Aggressive diets and lipid responses

Aggressive Diets and Lipid ResponsesClaudia Panzer, MD and Caroline M. Apovian, MD*

Address*Boston University School of Medicine, Boston Medical Center, Section of Endocrinology: Nutrition and Weight Management Center, 88 East Newton Street, Suite D-614, Boston, MA 02118, USA. E-mail: [email protected]

Current Cardiology Reports 2004, 6:464–473Current Science Inc. ISSN 1523-3782Copyright © 2004 by Current Science Inc.

IntroductionThe prevalence of obesity is approaching epidemic propor-tions. Recent statistics from the Centers for Disease Controland Prevention (CDC) based on data from the NationalHealth and Nutrition Examination Survey (NHANES)1999–2000 indicate that 64% of the US population isoverweight (body mass index [BMI] > 25 kg/m2) or obese(BMI > 30 kg/m2) with 31% being overtly obese [1]. Poordiet and physical inactivity, the two major contributors tothe development of overweight and obesity, were identifiedby the CDC in March 2004 as the second most commonactual cause of death in the United States, accounting forapproximately 400,000 deaths in the year 2000 [2••].Only cigarette smoking accounted for more deaths in thisanalysis. Diet and exercise are the first-line treatmentoptions used in the fight against obesity. In the past decadea myriad of diets have surfaced and resurfaced. Many ofthese diets focus more on the composition of nutrientsrather than on caloric restriction. In the following reviewwe will evaluate the effects of several aggressive diets andtheir effects on lipids. The classic dyslipidemia of obesity,characterized by higher triglycerides, decreased high-

density lipoprotein (HDL) levels, and a change in low-density lipoprotein (LDL) composition with small denseLDL particles [3], can be observed in cross-sectional studiesof obese women [4,5] and men [6], and obese children [7].Each individual lipid factor is associated with an increasedcardiovascular risk in observational studies [8–10]. Fora more in depth discussion of this topic, please seeDr. Emma Meagher’s article in this issue (pp 457–463).

Popular Diets for Weight LossThe Behavioral Risk Factor Surveillance System, a random-digit telephone survey conducted in 1996 by state healthdepartments revealed that at any given time, approximately44% of women and 29% of men in the United Statesare trying to lose weight [11]. Even though major healthorganizations such as the American Heart Association urgeadults who are trying to lose weight to consume no morethan 30% of total daily calories from fat and less than 10%from saturated fat, the most popular diets do not meetthese criteria. In addition, despite the well-known fact thatonly a negative caloric balance can achieve weight loss,several popular diets are based on the postulate that themacronutrient composition of the diet plays an importantrole in weight loss. Probably the best-known example isthe high-fat, low-carbohydrate Atkins diet, which hasreceived a lot of media attention. Opponents of the Atkinsdiet fear that the focus on high fat and cholesterol willhave detrimental effects on lipid levels, and we review theevidence for these concerns. We also address the effectsof other very aggressive diets on weight loss and lipidlevels, such as the very low-fat Ornish diet and the protein-sparing modified fast (PSMF), a very low-calorie diet(VLCD) frequently used for urgent weight loss.

High-fat, high-protein, low-carbohydrate dietsDespite ongoing controversies regarding the efficacy, bene-fits, and consequences of these diets, low-carbohydratediets are probably among the most popular weightloss regimens. The most famous are the Atkins diet,the Carbohydrate Addicts Diet, Dr. Bernstein’s DiabetesSolution, Life Without Bread, Protein Power, the Zone, andSouth Beach diets. Atkins claimed that his lifetimenutritional philosophy has been embraced by an estimated20 million people worldwide since the release of Dr. Atkins’Diet Revolution in the 1970s, which was updated 20 yearslater as Dr. Atkins New Diet Revolution [12]. The Atkins planstrongly emphasizes a low-carbohydrate, ketogenic, and

Poor diet and physical inactivity, the two major contribu-tors to the development of overweight and obesity, have recently been identified as the second most common actual cause of death in the United States. With the increasing awareness of the strong link between obesity and chronic disease, in particular cardiovascular disease, a myriad of diets have surfaced and many of them claim weight loss depends more on the macronutrient composition of the diet than the number of calories consumed. Long-term outcome data, particularly cardiovascular outcome data, on these diets are sparse. This article summarizes previous and recent reports of popular and aggressive diets, such as low-carbohydrate diets, low-fat diets, and very low-calorie diets, addressing their effects on weight loss and focusing on their effects on lipids and lipoproteins.

Aggressive Diets and Lipid Responses • Panzer and Apovian 465

high-fat diet, and postulates that individuals on a high-fatdiet can lose more weight than on an isocaloric high-carbohydrate diet. The Atkins plan challenges the conten-tion that eating foods high in fat poses a health risk, andclaims that this would only be the case as long as refinedcarbohydrates were present. It is stated on Atkins’ webpage that controlling carbohydrates does not only resultin weight loss and body fat loss but can correct seriousmedical problems, such as diabetes, hypertension, andheart disease [12]. However, several professional organiza-tions, including the American Heart Association and theAmerican Dietetic Association have raised concerns aboutthe potential negative effects of high-fat, low-carbohydrate,high-protein diets on cardiovascular and bone health,renal and hepatic function, and on cancer risk, as they arealso low in fruits, vegetables, and dietary fiber [13,14]. Thelow-carbohydrate diets derive a large proportion of caloriesfrom fat, and there has been a major concern that thesediets would have detrimental effects on lipids and lipo-proteins. The intake of fat, particularly saturated fat,increases to 56% to 66% of total calories in the Atkins diet,which is about twice the 30% or less recommended bycurrent dietary guidelines. Observational data publishedseveral decades ago showed that the increased intakeof fat, particularly saturated fat, precedes an increase intotal plasma cholesterol and LDL cholesterol [15–17]. Incontrast, a systematic review of the efficacy and metaboliceffects of low-carbohydrate diets from interventionalstudies, synthesizing 107 studies of 94 diets, did not findany significant adverse effects on total, LDL, and HDLcholesterol and triglyceride levels [18].

Recent Randomized Controlled Trials Comparing Very Low-carbohydrate Diets with Reduced-fat DietsFour randomized controlled trials in adults, publishedwithin the past year, have compared the effects of very low-carbohydrate diets with reduced-fat diets on body weightand lipid levels in adults (Table 1).

Brehm et al. [19••] randomized 53 healthy, obesewomen (mean BMI = 34 kg/m2) to either 6 months of an adlibitum very low-carbohydrate diet (20 g carbohydrate/d)or a calorie-restricted diet with 30% of calories as fat, asrecommended by the American Heart Association [19••].The very low-carbohydrate group lost significantly moreweight and more body fat than the low-fat group despitea similar reduction in daily caloric intake in both groups(4.8 ± 0.67 kg vs 2.0 ± 0.75). At baseline mean plasmaconcentrations of total cholesterol, triglycerides, LDL choles-terol, and HDL cholesterol were normal in each of thegroups. Lipid profiles improved during the duration of thestudy, with significant decreases in total, LDL cholesterol,and triglycerides at 3 months and significant increasesin HDL cholesterol at 6 months. Plasma lipids did notdiffer between groups at the 3- and 6-month assessment.

Similarly, women in both groups lowered their (at baselinenormal) levels of blood pressure, glucose, and insulinwith no difference between the two groups at the 3- or 6-month assessments

Samaha et al. [20••] (Table 1) also compared a low-carbohydrate diet with 30 g of carbohydrates per day orfewer with a low-fat diet in accordance with the obesitymanagement guidelines of the National Heart, Lung, andBlood Institute, including caloric restriction to create adeficit of 500 cal/d with 30% or less of total calories from fat[20••]; 39% of the 132 severely obese individuals (meanBMI = 43 kg/m2) suffered from diabetes, and 43% met thecriteria for the metabolic syndrome. Only 60% of enrolleescompleted the study with no statistical difference in dropoutrates of both groups at 6 months. Participants on the low-carbohydrate diet, who completed the 6-month study, hadagain experienced significantly greater weight loss than thelow-fat group at 6 months, but the magnitude of the weightloss difference (about 4 kg) was small. Individuals on thelow-carbohydrate diet also had greater improvement intriglyceride levels, which was independent of the use or non-use of lipid-lowering medication. The amount of weight lossparalleled the improvement in triglyceride levels, andassignment to the low-carbohydrate diet group itself, afteradjustment for the differences in weight loss, predicted agreater decrease in triglyceride levels. Total cholesterol, HDLcholesterol, and LDL cholesterol, however, did not changeover the duration of the study within or between the groups.Another interesting finding was that serum glucosedecreased more in the low-carbohydrate group than in thelow-fat group, but only for diabetic subjects, and thatinsulin sensitivity, which was only measured in nondiabeticindividuals, improved only in the low-carbohydrate dietgroup and was independent of weight loss. An unansweredimportant question, however, is whether long-term low-carbohydrate diet effects extend beyond 6 months. In a 1-year follow-up study [21••] the small, but significant differ-ences in weight loss at 6 months (about 4 kg) had narrowedto 2 kg by 1 year and were no longer statistically significant.The low-carbohydrate group maintained most of the weightloss seen at 6 months, but the reduced-fat group continuedto lose weight throughout the whole year. The beneficialeffect on triglycerides already seen at 6 months persisted at 1year and triglycerides decreased significantly more in thelow-carbohydrate compared with the low-fat group. Again,assignment to the low-carbohydrate group and greaterweight loss were each independent predictors of a decreaseof triglyceride levels. Changes in total and LDL cholesterolwere not significantly different between the groups; how-ever, mean HDL levels decreased more in the low-fat group,a result that had not been present at 6 months. The differ-ence in mean HDL cholesterol levels remained significantafter adjustment for weight loss and baseline variables, sug-gestive of diet-related effects. Overall responses of glucoseand insulin sensitivity were similar in both groups at 1 year;however, in the small group of diabetics, glycemic control

466 Lipid Abnormalities

Tab

le 1

.R

ando

miz

ed c

ont

rolle

d tr

ials

co

mp

arin

g ve

ry lo

w-c

arbo

hyd

rate

die

ts w

ith

redu

ced-

fat

die

ts

Mea

n ch

ange

s in

lipi

ds a

nd li

popr

ote

ins:

ba

selin

ele

vels

to

end

of s

tudy

Stu

dyD

urat

ion,

m

oP

opu

lati

on

Mea

n B

MI,

kg

/m2

Inte

rven

tio

nC

ont

rol

Cha

nge

in T

C, %

Cha

nge

in L

DL

, %C

hang

e in

HD

L, %

Cha

nge

in T

G, %

Breh

m e

t al.

[19•

•]6

53 w

omen

34A

d lib

itum

LC

D

(<20

g C

/d)

Cal

orie

-res

tric

ted

55%

C, 3

0% F

, 15%

PLC

DC

ontr

ol-0

.4-0

.9-0

.7-5

.313 8.

4-2

3-1

.64

Fost

er e

t al.

[22

••]

1263

men

an

dw

omen

34A

d lib

itum

LC

D

Atk

ins

4 p

hase

sC

alor

ie-r

estr

icte

d 60

%C

, 25%

F, 1

5%P

LCD

Con

trol

-0.1

-2.9

0.31

-3.1

+ 1

1.0*

+ 1

.6*

- 17

.0*

+ 0

.7*

Sam

aha

et a

l. [2

0••]

613

2 m

en a

nd

wom

en; 3

9%

DM

2,49

% M

S

43A

d lib

itum

LC

D

(<30

g C

/d)

Cal

orie

-res

tric

ted

<30

% F

LCD

Con

trol

1.1

-0.5

4.4

2.5

0 -2.4

- 20

*-

4*

Ster

n et

al.

[21•

•]12

132

men

and

w

omen

; 39%

D

M2,

49%

MS

43A

d lib

itum

LC

D

(<30

g C

/d)

Cal

orie

-res

tric

ted

<30

% F

LCD

Con

trol

3.3

-4.1

6.25

-3.3

- 2.

4*-

12*

- 28

.9*

+ 2

.4*

Yan

cy e

t al.

[23•

]6

120

men

an

dw

omen

34

Ad

libitu

m L

CD

(<

20 g

/d)

+ d

aily

nu

triti

onal

su

pple

men

ts

Cal

orie

-res

tric

ted

<30

% F

, < 1

0%

satu

rate

d F,

<

300

mg

chol

este

rol

LCD

Con

trol

-3.3

-5.7

1 -5+

9.9

*-

3.0*

- 0.

5*-

14.6

*

*Den

otes

sig

nific

ant

P va

lue

for

the

diffe

renc

es b

etw

een

the

grou

ps.

BMI—

body

mas

s in

dex;

C—

carb

ohyd

rate

; DM

2—ty

pe 2

dia

bete

s m

ellit

us; F

—fa

t; H

DL—

high

-den

sity

lipo

prot

ein;

LC

D—

low

-cal

orie

die

t; LD

L—lo

w-d

ensi

ty li

popr

otei

n; M

S—m

etab

olic

syn

drom

e;

P—pr

otei

n; T

C—

tota

l cho

lest

erol

; TG

—tr

igly

ceri

des.


improved more in the low-carbohydrate diet group, evenafter adjustment for weight loss. Limitations of this studyagain were an overall high dropout rate of 34% and inabilityof most people to reach their dietary targets of less than 30 gof carbohydrate per day in the low-carbohydrate group orreduction of 500 kcal/d in the conventional group.

Very similar effects on blood lipid levels were seen byFoster et al. [22••] (Table 1) in another 1-year, randomizedcontrolled trial of 63 obese men and women (mean BMI34 kg/m2) assigned to either the Atkins diet or a low-calorie, high-carbohydrate, reduced-fat diet. Similar to theresults of Samaha et al. [20••] and Stern et al. [21••],individuals on the low-carbohydrate diet lost significantlymore weight at 3 and 6 months, but the weight loss differ-ence was rather small (about 4 kg) and was no longersignificant at 12 months due to weight regain. Dropoutrates in both diet groups were approximately 40% at 1year. Again similar to the results of Samaha et al. [20••],triglycerides improved significantly more in the low-carbohydrate diet group compared with the low-fatgroup, with no significant differences between groups intotal or LDL cholesterol levels over the long-term. Only atmonth 3 were LDL cholesterol values lower in the low-fatgroup with an increase in LDL cholesterol in the low-carbohydrate group, so that the differences between thegroups were significant. The authors suggested thatincreased weight loss with the low-carbohydrate diet mighthave offset the negative effects of saturated fat intake onserum LDL cholesterol concentrations [22••]. Similar tothe longer-term effects seen in the Stern et al. [21••] andSamaha et al. [20••] trials the low-carbohydrate diet wasagain associated with greater increases in HDL cholesterol(18% vs 3% at 12 months) throughout most of the study.

A fourth study comparing the Atkins diet with anAmerican Heart Association diet is a 6-month study byYancy et al. [23•] (Table 1) funded by the nonprofit AtkinsFoundation, which randomized 120 overweight, hyper-lipidemic individuals to either a low-carbohydrate diet withless than 20 g of carbohydrates daily plus nutritional supple-mentation, or a reduced-fat diet with less than 30% of energyfrom fat, less than 300 mg of cholesterol daily, and a deficitof 500 to 1000 kcal/d. After 6 months, the low-carbohydrategroup lost significantly more weight than the low-fat group:12 kg versus 6.5 kg. Similar to all previously discussedstudies, the Atkins diet resulted in greater decreases in serumtriglyceride levels (-74 mg/dL vs -28 mg/dL), greater increasesin HDL cholesterol levels (5.5 mg/dL vs -1.6 mg/dL), andLDL levels that did not differ between groups. The recipientsof the low-carbohydrate diet in the study by Yancy et al. [23•]also received nutritional supplements with essential oils,such as flaxseed oil, borage seed oil, and fish oil. Thesesupplements contain large amounts of omega-3 and omega-6 fatty acids, which are known to be inversely associated withtriglyceride levels (omega-6) [24], and have been shown toreduce triglyceride levels by 18% to 35% (omega-3) [25,26].Capsules of omega-3 fatty acids are used for treatment of

hypertriglyceridemia [27]. Fish oil alone or the combinationof fish oil and borage seed oil, were found to lower triglycer-ide levels by 35% in healthy women [28]. The same studydemonstrated an increase of HDL cholesterol with either fishoil alone or in combination with borage seed oil [28].

Summary of Recent Randomized Controlled Trials Comparing Very Low-carbohydrate Diets with Low-fat DietsEffects on blood lipid levelsThe low-carbohydrate diets in all four studies had similareffects on blood lipid levels (Table 1). They decreased fast-ing triglyceride levels, increased HDL cholesterol slightly,and had no, or only small, effects on LDL cholesterol. Thelower triglyceride levels with the low-carbohydrate dietcannot solely be explained by weight loss, as weight lossdifferences were only modest in most studies. Reducedcarbohydrate intake leading to ketogenesis is generallyassociated with a decrease in triglyceride levels [29,30]. Inaddition, high-fat diets significantly increase postheparinplasma and skeletal muscle lipoprotein lipase activity,leading to increased triglyceride removal [31,32]. Anotherexplanation for the greater improvement in triglyceridelevels on the low-carbohydrate diet might be found in theindividual fatty acid classes consumed; however, most ofthe studies do not provide such information. Saturatedfatty acids in general elevate triglycerides to a modestdegree, but polyunsaturated fatty acids can actually reducethem similarly [27]. Larger effects on triglycerides can beseen with the consumption of large amounts of omega-3fatty acids, mainly found in the fat tissue of cold water fish[27] or in flaxseed. The changes in HDL cholesterol canpartially be explained by weight loss, as weight loss in andof itself can increase HDL cholesterol; however, the effectsseen in the studies are greater than what can be expectedfrom weight loss alone [22••,33]. The macronutrientcomposition of the diet plays an important role here, as allfatty acids, when substituted for carbohydrates, increaseHDL cholesterol with the most potent effect resulting fromsaturated fatty acids [27,34]. The suspected mechanismbehind the HDL elevation is an alteration in HDL sub-fractions, with increased apolipoprotein (Apo)AΙ secre-tion from the liver, intestine or both, which is morestimulated by saturated fatty acids than by polyunsaturatedfats [27]. It is unclear, however, if this elevation in HDLtranslates to a decrease in cardiovascular risk [35]. To whatextent low-carbohydrate diets affect highly atherogenicdyslipidemia, such as postprandial hypertriglyceridemia[36,37], LDL particle size [37], and LDL oxidation [38,39]was recently evaluated in normal-weight and normo-lipidemic young men [40]. Over 6 weeks, individualsconsumed a diet consisting of 8% carbohydrates, 60%fat and 30% protein. Similar to the above mentionedstudies, significant reductions in fasting triglycerides werenoted (-33%) as well as significant increases in HDL


cholesterol, which could not be fully explained by therelatively small weight loss of 2.2 kg. LDL particle sizeincreased and there was no change in fasting total and LDLcholesterol and oxidative LDL concentrations. Surprisingly,even postprandial hypertriglyceridemia and fasting insulinconcentrations improved after 6 weeks of the high-fat diet.This is in contrast to the vast evidence that high-fat mealscreate postprandial hyperlipidemia [41], so that a pro-longed high-fat diet would result in a highly atherogenicstate independent of alteration in lipids and lipoproteins.For example, postprandial lipemia or infusion of free fattyacids has been shown to cause impaired vasodilatation[42,43] and to be linked to increased oxidant stress andinflammation [44,45]. Therefore, it is important to designfuture studies to be able to evaluate if low-carbohydratediets not only show continued improvement in dyslipid-emia, but also have more favorable outcomes on the devel-opment of cardiovascular disease and diabetes.

Very low-fat dietsVery low-fat (VLF) diets are very low in fat, very high incarbohydrates, and moderate in protein. The best-knownproponents of the VLF diets are Dean Ornish and Nathanand Robert Pritikin. Their diets have historically been advo-cated for improving cardiovascular risk profiles, and pre-venting heart disease [46••]. The Ornish diet is vegetarian,low in fat and saturated fat (< 13% of calories), very highin carbohydrates (81% of calories), and very high in fiber(38 g). The Pritikin diet limits the amount of low-fat animalprotein to no more than 3.5 oz/d. Both programs promotelifestyle changes including exercise and behavior modifica-tion. Dean Ornish’s proclamation “eat more, weigh less”[47] is not an invitation to eat more calories, but the recom-mendation to go from simple carbohydrates to complex,denser carbohydrates, which are richer in fiber, such asbrown rice, fruits, vegetables, whole grains, and legumes.Many studies have shown that overweight subjects consum-ing a low-fat, high-carbohydrate ad libitum diet eat fewercalories, lose weight, and lose body fat [46••,48,49]. Verylow-fat diets were initially recommended to prevent orreverse heart disease, based on the relationship of dietaryfat intake and cardiovascular disease. Even though there areno definitive clinical trials of the effects of low-fat diets oncardiovascular events, several studies have investigatedchanges in serum lipoprotein and coronary angiographicfindings in response to these diets. The Ornish MulticenterProject (Table 2) enrolled a total of 333 patients withangiographically documented coronary artery diseasesevere enough to warrant revascularization [50••]. Inter-ventions in the experimental group included a very low-fatdiet (< 10% of fat, a whole foods vegetarian diet high incomplex carbohydrates and low in simple sugars), moder-ate exercise, stress management techniques, and psycho-logic support. Even though the program lasted only for1 year, significant changes were observed in total and LDLcholesterol over the duration of 3 years. Total cholesterol

decreased from a mean of 202 mg/dL to 183 mg/dL,LDL cholesterol decreased from a mean of 123 mg/dL to102 mg/dL after 3 years, and the long-term reduction inweight was approximately 8 lbs after 3 years. This trialincluded diet and exercise. Lipid-lowering medicationswere taken by 54% of the experimental group patients.The interplay between diet, exercise, and lipids was alsoaddressed by Barnard et al. [51] (Table 2) who demon-strated that a very low-fat, high complex-carbohydrate dietused in patients on lipid-lowering therapy achieved animpressive reduction in total and LDL cholesterol of anadditional 19% and 20%, respectively, beyond the effects oflipid-lowering medication [51]. One main criticism of thevery low-fat diets is that adherence may be low and weightloss and effects on lipids therefore short-lived. However, theLifestyle Heart Trial of intensive lifestyle changes (10% fat,whole foods vegetarian diet, aerobic exercise, stress man-agement, smoking cessation, group psychosocial support)showed a 40% reduction in LDL cholesterol at 1 year thatremained 20% below baseline at 5 years (Table 2). Individ-uals in the experimental group lost an average of 24 lbs inthe first year and maintained a weight loss of 13 lbs at5 years, whereas the weight in the control group changedlittle from baseline. Another criticism of VLF diets is theirtendency to increase triglyceride levels [27,34,52], as thecarbohydrate consumption on low-fat diets can be ashigh as 70% to 80% of daily calories. Higher triglyceridelevels are frequently associated with lower HDL cholesterollevels, higher total cholesterol (TC)/HDL ratios, andsmaller, denser LDL particles, which raises concerns abouttheir effects on cardiovascular disease [53]. The effects ontriglyceride levels, however, only seem to occur with anisoenergetic diet and only in the short-term. Schaefer et al.[54], for example, reported that consumption of a low-fat diet under weight maintenance conditions had signifi-cant lowering effects on plasma TC, LDL, and HDL levelswith a significant increase in plasma triglyceride andthe TC/HDL ratio [54] (Table 2). A low-fat at libitum diet,however, accompanied by significant weight loss of3.6 kg, did not promote adverse effects on triglyceride andTC/HDL ratio [54].

Kasim-Karakas et al. [55] examined the effects of iso-energetic as well as ad libitum dietary fat restriction dietson plasma lipoproteins in healthy women (Table 2) [55].In the controlled isoenergetic phase dietary fat was reducedfrom 35% to 25% to 15% over 4 months. Thereafter,individuals were switched to an ad libitum 15% fat dietfor 8 months, during which they lost a mean of 4.6 kg.Triglyceride levels increased during the initial isoenergeticlow-fat phase of the diet and returned to baseline levelsduring the ad libitum low-fat phase. HDL cholesteroldecreased during both phases of the diet.

Aside from duration and the energy level of theconsumed diet, the type of carbohydrates consumed seemsto be another important factor contributing to the hyper-triglyceridemia seen with low-fat, high-carbohydrate diets.


Tab

le 2

.E

ffec

ts o

f ver

y lo

w-f

at d

iets

on

lipid

s an

d lip

opr

ote

ins

Mea

n ch

ange

s in

lipi

ds a

nd li

popr

ote

ins:

ba

selin

e le

vels

to

end

of s

tudy

Stu

dyD

urat

ion,

m

oP

opu

lati

on

Mea

n B

MI,

kg

/m2

Inte

rven

tio

nC

ont

rol

Cha

nge

in T

C, %

Cha

nge

in L

DL

, %C

hang

e in

HD

L, %

Cha

nge

in T

G, %

Car

dio

vasc

ular

o

utco

me

Life

styl

e H

eart

T

rial

[80

]12

48, m

ainl

y m

en w

ith

CA

D

28Lo

w-fa

t ve

g.

diet

,aer

obic

ex

erci

se, s

tres

s m

anag

emen

t

Usu

al c

are

Orn

ish

Con

trol

-24 -5

-37 -6

-3 -322 -9

Life

styl

e H

eart

T

rial

[61

]60

35, m

ainl

y m

en w

ith

CA

D

28Lo

w-fa

t ve

g.

diet

,aer

obic

ex

erci

se, s

tres

s m

anag

emen

t

Usu

al c

are

Orn

ish

-17

-20

-13

4C

ardi

ac e

vent

s:

25 (

see

text

)

Con

trol

-13

-20

-6-5

Car

diac

eve

nts

45/ R

R fo

r an

y ev

ent:

2.47

Mul

ticen

ter

Life

styl

e D

emon

stra

tion

Proj

ect

[50•

•]

3633

3, m

ainl

y m

en w

ith

CA

D

NA

Low

-fat

veg.

di

et,a

erob

ic

exer

cise

, str

ess

man

agem

ent

PTC

A/

CA

BGO

rnis

hC

ontr

ol-9

No

data

av

aila

ble

-17

15-1

3N

o C

ABG

/ PT

CA

in 7

7%

Barn

ard

etal

.[51

]1–

3 w

eeks

39 m

en a

nd

wom

en

alre

ady

onst

atin

s

Die

t <

10%

fat,

aero

bic

exer

cise

Non

e-1

9-2

0-1

1-2

9

Scha

efer

et

al.[

54]

627

men

an

dw

omen

26Is

oene

rget

ic lo

w-

fat

diet

follo

wed

by

low

-fat

ad

libitu

m d

iet

Non

eIs

oene

rget

ic

low

-fat

diet

-12.

5*-

17.1

*-

22.8

*+

47*

Low

-fat

ad

libitu

m d

iet;

mea

n w

eigh

t lo

ss 3

.6 k

g

-18.

9*-

24.3

*-

19.7

*10

.9

Kas

im-K

arak

as

etal

. [55

]12

64 h

ealth

y w

omen

Isoe

nerg

etic

lo

w-fa

t di

et

from

35%

to 1

5%

follo

wed

by

15%

ad

libi

tum

die

t

Non

eIs

oene

rget

ic

low

-fat

diet

fr

om 3

5%

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Hypertriglyceridemia is less pronounced if oligo- andpolysaccharides, rather than monosaccharides, particularlyfructose, are consumed [56]. Also fiber-rich low-fat diets,in which the carbohydrates are derived from unprocessed,whole grains (legumes, fruit, vegetable and grains) are lesslikely to result in hypertriglyceridemia [56].

Another criticism of VLF diets is that HDL cholesterollevels are lowered more than LDL cholesterol, raisingconcerns about their safety for cardiovascular disease [57].The proposed mechanism for HDL cholesterol lowering isan increased fractional clearance of ApoAI [27], the majorprotein of HDL cholesterol, decreased ApoAI productionand decreased hepatic ApoAI mRNA expression [58••].It is unclear, however, if a physiologic reduction of HDLwith a low-fat diet confers the same risk of cardiovasculardisease as the low HDL levels that are seen in individualswith the metabolic syndrome. Populations in which low-fat diets are the norm do not have an increased cardio-vascular risk despite low HDL cholesterol [59,60]. Long-term trials of low-fat diets show variable results forHDL cholesterol and triglyceride levels. In the OrnishMulticenter Project [50••], HDL cholesterol levels initiallydecreased from 37 to 33 mg/dL after 3 months of inter-vention, but increased to 42 mg/dL after 3 years. Triglycer-ides initially increased nonsignificantly from 230 mg/dL to236 mg/dL after 3 months, but stabilized to 201 after3 years. Dietary fat intake was 6.5% after 3 months and8.3% at 3 years, based on results of 3-day diet diaries(Table 2). The Lifestyle Heart Trial [61] did not find anychanges in ApoAI at 1 and 5 years. Triglycerides increasedat 1 year, but had come close to baseline at 5 years. HDLlevels decreased significantly from 40 mg/dL at baseline to36 mg/dL at 1 year and 35 mg/dL at 5 years (Table 2).

Do very low-fat diets reverse heart disease?The Lifestyle Heart Trial [61] randomized 48 patientswith moderate to severe coronary heart disease to an inten-sive lifestyle group (10% fat whole foods vegetarian diet,aerobic exercise, stress management training, smokingcessation, group psychosocial support) or to usual care for5 years to assess the effects of these lifestyle changes on theprogression of coronary heart disease. A 91% and 72%reduction in frequency of angina was reported after 1 yearand 5 years, respectively. Thirty-five patients completedthe 5-year follow-up quantitative coronary arteriography.In the experimental group, the average percent diameterstenosis at baseline decreased by 1.75 absolute percentagepoints after 1 year and by 3.1 absolute percentage pointsafter 5 years, whereas an increase by 11.8 percentage pointswas seen after 5 years in the control group [61,62]. Cardiacpositron-emission tomography (PET) demonstratedsignificant improvement in size and severity of perfusionabnormalities in resting dipyridamole PET scans [63].These findings translated to significant fewer cardiac eventsin the experimental group with a risk ratio of 2.47 for anyevent in the control group [61]. The regression of coronary

atherosclerosis seen in this trial, however, cannot solely beattributed to the low-fat diet as the Lifestyle Heart Programalso included aerobic exercise and stress management.Many trials have shown a favorable effect of exercise oncardiovascular events above and beyond alterations in thetraditional risk factors [64]. Animal experiments havedemonstrated that moderate treadmill exercise in monkeyseven on an atherogenic diet led to a substantial reductionin the severity of atherosclerosis compared to nonexercis-ing monkeys [65]. In summary, it is unclear to what extentthe reduction in atherosclerosis was due to the VLF diet.The Ornish program is used as a multidisciplinary regimenand includes a diet low in fat, but also high in vegetables,fruits, and high-fiber grains, moderate exercise, significantweight loss, and stress reduction. Medicare is now offeringthe Lifestyle Modification Program Demonstration to 1800selected Medicare patients with severe coronary arterydisease to determine if a comprehensive lifestyle programis a cost-effective alternative to more traditional medicaltreatments [66].

Very low-calorie dietsVery low-calorie diets (VLCDs) are defined as hypocaloricdiets with energy levels less than 800 kcal/d, or less than12 kcal/kg of ideal body weight per day [67]. These dietsusually provide less than half on an individual’s energyand are used when rapid weight loss is required for surgeryor when health risks of obesity are particularly severe. Theadvantages of the VLCDs include rapid improvement inblood pressure, especially in the first week, and bloodglucose, with the ability to discontinue oral hypoglycemicagents and insulin doses under 50 units/d [68,69]. VLCDsare ketogenic, low in fat, and relatively high in protein.Two major forms of physician-monitored VLCDs arecurrently in use: one is a commercial preparation of“weight loss shakes” that contain 70 to 100 g of protein,50 to 100 g of carbohydrates, and up to 15 g fat per dayplus vitamins and minerals [68]. The other VLCD regimenis also referred to as the protein-sparing modified fast,based on lean meat, fish or poultry, egg whites, and low-fatcheese, plus supplements of potassium chloride and multi-vitamins [68]. These diets are generally considered safefor short and longer-term term dieting (12–16 weeks)with physician monitoring. Side effects include fatigue,muscle cramps, nausea, and coldness and an increased riskof gallstones [68].

Effects of very low-calorie diets on the lipid profileNumerous studies have documented favorable effects ofVLCDs on lipid profiles. Total serum cholesterol and LDLcholesterol levels decrease by about 5% to 35% [70–75]in the first 2 to 8 weeks of VLCDs. The percent decreasein total cholesterol was positively correlated with thepercent of weight loss in some [75], but not all studies[70]. Similarly, triglyceride levels decrease between 14%and 58% in the short-term [71–73,76,77]. HDL cholesterol


responses are not that uniform: several studies docu-mented a decrease of HDL cholesterol levels [70,73,76–79]when lipid profiles were measured within the first 2 to8 weeks of VLCDs. Others report increases in HDL choles-terol, but in these studies lipid profiles were measuredlater, at about 3 to 12 months into the VLCD program[72,74,79]. HDL cholesterol responses appear to be bipha-sic. Levels initially decrease with VLCDs, but later increasewith long-term weight reduction. In addition, most reportswith early lowering of HDL cholesterol resulted in animproved or stable HDL cholesterol/TC ratio because ofgreater LDL cholesterol lowering [70,73,76].

ConclusionsDiets are more prevalent than ever and there has beenresurgent interest in the low-carbohydrate, high-fat diets,such as the Atkins diet. Several randomized controlledweight loss trials have now shown that these diets are safein weight loss trials of 6 and 12 months. However, cautionis still needed before low-carbohydrate high-fat diets canbe generally recommended, as long-term lipid effectsbeyond 1 year are unknown, and other risks for bonehealth, renal and hepatic function, and cancer risk exist.Also, this diet is far from showing impressive weight loss:weight loss at 1 year was rather minimal (2 kg at 1 year).Longer-term data are available for the low-fat, high-carbo-hydrate diet by Dean Ornish, who demonstrated in severalclinical trials not only significant weight loss, but also areduced cardiovascular risk, despite the diet’s potentialnegative effects on triglyceride and HDL levels seen inshort-term use.

References and Recommended ReadingPapers of particular interest, published recently, have been highlighted as:• Of importance•• Of major importance

1. Healthy Weight, Overweight, and Obesity among U.S. adults. Accessible at http:/www.cdc.gov/nchs.data/nhanes/databriefs/adultweight/pdf

2.•• Mokdad AH, Marks JS, Stroup DF, et al.: Actual causes of death in the United States, 2000. JAMA 2004, 291:1238–1245.

Analysis of epidemiologic, clinical, and laboratory studies on risk behaviors and mortality identifying poor diet and physical activity as the second leading cause of death in 2000.

3. Howard BV, Ruotolo G, Robbins DC: Obesity and dyslipidemia. Endocrinol Metab Clin North Am 2003, 32:855–867.

4. Denke MA, Sempos CT, Grundy SM: Excess body weight. An under-recognized contributor to dyslipidemia in white American women. Arch Intern Med 1994, 154:401–410.

5. Despres JP, Moorjani S, Ferland M, et al.: Adipose tissue distri-bution and plasma lipoprotein levels in obese women. Importance of intra-abdominal fat. Arteriosclerosis 1989, 9:203–210.

6. Denke MA, Sempos CT, Grundy SM: Excess body weight. An underrecognized contributor to high blood cholesterol levels in white American men. Arch Intern Med 1993, 153:1093–1103.

7. Zwiauer KF, Pakosta R, Mueller T, et al.: Cardiovascular risk factors in obese children in relation to weight and body fat distribution. J Am Coll Nutr 1992, 11(Suppl):41S–50S.

8. Hokanson JE, Austin MA: Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk 1996, 3:213–219.

9. Castelli WP: Cardiovascular disease and multifactorial risk: challenge of the 1980s. Am Heart J 1983, 106:1191–1200.

10. Coresh J, Kwiterovich PO Jr.: Small, dense low-density lipo-protein particles and coronary heart disease risk: A clear association with uncertain implications. JAMA 1996, 276:914–915.

11. Serdula MK, Mokdad AH, Williamson DF, et al.: Prevalence of attempting weight loss and strategies for controlling weight. JAMA 1999, 282:1353–1358.

12. If you want to change your life Atkins can help. Available at http:/www.atkins.com

13. St Jeor ST, Howard BV, Prewitt TE, et al.: Dietary protein and weight reduction: a statement for healthcare professionals from the Nutrition Committee of the Council on Nutrition, Physical Activity, and Metabolism of the American Heart Association. Circulation 2001, 104:1869–1874.

14. American Heart Association statement on high-protein, low-carbohydrate diet study. Presented at the 75th annual AHA scientific sessions. Chicago, IL; November 17–20, 2002.

15. Hegsted DM, McGandy RB, Myers ML, et al.: Quantitative effects of dietary fat on serum cholesterol in man. Am J Clin Nutr 1965, 17:281–295.

16. Keys A: Effects of different dietary fats on plasma-lipid levels. Lancet 1965, 17:318–319.

17. Mensink RP, Katan MB: Effect of dietary fatty acids on serum lipids and lipoproteins. A meta-analysis of 27 trials. Arterio-scler Thromb 1992, 12:911–919.

18. Bravata DM, Sanders L, Huang J, et al.: Efficacy and safety of low-carbohydrate diets: a systematic review. JAMA 2003, 289:1837–1850.

19.•• Brehm BJ, Seeley RJ, Daniels SR, et al.: A randomized trial com-paring a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. J Clin Endocrinol Metab 2003, 88:1617–1623.

Randomized controlled trial to determine the effects of a very low-carbohydrate diet on body composition and cardiovascular risk factor in healthy women.20.•• Samaha FF, Iqbal N, Seshadri P, et al.: A low-carbohydrate as

compared with a low-fat diet in severe obesity. N Engl J Med 2003, 348:2074–2081.

Randomized controlled trial over the duration of 6 months to compare the effects of a low-carbohydrate diet with a low-fat diet on weight loss and cardiovascular risk factors in severely obese subjects with a high prevalence of diabetes and the metabolic syndrome.21.•• Stern L, Iqbal N, Seshadri P, et al.: The effects of low-carbohydrate

versus conventional weight loss diets in severely obese adults: one-year follow-up of a randomized trial. Ann Intern Med 2004, 140:778–785.

A 12-month update of the previous report on a randomized controlled trial to compare the effects of a low-carbohydrate diet with a low-fat diet on weight loss and cardiovascular risk factors in severely obese sub-jects with a high prevalence of diabetes and the metabolic syndrome.22.•• Foster GD, Wyatt HR, Hill JO, et al.: A randomized trial of

a low-carbohydrate diet for obesity. N Engl J Med 2003, 348:2082–2090.

One-year randomized trial comparing the effects of a low-carbohydrate diet with a low-fat diet on weight loss and cardiovascular risk factors.23.• Yancy WS, Jr., Olsen MK, Guyton JR, et al.: A low-carbohydrate,

ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: a randomized, controlled trial. Ann Intern Med 2004, 140:769–777.

Randomized controlled trial over 6 months comparing the effects of a low-carbohydrate diet with a low-fat diet on weight loss and cardio-vascular risk factors


24. Djousse L, Hunt SC, Arnett DK, et al.: Dietary linolenic acid is inversely associated with plasma triacylglycerol: the National Heart, Lung, and Blood Institute Family Heart Study. Am J Clin Nutr 2003, 78:1098–1102.

25. Harris WS: n-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr 1997, 65:1645S–1654S.

26. Harris WS, Lu G, Rambjor GS, et al.: Influence of n-3 fatty acid supplementation on the endogenous activities of plasma lipases. Am J Clin Nutr 1997, 66:254–260.

27. Ginsberg HN, Karmally W: Nutrition and Lipids. Philadelphia: American College of Physicians-American Society of Internal Medicine; 1999.

28. Laidlaw M, Holub BJ: Effects of supplementation with fish oil-derived n-3 fatty acids and gamma-linolenic acid on circulating plasma lipids and fatty acid profiles in women. Am J Clin Nutr 2003, 77:37–42.

29. Lewis SB, Wallin JD, Kane JP, et al.: Effect of diet composition on metabolic adaptations to hypocaloric nutrition: compari-son of high carbohydrate and high fat isocaloric diets. Am J Clin Nutr 1977, 30:160–170.

30. Golay A, Allaz AF, Morel Y, et al.: Similar weight loss with low- or high-carbohydrate diets. Am J Clin Nutr 1996, 63:174–178.

31. Campos H, Dreon DM, Krauss RM: Associations of hepatic and lipoprotein lipase activities with changes in dietary composition and low density lipoprotein subclasses. J Lipid Res 1995, 36:462–472.

32. Kiens B, Essen-Gustavsson B, Gad P, et al.: Lipoprotein lipase activity and intramuscular triglyceride stores after long-term high-fat and high-carbohydrate diets in physically trained men. Clin Physiol 1987, 7:1–9.

33. Dattilo AM, Kris-Etherton PM: Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis. Am J Clin Nutr 1992, 56:320–328.

34. Mensink RP, Katan MB: Effect of monounsaturated fatty acids versus complex carbohydrates on high-density lipoproteins in healthy men and women. Lancet 1987, 1:122–125.

35. Anderson JW, Konz EC, Jenkins DJ: Health advantages and disadvantages of weight-reducing diets: a computer analysis and critical review. J Am Coll Nutr 2000, 19:578–590.

36. Patsch JR, Miesenbock G, Hopferwieser T, et al.: Relation of triglyceride metabolism and coronary artery disease. Studies in the postprandial state. Arterioscler Thromb 1992, 12:1336–1345.

37. Stampfer MJ, Krauss RM, Ma J, et al.: A prospective study of triglyceride level, low-density lipoprotein particle diameter, and risk of myocardial infarction. JAMA 1996, 276:882–888.

38. Witztum JL, Steinberg D: The oxidative modification hypo-thesis of atherosclerosis: does it hold for humans?. Trends Cardiovasc Med 2001, 11:93–102.

39. Holvoet P, Vanhaecke J, Janssens S, et al.: Oxidized LDL and malondialdehyde-modified LDL in patients with acute coronary syndromes and stable coronary artery disease. Circulation 1998, 98:1487–1494.

40. Sharman MJ, Kraemer WJ, Love DM, et al.: A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men. J Nutr 2002, 132:1879–1885.

41. Bergeron N, Havel RJ: Assessment of postprandial lipemia: nutritional influences. Curr Opin Lipidol 1997, 8:43–52.

42. Gaenzer H, Sturm W, Neumayr G, et al.: Pronounced post-prandial lipemia impairs endothelium-dependent dilation of the brachial artery in men. Cardiovasc Res 2001, 52:509–516.

43. Steinberg HO, Paradisi G, Hook G, et al.: Free fatty acid eleva-tion impairs insulin-mediated vasodilation and nitric oxide production. Diabetes 2000, 49:1231–1238.

44. Inoguchi T, Li P, Umeda F, et al.: High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C--dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes 2000, 49:1939–1945.

45. van Oostrom AJ, Sijmonsma TP, Verseyden C, et al.: Postprandial recruitment of neutrophils may contribute to endothelial dysfunction. J Lipid Res 2003, 44:576–583.

46.•• Freedman MR, King J, Kennedy E: Popular diets: a scientific review. Obes Res 2001, 9(Suppl 1):1S–40S.

Excellent extensive review on the effectiveness of popular diets on weight loss and other health outcomes.47. Dean Ornish's MD Lifestyle Program. Available at http:/

www.ornish.com48. Mueller-Cunningham WM, Quintana R, Kasim-Karakas SE:

An ad libitum, very low-fat diet results in weight loss and changes in nutrient intakes in postmenopausal women. J Am Diet Assoc 2003, 103:1600–1606.

49. Hays NP, Starling RD, Liu X, et al.: Effects of an ad libitum low-fat, high-carbohydrate diet on body weight, body composition, and fat distribution in older men and women: a randomized controlled trial. Arch Intern Med 2004, 164:210–217.

50.•• Ornish D: Avoiding revascularization with lifestyle changes: the Multicenter Lifestyle Demonstration Project. Am J Cardiol 1998, 82:72T–76T.

Multicenter project demonstrating that patients with severe coronary artery disease were able to avoid revascularization by making compre-hensive lifestyle changes.51. Barnard RJ, DiLauro SC, Inkeles SB: Effects of intensive diet

and exercise intervention in patients taking cholesterol-lowering drugs. Am J Cardiol 1997, 79:1112–1114.

52. Grundy SM: Comparison of monounsaturated fatty acids and carbohydrates for lowering plasma cholesterol. N Engl J Med 1986, 314:745–748.

53. Lichtenstein AH, Van Horn L: Very low fat diets. Circulation 1998, 98:935–939.

54. Schaefer EJ, Lichtenstein AH, Lamon-Fava S, et al.: Body weight and low-density lipoprotein cholesterol changes after consumption of a low-fat ad libitum diet. JAMA 1995, 274:1450–1455.

55. Kasim-Karakas SE, Almario RU, Mueller WM, et al.: Changes in plasma lipoproteins during low-fat, high-carbohydrate diets: effects of energy intake. Am J Clin Nutr 2000, 71:1439–1447.

56. Parks EJ, Hellerstein MK: Carbohydrate-induced hypertriacyl-glycerolemia: historical perspective and review of biological mechanisms. Am J Clin Nutr 2000, 71:412–433.

57. Sacks FM, Katan M: Randomized clinical trials on the effects of dietary fat and carbohydrate on plasma lipoproteins and cardiovascular disease. Am J Med 2002, 113(Suppl 9B):13S–24S.

58.•• Schaefer EJ: Lipoproteins, nutrition, and heart disease. Am J Clin Nutr 2002, 75:191–212.

Excellent review on the current knowledge of lipoproteins, nutrition, and coronary heart disease.59. Connor WE, Cerqueira MT, Connor RW, et al.: The plasma

lipids, lipoproteins, and diet of the Tarahumara indians of Mexico. Am J Clin Nutr 1978, 31:1131–1142.

60. Knuiman JT, West CE, Burema J: Serum total and high density lipoprotein cholesterol concentrations and body mass index in adult men from 13 countries. Am J Epidemiol 1982, 116:631–642.

61. Ornish D, Scherwitz LW, Billings JH, et al.: Intensive lifestyle changes for reversal of coronary heart disease. JAMA 1998, 280:2001–2007.

62. Gould KL, Ornish D, Kirkeeide R, et al.: Improved stenosis geo-metry by quantitative coronary arteriography after vigorous risk factor modification. Am J Cardiol 1992, 69:845–853.

63. Gould KL, Ornish D, Scherwitz L, et al.: Changes in myocardial perfusion abnormalities by positron emission tomography after long-term, intense risk factor modification. Jama 1995, 274:894–901.

64. Skerrett PJ, Manson JE: Reduction in the risk of coronary heart disease and diabetes. In Handbook of Exercise in Diabetes. Edited by Ruderman N, Devlin JT, Schneider SS, Kriska A. Alexandria, VA: American Diabetes Association; 2002:155–182.

65. Kramsch DM, Aspen AJ, Abramowitz BM, et al.: Reduction of coronary atherosclerosis by moderate conditioning exercise in monkeys on an atherogenic diet. N Engl J Med 1981, 305:1483–1489.


66. Medicare demonstration to test lifestyle change program to reverse heart disease. Available at http:/www.lifestyle-advantage.org/medicare.html

67. Very low-calorie diets. National Task Force on the Prevention and Treatment of Obesity, National Institutes of Health. JAMA 1993, 270:967–974.

68. Dietary treatment of obesity. Available at http:/www.endo-text.com

69. Diet and the Initiation of Therapy for Obesity. Available at http:/www.uptdate.com

70. Vermeulen A: Effects of a short-term (4 weeks) protein-sparing modified fast on plasma lipids and lipoproteins in obese women. Ann Nutr Metab 1990, 34:133–142.

71. Anderson JW, Brinkman VL, Hamilton CC: Weight loss and 2-y follow-up for 80 morbidly obese patients treated with intensive very-low-calorie diet and an education program. Am J Clin Nutr 1992, 56:244S–246S.

72. Uusitupa MI, Laakso M, Sarlund H, et al.: Effects of a very-low-calorie diet on metabolic control and cardiovascular risk factors in the treatment of obese non-insulin-dependent diabetics. Am J Clin Nutr 1990, 51:768–773.

73. Henry RR, Wiest-Kent TA, Scheaffer L, et al.: Metabolic con-sequences of very-low-calorie diet therapy in obese non-insulin-dependent diabetic and nondiabetic subjects. Diabetes 1986, 35:155–164.

74. Wing RR, Marcus MD, Salata R, et al.: Effects of a very-low-calorie diet on long-term glycemic control in obese type 2 diabetic subjects. Arch Intern Med 1991, 151:1334–1340.

75. Osterman J, Lin T, Nankin HR, et al.: Serum cholesterol profiles during treatment of obese outpatients with a very low calorie diet. Effect of initial cholesterol levels. Int J Obes Relat Metab Disord 1992, 16:49–58.

76. Raitakari M, Ilvonen T, Ahotupa M, et al.: Weight reduction with very-low-caloric diet and endothelial function in over-weight adults: role of plasma glucose. Arterioscler Thromb Vasc Biol 2004, 24:124–128.

77. Parenti M, Babini AC, Cecchetto ME, et al.: Lipid, lipoprotein, and apolipoprotein assessment during an 8-wk very-low-calorie diet. Am J Clin Nutr 1992, 56:268S–270S.

78. Hainer V, Stich V, Kunesova M, et al.: Effect of 4-wk treatment of obesity by very-low-calorie diet on anthropometric, metabolic, and hormonal indexes. Am J Clin Nutr 1992, 56:281S–282S.

79. Shoji T, Nishizawa Y, Koyama H, et al.: High-density-lipoprotein metabolism during a very-low-calorie diet. Am J Clin Nutr 1992, 56:297S–298S.

80. Ornish D, Brown SE, Scherwitz LW, et al.: Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial. Lancet 1990, 336:129–133.

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Aggressive diets and lipid responses