Upload
giannidiet
View
233
Download
0
Embed Size (px)
Citation preview
7/29/2019 HMB 7 12 11
1/55
-Hydroxy--Methylbutyrate(HMB)
1
7/29/2019 HMB 7 12 11
2/55
Educa7onalObjec7vesforthe
-Hydroxy--Methylbutyrate(HMB)Presenta7on
ProvideageneraloverviewofHMBintakeandmetabolism Describemechanis;cstudiesoftherolesofHMBincellsignalingpathwaysgoverningbothmuscleproteinsynthesisanddegrada;on DiscussroleofHMBinreducingmuscledamageduringexercise
Reviewclinicaldataevalua;ngchangesinbodycomposi;onandperformanceinathletesreceivingHMBsupplementa;on
Usedaloneandincombina;onwithcrea;neorotheraminoacids Includingeffectsinhealthy,olderadults
Presentothertherapeu;candmedicalapplica;onsAddressthesafetyofHMBsupplementa;on
2
7/29/2019 HMB 7 12 11
3/55
-Hydroxy--Methylbutyrate(HMB)
3
Generaloverviewofintakeandmetabolism
7/29/2019 HMB 7 12 11
4/55
WhatIsHMB?
HMBisaleucinemetabolite Leucineisanessen;albranched-chainaminoacidthatcantriggermuscle
proteinsynthesisandmayinhibitproteindegrada;on1
Isitunknownwhetherleucineoritsmetabolitesac;velypar;cipateinproteinsynthesis/degrada;on
Leucineistransaminatedto-ketoisocaproate(KIC)bybranched-chainaminoacidtransferase,mainlyinmuscle;ssues
Approximately5%to10%of-ketoisocaproate(KIC)isconvertedtoHMB(byKIC-dioxygenase)inthecellcytosol
CalciumHMBhasthefollowingmolecularstructuralformula2
1. NemetD,etal.IMAJ.20057:328-332.2. Availableat:www.chemblink.com/products/135236-72-5.htm.AccessedMay10,2011.
Ca++HO O
O
O
O OH
4
7/29/2019 HMB 7 12 11
5/55
Forma7onofHMBDuringLeucineMetabolism
AdaptedwithpermissionfromNissenSLandAbumradNN.JNutrBiochem.19978(6):300-311.
Leucine
KIC Isovaleryl-CoA
-methyl-crotonyl-CoA(MC-CoA)
-hydroxy--methylbutyrate
(HMB)
HMB-CoA
HMG-CoA
Mevalonate
Acetyl-CoACholesterol
(5-10% of
Leu metabolism)
Acetoacetyl-CoA
(only when
biotin is deficient)
5
7/29/2019 HMB 7 12 11
6/55
SourcesofHMBintheDiet
Catabolismofleucine Meanintakeofleucinefromfoodandsupplements(1988-1994NHANESIII)was6.1g/day1
Assuming5%to10%conversioninthebody,thisrepresents0.3to0.6gHMBperday
Togetthe3-gHMBdosetypicallyusedinresearch,30-60gleucine/daywouldhavetobeconsumed
HMBinfoods TherearetracesofHMBinmanyanimal-andplant-basedfoods,especially
ca_ishandalfalfa2
1. Ins;tuteofMedicineoftheNa;onalAcademies.DietaryReferenceIntakesforEnergy,Carbohydrate,Fiber,Fat,FayAcids,Cholesterol,Protein,andAminoAcids.Washington,DC:TheNa;onalAcademiesPress2005:1008.
2. Availableat:hp://www.webmd.com/heart-disease/news/20000818/researchers-take-closer-look-at-supplement-sensa;on.AccessedMay10,2011. 6
7/29/2019 HMB 7 12 11
7/55
HMBAbsorp7onandKine7cs
ThemechanismofHMBabsorp;onfromtheintes;nehasnotbeenreported
In2kine;ctrials,plasmahalf-lifewas2.5hours HMBlevelsreturntobaselineat~9hoursaeringes;on Upto30%ofanoralHMBdoseisexcretedunchangedintheurine
Theaddi;onofglucosetoacalciumHMBsupplementdoesnotincreasebioavailabilityorcellularuptakeofHMB AddedglucosedoesslowHMBabsorp;onthroughdelayedgastric
emptying
VukovichMD,etal.JNutrBiochem.200112(11):631-639.7
7/29/2019 HMB 7 12 11
8/55
HMBBioavailability
ReprintedfromFullerJCJr,etal.BrJNutr.2011105:367-372.
BioavailabilityofafreeacidgelformwasgreatervscalciumHMBcapsules 2studies,eachwith8healthyadults(4male,4female) 3treatments 1gcalciumHMBincapsuleform
EquivalentamountofHMBinfreeacidforminagel(swallowedimmediately) FreeacidHMBgelheldsublinguallyfor15sec,thenswallowed
BloodandurinaryHMBlevelsweremonitoredfor3to24hoursaeringes;on Onlycommerciallyavailableformiscalciumsalt
aP
7/29/2019 HMB 7 12 11
9/55
-Hydroxy--Methylbutyrate(HMB)
9
Mechanismsofac7on
7/29/2019 HMB 7 12 11
10/55
PossibleHMBMechanismsofAc7on
HMBmaybeanan;catabolicagent Studieshavedocumentedpoten;allyinhibitedpathwayssuchasthe
ubiqui;n-proteasomepathwayinamurinemodel1,2
HMBmaybeasubstrateforcholesterolsynthesisinmuscle3 Forma;onof3-hydroxy-3-methylglutarylCoenzymeA(HMG-CoA,precursor
forcholesterolsynthesis)
Muscleisdependentoncholesterolsynthesistomeetitsneeds Increasedcellmembraneintegritywithimprovedmusclecholesterol
synthesis
StressedorinjuredmusclecellsmightnotsynthesizeenoughcholesterolHMBalsohelpstos;mulateproteinsynthesisviathemTORpathway4
Maybetherealfactorbywhichleucines;mulatesproteinsynthesisHMBmayhaveothereffects(eg,immunomodulatoryorhormonal)5
1. LeckerSH,etal.JNutr.1999129:227S-237S.2. SmithHJ,etal.CancerRes.200565:277-283.3. NissenSLandAbumradNN.JNutrBiochem.19978:300-311.4. EleyHL,etal.AmJPhysiolEndocrinolMetab.2008295:E1409-E1416.5. ZanchiNE,etal.AminoAcids.201140(4):1015-1025.
10
7/29/2019 HMB 7 12 11
11/55
TheUbiqui7n-ProteasomePathwayforProtein
Degrada7on
ReprintedfromLeckerSH,etal.JNutr.1999129:227S-237S.11
7/29/2019 HMB 7 12 11
12/55
EffectsofHMBontheUbiqui7n-ProteasomePathway
ReprintedfromSmithHJ,etal.CancerRes.200565:277-283.
aP
7/29/2019 HMB 7 12 11
13/55
EffectsofHMBonProteinSynthesisandDegrada7on
Initiator (PIF, LPS, TNF- , angiotensin II, etc.)
Caspase-8
Caspase-3
PKR
p38 MAPKPKR P
eIF2 eIF2 P
Translational efficiency
Protein synthesis
ROSNF- (nuclear accumulation)
Proteasome + E3 mRNA
Protein degradation
HMB blocks pathway
here
X
PIF,proteolysis-inducingfactorLPS,lipopolysaccharideTNF,tumornecrosisfactorPKR,RNA-dependentproteinkinaseMAPK,mitrogen-ac;vatedprotein
kinaseNF,nuclearfactorROS,reac;veoxygenspecieseIF,eukaryo;cini;a;onfactorP,phosphorylated.
BasedonEleyHL,etal.AmJPhysiolEndocrinolMetab.2008295:E1417-E1426.
13
7/29/2019 HMB 7 12 11
14/55
FurtherEffectsofHMBonCellularProteinSynthesis
HMBincreasesmTORsignalingpathwayac;vity
mTORincreasesprotein
transla;on
Promotesit Keepsitfrombeingturnedoff
EleyHL,etal.AmJPhysiolEndocrinolMetab.2008295:E1409-E1416.
AdaptedfromSABiosciences,aQIAGENcompany.Availableat:hp://www.sabiosciences.com/pathway.php?sn=mTORPathway.AccessedJune27,2011.14
7/29/2019 HMB 7 12 11
15/55
0.90.80.7
0.60.50.4
0-2D
ensitometryunits,
ph/tot
a
0.30.20.1
-1 0 2Time, h
p mTOR
Total mTOR
1.6
1.41.21.00.8
0-2
Densitometryunits,p
h/tot
b
0.60.40.2
-1 0 2Time, h
p P70S6K
Total P70S6K
EffectsofHMBonPhosphoryla7onStatusofmTOR
PathwaySignalingFactors
ReprintedfromEleyHL,etal.AmJPhysiolEndocrinolMetab.2007293:E923-E931.
HMB (50 M) added here to murine myotubes.
HMBincreasedphosphoryla;onofmTORsignalingfactors,s;mula;ngproteinsynthesis
HMBaenuatesthedepressiveeffectsofproteolysis-inducingfactoronproteinsynthesis
aDifferentfromcontrol,P
7/29/2019 HMB 7 12 11
16/55
-Hydroxy--Methylbutyrate(HMB)
16
HMBandindicatorsofmuscledamage
7/29/2019 HMB 7 12 11
17/55
EvidenceforaProtec7veEffectofHMBAgainstMuscle
CellMembraneDisrup7on
Exercisecanresultinmusclecellmembranedisrup;on1,2Eleva;onsofcrea;nekinase(CK)andotherenzyme(eg,lactatedehydrogenase[LDH])levelsinthebloodcanbeindicatorsofmusclecellmembranedisrup;on3,4
NotnecessarilymuscleproteinbreakdownAfewexercisestudieshavefoundabluntedCKresponseduringHMBsupplementa;on5,6
1. McBrideJM,etal.MedSciSportsExerc.199830(1):67-72.2. HurleyBF,etal.IntJSportsMed.199516(6):378-384.3. CabanissCD.In:WalkerHK,HallWD,HurstJW,eds.ClinicalMethods:TheHistory,Physical,and
LaboratoryExaminaKons.3rdedi;on.Boston:Buerworths1990:Chapter32.
4. SarriE,etal.BiochemJ.2006394(pt1):325-334.5. KnierAE,etal.JApplPhysiol.200089:1340-1344.6. vanSomerenKA,etal.IntJSportNutrExercMetab.200515(4):413-424.
17
7/29/2019 HMB 7 12 11
18/55
EffectofHMBSupplementa7ononCrea7neKinaseLevels
DuringExercise
KnierAE,etal.JApplPhysiol.200089:1340-1344.
Studyinvolving13par;cipants(5male,8female)thathadahistoryofrunningatleast48km/wk
Par;cipantsreceived3gHMBorplacebodailyfor6weeksbeforeaprolongedrun(double-blind)
Pair-matchedbasedonbest2-milerun;me Therunwas20kmonacollegiatecross-countrycourse
CKandLDHweremeasured2weeksbeforetherun(Pre),immediatelyaertherun(Post),andat1,2,3,and4daysaertherun
Results follow on next slide
18
ff f
7/29/2019 HMB 7 12 11
19/55
EffectofHMBSupplementa7ononCrea7neKinaseLevels
DuringExercise(Contd)
ReprintedfromKnierAE,etal.JApplPhysiol.200089:1340-1344.
MaineffectfortreatmentinCKmeasurement, P=.05,withnosignificantgroup;meinterac;on
AsignificantmaineffectfortreatmentinLDHmeasurement( P=.003),withnosignificantgroup;meinterac;on
450
400
350
300
250
0Pre
CPKactivity,U/L
200
150
100
1dPost
3dPost
Post 2dPost
4dPost
Time relative to the prolonged run
50
Placebo
HMB
19
ff f l 7 l
7/29/2019 HMB 7 12 11
20/55
EffectsofHMBSupplementa7ononMuscleDamage
DuringExercise
1studyshowedposi;veeffectsof3gHMBand0.3gKIC/dayversusplacebowhenreceivedfor2weekspriortoexercise(bicepscurlwithprolongedeccentricphase) 1
In6nonresistance-trainedmalesubjects Supplementa;onreducedthedelayedonsetofmusclesoreness(DOMS)ra;ngs
(P
7/29/2019 HMB 7 12 11
21/55
-Hydroxy--Methylbutyrate(HMB)
21
EffectsofHMBonbodycomposi7onandstrength
7/29/2019 HMB 7 12 11
22/55
HistoricalBackgroundonHMBSupplementa7on
NumerousstudiesofHMBsupplementa;oninseveralanimalmodels(steers,lambs,rats,chickens,trout,andhorses)showedposi;veeffects
on
Carcassquality,proteinmetabolism,immuneresponse,muscledamage,an;oxidantstatus,andbloodlipidprofile
Dr.SteveNissen(AnimalScience,IowaStateUniversity)isessen;allythefatheroftheHMBstory
Performedini;alhumanstudiesofHMBsupplementa;oninthe1990s 1 Alsoperformedameta-analysisofsupplementa;onstudiesin2003with
respecttoeffectsonleanbodymassandstrengthgains 2
1. NissenS,etal.JApplPhysiol.199681(5):2095-2104.2. NissenSLandSharpRL.JApplPhysiol.200394:651-659.
22
Ch i O ll M l St th D i HMB
7/29/2019 HMB 7 12 11
23/55
ChangeinOverallMuscleStrengthDuringHMB
Supplementa7on:Ini7alStudy
ReprintedfromNissenS,etal.JApplPhysiol.199681(5):2095-2104.
aP
7/29/2019 HMB 7 12 11
24/55
ChangeinUrinary3-Methylhis7dine(3-MH)Excre7on
DuringHMBSupplementa7on:Ini7alStudy
ReprintedfromNissenS,etal.JApplPhysiol.199681(5):2095-2104.EliaM,etal.BrMedJ.1981282:351-354.
3-MHisamuscle-specificaminoacid Formedduringbreakdownofmuscleproteins(ac;nandmyosin) Excretedunchangedinurine
HMBsupplementa;onreducedthephysiologicincreasein3-MHduringexercise
aP
7/29/2019 HMB 7 12 11
25/55
ChangeinFat-FreeMassDuringHMBSupplementa7on:
Study2
Totalbodyelectricalconduc;vity(TOBEC)wasusedforbody
composi;onanalysis
HMBsupplementa;onincreasedfat-freemassearlyinexercise
regimencomparedwithplacebo
Significantgainscon;nuedthroughday39
ReprintedfromNissenS,etal.JApplPhysiol.199681(5):2095-2104.
32healthyadults(19-22yearsmeanbodyweight,99kg),almostallengagedinanexerciseprogrambeforestudyentryandateatuniversitytrainingtable
Randomizedtoplaceboor3gHMBperdayfor7weeks HMBprovidedinanutrient/proteinpowderplacebowasisocaloricorangejuice
Par;cipantsatenormaldiet(nostrictdietarycontrol) Dailyproteinintakewases;matedat200g(HMB)vs180g(placebo)
Par;cipantsliedweights2to3hours/day,6days/week
aP
7/29/2019 HMB 7 12 11
26/55
Posi7veEffectsofHMBSupplementa7ononStrength,
Power,and/orBodyComposi7on
26
StudyDesign Treatment Training Results
Double-blindin
untrainedcollege
men,N=371
0,38,or76mg/kg/
dayHMB(equivalent
to0,3,or6g/day)for8wks
Resistance,
3;mes/wk(80%1-
RM)assessedevery2wks
Comparedwithother2groups,Fat-freemassincreasedinthe38mg/kgdosegroup(P
7/29/2019 HMB 7 12 11
27/55
StudiesShowingNoEffectsofHMBSupplementa7onon
StrengthandBodyComposi7on
27
StudyDesign Treatment Training Results
Randomized,double-
blindinexperienced
(5.5years),
resistance-trained
athletes,N=401
0,3,or6g/dayHMB
for28daysina
carbohydrate/protein
powder
Maintained
individualized
resistancetraining
program(~7hrs/wk)
andkepttraining
logs
NeitherdoseofHMBinfluencedStrength(1-RM)Bodycomposi;on(bydualenergyX-rayabsorp;ometer)Bodyanabolic/catabolicstatusBloodchemistries
Randomized,double-
blindinna;onal-level
athletes(polo,17
rowers,10)with2yearsofresistance
training,N=272
3g/dayHMB(;med-
releaseorstandard
capsule)orplacebo
for6wks
Resistance,
2-3;mes/wk
(Pre-compe;;on
phaseoftraining)
NeitherdoseofHMBinfluencedStrengthBodycomposi;onCrea;nekinaselevels Trendtowardhighercrea;nekinaselevelinplacebogroup(P=.07forgroupx;meinterac;on)
Randomized,
crossoverin
collegiatefootball
players,N=353
3g/dayHMBor
placebofor4wks
(16playersgotHMB
first,19gotplacebo
first)
Intensiveresistance,
20hrs/wkand
variousothertypes
Nochangesinbodycomposi;onorstrengthforeitherplaceboorHMBgroupsLackofchangeinplacebogroupsuggestsovertraining
Randomized,single-
blindincollegiate
footballplayers,
N=264
3g/dayHMBor
placebofor10days
Preseasontraining
campNochangesbetweenbaselineandposttrainingineitherplaceboorHMBgroupsforanaerobicpower
NochangesbetweenplaceboandHMBgroupsforchangesincrea;nekinase,myoglobin,
testosterone,orcor;sollevels
Abbrevia;ons:RM,repe;;onmaximum.1.KreiderRB,etal.IntJSportsMed.199920(8):503-509.2.SlaterG,etal.IntJSportNutrExercMetab.200111(3):384-396.3.RansoneJ,etal.JStrengthCondRes.200317(1):34-39.4.HoffmanJR,etal.JStrengthCondRes.200418(4):747-752.
7/29/2019 HMB 7 12 11
28/55
WhytheDiscrepancyinHMBStudies?
Therearepoten;aldifferencesinmusclemetabolismbetweenmorehighlytrainedanduntrainedathletes
Morepoten;alforbenefitprobablyinuntrainedathletesLengthofHMBsupplementa;onmayhavebeeninsufficientinnega;vestudies
Morehighlytrainedathletesmightrequirelongersupplementa;on(only1nega;vestudy>4weeksdura;on)
Verylimiteddata(only2studies)onHMBdosesover3g/day Largerbodysizemightrequirealargerdose
TypeoftrainingmaybeimportantDifferencesbetweenlaboratoriesThereareseveralgoodmeta-analysesandreviewsofHMBandathle;cperformance1-6
1. PortalS,etal.JPedEndocrinolMetab.201023(7):641-650.2. ZanchiNE,etal.AminoAcids.201140(4):1015-1025.3. AlonT,etal.ResCommMolPatholPharmacol.2002111(1-4):139-151.4. NissenSLandSharpRL.JApplPhysiol.200394:651-659.5. RowlandsDSandThomsonJS.JStrengthCondRes.200923(3):836-846.6. WilsonGJ,etal.NutrMetab.20085:1DOI:10.1186/1743-7075-5-1.
28
7/29/2019 HMB 7 12 11
29/55
CounterfeitHMB?
Theini;alhumanresearchonHMBcamefromSteveNissenslaboratoryatIowaState
Thecompoundtheystudiedandtheoneintheirassociatedpatentscalcium-hydroxy--methylbutyrate
AproductmarketedintheUK(HMB-1000,MaximuscleLtd.)hasbeenshowninonestudytobeineffec;veatreducingexercise-
inducedmuscledamage1SubsequentanalysisoftheHMB-1000productrevealedthatitactuallycontainednoHMB2
Itcontainsarelatedleucinemetabolite(calciumhydroxy-methylbutyrate)Thisraisesthepoten;alissuethatsomenoeffectstudieswithHMBcouldbeduetouseofaproductthatdoesnotcontainHMB,butrathersimilarcompoundsthatmightnothavethesamebiologicalac;vity
1Nunan et al. J Strength Cond Res 2010;24:531-537.2Abumrad NN, Rathmacher JA. J Strength Cond Res 2011:25(7):1-2.
7/29/2019 HMB 7 12 11
30/55
-Hydroxy--Methylbutyrate(HMB)
30
HMBandaerobicperformance
7/29/2019 HMB 7 12 11
31/55
HMBandMeasuresofAerobicCapacity
MostoftheresearchregardingHMBhasfocusedonstrengthandbodycomposi;on
AbilitytotrainharderwithlessmusclebreakdownfromexercisemaybeamechanismthroughwhichHMBcouldfacilitateaerobicperformance
2studieshaveevaluatedaerobiccapacityduringHMBsupplementa;on1,2 Inthesestudies,themechanismofhowHMBmightworkisnotclear
1. VukovichMDandDreifortGD.JStrengthCondRes.200115(4):491-497.2. LamboleyCR,etal.IntJSportNutrExercMetab.200717(1):56-69.
31
7/29/2019 HMB 7 12 11
32/55
MeasuresofAerobicCapacity:Study1
Randomized,double-blind,crossoverstudyinvolving8endurance-trainedcyclists
Received3g/dayHMB,leucine,orplaceboforthree2-weeksupplementa;onperiods,with2-weekwashoutperiodsinbetween
Par;cipantsperformedgradedcycleergometrytests VO2peak,VO2max,andlactateaccumula;onpeakweresimilarbetweenall
groups
Onsetofbloodlactateaccumula;on(VO2atbloodlactatelevelof2mM)wasincreasedinboththeHMBandleucinegroupscomparedwiththeplacebogroup(9.1%,2.1%,and0.8%,respec;vely)
Leucinehadnoothernotableeffectsonaerobicparameters Lactatethreshold(%VO2max),and;metoreachVO2peakwerealso
increasedintheHMBgroupcomparedwiththeleucineandplacebogroups
BloodHMBlevelsweremuchlower(40-to60-fold)intheleucinegroupversustheHMBgroup
SupportspreviousdataonlowconversionratesofleucinetoHMBVukovichMDandDreifortGD.JStrengthCondRes.200115(4):491-497.
32
7/29/2019 HMB 7 12 11
33/55
MeasuresofAerobicCapacity:Study2
Randomizedstudyinvolving16collegestudents
Received3g/dayHMBorplacebofor5weeks
Studentsperformedintervaltraining3;mes/weekonatreadmill Comparedwiththeplacebogroupat5weeks,theHMBgrouphad
IncreasedVO2max(13.4%vs8.4%forplaceboP
7/29/2019 HMB 7 12 11
34/55
-Hydroxy--Methylbutyrate(HMB)
34
HMBstudieswithcrea7neorwithaminoacids
7/29/2019 HMB 7 12 11
35/55
HMBinCombina7onWithCrea7ne
Anaturalques;oniswhethersynergis;coraddi;veeffectswilloccurduringsimultaneoussupplementa;onwithcrea;neandHMB
Clinicaldatahavereportedmixedresults Randomized,double-blindstudyinvolving40volunteers
Received3g/dayHMB,20g/dayfor7daysfollowedby10g/dayfor14dayscrea;ne(Cr),crea;neplusHMB(CrHMB),orplacebofor3weeks
Volunteersperformedprogressiveresistancetraining Leanbodymassgains(assessedviabioelectricimpedance)were0.92kg,0.39kg,and1.54kggreaterforCr,HMB,andCrHMBgroups,respec;velycomparedwithplacebo
SignificantmaineffectforCrgroup(P=.05),andatrendforHMBgroup(P=.08) Datawereaddi;ve,noCrHMBinterac;on(P=.73)
Similarresultswerereportedforstrengthgains,withaddi;veeffectsforCrandHMB Reduc;oninexercise-inducedcrea;nephosphokinaselevelswasgreatestinthe
HMBgroup(maineffect,P=.01) Addi;onofcrea;neantagonizedtheHMBeffect( P=.04forCrHMBinterac;on)
JwkoE,etal.NutriKon.200117(7-8):558-566.35
7/29/2019 HMB 7 12 11
36/55
HMBinCombina7onWithCrea7ne
Randomizedstudyinbasketballplayers1 Receivedcrea;ne,HMB,crea;neandHMB,orplacebofor30days
Doseswerenotspecified Playersinthecombina;ongrouphadincreasedmaximumpowerandtotal
workoutputcomparedwiththeothergroups
Noaddi;onalincreaseinlactateorfallinmusclepH2studiesdidnotshowbenefitsofthecrea;ne/HMBcombina;on
2,3
Bothstudieswerein57eliterugbyplayers(N=30N=27) Received3g/dayHMB,3g/daycrea;ne,crea;neandHMB,orplacebofor6
weeks
NobenefitswereobservedonMuscularstrengthandendurance
Legpower Anthropometry Aerobicability Anaerobicability
1. ZajacA,etal.JHuminet.200310:95-108.2. OConnorDMandCroweMJ.JStrengthCondRes.200721(2):419-423.3. OConnorDMandCroweMJ.JSportsMedPhysFitness.200343(1):64-68.
36
HMB in Combina7on With the Amino Acids Arginine
7/29/2019 HMB 7 12 11
37/55
HMBinCombina7onWiththeAminoAcidsArginine,
Glutamine,andTaurine
Randomized,double-blindstudyinvolving17healthymenwhowererecrea;onallyac;ve(noresistancetraininginprevious6months)
ReceivedHMBplusaminoacids(MA)oranisonitrogenouscontroltwicedailyfor12weeks
MAformula=1.5gHMB,7gglutamine,7garginine,3gtaurine,5.8gdextrose Control=10gglycine,11.5galanine,1.5gglutamate,1.5gserine
Volunteersperformedresistancetraining3;mes/week(10exercisesforwholebody) Onelight(12-to14-repe;;onmaximum[RM]),1moderate(8-to10-RM),and
1heavy(3-to5-RM)dayeachweek
Outcomevariables Strength(1-RM) Ver;caljumppower Hormonalandmuscledamageresponsestoanacuteboutofresistance
training
Bodycomposi;onandcircumferences Tendonsize
ResultsfollowonnextslidesKraemerWJ,etal.MedSciSportsExerc.200941(5):1111-1121.
37
Body Composi7on Changes During Supplementa7on
7/29/2019 HMB 7 12 11
38/55
BodyComposi7onChangesDuringSupplementa7on
WithHMBandAminoAcids
aSignificantdifferencefromV1,P.05bSignificantdifferencefromcontrol,P.05
Abbrevia;ons:V1,beforetrainingV5,aer6wksV8,aer12wks.
KraemerWJ,etal.MedSciSportsExerc.200941(5):1111-1121.
Bodymassandleanbodymasscon;nuouslyincreasedinbothgroups Bodyfatcon;nuouslydecreasedinbothgroups Aer12weeksoftraining,thesupplementa;ongrouphadsignificantlyimprovedbodycomposi;on
a
95
90
85
80
75
70V1 V5 V8
Time point
Bodymass,kg
a,b
CON
MA
A
a
80
75
65
60
55
50V1 V5 V8
Time point
Leanbodymass,kg
a,b
B
a
32
30
26
22
1816
V1 V5 V8Time point
Bodyfat,%
a,b
C
28
24
20
70
CON
MA
CON
MA
38
Strength and Power Changes During Supplementa7on
7/29/2019 HMB 7 12 11
39/55
StrengthandPowerChangesDuringSupplementa7on
WithHMBandAminoAcids
aSignificantdifferencefromV1,P.05bSignificantdifferencefromcontrol,P.05
Abbrevia;ons:V1,beforetrainingV5,aer6wksV8,aer12wks.
KraemerWJ,etal.MedSciSportsExerc.200941(5):1111-1121.
Bothmusclestrengthandpowercon;nuouslyincreasedinbothgroups Aer6weeksoftraining,thesupplementa;ongrouphadsignificantlyimprovedmusclestrengththatremainedenhancedatthe12-weekassessment
At12weeks,thesupplementa;ongrouphadsignificantlyimprovedmusclepower
140
120
100
80V1 V5 V8
Time point
Squat,kg
A
120
80
60
V1 V5 V8Time point
Bench,kg
B
6000
5000
4500
3500
3000V1 V5 V8
Time point
Verticaljumppower,w
C
5500
4000
100
a
a,b
a,b
a
a,b
a
CON
MAa,b
a
a,b CON
MA
CON
MA
39
Changes in Hormone Levels and Indicators of Muscle Damage
7/29/2019 HMB 7 12 11
40/55
ChangesinHormoneLevelsandIndicatorsofMuscleDamage
DuringSupplementa7onWithHMBandAminoAcids
Comparedwiththeplacebogroup,thesupplementa;ongrouphad Increasedres;ngandexercise-inducedtestosteronelevels Increaseres;nggrowthhormoneconcentra;ons Reducedpre-exercisecor;solconcentra;ons Aenuatedcircula;ngcrea;nekinaseandmalondialdehydeconcentra;ons
Indica;veoflessmuscledamage Ingeneral,theeffectsfromsupplementa;ononcrea;nekinase,malondialdehyde,andcor;solweremorepronouncedatthe12-week
pointinthestudy
Nodietaryintakedatawerereportedforthestudy
KraemerWJ,etal.MedSciSportsExerc.200941(5):1111-1121.40
7/29/2019 HMB 7 12 11
41/55
-Hydroxy--Methylbutyrate(HMB)
41
HMBintheelderly
andtherapeu7c/medicalapplica7ons
7/29/2019 HMB 7 12 11
42/55
HMBintheElderly
Thereareanumberofnutri;onalproblemsintheelderlypopula;onforwhichtheremaybeapplica;onsforHMB
Sarcopeniaduetoagingandinac;vity1 Bedrest Inabilitytoperformexercisethatcanhelpmaintainmusclemass
Woundhealing(eg,decubi;)2 Presenceofdiseasestates(eg,cancer,conges;veheartfailure)associated
withsignificantcachexia3,4
Generalizedmalnutri;on5HMBhasbeenstudiedinbothhealthyelderlyandthosewithvariouscondi;onsassociatedwithlossofmusclemassandwoundhealingcapacity
1. BaierS,etal.JPENJParenterEnteralNutr200933(1):71-82.2. WilliamsJZ,etal.AnnSurg.2002236(3):369-375.3. HsiehLC,etal.AsiaPacJClinNutr.200615(4):544-550.4. MayPE,etal.AmJSurg.2002183(4):471-479.5. HsiehLC,etal.AsiaPacJClinNutr.201019(2):200-208.
42
BodyComposi7onandProteinMetabolisminHealthy
7/29/2019 HMB 7 12 11
43/55
ody Composi7on and Protein Metabolism in Healthy
OlderAdultsDuringHMBSupplementa7on
3studieshaveevaluatedHMBinrela;velyhealthyelderlyadults(>70years) Randomized,double-blindstudyinvolving31adults(men,15women,16)
70yearsofage1
Received3g/dayHMBorplacebofor8weeks Par;cipantsunderwentanexerciseprogram5day/week
2randomized,double-blindstudiesinvolving127elderlyadults(N=50,allwomenN=77,men38andwomen39) 2,3
Received2to3gHMB+1.5to2.25glysine+5to7.5garginineperdayorisocaloric,isonitrogenousplacebo
Studydura;onswere12weeks2and1year3 Noexercisecomponent
Generalfindingsfromthesestudies Someimprovementsinbodycomposi;on(leanmass,fatmass) Increasedproteinturnover Improvementinselectedmeasuresofstrengthandfunc;onaltests
ImprovementsdidnotalwaysoccurineitherplaceboorHMBgroup Indicatesthatthepar;cipantsmightnothavebeenabletodotheexercises
adequately
Benefitswerestrongerduringtheearlierperiodofthestudiesandtaperedtowardthestudyend
1. VukovichMD,etal.JNutr.2001131:2049-2052.2. FlakollP,etal.NutriKon.200420(5):445-451.3. BaierS,etal.JPENJParenterEnteralNutr.200933(1):71-82.
43
7/29/2019 HMB 7 12 11
44/55
HMBandWoundHealing
EffectsofHMBonbodycomposi;onandproteinturnoverledtoinves;ga;onsofHMBeffectsoncollagensynthesisandwoundhealing
Randomizedstudyinvolving35healthyadults(men,8women,27meanage,75years)
Crea;onofsmallwoundswithplas;ctubularinsertsthatwereplacedinthedeltoid Received14garginine+3gHMB+14gglutamineperday(n=18)oranisocaloric,
isonitrogenouscontrol(n=17)for2weeks
At2weeksposreatment Hydroxyprolineconcentra;on(surrogateforcollagenproduc;on)wasincreasedintheHMBgroupcomparedwiththecontrolgroup(72.2nmol/cmimplantvs43.2
nmol/cmimplantP
7/29/2019 HMB 7 12 11
45/55
p
HIV-InfectedPa7ents
Randomized,double-blindstudyinvolving43pa;entsinfectedwithHIVwhohaduninten;onalweightloss>5%overthe
previous3months
Received3gHMB+14gglutamine+14garginineperdayorplacebo(maltodextrin,isocaloric)for8weeks
WouldhavebeenbeertoalsohaveisonitrogenousplaceboOutcomevariables
Bodycomposi;onbyairdisplacementplethysmographyandskinfolds T-cellsubsets Changeinviralload
Resultsfollowonnextslide
ClarkRH,etal.JPENJParenterEnteralNutr.200024(3):133-139.45
OutcomesDuringSupplementa7onWithHMBand
7/29/2019 HMB 7 12 11
46/55
g pp
AminoAcidsinHIV-InfectedPa7ents
Bodycomposi;onimprovedinthesupplementa;ongroupcomparedwiththeplacebogroup Differencesweresignificantwithin8weeks
T-cellsubsets(CD3andCD5)werealsoincreasedsignificantlyinthesupplementa;ongroupcomparedwiththeplacebogroup
ViralloaddecreasedsignificantlywithHMB/Arg/Glutsupplementa;oncomparedwithplacebo
ReprintedwithpermissionfromClarkRH,etal.JPENJParenterEnteralNutr.200024(3):133-139.
aP=.009bP=.003
Placebo
HMB/Arg/Gln
5
4
-1
Cum
ulativeweightgain,kg
3
2
1
Start
0
4 weeks 8 weeks
a
PlaceboHMB/Arg/Gln
-1Cum
ulativeleangain,kg
3
2
1
Start
0
4 weeks 8 weeks
b
46
OtherPosi7veHMBStudiesinCachec7c-Prone
7/29/2019 HMB 7 12 11
47/55
Popula7ons
Studieswith3gHMB+14gglutamine14garginineperday Randomized,double-blindstudyinvolving32pa;entswithsolidtumors
whohaduninten;onalweightloss>5%1
ReceivedHMB/arginine/glutamine,orisonitrogenous,isocaloricplacebofor24weeks
By4weeks,gainsinbodyweightandfat-freemasswereobservedinthesupplementa;ongroupcomparedwiththeplacebogroup
At23weeks,posi;veeffectsfromthesupplementa;onweremaintained Randomized,blindedstudyinvolving100cri;callyilltraumapa;ents2
ReceivedHMG,HMB/arginine/glutamine,orisonitrogenous,isocaloricplacebofor28days
Aer7daysofsupplementa;on Nitrogenreten;onwassignificantlyimprovedinthesupplementedgroupscompared
withtheplacebogroup(P=.05)
Urinary3-methylhis;dine(indicatorofmuscleproteolysis)wasunaffectedbysupplementa;on
1.MayPE,etal.AmJSurg.2002183(4):471-479.2. KuhlsDA,etal.JTrauma.200762(1):125-132.
47
OtherPosi7veHMBStudiesinCachec7c-Prone
7/29/2019 HMB 7 12 11
48/55
Popula7ons
StudieswithHMBalone1,2 In34pa;entswithchronicobstruc;vepulmonarydiseasewhowererandomizedto
3g/dayHMBorcontrolfor7days,HMB-treatedpa;entshadimprovedindicatorsforinflamma;onandproteinbalancecomparedwiththecontrolgroup
In79bed-riddenelderlyadultswhowererandomizedto2g/dayHMBorcontrolfor14days,HMB-treatedadultshadreducedmuscleproteinbreakdowncomparedwith
thecontrolgroup
1.HsiehLC,etal.
AsiaPacJClinNutr.200615(4):544-550.2. HsiehLC,etal.AsiaPacJClinNutr.201019(2):200-208.
48
StudiesShowingNoEffectsofHMB/Arginine/Glutamine
7/29/2019 HMB 7 12 11
49/55
g g
Supplementa7on
Randomizedstudyinvolving40pa;entswithrheumatoidcachexia1 ReceivedHMB/arginine/glutamineorisocaloric,isonitrogenousplacebofor
12weeks
Similarimprovementsinbodycomposi;onandphysicalfunc;onwerereportedinbothgroups
Pa;entsreceivingsupplementa;onwerelesscachec;cvsotherstudies However,theMayPE,etal.studyhadhighdropoutrateduetoverysickpopula;on
Randomizedstudyinvolving30pa;entsundergoinglaparoscopicgastricbypasssurgery2 Received24gHMB/arginine/glutaminetwicedailyornosupplementa;on
post-opera;velyfor8weeks
Nodifferencesbetweengroupsinchangesofbodyweight,composi;on,orres;ngmetabolicrate
Noadverseeffectsonweightloss
1. MarcoraS,etal.ClinNutr.200524(3):442-454.2. ClementsRH,etal.SurgEndosc.201025(5):1376-1382.49
7/29/2019 HMB 7 12 11
50/55
-Hydroxy--Methylbutyrate(HMB)
50
HMB:Safety
7/29/2019 HMB 7 12 11
51/55
SafetyProfileofHMB:AnimalStudies
Variousanimalstudies(laboratoryandlivestockanimals)haveshownnoadverseeffectsevenathighdoses(upto4g/kg)1and
someposi;veeffects
Decreasedmortality(probablyduetoenhancedimmunity)2,3 Decreasedmuscleproteinbreakdown4 Improvedcarcassquality(morelean,lessfat)5
A90-daytoxicologystudyinratswithHMBat5%ofdiet(3.49g/kgformales,4.16g/kgforfemales)showedthatthisdosehadno
observedadverseeffects6
Thisincludedchangesinfoodconsump;onandbodyweight,aswellasclinicalchemistries,organweights,hematology,andmacro-andmicroscopic;ssueexamina;ons
1. PapetI,etal.BrJNutr.199777(6):885-896.2. NissenS,etal.PoultSci.199473(1):137-155.3. PetersonAL,etal.ImmunopharmImmunotox.199921(2):307-330.4. HolecekM,etal.FoodChemToxicol.200947(1):255-259.5.
VanKoeveringMT,etal.JAnimSci.199472(8):1927-1935.6. BaxterJH,etal.FoodChemToxicol.200543(12):1731-1741.
51
7/29/2019 HMB 7 12 11
52/55
SafetyProfileofHMB:HumanStudies
HMBhasbeenmarketedextensivelyasadietarysupplementsince1996withnopaernofadverseeventreports
Clinicalstudiesevalua;ngHMBorHMB+crea;nesupplementa;onforperiodsof3to8weekswithdosesupto6g/dayHMBhaveshown1-3 Noadversehematological,hepa;c,orrenaleffects Sometendencytodecreasetotalandlow-densitylipoprotein
cholesterol(5.8and7.3%,respec;vely)andreducesystolicbloodpressure(4.4mmHg)2
AlthoughHMBcanbeusedforcholesterolsynthesis,itappearsthatthecholesterolsynthesisislocalized(eg,muscle)anddoesnotadverselyaffectbloodcholesterollevels
Clinicalstudiesevalua;ngthecombina;onofHMB/Arginine/Glutamineinhealthyvolunteersandpa;entswithHIVorcancershowed4 Combina;onwassafe Improvementincertainhematologicalparameters
1. GallagherPM,etal.MedSciSportsExerc.200032(12):2116-2119.2. NissenS,etal.JNutr.2000130(8):1937-1945.3. CroweMJ,etal.IntJSportNutrExercMetab.200313(2):184-197.4. RathmacherJA,etal.JPENJParenterEnteralNutr.200428(2):65-75.
52
7/29/2019 HMB 7 12 11
53/55
Addi7onalInforma7onRegardingtheSafetyofHMB
NopublishedstudyhasreportedanyadverseeffectsofHMB However,someofthesestudiesdidnotreportadverseeventdataas
partofthedatapresented
ThereareverylimiteddatainhumansonHMBdosesupto6g/day
Notreatment-relatedadverseeventswerereportedMostHMBstudiesinhumanshavebeen8weeks
Therearesomedataoutto24weeksshowingsafetyDataonelderlyarelimited,butstudiesreviewedinthispresenta;oninbothhealthyandclinicalpopula;onshave
notreportedadverseevents
53
7/29/2019 HMB 7 12 11
54/55
HMBSummary
PrimarysourceofnaturalHMBiscatabolismoftheaminoacidleucine HMBs;mulatesmuscleproteinsynthesisandmayalso
Increasecellmembraneintegrityviacholesterolsynthesis Decreaseindicatorsofmuscledamage(crea;nekinaselevels) Beanan;catabolicagent
Clinicalresultsevalua;ngthebenefitsofHMBsupplementa;onaloneorwithothersupplementa;ononbodycomposi;onandstrengthhavebeen
mixed
Benefitsmaybereportedonceanop;malHMBdoseanddura;onthatcorrelateswithanathletessizeandtraininglevelisestablished
ClinicalresultssuggestthatHMBimproves Aerobicperformance Condi;onsassociatedwithlossofmusclemass Woundhealingcapacity
HMBhasbeenreportedtobesafeandwelltolerated Dataislimitedandfromshort-dura;onstudies
54
7/29/2019 HMB 7 12 11
55/55
2012 Abbott LaboratoriesThe EAS ACADEMY website and its content is owned by Abbott Nutrition, a division of AbbottLaboratories. All rights reserved.Any redistribution or reproduction of any part or all of the contents in any form is prohibited other than thefollowing:
1. you may print or download to a local hard disk extracts for your personal and non-commercial useonly;
2. you may copy the content to individual third parties for their personal use, but only if youacknowledge the website as the source of the material.
You may not, except with our express written permission, distribute or commercially exploit the content.
Nor may you transmit it or store it in any other website or other form of electronic retrieval system.