Contemporary Strategies for Weight Loss and Cardiovascular Disease Risk

Factor ModificationAlison M. Hill, PhD, and Penny M. Kris-Etherton, PhD, RD

Corresponding authorPenny M. Kris-Etherton, PhD, RDDepartment of Nutritional Sciences, S-126 Henderson Building South, The Pennsylvania State University, University Park, PA 16802, USA. E-mail: pmk3@psu.edu

Current Atherosclerosis Reports 2008, 10:486–496Current Medicine Group LLC ISSN 1523-3804Copyright © 2008 by Current Medicine Group LLC

Because of the overweight/obesity epidemic and atten-dant increase in risk of chronic disease worldwide, there is a pressing need to identify effective weight loss strategies. Current recommendations for weight loss advocate a reduced-calorie dietary pattern (lower in total fat) in conjunction with regular physical activ-ity and behavior change. This combined approach is important for long-term adherence and weight mainte-nance. Several large-scale clinical trials implementing different reduced-calorie dietary patterns have shown that 4 to 10 kg of weight is typically lost. The differ-ent hypocaloric dietary patterns shown to be effective include reduced-fat diets (10%–30% of calories from fat), a Mediterranean-style diet, and diets that are reduced in energy density. The weight loss achieved is accompanied by beneficial changes in cardiovascular disease risk, including the lipid and lipoprotein profile and blood pressure. This article summarizes our current understanding of effective weight loss programs.

IntroductionThe prevalence of overweight and obesity in the United States is increasing; over two thirds of the population are overweight or obese (body mass index [BMI] > 25 kg/m2 or 30 kg/m2, respectively) [1]. Obesity is a major risk fac-tor for cardiovascular disease (CVD), and it clusters with other risk factors such as hypertension, dyslipidemia, and hyperglycemia as part of the metabolic syndrome (MetSyn). In 1998, the National Heart, Lung, and Blood Institute (NHLBI) [2], in conjunction with the National Institute of Diabetes and Digestive and Kidney Disorders,

published clinical guidelines for the treatment of obesity and its associated metabolic conditions. These guidelines advise weight loss via lifestyle interventions that include diet modification and increased physical activity, as well as behavior change. The primary strategy advocated is a reduced-calorie diet, with a focus on lowering intake of total fat and saturated fatty acids (SFA). More recently, the US Department of Agriculture (USDA) [3] released the Dietary Guidelines for Americans, 2005, which have been translated into food-based recommendations for the general public that are implemented via the website MyPyramid.gov (http://www.MyPyramid.gov) [4]. The American Heart Association (AHA) [5] also has released guidelines for CVD risk reduction that include consum-ing an overall healthy diet and achieving and maintaining a healthy body weight. The more recent dietary recom-mendations from the USDA and AHA are consistent with the earlier clinical guidelines from the NHLBI in that they promote a dietary pattern that is lower in SFA and total fat, and higher in fruits, vegetables, and complex carbo-hydrates, in conjunction with increased physical activity. This guidance is intended for chronic disease risk reduc-tion for all persons, including individuals who wish to lose weight. These dietary patterns aim to promote a low CVD risk status that includes plasma lipids, lipoproteins, and blood pressure (BP), among others.

One confounder to weight loss that consistently emerges from all dietary studies is adherence. Individu-als who adhere to a weight loss diet are more likely to lose weight and maintain weight loss. Weight loss and cardiovascular outcomes may be further improved by the incorporation of regular physical activity. In addition to creating a greater energy deficit, the energy expended dur-ing physical activity may serve to offset lapses in dietary adherence. In a recent systematic review, Franz et al. [6] reported that diet plus physical activity is more effective than diet alone for initial (6 months) and sustained weight loss (up to 48 months). This highlights the importance of weight loss interventions that incorporate both diet and physical activity, particularly in a free-living setting when dietary adherence is problematic. Indeed, there is a noted disparity between diet-induced weight loss achieved

Strategies for Weight Loss and CVD Risk Factor Modification Hill and Kris-Etherton 2

in a controlled versus free-living setting. In addition to physical activity, behavioral modification strategies that promote adherence may facilitate weight loss outside of a controlled clinical environment.

As the number of weight loss interventions increases, we must identify and critically evaluate weight loss and weight maintenance strategies and their efficacy. This review describes and discusses the results of selected clinical trials that have evaluated combined diet and physical activity interventions for weight loss and that are consistent with current recommendations. These clinical trials have been conducted in free-living popula-tions, with a minimum 12-month follow-up (Table 1). In addition to weight loss, this review also reports effects on plasma lipids, lipoproteins, and BP.

Dietary and Physical Activity Recommendations for Weight LossThe clinical guidelines to treat overweight and obesity that were published by the NHLBI in conjunction with the National Institute of Diabetes and Digestive and Kidney Disorders [2] advise following a calorie-restricted diet (deficit of 500–1000 kcal/d) that is consistent with the National Cholesterol Education Program’s second Adult Treatment Panel (NCEP-ATP II) Step I or Step II diets. These diets recommend an intake of total fat that is 30% or less of energy (carbohydrate contributes approximately 55% of calories), with emphasis on lowering SFA (Step I ≤ 10% or Step II ≤ 7% of energy) and cholesterol (Step I ≤ 300 mg/d or Step II ≤ 200 mg/d) [7,8]. In addition to calorie restriction, these guidelines advise increased physi-cal activity (30 minutes of moderate intensity exercise on most, and preferably all, days of the week) and behavior modification (including self-monitoring, stress manage-ment, and social support).

MyPyramid was released by the USDA in 2005, and is the most recent food-based dietary guidance for Americans [4]. This guide is unique in that dietary recommendations are based on foods rather than nutrients or other dietary components. MyPyramid promotes a dietary pattern that is rich in fruits and vegetables, grains (half from whole grains), lean protein foods, skim milk, and reduced-fat dairy products. Although specific recommendations for weight loss are not made, individuals are able to select an energy level and associated food pattern that induces a calorie deficit. The food-based dietary pattern that is cre-ated for a specified calorie deficit based on MyPyramid is consistent with the clinical guidelines released by the NHLBI [9]. In addition, MyPyramid guidelines emphasize balancing food intake with physical activity.

As part of a strategy to reduce CVD risk, the AHA recommends consuming a healthy diet that provides less than 7% total energy from SFA, less than 1% energy from trans fatty acids, 25% to 35% of energy from total fat, less than 300 mg/d of dietary cholesterol, 2300 mg/d

or less of sodium, and is low in added sugars [5]. These guidelines emphasize whole grains (> 3 servings per day), fruits, and vegetables, along with lean protein and low-fat dairy products. In addition, 2 servings of fish, preferably fatty fish, are recommended per week. The AHA advises balancing caloric intake with physical activity to achieve and maintain a healthy body weight, and recommends that all adults accumulate 30 minutes of physical activity most days of the week.

Until recently, the American public has been guided by physical activity recommendations published in 1995 by the Centers for Disease Control and Prevention (CDC) and the American College of Sports Medicine (ACSM) [10], which recommend that adults accumulate at least 30 minutes of moderate-intensity physical activity on most, preferably all, days of the week [10]. These guidelines recently were updated by the AHA and ACSM. Adults should spend a minimum of 30 minutes, 5 days per week, engaged in moderate aerobic activity, or 20 minutes, 3 days per week in vigorous aerobic activity (a combination of the two is also acceptable) to promote and maintain health [11]. This can be translated to a minimum of 150 minutes of physical activity per week, and is in addition to other light physical tasks such as household chores, gardening, and activities lasting less than 10 minutes. Individuals also are advised to perform muscle strength and endurance activities on two days per week. However, while this level of activity may be sufficient for the preven-tion of chronic disease, it may not be effective for weight loss. As part of their Dietary Guidelines for Americans 2005, the USDA recommends that individuals trying to lose weight should complete at least 60 minutes of moder-ate to vigorous exercise on most days of the week, while additional activity (60–90 min/d) may be required for weight maintenance after weight loss [3].

Cardiovascular Benefits of Weight Loss and Physical Activity: Blood Pressure, Lipids, and LipoproteinsWeight loss is an effective strategy for improving several CVD-related lipid risk factors. A modest 5% to 10% reduction in body weight can lower low-density lipopro-tein cholesterol (LDL-C) by approximately 15%, can lower triglycerides (TG) by 20%, and can increase high-density lipoprotein cholesterol (HDL-C) by 8% to 10% [12]. An early meta-analysis by Dattilo and Kris-Etherton [13] reported that every 1-kg decrease in body weight is asso-ciated with a mean reduction of 0.02 mmol/L in LDL-C, 0.015 mmol/L in TG, and 0.05 mmol/L in total cholesterol (TC). In comparison, active weight loss reduced HDL-C, although this was followed by a significant, proportional increase in HDL-C during weight maintenance (+0.009 mmol/L per 1 kg of weight lost). Weight loss also has been shown to be effective for hypertension reduction and/or prevention in overweight men and women. Results from

3 Nutrition

Tabl

e 1.

Sel

ecte

d fr

ee-l

ivin

g w

eigh

t lo

ss in

terv

enti

on t

rial

s w

ith

a m

inim

um 1

2-m

onth

follo

w-u

p

Stud

y /

year

Popu

lati

onPa

tien

ts, n

Dur

atio

nIn

terv

enti

onA

vera

ge w

eigh

t lo

ss

Kno

wle

r et

al.

[19]

/ 20

02 (D

PP)

Adu

lts w

ith IG

T (fa

stin

g pl

asm

a gl

ucos

e >

95

mg/

dL)

3234

Mea

n fo

llow

-up,

2.

8 y

Free

-livi

ng s

ettin

g. P

atie

nts

rand

omiz

ed to

1

of 3

gro

ups:

Stan

dard

inte

rven

tion

+ p

lace

bo0.

1 kg

Stan

dard

inte

rven

tion

+ m

etfo

rmin

(8

50 m

g tw

ice

daily

)2.

1 kg

Inte

nsiv

e lif

esty

le in

terv

entio

n th

at in

clud

ed

incr

ease

d ph

ysic

al a

ctiv

ity (1

50 m

in/w

k)

and

a lo

w-c

alor

ie, l

ow-f

at (<

25%

tota

l en

ergy

inta

ke) d

iet w

ith th

e ov

eral

l aim

to

redu

ce b

ody

wei

ght b

y 7%

5.6

kg

Pi-S

unye

r et

al.

[22•

•]

/ 200

7 (L

ookA

HEA

D)

Ove

rwei

ght (

BM

I > 2

5 kg

/m2 )

adul

ts w

ith ty

pe 2

dia

bete

s51

4512

mon

ths

(o

ngoi

ng)

Free

-livi

ng s

ettin

g. P

atie

nts

rand

omiz

ed to

1

of 2

gro

ups:

Usu

al c

are

of d

iabe

tes

supp

ort a

nd e

duca

tion

0.7%

of b

ody

wei

ght:

men

0.7

6 kg

, w

omen

0.6

7 kg

Inte

nsiv

e lif

esty

le in

terv

entio

n th

at a

imed

to

red

uce

body

wei

ght b

y 7%

thro

ugh

incr

ease

d ph

ysic

al a

ctiv

ity (1

75 m

in/w

k)

and

a lo

w-c

alor

ie, l

ow-f

at (<

30%

tota

l en

ergy

inta

ke) d

iet

8.6%

of b

ody

wei

ght:

men

9.4

kg,

w

omen

8.2

kg

Koer

tge

et a

l. [2

3] /

2003

(MLD

P)A

dults

with

CA

D44

012

mon

ths

Free

-livi

ng s

ettin

g. P

atie

nts

coun

sele

d to

in

crea

se ti

me

spen

t in

phys

ical

act

iv-

ity a

nd s

tres

s m

anag

emen

t and

follo

w

a lo

w-f

at v

eget

aria

n di

et h

igh

in fr

uits

, ve

geta

bles

, gra

ins,

legu

mes

, and

soy

pr

oduc

ts. A

nim

al p

rodu

cts

wer

e lim

ited

to n

onfa

t dai

ry a

nd e

gg w

hite

s: 7

0%–7

5%

CH

O /

15%

–20%

pro

tein

/ 10

% fa

t.

3 m

onth

s: m

en 4

kg,

wom

en 4

.6 k

g;

12 m

onth

s: m

en 4

.4 k

g,

wom

en 5

.6 k

g

App

el e

t al.

[31]

/ 20

03

and

Elm

er e

t al.

[32]

/ 20

06 (P

REM

IER)

Adu

lts w

ith u

ntre

ated

, ele

vate

d BP

: SBP

120

–159

mm

Hg,

D

BP 8

0–9

5 m

m H

g

810

6 m

onth

s (1

8-m

onth

follo

w-u

p)Fr

ee-li

ving

set

ting.

Pat

ient

s ra

ndom

ized

to

1 of

3 g

roup

s:

Adv

ice

only

6 m

onth

s, 1

.1 k

g; 1

8 m

onth

s, 1

.5 k

g

Esta

blis

hed

lifes

tyle

rec

omm

enda

tions

6 m

onth

s, 4

.9 k

g; 1

8 m

onth

s, 3

.8 k

g

DA

SH +

est

ablis

hed

lif

esty

le r

ecom

men

datio

ns6

mon

ths,

5.8

kg;

18

mon

ths,

4.3

kg

ATP

III—

Adu

lt Tr

eatm

ent P

anel

III;

BM

I—bo

dy m

ass

inde

x; B

P—bl

ood

pres

sure

; CA

D—

coro

nary

art

ery

dise

ase;

CH

O—

carb

ohyd

rate

; CR

P—C

-rea

ctiv

e pr

otei

n; D

ASH

—D

ieta

ry A

ppro

ache

s to

Sto

p H

yper

tens

ion;

DB

P—di

asto

lic b

lood

pre

ssur

e; H

DL-

C—

high

-den

sity

lipo

prot

ein

chol

este

rol;

IGT—

impa

ired

glu

cose

tole

ranc

e; S

BP—

syst

olic

blo

od p

ress

ure;

SFA

—sa

tura

ted

fatt

y ac

id;

TC—

tota

l cho

lest

erol

.

Strategies for Weight Loss and CVD Risk Factor Modification Hill and Kris-Etherton 4

Tabl

e 1.

Sel

ecte

d fr

ee-l

ivin

g w

eigh

t lo

ss in

terv

enti

on t

rial

s w

ith

a m

inim

um 1

2-m

onth

follo

w-u

p

Stud

yPo

pula

tion

Pati

ents

, nD

urat

ion

Inte

rven

tion

Wei

ght

loss

Bur

ke e

t al.

[34]

/ 20

05 (A

DA

PT)

Adu

lts tr

eate

d fo

r hy

pert

en-

sion

with

a B

MI >

25

kg/m

224

14

mon

ths

(follo

w-

up a

t 16

mon

ths)

Free

-livi

ng s

ettin

g. P

atie

nts

rand

omiz

ed to

:

Usu

al c

are

(rece

ived

pub

licat

ions

rel

atin

g to

man

agem

ent o

f hyp

erte

nsio

n)4

mon

ths,

1.2

kg;

16,

mon

ths

1.0

kg

Inte

rven

tion

grou

p fo

cusi

ng o

n w

eigh

t los

s,

a lo

w-s

odiu

m D

ASH

-typ

e di

et, i

ncre

ased

fis

h co

nsum

ptio

n, in

crea

sed

phys

ical

ac

tivity

, and

red

uced

alc

ohol

inta

ke

4 m

onth

s, 4

.0 k

g; 1

6 m

onth

s, 3

.5 k

g

Dan

sing

er e

t al.

[38]

/ 2

005

Adu

lts w

ith B

MI o

f 27

–40

kg/m

2 16

012

mon

ths

Free

-livi

ng s

ettin

g. P

atie

nts

rand

omiz

ed to

1

of 4

gro

ups:

For

all d

iets

, wei

ght c

hang

e w

as

asso

ciat

ed w

ith d

ieta

ry a

dher

ence

bu

t not

die

t typ

e. W

eigh

t los

s w

as

asso

ciat

ed w

ith a

dec

reas

e in

TC

:H

DL-

C r

atio

, ins

ulin

, and

CR

P

Orn

ish:

prim

ary

emph

asis

on

redu

cing

fat

inta

ke to

< 1

0% o

f tot

al e

nerg

y

Zon

e: e

mph

asiz

ed e

nerg

y re

stric

tion

and

a m

acro

nutr

ient

dis

trib

utio

n of

40%

CH

O /

30%

pro

tein

/ 30

% fa

t

Atk

ins:

< 2

0 g/

d of

CH

O fo

r “i

nduc

tion”

(2

–3 m

onth

s) a

nd <

50

g/d

of C

HO

for

ongo

ing

wei

ght-l

oss

phas

e

Wei

ght W

atch

ers:

die

tary

inta

ke b

ased

on

“poi

nts”

in a

ran

ge d

eter

min

ed b

y cu

rren

t w

eigh

t; en

ergy

res

tric

tion

Gar

dner

et a

l. [3

9] /

2007

(A T

o Z

Wei

ght

Loss

Stu

dy)

Prem

enop

ausa

l wom

en w

ith

BM

I of 2

7–40

kg/

m2

311

12 m

onth

sFr

ee-li

ving

set

ting.

Pat

ient

s ra

ndom

ized

to

1 of

4 g

roup

s:A

tkin

s gr

oup

lost

mor

e w

eigh

t tha

n al

l ot

her g

roup

s at

2 m

onth

s (4

.4 k

g) a

nd

6 m

onth

s (5

.6 k

g), b

ut b

y 12

mon

ths

was

sig

nific

antly

diff

eren

t onl

y to

the

Zone

gro

up (4

.7 k

g vs

1.6

kg)

Orn

ish:

prim

ary

emph

asis

on

redu

cing

fat

inta

ke to

< 1

0% o

f tot

al e

nerg

y

Zon

e: e

mph

asiz

ed e

nerg

y re

stric

tion

and

a m

acro

nutr

ient

dis

trib

utio

n of

40%

CH

O /

30%

pro

tein

/ 30

% fa

t

Atk

ins:

< 2

0 g/

d of

CH

O fo

r “i

nduc

tion”

(2

–3 m

onth

s) a

nd <

50

g/d

of C

HO

for

ongo

ing

wei

ght l

oss

phas

e

ATP

III—

Adu

lt Tr

eatm

ent P

anel

III;

BM

I—bo

dy m

ass

inde

x; B

P—bl

ood

pres

sure

; CA

D—

coro

nary

art

ery

dise

ase;

CH

O—

carb

ohyd

rate

; CR

P—C

-rea

ctiv

e pr

otei

n; D

ASH

—D

ieta

ry A

ppro

ache

s to

Sto

p H

yper

tens

ion;

DB

P—di

asto

lic b

lood

pre

ssur

e; H

DL-

C—

high

-den

sity

lipo

prot

ein

chol

este

rol;

IGT—

impa

ired

glu

cose

tole

ranc

e; S

BP—

syst

olic

blo

od p

ress

ure;

SFA

—sa

tura

ted

fatt

y ac

id;

TC—

tota

l cho

lest

erol

.

(Continued)

5 Nutrition

Tabl

e 1.

Sel

ecte

d fr

ee-l

ivin

g w

eigh

t lo

ss in

terv

enti

on t

rial

s w

ith

a m

inim

um 1

2-m

onth

follo

w-u

p

Stud

yPo

pula

tion

Pati

ents

, nD

urat

ion

Inte

rven

tion

Wei

ght

loss

LEA

RN

: pru

dent

die

t tha

t inc

lude

d 55

%–

60%

CH

O a

nd <

10%

SFA

, with

cal

oric

re

stric

tion

and

incr

ease

d ex

erci

se

Espo

sito

et a

l. [4

5] /

2004

Adu

lts w

ith m

etab

olic

sy

ndro

me

(d

efine

d by

ATP

III)

180

24 m

onth

sFr

ee-li

ving

set

ting.

Pat

ient

s ra

ndom

ized

to

1 of

2 g

roup

s:

Prud

ent (

cont

rol)

diet

(57%

CH

O /

13%

pr

otei

n / 3

0% fa

t)1.

2 kg

Med

iterr

anea

n di

et: p

atie

nts

wer

e ad

vise

d to

incr

ease

thei

r co

nsum

ptio

n of

who

le

grai

ns, w

alnu

ts, f

ruits

, veg

etab

les,

and

ol

ive

oil.

This

die

t was

sim

ilar

in m

acro

nu-

trie

nt d

istr

ibut

ion

to th

e co

ntro

l die

t.

4.0

kg

Ello

-Mar

tin e

t al.

[47•

] / 2

007

Obe

se w

omen

(B

MI >

30

kg/m

2 )97

12 m

onth

sFr

ee-li

ving

set

ting.

Pat

ient

s ra

ndom

ized

to

1 of

2 g

roup

s:

Redu

ced

fat

6 m

onth

s, 6

.7 k

g; 1

2 m

onth

s, 6

.4 k

g

Redu

ced

fat a

nd in

crea

sed

frui

ts

and

vege

tabl

es6

mon

ths,

8.9

kg;

12

mon

ths,

7.9

kg

No

spec

ific

goal

s fo

r en

ergy

or

fat i

ntak

e fo

r ei

ther

gro

up

ATP

III—

Adu

lt Tr

eatm

ent P

anel

III;

BM

I—bo

dy m

ass

inde

x; B

P—bl

ood

pres

sure

; CA

D—

coro

nary

art

ery

dise

ase;

CH

O—

carb

ohyd

rate

; CR

P—C

-rea

ctiv

e pr

otei

n; D

ASH

—D

ieta

ry A

ppro

ache

s to

Sto

p H

yper

tens

ion;

DB

P—di

asto

lic b

lood

pre

ssur

e; H

DL-

C—

high

-den

sity

lipo

prot

ein

chol

este

rol;

IGT—

impa

ired

glu

cose

tole

ranc

e; S

BP—

syst

olic

blo

od p

ress

ure;

SFA

—sa

tura

ted

fatt

y ac

id;

TC—

tota

l cho

lest

erol

.

(Continued)

Strategies for Weight Loss and CVD Risk Factor Modification Hill and Kris-Etherton 6

the Trials of Hypertension Prevention demonstrate that even a 4.5-kg (10-lb) reduction in body weight can lower systolic BP/diastolic BP (SBP/DBP) by 3.7/2.7 mm Hg.

Several meta-analyses have evaluated the effects of regular exercise training on lipids and lipoproteins [14–16]. These analyses generally conclude that regular physical activity (at levels relatively consistent with physical activity guidelines [10,11]) has limited effects on TC and LDL-C, with more consistent effects on TG (decreases of 3.7%–12%) and HDL-C (increase of 4%) [14–16]. Without concomitant energy restriction, this level of physical activity (equivalent to an energy expenditure of 1000 kcal/wk [10]) produces only small changes in body weight (1–2 kg), indicating that these improvements are relatively independent of weight loss. Interestingly, Kodama et al. [17] recently reported that a minimum energy expenditure of 900 kcal/wk (or 120 min/wk) is required to elicit changes in HDL-C, and above this threshold their exists a dose-response relationship; every 10-minute prolongation of exercise per session (ie, above 120 min/week) is associated with a 1.4 mg/dL increase in HDL-C. Regular physical activ-ity also is effective for management of BP, particularly in persons with hypertension (-6.9/-4.9 mm Hg) versus nor-motensive individuals (-1.9/-1.6 mm Hg) [18].

Intensive Lifestyle Strategies for Weight LossThe clinical guidelines for weight loss and health promo-tion that have been issued by numerous organizations recommend a combined treatment strategy that incorpo-rates diet, physical activity, and behavioral modification [2,3,5]. Several large-scale clinical trials have imple-mented such strategy with the primary goals of weight loss and prevention or treatment of chronic disease. They provide important information about what can be achieved in clinical practice for weight loss and CVD risk factor modification (summarized in Table 1).

Diabetes Prevention ProgramThe Diabetes Prevention Program (DPP) [19,20••] com-pared the efficacy of three treatments in preventing type 2 diabetes and MetSyn in individuals at high risk based on elevated fasting blood glucose and impaired glucose tolerance. Participants were randomized to receive stan-dard intervention (written material advising lifestyle changes) alone (ie, placebo), standard intervention with drug therapy (metformin, 850 mg twice daily), or inten-sive lifestyle intervention, which aimed to achieve 7% weight loss through a healthy low-calorie, low-fat diet and 150 min/wk of physical activity. Dietary guidance for the lifestyle intervention was based on the NCEP Step I diet and focused on restricting total fat to less than 25% of energy. This group also received intensive individual counseling on diet, exercise, and behavior modifica-tion (eg, goal setting, self-monitoring, stimulus control, relapse prevention, and problem solving) during the first

6 months, followed by individual and group sessions reinforcing lifestyle behavior changes. At the time of most recent follow-up (average follow-up was 2.8 years), 38% of participants in the lifestyle intervention group had a weight loss of at least 7%, and 58% were achieving the minimum physical activity goal of 150 min/wk. At 1 year, average fat intake was 27.5% of energy. The life-style intervention group lost substantially more weight by 12 months (6.5 kg) than either the placebo (0 kg) or metformin (2.2 kg) groups. Average weight loss (mean, 2.8 years) for the placebo, metformin, and lifestyle intervention groups was 0.1, 2.1, and 5.6 kg, respectively [19]. Weight loss was a significant predictor for reduced incidence of diabetes [21], which was 58% and 31% lower in the lifestyle and metformin groups, respectively, compared with placebo [19]. After 3 years, 38% of individuals in the lifestyle intervention group no longer had MetSyn, compared with 23% in the met-formin group and 18% in the placebo group [20••]. Intensive lifestyle therapy also was most effective in pre-venting the development of MetSyn in those who were free of the syndrome at baseline. At 3 years, incidence rates for MetSyn were 53% for the placebo group, 47% for the metformin group, and 38% for the lifestyle group [20••]. Importantly, lifestyle intervention was more effective than metformin in improving individual criteria for MetSyn, indicating that this is an effective treatment strategy for individuals with multiple cardiovascular risk factors.

Look AHEADThe Look AHEAD (Action for Health in Diabetes) trial [22••] is an ongoing, multicenter clinical trial investi-gating the long-term effects (11.5-year follow-up) of an intensive lifestyle intervention program in persons with type 2 diabetes. Modeled after the DPP, this intervention also combines dietary modification, behavior therapy (based on programs employed in DPP), and increased physical activity (175 min/wk of moderate exercise) to achieve a 10% reduction in body weight. Dietary guide-lines include a maximum of 30% of energy from fat (with a maximum of 10% of energy from SFA) and a minimum of 15% of calories from protein. In compari-son to DPP, which focused on fat restriction to decrease calories, the primary method of achieving weight loss in Look AHEAD is through calorie restriction (although fat intake is considered). Patients randomized to the intensive lifestyle program are compared with those receiving usual care of diabetes support and educa-tion. At 1 year, the lifestyle intervention significantly reduced body weight (8.6%), improved glucose control (-21.5 mg/dL), SBP (-6.8 mm Hg), DBP (-3.0 mm Hg), TG (-30.3 mg/dL), and HDL-C (+3.4 mg/dL) compared with individuals receiving usual care of diabetes support and education. At this stage, determinants of compliance have not been published.

7 Nutrition

The Multicenter Lifestyle Demonstration ProjectThe Multicenter Lifestyle Demonstration Project (MLDP) [23] consisted of a comprehensive lifestyle intervention that examined the combined effects of diet, exercise, stress management, and group support on medical and psychosocial characteristics in men and women with coro-nary artery disease (CAD). Modeled after the successful Lifestyle Heart Trial [24], individuals were counseled to follow a low-fat (< 10% of calories) vegetarian diet that emphasized fruits, vegetables, grains, legumes, and soy products. Animal products were limited to nonfat dairy products and egg whites. The macronutrient composition of this diet was approximately 10% fat, 15% to 20% pro-tein, and 70% to 75% complex carbohydrates. Additional intervention criteria included participation in 1 hour per day of stress management, 3 hours per week of moderate exercise (according to ACSM guidelines for CAD patients), and twice weekly group support sessions. By 3 months of intervention, all participants had reduced their total fat intake to approximately 7% of calories and increased their time spent in physical activity (men, 4.0 h/wk; women, 3.2 h/wk) and stress management (men, 5.6 h/wk; women, 5.4 h/wk). These changes were relatively well maintained at 12 months. Significant improvements were observed in several cardiovascular risk factors at 3 months: body weight (men, -4 kg; women, -4.6 kg), BP (men, -5/-5 mm Hg; women, -6/-3 mm Hg), TC (men, -18 mg/dL; women, -14 mg/dL), LDL-C (men, -19 mg/dL; women, -17 mg/dL), heart rate (men, -4 beats per minute; women, -4 beats per minute), and exercise capacity (men, +5.95 mL/kg/min; women, +3.5 mL/kg/min). These cardiovascular benefits remained at 12 months. In addition, participants experi-enced a substantial reduction in the incidence of angina [23], and glucose control was improved in 20% of patients with diabetes mellitus [25]. More recent analyses demon-strate that the MLDP was equally effective in improving cardiovascular outcomes in individuals at low or high risk for heart failure (as determined by a left ventricular ejec-tion fraction of 40%) [26], and that these behavioral modifications (specifically reduced dietary fat, exercise, and stress management) had independent and additive effects for coronary disease risk reduction [27]. However, although successful, 21% of men and 27% of women did not complete the 12-month follow-up.

The Dietary Approaches to Stop Hypertension lifestyle trials: PREMIER and ADAPTThe Dietary Approaches to Stop Hypertension (DASH) diet is a reduced-fat (< 30% of calories, SFA < 10% of calories) dietary pattern that emphasizes fruits (4–5 servings per day), vegetables (4–5 servings per day), whole grains (7–8 servings per day), and low-fat dairy (2–3 servings per day), with limited consumption of meats (red meat, fish, and poultry < 2 servings per day), added fats, and sweets. In a controlled, stable-weight environment, the DASH diet lowers SBP (-5.5 mm Hg) and DBP (-3.0 mm Hg) [28], and

reduces TC (-7.3%) and LDL-C (-9.0%) compared with an average American diet [29]. However, recommendations for hypertension management also include weight loss, sodium reduction (< 100 mg/d), increased physical activity (180 min/wk), and limited alcohol intake. Sacks et al. [30] reported that a sodium-restricted (three levels of sodium were tested: 150, 100, and 50 mmol/d) DASH diet has even greater effects on BP, lowering SBP by 11.5 mm Hg and 7.1 mm Hg in people with and without hypertension, respectively.

The Prevention of Myocardial Infarction Early Remodeling (PREMIER) trial was designed to maximize the BP-lowering and lipid-lowering effects of the DASH diet by incorporating all additional lifestyle modifications shown to lower BP [31]. Individuals with untreated, ele-vated BP (120–159/80–80–95 mm Hg) were randomized to one of three intervention groups: advice only (control), established lifestyle recommendations (as described previously), or DASH diet plus established lifestyle rec-ommendations. At 6 months, weight loss was significantly greater in the established (-4.9 kg) and DASH-plus-estab-lished (-5.8 kg) groups compared with the control (-1.1 kg) group [31], with some weight regain in the interven-tion groups by 18 months (control, -1.5 kg; established, -3.8 kg; DASH plus established, -4.3 kg) [32]. Similar trends were observed for BP, which, after accounting for changes in the control group, was significantly reduced in the established (SBP, -3.7 mm Hg; DBP, -1.7 mm Hg) and DASH-plus-established groups (SBP, -4.3 mm Hg; DBP, -2.6 mm Hg) by 6 months. However, these changes were not significantly different from those observed in the con-trol group by 18 months. At present, effects on lipids and lipoproteins have not been published for the entire study population, although a secondary analysis has reported on changes in MetSyn [33]. Compared with the control group, TC was lowered by both the established and DASH-plus-established interventions in participants with (-7.98 and -5.91 mg/dL, respectively) and without MetSyn (-7.41 and -7.06 mg/dL, respectively). In all participants, the established intervention lowered TG (log transformed: with MetSyn -0.16 mg/dL, without -0.10 mg/dL), whereas improvements in LDL-C were only observed in partici-pants without MetSyn (established, -6.89 mg/dL; DASH plus established, -5.13 mg/dL). In comparison, only the DASH plus established lifestyle recommendations were effective in lowering SBP (-11.1 mm Hg) in individuals with MetSyn [33].

When combined with other lifestyle modifica-tions, the DASH diet also is effective in improving cardiovascular risk factors in medicated hypertensive individuals. The Activity, Diet and Blood Pressure Trial (ADAPT) [34] showed that a 4-month lifestyle program (focusing on weight loss, a low-sodium DASH-type diet, increased fish consumption, increased physical activity, and reduced alcohol intake) was more effective relative to usual care in improving 24-hour ambulatory BP (-4.1/-2.1 vs -1.0/-0.3 mm Hg), although these differences

Strategies for Weight Loss and CVD Risk Factor Modification Hill and Kris-Etherton 8

were not significant at 1-year of follow-up. Relative to usual care, short-term benefits (4 months net change) also were observed in the intervention group for body weight (-2.8 kg), waist circumference (-3.1 cm), TC (-7.8 mg/dL), and TG (-10.7 mg/dL), with changes in body weight and waist circumference maintained at 12-month follow-up. Participation in physical activity was considered an important contributor to weight loss; at 4 months, 59% of the usual-care group and 75% of the intervention group met physical activity guidelines [10], and this was maintained by 58% and 62%, respectively, at follow-up.

Summary of intensive lifestyle interventionsCollectively, these studies support the use of intensive lifestyle interventions that simultaneously incorporate behavioral therapy, dietary change, and increased physical activity as successful strategies for weight loss. Further-more, such strategies are highly effective for preventing the development of chronic disease (such as diabetes and MetSyn) and improving risk status in persons with hyper-tension and CAD. Common to these clinical trials were a calorie-restricted diet with specific goals for total and SFA intake and targets for physical activity level. Additionally, participants attended group support and exercise sessions. DPP and Look AHEAD also incorporated a “toolbox” approach that included additional strategies to encour-age adherence, including portion-controlled foods, meal replacements, provision of an exercise tape or equipment, cookbooks, grocery store vouchers, enrollment in an exer-cise or cooking class, and weight-loss medication [35,36]. It is important to appreciate that these intensive interven-tion programs require substantial commitment by both patients and health care providers versus typical usual-care interventions that are common in clinical practice.

Alternate Strategies for Weight LossWhether diets that incorporate macronutrient profiles that vary from current recommendations are more or less ben-eficial for weight loss and other cardiovascular outcomes compared with traditional (recommended) macronutri-ent targets is still a matter of debate [37–41]. The results of the MLDP trial (described previously) suggest that appreciable macronutrient changes can be achieved and maintained, resulting in weight loss when accompanied by strategies that facilitate adherence. In addition, trials comparing popular weight loss diets that vary appreciably in macronutrient profiles (eg, Atkins, Zone, and Ornish) [38,39] demonstrate that dietary adherence is crucial to achieve weight loss. Dansinger et al. [38] compared the effects of four popular diets (Atkins, Zone, Ornish, and Weight Watchers) on weight loss and other cardiovascular risk factors in a 12-month randomized trial involving 160 overweight or obese individuals. Each diet significantly improved the LDL-C to HDL-C ratio (-10%) but had no

effect on TG, BP, or glucose. Although body weight was reduced in each diet group (range, 2.1–3.3 kg), the magni-tude of weight loss was determined by dietary adherence rather than diet type. The A to Z weight loss study [39] compared three popular diets (Ornish, Zone, and Atkins) with a conventional low-fat, high-carbohydrate diet (Life-style, Exercise, Attitudes, Relationships, and Nutrition [LEARN]) on weight loss in 311 premenopausal women. The Atkins diet induced greater weight loss than the Ornish, Zone, or LEARN diets at 2 months (4.4 kg) and 6 months (5.6 kg) months, but only differences between the Atkins (4.7 kg) and Zone (1.6 kg) diets were significant at 12 months. Within each diet, weight loss was associated with greater dietary adherence [42]. By 12 months, the Atkins diet produced substantially greater changes in TG (-29.3 mg/dL, significantly different from Zone), HDL-C (+4.9 mg/dL, significantly different from Ornish), and SBP (-7.7 mm Hg, significantly different from all other diets).

McManus et al. [43] compared a low-fat (20% of energy), low-energy diet with a moderate-fat (35% of energy), low-energy diet on weight loss in overweight adults. Weight loss was comparable between groups at 6 months (-5 kg), but dietary adherence was substantially lower in the low-fat versus moderate-fat group, resulting in weight regain in the low-fat group by 18 months. In comparison, weight loss was maintained in the moderate-fat group.

The Mediterranean-style diet has gained widespread popularity due to its many reported health benefits [44], including maintenance of a healthy weight. In a 2-year intervention, Esposito et al. [45] compared the effects of a Mediterranean-style diet (participants were advised to increase their consumption of whole grains, walnuts, fruits, vegetables, and olive oil) versus a prudent (control) diet of similar macronutrient distribution (57% carbo-hydrate, 30% fat, 13% protein) on cardiovascular risk factors and inflammation in individuals with MetSyn. By the end of the intervention, both groups had increased their level of physical activity, and despite reportedly receiving no guidance to do so, had reduced their energy intake, with a small (but significantly) lower energy intake in the Mediterranean group (mean difference between groups, 100 kcal/d). This difference may partially explain the greater weight loss observed in participants consuming the Mediterranean-style diet (-4 kg) compared with the control diet (-1.2 kg). Compared with the control diet, the Mediterranean-style diet improved several cardiovascular risk factors, including TC (-11 mg/dL), TG (-18 mg/dL), HDL-C (+4 mg/dL), and SBP/DBP (-4/-3 mm Hg), as well as markers of inflammation (C-reactive protein, inter-leukin (IL)-6, IL-7, IL-18). The Mediterranean dietary pattern emphasizes unsaturated fats from olive oil, nuts, seeds, and fish, and also increased intake of whole grains, fruits, vegetables, and wine. Consuming a Mediterranean diet ad libitum may be more effective for weight loss and weight maintenance than a reduced-fat, low-calorie diet because it may increase satiety and control hunger, due to

9 Nutrition

higher proportions of protein and fat [40]. Indeed, early results from the Diet, Obesity and Genes (DIOGENES) study [46], a highly controlled intervention trial, indicate that a higher-protein diet consumed ad libitum improves weight loss maintenance [46].

Another dietary approach that has been proposed to facilitate weight loss through increased satiety is the concept of reduced energy density, which refers to the amount of energy provided in a specific quantity of food (kcal/g). Ello-Martin et al. [47•] recently compared two dietary strategies designed to reduce overall energy den-sity on weight loss. Obese women (BMI > 30 kg/m2) were advised to reduce their fat intake (RF) or reduce fat intake and increase fruits and vegetables (RF + FV), but were not given specific goals for energy or fat. Over 1 year, all participants significantly increased their level of physi-cal activity (as determined by an increase in daily step counts) and reduced their intake of total fat (< 29% of energy). There were no differences between groups for consumption of protein (18%) or carbohydrate (54%). As expected, women in the RF + FV group reported a sig-nificantly greater intake of fruits and vegetables than the RF group, contributing to higher intake of dietary fiber and lower overall dietary energy density. Although total weight loss was not different between groups by the end of the intervention (1 year), there were distinct differences in the pattern of weight loss. Obese women randomized to the RF + FV group lost more weight than women in the RF group (8.9 kg vs 6.7 kg) by 6 months, although this pattern of weight reduction did not differ between groups during months 6 to 12. A similar relationship between energy density and body weight was observed for partici-pants in the PREMIER trial, where consumption of less energy-dense foods was associated with greater weight loss, irrespective of intervention group [48].

ConclusionsCurrent guidelines advocate multiple strategies for body weight reduction, including dietary change, increased physical activity, and behavioral therapy. Clinical trials have demonstrated that when implemented together, these strate-gies are successful not only for weight loss (5–10 kg), but also for improvements in obesity-related cardiovascular risk fac-tors (particularly TG, HDL-C, and BP). The major clinical trials conducted to date have implemented a reduced-calorie, lower-fat dietary pattern consistent with current dietary recommendations. Although still requiring further evalu-ation, other dietary approaches also may be beneficial for weight loss. These include the Mediterranean diet and diets with reduced energy density, both of which may facilitate dietary adherence by increasing satiety. Diets of this type have resulted in weight loss of 4 to 8 kg. The findings from these latter studies demonstrate that weight loss interventions do not necessarily need to focus on severe energy restriction or extreme modifications in the macronutrient profile. At

present, the evidence base demonstrates that we have greatly increased our understanding of dietary interventions, such that there are a number of different dietary approaches to select for relatively shorter-term weight loss (even up to 18 months). Although the weight loss achievable is relatively modest, it is accompanied by improvements in several CVD risk factors. However, further research is needed to establish effective long-term weight loss practices that span a lifetime. Until such time, based on research to date, a food-based, reduced-calorie dietary pattern that meets contemporary dietary guidelines (available at http://www.mypyramid.gov) can be successfully implemented for weight loss and improved CVD risk status. A challenge for practitioners will be to individualize a strategy that achieves sustained weight loss by balancing lifestyle interventions that include a healthy dietary pattern, a program of regular physical activity, and behavioral change.

DisclosuresNo potential conflicts of interest relevant to this article were reported.

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