Research

Original Investigation

Comparison of Weight Loss Among Named Diet Programsin Overweight and Obese Adults
A Meta-analysis
Bradley C. Johnston, PhD; Steve Kanters, MSc; Kristofer Bandayrel, MPH; Ping Wu, MBBS, MSc; Faysal Naji, BHSc;
Reed A. Siemieniuk, MD; Geoff D. C. Ball, RD, PhD; Jason W. Busse, DC, PhD; Kristian Thorlund, PhD;
Gordon Guyatt, MD, MSc; Jeroen P. Jansen, PhD; Edward J. Mills, PhD, MSc
Editorial page 900
IMPORTANCE Many claims have been made regarding the superiority of one diet or anotherfor inducing weight loss. Which diet is best remains unclear.

Author Audio Interview atjama.com

OBJECTIVE To determine weight loss outcomes for popular diets based on diet class

Supplemental content atjama.com(macronutrient composition) and named diet.
DATA SOURCES Search of 6 electronic databases: AMED, CDSR, CENTRAL, CINAHL, EMBASE,

and MEDLINE from inception of each database to April 2014.

CME Quiz at
jamanetworkcme.com and
CME Questions page 958

STUDY SELECTION Overweight or obese adults (body mass index ⱖ25) randomized to a
popular self-administered named diet and reporting weight or body mass index data at
3-month follow-up or longer.
DATA EXTRACTION AND SYNTHESIS Two reviewers independently extracted data on
populations, interventions, outcomes, risk of bias, and quality of evidence. A Bayesianframework was used to perform a series of random-effects network meta-analyses withmeta-regression to estimate the relative effectiveness of diet classes and programs forchange in weight and body mass index from baseline. Our analyses adjusted for behavioral
support and exercise.
MAIN OUTCOMES AND MEASURES Weight loss and body mass index at 6- and 12-monthfollow-up (±3 months for both periods).
RESULTS Among 59 eligible articles reporting 48 unique randomized trials (including 7286
individuals) and compared with no diet, the largest weight loss was associated with
low-carbohydrate diets (8.73 kg [95% credible interval {CI}, 7.27 to 10.20 kg] at 6-monthfollow-up and 7.25 kg [95% CI, 5.33 to 9.25 kg] at 12-month follow-up) and low-fat diets (7.99
kg [95% CI, 6.01 to 9.92 kg] at 6-month follow-up and 7.27 kg [95% CI, 5.26 to 9.34 kg] at
12-month follow-up). Weight loss differences between individual diets were minimal. For
example, the Atkins diet resulted in a 1.71 kg greater weight loss than the Zone diet at
6-month follow-up. Between 6- and 12-month follow-up, the influence of behavioral support(3.23 kg [95% CI, 2.23 to 4.23 kg] at 6-month follow-up vs 1.08 kg [95% CI, −1.82 to 3.96 kg]
at 12-month follow-up) and exercise (0.64 kg [95% CI, −0.35 to 1.66 kg] vs 2.13 kg [95% CI,
0.43 to 3.85 kg], respectively) on weight loss differed.
CONCLUSIONS AND RELEVANCE Significant weight loss was observed with any
low-carbohydrate or low-fat diet. Weight loss differences between individual named diets
were small. This supports the practice of recommending any diet that a patient will adhere to
in order to lose weight.
Author Affiliations: Author
affiliations are listed at the end of thisarticle.

JAMA. 2014;312(9):923-933. doi:10.1001/jama.2014.10397

Corresponding Author: Edward J.
Mills, PhD, MSc, Stanford University
School of Medicine, 1265 Welch Rd,
Stanford, CA 94305(millsej@stanford.edu).

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Research Original Investigation

Weight Loss Among Named Diet ProgramsNamed or branded (trade-marked) weight loss programs are broadly available to the general public,
providing structured dietary and lifestyle recommendations via popular books and in-person or online
behavioral support. These programs represent a multibillion
dollar industry.1 Debate regarding the relative merit of thediets is accompanied by advertising claiming which macronutrient composition is superior, such as a low-carbohydrate
diet being better than a low-fat diet, and the benefits ofaccompanying lifestyle interventions. Establishing which of
the major named diets is most effective is important because
overweight and obese patients often want to know which
diet results in the most effective weight loss.
Some physiological explanations regarding the merits ofdifferent macronutrient compositions, including variable genetic response to diets with different recommended dietary
fat intake, make intuitive sense.2,3 Low-carbohydrate diets may
drive weight loss due to a higher intake of protein, which may
induce a stronger satiating effect than fats and carbohydrates.4
Despite potential biological mechanisms explaining whysome popular diets should be better than others, recent reviews suggest that most diets are equally effective,2,5,6 a message very different from what the public hears in advertisements or expert pronouncements. Only a few of the reviewsof named diets have used rigorous meta-analytic techniques
to provide quantitative estimates of how much better one dietis compared with another. They also relied on aggregating studies comparing one diet with another and did not have the ability to determine the relative performance of diets when they
were not directly compared with one another in clinical trials.
By not exploring the full range of potential comparisons in astatistically and methodologically rigorous fashion, these reviews could have missed important benefits of specific dietsor their compositions.
Network meta-analysis facilitates comparison of different diets using all available randomized clinical trial (RCT)
data.7 In the absence of published head-to-head clinical trialsof each diet against each other diet, network meta-analysis uses
both direct and indirect clinical trial evidence to estimate theirrelative effects. Using a network meta-analytic approach, we
assessed the relative effectiveness of different popular dietsin improving weight loss.

Methods
Eligibility Criteria
As described in a protocol outlining our study methods,8 weincluded RCTs that assigned overweight (body mass index[BMI; calculated as weight in kilograms divided by height inmeters squared] of 25-29) or obese (BMI ≥30) adults (≥18 yearsof age) to a popular branded diet or an alternative. We included RCTs that reported weight loss or BMI reduction at
3-month follow-up or longer.
Named diets were identified through the explicit namingof the brand, the referencing of branded literature, or thenaming of a brand as funders of an article reporting weightloss outcomes from the diet. The diet was labeled as brand924

like when the diet met the definition of a branded diet, butfailed to name or reference the brand in the article. For
example, dietary programs that did not refer to Atkins but
consisted of less than 40% of kilocalories from carbohydrates per day for the duration of study or were funded by
Atkins were considered Atkins-like.9,10
We included dietary programs with recommendations fordaily macronutrient, caloric intake, or both for a defined period (≥12 weeks) with or without exercise (eg, jogging, strength
training) or behavioral support (eg, counseling, group support). Eligible programs included meal replacement products
but had to consist primarily of whole foods and could not include pharmacological agents. Because it is impossible to provide a placebo diet in a clinical trial, eligible control diets included wait-listed controls, no specific assigned diet, orcompeting dietary programs. The characteristics of eligible
branded dietary programs are reported in eTable 1 in the
Supplement.

Outcomes and Effect Modifiers
The primary outcomes were weight loss at 6- and 12-month follow-up (±3 months for both periods). Secondary outcomes included BMI and adverse events. We considered 3 weight loss
effect modifiers that were modeled as present or absent if they
were included in an overall dietary program: calorie restriction, exercise, and behavioral support. Based on the lowest estimated caloric intake for sedentary adults, we defined calorie restriction as less than 1800 kcal/d.11
Exercise was defined as having explicit instructions forweekly physical activities and simply dichotomized when differences between varying degrees of exercise frequencies appeared to have negligible effects. Diets with at least 2 groupor individual sessions per month for the first 3 months wereconsidered as providing behavioral support.12

Search Strategy
We searched 6 electronic databases: AMED, CDSR, CENTRAL,
CINAHL, EMBASE, and MEDLINE from inception of each database to April 2014. Search terms included extensive controlled vocabulary and keyword searches for (RCTs) AND (diets)
AND (adults) AND (weight loss). The search strategy is available from the authors upon request.
We reviewed bibliographies of review articles and eligible trials, and searched the registries of ClinicalTrials.gov andthe metaRegister of Controlled Trials. We contacted the named
diet companies and individuals working in the field of obesity and weight management to identify additional or unpublished trials.

Study Selection
Reviewers, in pairs, independently screened titles and abstracts of articles and reviewed the full text of any title or abstract deemed potentially eligible by either reviewer. Reviewers resolved disagreements by discussion.

Risk of Bias Assessment of Individual Studies
Pairs of reviewers independently assessed the risk of bias associated with individual trials using the Cochrane Collabora-

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jama.comWeight Loss Among Named Diet Programs

Original Investigation Research

Table 1. Diet Classes Based on Macronutrient CompositionaType of Diet

Branded Dietsa

Carbohydrates, % kcal

Protein, % kcal

Low carbohydrate

Atkins, South Beach, Zone≤40

Approximately 30

30-55

Moderate
macronutrients

Biggest Loser, Jenny Craig, Nutrisystem,
Volumetrics, Weight Watchers

Approximately 55-60

Approximately 1521-≤30

Low fatOrnish, Rosemary Conley

Approximately 60

Approximately 10-15≤20Fat, % kcal

The Lifestyle, Exercise, Attitudes, Relationships, and Nutrition (LEARN) diet
was applied as both a low-fat diet (2 trials) and a moderate macronutrient diet
(5 trials) among the 7 included trials having used the LEARN diet (Table 2).

Slimming World was excluded from the diet class analyses because it does not
fit any of the definitions above.

tion instrument.13 We assigned 1 of 2 summary assessments
for each included study: low risk of bias for key domains, allocation concealment, and missing participant data or high riskof bias for key domains.14

To determine weight loss outcomes between diets withall potential comparisons between them, we performed
Bayesian network meta-analyses among 5 diet class nodes(no diet, moderate macronutrients, low carbohydrate, lowfat, usual care) and each of the 11 eligible named diets.20
When P values were used, all tests were 2-sided with a significance level of .05. All analyses were conducted using
WinBUGS version 1.4 (Medical Research Council Biostatistics
Unit) and R version 3.0.1 (R Project for Statistical Computing)with the R2WinBUGS, xlsx, and the metafor packages. A
detailed description of the statistical analysis appears in theeMethods in the Supplement.

Data Extraction
Pairs of reviewers independently, and in duplicate, extracted
the following data items: study setting, type of trial (parallelor factorial), demographic information, experimental interventions, control interventions, exercise information, degreeof calorie restriction, degree of behavioral support, and eachof the outcomes of interest. We categorized dietary treatment groups in 2 ways: using diet classes (moderate macronutrient distribution, low carbohydrate, and low fat)15 and according to diet brands. Diet classes were established bymacronutrient content (Table 1).
We considered the Lifestyle, Exercise, Attitudes, Relationships, and Nutrition (LEARN) diet akin to a usual care comparator because it is based on a popular program among healthprofessionals, many of whom have been trained in or endorse the program because of it’s practicality, it’s emphasis on
behavioral modification, and it’s adaptability to various dieters (eg, applied as either a low-fat or moderate macronutrient
composition diet).16-18
Continuous outcomes were most often reported as meanchange, but sometimes were reported as preintervention andpostintervention measures or percentage change. In the latter cases, transformations were used to express weight loss and
BMI as mean change. When available, we used P values forgroup differences to derive the standard deviation of change
from baseline. Otherwise, we used the pre- and postintervention standard deviations along with a correlation estimatedfrom studies that reported both change and pre- and postintervention results. In the case of percentage change, we assumed independence.

Data Synthesis and Analysis
Analyses were conducted using 6- and 12-month data, with a
3-month window (eg, if a study reported weight loss at 5
months, it was used in the 6-month analysis). The connectivity of each network meta-analysis was described using density, which was calculated as the ratio of the number of treatment pairs with head-to-head evidence over the total numberof treatment pairs. Random-effects pairwise meta-analyses(using the method by DerSimonian and Laird19) were used todetermine direct and indirect associated treatment effects for
all network meta-analyses.

Confidence in Estimates of Effect
For diet classes at 12-month follow-up, we assessed the quality of evidence associated with specific comparisons using the
Grading of Recommendations, Assessment, Development and
Evaluation (GRADE) approach.21 For both direct and indirectcomparisons, the starting point for confidence in estimates washigh, but could be rated down to moderate, low, or very low
based on risk of bias, imprecision, inconsistency, and indirectness.

Assessment of Publication Bias
For our branded diet analysis, we made a visual assessmentof funnel plots for publication bias for direct comparisons that
included 10 or more studies.

Results
Searches of 6 primary electronic databases identified 20 835
unique abstracts, titles, or both identified as original publications. The gray literature search identified 213 additional articles. Of the total, 889 proved potentially relevant for fulltext review and 59 articles that reported 48 RCTs of 11 branded
diets proved eligible (eFigure 1 in the Supplement).9,10,17,18,22-65
The 48 RCTs included 7286 individuals with a median ageof 45.7 years (median SD, 9 years), median weight of 94.1 kg(median SD, 14.6 kg), and median BMI of 33.7 (median SD, 4.3).
The median duration of the diet intervention across trials was
24 weeks (interquartile range, 16-52 weeks). The key characteristics of each included trial appear in Table 2. Forty-three
trials (n = 5608) comprising 103 study groups reported weightloss at 6-month follow-up. The 6-month network metaanalyses were categorized according to diet class (eFigure 2 in
the Supplement) and diet brand (eFigure 3).

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Weight Loss Among Named Diet Programs

Table 2. Characteristics of Included StudiesbFemaleSex,
No. (%)BMI,
Mean (SD)cBody Weight,
Mean (SD),kg
91.7 (7.2)

SourceDiet Program (Class)

Population Description

No.

Age,
Mean (SD), y

Brehm et al,22 2003

Atkins (low carbohydrate)

Obese, otherwise healthy

5343.6 (7.7)

42 (100.0)

33.6 (1.8)

Brehm et al,23 2005

Atkins (low carbohydrate)

Obese, otherwise healthy5043.1 (12.5)

40 (100.0)

33.1 (2.2)

90.7 (10.1)

Brinkworth et al,24,66 2009

Atkins (low carbohydrate)

Abdominal obesity and 1 othermetabolic syndrome risk
factor118

49.8 (8.1)

75 (63.6)

33.7 (4.3)

95.5 (15.6)

Daly et al,25 2006

Atkins (low carbohydrate)

Obese, poorly controlled type2 diabetes

102

58.6 (10.8)

53 (51.9)

36.0 (6.9) 101.9 (15.4)

Dansinger et al,26 2005

Atkins (low carbohydrate),
Ornish (low fat), Weight
Watchers (moderate), Zone
(low carbohydrate)

Obese and 1 other metabolic
cardiac risk factor

160

49.0 (11.0)

81 (51.0)

35.0 (3.9) 100.0 (15.0)

Davis et al,27 2009

Atkins (low carbohydrate)

Obese, type 2 diabetes

105

53.5 (6.5)

82 (78.1)

36.0 (6.0)

97.3 (18.5)

Foster et al,17 2003

Atkins (low carbohydrate),
LEARN (moderate)

Obese, otherwise healthy

6344.1 (8.2)

43 (68.2)

34.15 (3.4)

98.5 (17.9)

Foster et al,28 2010

Atkins (low carbohydrate)

Obese, otherwise healthy307

45.6 (9.7)

208 (67.8)

36.1 (3.5) 103.4 (14.9)

Gardner et al,18 2007

Obese, otherwise healthy
Atkins (low carbohydrate),
LEARN (low fat), Ornish (lowfat), Zone (low carbohydrate)

311

41.0 (6.0)

311 (100.0)

32.0 (4.0)

Iqbal et al,29 2010

Atkins (low carbohydrate)

Obese, type 2 diabetes

144

59.2 (9.2)

15 (10.4)

37.6 (5.5) 116.9 (19.0)

McAuley et al,30 2005

Atkins (low carbohydrate),
Zone (low carbohydrate)

Obese, otherwise healthy

9645.6 (7.6)

93 (100.0)

35.7 (4.9)

95.7 (13.4)
99.9 (14.6)

a31

Ruth et al,

2013

85.0 (12.0)

Atkins (low carbohydrate)

Obese, otherwise healthy55

42.5 (12.1)

49 (89.1)

36.5 (4.7)

Stern et al,9 2004 andSamaha et al,67 2003

Atkins (low carbohydrate)

Diabetes and metabolic
syndrome

132

53.5 (9.0)

23 (17.4)

42.9 (7.1) 130.9 (25.0)

Shai et al,32 2008

Atkins (low carbohydrate)

Obese (BMI ≥27), type 2
diabetes, or coronary heartdisease regardless of BMI

322

52.0 (7.0)

45 (14.0)

30.9 (3.6)

91.4 (13.4)

Tay et al,33 2008

Atkins (low carbohydrate)

Abdominal obesity and 1 othermetabolic syndrome risk
factor118

50.6 (7.9)

57 (64.8)

33.7 (4.2)

94.8 (14.0)

Thomson et al,34 2010

Atkins (low carbohydrate)

Stage 1 or 2 breast cancer

4356.2 (9.4)

40 (100.0)

31.8 (4.3)

84.1 (12.3)

Truby et al,35 2006 andMorgan et al,68 2009

Atkins (low carbohydrate),
Rosemary Conley (low fat),
Weight Watchers (moderate)

Obese, otherwise healthy29340.2 (10.2)

214 (73.0)

31.6 (2.6)

89.3 (13.3)

Volek et al,10,69 2009

Atkins (low carbohydrate)

Obese, atherogenic
dyslipidemia

40

34.8 (11.9)

20 (50.0)

32.8 (4.7)

95.5 (14.5)

Westman et al,36 2008

Atkins (low carbohydrate)

Obese, type 2 diabetes

97

51.8 (7.5)

66 (78.6)

38.1 (5.8) 105.9 (19.8)

Yancy et al,37 2004,
Westman et al,70 2006, andYancy et al,71 2009

Atkins (low carbohydrate)

Obese, otherwise healthy12044.9 (9.5)

91 (76.5)

34.3 (5.0)

Collins et al,38 2012

Biggest Loser (moderate)

Obese, otherwise healthy309

42.0 (10.2)

180 (58.0)

32.3 (4.0)

94.0 (14.6)

Rock et al,39 2007

Jenny Craig (moderate)

Obese, otherwise healthy7041.1 (11.5)

70 (100.0)

34.0 (3.6)

92.0 (10.8)

97.3 (17.1)

Rock et al,40 2010

Jenny Craig (moderate)

Obese, otherwise healthy44644.3 (10.3)

442 (100.0)

33.9 (3.6)

92.0 (9.9)

Blumenthal et al,41 2000

LEARN (low fat)

Obese, unmedicated highnormal blood pressure or
stage 1 or 2 hypertension

133

47.5 (8.9)

74 (56.0)

32.5 (4.4)

94.2 (16.5)

Goodrick et al,42 1998

LEARN (moderate)

Overweight, binge eating,otherwise healthy219

40.0 (6.3)

219 (100.0)

33.0 (3.2)

87.8 (9.9)

Wadden et al,43 2004

LEARN (moderate)

Obese, otherwise healthy

12344.1 (9.9)

123 (100.0)

35.9 (4.5)

97.3 (13.0)

Wing et al,44 1998

LEARN (moderate)

Obese but without diabetes; 1
or both parents with type 2
diabetes

154

45.7 (4.4)

122 (79.0)

35.9 (4.3)

98.7 (15.0)

Womble et al,45 2004

LEARN (moderate)

Obese, otherwise healthy

4743.7 (10.2)

47 (100.0)

33.5 (3.1)

90.6 (11.7)

Figueroa et al,46 2013

Nutrisystem (moderate)

Obese females, otherwise
healthy41

54.3 (3.7)

41 (100.0)

33.4 (3.8)

89.2 (14.6)

Foster et al,47 2009

Nutrisystem (moderate)

Obese, type 2 diabetes

69

52.2 (9.5)

49 (71.0)

39.0 (6.2) 111.2 (21.3)

Aldana et al,48 2007

Ornish (low fat)Coronary artery disease orcoronary-related health issues

98

62.0 (9.1)

41 (44.0)

31.0 (6.1)

90.0 (21.2)

Jolly et al,49 2011

Rosemary Conley (low fat),Slimming World (NA), Weight
Watchers (moderate)

Obese, otherwise healthy740

49.3 (14.7)

513 (69.3)

33.6 (3.7)

93.3 (14.4)

Swenson et al,50 2007

South Beach (lowcarbohydrate)

Obese, otherwise healthy

3240.7 (8.7)

29 (90.6)

48.5 (9.1) 182.0 (78.0)(continued)

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Original Investigation Research

Table 2. Characteristics of Included Studies (continued)
FemaleSex,
No. (%)BMI,
Mean (SD)cBody Weight,
Mean (SD),kg
90.5 (9.5)

SourceDiet Program (Class)

Population Description

No.

Ello-Martin et al,51 2007

Volumetrics (moderate)

Obese, otherwise healthy

9744.9 (9.4)

97 (100.0)

33.3 (2.6)

Djuric et al,52 2002

Weight Watchers (moderate)

Stage 1 or 2 breast cancer

48

51.7 (8.4)

48 (100.0)

35.5 (3.9)

95.4 (13.6)

Heshka et al,53,72 2000

Weight Watchers (moderate)

Obese, otherwise healthy423

44.5 (10.0)358 (84.6)

33.7 (3.5)

93.6 (13.7)

Jebb et al,54 2011

Weight Watchers (moderate)

Obese and 1 other risk factor
for obesity-related disease772

47.3 (12.8)

668 (86.5)

31.4 (2.6)

86.7 (11.5)

55

Pinto et al,

2013

Weight Watchers (moderate)

Obese, otherwise healthy

14449.7 (9.2)

127 (90.0)

36.1 (5.4)

96.5 (17.5)

Rippe et al,56 1998

Weight Watchers (moderate)

Overweight, otherwise
healthy80

36.5 (6.9)

44 (100.0)

NS

81.7 (6.4)

Brinkworth et al,57,73
2004, Farnsworth et al,74
2003, Layman et al,75
2003, and Parker et al,76
2002

Zone (low carbohydrate)

Obese, type 2 diabetes

66

61.8 (7.8)

23 (60.5)

33.4 (5.4)

93.7 (18.0)

Das et al,58 2007

Zone (low carbohydrate)

Obese, otherwise healthy3435.0 (6.0)

NS

27.6 (1.4)

79.0 (10.6)

Ebbeling et al,59 2007

Zone (low carbohydrate)

Obese, otherwise healthy73

27.6 (4.0)

58 (79.0)

NS

103.4 (16.2)

Galletly et al,60 2007

Zone (low carbohydrate)

Overweight, polycystic ovary
syndrome

28

32.5 (1.2)

28 (100.0)

37.4 (6.6)

101.4 (4.9)

Lasker et al,61 2008

Zone (low carbohydrate)

Obese, otherwise healthy

6547.2 (7.0)

31 (62.0)

33.6 (4.5)

95.4 (15.0)

Layman et al,62 2005

Zone (low carbohydrate)

Obese, otherwise healthy

48

46.7 (4.9)

48 (100.0)

32.9 (5.1)

87.6 (13.7)

Layman et al,63 2009

Zone (low carbohydrate)

Obese, otherwise healthy

13045.4 (13.7)

71 (54.6)

32.6 (9.1)

92.7 (14.5)

Luscombe et al,64 2002

Zone (low carbohydrate)

Type 2 diabetes

32

63.2 (9.7)

15 (57.7)

33.3 (4.7)

92.6 (15.8)

Luscombe et al,65 2003

Zone (low carbohydrate)

Obese, hyperinsulinemia

36

54.0 (6.0)

26 (72.2)

34.1 (4.2)

94.0 (15.0)

author. If an author published more than 1 trial on the same branded diet (eg,Rock et al39,40 published 2 trials evaluating Jenny Craig), we ordered thestudies in chronological order according to the year the trial was published.

Abbreviations: BMI, body mass index; LEARN, Lifestyle, Exercise, Attitudes,
Relationships, and Nutrition; NA, not applicable; NS, not specified.
a

b

Age,
Mean (SD), ya

Moderate macronutrient class is abbreviated as moderate in this table. Eligible
comparators were wait-listed controls, no assigned diet, or competing dietary
programs. The order of studies is alphabetical according to branded dietintervention (eg, Atkins, Biggest Loser, Jenny Craig). Among branded dietsthat have multiple studies, trials are listed according to the last name of theModerate macronutrient and low-carbohydrate diets
were the most common diet classes; among these, Atkins,
Weight Watchers, and Zone were the brands with the mostcomparisons. Twenty-five trials (n = 5386) with 67 groups
reported weight loss at 12-month follow-up (eFigures 2 and3 in the Supplement). The diet class network meta-analysis
at both time points had a density of 1.0. Because these network meta-analyses were completely connected, all estimated effects were informed by both direct and indirect evidence. Aside from the 4 named diets that were only
connected to a single node (Biggest Loser, Jenny Craig,
Nutrisystem, and Volumetrics), the 6- and 12-month brand
network meta-analyses were well connected with densities
of 0.36 and 0.47, respectively.

Risk of Bias
Risk of bias of included studies was assessed by diet classand by diet brand (eTable 2 in the Supplement). Twentynine trials were at low risk of bias and 19 were at high riskof bias.

Weight Loss Diet Classes
In the analysis adjusted for diet class, all treatments were superior to no diet at 6-month follow-up (Figure 1). Comparedwith no diet, low-carbohydrate diets had a median differencein weight loss of 8.73 kg (95% credible interval [CI], 7.27-10.20

bThis column includes the number of randomized participants included in trial.

c

Calculated as weight in kilograms divided by height in meters squared.

kg) and low-fat diets had similar estimated effects (7.99 kg [95%CI, 6.01-9.92 kg]). A low-carbohydrate diet resulted in increased weight loss compared with other diet classes (LEARN,
moderate macronutrient distribution), but was not distinguishable from low-fat diets.
At 12-month follow-up, the estimated average weightlosses of all diet classes compared with no diet wereapproximately 1 to 2 kg less than after 6-month follow-up.
The diet classes of low fat (7.27 kg [95% CI, 5.26-9.34 kg])and low carbohydrate (7.25 kg [95% CI, 5.33-9.25 kg) continued to have the largest estimated treatment effects. At
6-month follow-up, the low-carbohydrate diet class had thehighest estimated probability of being superior to all otherdiet classes at 83%; however, at 12-month follow-up, thelow-fat diet demonstrated the highest probability at 50%(Figure 1).
Meta-regression used to account for the use of exercise,
calorie restriction, and the degree of behavioral support ofeach diet group at 6-month follow-up led to a model forweight loss with both exercise and behavioral support factors. Effect modification at 6-month follow-up differed fromestimates at 12-month follow-up for behavioral support (3.23
kg [95% CI, 2.23 to 4.23 kg] vs 1.08 kg [95% CI, −1.82 to 3.96kg], respectively) and exercise (0.64 kg [95% CI, −0.35 to 1.66kg] vs 2.13 kg [95% CI, 0.43 to 3.85 kg]). Calorie restriction did
not modify the effects.

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Research Original Investigation

Weight Loss Among Named Diet Programs

Figure 1. Difference in Mean Weight Loss at 6- and 12-Month Follow-up Across All Diet Classes With 95% Credible Intervals

6-mo Weight Loss, kg

12-mo Weight Loss, kg
No diet(6 mo: 0; 12 mo: 0)a5.16(2.68 to 7.63)

5.70(4.14 to 7.35)

7.25(5.33 to 9.25)

7.27(5.26 to 9.34)

6.07(4.23 to 7.84)

LEARN(6 mo: 0; 12 mo: 0.02)a

0.55(−1.71 to 2.87)

2.10(−0.20 to 4.47)

2.12(−0.33 to 4.59)

6.78(5.50 to 8.05)

0.71(−0.97 to 2.44)

Moderate macronutrients(6 mo: 0; 12 mo: 0)a1.55(0.13 to 2.95)

1.56(−0.17 to 3.30)

8.73(7.27 to 10.20)

2.66(0.93 to 4.44)

1.95(1.13 to 2.79)

Low carbohydrate(6 mo: 0.83; 12 mo: 0.48)a

0.02(−1.78 to 1.79)

7.99(6.01 to 9.92)

1.92(−0.19 to 4.06)

1.20(−0.42 to 2.79)−0.74(−2.31 to 0.78)

Low fat(6 mo: 0.17; 12 mo: 0.50)a

The values above the diet classes (blue boxes) correspond to the difference inmean weight lost between the columns and row at 12 months (eg, thedifference in average weight lost between moderate macronutrients and nodiet at 12 months is 5.70 kg). The values below the diet classes correspond to
the difference in mean weight lost between the row and the column at 6
months (eg, the difference in average weight lost between moderate

Sensitivity Analysis
The findings of our sensitivity analyses in which populations withspecific health problems (eg, breast cancer) were removed appear in eTable 3 in the Supplement. The findings were similar to
the full analysis; low-carbohydrate diets demonstrated the mostfavorable estimates at 6-month follow-up, whereas low-fat diets
were most favorable at 12-month follow-up.
Sensitivity analyses for low risk of bias, proportion lost tofollow-up, baseline weights, and proportion female at 6- and
12-month follow-up also showed similar results (eTables 4-7
in the Supplement).

Individual Named Diets
In the adjusted named analysis, all diets demonstrated weight
reduction at 6-month follow-up compared with no diet
(Figure 2). The largest estimated effects at 6-month follow-up were found with the Atkins diet with a median difference in weight loss of 10.14 kg (95% CI, 8.19-12.12 kg), followed by the Volumetrics diet (9.87 kg [95% CI, 5.54-14.23 kg])and the Ornish diet (9.03 kg [95% CI, 6.44-11.66 kg]). The estimated effect of behavioral support (3.67 kg [95% CI, 1.455.88 kg]) and exercise (1.15 kg [95% CI, 0.14-2.16 kg]) were similar to those obtained in the diet class network meta-analysis.
All diets except Jenny Craig slightly decreased in their estimated effects at 12-month follow-up compared with 6-monthfollow-up. The Ornish, Rosemary Conley, Jenny Craig, and Atkins diets were associated with the largest weight loss at thistime point and all varied between 6.35 kg and 6.55 kg.
The findings of the sensitivity analyses for the named diets
network meta-analysis in which populations with specifichealth problems and high risk of bias studies were removed
appear in eTables 8 and 9 in the Supplement. In these analyses, some head-to-head comparisons from the primary analysis were no longer present, thus leaving the network metaanalysis sparser.
Our findings were not sensitive at 6- and 12-month follow-up to the removal of populations with additional healthissues. Among studies at low risk of bias, the point estimates928

macronutrients and no diet at 6 months is 6.78 kg). LEARN indicates Lifestyle,Exercise, Attitudes, Relationships, and Nutrition.
a

The values in parentheses represent the estimated probability of thattreatment being the best.

are smaller than our primary analysis; however, tests for interaction demonstrated no significant differences among trials
at low vs high risk of bias.
For assessing publication bias, one comparison at 6-monthfollow-up and no comparisons at 12-month follow-up included 10 or more studies. Based on 15 studies comparing Atkins with moderate macronutrient diets, a funnel plot demonstrates asymmetry, suggesting publication bias (eFigure 4
in the Supplement).77

Confidence in Estimates
The overall quality of the evidence using GRADE methods forour direct, indirect, and overall network meta-analysis estimates appear in eTables 10-12 in the Supplement. We assessed the confidence in estimates of effect for weight loss at
12-month follow-up as moderate to low for all comparisons,suggesting that further research is likely to have an important effect on our confidence in the estimation of effect andmay change the estimate (eTable 12 in the Supplement).

Body Mass Index
Due to a considerably lower number of studies reporting BMI
measures, the associated network meta-analyses were sparseand do not permit trustworthy inferences (eFigures 5-6 andeTables 13-14 in the Supplement).

Adverse Events
Adverse events were reported in 5 included trials, all of which
evaluated the Atkins diet.9,28,29,36,37 Although there were no
significant differences in serious adverse events among treatment groups, the only trial to find significant differences in mild
adverse events reported that they occurred more frequently
in the low-carbohydrate diet group (n = 60) than in the lowfat diet group (n = 60), including constipation (68% vs 35%, respectively; P < .001), headache (60% vs 40%; P < .03), halitosis (38% vs 8%; P < .001), muscle cramps (35% vs 7%; P < .001),
diarrhea (23% vs 7%; P < .02), general weakness (25% vs 8%;
P < .01), and rash (13% vs 0%; P < .006).37

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3.86(−0.37 to 8.11)

0.54(−3.51 to 4.55)−0.58(−4.42 to 3.23)

1.40(−1.66 to 4.43)

NA

9.87
(5.54 to 14.23)

6.56(2.75 to 10.29)

5.43(1.50 to 9.31)

7.41(4.63 to 10.18)

NA

8.44
(6.42 to 10.44)−0.23(−3.26 to 2.81)

2.42(0.60 to 4.26)

10.14(8.19 to 12.12)

5.78(3.29 to 8.29)

4.13(2.40 to 5.88)

8.26(5.87 to 10.66)

3.02(0.62 to 5.45)

2.25(−0.18 to 4.72)

7.67(5.79 to 9.56)

9.03(6.44 to 11.66)

1.65(0 to 3.34)

6.02(4.20 to 7.81)

1.24(−1.08 to 3.58)

LEARN

No diet7.26(5.25 to 9.27)

4.10(1.30 to 6.91)

NA

−0.26
(−3.39 to 2.85)−2.23(−6.22 to 1.69)−1.13(−5.09 to 2.77)

2.20(−1.71 to 6.11)−1.89(−4.99 to 1.22)

1.36(−0.72 to 3.43)−0.41(−2.35 to 1.54)

0.77(−0.39 to 1.92)

2.48(1.55 to 3.44)

0.59(−1.75 to 2.95)

Moderate
macronutrient

0.41(−1.98 to 2.82)

4.51(2.37 to 6.73)

Atkins−0.83(−4.46 to 2.75)

1.86(0.29 to 3.40)

2.27(−0.22 to 4.77)

6.35(3.88 to 8.89)

Zone

−0.42
(−2.79 to 1.96)−1.23(−4.56 to 1.97)

1.45(−0.75 to 3.61)

1.85(−0.97 to 4.65)

5.95(3.23 to 8.72)−1.12(−3.24 to 1.00)

0.59(−1.58 to 2.75)−3.60(−7.54 to 0.29)−0.28(−4.30 to 3.74)−1.90(−5.89 to 2.08)

1.44(−2.63 to 5.51)

NA

−0.85
(−4.58 to 2.83)
NA

−2.74
(−5.90 to 0.41)
NA

−1.03
(−4.27 to 2.24)

−2.84
−4.71
−3.00
(−7.49 to 1.73) (−8.70 to −0.78) (−7.10 to 1.05)−1.72(−5.98 to 2.48)

1.62(−2.95 to 6.16)

−2.49
−4.36
−2.66
(−5.93 to 0.95) (−7.53 to −1.22) (−5.79 to 0.52)

0.77(−2.18 to 3.67)

−0.99
−2.88
−1.17
(−3.69 to 1.63) (−4.94 to −0.88) (−3.27 to 0.90)

0.17
−1.71
(−2.05 to 2.36) (−3.09 to −0.35)

1.88(−0.55 to 4.34)

Low fat2.69(−0.73 to 6.10)

3.08(−0.52 to 6.76)

7.19(3.83 to 10.63)

NA

0.15
(−3.38 to 3.65)−1.82(−6.27 to 2.59)−0.70(−4.53 to 3.02)

2.61(−1.76 to 6.98)−1.48(−4.65 to 1.67)

1.77(−0.84 to 4.40)

WeightWatchers−0.05(−2.66 to 2.62)−0.45(−2.74 to 1.90)−1.28(−4.84 to 2.31)

1.40(−0.54 to 3.37)

1.79(−1.02 to 4.70)−3.33(−8.87 to 2.14)

Volumetrics−0.44(−6.76 to 6.06)−0.57(−6.19 to 5.05)

0.08(−5.29 to 5.39)

0.04(−5.32 to 5.42)−0.37(−5.54 to 4.82)−1.20(−7.27 to 4.80)

1.48(−3.45 to 6.40)

1.88(−3.62 to 7.43)

5.98(0.63 to 11.46)

Rosemary
Conley0.49(−5.31 to 6.20)

0.05(−4.35 to 4.53)−0.08(−3.88 to 3.64)

0.57(−2.41 to 3.44)

0.52(−2.93 to 3.97)

0.11(−3.05 to 3.25)−0.71(−4.88 to 3.41)

1.96(−0.98 to 4.87)

2.36(−1.24 to 6.00)

6.47(3.56 to 9.45)

NA

1.62
(−2.12 to 5.38)

NA

−2.45
(−7.53 to 2.53)

NA

0.86
(−3.98 to 5.72)

−0.35
−4.42
−1.13
(−4.89 to 4.16) (−10.04 to 1.14) (−6.40 to 4.24)

0.76(−3.69 to 5.17)

4.09(−0.89 to 9.11)

Jenny Craig−0.12(−4.86 to 4.40)

0.52(−3.50 to 4.31)

0.48(−3.93 to 4.73)

0.07(−4.25 to 4.19)−0.77(−5.72 to 3.93)

1.92(−2.20 to 5.87)

2.34(−2.07 to 6.59)

6.42(3.04 to 9.70)

NA

1.97
(−2.18 to 6.19)

Biggest Loser

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

Nutrisystem

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

Slimming
World

NA

NA

−2.32
(−6.44 to 1.87)−1.82(−8.08 to 4.32)−2.26(−7.20 to 2.86)−2.39(−6.88 to 2.05)−1.75(−5.52 to 1.96)−1.80(−5.98 to 2.46)−2.22(−6.17 to 1.79)−3.02(−7.93 to 1.87)−0.36(−4.06 to 3.39)

0.05(−4.14 to 4.30)

4.15(0.36 to 8.05)

the row and the column at 6 months (eg, the difference in average weight lost between the Ornish diet and nodiet at 6 months is 9.03 kg). LEARN indicates Lifestyle, Exercise, Attitudes, Relationships, and Nutrition.

NA

−1.62
(−5.27 to 2.03)−3.58(−8.03 to 0.80)−2.50(−6.83 to 1.80)

0.84(−3.59 to 5.31)−3.25(−6.85 to 0.32)

Ornish0.65(−2.37 to 3.61)

0.60(−2.25 to 3.46)

0.19(−2.50 to 2.91)−0.64(−4.58 to 3.31)

2.04(−0.55 to 4.69)

2.45(−0.63 to 5.59)

6.55(3.42 to 9.79)

12-mo Weight Loss, kg
5.90(3.88 to 8.05)

The values above the named diets (blue boxes) correspond to the difference in mean weight lost between thecolumns and row at 12 months (eg, the difference in average weight lost between the Ornish diet and no diet at 12
months is 6.55 kg). The values below the diet classes correspond to the difference in mean weight lost between

6-mo Weight Loss, kg

Figure 2. Difference in Mean Weight Loss Across Diets With 95% Credible Intervals

Weight Loss Among Named Diet Programs
Original Investigation Research

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929

Research Original Investigation

Weight Loss Among Named Diet Programs

Discussion
Among the 48 original RCTs included in our network metaanalysis, evidence of low to moderate quality showed that both
low-carbohydrate and low-fat diets were associated with anestimated 8-kg weight loss at 6-month follow-up comparedwith no diet. Approximately 1 to 2 kg of this effect was lost by
12-month follow-up. Although statistical differences existed
among several of the diets, the differences were small and unlikely to be important to those seeking weight loss.
These findings support recent recommendations for weightloss in that most calorie-reducing diets result in clinically important weight loss as long as the diet is maintained.6 Network meta-analysis showed that although there are statistically significant differences between some of the named diets,
these differences are small and likely to be unimportant tomany seeking to lose weight. For example, the Atkins diet resulted in an estimated weight loss of only 1.71 kg (95% CI, 0.353.09 kg) more than the Zone diet at 6-month follow-up. Because different diets are variably tolerated by individuals, theideal diet is the one that is best adhered to by individuals sothat they can stay on the diet as long as possible.
Network meta-analysis yielded larger weight loss estimates for diets compared with no dieting than the observed
weight loss in the primary studies. This is explained by the effect of statistical adjustment for exercise that results in an apparent net weight gain for the no diet group. A similar effectis observed for behavioral support adjustment. The network
meta-analysis estimates for trials that failed to include behavioral support were adjusted accordingly, leading to higher estimates than those originally reported.
The strengths of this review include our use of network
meta-analyses that allowed for simultaneous direct and indirect comparisons of both dietary classes and individual named
diets, a comprehensive literature search, an assessment of riskof bias, and application of the GRADE approach to rating confidence in estimates of effect of diet classes at 12-month followup. We also systematically addressed the potential harms ofnamed diets; however, only 5 of 48 included trials reported information about adverse events.
To provide insight into the quality of the evidence, we applied GRADE methods to rate our confidence in the estimatesof effect. To avoid redundancy, we only did so to the 12month comparisons and not the 6-month comparisons for thediet classes (eTables 10-12 in the Supplement). However, theestimates at 12-month follow-up are the most relevant for individuals concerned about long-term weight loss. Furthermore, because there are considerably more trials reporting
6-month data, the network meta-analysis had increased density and the comparisons had more power, thus our confidence in the 6-month estimates is at least as great as those reported at 12-month follow-up using GRADE methods.
Our study has limitations related to the underlying evidence base for clinical trials on weight loss. For the 10 directcomparisons in which more than 1 study was available, 7comparisons (eTable 10 in the Supplement) demonstrated
substantial heterogeneity between studies, manifested by an
930

I2 exceeding 70%, and visual inspection of forest plots confirming large inconsistencies between study results. Within
our GRADE assessment, we rated the quality of evidence forour direct estimates for inconsistency as weaker inferences.
Because we were unable to demonstrate that the differencesin patients, interventions, or adherence influenced the magnitude of effect, we did not rate the quality of evidence
down for indirect estimates across studies (eTable 11 in the
Supplement).
Furthermore, 19 of 48 trials were at high risk of bias mostly
as a result of missing participant outcome data, and the low
and high risk of bias trials were not uniformly distributed acrosscomparisons (eTable 2 in the Supplement). Nevertheless, we
did not exclude studies because of risk of bias, primarily because the effect of treatment did not significantly vary after
adjusting for missing participant outcome data and overall riskof bias (eTables 4-5 and eTable 9 in the Supplement). Our approach is consistent with the practices used in the systematic
review methodological community.77,78
Our study also has limitations related to network metaanalysis connectivity, evaluation of effect modifiers, and assessment of publication bias. First, confidence in estimates islower for individual brand-named diets (in particular for somecomparisons) because they were poorly connected to the network meta-analysis, have small sample sizes, or both. In particular, Volumetrics (n = 97) and Jenny Craig (n = 516), which
both fared well at 6- and 12-month follow-up, were only connected to a single other diet.
Second, although we accounted for the variability due tocalorie restriction, exercise, and behavioral support using metaregression, there were limitations in the explicit presentationof data regarding calorie restriction. Exercise and behavioral
support were associated with increased weight loss, though
we found no association with behavioral support at 12month follow-up. This lack of effect at 12-month follow-up may
be explained by our definition of behavioral support, whichplaced more importance on the intensity of support within thefirst 3 months of a diet.12
Third, a limitation of our review is that analyses were basedon the original intended randomized design, not by adherence to the actual macronutrient composition (class) and caloric intake consumed.2 This means that although patients wererandomized to various diets or controls, details on their actual adherence to the dietary program (eg, daily caloric intake, macronutrient consumption, and length and intensity of
exercise was limited to the published reports) were not accounted for in the analyses.
Fourth, because there were fewer than 10 trials in all but 1
paired comparison, our assessment of publication bias was very
limited.77
Although we used different methods, our study findings
are similar to the review by the Joint Guidelines from the American Heart Association, the American College of Cardiology, andthe Obesity Society, concluding that popular diets are roughly
equally effective,6,79 and that evidence is inadequate to recommend any particular diet.80 Even though we found that lowcarbohydrate (eg, Atkins) and low-fat (eg, Ornish) dietary programs are associated with the greatest weight loss, these

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Original Investigation Researchdifferences were minor and likely unimportant to those interested in losing weight. The methodological differences between our analysis and the Joint Guidelines6 appear in eTable
15 in the Supplement.
We did not exclude studies based on any criteria beyond
study design. There is concern within the clinical research community that excluding studies based on arbitrary thresholds
for study quality may have an important influence on the study
results of systematic reviews81 because subsequent evidence
may demonstrate that assumed quality items have less effectthan expected.82 Using the approach advocated by both the
Cochrane Collaboration and the GRADE working group, we included all RCTs and considered rating down confidence in estimates because of risk of bias (eTables 4-5 and eTable 9 in the
Supplement).77,78
We examined the relationship between estimated effectsize, loss to follow-up, and overall risk of bias, and after finding no relationship, did not consider risk of bias an important
effect modifier. As we have noted previously in this discussion, this approach is perhaps the most potentially controversial of our methodological decisions. There is a clear need fora better understanding between clinical trialists and guideline developers regarding the influence of loss to follow-up andother risk of bias issues. This issue is not limited to diets, but
probably affects all fields of medicine.83
Similar to previous reviews, we found that weight loss decreased at 6-month follow-up,84,85 and began to regress to the

ARTICLE INFORMATION
Author Affiliations: Hospital for Sick Children
Research Institute, Toronto, Ontario, Canada(Johnston, Bandayrel); Institute of Health Policy,
Management and Evaluation, University of Toronto,
Toronto, Ontario, Canada (Johnston); Departmentof Clinical Epidemiology and Biostatistics,
McMaster University, Hamilton, Ontario, Canada(Johnston, Busse, Thorlund, Guyatt); Departmentof Anesthesia and Pain Medicine, Hospital for Sick
Children, University of Toronto, Toronto, Ontario,
Canada (Johnston, Bandayrel); School of
Population and Public Health, University of British
Columbia, Vancouver, Canada (Kanters); Faculty of
Health Sciences, University of Ottawa, Ottawa,
Ontario, Canada (Kanters, Wu); Redwood
Outcomes, Vancouver, British Columbia, Canada(Kanters, Thorlund, Jansen, Mills); Michael G.
DeGroote School of Medicine, McMaster University,
Hamilton, Ontario, Canada (Naji); Department ofMedicine, University of Toronto, Toronto, Ontario,
Canada (Siemieniuk); Department of Pediatrics,
University of Alberta, Edmonton, Canada (Ball);
Department of Agricultural, Food and Nutritional
Science, University of Alberta, Edmonton, Canada(Ball); Michael G. DeGroote Institute for Pain
Research and Care, McMaster University, Hamilton,
Ontario, Canada (Busse); Department ofAnesthesia, McMaster University, Hamilton,
Ontario, Canada (Busse); Stanford Prevention
Research Center, Stanford University School of
Medicine, Stanford University, Stanford, California(Thorlund, Mills); Department of Public Health andCommunity Medicine, Tufts University, Boston,
Massachusetts (Jansen).

baseline mean at 12-month follow-up, suggesting that future
trials of dietary programs should focus on maintenance of longterm weight loss.86 Our findings should be reassuring to clinicians and the public that there is no need for a one-size-fitsall approach to dieting because many different diets appear tooffer considerable weight loss benefits. This is important because many patients have difficulties adhering to strict dietsthat may be particularly associated with cravings or be culturally challenging (such as low-carbohydrate diets).2 Our findings suggest that patients may choose, among those associated with the largest weight loss, the diet that gives them theleast challenges with adherence. Although our study did not
examine switching between diets, such a strategy may offer
patients greater choices as they attempt to adhere to diet andlifestyle changes.

Conclusions
Low-carbohydrate and low-fat dietary programs were associated with more weight loss than no dietary intervention overa 12-month period; behavioral support and exercise enhanced weight loss. The weight loss differences between indivdual named diets were small with likely little importanceto those seeking weight loss. This supports the practice of recommending any diet that a patient will adhere to in order tolose weight.

Author Contributions: Mr Kanters and Dr Mills had
full access to all of the data in the study and takeresponsibility for the integrity of the data and theaccuracy of the data analysis.
Study concept and design: Johnston, Kanters,
Siemieniuk, Ball, Busse, Thorlund, Mills.
Acquisition, analysis, or interpretation of data:
Johnston, Kanters, Bandayrel, Wu, Naji, Siemieniuk,Busse, Thorlund, Guyatt, Jansen, Mills.
Drafting of the manuscript: Johnston, Kanters,
Bandayrel, Naji, Ball, Thorlund, Mills.
Critical revision of the manuscript for important
intellectual content: Johnston, Kanters, Wu,
Siemieniuk, Busse, Thorlund, Guyatt, Jansen, Mills.
Statistical analysis: Johnston, Kanters, Thorlund,Mills.
Obtained funding: Johnston, Ball, Busse, Thorlund,Mills.
Administrative, technical, or material support:
Johnston, Bandayrel, Wu, Naji, Mills.
Study supervision: Johnston, Thorlund, Guyatt,Mills.
Conflict of Interest Disclosures: The authors havecompleted and submitted the ICMJE Form forDisclosure of Potential Conflicts of Interest andnone were reported.
Funding/Support: This work was supported by a
Canadian Institute of Health research knowledge
synthesis grant 201104 via the Public HealthAgency of Canada. Dr Busse holds a Canadian
Institute of Health Research new investigator
award. Dr Mills holds a Canada Research Chair in
global health.
Role of the Funders/Sponsors: The funding
sponsor had no role in the design and conduct of
the study; collection, management, analysis, andjama.com

interpretation of the data; and preparation, review,or approval of the manuscript.
Additional Contributions: We thank Christopher
Gardner, PhD (Stanford Prevention ResearchCenter, Stanford University School of Medicine,
Stanford, California), for his guidance and review ofthe manuscript. Dr Gardner did not receive any
financial compensation for his guidance and reviewof the manuscript.
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