exercise and rebuild them during recovery. Tofacilitate fat utilization, muscle triglycerides in trained individuals arelocalized near mitochondria within cells. In obesity, the muscletriglyceride pool ismore inert and tends to be stored in droplets awayfrom mitochondria. There is also a decreased number and size ofmitochondria and overall reduced oxidative capacity in the untrainedobeseperson. It is hypothesized that themismatch between increasedavailability and decreased use of fat results in accumulation of lipidderivatives (e.g., diacylglycerol, ceramides) that garble the insulinsignaling message causing insulin resistance. Paradox potentiallyexplained.

Insulin resistance in adipocytes is also associated with a distortedsecretionofadipokines.Severaladipokinesthatpromotehyperglycemiaareincreased(e.g.,resistin,TNF-a,IL-6,RBP4)andthosethatpromoteinsulin sensitivity decreased (e.g., adiponectin, visfatin, omentin).A lowcarbohydrate diet ismoreeffective thana low fat diet at correcting theabnormal pattern of adipokine secretion in insulin resistance. Forexample,retinolbindingprotein-4(RBP4)levelsdecreasedinsubjectsonalowcarbohydratedietbutnotalowfatdiet[56](seesidebar-RBP4:ANovelAdipokineLinkedtoInsulinResistance).

Leptin levels inplasmaaresignificantly increased inobesityand insulinresistance but the presence of leptin resistance prevents its normalactions(increasedenergyexpenditure,decreasedfoodintake,increasedmuscle and liver fatty acid oxidation). We recently showed a markedreduction in leptin in response to a low carbohydrate diet (-42%)compared to a low fat diet (18%)[56]. The greater decrease in leptinconcentration persisted after normalization of values to account for thegreaterreductionsinbodymassandfatmassinthesubjectsconsumingalowcarbohydratediet,suggestinganimprovement in leptinsensitivity.Emerging evidence has shown proinflammatory effects of leptinimplicating it in the pathogenesis of inflammatory conditions[108], andthus lower leptin isconsistentwithanoverallanti-inflammatoryeffectofcarbohydraterestriction(discussedlaterinthischapter).RBP4:ANovelAdipokineLinkedtoInsulinResistance

In 2005, an article in the journal Nature identified RBP4 as a potentadipokine[109]. Since then, a number of studies have confirmed andelucidateditsroleinmetabolicsyndrome.RBP4isexpressedprimarilyinliver and adipocytes. Genetic deletion of RBP4 enhances insulinsensitivity, and over-expression causes insulin resistance in mice. Inhumans, elevation of serum RBP4 is highly correlated with insulinresistance andmetabolic syndrome components suggesting thatRBP4may be an important contributor to cardiovascular risk. Therefore, wehypothesized that RBP4 levels would be reduced by carbohydraterestriction. Overweight/obese non-diabetic subjects with metabolicsyndromewererandomizedtoeitheraverylowcarbohydrateketogenicdietoralowfatdietfor12weeks[56].Comparedtosubjectsconsuminglowfat,subjectsonthelowcarbohydratedietshowedimprovedglycemiccontrol, insulin sensitivity and atherogenic dyslipidemia (decreasedtriglyceride, increasedHDL-C, and increasedLDLparticle size).SerumRBP4levelswerereducedmoreinsubjectsonthelowcarbohydratediet(-20%)comparedtothelowfatdiet(+5%)(P=0.02).Forallsubjects,thechange in amount of dietary carbohydrate intake correlated with thechange in RBP4; the correlation was stronger in subjects on the lowcarbohydratediet (r=0.54).Theabsoluteandpercentchanges inRBP4correlatedwithweightloss,fatloss,andimprovementinglucose,insulin,

triglycerides,andthequantityofsmallLDLparticles.

These findings link the role of RBP4 in insulin resistance with studiesshowingatightconnectionbetweencarbohydraterestrictionandfeaturesof metabolic syndrome. Dietary interventions that do not reducecarbohydrate intake may be ineffective in lowering serum RBP4, evenwhen significantweight loss is achieved. In addition to improvement inmarkers of metabolic syndrome, elevated serum RBP4 may be animportantpathogenic featureofmetabolicsyndromewhose reduction istightlycorrelatedwithreduceddietarycarbohydrateintake.

InsulinResistanceandDyslipidemia

Theprimaryabnormalitiesseen inblood lipidswithmetabolicsyndromearevaryingcombinationsofelevatedplasmatriglyceride,lowHDL-C,andapredominanceof smallLDLparticles. Insulin resistance inadipocytesand liver facilitate this disturbed lipid pattern. In addition to decreasinghepaticglucoseoutput, insulinalsoinhibitshepatictriglyceridesecretionbysuppressingVLDLoutput.Thusinsulinresistanceintheliverresultsinoverproduction and release of both glucose and triglyceride into thecirculation. The process is exacerbated by greater delivery of plasmafattyacidstotheliverasaresultofadipocyteinsulinresistance.Hepaticre-esterification of fatty acids and subsequent overproduction of largetriglyceride-richVLDLensue.This,combinedwith impairedclearanceofplasmatriglyceride,results inaconstantstateofhypertriglyceridemia inboth the postabsorptive and postprandial periods. This in turn leads tothe exchange of triglyceride in VLDL for cholesteryl ester in LDL. Theresultingtriglyceride-richLDLparticleisapreferredsubstrateforhepaticlipaseandlipoproteinlipaseandthereforebecomesthesourceofsmall,dense LDL. Similarly, triglyceride-rich HDL is hydrolyzed by lipoproteinlipaseresultinginthegenerationofsmallerHDLparticlesthatarerapidlyremoved from the circulation. In thisway elevated triglyceride resultingfrom disruption in insulin function plays a central role in regulating theatherogenicdyslipidemiaofmetabolicsyndrome.

InsulinResistanceandLow-GradeInflammation

A large body of research has implicated elevated inflammation inmetabolic syndrome and the pathogenesis of diabetes, heart disease,and other chronic diseases[110]. What is the link between insulinresistance and increased constituitive inflammation? There are severaltheories, but first it is informative to explore the effects of insulin oninflammatorypathways.Insulinnormallyexertsanti-inflammatoryeffects.Forexample,insulindecreasesgeneexpressionofseveralinflammatorytranscription factors in leukocytes inducing a broad spectrum anti-inflammatory effect. In the presence of inflammation induced byendotoxin or diabetes, acute increases in insulin suppress theconcentration of inflammatorymediators. Insulin sensitizing drugs havebeenshowntoexertanti-inflammatoryeffects.Thusaslongascellsareresponsive to insulin, inflammation appears to remain in check.Impairmentof insulinaction,however, results in increased inflammationand explains why metabolic syndrome is associated with low-gradeinflammation. Just as insulin resistance induces inflammation, severalstudies have implicated inflammatory mediators in promoting insulinresistance.Understandingtheoriginsoftheinflammationisimperativetopreventthispotentialviciouscyclefromescalating.Italsoopensthedoortounderstandinghowbesttomanageelevatedinflammation.

Whatisinflammation?Frankly,itmightbeeasiertoexplainthemeaningof life.Why?Becausethereisanintricatewebof interactinghormones,cytokines, and oxy-lipids (eicosanoids) that constitute what we looselycallthebody’simmunesystem.Oneviewisthatchronicinflammationisthe net effect of repeated exposures to substances that trigger animmuneresponse.Forexampleceliacdiseaseisachronicinflammatorycondition of the small intestines characterized by an aberrant immuneresponse to gluten. Removal of gluten from the diet results in rapidremissionoftheinflammationandintestinalsymptoms.

Inaninsulinresistantstate,suchasmetabolicsyndrome,thesubstanceconstantly irritating and provoking the body is carbohydrate.Carbohydrate ingestion and acute hyperglycemia activate a host ofinflammatory and free radical-generating pathways[111, 112]. Some ofthese include:stimulationofNAPDHoxidase,superoxidegenerationbyleukocytes, TNF-a production, and activation ofNF-kBwhich regulatesthetranscriptionalactivityofover100proinflammatorygenes.Consistent

with the notion that carbohydrate can aggravate inflammatory balance,many studies have reported that low carbohydrate diets decreasemarkersofconstituitiveinflammation[29,113].

InsulinResistanceinEndothelialCells

Endothelial cells line the entire circulatory system, providing a barrierbetweenbloodandthevesselwall.Ithasbecomeincreasinglyapparentthat endothelial cells produce several vasoactive substances and otherinflammatory mediators that regulate vasomotor function and vascularhealth.Endothelialcellshaveinsulinreceptorsthattriggerclassicinsulinsignalingpathwaysverysimilar toskeletalmuscle. Insulin resistance inendothelial cells has been shown to be due to impairment in thephosphatidylinositol3-kinase-dependentsignalingpathwaythatleadstoproductionofthepotentvasodilatornitricoxide.Tomakemattersworse,insulin also increases secretion of the vasoconstrictor endothelin-1 andthisinsulinsignalingpathwayappearstoremainintactinthepresenceofinsulin resistance[114]. This is an example of pathway specific insulinresistance that in this case inhibits a potent dilator and stimulates astrongconstrictor. Inotherwords,an insulin resistantendothelial cell islikedrivingacarwithabrokenacceleratorandtheparkingbrakeon.

CarbohydrateIntake,GlucoseandInsulin

Dietary carbohydrate is a direct source of blood glucose. Thereforerestrictionindietarycarbohydrateintuitivelyleadstofewerfluctuationsinbloodglucose.Ingestingcarbohydrate,especiallyrapidlydigestedforms,stimulates a rapid increase in insulin from the pancreas. Continuedstimulationbyinsulin,aswithmosthormones,hasbeenshowntodown-regulate the insulin response in a host of tissues (i.e., adipose tissue,liver, cardiac, smooth and skeletal muscles)[115, 116]. This insulin-stimulatedinsulinresistanceisreversiblebydecreasingtissueexposuretoinsulin.

Insulinresistanceitselfleadstocompensatoryhyperinsulinemia,initiatinga positive feedback loop (a vicious cycle).At somepoint the individualsigns and symptoms of metabolic syndrome will emerge, especiallyunder constant stress to increase insulin (i.e., carbohydrate intake).

Depending on carbohydrate intake and the level of carbohydratetolerance, themetabolic syndromemarkerscanandusuallydochangequickly, for the better or worse. One of the metabolic rationales forcarbohydrate restriction is that reduced dietary glucose leads to betterinsulin control which disrupts the stimulus promoting insulin resistance(i.e., it breaks the vicious cycle). Studies using carbohydrate-restricteddietsconsistentlyshowbetterglucoseandinsulincontrolandincreasedinsulin sensitivity, both in healthy populations[56] and especially inpatientswithpre-existingmetabolicsyndromeortype-2diabetes[45].

DefiningCarbohydrateIntolerance

Given this emerging understanding of dietary carbohydrate as both anunderlying cause and exacerbator of extant insulin resistance, it isinstructive to view insulin resistance, metabolic syndrome and type-2diabetesascarbohydrate intolerantconditions.Whatdoescarbohydrateintolerancemean? Inmedicine, intolerance ischaracterizedbyextremesensitivity (in a negative way) or allergy to a drug, food, or othersubstance. Common forms of food intolerances include abnormalresponses to lactose and gluten ingestion that in both cases promptlyimprove when the offending substances are restricted in the diet. In aperson intolerant tocarbohydrate, there isanexaggeratedglucoseandinsulinresponsetoagivenamountofcarbohydrateingested.

Amoreinsidiousmanifestationofinsulinresistance,becauseofimpairedglucose uptake into muscle, is a propensity to divert ingestedcarbohydrate to the liver where it is converted to fat. Metabolism ofcarbohydrate through de novo lipogenesis leads to increased plasmatriglycerides and dyslipidemia. This is partially driven by a down-regulation of the insulin response and decreased glucose uptake inextrahepatictissues.

Less well understood is how dietary carbohydrate impacts immunefunction and inflammatory mechanisms, but another facet ofcarbohydrate intolerance is likely anaberrant inflammatory response tocarbohydrate intake. Clearly the normal response to carbohydrate ininsulin sensitive tissues is disturbed in insulin resistance, whichsubscribes to the definition of intolerance. Put simply, consuming too

muchcarbohydrateislikemetabolickryptoniteifyoualreadyhaveinsulinresistance.

Carbohydrate Restriction: the Rosetta Stone for Preventing andTreatingMetabolicSyndrome

Reviewing the literature, one finds a remarkable consistency in studiesthat have compared low fat and low carbohydrate diets onmarkers ofmetabolic syndrome. Low carbohydrate diets perform at least as well,and usually better than low fat diets[56, 117, 118]. This includesimprovements in triglycerides, HDL-C, LDL particle size, glucose, andinsulin.Instudieswherethelevelofcarbohydraterestrictionisverylow,there are often striking differences. For example, the benefits ofcarbohydrate restriction on markers of metabolic syndrome have beenobservedinnormaloroverweightindividualswithorwithoutthepresenceofmetabolicsyndrome,althoughthemagnitudeof improvementisoftengreatestinindividualswithinsulinresistanceandfranktype-2diabetes.

Thebenefitsofcarbohydraterestrictionarealsoapparentwhetherweightlossoccursornot,suggestingitisthereductionindietarycarbohydrate,notcaloriesorbodyfatmassperse,thatisresponsiblefortheimprovedmetabolicoutcomes.Thatthesignsofmetabolicsyndromearepreciselythe ones targeted by diets that restrict carbohydrate should not besurprising,since the literature is rich instudiessupporting this idea,yetthere has been a palpable reluctance tomake this explicit connection.Wepublishedareviewpaperin2004[118]titled“Carbohydraterestrictionimproves the featuresofmetabolicsyndrome:metabolicsyndromemaybe defined by the response to carbohydrate restriction” in which wecollectedinformationintheliteraturesupportingthenotionthatthemajormetabolic problems are specifically ameliorated by reduction in dietarycarbohydrate, and thus had an advantage over low fat diets.However,thisreviewseemstosufferfromtheWarren&MarshallSyndrome,asithas neither been refuted nor accepted by mainstream government orprofessionalmedicalorganizations.

Summary

Metabolic syndrome encompasses a widening circle of metabolic

derangements that arise from a down-regulation of insulin-response indifferent cells. Given the established close connection between dietarycarbohydrateand insulinphysiology,carbohydrate restriction representsapowerfultoolcapableofinducingauniquemetabolicstatethattargetsthe underlying cause of insulin resistance andmetabolic syndrome. Inview of the poor track record of low fat, high carbohydrate diets incontrollingourcurrentepidemicofobesityanddiabetes,plusthelimitedimpact of both pharmacologic and even exercise interventions onmetabolic syndrome markers, a wellformulated low carbohydrate dietoffersaneffectivealternativeforthemillionsofAmericanssufferingfromthisreversiblecondition.

Sowhatistheverdictinthis‘whodunit’case?Theculpritisourexcessiveintake of insulin-stimulatory dietary carbohydrates, especially simplesugarsandrefinedstarches.Lockenoughof themuppermanently,andthe metabolic crime spree will end. Good work detective – metabolicsyndromesolved–caseclosed!

Chapter15

TREATINGTYPE-2DIABETESASCARBOHYDRATEINTOLERANCE

Introduction

The hallmark of type-2 diabetes is insulin resistance, but the actualbiologyof itsunderlyingcauseremainsobscure.However, the twobestpredictorsofwhowilldevelopdiabetesinacohortofhealthysubjectsarebiomarkers of inflammation (such as c-reactive protein [CRP] andinterleukin-6 [IL-6]) and the biomarker of lipogenesis, palmitoleic acid(POA) in the serum cholesteryl ester fraction. So absent a betterexplanation of the root cause of this disease, itmakes sense that it isdriven by inflammation and the diversion of dietary carbohydrate intosecondarydisposalpathways.Furthermore,aswediscussedinChapter9,thesetwoprocessesaremechanisticallylinkedtogetherbyincreasedROSproductiondamagingmembranes,leadingtoinsulinresistance.

Ifthisisindeedaprimaryunderlyingpathophysiologyoftype-2diabetes,then it followsthat theoptimumtreatmentof type2diabetes isreduceddietarycarbohydrateintake.Afterall,verylowcarbohydratedietsreducethe body’s level of inflammation, particularly in conditions such asmetabolic syndrome in which it is typically elevated. And restrictingcarbohydrate intake reduces the total burden of glucose needingdisposal, taking the pressure off of secondary disposal pathways likelipogenesis.

On thecontinuumof insulin resistance, impairedglucose toleranceandmore generally metabolic syndrome often progress to overt type-2diabetes, and therefore the latter represents a more severe form ofcarbohydrate intolerance. This may mean that in its long-termmanagement,dailycarbohydrateintakehastobekeptlowerinatype-2diabetic than insomeonewith lesssevere insulinresistance.But italso

meansthatawell formulated lowcarbohydratedietwill tendtoproducestrikingimprovementswhenimplementedintype-2diabetics.

So what evidence is there that this approach actually works? Thatdepends upon who you ask. The American Diabetes Association hasbeen strongly against low carbohydrate diets for decades, but recentlyaltered their position toacknowledge that theremaybea role fordietslowerincarbohydratethantheyhavepreviouslybeenadvocating[119].

And then there is clinical experience and the published literature. Let’sstart with a clinical case. This case was the first patient that StevePhinney ever put on a ketogenic diet, occurring during his medicalresidency under the direction of Dr. Ethan Sims at the University ofVermont.Theoutcomefor thispatientwassoremarkable that ithelpedshapeStevePhinney’sresearchcareer.ClinicalCase:Type-2DiabeticwithCongestiveHeartFailure

(MedicalCenterHospitalofVermont,MaryFletcherUnit,October1975)

TR was an obese male in his late 40’s with a long history of type-2diabetes. Hewas admitted to hospital formanagement of his severelyelevatedbloodsugarinanticipationofelectivesurgerytoremovealargecalcified gallstone. On exam, he had severe lower extremity edemaresistant to high dose furosemide. His labs revealed normal kidneyfunctionbutfastingglucosesbetween250and300mg/dl.For3days,wetried the standard treatment of an 1800 Calorie ADA diet, oralsulfonylurea agents, and 4 dose per day insulin; but TR’s clinicalresponse to these measures was unsatisfactory. Neither his severeedemanor hismarkedly elevated glucose values improved verymuch.Thepatientcontinuedtohaveorthopnea(shortnessofbreathwhenlyingflat),andhissevereedemalimitedhisactivitytoabed-to-chairexistence.

On the 4th day, Dr. Sims mentioned that one of his former researchfellows,Dr.BruceBistrian,wasstudyingaverylowcarbohydratediettomanagetype-2diabetesatHarvard.SowecobbledtogetheraresearchprotocolandputTRon thisdiet,whichconsistedofmodestportionsofleanmeat, fish,andpoultryproviding90-100g/dofprotein ina totalof

600 Calories, plus about 10 grams of carbohydrate. The diet wassupplementedwithpotassium,traceminerals,andvitamins.

Within 48 hrs, TR’s blood glucose values began to plummet towardsnormal,allowingustocutwaybackonhisinsulindosage.Inaddition,hisurineoutputwentupsharply,resulting inweight lossesof5poundsperday.By theendofaweekon thediet,his fastingbloodglucoseswereunder120,wehadstoppedallofhisinjectedinsulin,he’dlost30poundsand his edema had completely resolved despite our reducing hisfurosemide dose from 320 to 40 mg/day. But most striking of all, thepatientwasoutofbedandpacing lapsupanddownthehospitalward,claimingthathe’dnotfeltthisgoodinyears,andaskingtobedischargedsohecouldgofishing.

Afewdayslater,thepatientwasdischargedhomeonthesamediet.Helostanotherlost50poundsin5months,andwasthenreadmittedtohavehis cholecystectomy, which was performed without complications orrecurrentsignsofhisdiabetes.

VeryLowCalorieKetogenicDietsinType-2Diabetes

Concurrent with this and subsequent cases that we generated inVermont, Dr. Bistrian completed a series of seven closely monitoredcases in Cambridge/Boston[120]. It was his very low carbohydrateketogenic (VLCKD)dietprotocol thatweused in thecasestudyabove.Allsevenofthesubjectsinhispublishedreportwereobese,insulin-usingtype-2diabetics,andallwereable tobewithdrawnfrominsulin therapy(up to 100 units per day) in an average of 7 days after starting theVLCKD.Allof thesesubjectswentonto loseaconsiderableamountofweight,anachievementthatisdecidedlyuncommonindiabeticswhoareusinginjectedinsulin.

ThepivotalissuewiththisuseoftheVLCKDintype-2diabeticswastheirdietarymanagementonce thedesiredweight losswasachieved.Whileveryeffectiveinachievingweightloss,adietproviding600-800Caloriesper day was clearly unsustainable in the long run. For some of theseformerlyobesepatientswhowereseverelydiabeticattheoutset(likethe

case history above), their insulin resistance improved so much aftermajorweightlossthattheycouldtransitiontoalow-glycemicindexmixeddiet without the return of overt diabetes. But for many others, the re-introductionofevenamoderateamountofdietarycarbohydratepromptlyresulted in elevated serum glucose values despite maintaining asignificant weight loss. And for all of these patients, there lurked theproblem of eventual weight regain, and with it increasing insulinresistance.

Clearly the key to the long-term success inmanaging type 2 diabeteswith carbohydrate restriction has been figuring out how to safely andeffectively maintain the carbohydrate restriction into the weightmaintenancephaseofthediet.Fromthesafetyperspective,ithelpsalotthat we have demonstrated that blood levels of saturated fats declinedespite eating a high fat, energy maintenance diet[30], and also thatinflammationbiomarkers(likeIL-6andCRPthatareassociatedwiththecauseof type-2diabetes)arealso significantly reduced.These factors,alongwith theoftendramatic improvements inserumtriglycerides,HDLcholesterol,andLDLparticlesize,presentapictureofacross-the-boardimprovements inknownhealthriskpredictorswhenpatients(diabeticornot)adheretoawellformulatedcarbohydraterestricteddiet.

Butthisthenbringsustothequestion:whatistheproperdietformulationfor theformerlydiabetic individualoncarbohydraterestrictiongoing intothe maintenance phase? The answer, as we have emphasizedthroughoutthisbook,isthat it isadietadequateinenergy,moderateinprotein, and high in fat.However, the key question is: howmuchdoesone need to restrict carbohydrate long-term?Or put another way, howdoestheindividualknowifs/heiseatingtoomuchcarbohydrate?

One way to assess this would be to monitor blood glucose values asone’sweightlossslows,wherethegoalistoholdcarbohydratesdowntothatlevelthatkeepsbloodglucoseinthenormalrange.Whilethisis, inand of itself, an excellent therapeutic success for someone who wasformerlyatype-2diabetic,itmaynotbeenoughforthatindividualtostaynormoglycemic long term.Whymight this be? Isn’t keeping your bloodsugarnormalevidencethatyourdiabetesisincompleteremission?

The answer is that it’s great to have normal blood sugars, but thiswillonly last if you also keep off the lost weight. For this, success atmaintainingyourweightlossmaytakeagreaterdegreeofcarbohydraterestriction that that needed to maintain blood sugar control. Why?Because, at the most basic level, successful weight maintenancerequires not having blood sugar diverted into secondary disposalpathways like lipogenesis. To monitor this, you can monitor bloodtriglycerides and adjust dietary carbohydrate to keep them low. Inaddition,weareworkingondevelopingatestforPOAlevelsasamoredirect way to monitor the body’s rate of lipogenesis (discussed inChapters9and11).

HepaticGlucoseOutputWithVaryingCarbohydrateRestriction

Along with insulin resistance and accelerated lipogenesis, anotherhallmark of abnormal metabolism associated with type-2 diabetes isincreasedhepaticglucoseoutput.Normallytheliverreleasesglucosetoprevent hypoglycemia, whereas glucose output by the liver goes waydownwhen blood glucose values are elevated. But in type-2 diabetes,the insulinresistant liver inappropriately keeps on dumping glucose intothecirculation inspiteofhighbloodsugar levels,makingbloodglucosecontrolthatmuchmoredifficult.

In1996,Dr.BarryGumbinerandcolleaguespublishedaseminalstudyshowingtheeffectsofcarbohydraterestrictiononhepaticglucoseoutputin obese subjects with type-2 diabetes[121]. They constructed twoVLCD’swith thesameproteinand total energy (650Calories), butoneprovidedanaverageof24gramsperdayofcarbohydrate,whereastheother contained 94 grams of carbs. The subjects followed each diet inrandomorder for3weeks,andtheaveragetotalweight losswas11kgoverthe6-weekstudy.

Interestingly,despite thebigdifference incarbohydrate intakesbetweenthe twodiets, the ratesofweight losswere thesame for the twodiets.However fastingbloodsugars,whilecomingdowndramaticallyonbothdiets, were consistently lower during the lower carbohydrate diet. Thelower carbdiet also raised serumketonesabout twiceasmuchas thehighercarbdiet.Bothdietssignificantlyreducedhepaticglucoseoutput,

butthemoreketogenicdietreduceditby22%more.

When the data from both diets were analyzed together, Dr. Gumbinerreported a strong and highly significant negative correlation betweenbloodketonesandhepaticglucoseoutput.Whatthismeans,quitesimply,is that two diets identical in protein and total calories had distinctlydifferent effects on type-2 diabetics, based solely upon their differingcarbohydratecontents.Thus,despitesimilarratesofweightloss,thedietproviding 24 grams/day of carbohydrate resulted in better diabetescontrolthantheoneproviding94grams/day.Andthenegativecorrelationbetween serum ketones and hepatic glucose output indicates that thenutritional ketosis induced by the greater degree of carbohydraterestrictionmoreeffectivelyreversedunderlyinghepaticinsulinresistance.

Asanaside, it is interestingto track thefateof thispaperand itsnovelfindingssinceitwaspublishedin1996.Althoughithasnotbeenrefuted,thispaperhasbeencitedinthemedicalliteraturejust12times,evenasthe prevalence of type-2 diabetes is increasing in the developed anddevelopingnationsatatorridpace.It ishardtoknowpreciselywhythispaper has been relegated to the doghouse, but perhaps it is becauseketones and nutritional ketosis continue to be casually discounted byboth dietetic and medical educators, many of whom lack a basicunderstandingoftheroleketonesplayinhumanenergymetabolism.Fora bit more in-depth look at some of the polarity that exists betweenresearchdataandconsensusexperts,seeChapter12.

ASustainableandEffectiveKetogenicDietforType-2Diabetes

Not all clinically relevant studies need to be randomized or placebo-controlledtrials.Aswiththe1976Bistrianstudy[120] justdescribedandBoden’s recent study[45], a recently published pair of papers fromKuwait[122,123]offerssomeimportantandclinicallyusefulobservations.Thesepapers report the results froma largeclinicalpracticemanagingadults with severe obesity. A cohort of 185 subjects was identified aspotentialcandidatesforthestudy,ofwhom66agreedtoparticipate.Themean initial BMI of the subjects was 39 (i.e., as a group, they wereseverelyobese).Baselineserumanalysiswasusedtodividethecohortinto two subgroups: those with (n=35) and without (n-31) severe

dyslipidemia.The‘dyslipidemicgroup’,althoughnotidentifiedasdiabetic,also had amean baseline fasting glucose of 9.4mM (169mg/dl), andthus was composed predominantly of individuals with either severemetabolicsyndromeorovertdiabetes.

The same diet was used for both cohorts, consisting of meat, poultry,fish, eggs, and cheeseplus vegetables providing 80-100g/d of proteinand 20 grams of total carbohydrate. To this was added 5 tablespoons(600 Calories) per day of olive oil used in cooking and on salads.Includingthefatsinherentintheproteinsources,thisdietprovided1200-1500Caloriesperday.After12weeks,thecarbohydraterestrictionwasincreased to 40 grams per day, allowing inclusion of a wider list ofvegetables, olives, avocados, and berry fruits. Beyond this, no furtherexpansionofdietchoiceswasrecommendedforoneyear.

Of the initial 66 subjects, 49 remained in the study after 56 weeks,including26of the initial35withdyslipidemia.Themeanweight loss inthissubgroupwas27kg,with11kgofthisweightlossoccurringbetweenmonths6and12.At8weeks,meanfastingbloodglucosehadfallenfrom9to6mM(theupperlimitofnormal),fromwhichpointitdeclinedfurtherto5mMat56weeks.Inaddition,LDLcholesteroldeclinedsignificantly,triglycerides were reduced 3-fold, and HDL cholesterol increased by63%. Similar weight loss and improved (albeit not as dramatic) bloodlipids were observed in the non-dyslipidemic group. When the lastobservation from the 17 dropouts was carried forward to the 56-weekmark, these dramatic changes were not significantly attenuated, whichmeansthatthediethadauniformbeneficialeffectonthesubjectsiftheycompletedthestudyornot.

Asthiswasnotarandomizedtrial,theremayhavebeensomeselectionbias inenrollingsubjects.But thatnotwithstanding, the remarkable totalweight loss by this group, plus the fact that the weight loss continuedthrough the second 6 months of the study, is striking. But the mostprofound change observed in this report was that 26 of the initial 35‘dyslipidemic’ group normalized their markedly elevated blood glucosevalueswithin2monthsand remainedatnon-diabeticglucose levels fortherestof theyearofobservation.Simplyput,here isanexampleofacohort of type-2 diabetics who had their disease put into complete

remissionforayear(withanopen-endedoptiontocontinueonthisdiet),duringwhichtimetheylostandmaintainedadramaticamountofweightwhilemarkedlyimprovingseveredyslipidemia.

There is no other combination of diet and/or drugs that has beendemonstratedtoachievethisdegreeofweight lossplusdiabeticcontrolinasizeableoutpatientcohort. If thestandard low fat,calorie restricteddiet plus oral agents and insulin had been employed with the vigornecessarytoachievethislevelofglucosecontrolinoutpatients,thepriceoftheglucosecontrolwouldhavebeenanincreaseinweightandfurtherelevatedtriglycerides.Why?Becauseweightgainhasbeenaconsistentobservation whenever diabetic groups are encouraged to pursue ‘tightcontrol’, and this is easily understood due to insulin’s potent role as astorage hormone. In addition, ‘tight control’ achieved by insulin plusinsulin stimulating/ sensitizing medications carries an increased risk ofhypoglycemic episodes, which are not benign. However, the oppositeeffectisachievedbyremovingmostofthecarbohydratefromthedietsofindividualswho are severely insulin resistant, facilitating better glucosehomeostasis while at the same time allowing the body to access itsexcess fat reserves. Thus this study demonstrates excellent bloodglucosecontrol,majorweight loss,plusdramatic improvement inbloodtriglyceridesonalowcarbregimen.

Critics of this paper point to themagnitude of the reportedweight lossandaskhowthisstudywasabletoachievemorethantriplethatreportedin published randomized controlled trials, and how the subjects couldsustainthedietforayearwithcontinuingweightloss.Thereisnosimpleanswertothiscriticism,becauseclearlytherewereanumberofpotentialcontributing factors. One factor was the severe obesity of this cohort.StartingataBMIof39,theyhadalotofweighttolose.

A second factor was precisely the fact that this was not a randomizedtrial.Theclinic inwhich thestudywasdonehasused thisdiet, found iteffective,andbelievesinitssafetyandefficacy.Thismessageisnotlostonpatientsand/orresearchsubjects.Ifastudyisdoneemployingadietthat the research physician or dietitian is not comfortable with, this iseffectively communicated to the subjects, and the resultant outcome iscompromised. It is not uncommon to hear consensus experts say “We

triedthatdiet,anditdidn’twork”.Butwhatdoyouexpectwhenyouaskaperson to give up some of their favorite foods and change habitsingrained over decades, yet at the same time communicate to them(whether verbally or non-verbally) that you really don’t believe thesedifficultlifestylechangesarenecessaryorsafe?

Athirdfactor,andoneprobablyequallyasimportantastheabovetwo,isthe prescription of added fat to the diet from its outset. Thiscommunicates to patients that dietary fat is good for them and anecessarypartoftheirdiet.Whileproteinhasanimportantroleinsatietyduringweight lossdieting, it isnowherenearaseffectiveas fat.Sobyadding600Caloriesofoliveoil to theirdailydiet, individualswhowereburningupwardsof3000Caloriesperdayachievedaddedsatietywhilestillmaintainingasizeableenergydeficit.

And finally, theadditionofcarbohydrateback into thediet in thiscohortwasstrictlylimitedtoamaximumof40grams.Biologically,particularlyforindividualswith severe insulin resistanceor type-2diabetes, this keepsthem in ketosis and avoids their crossing back over that threshold(defined by Dr. Gumbiner’s study[121]) where hepatic glucose outputincreases and diabetic control is lost. Also important froma behavioralperspective, telling a person that they can progressively addmore andmore dietary carbohydrate means that they don’t need to make theirpeacewithnothavingit.Alltheyneeddoiswaitafewmonths(orevenjustuntildark,whennooneislooking!)Whyarewethensurprisedwhenthe average research subject in an outpatient carbohydrate restrictionstudygivenunlimited,open-endedaccesstocarbohydratefoodstotalingmorethan100gramsperdaystartsregainingweightafter6months?

Doesthismeanthateveryoneonacarbohydraterestricteddietneedstostay under 40 grams per day? Of course not! Individuals varytremendously in their degrees of carbohydrate tolerance. But in thecontext of this chapter about managing type-2 diabetes, we need toremember that insulin resistance is a hallmark of carbohydrateintolerance. For many patients starting out with type-2 diabetes, evenaftermajorweightlossandmaintainingnormalbloodsugarsformonths,their underlying carbohydrate intolerance remains. That in turn meansthat these individualswillneed tomaintaina tight levelofcarbohydrate

restriction(beit30grams,60,or90)fordecades(notjustafewmonths)toremainhealthyandnon-diabetic.

It’s a bit simplistic but helpful to view a low carbohydrate diet as the‘natural’nutrientmixthatatype-2diabetic’sbodyiswiredtohandle.Byrestricting the primary source of the problem, everything gets better. Ifyougetathorninyourfoot…ithurts,soyouremovethethornasfastaspossible.Youdon’ttakeapainkillerandthenkeepwalkingonithopingitwillgetbetter.Ahighcarbohydratedietistheproverbial‘metabolicthorn’fordiabetics,andcuttingdownondietarycarbohydrate intakestopsthemetabolicpainatitssource.

Summary

There are hundreds of published studies pertaining to the use ofcarbohydraterestricteddietsintype-2diabetes,someofthemgoingbackover a century. It has not been the goal of this chapter to perform acomprehensivereviewofthisvastliterature,butrathertofocusonafewstudiesthatrevealimportantaspectsofdevelopingasafe,effective,andsustainableclinicaltoolforthemanagementoftype-2diabetes.

Thethreekeytake-awaypointsmadeabovecanbesummarizedasfollows:

1.Althoughcarbohydrate-restricteddietscanbedramaticallyeffectiveincorrecting blood glucose and lipid disorders associated with type-2diabetes, inmany if notmost patients, these improvements donot lastvery longafterthecarbohydraterestrictionends.Thusthere is littleroleforthistypeofdiettobeemployedinthemanagementofdiabetesintheshort term. For most diabetic patients choosing to start a lowcarbohydrate diet (or being encouraged to start one by a health careprofessional),theindividualneedstobeawareofthelikelihoodthatsomedegreeofcarbohydraterestrictionwillhave tobecomearegularpartoftheirongoinghealthylifestyle.

2.Thedegreeofcarbohydraterestrictionneededtoachieveone’sgoalsofweightlossanddiabetescontrolwillvarygreatlyamongindividuals.Itmay also vary within any one individual as well, in the sense that the

degreeofrestrictiontopromoteweightlossmaybelessstrictordifferentfrom that needed to optimally control the metabolic abnormalitiesassociatedwith type-2 diabetes. For example, Dr.Gumbiners’ subjectsonhishighercarbohydratediet lostthesameamountofweightbuthadless effective suppression of their high blood glucoses and hepaticglucose output. Seen from this perspective, maintaining a state ofmoderatenutritionalketosis(1-2mMserumbetahydroxybutyrate)maybeabeneficialbiomarkerofefficacy,andthisusuallyrequiresholdingdailycarbohydrateintakesinthe20-50g/dayrange.

3.Theability tosustainsucha lowintakeofcarbohydrate indefinitely issynonymouswitheatinghigherthanusualamountsoffatforalong,longtime.Tobeabletodothis,therighttypesoffatneedtobeemphasized(discussedinChapter16)andtheindividualneedstoliveinasupportivesocial and clinical sphere. If the individual is constantly told by family,doctor,ordietitianthateatingahighfatdietisdangerous,onlythemostcurmudgeonly among us will succeed. Even if you are not convincedabouttheabsolutesafetyofawellformulatedlowcarbohydratediet,weaskyou toconsider these twochoices:a) remainoverweighton insulinandtakingtwooraldrugswhileyourfastingbloodglucoseremainsabove200mg/dl (11mM)andyoudevelopearlymicroalbuminuria, or b) loseweightandhavenormalbloodsugarsandnormalkidneyfunctionwithoutdrugs by forgoingmost dietary carbohydrate long-term.What unknownriskpotentiallyassociatedwiththelatter(i.e.,awellformulated,moderateprotein, high fat diet) can outweigh the likelihood of becoming a blindamputeeondialysisassociatedwiththeformer?

Postscript:ClinicalDetails

This chapter is intended to inform the reader why a carbohydraterestricted diet is a highly effective clinical tool for the management oftype-2 diabetes. It is not intended to provide instructions how to do it.That said, how to do the diet itself is well described in the authors’bookTheNewAtkinsforaNewYou[5]publishedinMarch2010.

Wehavefocusedinthischapterontype-2diabetes,whichisprimarilyadisease of insulin resistance. Type-1 diabetes is physiologically verydifferent, and this disease is not discussed here. Type-1 diabetics and

some late stage type-2 individuals with very limited insulin productionbehavedifferently ona lowcarbohydratediet.Asageneral rule, theseindividualsneed tostayon lowdose injected insulin for thedurationoftheircarbohydraterestriction.Forinformationontheuseofcarbohydraterestriction in these patients, see the excellent book by Dr. Richard K.Bernstein[2],whoishimselfatype-1diabetic.

Managing the first few weeks of a low carbohydrate diet in a type-2diabetic is a very dynamic process, particularly if the patient is takingmedicationfordiabeticcontrol,hypertension,orcongestiveheartfailure.In the last century, we just admitted those patients to hospital for theinitialadaptationperiod. In thiscentury,wedo itasoutpatientsusinge-mailandtextmessaging.Thereisnocookie-cutterwaytodothis,butthekey factor is open and effective 2-way communication between doctorandpatient.Bothneed tobeprepared for rapid reductions indiabetes,hypertension,andCHFmedicationsasadaptation to thedietproceeds.AsnotedinDr.Bistrian’s1976study[120],insulinisusuallywithdrawninanaverageof7days.

Buttheoppositeisalsotrue.Ifalowcarbadaptedpatient‘breaksthediet’by eating even transient and/or modest amounts of refinedcarbohydrates, all of those hard-won benefits can promptly disappearwithin a matter of hours and don’t reappear for 3-7 days. So thewithdrawnmedicationsneed tobekeptcloseathand,notasasignofdistrust, but as an insurance policy against the unexpected. On mostdays, the unused pills function as a kind of memorial to one’s formerdrug-dependent life. But come a stress like a death in the family, aspouse bringing home the celebratory birthday cake, or winning thelottery,havingtheformermedicationsinhandonSaturdaynightsavesatriptotheER(orperhapsalife).

For whatever reason, diabetics seem to have lots of muscle cramps.Potassium replacement if the serumvalue is low sometimeshelps, butthe true underlying cause commonly turns out to be renal magnesiumwasting driven by osmotic losses. The physiology andmanagement ofthisproblemarediscussedinChapter18,Pearl#9.

Chapter16

THEIMPORTANCEOFDIETARYFATINLONG-TERMMAINTENANCE

Introduction

Thepopularuseoflowcarbohydratedietsoverthelastcenturyhasbeenpredominantly for weight loss. But as with any dietary intervention foroverweight or obesity, the weight loss phase is relatively short termcompared to the years and decades of reduced weight and improvedhealththathopefullyfollow.Howeverthemajorityofindividualswhodietto loseweight do not reach their desired goal weight, and furthermoretendtoregainsomeoftheweighttheydidlosewithinayear[43,66,124,125]. Typically in these studies, a group of subjects enrolled in arandomized controlled trial reach their maximum weight loss within 6monthsofstartingthediet,andthenbegintoshowweightregainby9or12months.Thishaspromptedskepticstobrandlowcarbohydratedietsasuseless“becausenoonecanfollowthemlongterm”.Thefactthatthissamepattern of loss followedby regain is also seenwith other calorierestrictedregimensissometimeslostonthesecritics.

Bethatas itmay, longtermadherencetocarbohydraterestriction isanimportant issue, and capturing the benefits of a low carb diet for themanagement of chronic conditions associated with insulin resistancerequires that we address this challenge. Given the dramaticimprovements in the dyslipidemia associated with metabolic syndromeand themarked improvement in diabetesmanagementwhenadequatecarbohydrate restriction is sustained, our purpose here is to reducebarrierstolongtermadherencetothistypeofdiet.

One such barrier that is commonly perceived but seldomaddressed inthe research literature is how to feed the post-weight loss patientadequate energy for weight stability while maintaining the degree of

carbohydrate restriction necessary to sustain the diet’s benefits.Specifically, what ratio of macronutrient intake should a weight stableperson eat if carbohydrates are restricted to, say, 50 grams per day?Should that person just eatmore of the relatively high proteinmix thatwasconsumedduring the initialweight lossphase,ordoes thispersonneedtoaddmorefatenergytoachieveweightstability?

This isnota rhetoricalquestion.Nor is iteffectivelyaddressedevenbyexperienced low carbohydrate practitioners. Some practitioners tacitlyassume that the obese person’smetabolismwill slow to the point thattheirreducedenergyintakewillmeetdailyenergyneeds.Othersleaveitto taste, appetite, and cravings to empirically lead the individual to aneffectivemaintenancediet.

Given how poorly these ‘hands off’ or ‘casual’ approaches to lowcarbohydratemaintenanceworkintherealworld,itisthepurposeofthischapter to address the need for added dietary fat while keepingcarbohydrates within an acceptable level of tolerance in the long-termmaintenancephaseofcarbohydraterestriction.Thisisnecessaryfortworeasons. First, the popular myth that a carbohydrate restricted diet isnecessarilyhighinproteintendsto leadthepatient intoaddedexpenseand sometimes dysphoria and gastrointestinal malaise associated withtoo much dietary protein. Second, the demonization of fat by bothconsensus experts and the media has made many patients fearful ofconsuming the amount of fat necessary for a satisfying weightmaintenancedietwiththeproperlowcarbmacronutrientbalance.

ChangesinEnergyIntakeandExpenditureAcrosstheDietPhases

Inordertojudgehowbesttoformulatethemixofmacronutrientsinalowcarbohydratediet, it is helpful to visualizehowyour total energy intakewillchangefrominductiontomaintenance.Asindicatedinthegraphonthenextpage,atypicalmalewithaBMIof34mightstartouteating1600kcalininductionwhilehisbodyburns3200kcalperday(thustheweightloss).Butafter losing50poundstoaBMIof27,hisdailyenergyintakewill need to increase substantially to eventuallymaintain him stable atthatreducedweight.

Yes, when very heavy people lose a lot of weight, both their restingenergyexpenditureandtheenergycostof‘gettingaround’aresomewhatreduced. But then, so are the impediments (both physical andpsychological) to being more active. Thus this individual mightreasonably be expected to be burning 2800 kcal per day after his 50pound loss. As an aside, the casual reader might protest that theseenergy expenditure numbers look pretty high. But for anyonewho hasworkedwithobesehumansinametabolicresearchward,30kcalperkgofactualbodyweightinthesedentaryobeseand35kcal/kginthepost-obesemoderatelyactiveadultareactuallyquiteconservativeexpenditurevalues.

Nowifour‘bigloser’startedoutwith150gramsofprotein(600kcal)and25gramsofcarbs(100kcal)ininduction,this700kcaltotalsalmosthalfofhis intake,with the restof the1600kcal (56%,orabout100grams)comingfromdietaryfat.Whenhereacheshismaintenanceweightandiseating2800kcal/day,thereisneitherneednorreasonforhimtoincreasehisproteinintakeabove150grams,whichnowcalculatesoutas21%ofhistotal intake.Let’salsoassumethathehasprettygoodcarbohydratetolerance,allowinghimtoincreasethatto100grams(400kcal)perday.Howevertheremainderofhisdailyenergyintake(whichnowmustmatchhisexpenditure)hastocomefromdietaryfat–1800kcalor200gramsperday.

image

imageExample:Dailycaloricintakeandexpenditureina5’10”manlosingfrom230to180lbs(top)andbreakdownofnutrientintakeemphasizingprogressiveincreaseinfatcalories(bottom).Assumes30kcal/kgbeforeand35kcal/kgafterweightloss.

“Wow”,youmightbesaying,“that’swaytoomuchfat!”

OK,wehearyou–thatsoundslikealot.Butwhatarethealternatives?

•Eat lesstotalenergy?Butthenourbigloserwillkeeplosing,and eventually be plagued by hunger, cravings, and lowenergy.Thedefinitionof‘maintenance’isthatyourdailyenergyintakeequalsyourdailyexpenditure.

• Burn less energy? We want our subject to be reasonablyactive (not necessarily athletic), and that means burning atleast35kcal/kgdaily.

• Eat more carbohydrate? Even at 100 grams per day, oursubject is ‘flirting’with losing any benefits of the ketoadaptedstate. So adding more carbs while retaining the benefits ofcarbohydraterestrictionisnotanoption.Infact,manypeople,particularly thosewho aremore insulin resistant, need to eatevenlesscarbs(e.g.,40or50gramsperday).

• And finally, how about more protein? Well, his 600 kcal ofproteinrepresented38%ofhisenergyintakeduringinduction,but it was only 19% relative to his body’s 3200 kcalexpenditure.Nowinmaintenancewhenhe’sburning2800kcalper day, this 150 grams of protein equals 21% of his energyintake/expenditure.One could eatmore protein than this, butthere’snometabolicreasonwhythiswouldbebeneficial,andavarietyofdataindicatethattoomuchproteincausesmalaiseorworse (see sidebar). Even in the context of a weightmaintenance very low carbohydrate diet, as the proportion ofprotein is increasedabove30%ofcalories, there isamarkedincreaseinbloodureanitrogen[126].Fatcostslessandismoresatiating,andwe’vedemonstratedthatevenvigorousathleteson lowcarbdo just finewhen just15%of theirenergy intakecomesfromprotein.

HumanProteinTolerance

The upper limits of human protein tolerance have not been rigorouslydefined. However that’s not to say that this topic is completedunexplored.TheInuitknewtokeeptheirproteinintakemoderatetoavoidthe lethargy andmalaise that they knewwould occur if they atemoreproteinthanfat.Stefansson,duringhisyearintheBellevueexperiment,wasencouragedbythestudy investigatorstoeatahighproteindiet forthefirstfewweeks,causinghimtobeweakandsicktohisstomach[11].Finally, the Swedish investigators who developed thecarbohydrateloading hypothesis in the 1960’s used lean steak as theprincipal food for their lowcarb diets, and they had trouble keepingsubjectsonsuchadietformorethan10days.

Anotherway toexamineupper limitsofprotein tolerance is toexaminethe effect of protein meals varying in amount on muscle proteinsynthesis. Dose response studies indicate a linear increase in skeletalmuscleproteinsynthesiswithingestionofhighqualityproteinuptoabout20-25gramspermeal[127].Withproteinintakestwicethisamount,thereis a marked increase in protein oxidation with no further increase inproteinsynthesis.When lookedatover thecourseofaday, there isno

credibleevidencethatproteinintakesabove2.5g/kgbodyweightleadtogreaternitrogenbalanceoraccumulationofleantissue.

Anotherreasontoavoideatingtoomuchproteinisthat ithasamodestinsulinstimulatingeffectthatreducesketoneproduction.Whilethiseffectismuch less gram-for-gram than carbohydrates, higher protein intakesreduceone’sketoadaptationandthusthemetabolicbenefitsofthediet.

As a result of these observations, plus our studies ofmuscle retentionand functionduringcarbohydrate restriction[27,78,87],we recommenddaily protein intakes between 1.5 and 2.5 gram per day per kg ofreference weight[5]. For a person on a weight maintaining lowcarbohydrate diet, this typically translates to somewhere between 15%and25%ofyourdailyenergyintakecomingfromprotein.

Theanswer to this conundrum is thatour subject (andperhapsyouaswell)needstomakehispeacewitheatingfatashisprimarymaintenancefuel.Thisisnotaradicalconceptanymore.Wehavedemonstratedhowitcanbesafeandprovideareadyandsustainedfuelsupplytoallpartsofthebody.His1800kcalperdayintakeoffatis65%ofhistotalcalories.Restassuredthatanadultmalecaneasilyoxidizethisamountoffatovera 24 hour period.Using indirect calorimetry in subjects adapted to lowcarbdiets,wetypicallyseeaveragerespiratoryquotient(RQ)valueswellbelow0.8(evenduringmoderateintensityenduranceexercise),andthisis consistentwith someone burning less than 100 grams of total carbsperday,withmostoftherestcomingfromfat.

And finally, how does this work for the typical woman? Here’s theanalogous graphic for a 5’6’womanwho loses 30 pounds.We’ll spareyou the above litany of numbers for her case, but let’s give her 100gramsperdayofproteinand75gramsofcarbohydrateandthenfigureouther fat intake inmaintenance.Sinceherproteinandcarbs togetheraddupto700kcal,toreachher2200kcal/daymaintenanceintake,sheneeds 1500 kcal of fat daily. With that number in your head, you willperhapsappreciatewhywe’veincludedthischapterandthenextoneinthisbook.

imageExample:Daily caloric intake and expenditure in a 5’6” woman losing from 180 to 140 lbs.Assumes30kcal/kgbeforeand35kcal/kgafterweightloss.

DietaryFatfromanAboriginalPerspective

Given thatmanyofourdistantancestors innon-equatorialclimatesatelow carbohydrate diets for at least a million years[128], it is worthconsidering that theymay have learned useful lessons about the rightmixof fat andproteinbyempiric observation (i.e., trial anderror). Thisinformation can be gleaned from archeological observations, and alsofrom the interaction of literate individuals with aboriginal people beforetheiraboriginaldietarypracticeswereirrevocablyalteredorreplaced.

That said, however, a necessary caveat in this setting is the clearevidence for ethnocentric interpretation of aboriginal behaviors. It is anormalhumantendencyforustointerpretthebehaviorofothersthroughthelensofourownculturalpractices.Nomadicpeople,forexample,areoften viewedasunsettledor uncivilizedbecause theydonot build andmaintainpermanenthousesorvillages.As fordietarypractices,peoplewho cannot imagine themselves living without copious dietarycarbohydrate will tend to look for the hidden dietary carbohydratesources,howeverimprobableorobscure,inthedietsofhunters.

As noted in Chapter 2, we have considerable evidence that cultures

evolving around hunting and herding practices selectively harvested,processed, and stored dietary fats as a weight-efficient energy sourcematched to theirnomadic lifestyles[6,11].Asnomads, theywouldhavehadawider rangeoverwhich tohuntgame (orseekpastures for theirherds)thananagriculturalgrouplivingatonefixedsite.Thustheirfoodsupplywouldlikelyhavebeenricherandmorevariedthanforavillageorcavedwelling culture whose refuse heaps were more convenientlystudied. So again, we repeat our warning from Chapter 2, beware ofgarbagedumpscience.

FactorsInfluencingTypesofFatConsumed

It’s a common assumption that hunter-gatherers lived from hand tomouth,andthatatanypointintheannualfoodcycle,theyweregratefulfor any foods they could find.While thismay have been the apparentcaseasEuropean incursion reduced theaboriginals’ access to huntingand fishing, there is considerable evidence that pre-contact aboriginalhuntersofNorthAmericaactuallyenjoyedreasonablefoodsecurity.Thiswasaccomplishedthroughevolvedculturalpracticessuchastimingthehunt to obtain optimum carcass fat content, plus traditional foodprocessing that preserved high fat foods to cover lean times in thehunting cycle. Examples of this mentioned above include the Inuit’sautumncache, themanufactureofpemmican,smokinganddrying fattyfish (salmon, oolichan, eels), and production and storage of oolichangrease.

Whatthismeansisthatformuchoftheyear,thesehuntingcultureshadnotonlyachoiceofhowmuch fat theyconsumed,but tosomedegreethekindoffataswell.Forexample,ontheNorthPacificCoast,sealionsand seals could be (and were) harpooned for food and skins. Andalthough theyare rich in fat, the people of the region chose instead tofocus on catching and processing the tiny oolichan as their primary fatsource[12]. The reason for that is found in the chemical and physicalproperties of oolichan grease compared to seal oil. The latter, rich inomega-3 fats, promptly goes rancid upon exposure to air. Oolichangrease, which is low in polyunsaturates (it consists mostly ofmonounsaturated and saturated fats), is muchmore stable in storage,

allowingittobekeptforayearormorewithout‘goingbad’.

There is also a similar rational for pemmican, as the body fat of thebuffalo, particularly in the summer, is rich in saturated fats and low inpolyunsaturates, which allows the manufactured pemmican to remainsolidyeararound,andalsoreducestheriskofrancidity.

But this then raises the question of the balance between desirablephysical properties (solidity, low rancidity) versus the health effects ofeating that fat. Perhaps these aboriginal cultures were harmingthemselvesbyeatingmoremonounsaturatesandsaturatesbyavoidingsourcesrichintheessentialpolyunsaturates.

Twopointsmentionedpreviouslyinthisbookaregermanetothisissue.First, polyunsaturated oils rich in essential fats are important dietaryconstituentswhenone iseatinga low fatdiet.However ifone iseatinglots of fat, to get the same absolute amount of essential fats, amuchsmallerproportionofpolyunsaturated fats (bothomega-6andomega-3)will suffice. Second,we have demonstrated in both human and animalstudies that a low carb diet is associated with increased levels ofessential fatty acid products (i.e., arachidonate and DHA) in bloodphospholipids and tissue membranes. This occurs without signs of anincrease in production, suggesting that their rate of degradation goesdownwhen dietary carbs are limited. Thus the human requirement foressential fatty acid productsmay actually be somewhat reducedon anaboriginalhuntingdiet.

Summary

Itmayseemobvious,butit’simportantenoughtoreiteratethatinordertopreservethetherapeuticbenefitsfromcarbohydraterestriction,youhaveto be able live a low carbohydrate lifestyle. In other words a lowcarbohydratedietdoesnotcureinsulinresistanceordiabetes,butitveryeffectively does put it in remission. Therefore it is critical to stay at orbelow your unique level of carbohydrate tolerance to continue to reapthesebenefits long term.When transitioning fromweight loss toweightmaintenance (the diet you will be eating the rest of your life), caloriesinevitablyneedtobeincreased.There’salotonthelinesothedecision

of how to do this is important. Adding carbohydrates back is a riskystrategybecauseifyouexceedyourtolerance,thenyourprevioussignsandsymptomsmayreturnwithavengeance.

Forthosereaderswhoplaypoker,addingcarbsbackisabitliketakingahitinblackjackwhenyouareholdingahard17,18,19or20.Whilethereisachanceyoucanimproveyourhand(i.e.,youmightbeabletotoleratethe carbs), the odds are you will bust (i.e., insulin resistance signsreturns).Asaferalternativeistoaddmorefatintoyourdiet–likehavinganaceinyourpocket(note–we’renotpromotingcheating).Bottomlineit’ssafertostaylowcarbthantohopeforalowcard.

Chapter17

THEJOYOFCOOKING(ANDEATING)FAT

Introduction:

Let go of your guilt for a second and think back.Most of us have hadperiodsofdietaryrestrictionafterwhichwehadfreeaccesstoanythingwe wanted. Maybe it was a diet camp you got sent to as a teen, anextendedperiodof intenseexercisewith limitedfoodchoices,ormaybejustaweekatyouraunt’shouse(youknow,theonewhoservedyoucoldcereal with skimmilk for breakfast and then spaghetti-O’s and iceberglettuce with low fat ranch dressing for supper). What was themacronutrientyoureallycraved?Wegiveyouten-to-oneoddsitwasfat,and you probably remember just howgreat it tasted.No, you probablydidn’tsitdownandeatacanofbutter(seesidebar),butwhetheritwasBen and Jerry’s ice cream, a grilled cheese sandwich, or a baconcheeseburger,itwasfatyouwerecraving.Butyouprobablyateitmixedwithsomethingelse,unlikeJoranKropp’sinfamouscanofbutter.In his 1996 trek to the summit of Everest after riding his bicycle therefromSweden,theadventurerJoranKroppmadethreeattemptstoreachthe summit before finally doing so.Up through the second attempt, hehadbeeneatingavegetarianlowfatdiet.Whenhedescendedafterhissecondattemptfailed,hewassoexhaustedanddepletedthathebrokefromhisvegetariandietandatea largecanofpurebutter thathepan-handledoffofthefilmcrewthatwasdocumentinghisclimb.Withenoughfatback inhisdiet,onhisthirdattempthewentontoreachthe30,030footsummitwithoutusingsupplementaloxygen.

After50yearsofdemonizing fat, thereare twoobvious impediments toaddinggood fatsback intoourdiet.The first is limitedaccess,and the

secondisitspreparationasfoodsweliketoeat.

Access to fat? You ask. There’s lots of fat to be had in stores andrestaurants.Yes,butwhatkind?Mostofthefatinpreparedmayonnaise,dressings, sauces, andmarinades is thewrong kind for a persononahigh fat diet – high in polyunsaturated fat (PUFA) from the cheap,government subsidized soy, corn, and cottonseed oils used asingredients.Oliveoil isconsidered tooexpensivean ingredientbymostmanufacturers,andthelessexpensivehigholeic(lowPUFA)versionsofsafflowerandsunfloweroilsareslowcomingtomarket.Afterdecadesoftellingconsumers thathighPUFAoilsaregoodforyou, it’shard for themarketing folks in the big food companies to start saying the oppositewithoutlookingfoolish.

Because restrictingdietarysaturated fathasbeena focusofnutritionalrecommendations since the 1970s, an unfortunate consequence hasbeen reducedavailabilityof the tastyandhealthy traditionalanimal fatsenjoyedbyourancestorsfor thousandsofyears.Fiftyyearsago,everybutcherstocked lard,porkbelly,andbeef suet.Nowadiligent shopperhastoscroungetofindanyofthem.Duck,gooseliver,beeftongue,andmarrowboneswerecommonlyeatenasgourmetfoods.Nowtheyhaveall but vanished from both our plates and our memories. In the past,cheesewas a high fat food.Now you have to be careful when buyingcheesetoavoidgettingthe‘reducedfat’or‘lowfat’optionsthattastelikerubberorStyrofoam.

Sohowdowedealwiththisreducedaccesstothekindsoffat thataredesirable(frombothtasteandhealthperspectives)whenfollowingahighfat,lowcarbohydratediet?Clearlyakeybehavioristobecomeacarefulanddiscriminatingshopperwhenitcomestofat.Perhaps,asmoreofusaskfortraditionalfats,theywillagainbecomemoreavailable.

The second impediment to consuming the right kinds of fat is that wehave lost the preparation skills needed to include it in our diet.Even ifyoudidmanagetobuyanicethickslabofporkbelly,whatwouldyoudowithit?Todealwiththisimpediment,therestofthischapterisdevotedtoselectedrecipesthatallowyoutoincludetastyandhealthyhighfatfoodsin your daily intake. For convenience, all of these can be made with

readily available ingredients – no need to go scrounging for pork bellyand/or hide your face from embarrassment when paying for it at thecheckoutisle.

HighFatSideDishes

Sautéedkalewithgarlicandoliveoil

Sadly,inmodernAmerica,kaleismoreoftenseenthaneaten.It’sthoseleavesthatarestuffedbetweenthebowlsofvegetablesandcondimentsin the typical salad bar. It is great for this because it is a pretty ruffleddark green, and it doesn’t wilt for days. However when some boldindividualbuysitinthegroceryandtrieseatingit,theoutcomeisusuallygrim.Why is this?And if it’s sobad,whydid our grandparents grow itanyway?

Kale is a member of the cabbage family, whichmeans that it is frost-hardy and grows well in cool climates. This is actually importantinformation. Its frost hardiness stems from its ability to shift a bit ofcomplexsugarfromitsrootsintoitsleaveswhentheweatherturnscold.This in turnmeans that kale harvested in the late fall tastes sweet, incontrast toamorebitter flavorwhen it is harvested in summer.So thetime toeat kale is in the late fall andallwinter long. Let themuse thesummerharvesttomakesaladbarslookappealing.Ohyes,the‘sugar’intheleavesoffall/winterkaleonlyaddsupto3gramsofcarbohydrateper half cup cooked serving, so eat it without worry about yourketoadaptation.

Ingredients:20orsokaleleaves6’10”long(1-2bunchesinthemarket)2clovesofgarlicpeeledandchopped(about2teaspoons)3tablespoonsoliveoil¼teaspoonsalt

Rinse thekale incoldwaterandstrip the flesh from thestems, tearingintopostagestamp-sizedpieces,allowtodraininacolanderorsieve.

Brownthegarliclightlyintheoliveoilovermediumheatinalargeskillet,

thenaddtheshreddedkaleandsalttothehotoilandcover.Reducetheheattosimmercoveredfortenminutes,stirringonceortwicesoitcooksevenly.Serves3-4,10gramsoffatperserving.

Alternative: rather thanoliveoil,useanounceor twoof finelychoppedsowbelly, fried lightly before adding the garlic. This dish can bemadewithcollardsaswell.

Cucumberyogurtsalad

Yogurt-baseddressingsarecommoninGreece,theMiddleEast,andtheIndiansubcontinent.Yogurtgoeswellwithbasil,dill,andlemon,allowingavarietyofflavorvariations.Thisrecipeusesquiteabitofyogurtrelativeto the cucumbers, so the result is a bit like a cold yogurt soup withcucumber slices. And as an aside, as long as you use ‘live cultureyogurt’,ignorethe‘sugars’listedontheyogurtcontainer’snutritionfactslabel. This is the amount of lactose (milk sugar) in the ingredient milkbeforetheyogurtwasmade.Inlivecultureyogurt,morethanhalfofthisisbrokendowntolacticacidduringthefermentationprocessthatmakesyogurt.Unlikelactose,lacticacid(lactate)iseasilyabsorbedbythebodywithoutraisingyourinsulinlevel.

Ingredients:6mediumor4largecucumberspeeledandsliced4sprigsofdill,chopped(about2teaspoons)2cupsfullfatplainyogurt(notthesweetenedvanillaflavor)2tablespoonsfreshlemonjuice2clovesofgarlic,peeled4tablespoonsoliveoil,preferablyextravirgin½teaspoonsalt¼teaspoonfinelygroundblackpepper

Putthedill,garlic,oliveoil, lemonjuice,pepper,andsalt inan8-12cupfood processor and blend with the metal blade until smooth. Add theyogurtandblendbrieflyuntilwellmixed.

Pourtheyogurtmixoverthecucumbersinacoveredbowlandchill.

Makes 4-6 servings, each containing 12 grams of fat and 4 grams ofcarbohydrate.

For a nice presentation, serve in small bowls with 5-6 Belgium endiveleavesasscoops.

Creamedspinach

Ingredients:2poundsfreshspinach2mediumonionsfinelychopped2-3clovesofgarlicfinelychopped1cupheavycream2tablespoonsbutter2tablespoonsoliveoilSaltandpepperParmesancheese(optional)

Washanddrainspinachandremovetoughstems. Ina largepot,sautéonions and garlic in butter and olive oil until translucent. Add spinach,constantly stir and press down until leaves are wilted. Add cream andcookuntildesiredtexture.Addsaltandpeppertotaste.Topwithshavedparmesancheese(optional).

FrenchFriedGreenBeans

Fingerfoodtogowithasteakorburger,orjustbythemselvesforthefunofit!

Ingredients:1poundoffreshgreenbeans1teaspooncoarseseasalt

½teaspoonblackpeppercornsorrosepeppercorns¼teaspoongarlicpowder½teaspoondriedItalianseasoningmix1eggwhite

Pre-heatadeepfat fryerto240oF(hot)–preferablyfilledwithhigholeicsaffloweroilRinsegreenbeans,trim,andpatdryonatowelGrindspicestogetherinamortarandpestleWhipeggwhiteuntilfoamy,thencoatthegreenbeansinegg,Putegg-coatedbeansina1-qtplasticbaganddustwithgroundspices,shake vigorously, and drop into hot oil. Fry for 2-3 minutes. Removewhentheeggcoatingjuststartstobrown.

Tomatobisque

For thoseofuswhogrewup thinking that soup isborn ina can, it’sadelightfuldiscoveryhowgoodhomemadesoupscanbe,andhoweasythey are tomake. Also, if youmake your own soups from your homemadebroth,aservingofsoupdoublesasaservingofbrothaswell.

This recipe isbest if youhave ripe tomatoesand freshbasil fromyourgarden,otherwiseuseplum(roma)tomatoesfromthestore.

Ingredients:1largeonionsliced¼inchthick6largeor12smalltomatoes(thetotalvolumeshouldbe2-3cups)10-15freshbasilleaves¼cuplightoliveoil½teaspoonfinelygroundblackpepper4cupshome-madechickenbroth1cupmedium(25%fat)orheavy(40%fat)cream

Rinsethetomatoesandbasilleavesincoldwateranddrainonatowel.

Put olive oil and onions in a medium (3-4 quart) pot and brown overmediumheatforabout5minutes.Theonionsshouldenduplightbrown,soft,andtranslucent.

Cut the tomatoes inhalfandadd themalongwith thebasil leavesandpepper.Coverandsimmerfor10minutes,untilthetomatoesaresoftandcookedthrough.

Allow to cool for 5 minutes and place tomato/onion mixture in a foodprocessor and blend for 60 seconds, pulsing frequently to be sure alllargehunksarechoppedfine.

Rinsethecookingpot,placealargesieveoverit,andstraintheblendedtomatoonionmixthroughit,discardinganysolidsthatdon’tgothruthesieve.Dependingonhowsmoothyouwantthetextureofthesoup,youcanchoosethesievemeshsizefromcoarsetofine.

Addthechickenbrothtothetomatoonionpureeandwarmoverlowheat.Heatuntilitjuststartstosteam(160-170oF)--don’tletitboil!

Takesoupofftheheatandwhiskintheheavycream.

Salttotaste(theamountdependsifyourchickenbrothwassalted).

Serve warm. Serves 6. Provides 20-25 grams fat and 5 gramscarbohydrateper10ozserving,

Wedgie

Rememberwhenacheesesandwichandaniceberglettucewedgewithranch dressing was lunch? Now some people look back fondly at thaticeberg wedge as comfort food.Well, here’s amodern version, dosedwithenoughotherstuffthatitactuallyhasmeasurablenutritionalvalue.

Ingredients:1 head of iceberg lettuce, stripped of wilted outer leaves, rinsed anddrained

½cupofcrumbledbluecheese½cupofbaconfriedlightlycrispandchopped1cupofslicedordicedfreshtomatoes1cupofslicedordicedcucumber1cupofyogurtbluecheesedressing(recipebelow).

Slicethelettuceintoquartersthroughthestemandremovethecorefromeachpiece.

Sliceeachquarteragaintomakeequalwedges(eights)andlaythetwonarrowedgestogetherinthecenterofasaladplate.

Arrange the toppings in the ‘centralvalley’– forexampleputcucumberand tomatoes on either end and the blue cheese and bacon in themiddle.

Drizzle 4 oz of the yogurt blue cheese dressing over the top whenserved.

Serves4.Fatcontent30gramsperserving.HighFat,ModerateProtein,LowCarbBreakfastSmoothies

Recipesfor‘lowcarbohydrate’smoothiesabound,butmostarealsolowinfatandassumethatanythingunder200Caloriesfromsugarsqualifiesas ‘low carb’. Here are two basic recipes that provide enough fat andproteintokeepyousatisfieduntillunch,andbothcomeinatorunder10gramsofcarbohydrates.Notethatyouhaveyourchoiceofsweeteners,but the argument for adding some xylitol to themix is that it does notraiseyourinsulinlevel,providesusefulenergy,andprotectsyourdentalhealth.

Also note that there are lots of different protein powders for sale, butmost whey products are flavored and sweetened. Shop until you findunflavored whey powder with the lactose removed – the label shouldindicate about 15 grams of protein and less than one gram ofcarbohydrate per serving. Do not buy soy protein powder or whey/soymix, as the soy does not dissolve well into the smoothie. This wheypowder looksexpensive (about $1per 15gramserving) but this is the

sameamountofproteinasyougetfrom2eggs.

BreakfastBerrySmoothie

Ingredients:3ozfreshorfrozen(unsweetened)berries(strawberries,blueberries,orraspberries)¼cupwhipping(orheavy)cream1tablespoonlightoliveoil2tablespoonsunflavoredwheyproteinpowder(delactosed)sweetenerofchoice(e.g.,1tablespoonxylitoland1packetSplenda)2-3ozice

Blendtheingredientsathighspeeduntilsmooth(30-60seconds)

Protein15grams,Fat25-30grams,Carbs10grams,Calories330-380

BreakfastMoccaSmoothie

Ingredients:4ozcoffeeice(frozeninicecubetray–iffrozenasabiglumpinacuporbowel,itshardtoblend)¼cupwhippingorheavycream1tablespoonunsweetenedcocoapowder1tablespoonlightoliveoil2tablespoonsunflavoredwheyproteinpowder(delactosed)sweetenerofchoice(e.g.,1tablespoonxylitoland1packetSplenda)

Blendtheingredientsathighspeeduntilsmooth(30-60seconds)

Protein15grams,Fat25-30grams,Carbs6grams,Calories310-350HighMonoDressings

Yogurtbluecheesedressing

Commercial blue cheese dressings abound out there, sowhy should Imakemyown?

Answer:Bettertaste,betternutrition,andtherightkindoffat.Andifyouneedanotherreason, thisrecipecanbemade inquantityandstored inyour freezer insingleservingdoses.Spend15minutesmakingabatchnow,andget10servingswheneveryouwantthemlater.

Ingredients:2clovesofgarlic,10freshbasilleaves2tablespoonsfreshlemonjuice¼cupoliveoil4 cups plain unsweetened yogurt (full or low fat, not fat-free anddefinitelynotvanilla!)8ozcrumbledbluecheese1/8teaspoonfinelygroundblackpepper1teaspoonsalt

Putthegarlic,basil,lemonjuice,oliveoil,pepper,salt,and4oz(half)ofthebluecheeseinablenderorfoodprocessorandprocessuntilsmooth.Add the yogurt and pulse until wellmixed. Add the other 4 oz of bluecheeseandprocessbrieflytomix(butnotblend).

Parcelout½cupunitsintosnackzip-lockbags,squeezingoutanyextraair.Putinacontainerandfreeze.

Whenneeded,takeindividual½cupunitsoutofthefreezerandthawforafewminutesincoolwater.

Makes10half-cupservings,eachcontaining16gramsoffat.

Honeybasildressing

Thisdressingismadewithrealhoney,butsinceitismostlyoliveoil,thesugar content of the dressing per serving is quite low. This dressing

keeps well in the refrigerator, and the roasted garlic is an excellentemulsifier, so it usually doesn’t separate like most oil and vinegarconcoctions.

Ingredients:10clovesofroastedgarlic20freshmediumor10largebasilleaves¼cupunsweetenedricevinegar(finditintheAsianfoodssectionofyourgrocery)¼cuphoney2packetsofSplendaor2leveltablespoonsxylitol1cuplight(notextravirgin)oliveoil½teaspoonsalt

Thebestway to roast garlic is toget a coveredceramicgarlic roaster,slicethetopsoffafullgarlicbulb,drizzleitwithatablespoonofoliveoiland roast in the over for 45 min at 400 oF. Alternatively use a metalmuffintin,placethetrimmedgarlicbulbbasedown,drizzlewitholiveoil,covereachbulbwithaluminum foil, andbake for30-40minat400oF.Whendone,thegarlicclovesaresoftandstartingtopushupoutoftheholesyoucutinthetopofeachclove.

Puttheroastedgarliccloves,basilleaves,ricevinegarandhoneyintoafood processor or blender and process until very smooth (at least 2minutes).Add theoliveoil, sweetener, andsalt.Blenduntilwellmixed.Refrigerateextrainaclosedcontainer.

Makes12oneozservings,eachcontaining20gramsoffatand5gramsofcarbohydrate.

Sun-driedtomatocaperdip(tapenade)

Thisdip isusuallyusedonbread,but it isgreatwith freshvegetables,particularlyBelgian endive. It is nicewhenmadewith commercial sun-dried tomatoes, but it is outrageously goodwhenmadewith your ownhomegrownripetomatoesthatyoudryyourself.

Here’s a simple way to dry tomatoes. Using a sharp knife, slice ripetomatoes in ¼ inch thick slices blot dry on a paper towel, and lay onwaxed paper in a dish in the bottom of the microwave. If you have amicrowave shelf, cover it with more tomato slices as well. Run themicrowavefor5minutesat30%power(defrost)andthenfor60minutesat10%power.A1000Wattmicrowaveputsout100Wattsat10%power,so it’s making about as much heat as a 100Watt light bulb, and thetomato slices should be slightlywarmbut not hot.Check the tomatoesafter each hour, turning and rearranging as needed to help them dryevenly,repeatingthesame5/60minuteheatingcycleeachtime.Thiswilldry3-4poundsof tomatoes inabout5hrs.Whendone, theyshouldbeleathery in texture and still dark red. Do not dry them to black crispywisps.

Ingredients:3ozofdriedtomatoes(from1.5to2poundsoffreshtomatoes)2oznon-pareilpickledcapers,lightlyrinsedanddrained20freshbasilleaves3-5clovesroastedgarlic1packetSplendaoroneleveltablespoonxylitol2tablespoonsunsweetenedricevinegarorwinevinegar1cuplightoliveoil

Addeverything together ina foodprocessorandblenduntil the tomatoandbasilaredowntofinebits.Theflavorisbestifmadeatleastanhourbeforeserving.Remainingdipcanberefrigeratedforaweek.

Eachtablespooncontains10gramsoffat.Desserts

Maplewalnuticecream

Delicious,easytomake,andguiltfreeicecream.

Ingredients:

½cupEnglishwalnuts2tablespoonsbutter2tablespoonsrealmaplesyrup4cupsheavyorwhippingcream2/3cupxylitol8packetsSplenda2-3dropsofartificialmapleflavor

Chopthewalnutstopeasize.Putthenutsinasmallfryingpanwiththebutterandheatover lowheatuntil thenuts juststart tobrown.Addthemaple syrup to nuts and butter and stir gently over low heat until thesyrup thickensandcoats thenuts.Takeoff theheatandallow to cool.Whencool,thenutsshouldhardenintofirmstickylumps.

Mixthecreamandsweetenerstogetherandstirwithaspoonuntilallaredissolved.Addthemapleflavorandputinanicecreammaker,churninguntil it is thickenough to formastablemoundonaspoon.Breakapartthe lumps of sugary nuts and drop them into the ice creamand churnonlyuntilwelldistributed.Putinthefreezertofirmup.

Makes 10 half-cup servings, each containing 25-40 gramsof fat and 4gramsofcarbs.

Blueberrycheesecake

Cheesecakewould be a great source of dietary fat if it weren’t for thecrustandallof thesugar in it.Sohere’sacrustlesscheesecakemadewithoutany‘sugar’,i.e.,thestuffthatraisesyourinsulinlevel.

Ingredients:2packetsplainunsweetenedgelatin1cupxylitol(alternative½cupxylitoland6packetsSplenda).1½cupswater12ozcreamedcheese

1/4cuplightoliveoil2teaspoonsvanillaextract2cupsfreshblueberries(orslicedstrawberries)

Heat the water to boiling, remove from heat and sprinkle the gelatinpowderinwhilestirringvigorouslyuntilitisdissolved(clear).

Putthecreamedcheese,oliveoil,xylitol,andvanillainafoodprocessor,pourinthehotgelatinsolution,andprocessuntilsmooth.

Rinsetheblueberries,patdry,andputinthebottomofa9-inchpieplate.Pour the stillwarmgelatin-cheesemix over the berries and chill in therefrigeratoruntilitsets(30-60min).

Makes 12 4-5 oz servings, each with 15 grams of fat and 4 grams ofcarbohydrate.

Alternatively,distribute theberries into6 ‘snacksize’Zip-Loc’bagsandpour inenoughcheesecake liquid to filleachbag.Squeezeoutanyair,seal immediately, and refrigerate). The sealed bags keep for up to aweekrefrigeratedandadayunrefrigerated.

Summary

Wehopeyounowhaveabetterappreciationofhowimaginativeyoucanbe with using fat to create appetizing dishes. Yes, adhering to a lowcarbohydratedietdoesrequireyoutogiveupmostofthosesweetsandstarches thatoncecontrolledyou,but that’sasmallsacrificewhenyouconsiderwhatyou’retradingupto.Nowthatyouareketoadapted,usingtraditional fats like butter, olive oil, heavy cream, cheeses, and creamcheeses in combination with a variety of vegetable dishes are highlyencouraged and part of what makes a low carbohydrate diet lifestyleenjoyableandsustainable.

Postscript:SevenDaysofLowCarbLiving

Herearesevendaysofmenusonemight followonamaintenancedietprovidinglessthan50gramsperdayoftotalcarbohydrates.Theportions

indicatedprovidebetween2400-2800kcalperday,suitableforanormalweight, active male 5’9” tall. The division between fat, protein, andcarbohydrates are listed at the bottom of each day’s menu in bothkilocaloriesandaspercentoftotalenergy.

Thesearenotprovidedasadietprescriptionforanyoneperse,butasan illustration of the amount and variety of foods one can eat on awellformulated low carbohydrate diet. Note also that this variety isachievedwhilekeeping the totaldailycarbohydratebetween30and50grams. Thus someonewith less carbohydrate intolerance (e.g., able totolerate80gramsperday)willhaveevenanevengreatervarietyoffoodchoices.

Day1intheLowCarbLifeBreakfastberrysmoothie(lowcarb,highfat)

Lunch2cupsmixedgreens6ozwaterpacktuna10blackolives½cupbluecheesedressing(yogurt,oliveoil)

Snacks2ozmixednuts,broth2ozsoftcheesewith6ozcelery

Dinner8oztomatobisque8ozsteak

4ozbutteredgreenbeans4ozsauteedmushrooms4ozmaplewalnuticecream(madew/sucralose/xylitol)Total:2100kcalfat,600protein,150carbs(74%fat,5%carb,21%protein)

Day2Breakfast2eggs2slicesbacon½cupsauteedmushrooms

Lunch1cupbeefbroth6ozcoldroastporklettucewedge2ozhoneybasildressing

Snacks2ozmixednuts,broth2ozcheddarcheese

Dinner6ozroastchickenwithfennelkalesauteedwithbacon,garlic,andoliveoil4ozberrieswithcreamTotal:1800kcalfat,520protein,130carbs(73%fat,5%carb,22%protein)

Day3

Breakfastblackcoffeecauliflowercorned-beefhashwithpeppersandonions(1tbsoliveoil)

LunchChickenCaesarsalad(takeout,4ozchicken)½packetcommercialCaesardressing(madewithsoybeanoil)1tablespoonoliveoilunsweetenedicedtea

Snacks2ozmixednuts,broth2ozsoftcheesewith6ozcelery

Dinner8ozsorrelsoup8ozbabybackporkribslettucewedge(8oz)2ozyogurt/bluecheesedressing1ozbaconbits1ozbluecheesecrumbles2ozchoppedtomatoes2ozchoppedcucumberTotal:1880kcalfat,490protein,120carbs(76%fat,5%carb,19%protein)

Day4Breakfast2-eggomelet

(1ozeachbacon,mushrooms,cheese,tomato)blackcoffee

Lunch2cupsCobbsalad(takeout)1tablespoonoliveoilUnsweetenedicedtea

Snacks2ozmixednuts,broth10blackolivesstuffedwithripebriecheese

Dinner8ozFrenchonionsoup(with2ozguerrecheeseand2ozonion)SolestuffedwithcreamedspinachincheesesauceBlueberrycheesecakeTotal:1600kcalfat,440protein,120carbs(74%fat,6%carb,20%protein)

Day5

Breakfastblackcoffee3ozsmokedsalmon1ozcreamedcheese1tbspcapers6lettuceleafwrappers

Lunch2cupsmixedgreens6ozwaterpacktuna

10blackolives½cupbluecheesedressing(yogurt,oliveoil)

Snacks2ozmixednuts,broth2ozsoftcheesewith6ozcelery

Dinner12ozlowcarbsausagechili8ozgrilledasparaguswithherbbutter4ozcocoapecanicecreamTotal:1810kcalfat,530protein,200carbs(71%fat,8%carb,21%protein)

Day6

Breakfastblackcoffee4ozhamsliceswrappedaround4ozcoldgrilledbutteredasparagus

LunchDoublebaconcheeseburger(nobun)Unsweetenedicedtea

Snacks2ozmixednuts,broth4ozdicedcucumber,2ozdicedtomato2ozyogurtbluecheesedressing

Dinner8ozbaconwrappedsteak4ozfrench-friedgreenbeans

4ozsauteedmushrooms4ozmaplewalnuticecream(madew/sucralose/xylitol)Total:1755kcalfat,564protein,132carbs(72%fat,5%carb,23%protein)

Day7

Breakfastmoccafreezesmoothie

Lunch2cupsmixedgreens6ozwaterpacktuna10blackolives½cupbluecheesedressing(yogurt,oliveoil)

Snacks2ozmixednuts,broth2ozsoftcheesewith6ozcelery

DinnerCoqauvin(stewedchicken)4oztomato4ozsauteedmushrooms2ozonionlettucewedgewithhoneybasildressingTotal:1727kcalfat,520protein,224carbs(70%fat,9%carb,21%protein)

Chapter18

TENCLINICALPEARLS

Oneof theauthorswasoncecharacterizedby thestatement: “Askhimdirections toget toacertainbridgeandhe’ll tellyouhow tobuildone.”And perhaps there’s a morsel of truth to that bit of hyperbole. We’vededicatedaconsiderablepartof thisbook tellingyouhowandwhy lowcarbohydrate diets can be safe, effective, and sustainable; but as aresult, some of the straightforward “what” informationmay have gottenlostintheclutter.Sohereare10reasonablybrieftake-awaypoints(aka‘pearls’) thatareessential to theclinicaluseofcarbohydraterestriction,whetherforyourselforforyourpatient/client.

1.Honorthe‘SchwatkaImperative’

ThisquotefromFrederickScwhatka’sdiarywrittenduringhisepic3000-mile trek across the Canadian Arctic in 1879-80 is the first cleardescriptionofketoadaptation.

“Whenfirstthrownwhollyuponadietofreindeermeat,itseemsinadequate to properly nourish the system and there is anapparent weakness and inability to perform severe exertive,fatiguing journeys.But this soonpassesaway in the courseoftwotothreeweeks.”[10]

Thisremarkablyclearsummaryofthephysicaleffectsofstartingonalowcarbohydrate diet has been corroborated by Steve Phinney’s twostudies[27, 76]. Andwhile other biochemical variables show continuingchangeintheadaptationprocessbeyond2-3weeks,mostofaperson’sperceivedlaginintensityandstaminaareeliminatedsometimewithinthistimeperiod.

Sothesimpleimperativeistogiveyourself(orsocounselyourpatients)2weeksafterstartinga lowcarbdietbeforebeginningor increasinganexerciseprogramorresumingaphysicallydemandingjob.Andalthoughithasnotbeenformallystudied,thissameintervalisrequiredifonegoesoff of carbohydrate restriction (be it a week or a month) and thenresumes the low carb diet. This in turn suggests that onewill feel andfunctionbest ifcarbohydraterestriction isconsistentlymaintainedratherthanfollowedintermittently.

2.ItOnlyAppearstobeHighProtein

Most people starting out on a low carbohydrate diet intend to (andsubsequentlydo) loseweight.Thisweight lossoccursbecauseyouareeatingmuchlessenergythanyourbodyisburning–typicallyearlyonuptohalfofyourdailyenergyneedsarecomingoutofyour lovehandles.However one’s protein needs (expressed as grams per day) are aboutthesameacrossallphasesofcarbohydraterestriction,whetherit’syourfirstweekinInductionoryoursecondyearinweightmaintenance.

Thismeans that your dietary protein intake is proportionately higher atthe start of the diet when weight loss is occurring than later on whenweightlosshasstopped.UsingourmaleexamplefromChapter16,ifyoueat150gramsofprotein(600Calories)in1600Caloriesperday,thedietlooks to be 38% protein. Later on, when you eventually advance yourenergyintaketothepointofachievingweightstability,say2800Caloriesperday,thatsame150gramsofproteinisnowonly21%%ofyourdailyenergy intake. That’s because in both situations most of your dietaryenergyneedsarecomingfromfat.Butinweightmaintenance,allofthisfatneeds to come fromyourdiet, so theprotein content in yourdiet isproportionatelyless.

3. If You Can’t Lose Your Fear of Fat, You Can’t Do Low CarbMaintenance

If youhadaproblemmetabolizingcarbohydrates tostartwith,chancesare thatproblemwill notgoawaycompletelyevenaftera lotofweightloss.Manypeople find that theyget back intometabolic trouble if theyadd too much carbohydrate as their diet transitions into maintenance.

Somepeoplewithmetabolicsyndromecantolerateupto100gramsperday of total carbs, whereas others find they need to stay under 40 toavoidthereturnofunhealthybloodlipidsorweightregain.

But be it 40gramsor 100, that’s alwaysgoing to be less than20%ofyour daily energy intake for a healthy active adult who burns between1800and3000Caloriesperday. Insomecases (e.g., inapersonwithseverecarbohydrateintolerance)carbsmaytotalaslittleas5%ofdietaryenergy. So if protein provides 15-20% and carbs range from 5-20%,anywherebetween60%to80%ofyourdailyenergyintakehastocomefromfatwhenyougettothepointthatyouaremaintainingyourweight.

Simply put, there is no option for weight maintenance that issimultaneouslylowincarbohydrateandlowfat.Yourenergyhastocomefromsomewhere,andforpeoplewithcarbohydrateintolerance,theirbest(andsafest) long-termenergysourceisdietaryfat.Practicallyspeaking,that means purposefully seeking out enjoyable sources of fat androutinely including them in your diet. Given how much we’ve beenbrainwashed that fat is bad, this means patting yourself on the head,holdingyourhand,andtellingyourself“Iunderstand,it’sOK”.

Now, does this mean that you can’t eat any carbs? Of course not!Whetheryourmaintenancedietallows40gramsor100gramperdayofcarbohydrate, you have a list of over 50 vegetables, nuts, and fruit tochoose multiple servings from every day (see The New Atkins for aNew You[5]). Our point here is that with your dietary carb intakeconstrainedbyyourindividuallevelofcarbohydratetolerance(beit40or100grams),youmustgetcomfortableeatingfatasyourprimarysourceofdietaryenergyifyouwanttosucceedinlowcarbmaintenance.

4.BePickyAboutFats

Notallfatsarethesame,andyouneedtobeselectiveaboutwhichonesyoueat forenergy.Ona low fatdiet,because there isso little total fatintake,afairlyhighproportionofwhatmodestfatyoueatneedstocomefrom the two essential fat classes, omega-6 and omega-3. But theopposite is truewhen youareeatingahigh fat diet. There is somuchomega-6fatinourfoodsupplythatif60%ormoreofyourdailyenergyis

comingfromfat,it’shighlyunlikelyyou’devercomeupshort.Asfortheomega-3’s,either3fishmealsperweekoragramofsupplemental fishoildailysuffices.

Ithelpstothinkofthesetwoessentialfatclassesasiftheyarefatsolublevitamins.Whileyouneedamodestamountofeachtostayhealthy,moreisnotnecessarilybetter.Inaddition,ourstudieshaveshownthatinbothhumans and animals adapted to low carb diets, the bodymakesmoreefficient use of both classes of essential fats compared to when fed ahighcarbdiet.

In terms of practical choices, this implies that we give high priority tomonounsaturates, thensaturates,andmakereasonableefforts toavoidrichsourcesofomega-6polyunsaturates.Read labelsandselect foodscontaining olive, high-oleic safflower, and canola oils. Use olive oil orhigh-oleic safflower in cooking. Butter and full-fat cheese are OK, andtrimming fat off ofmeat and skin off of poultry is no longer necessary.When possible, avoid mayonnaise and dressings made with soybean,corn,sunflower,andcottonseedoils.

5.TheSaltParadox

When the human body adapts to a low carb diet, the kidneysfundamentally change how they handle sodium. Removingmost carbsfrom thediet causesyour kidneys toaggressively secretesodium (andalongwithit,extrafluid).Thisiswhymanypeopleexperienceadramaticearlyweight losswithcarbrestriction.But thismeans thatacontinuousmoderate intake of sodium is necessary to keep your circulationadequatetohandle‘heatstresses’likehotweather,enduranceactivity,orevenahotshower.

Ifyouareeatinglessthan60gramsofcarbohydrateperday,youneedtopurposefullyadd2-3gramsofsodiumtoyourdailyintake(unlessyouarestill taking diureticmedication under a doctor’s direction for high bloodpressure or fluid retention). And if you do hard or prolonged exercise(enough to make you sweat), one of those ‘grams’ needs to beconsumedwithinthehourbeforeyoustart.Atorabove60gramsperdayof carbs, this prescription becomes optional. However if you go out

planning to exercise for 30minutes, but find you have to stop after 15becauseyoufeel lousyor lightheaded, try it thenext timewithacupofbrothwithinanhourbeforeexercisingandseehowthingsgo.

Practically speaking, the easiest way to get this sodium is to buystandard bouillon cubes and consume 2 per day. They are cheap,compact,lastmonthswithoutrefrigeration,andhotwateriseasilyfound.A more traditional path is to make your own meat or vegetable brothcontaining1teaspoonofsaltperquart.

6.Don’tTrusttheBathroomScaleWithYourMentalHealth

Wehumansareabout2/3water.Eachofuscontainsabout40liters(orquarts)ofthestuff,andeachliterweighsabitover2pounds.Ourbodieseffectively regulate fluidbalancebyadjustingurineoutputandsenseofthirst,butthisisdonewithina2-literrange.Withinthisrange,yourbodydoesn’treallycareifitisuptoaliteraboveorbelowitsidealfluidlevel.

Whatthismeansisthatweall liveinsidea4-pound-widegreyzone,sothat from day to day we fluctuate up or down (i.e., plus or minus) 2pounds.Thishappensmoreor lessat random,sowithanyoneweightreadingyoudon’tknowwhereyourbody iswithin that fluidrange.Yourweightcanbe thesame for3days ina row,and thenextmorningyouwake up and the scale says you’ve ‘gained’ 3 pounds for no apparentreason. For people who weigh themselves frequently, this can bemaddening.

Thereare twosolutions to thisproblem.One, justdon’tweighyourself.Or two, defeat this variability by calculating average weights. You canweighyourselfeveryday,andthenononedayperweek,calculateyouraverageforthatweek(i.e.,theaverageormeanof7values).

If youare really intomath, youcanweighyourself everydayand theneachdaycalculateanewmeanover the last7days.Eachdayyoudothis,youdroptheoldestvalueandaddthenewestonetothecalculation.Andofcourse, for10bucks there’san iPhone ‘App’ thatwilldo this foryou(WeightMonitorbyEssenceComputing).

7.Exerciseisawellnesstool.Itisnotaweightlosstool.

Mostpeoplefeelbetterandfunctionbetteriftheygetamodestamountofregularexercise.Onaverageacrossthepopulation,thinpeoplegetmoreexercise than heavy people. People who exercise regularly across alifetime live longer.But theextrapolationof theseobservations– that ifheavypeopleexercisedalotmorethey’dbethinandlivelonger–isnotsupportedbyscience.Nonetheless,thatisthemessagethatmanyhealthcare professionals and the media consistently communicate to heavypeople.

Here are some basic (but often ignored) facts. Fitness is primarily aninherited trait.Trainingcan increaseaerobicpoweratmostby10-20%,but(figurativelyspeaking)adifferentchoiceofparentswouldincreaseordecreaseyourfitnessbyasmuchas50%[129].Ittakesabout350milesof running or 1000 miles of cycling to burn off 10 pounds of body fat(assumingthatyourappetitedoesn’t increaseoryourmetabolismslowsdown).Unfortunately,whenheavypeopleexerciseregularly,theirrestingmetabolism slows – this is not a typo! – it SLOWS by 5 to 15% onaverage. Based on the results of 4 tightly controlled, inpatient humanstudies,insteadoflosing10pounds,theaveragepersonloses7poundswith thismuch exercise, and some people lose as little as 2 or 3[130-133]. These studies specifically demonstrated that this less-than-expectedweightlosswasattributabletotheobservedreductioninrestingmetabolicrate.

Exercisedonebyheavypeoplecausesalotofcollateraldamage.Thinkankles, knees, hips, and low backs. So here’s a radical idea (which ofcourse is totally out of place in this book): let heavy people trycarbohydrate restriction first, lose someweight (whichmost dowithoutresorting toexercise), and then let themdecidewhen tobecomemoreactiveoncetheyareempowered,energized,andlighteroffoot.

Makingheavypeopleexerciseispunitive.Enablingheavypeopletoloseweightandthenbecomemorefitissmart.

8.ASoreMuscleisaSwollenMuscle

Exercising an unfit muscle causes soreness, which is followed byimproved muscle function and increased resistance of that muscle tobecomesore.Inthatsense,sorenessafterexerciseisgood(aslongasitlastslessthanaweekanddoesn’tcomeback).Sorejoints,ontheotherhand,arecollateraldamage(seeabove).

Mostpeoplethinkthat if theydoan intenseworkout(say90minutesofcircuittraininginagym)thattheyshouldloseweight.Andindeed,ifyouweigh before and right after such a workout, the scale goes downbecause of sweating and water weight loss. However, if it makes yousore for the next few days don’t be surprised to see the scale go up.That’s because muscle soreness indicates that your muscles aretemporarily inflamed, and inflammation causes fluid retention andswellinginthatmuscle.Onceagain,don’t letthescalemakeyoucrazy.Once thesoreness isgone, theswelling isgone,and thescale comesbackdownwhereit’ssupposedtobe.

9.MuscleCramps:UnnaturalComplicationsofaHighlyRefinedDiet

Adistressingnumberofotherwisehealthypeoplehavefrequentmusclecramps, and in the worst case, a muscle cramp of the heart equalssuddendeath.Physiciansdon’tliketodealwithmusclecrampsbecausetheonlyeffectivemedicationwehad tostop themwasbanned in1992duetounacceptablesideeffects.

Musclecrampsaretheendresultofmanycontributingfactors,includingoveruse, dehydration, andmineral inadequacies. Lowserumpotassiumisnotuncommoninpeoplewithfrequentcramps,sophysiciansoftentrypotassium supplements. However there is a daisy-chain leading backfrommusclecramps to lowbloodpotassium to intracellularmagnesiumdepletion. Low carbohydrate diets don’t cause muscle cramps per se(meatandleafygreensaregoodsourcesofmagnesium),butneitherdotheymiraculouslygetbetteronlowcarbregimensunlesstheunderlyingproblemisdealtwith.Thisisjustonemorereasonwhyleafygreensandhome-made broths (good sources of magnesium) are desirablecomponentsofahealthylowcarbdiet.

Sohere’stheshortcuttoendingmostnocturnalorpost-exercisemuscle

cramps.Take3 slow-releasemagnesium tabletsdaily for 20days.Theproprietarybrand-nameproduct is ‘Slow-Mag’®,butthereareanumberofequallyeffectivegenericsata fractionof thebrand-nameprice (e.g.,Mag-64®orMag-Delay®).Mostpeople’scrampsceasewithin2weeksofstarting ‘Slow-Mag®’,butyoushouldcontinue to take the full20-daycourse (60 tabs per bottle at 3 per day lasts 20 days). If the crampsreturn, do it again, and then continue taking one tab per day. If thecrampsreturn,take2tabsperday.Mostpeoplecanbetitratedtoremaincrampfree by this method. Why use a more expensive slow-releasemagnesium preparation like Slow-Mag®? Because magnesium oxidepreparationslike‘milkofmagnesia’causediarrhea,passingthroughthesmallbowelbeforetheycanbeeffectivelyabsorbed.

WARNING:Theonlycontraindicationtooralmagnesiumsupplementsissevererenalfailure(e.g.,aGFR<30).IfyouhaveanyhistoryofkidneyproblemsorknownlossofkidneyfunctioncheckwithyourdoctorbeforetakingSlow-Mag®oritsgenericequivalents.

10.InTime,YourHabitsWillChange

When people contemplate permanently eliminating mostcarbohydraterich foods fromtheirdiet, itoftenseemsoverwhelming.Somany of our habits, both personal and social, revolve aroundcarbohydrate foods like orange juice for breakfast and doughnuts withcoffee. And some carbohydrate foods are icons of whole cultures, likebread for the French, tortillas for Mexicans, and rice for Asians.Separatingyourselffromthesedeeplyingrainedbehaviorsisnevereasy.

Howeveronceanindividualgetspastthefirstfewweeksofadaptationtoa low carbohydrate diet, the positive changes in one’s life (not justweight, but wellbeing and sense of empowerment) become positivelyreinforcing.Everydayyouwakeupanddon’thavetotakeasmuch(orany) medication for diabetes, fluid retention, high blood pressure, orchronic pain is another nail in the carbohydrate coffin. Every day youstandonthescaleandseethatthere’salotlessofyou(oreventhatyoucanlookpastyourtummytoseethenumberatall)isanotherstepdownyourpath to independence fromsugarsandrefinedcarbohydrates,andtowardsbetterhealthandwellbeing.

Atsomepoint,beitmonthsoryearsintotheprocess,stickingwithyourlow carbohydrate lifestyle is no longer a battle of intellect (I know I’mbetteroffnoteatingthatstuff)overdesire.Eventually,itjustfeelsright.

Section5

GUESTCONTRIBUTORS

Chapter19

KETOGENICDIETSINSEIZURECONTROLANDNEUROLOGICDISORDERS

byEricKossoff,MD

JohnsHopkinsHospital,Baltimore,Maryland

Introduction

Theyearwas1921.Notmanyyearsprior,neurologistshadjuststartedtorealize that epilepsywas an electrical problem of the brain, not due toemotionalturmoilorcertainlynotdemonicpossession.Treatmentswerelimited to sodium bromides which could cause sexual dysfunction andphenobarbital that led to mental slowing and sedation. However, fornearly 2000 years it had been common knowledge that prolongedperiodsof fastingandaso-called “waterdiet” in thepast fewdecades,could lead to improvement in seizures. Interestingly, even when foodswererestartedaftersometimesweeks,seizureswouldnotalwaysreturn.Dr.Wilderat theMayoClinic inRochester,Minnesotahadheardaboutthework of a faith healer BernarrMacfadden andDr.Geyelin, both ofwhomhadusedperiodsofstarvationtohelpchildrenwithepilepsy.Asanendocrinologist,he theorized thatahigh fat, lowcarbohydratedietwithadequateproteintomaintaingrowthandmusclecouldmimictheeffectsof starvation. This diet, which he called the “ketogenic diet” could becontinuedindefinitely[134].

Itwasa revolution.Startingat theMayoClinicandspreading likewild-fire,thedietarytreatmentofepilepsybecameverypopular,especiallyinchildren, many of whom had been institutionalized due to no prioreffectivetreatments.In1924,Dr.PetermanfromtheMayoClinicreportedthatthevastmajorityofchildrenstartedontheketogenicdiet,83%,weresignificantlybetter,with60%completelyseizure-free.Sixyearslater,hispartner Dr. Barborka used the ketogenic diet in 100 adults, with 56%

showing improvement in theirseizures. In the1930s, theketogenicdietwasoneofthetreatmentsofchoiceforepilepsy.

Thingschangedin1938.AmedicationcalledDilantin®wasinventedandwas touted as the “cure” for epilepsy. High fat, low carbohydrate dietswere now perceived as expensive, less effective, and unnecessary.Althoughanticonvulsantdrugshavecomeandgone,andsadlyaboutathird of patients do not respond to them to treat their seizures, theketogenic diet took a serious hit from which it has not fully recoveredeven to this day. Limited to select US epilepsy centers such as mine(JohnsHopkinsHospitalinBaltimore),inrecentdecadesketogenicdietshavebeenonlyusedasalastresortforchildrenwithverytoughepilepsy.

In November 1993, a 20-month-old boy with severe seizures namedCharlieAbrahamswasbroughtfromCaliforniatoJohnsHopkinsHospitaltobestartedontheketogenicdietbyDr.JohnFreemanandhisdietitian,MillicentKelly,RD.Charlie’s father had to find out about the ketogenicdietinalibraryasitwasnotevenmentionedasanoptionbyhiscurrentneurologist.Afteronly4daysonthediet,hisseizuresstoppedandneverreturned.Charlieisnow18yearsoldandnowhasbeenoffthedietfor14years.Needlesstosay,hisfatherJimwasangry.Hisdesiretohelpotherfamilies was realized through creation of the Charlie Foundation. Histalentasasuccessfulmovieproducer(filmssuchasAirplaneandPoliceSquad) prompted him to enlist the help of Meryl Streep to produce amovie,FirstDoNoHarm,aboutachildstartedonthediet.

In2010,theketogenicdietisinanewRenaissance.Itisavailabletomycount inover60countries,manyofwhomhavemultipleketogenicdietcenters. There are now four ketogenic diets available: the classicketogenic diet, the MCT (medium-chain triglyceride) diet, the modifiedAtkins diet (MAD), and the low-glycemic index treatment (LGIT).Ketogenic diets are being used for adults, babies, and in developingcountries. No longer perceived as a treatment of last resort, they arebeing used first for conditions such as infantile spasms and Doosesyndrome (an epilepsy syndrome in which young children suddenlydevelopdropseizuresyethavenormalintelligence).

Ketogenic diets are also being studied for use in conditions other than

epilepsy, including autism, brain tumors, Alzheimer’s disease, and LouGehrig’sDisease(ALS).A2009expertconsensusstatementforoptimalclinicalmanagementof childrenonketogenicdietsbrought together26internationalexperts[135].Firstin2008inPhoenix,Arizona,thenin2010in Edinburgh, Scotland, approximately 250 physicians, dietitians, andscientists gathered to discuss their research on dietary treatments forneurologicdisorders.

Whyarethesedietssohelpfulforyourbrain?Basicscientistsaretryingto figure it out. If they can, it may open up a whole new avenue oftreatmentsforneurologicdisordersnotcurrentlyavailable.Inthischapter,the evidence of ketogenic diet therapy for brain disorders will bediscussed.

TheKetogenicDietforEpilepsy

Theketogenicdietstartedasatreatmentforseizuresanditremainsbyfar themostcommon reasonweuse it.Studies fromallover theworldhave consistently shown that, when used as the first treatment, about60%ofchildrenwillhaveatleasta50%reductionintheirseizureswithin6months.Evenafternotrespondingto3-4differentmedicationsfirst,thechances of this happening are about 30%. About 1 in 10 in this drug-resistant group will become completely seizure-free, compared to halfthat for tryingyetanotherdrug.Given these facts, theketogenicdiet isoftenregardedasaveryattractiveoptionforparents.

Theketogenicdietworksquickly,usuallywithin2weeks.Afterafewdaysonthisdiet,childrenwillstartproducingketones,whichcanbemeasuredathome.Fordecades,ketoneswereseenasactinglikeadrug,withtheirelevated levels being the sole reason this diet worked. However,researchers now believe the diet has favorable effects on yourmitochondria(energyproducingpartsofyourbraincells),whichmaybedue to the high fat intake, stabilized blood glucose, or increased brainchemicalscalledneurotransmitterswhichcansuppressseizures.

ClinicalCase:6montholdinfantwithepilepsy(JohnsHopkinsHospital,February2007)

CH was a 6-month-old infant who suddenly developed lightening-likejerksofherheadandshoulders inclustersafternaps. Increasingdaily,her parents brought her to the emergency room, but no onewas surewhatwasgoingon.Thenext day, her parents brought her backandachild neurologist saw one and diagnosed infantile spasms. In thiscondition, infants can suddenly develop “atonic” seizures and anelectroencephalogram(EEG)filledwithconstant,chaoticseizureactivity.It isamedicalemergencydue to thehigh likelihood (80%)of cognitiveimpairmentifitcontinues.

The family was offered the two usual treatments used by childneurologists,high-dosesteroidsinjectedtwicedailyintothemuscle,andadrugcalledvigabatrin.Bothcanbesuccessful,butsteroidscancauseirritability,highbloodpressure,stomachbleeds,andswelling.Vigabatrincansometimesleadtoirreversiblevisiondamage.Theparentsaskedforanotheroption.

Since they came in so quickly, the ketogenic diet was offered as a 2-weektrialbeforesteroidsorvigabatrin.CH’sbabyformulawasswitchedtoonecalledKetoCal®afterabrieffastingperiod.Herlastseizurewas3dayslater.Twomonthslater,herEEGnormalized.Now4yearsold,CHis a completely normal, adorable little girl. Her parents have set up afoundationtopromotetheketogenicdiet,specificallytobeofferedbeforemedications.Theybelievestronglyparentsshouldbegiventhischoice.

Theketogenicdietusedtotreatepilepsyhassomedifferencesfromthevery lowcarbohydratedietsdevelopedbyaboriginalcultures(describedinChapter2)and the researchstudiesconductedbyDrs.PhinneyandVolek. It is higher in fat and lower in protein and carbohydrate. About90% of the calories are derived from fat (both saturated andunsaturated),withmostof theremainder(8%)protein. It isdescribed in“ratios”,witha4:1ratioofgramsof fatvs thesumofcarbohydrateandprotein being themost common version. Typically started in a hospitalwith a 24-hour fasting period (only clear, carbohydrate-free fluidsallowed), it is advanced over 4 days for the child, with the parentseducated by trained dietitians on how to prepare, weigh and measurefoodsduringthattime.

Theketogenicdietseemstoworkslightlybetterforgeneralizedseizures(comingfromtheentirebrainallatonce) thanpartial (focal)seizures. Itworks extremely well for certain types of epilepsy, including infantilespasms,Doosesyndrome, tuberoussclerosis,andDravetsyndrome. Intheseconditions,thedietisnowstartingtobeusedsooner…evenbeforemedications if the family is interested. For children already onmedications,manycanhavetheiranticonvulsantdrugsreducedorevenstopped, and often parents report their children as brighter and morealert. The diet is usually continued approximately 2 years and then anattempt is usually made to taper and stop the diet, after which manychildren remainseizure-free.However, for thosewhoseseizures return,the diet can be resumed, and we have many children on the diet fordecadesduetocontinuedseizurecontrolbenefits.

Ketogenicdietsusedtotreatseizuresdohavesideeffects,buttheyarepredictable,oftenpreventable,anddonotusually lead toan immediatestop to the diet. Common ones include constipation, gastroesophagealreflux,andelevationsoftotalcholesterolandtriglycerides.Moreraresideeffects, usually preventable, are kidney stones, bone density changes,acidosis,andslowingofheightgain.Multivitaminswithcalcium,VitaminD, selenium, and zinc must be provided. Some children need extracarnitineaswell.Weightlossdoesnotusuallyoccurunlessthedietitianrecommends that theparents limit total calories in thediet.These sideeffectsmaybemorecommoninchildrenduetotherestrictionsontheircarbohydrate and protein content using these diets and their differentmetabolicneeds.

TheModifiedAtkinsDiet

“Alternative” diets exist, including the modified Atkins diet, oftenabbreviated“MAD”.Thisdietwascreatedin2002asaresultofparentswho observed (often on their own!) that the restrictiveness of theketogenic diet could be lessened over time without suffering moreseizures.Wehavesinceputchildrenonthislessrestrictivedietfromtheverybeginning[136].

The “modified”Atkinsdiet is started in theoutpatient clinic (nohospitaladmissionrequired),withchildren limiting tocarbohydrates to10grams

perdayand20gramsperdayforadults.HoweverunliketheAtkinsdiet,thiscarbohydraterestrictionisnotchangedafterwards.Additionally,fatisstrongly encouraged – we tell families the food should “shine” when aphotoistakenofit.Protein,calories,andfluidsarenotmeasured;ratherthe parents track daily carbohydrates using carb-counting guides. Thisdiet can be done with less cost and dietitian support, and is thereforebeing studied in developing countries with limited resources (e.g.,HondurasandpartsofIndiaandChinatonameafew).

Results are similar to the ketogenic diet so far, with 78 (49%) of 160childrenandadultsresponding.Todaywerecommendthisalternativetotheketogenicdietmostly for teenagers,adults,andchildrenwhoeithercannottoleratethelevelofrestrictivenessoftheketogenicdietorwishtoswitchfromtheketogenicdietafterseveralyears.Inourclinic,theMADisusedinselectedpatientsalongsidethemorerestrictedketogenicdiet,ratherthanasasubstitute.

Anotheralternative to thestrictketogenicdiet is the low-glycemic indextreatment, created at Massachusetts General Hospital in Boston. Thisdietprimarilywatchestheglycemicindex(GI)offoodsandrecommendsonly carbswithaGI<50 tominimizeexcursions inplasmaglucose. Italsoseemstowork!

Ketogenicdietsforotherneurologicdisorders

AnticonvulsantdrugssuchasTopamax®,Neurontin®,andLamictal®areusedformanypeoplewithepilepsyaroundtheworld.However,thisuseisonlyabout1%of the totaluseof thesedrugs!How is thispossible?Psychiatrists use anticonvulsants for depression, bipolar disorder, andchronicpain.Neurologistsusesomeof thesemedicationsformigrainesandneuropathy.Theseconditionsaremuchmorecommonthanepilepsybyfar.

Similarly, many neurologists are very interested today in the use ofketogenicdiets(boththeclassicandmodifiedAtkinsdiet) forconditionsother thanepilepsy[137].Doctors inCretehaveused theketogenicdietfor childrenwithautism,andperhaps similar to reportsof agluten-freedietbeinghelpful,somayhigh fatdiets.Clinical trialsareunderway for

treatmentofbraintumors.Smallamountsofketoneshavebeenshowninmice to help reduce the plaques seen in Alzheimer’s. There is now ahumanclinicaltrialtestingifaketogenicmilkshakecalledAxona®resultsin the same benefit for people with Alzheimer’s. This milkshake isavailablebyprescription.WetestedamodifiedAtkinsdietforteenagerswithseveremigraines,butunfortunatelymanydecidedtostopearlyanditdidn’tappeartoworkwell inthosewhostayedonit.Clinicaltrialsarealsounderwayforheadtrauma,stroke,LouGehrig’sdisease(ALS),anddepression.

ClinicalCase:7yearoldwithautism(JohnsHopkinsHospital,October2004)

RAwasa6-year-oldboywithautismwhodevelopedintermittentseizuresattheageof2years.Althoughhehadseizurecontrolwithtwodrugs,hisparents did not like the side effects on his mood and alertness. Theystarted theketogenicdietat theageof4yearsandafter3monthshismedications were slowly and carefully reduced and after 6 monthsstoppedcompletely.

After 2 years on the ketogenic diet, our team recommended trying tocomeoffthediet.AnEEGwasnormalandthedietwasweanedover3-4months. Although seizures did not return, his parents noticed animmediate increase in aggressiveness and hyperactivity once “normal”foodswererestarted.Withourpermission, themodifiedAtkinsdietwasstarted, restrictingcarbohydrates to10gramsperdayandencouraginghigh fat foods. As his parents had implemented the more restrictiveketogenic diet for 2 years, this was not difficult for them to do. RA’sbehavior improved rapidly and he remains on the modified Atkins diettoday. He likes the structure of the diet and does not cheat or ask forsugaryfoods.

Only time will tell which of these other neurological disorders will beresponsive to the ketogenic diet andwhich oneswill not. Researchers

suspectthatforcertainconditionsdifferentmechanismsofactionmayberesponsible foranyobservedbenefit.Forexample, forbrain tumorswemay find that reducedglucose iswhathelps,but forAlzheimer’s itmaybe direct effects of ketones. What is certain is that many neurologicconditionshaveeithernocureorlimiteddrugtreatments,andketogenicdietsarecertainlyworthtrying.

Summary

We are now at a turning point in the history of ketogenic diets forneurologic conditions. They are now back in the mainstream, widelyused,andbeingstudied in trialsworldwide forbothhumansaswell asanimals to figure out how they work. No longer a last resort, they arebeingusedinsomesituationsbeforemedications.Weareusingthemforadults as well as children, conditions other than epilepsy, and indevelopingcountries[138].

Chapter20

THIRTYYEARSOFCLINICALPRACTICEWITHDR.ROBERTATKINS:KNOWLEDGEGAINED

byJacquelineA.Eberstein,R.N.

Introduction

At the start ofmy career in nursing, I spent 5 years working intensivecareunitandrecoveryroomjobsinbigcityhospitals.Afterthat,in1974,Iwas ready to findamorestable9 to5 job–orso I thought.Someonetalkedme into going for an interview at the diet practice of Dr. RobertAtkins,whosefirstbookwaspublishedin1972.Ihatednutritionanddiettherapyinnursingschool.Itwasboringandunimportant,andIassumedI’d have no interest in working with Dr. Atkins. The job interview was“interesting”.IinformedhimonnouncertaintermsthatIhadnodesiretoworkwithhim;nordidIagreewithhisapproach.HeofferedmethejobanywayandforsomeunexplainablereasonIacceptedit.Thatwas1974and I worked closely with him until I closed his medical practice sixmonthsafterhisdeathin2003.

Likemanyinthemedicalprofession,Ipaidvery littleattentiontowhatIateuntil Igaineda fewpounds. Ihadstruggledwithmyweightsince Iwas12, sodieting formewas thesameas formostotherpeople; lowcalorie, skipping meals: being hungry on and off diets. Luckily, I hadsenseenoughnottogetintodietpills.Ihadafamilyhistoryofdiabetesand morbid obesity so I knew that I couldn’t allow myself to gain toomuchweightbeforetakingaction.

I started work as a staff nurse in Dr. Atkins’ busy practice with everyintentionofleavingassoonasIfoundsomethingelse.ButtomysurpriseIquicklyobserved thathisvery lowcarbohydrateplanworked.Patientslostweightandincheseasilyandwithouthungerandcravings.Nowthat

way of dieting appealed to me!What was also so surprising was thatfrequently his patients’ other health complaints got better simply bychangingwhattheyate.

Before Istartedworking forDr.Atkins, Ihad intermittentsymptomsthatdoctorscouldnotdiagnose.Afterhyperthyroidismandanadrenaltumorwereruledout,alldoctorscouldoffermeweremedications.OnedayDr.Atkinsnoticedmysymptomsandimmediatelytoldmetohaveaglucosetolerancetest(GTT)attheoffice.HewassurprisedthatnotonedoctorIsawaskedmewhatIateorifIhadafamilyhistoryofdiabetes.TheGTThe administered showed severe reactive hypoglycemia (RHG). At thattime, one of the many criticisms of Dr. Atkins was that he diagnosedmanywithRHG.For thishewascalleda “quack”.After seeing the labresults,IimmediatelybegantheInductionphaseofhisdietandsoonfeltbetter, justashispatientsdid.As longas Iatecorrectlyanddidn’tskipmealsIrarelyexperiencedmypriorsymptoms.Thatremainstruetothisday. This wasmy first lesson in the power of practical nutrition (albeitoutsideofmainstreammedical opinion). I amconvinced that if I hadn’tfollowedDr.AtkinsadviceIwouldhavehadtype2diabetes longago. Icanthankhimformanythingsbutmostespeciallyforthat.

ThepublicationofDr.AtkinsDietRevolutionin1972andtheyearssincedidindeedstartarevolutionthatsetoffafire-stormofsensationalmedia,criticism,misinformationanddistortion;someofwhichcontinues to thisday. Fortunately, however, in the last 10 years, additional researchsupportingDr.Atkins’conceptshasbeenpublished.NowtheAtkinsplanisevenpresentedatmedicalconferencesasasafe,healthyandusefulchoice to address our ever-increasing obesity and diabetes epidemics.Perhaps because of this new research, more and more health carepractitionersarenowcomfortableusingtheplanforthemselvesandtheirpatients

ItBeganintheMedicalLibrary

Decades ago Bob Atkins, a young doctor, found himself with anexpanding belly andmore than one chin. Since he had a pathologicalfear of hunger and loved food, he failed on low calorie diets. Out offrustrationhemadehiswaytothemedical libraryto findasolutionthat

hecouldsustainwithout fightingconstanthunger.Thatquest ledhimtoanarticlebyGordonetal.[139]intheOctober1963issueofTheJournalof theAmericanMedicalAssociationthat intriguedhim.Theweight lossplanhefoundwasverysimilartowhatwouldbecometheAtkinsDiet.Hefollowed theplanandexperienced rapid, comfortableweight losswhileconsumingwhole,nourishing,andsatisfyingfoods.

Afterhisownweightlosssuccess,hisfirstopportunitytoretesttheplanwaswhile working in themedical department at AT&T. He enrolled 20overweight executives to follow the plan for 20 weeks. They all lostweightwithouthungerandthefollowuprecordsshowthattheycontinuedto keep it off for at least one year. The program was offered to otheroverweight employees and resulted in the same success. Not only didweight loss occur in relative comfort, but cholesterol values improved,subjects felt better, and common symptoms such as joint painsdisappeared.

PuttingItinPractice

AfterestablishinghisowninternalmedicinepracticeinNewYorkCity,Dr.Atkinsfinetunedthe1963GordonlowcarbplanfromJAMA,makingitanimportant part of his practice. Word spread, especially as some NewYorkersofwealthandfameadoptedthediet.Itwasevenpublishedasa7daydietplaninVoguemagazine.

After his waiting list for office appointments became much too long,someone recommended Dr. Atkins write a diet book enabling him toreach more people. In October 1972, ‘Dr. Atkins’ Diet Revolution’ waspublishedtoinstantsuccessandimmediatecontroversy.Rememberthatbythemid1970sthe“fatisbadmessage”wasbecomingthemantraoftheday.Ironically,theAmericanMedicalAssociationwasoneofthemostvocal critics ofDr. AtkinsDiet, even though it was based on a diet hereadaboutinJAMA,theAMA’sownjournal.

As chronicled in Gary Taubes’ ‘Good Calories, Bad Calories’[13], thisunfoundedcriticismofDr.Atkinscontinuestothisday.Instead,thoseofuswhoworkedwithhimconsiderhimacourageouspioneer.Heshouldbe acknowledged for being a leader in pointing to the importance of

stablebloodsugar,insulin,triglycerides,HDLcholesterol,eggsaspartofahealthydietandfor teachingus thedifferencebetweenmanufacturedtransfatsandnaturalfats.

AfterIbeganworkathis“dietpractice”in1974Iquicklyrealizedthathewasn’tjustadietdoctor–heactuallypracticedmedicine.Admittedly,hewas certainly outside of the mainstream even then. His initial patientevaluation included a 3 hour glucose tolerance test, which he laterexpanded to4 then5hoursandadded fastingandpostprandial insulinlevels.Heroutinelymeasuredtriglycerides,HDLandLDLcholesterolwellbefore these became the norm. It was by studying these results andcorrelating them with patient symptoms that he understood just howimportant controlling carbohydrate foods was to long term health. Helearnedagreatdealfromhispatients.Thatclinicalexperiencereinforcedhis belief in the importance of eating a very low carbohydrate dietconsisting of unprocessed whole foods and the vast health benefits itcouldbring.

Dr. Atkins found that it was both the poor quality and large quantity ofcarbohydrate foodsthatprovokednotonlyanumberofchronicmedicalconditionsbutnumerousday-to-daysymptomsplaguinghispatients.Justas a poor quality diet provoked illness, the right foods could restorehealth and wellbeing, especially in a susceptible individual. Over theyearsmanypeoplecametoseeDr.Atkinsbecauseheandtheybelievedthat diet was a therapeutic tool. Many found answers to their healthproblemsafter themedical establishment failed them.Trusting his ownclinicalexperienceallowedhimtohelpothersregardlessoftheconstantbarrageofcriticismheendured.Seeinghispatientsgetbettermatteredmoretohimthanofficialacceptance.

Itwasourclinicalexperiencethattailoringdietaryadvicewasespeciallyimportant to our patients, most especially to those who werecarbohydrate intolerant. It was extremely gratifying to see our patients’lab tests improve, their symptoms disappear, and the need forprescription medications minimized simply by using a very lowcarbohydratedietarylifestyle.

TheRoadtoType2Diabetes

Dr. Atkins saw type 2 diabetes as the end result of years of ‘dietaryabuse’,especially in thosewithageneticpredisposition todiabetes.Heviewed it as a nutritional wear-and-tear disease. Before developing fullblowndiabetes,manysufferwhatDr.Atkinscalledreactivehypoglycemiaorunstablebloodsugar[140].Itdidn’ttakeDr.Atkinslongtocorrelateanunstable blood sugar, high insulin production with weight gain, hightriglycerides,lowHDLcholesterolandnumeroussymptoms,andthatthiscombination of symptoms followed from eating a diet containing largeamountsofpoorqualitycarbohydrates.

Surprisingly, itwasnotuncommontofindwideswingsinbloodsugarinpeopleofnormalweight,notjustthosewithexcessbodyfat.Peoplewithanunstablebloodsugarsuffernumeroussymptomsthatnegativelyaffecttheir everyday lives. These problems resolve quickly once the optimallevel of carbohydrate restriction is found. The careful assessment ofglucoseandinsulinthatDr.Atkinsdidcanbeextremelyusefultoidentifythese individuals, but it may not be a viable choice for your patient.However,evaluatingsymptomsandtestingtheir responsetoavery lowcarbohydratedietcaneasilybedone.

WhatisUnstableBloodSugar?

Developingtype2diabeteshappensovertime.Beforebloodsugarlevelsaretoohigh,anoverproductionof insulincandropbloodsugartoolow.Some of the body’s most prominent symptoms occur when the bloodsugar is either too low or drops too quickly, setting off compensatorymechanisms to normalize blood sugar. This process results in adrenalstress and symptoms that are commonly found in our unhealthypopulation. People live with these symptoms every day assuming theyaresimplynormalorpartoftheagingprocess.Whilethesenon-specificsymptoms are often treated withmedications, they actually result frompoordietarychoicesandarebestdiagnosedandtreatedbycarbohydraterestriction. The dramatic difference in wellbeing and self-control whencarbohydratesarelimitedimpliesunderlyingcarbohydrateintoleranceoraddiction.Recognizingacarbohydrateintolerantpatientisn’tdifficult!

RecognizinganUnstableBloodSugar

Have you encountered patients with a family history of diabetes,gestationaldiabetes,orpolycysticovarysyndrome(PCOS)?Whataboutmetabolicsyndrome,aninsulinresistantconditionthatrespondswelltoavery low carbohydrate diet[118]? Does your patient have excessivehunger,apreoccupationwith foodevenaftereating,andan inability tocontroltheintakeofcarbohydratefoods?Aresymptomsrelieved,atleasttemporarily,byeating?Thesearecommonexperiences forpeoplewhoarecarbohydrate intolerantoraddicted.Yes, carbohydrateaddiction,orsome may prefer to call it carbohydrate dependence, is real. Thetreatment is the sameas for any dependence/addiction that is causingharmtotheperson:restrictthefoodsthatprovoketheaddiction.

Common symptoms of unstable blood sugar can include any of thefollowing.

• Mood and/or energy swings that can occur several timesduringtheday.Thesecanbetriggerstoovereatorgetaquickfixfromacandybaroranotherhighcarbfood.

•Anincreasedresponsetostresscan leadtoprescriptionusesuchastranquilizeroranti-depressantmedicationalongwithadecreaseinone’sabilitytocopeorfunctionatanoptimallevel.

• Poor sleep caused by an unstable blood sugar leads tochronicsleepingpilluse.

Theoveruseofmedications is especially tragic because theyareoftenexpensive, have side effects, canmake blood sugar regulation worse,and cause more weight gain as well as depleting the body of vitalnutrients.Whyriskputtingyourpatientthroughthisroller-coaster,treatingsymptoms with a prescription band-aid rather than practice preventivemedicinebyusingappropriatelifestylechange?Carbohydraterestrictioncan address the true underlying condition, correcting these symptomsbetterthanmedication.Dr.Atkinsalwaysbelievedthatmedicationswerealastresort–notthefirst.Rememberthatwhileyouareaddressingtheunderlying cause of your patient’s symptoms with carbohydraterestriction, you are also protecting their pancreatic beta-cells andpreventingtheonsetofdiabetes.

You can find a more complete list of symptoms that may indicate anunstable blood sugar in ‘Dr. Atkins’ NewDiet Revolution’, published inpaperbackbyAvonHealth,2002,page150.Considerhavingyourpatientcompletethelistbeforemakinganydietchanges,andthenagain4to6weeks later to track progress. This is an excellent motivational tool toteachpeoplewhoarecarbohydrate intolerant thecontrol theycanhaveovertheirsymptomsandqualityoflifesimplybychangingwhattheyeat.

AnotherimportantobservationmadebyDr.Atkinswashowoftenhesawabnormalities in postprandial blood sugar and insulin levels in patientswhosefastingglucosevalueswereclosetonormal.Whatwepreviouslyconsiderednormal is not necessarily a safe level, as evidencedby theAmericanDiabetesAssociation’s recent reduction of acceptable fastingglucosefrom140to126mg/dlandadditionofhemoglobinA1ctobetterdiscoverpostprandialglucoseelevations.Aswelearnmoreaboutbloodsugar and insulin levels we are finding that even small elevations aremore damaging than was first thought. Missing this finding and notmakingtheproperdietaryrecommendationscanmeanincreasingstressonbetacellsandultimatelydiabetes.

IsItSimply“CaloriesIn,CaloriesOut”?

We hear this all the time. The more people hear it the more peoplebelieveitmustbetrue.Similartothephrase‘acalorieisacalorie’,weightcontrolbecomesseductivelysimple.Exceptweightgainandweightlossarefarmorecomplex.

Wenowknowa lotmoreaboutmacronutrienteffectsonhormonesandgeneregulationandhowtheserelatetofatstorageandfatutilization.Tocontinue to push the simplistic calories-in-calories-outmantra limits ourtherapeutic options. This is especially tragic for people who arecarbohydrateintolerant.Inthelongruntheywilllikelyfailinmakinglongtermdietchangeswitha lowcalorieapproachwhich isgenerally low infatandhighincarbohydrate.Thisleadstoweightcyclingandultimatelyhigherbodyfat.Notonlyisthisphysicallydamaging,butthereisalsothepsychologicalcostofaddinganotherfailure,moreguiltbecauseofalackof“willpower”andlackofcontrol.

Rememberthatitiseasiertochangebehaviorwhenwhatyouareeatingissupportingyourbodytoworkproperly.Thatthisisparticularlytrueforpeoplewith carbohydrate intolerancewas recentlydemonstratedbyDr.Gardner’sA-to-ZStudyanalysis(seeChapter7).It isuptoyouastheirpractitionertohelpeachpatientwiththebestdietchoicetoachievelongtermsuccessbasedontheirindividualmetabolicresponsestofood.

OneSizeDoesNotFitAll

The one size fits all approach as demonstrated by the USDA DietaryGuidelinesandtheAmericanDiabetesAssociation’s(ADA)positionthatpeoplewithdiabetescaneatthesamefoodsaspeoplewithoutdiabetesdoes a huge disservice to those who are carbohydrate intolerant. Inessence,thisposition isthatdiabeticscaneatall thecarbohydratetheywant;alltheyhavetodotocompensateistakemoredrugs.

TheattitudeIhearexpressedattheannualInternationalADAconferenceis that most people with diabetes won’t change their diets. This is anassumption that we can’t afford to believe. Patients must be givenunbiased access to the full range of choices, including the choice tocontrol blood sugar by restricting both the quality and quantity of theircarbohydrate intake. When given reasonable support in selecting thisoption,manypeople cananddomake this change.Toassumepeoplewon’torcan’tissimplywrong.

Howmuchmoremedicationandatwhatcostdoesatype-2diabetichavetobearbecauseofthesenarrowrecommendations?Itiswellknownthatmany people with diabetes aren’t attaining their treatment goals evenwith intensive drug therapy. Furthermore, co-payments and treatmentdenialscausemanypeoplewithhealth insuranceorMedicare toskimpontestingandmedicationstosavemoney.

At The Atkins Center it was almost a given that people with type 2diabetescouldreduceoreliminatetheirdiabeticmedicationswithaverylow carbohydrate diet. This effect can be so prompt that medicationsoften needed to be reduced from the first day to avoid drug inducedhypoglycemia. Importantly, by being able to cut medication dosages,obesediabeticswhohavebeenstrugglingwithresistancetoweightloss

madeworsebytheirdrugsnowhadthechancetosucceed.

WhatYouandYourPatientsCanExpect

Most people think that all ofDr. Atkins patients came to him solely forweight management. This is far from the truth. Many overweight andobesepatientspresentedwithalitanyofchronichealthchallenges,mostcausedbyorexacerbatedbycarryingexcessweight.Headdressedalloftheirissues.

Healsohadconsiderableexperiencewith thosewhoappear tobeatanormal, healthy weight or even underweight but ill because of poordietary choices.Basedonobjective clinical testing, he knew that somepeoplecouldbeseverely insulin resistantwithoutbeingoverweight.Forthesepeoplehefoundequallygoodresponsestoanappropriatelevelofcarbohydraterestriction.

Inadditiontooverweightandobesityrelatedconditions,Dr.Atkinsusedcarbohydrate restriction to successfully treat many other healthchallengesincludingbutnotlimitedtothefollowing:allthecomponentsofmetabolicsyndrome,type2diabetes,type1diabetes(reducedneedforinsulin and decreased hypoglycemic events), asthma, mood swings,fatigue, insomnia, depression, anxiety, headaches,migraines, allergies,inflammatory bowel syndrome, colitis, gas, bloating,GERD, joint pains,various skin eruptions including acne and psoriasis, poormemory andconcentration,PCOS,andpremenstrualsyndrome.

BeyondWeightLoss

Dr.Atkinskeptcurrent,alwayscarryingamedical journalandattendingconferences, especially in Europe.Outside theUS, he learned a greatdeal about non-drug therapies.He felt thatmedicine in theStateswastoo drug oriented and that pharmaceuticals in many cases simplytargeted symptoms and did not address the underlying cause of theillness.By theendof the1970shebegan toexpandhispracticeusingnutrientsalongwithdiet toaddressnumerousphysicalcomplaints.Thebasis of his treatment was always some degree of individualizedcarbohydrate restriction because no amount of nutritional supplements

will counter thedamagingeffectsofapoordiet.Thisapproachallowedhim to avoid drug therapy or use lower doses for numerous diseaseconditions.

Inmanyrespectshewasaheadofhistime.Forexample,inthe1980shewas using fish oil supplements for inflammation and cardiovascularconditions; magnesium for heart rhythm regulation, blood pressurecontrolandasthma;andtaurinewiththeketogenicphasesofhisdietforseizures. Well before the concept of insulin resistance syndrome andmetabolicsyndromewerewrittenabout,hehadmadetheconnectionthatdyslipidemia,glucoseintolerance,andobesityclusteredtogetherandthatallthesemarkerswereresponsivetocarbohydraterestriction.Dr.Atkinswas also one of the first to talk about the negative effects of standardhormonereplacementtherapyandthebloodsugarandweightgainsideeffectsofavastnumberofdrugs.

Oneoftherarelytalkedaboutresultsofourexcessiveuseofprescriptiondrugs to treat lifestyle related conditions especially in an overweightpopulationaretheunwantedmetabolicsideeffects.Theseincludebloodsugarimbalancessuchashyperglycemia,hypoglycemiaandweightgain.Many of the common categories of drugs prescribed today have theseeffects.Yetmanyphysiciansandpatientsareunawareofthisfact.Howmany patients would be willing to forego another drug if it meant theycouldaddresstherealcauseoftheirsymptomsandhaveaneasiertimewith weight management? This is exactly why addressing lifestylechangesareneededratherthanwritinganotherRx.

ThisisjustthetipoftheicebergonhowDr.Atkinspracticedforthelast2decadesofhislife.Formoreinformationabouthisprotocols,‘Dr.Atkins’Vita-NutrientSolution’publishedin1998isstillavailabletoday.

Dr. Atkins wanted to be remembered as a doctor of ComplementaryMedicineratherthana“dietdoctor”.Thisisonewishthathasyettocometrue.But Idon’t thinkhewouldbe toodisappointed.Afterall,hewasaphysicianwhostrivedtoofferthebestandsafesttreatmenthebelievedhecould.Intheprocess,hehelpedmany,andheisstilldoingsoyearsafter his death. Research now supports much of what Dr. Atkinsobserved in our clinical practice. He believed that when open-minded

practitioners are given a choice of facts over dietary dogma, they willrecognizethatcarbohydraterestriction isapracticalsolutiontomanyofthehealthcareillsofourmodernwayoflife.

Chapter21

APATIENT’SPERSPECTIVE

byJimmyMoore

DearDoctor,

You have read about low carbohydrate diets from two well respectedauthoritiesonthetopic;nowletmegiveyouthepatientperspective.Myname is JimmyMooreandmystory is that of apatientwho tookbackcontrolofhisownhealth.Iamnotunlikemanyotherswhohavebecomeincreasingly frustrated by the failure of conventional wisdom regardingdietandhealth.Ihadtriedtherecommendedhigh-carb,low-fatdietmanytimesover theyears inmyattempt tobattle thebulgethathadplaguedmeformostofmychildhoodandadultlife.AndwhileIexperiencedsometransient weight loss success eating that way, one thing becameabundantlycleartome–itwasnotasustainableplantomeeteithermynutritionalrequirementsortokeepmesatiatedandhappy.

Iknowyoumustbeextremelyfrustratedbythenaggingproblemofheavypatientswhonever seem to loseweight and keep it off nomatter howmuch you plead with them to comply with your dietary advice. Butsucceedingonadietlong-termisnexttoimpossibleifyouareconstantlyplaguedwithhunger,cravings,irritability,andalackofenergy.The“one-size-fits-all” approach to nutrition promoted by well-meaning healthorganizations has been an utter and dismal failure when applied topeople likeme.Sadly, those of us forwhom it doesn’twork are left tostruggletofindourownappropriatewayofeating.

My first threedecadesof lifewerecharacterizedby theextremelypooreatinghabits Ihad learnedasakid. Inaddition, Ihadacquiredapathytowardsbeinghealthybecauseofnumerousfailedattemptstomakethathappen. Inmyearly thirties, I foundmyselfacceptingthatbeingfatandsickwasthehandIhadbeendealtwithnohopeofeverovercomingit.

It’sagenuinelyhelplessfeelingtothinkyouwillalwaysbethiswaywithnothingyoucanreallydoaboutit.

Trust me, it wasn’t for a lack of trying to do all of the “right” thingsincluding trying many versions of low-fat diets, diet pills, and hours ofcardiovascular exercise each week. I even took statin drugs likeLipitor® and Crestor® to help lower my cholesterol (although Iexperienced excruciatingmuscle and joint pain as a result). Likemostpatients,Ithoughttheproblemwasme,notthepresumedhealthydietIwas following. In 1999 I knuckled down and started an ultra low-fat(virtually no-fat) diet. Interestingly, I did surprisingly well on it, losingaround 170 pounds in just ninemonths.However, I literally had towillmyselftobesuccessfulonthiswayofeating.

Therewasonemajorproblemwiththislow-fatdiet,andformeanditwasa biggie–I was constantly hungry, irritable, tired, and feeling like I waslosingmymind!IliterallythoughtIwasheadedstraightforthefunnyfarm(Inowrealizethelackoffatinmydietcanleadtosomedubiousmentalsideeffects).MywifeChristinewillbethefirsttotellyouhowunpleasantI was to be around during that time. Plus, despite my weight losssuccess, my stomach was so bloated and big I felt like I was a lotWORSEoffeventhoughIwasfittingintosmallerclothes.

Amonthafter losingall thisweightChristineaskedme if Iwouldgo toMcDonald’sandgethera chickennuggetsmeal. I askedher if I couldhaveaBigMac®meal“justthisonetime.”Anyonewhohaseverbeenfatknows what happened next. Frustrated by the ravenous hunger I wasexperiencingonmylow-fatdietandrefusingtolivethatwayfortherestofmylife,Ibinged!Notjustforafewdaysorweeks,butformonths.InjustfourmonthsIregainedallofmyweightbackandthensome.

ByNewYear’sDayin2004,Imademywayupto410poundsonmy6’3”body.Mywifewasbecomingincreasinglyworriedaboutmyhealth--forgoodreason.AlthoughIdidn’tsufferfromanymajorhealthproblemsatthe time,mydoctorhadalreadyputmeonprescriptionmedications forhigh cholesterol, high blood pressure and some breathing/wheezingissues.He justwrote theprescriptionsandIdutifully tookthem. IneverquestionedwhyIwastakingthedrugsevenwhenIbeganexperiencing

paininmyjointsandmusclesfromthestatinI’dbeengiven.

IntheFallof2003,afterrippingmypantsgettinginmycaryetagain,plusa snide comment about my weight from a 6th grader, I becameremotivatedtogiveityetanothergo.ButIreallydidn’twanttofeellikeIdidin1999withallthehunger,frustration,andmiseryassociatedwiththelow-fatdiet.ItwasatthispointinmylifethatIbegantosearchforotherdietaryapproachesthatmightbeabetterfitformybody.

Mydearmother-in-lawheardIwantedtotrysomethingdifferentandshegaveme a copy of Dr. Atkins’ NewDiet Revolution for Christmas thatyear.Inthedaysleadinguptothenewyear,Ireadthebookfromcoverto cover. I made the fateful decision to start the Atkins diet in earnestbeginningonNewYear’sDay2004.Thiswasamajorturningpointinmylife… but of course, at the time, I was totally oblivious to just howmonumentalthiswasgoingtobe.

Itwasapparentfromtheget-gothiswasgoingtobeachallengeearlyonsinceIwassoseverelyaddictedtosugar/carbohydrate.Inthosefirstfewdays,Iwentthroughmajorcarbohydratewithdrawal.Afterall,uptothatpoint I’d had a 16-cans-of-Coke-a-day habit, along with eating wholeboxesofLittleDebbie®snackcakes(amongotherthings).Forawhile,Ifelt like Iwanted to killmyself -- I’m not kidding! The sugarwithdrawalwasexcruciating --perhapsasstrongassomeone trying todetox fromcrackcocaine.ButthankfullyIstuckwiththeAtkinsplanbecauseIknewIHADtodosomethingaboutmyweight this timearoundandNOTHINGwasgoingdetermefrommeetingmyobjective.

BytheendofthefirstmonthIhadshedatotalof30pounds.BytheendofFebruary,another40poundsweregone,andafter100daysmyscaletold me that 100 pounds were gone. WOW! Words simply cannotdescribe how I felt going through this incredible journey after somanyyearsofrecurringfailureondietafterdiet.Atlonglast,IhadfoundaplanthatwouldworkformeandIwasdoingit.

Butwait,youmightexclaim!Youlost170poundsbackin1999.Howwasit different this time on a lowcarb nutritional approach?Good question,because this is thebestpart.Thekeydifferencewas that thoseall-too-familiarhungerpangsand theweakness thathadplaguedmeonhigh-

carb, low-fat dietswere completely gone.Now that Iwas consuming asatisfyingly healthy high-fat,moderate (adequate) protein, lowcarb diet,mybodyseemedtobe“atpeace”metabolicallyspeaking.Icouldsensethat thiswasthewayofeatingmybodyhadbeen longingforallalong,andnowitwasrewardingmeforfeedingitproperly.Isometimesreflecton all of those years I could have been eating this way had just oneinsightfuldoctor,nutritionist,ornursesimplygivenmepermissiontodoit.Yes,theAtkinsdietisstillconsideredan“outside-the-box”approach,butnowyouknowit’saviableoptionthatcouldhelpmanyofyourstrugglingpatientsgainmorecontrol.

Althoughitwasn’taneasyroadbyanystretchoftheimagination,IamsothankfulIfoundthehealthylowcarblifestylebecauseIwentontoloseatotalof180poundson it in2004.Writing this in2010, I’vestillkept themajorityof thatweightoffbycontinuing toapply lowcarbprinciples intomydailymenus.More important thanmyweight loss, though,was thefact that lowcarb livinggavememyhealthback.Withinninemonthsofbeing on the Atkins lowcarb lifestyle, all the medication I was takingbecamehistory…gonefrommylifeforever!

Tothisday,IhaveyettotakeanothermedicationforanyhealthailmentandIproudlytelleveryonethatlowcarbisarguablyoneofthebestwaystoimproveyourhealthnaturallywithouttheuseofdrugs.Whosaysyourhealthdoesn’t improveon the lowcarb lifestyle?That’soneof themainreasons why I wrote the book 21 Life Lessons From Livin’ La VidaLowCarb to demonstrate all of theways lowcarbworks beyondweightloss.You’vealreadylearnedquiteabitaboutthatinthisbookaswell.

Following my tremendous triple-digit weight loss in 2004, I beganbloggingaboutmyexperiencestoencourageotherpatientsouttherethattheytoocanloseweightandgethealthythelowcarbway.InApril2005,Istarted the “Livin’ La Vida LowCarb” blog (http://www.livinlavidalow-carb.com/blog) as a means for educating, encouraging and inspiringothers to take carbohydrate-restriction seriously when everything elsehadfailedthem.Iknewfromfirst-handexperiencethat itcouldbedoneandIsoughttosharemystoryinthehopesthatthelegacyofthelateDr.RobertC.Atkinscouldliveonthroughmystory.

Isincerelybelieve ifothercarbohydrate-intolerantpatients likemeknewthey had healthy nutritional alternatives available to them, then theywould enthusiastically give it a go, potentially seeing the results theyhavebeen longing for.Forusaspatients, support fromourdoctoranddietitianisinvaluablewhendealingwithourweightandhealthproblems,butthisonly‘works’ifthatsupportmatchesourmetabolicneeds.Thatiswhy the information provided in this book is so critical for medicalprofessionalslikeyourselvestobeexposedto.

Formypart, Iamprivilegedtohaveoneof themostwidely-readhealthblogs on the Internet, a Top 25 Nutrition & Fitness iTunes podcast(http://www.thelivinlowcarbshow.com/shownotes) featuring twice-weeklyinterviewswith the world’s best health experts. I have also created anonlineresource(http://lowcarbdoctors.blogspot.com)tohelppatientsfindmedicalprofessionalsintheirareawhoareknowledgeableandwillingtosupport their lowcarbdietarychange. Ifyouareconvinced that this isaviabletreatmentoptionforyourpatientstotryandwouldliketobeaddedtothislist,thenI’dlovetoincludeyournameandcontactinformationtothegrowingnumberof forward-thinkingdoctorsandnurseswho realizethevalueofofferingthelowcarblifestyletotheirpatients.

You possess an enormous potential to change the lives of real peoplewho come to you for advice about how to lose weight, improve theirhealth,andbecomethepersontheyhavealwayswantedtobe.Applytheprinciplesyou’velearnedinthisbooktoyourpatientsandthinkaboutmystoryasyouaredoingit.Medicalprofessionalslikeyoucouldbeapartofreigniting the revolution that people like Dr. Atkins and others startedmanydecadesago.Awholenewgenerationof carbohydrate intolerantpeople are desperately looking for an alternative truth. It all revolvesaround healthy lowcarb living andmaking patients feel confident aboutdoingitforthemselves.Youpossessthepowerrightnowtoallowthemtostart“livin’lavidalowcarb.”Theballisnowinyourcourt.

SincerelyYours,Jimmy

ReplytoJimmy

DearJimmy,

We wish to thank you for your heartfelt and inspiring story, and weunderstandthefrustrationthatyouexperiencedasyoustruggledtofindan effective low carbohydrate solution for your problem. We alsoappreciate the role that you have played in helping others avoid thesefrustrations,andyes,ininspiringotherstogoagainstthe‘highcarb,lowfat’consensus.

As a result of your efforts and those of many other courageousindividuals(seeAcknowledgements,pg277),wehaveastrongsenseofchange in attitudes and posture towards a low carbohydrate lifestyle.However the time required to significantly alter themedical consensusmight be likened to an ocean liner reversing its course. Based on theescalating prevalence of obesity and metabolic syndrome, staying thecoursemightmeanwehitaproverbialiceberg.Atthetimeofthiswriting,wehavenot‘turnedthecorner’,sotospeak.AsthecaseofDrs.WarrenandMarshalldemonstrated (seepg177),evenafter thedefinitiveneedforamajorturnisdemonstrated,theactualcoursecorrection(changeinmainstreamacademicandclinicalconsensus)comesadecadelater.

Sowhenwas that turn signal activated?Was it the spate of publishedclinicalstudiesbeginningin2003,yourexperiencebeginningin2004,oreven later?Only timewill tell. Up until that point, youwill still need topatientlyand firmlystandyourgroundagainstskeptics.After thatpoint,youwillproudlystandasaleader-onewhobyexamplehelpedusturnthecornerawayfromtheprimrosepathpavedwithsugarandstarchthatledmanyofustoobesityanditscomplications.

Finally, what will that change ‘look like’ when it happens? Will theconsensusflipallthewayovertotheoppositeviewthatdietaryfatsaregood and carbs bad? We fervently hope not! Rather, if we ‘stick thelanding’onthisparadigmshift,ourflipintheconsensuswill leavesomeofus(thosewhoarefullyinsulinsensitive)withthechoiceofcontinuingahighcarbohydrate, lowfatdiet.Butforthoseofuswhohavedevelopedinsulin resistance, we will finally have the unbiased option to follow awellformulated low carbohydrate, high fat diet; allowing this majorsegment of humanity to recover their self-respect, wellbeing, and

function.

Welivein interestingtimes.Maywecontinuetoworktogetheruntil thatdaywhen, walking down the street, we find that obesity is once againrareandnolongerthenorm.

BestRegards,Drs.PhinneyandVolek

ACKNOWLEDGEMENTSWeareblessed to be livingat the right time to beable to connect thevariousdotsthathavebecomethisbook.

Almost20yearsago,agraduatestudentslippedintoasymposiumwhereaprofessorwasgivingatalkaboutketogenicdiets.Afterthelecture,theyconversed for a time. Five years ago,we resumed that ‘conversation”,fromwhichresultedourcontributionsto‘TheNewAtkinsforaNewYou’,andnowthisbook.

Agreatmanygenerousandtalentedindividualshaveassistedusinthisproject. Foremost amongst these we thank Jackie Eberstein, EricKossoff, and JimmyMoore for invaluable contributions that extend andcomplement our own experience. We thank Abby Bloch, ShelleySchlender,Graciela Anrrich,Gary Taubes, Karl andSpencerNadolsky,Peter Defty, Anna Issakoff-Mellor, Marni Jameson, Craig Warden,RichardSeip,CarlMaresh,LauraCusack,LauraKunces,BrittanieVolk,Noreen Carpenter, Taryn Hand, and Richard Wood for their time andthoughtfulcommentsonearlydraftsofthebook.

Ourcurrentunderstandingoflowcarbohydratedietsstemsfromtheworkofmanyprofessionalsextendingbackahundredyearsormore.Howeverbeingabletoparticipateintheresurgentinterestinresearchandclinicalapplications in the last decade has been both gratifying and humbling.WearehonoredtobeincludedamongaremarkablegroupofcolleaguesincludingWilliamKraemer,RichardFeinman,MariaLuzFernandez,MaryVernon, James Wortman, Douglas Bibus, Christopher Gardner,CassandraForsythe,EricWestman,GaryTaubes,DonaldLayman,MaryDanandMichaelEades,andRichardK.Bernstein.

I (StevePhinney)wishtopersonally thankmymanyteachers,mentors,and colleagues who have stimulated and guided me along the way,including: Jeff Volek, James Wortman, Richard Carpenter, GeraldReaven,EthanSims,EdwardHorton,BruceBistrian,GeorgeBlackburn,William J. Evans,RalphHolman, SteveD.Clarke,ManabuNakamura,Joanne Slavin, Judith Stern, Carol Stratford, and Darlene Dreon. My

greatest appreciation goes tomy children, Lauren and Eric, who havegrowntotoleratemycooking,andtomyremarkablewifeHuong,withoutwhosegraspofthe‘bigpicture’I’dbeforeverlostinthedetails.

I(JeffVolek)wishtopersonallythankmanyindividualswhohaveadvisedand inspiredme, including:StevePhinney,WilliamKraemer,MariaLuzFernandez, Richard Seip, Richard Bruno, and Richard Feinman. Aspecial thanks to the many outstanding graduate students who havecontributed to the myriad of low carbohydrate diet studies in mylaboratory.Mostimportantly,I’mgratefulformysupportiveparentsJerryandNina,mytwoyoungchildren-in-chargePreston(3yr)andReese(1yr), and especially my extraordinary wife Ana who slows me downenoughtoappreciatewhatreallymatters.

ABOUTTHEAUTHORSJeffVolekisadietitian-scientistwhohasspent15yearsstudyingdietandexercise effects on health and performance.He has held an academicpositionatBallStateUniversityandiscurrentlyanassociateprofessoratthe University of Connecticut. Dr. Volek has contributed to 3 books, 2patents, and over 200 papers. He received his dietetic training atMichiganStateUniversityandPenroseStFrancisHospitalandhisPhDinExercisePhysiologyfromPennStateUniversity.

StevePhinney isaphysician-scientistwhohasspent35yearsstudyingdiet, exercise, fatty acids, and inflammation. He has held academicpositions at the Universities of Vermont, Minnesota, and California atDavis,aswellasleadershippositionsatMonsanto,GalileoLaboratories,and Efficas. Dr. Phinney has published over 70 papers and severalpatents. He received his MD from Stanford University, his PhD inNutritional Biochemistry from MIT, and post-doctoral training at theUniversityofVermontandHarvard.

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