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thebmj
BMJ
2020;369:m696 | doi: 10.1136/bmj.m696 1
RESEARCH
Comparison of dietary macronutrient patterns of 14 popular
named dietary programmes for weight and cardiovascular risk
factor reduction in adults: systematic review and network
meta-analysis of randomised trials
Long Ge,1,2,3 Behnam Sadeghirad,3,4 Geo D C Ball,5 Bruno R da Costa,6,7,8
Christine L Hitchcock,5,9 Anton Svendrovski,9 Ruhi Kiflen,3 Kalimullah Quadri,10
Henry Y Kwon,11 Mohammad Karamouzian,12,13 Thomasin Adams-Webber,14 Waleed Ahmed,15
Samah Damanhoury,16 Dena Zeraatkar,3 Adriani Nikolakopoulou,17 Ross T Tsuyuki,18
Jinhui Tian,19 Kehu Yang,1,19 Gordon H Guyatt,3 Bradley C Johnston3,9,20
ABSTRACT
OBJECTIVE
To determine the relative eectiveness of dietary
macronutrient patterns and popular named diet
programmes for weight loss and cardiovascular risk
factor improvement among adults who are overweight
or obese.
DESIGN
Systematic review and network meta-analysis of
randomised trials.
DATA SOURCES
Medline, Embase, CINAHL, AMED, and CENTRAL from
database inception until September 2018, reference
lists of eligible trials, and related reviews.
STUDY SELECTION
Randomised trials that enrolled adults (≥18 years)
who were overweight (body mass index 25-29) or
obese (≥30) to a popular named diet or an alternative
diet.
OUTCOMES AND MEASURES
Change in body weight, low density lipoprotein
(LDL) cholesterol, high density lipoprotein (HDL)
cholesterol, systolic blood pressure, diastolic blood
pressure, and C reactive protein at the six and 12
month follow-up.
REVIEW METHODS
Two reviewers independently extracted data on
study participants, interventions, and outcomes and
assessed risk of bias, and the certainty of evidence
using the GRADE (grading of recommendations,
assessment, development, and evaluation) approach.
A bayesian framework informed a series of random
eects network meta-analyses to estimate the relative
eectiveness of the diets.
RESULTS
121 eligible trials with 21 942 patients were included
and reported on 14 named diets and three control
diets. Compared with usual diet, low carbohydrate
and low fat diets had a similar eect at six months on
weight loss (4.63 v 4.37 kg, both moderate certainty)
and reduction in systolic blood pressure (5.14 mm
Hg, moderate certainty v 5.05 mm Hg, low certainty)
and diastolic blood pressure (3.21 v 2.85 mm Hg,
both low certainty). Moderate macronutrient diets
resulted in slightly less weight loss and blood
pressure reductions. Low carbohydrate diets had less
eect than low fat diets and moderate macronutrient
diets on reduction in LDL cholesterol (1.01 mg/dL,
low certainty v 7.08 mg/dL, moderate certainty v
5.22 mg/dL, moderate certainty, respectively) but
an increase in HDL cholesterol (2.31 mg/dL, low
certainty), whereas low fat (−1.88 mg/dL, moderate
certainty) and moderate macronutrient (−0.89 mg/dL,
moderate certainty) did not. Among popular named
diets, those with the largest eect on weight
reduction and blood pressure in comparison with
usual diet were Atkins (weight 5.5 kg, systolic blood
pressure 5.1 mm Hg, diastolic blood pressure 3.3
mm Hg), DASH (3.6 kg, 4.7 mm Hg, 2.9 mm Hg,
respectively), and Zone (4.1 kg, 3.5 mm Hg,
2.3 mm Hg, respectively) at six months (all moderate
certainty). No diets signicantly improved levels of
HDL cholesterol or C reactive protein at six months.
Overall, weight loss diminished at 12 months among
all macronutrient patterns and popular named diets,
while the benets for cardiovascular risk factors of
For numbered aliations see
end of the article.
Correspondence to:
B C Johnston
bradley.johnston@tamu.edu
(ORCID 0000-0001-8872-8626)
Additional material is published
online only. To view please visit
the journal online.
Cite this as: BMJ 2020;369:m696
http://dx.doi.org/10.1136/bmj.m696
Accepted: 14 February 2020
WHAT IS ALREADY KNOWN ON THIS TOPIC
A plethora of recommendations have suggested a variety of dietary programmes
for weight management and cardiovascular risk reduction, primarily
Mediterranean and DASH-style diets
Systematic reviews and meta-analyses of randomised trials have suggested that
dierences in weight loss between popular named diets are small and unlikely to
be of importance to those seeking to lose weight, whereas meta-analyses have
yielded conflicting results for cardiovascular risk reduction
Pairwise meta-analyses are limited in examining the relative merit of the range of
popular named diets, and no comprehensive comparative eectiveness review,
using network meta-analyses of diets for both weight loss and cardiovascular
risk factors, has been carried out
WHAT THIS STUDY ADDS
Based on 121 randomised trials with 21 942 patients, low carbohydrate (eg,
Atkins, Zone), low fat (eg, Ornish), and moderate macronutrient (eg, DASH,
Mediterranean) diets had, compared with usual diet, compelling evidence for
modest reduction in weight and potentially important reduction in both systolic
and diastolic blood pressure at six months
Weight reduction at the 12 month follow-up diminished, and aside from the
Mediterranean diet for LDL reduction, improvements in cardiovascular risk
factors largely disappeared
Dierences between diets were typically small to trivial and oen based on low
certainty evidence
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all interventions, except the Mediterranean diet,
essentially disappeared.
CONCLUSIONS
Moderate certainty evidence shows that most
macronutrient diets, over six months, result in
modest weight loss and substantial improvements
in cardiovascular risk factors, particularly blood
pressure. At 12 months the eects on weight
reduction and improvements in cardiovascular risk
factors largely disappear.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42015027929.
Introduction
The worldwide prevalence of obesity nearly tripled
between 1975 and 2018.1 In response, authorities
have made dietary recommendations for weight
management and cardiovascular risk reduction.2 3
Diet programmes—some focusing on carbohydrate
reduction and others on fat reduction—have been
promoted widely by the media and have generated
intense debates about their relative merit. Millions of
people are trying to lose weight by changing their diet.
Thus establishing the eect of dietary macronutrient
patterns (carbohydrate reduction v fat reduction v
moderate macronutrients) and popular named dietary
programmes is important.
Biological and physiological mechanisms have been
proposed to explain why some dietary macronutrient
patterns and popular dietary programmes should be
better than others. A previous network meta-analysis,
however, suggested that dierences in weight loss
between dietary patterns and individual popular
named dietary programmes are small and unlikely to
be important.4 No systematic review and network meta-
analysis has examined the comparative eectiveness of
popular dietary programmes for reducing risk factors
for cardiovascular disease, an area of continuing
controversy.5-8
Proponents of Mediterranean-type and DASH-type
(Dietary Approaches to Stop Hypertension) diets
suggest that these diets can improve risk factors for
cardiovascular disease through weight loss itself and
owing to their limited sodium content and claimed
anti-inflammatory properties.9 Systematic reviews
and meta-analyses have shown conflicting results
for the dietary eect on markers of cardiovascular
disease risk, including blood pressure, low density
lipoprotein (LDL) and high density lipoprotein (HDL)
cholesterol, and C reactive protein.6 8-12 Few reviews
have used rigorous meta-analytical techniques to obtain
quantitative estimates of the relative eect of dierent
diets.4 13 14 Systematic reviews have relied on pairwise
comparisons. These comparisons have failed to examine
direct and indirect clinical trial data by conducting a
network meta-analysis, and they have not dealt with the
certainty (quality) of evidence using the widely accepted
standard, the GRADE (grading of recommendations,
assessment, development, and evaluation) approach.15
We performed a systematic review and network
meta-analysis of randomised controlled trials for
improvements in weight loss and cardiovascular risk
factors to determine the relative eectiveness and
certainty of evidence among dietary macronutrient
patterns and popular named dietary programmes for
adults who are overweight or obese.
Methods
We searched Medline, Embase, CINAHL (Cumulative
Index to Nursing and Allied Health Literature), AMED
(Allied and Complementary Medicine Database),
and the Cochrane Central Register of Controlled
Trials (CENTRAL) from database inception until
September 2018. Search terms included extensive
controlled vocabulary and keyword searches related
to randomised controlled trials, diets, weight loss, and
cardiovascular risk factors. Appendix text S1 presents
the Medline search strategy. We reviewed reference lists
from eligible trials and related reviews for additional
eligible randomised controlled trials.
Eligible studies randomised adults (≥18 years) who
were overweight (body mass index 25-29) or obese
(≥30) to an eligible popular named diet or an alternative
active or non-active control diet (eg, usual diet), and
reported weight loss, changes in lipid profile, blood
pressure, or C reactive protein levels at three months’
follow-up or longer.
We categorised dietary treatment groups in two
ways: using dietary macronutrient patterns (low
carbohydrate, low fat, and moderate macronutrient—
similar to low fat, but slightly more fat and slightly less
carbohydrate) and according to individual popular
Study design Systematic review with
network meta-analysis
Heterogeneous participants, including
those with cardiovascular risk factors
Visual Abstract Do macronutrient diet patterns work?
Comparing diets for weight and blood pressure reduction
Most macronutrient diets, over six months, resulted in modest weight
loss and improved blood pressure. At months, weight reduction
diminished, and blood pressure improvements largely disappeared
Summary
Comparison Interventions Comparator
Usual diet
Dietary
advice
Low
carbohydrate
such as
Atkins, Zone
Low fat
such as Ornish
Moderate
macronutrients
such as DASH,
Mediterranean
Usual diet
1
9
11
44
1
4
6
18
Link width proportional
to number of studies
comparing interventions
for weight loss
21 942
participants
121
RCTs
Data sourcesMean age:
. years
Median intervention
length: weeks
Median
% women
Low fat
Dietary advice
MM *
Outcomes at
six months
compared with
usual diet
Blood pressure reduction mm Hg Weight loss kg
DiastolicSystolic
© 2020 BMJ Publishing group Ltd.
http://bit.ly/BMJmndiet
Low carbohydrate
- - -
Network meta-analysis, mean difference % CI
Low Moderate
GRADE
score
* MM = Moderate
macronutrients
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2020;369:m696 | doi: 10.1136/bmj.m696 3
named dietary programmes.4 Dietary macronutrient
patterns were established by macronutrient content (see
table 1). Leading dietary programmes were identified
through the explicit naming of the branded or popular
diet, the referencing of popular or branded literature,
or the naming of a brand as a funder of a randomised
controlled trial reporting our target outcomes. The diet
was labelled as brand-like when it met the definition
of a branded diet but failed to name or reference the
brand in the article. For example, dietary programmes
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.16 17 Appendix table S1 presents
the characteristics of eligible dietary programmes.
We included dietary programmes with structured
advice for daily macronutrient, food, or caloric
intake for a defined period (≥3 months). Eligible
studies could or could not provide exercise (eg,
walking, strength training) or behavioural support
(eg, counselling, group support online or in person),
and could include meal replacement products, but
had to consist primarily of whole foods and could not
include drugs.
We categorised eligible control diets as: usual
diet (eg, wait list: participants were instructed to
maintain their usual dietary habits), dietary advice
(eg, received brochures, dietary materials including
dietary guidelines, or consultation with a professional
dietician by email or telephone), and low fat diet (≤30%
fat with or without advice about lowering calories). We
used the usual diet as our reference diet and presented
results for the other diets against the reference diet.
Teams of two reviewers independently screened titles
and abstracts for possible inclusion. If either reviewer
considered a study potentially eligible, reviewers
obtained and screened the full text. Reviewers resolved
disagreements by discussion and, when necessary,
through adjudication by a third reviewer.
Data abstraction and risk of bias assessment
After pilot testing our data extraction forms, teams of
two reviewers independently extracted demographic
information, experimental and control interventions
including exercise and behavioural support, and
data on each outcome of interest. We focused on two
sets of outcomes: weight loss and related markers of
cardiovascular disease risk (systolic blood pressure,
diastolic blood pressure, LDL cholesterol, HDL
cholesterol, and C reactive protein) at six and 12 month
follow-up (±3 months for both periods).
Reviewers assessed the risk of bias for each
individual randomised controlled trial independently
and in duplicate using the Cochrane risk of bias tool.18
We assigned individual trials as high risk of bias if one
of two key domains, allocation concealment or missing
outcome data, was deemed high risk of bias; otherwise,
we assigned individual trials as low risk of bias.
Data synthesis and statistical methods
When reported, we used mean change and standard
deviations. When authors reported data as measures
before and after intervention, we used methods
outlined in the Cochrane Handbook to calculate
mean change and standard deviations for change.18
When standard deviations were missing, we estimated
them from standard errors, P values, confidence
intervals, or graphs. If none of these methods was
possible, we derived standard deviations from other
studies included in our network meta-analysis using
a validated imputation technique.19 Appendix text S2
presents details of the missing standard deviations
imputed for each outcome.
We performed statistical analyses for dietary macro-
nutrient patterns based on five nodes (moderate
macronutrients, low carbohydrate, low fat, dietary
advice, and usual diet) and for popular named
diets based on 17 nodes (14 popular named dietary
programmes and three control diets). We used
bayesian random eects models to obtain the pooled
direct estimates and corresponding forest plots of
the available direct comparisons.20 We assessed
heterogeneity between randomised controlled trials
for each direct comparison with visual inspection of
the forest plots and the I2 statistic.
We then performed a series of random eects network
meta-analyses within a bayesian framework using
Markov chain Monte-Carlo simulation methods.21 22
For each analysis, we used three chains with 100 000
iterations after an initial burn-in of 10 000. We
assessed convergence based on trace plots and time
series plots. We measured the goodness of model fit by
the posterior mean of the overall residual deviance; in a
well fitting model the residual deviance should be close
to the number of data points included in the analysis.19
We used vague priors and dealt with the extent of
heterogeneity in each network analysis using a common
heterogeneity variance (τ); we categorised results as
low (from 0.1 to 0.5), moderate (>0.5 to 1.0), and high
(>1.0).23 24 To estimate the precision of the eects, we
used 95% credible intervals, by means of the 2.5 and
97.5 percentiles obtained from the simulations.25 We
Table1 | Nutritional patterns based on macronutrient composition
Type of diet Popular diets* Carbohydrates, % kcal Protein, % kcal Fat, % kcal
Low carbohydrate Atkins, South Beach, Zone ≤40 Approximately 30 30-55
Moderate macronutrients Biggest Loser, DASH, Jenny Craig, Mediterranean, Portfolio,
Slimming World, Volumetrics, Weight Watchers Approximately 55-60 Approximately 15 21-≤30
Low fat Ornish, Rosemary Conley† Approximately 60 Approximately 10-15 ≤20
1 kcal=4.18 kJ.
*A paleolithic diet was reported in two randomised controlled trials (Lindeberg 2007 and Mellberg 2014; appendix table S2), we categorised Lindeberg 2007 as moderate macronutrient based
on energy intake (40.2±8.3% carbohydrate, 27.9±6.8% protein, 26.9±6.4% fat). Mellberg, 2014 was categorised as low carbohydrate (30% carbohydrate, 30% protein, 40% fat).
†We categorised Rosemary Conley diet (Truby 2006) as moderate macronutrient (42% carbohydrate, 16% protein, 37% fat).
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used the node splitting method to generate the eect
size and credible intervals for the indirect comparison
and for the statistical test of incoherence (also
known as inconsistency) between direct and indirect
estimates.26 We calculated the ranking probabilities of
being the best, second best, and so on for all treatment
options and used the surface under the cumulative
ranking curve to rank the intervention hierarchy in the
network meta-analysis.27
We considered two eect modifiers that were
modelled as present or absent if they were included
in an overall dietary programme: exercise and
behavioural support. Exercise was defined as having
explicit instructions for weekly physical activities and
categorised as exercise or no exercise. Diets with at
least two group or individual sessions a month for
the first three months were considered to provide
behavioural support.28 We performed a network
meta-regression assuming a common coecient
across comparisons to explore the eect of exercise
and behavioural support for each outcome.29 Three
sensitivity analyses were conducted by restricting
studies to trials with individuals who were overweight
or obese, but who were otherwise healthy; those
with a low risk of bias; and investigator initiated
randomised trials, thus removing trials that were
funded partly or wholly by diet companies.
We used the networkplot command of Stata version
15.1 (StataCorp, College Station, TX) to draw the
network plots,30 and WinBUGS version 1.4.3 (MRC
Biostatistics Unit, Cambridge, UK) and R version 3.4.3
(R Core Team, Vienna, Austria) with gemtc package
for statistical analyses.
Assessing certainty of evidence
We rated the certainty of evidence for each network
estimate using the GRADE framework, which classi-
fies evidence as high, moderate, low, or very low
certainty. The starting point for certainty in direct
estimates for randomised controlled trials is high,
but could be rated down based on limitations in risk
of bias, imprecision, inconsistency (heterogeneity),
indirectness, and publication bias.15
We rated the certainty of evidence for each direct
comparison according to standard GRADE guidance
for pairwise meta-analysis.31 32 Indirect eect
estimates were calculated from available “loops” of
evidence, which included first order loops (based on
a single common comparator treatment—that is the
dierence between treatment A and B is based on
comparisons of A and C as well as B and C) or higher
order loops (more than one intervening treatment
connecting the two interventions). We assessed the
evidence for indirect and network estimates focusing
on the dominant first order loop,31 rating certainty of
indirect evidence as the lowest certainty of the direct
comparisons informing that dominant loop. In the
absence of a first order loop, we used a higher order
loop to rate certainty of evidence and used the lowest
of the ratings of certainty for the direct estimates
contributing to the loop. We considered further rating
down each indirect comparison for intransitivity if
the distribution of eect modifiers diered in the
contributing direct comparisons.31
For the network estimate, we started with the
certainty of evidence from the direct or indirect
evidence that dominated the comparison and, sub-
sequently, considered rating down our certainty
in the network estimate for incoherence between
the indirect and direct estimates for imprecision
(wide credible intervals) around the treatment eect
estimates. When serious incoherence was present,
we used, as the best estimate, that with the higher
certainty of the direct and indirect evidence.32
Appendix text S3 presents additional details of the
GRADE assessment.
Summary of more and less preferred treatments
To optimise the presentation of results for the 17 diet
(14 popular, three control) network meta-analysis,
we applied a new approach to summarise the results,
establishing dierent groups of interventions (from
the most to the least eective) based on the eect
estimates obtained from the meta-analysis and their
certainty of evidence.33 For each outcome, we created
three groups of interventions. Firstly, the reference
diet (usual diet) and diets that did not dier from the
reference (that is, confidence interval crossed mean
dierence=0), which we refer to as “among the least
eective”. Secondly, diets superior to the reference,
but not superior to any other diet superior to the
reference (which we call category 1 and describe as
“inferior to the most eective, but superior to the least
eective”). Lastly, diets that proved superior to at least
one category 1 diet (which we call “among the most
eective”). We then divided all three categories into
two groups: those with moderate or high certainty
evidence relative to the usual diet, and those with low
or very low certainty evidence relative to the usual diet.
Patient and public involvement
No patients were involved in setting the research
question or the outcome measures, in developing
plans for design or implementation of the study, or in
the interpretation or write up of results. We did not
evaluate whether the studies included in the review
involved patients in planning or implementing the
study.
Results
Search
The electronic searches yielded 27 238 unique
studies, and the grey literature search identified 213
additional studies. Of the total, 1411 were potentially
eligible, and 137 articles reporting 121 randomised
controlled trials proved eligible (fig 1). Appendix text
S4 presents the list of eligible studies.
Study characteristics, risk of bias, and certainty of
evidence
Appendix table S2 summarises the characteristics of
the 121 randomised controlled trials, which included
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from 21 to 1269 participants (total 21 942) with a
median of mean age of 49.0 years, a median of mean
body mass index of 33.0, a median of mean weight
of 92.9 kg, a median proportion of women of 69.0%,
and a median intervention duration of 26 weeks.
Figure 2 provides the network plot of macronutrient
consumption patterns and the popular named diets.
Appendix figures S1-S6 present the network plot for
each outcome, appendix table S3 presents the number
of studies and participants for the popular named diets
for all outcomes, and appendix table S4 summarises
the funding sources and primary and secondary
outcomes reported in included trials.
Ninety four randomised controlled trials were at low
risk of bias and 27 were at high risk of bias (appendix
table S5).
For the outcomes of weight and blood pressure,
many comparisons of popular diets versus the
reference standard, usual diet, provided moderate
certainty evidence. For other outcomes, and for most
comparisons of popular diets against one another,
results provided only low certainty evidence.
Provided by industry contacts
Articles excluded
Not target intervention
Duplicates
Abstract only
Non-randomised controlled trial
Not target population
Not outcomes of interest
Non-English
591
295
113
129
78
44
24
Titles and abstracts screened
Potentially relevant titles and abstracts
Not relevant
Articles for full text review
Articles included (121 unique studies)
213
22 252
Duplicates
23 663
137
3788
1411
1274
27 238
Fig1 | Flow diagram of literature selection
Dietary advice
Low carbohydrate
Low fat
Moderate
macronutrients
Usual diet
Atkins
Biggest Lose
r
DASH
Dietary advice
Jenny
Craig
Low fat
Mediterranean
Ornish
Paleolithic
Portfolio
Rosemary Conley
Slimming World
South Beach
Usual diet
Volumetrics
Weight Watchers
Zone
Fig2 | Network plots of all included studies for macronutrient patterns and popular named diets
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Dietary macronutrient patterns
Appendix tables S6-S11 present GRADE assessments for
all outcomes at six months (±3 months), with the number
of included randomised controlled trials, sample size, I2,
direct estimates, indirect estimates, intransitivity, and
incoherence assessment. Much of the evidence was
judged as moderate certainty, rated down most often
because of serious inconsistency. Compared with a usual
diet, low carbohydrate diets had median dierences in
weight loss of 4.63 kg (95% credible interval 3.42 to 5.87;
moderate certainty; fig 3), a reduction in systolic blood
pressure of 5.14 mm Hg (3.01 to 7.32; moderate certainty;
fig 4), a reduction in diastolic blood pressure of 3.21 mm
Hg (1.89 to 4.53; low certainty; fig 4), an increase in HDL
cholesterol of 2.31 mg/dL (0.68 to 3.87; low certainty;
fig 5), and a reduction in LDL cholesterol of 1.01 mg/dL
(−2.96 to 4.96 mg/dL; low certainty; fig 5). Low fat diets
had estimated eects similar to those of low carbohydrate
diets for weight loss (fig 3) and blood pressure (fig
4), but a greater eect on LDL cholesterol reduction
(7.08 mg/dL; moderate certainty; fig 5). Based on
moderate to low certainty evidence, moderate macro-
nutrient diets had slightly smaller eects than low
carbohydrate diets on weight loss (fig 3), blood pressure
(fig 4), and HDL cholesterol increase (fig 5), but a greater
eect on LDL cholesterol reduction (fig 5). Appendix
table S12 presents the network meta-analysis results for
C reactive protein, showing no statistically significant
dierences between diets.
At the 12 month (±3 months) follow-up, the estimated
average weight loss of all dietary macronutrient
patterns compared with usual diet was 1 to 2 kg less,
generally with low certainty evidence (appendix table
S13). We found no significant dierences between
the macronutrient dietary patterns and usual diet for
systolic and diastolic blood pressure, LDL cholesterol,
and C reactive protein reductions, except low fat
and moderate macronutrients, which each showed
significant adverse reductions in HDL cholesterol
(−2.90 mg/dL, −2.81 mg/dL, respectively; appendix
tables S12, S14, and S15).
Appendix tables S16-S25 present sensitivity analyses
showing that the findings were similar to those of the
primary analyses. Network meta-regression accounting
for both exercise and behaviour support also showed
similar results (appendix tables S26-S28).
Individual popular named diets
Appendix tables S29-S34 present the GRADE
assessment details for all outcomes at six months (±3
months). Figure 6 and appendix table S35 summarise
the results for all outcomes at six months in comparison
with a usual diet, organised by GRADE certainty of
evidence.
Weight loss
Appendix table S36 presents the league table of
weight loss at six months. Among the diets with high
or moderate certainty evidence relative to usual diet,
Jenny Craig and Atkins proved the most eective
popular named diets, whereas Volumetrics, paleolithic,
low fat, Zone, Weight Watchers, Rosemary Conley,
DASH, Ornish, and Mediterranean were inferior to the
most eective but superior to the least eective diet
interventions. The Biggest Loser, Slimming World, and
dietary advice were the least eective diet interventions
(fig 6, appendix table S35). Among the diets with only
low or very low certainty evidence relative to usual
diet, South Beach might be the most eective (fig 6).
All named diets, except a paleolithic diet, decreased
their estimated eects at the 12 month follow-up by, on
average, 1.5 kg compared with the six month follow-up
(appendix tables S36 and S37).
Systolic blood pressure
Appendix table S38 presents the league table of
reduction of systolic blood pressure at six months.
Among the diets with moderate certainty evidence
relative to a usual diet, paleolithic was probably the
most eective, whereas Atkins, DASH, Portfolio, low
fat, Zone, and Mediterranean were probably inferior to
the most eective, but superior to the least eective,
Usual
diet
Dietary
advice
0.02 (-1.71 to 1.76)
4.37 (3.03 to 5.74) 4.35 (2.56 to 6.15)
4.63 (3.42 to 5.87) 4.61 (3.01 to 6.23) 0.26 (-0.92 to 1.45)
3.06 (2.04 to 4.10) 3.04 (1.60 to 4.48)
-1.31 (-2.40 to -0.22) -1.57 (-2.29 to -0.86)
High certainty Moderate certainty Low certainty Very low certainty
Low
fat
Low
carbohydrate
Moderate
macronutrients
Fig3 | Macronutrient pattern network meta-analysis results with corresponding GRADE (grading of recommendations,
assessment, development, and evaluation) certainty of evidence for six month weight loss (kg). Values correspond to
dierence in median weight loss between column and row at six months, for positive values the diet indicated in the
column is favoured (eg, low fat had a median weight loss of 4.37 kg at six months compared with usual diet). Values in
bold indicate a statistically signicant treatment eect
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diets. The Biggest Loser and Ornish proved the least
eective diets. Among the diets with only low or very
low certainty evidence relative to usual diet, Jenny Craig
might be the most eective (fig 6, appendix table S35).
Eects for all popular named diet programmes had
decreased at the 12 month follow-up compared with
the six month follow-up. No statistically significant
dierences were found between popular named diets
and a usual diet (appendix tables S38 and S39).
Diastolic blood pressure
Among the diets with moderate certainty evidence
relative to a usual diet, Atkins proved the most eective
popular named diet at six months, whereas DASH,
low fat, and Zone were probably inferior to the most
eective, but superior to the least eective, diets.
Paleolithic, Biggest Loser, Mediterranean, and Ornish
proved the least eective diets. Among the diets with
only low or very low certainty evidence relative to
a usual diet, Jenny Craig might be the most eective
(fig 6, appendix tables S35 and S38). We found no
statistically significant dierences between popular
named diets and usual diet at the 12 month follow-up
(appendix table S39).
Blood lipoproteins
Among the diets with moderate certainty evidence
relative to usual diet, the Mediterranean diet proved
the most eective popular named diet for LDL
cholesterol reduction; Ornish, DASH, Biggest Loser,
low fat, and dietary advice were probably no better
than usual diet. Among the diets with only low or
Usual
diet
Dietary
advice
1.45 (-1.80 to 4.69)
5.05 (2.51 to 7.58) 3.59 (0.22 to 6.99)
5.14 (3.01 to 7.32) 3.69 (0.69 to 6.74) 0.10 (-1.95 to 2.17)
3.48 (1.72 to 5.26)
1.88 (0.80 to 2.96)
0.83 (-0.83 to 2.48)
-0.96 (-2.25 to 0.30)
-1.33 (-2.16 to -0.51)
2.03 (-0.68 to 4.78)
3.21 (1.89 to 4.53)
2.16 (0.32 to 4.01)
0.36 (-0.95 to 1.66)
-1.57 (-3.56 to 0.45)
2.85 (1.29 to 4.42)
6 month diastolic blood pressure reduction
6 month systolic blood pressure reduction
1.80 (-0.28 to 3.88)
-1.66 (-2.98 to -0.36)
1.05 (-0.92 to 3.02)
High certainty Moderate certainty Low certainty Very low certainty
Low
fat
Low
carbohydrate
Moderate
macronutrients
Fig4 | Macronutrient pattern network meta-analysis results with corresponding GRADE (grading of recommendations,
assessment, development, and evaluation) certainty of evidence for six month systolic blood pressure (SBP) and
diastolic blood pressure (DBP) reduction (mm Hg). Values correspond to dierence in median DBP reduction (above,
right of macronutrient patterns) and SBP reduction (below, le of macronutrient patterns) between column and row at
six months (eg, low fat had a median DBP reduction of 1.80 and a median SBP reduction of 3.59 compared with dietary
advice). Values in bold indicate a statistically signicant treatment eect
Usual
diet
Dietary
advice
1.6 (-5.03 to 8.20)
7.08 (2.48 to 11.68)
5.47 (-1.19 to 12.16)
1.01 (-2.96 to 4.96)
-0.60 (-6.68 to 5.56)
-6.08 (-9.60 to -2.53)
5.22 (1.90 to 8.68)
-0.89 (-2.31 to 0.44)
1.09 (-1.28 to 3.37)
0.98 (-0.45 to 2.36)
-3.20 (-4.08 to -2.34)
3.61 (-1.97 to 9.44)
2.31 (0.68 to 3.87)
4.29 (1.77 to 6.74)
4.19 (2.69 to 5.64)
-1.85 (-5.30 to 1.70)
-1.88 (-3.73 to -0.04)
6 month high density lipoprotein increase
6 month low density lipoprotein reduction
0.10 (-2.61 to 2.80)
4.22 (2.04 to 6.49)
-1.97 (-4.68 to 0.70)
High certainty Moderate certainty Low certainty Very low certainty
Low
fat
Low
carbohydrate
Moderate
macronutrients
Fig5 | Macronutrient pattern network meta-analysis results with corresponding GRADE (grading of recommendations,
assessment, development, and evaluation) certainty of evidence for reduction in low density lipoprotein (LDL)
cholesterol and increase in high density lipoprotein (HDL) cholesterol (mg/dL) at six months. Values correspond to
dierence in median HDL cholesterol increase (above, right of macronutrient patterns) and LDL cholesterol reduction
(below, le of macronutrient patterns) between column and row at six months (eg, low fat had a median HDL
cholesterol increase of 0.10 mg/dL and a median LDL cholesterol reduction of 5.47 mg/dL at six months compared
with dietary advice). Values in bold indicate a statistically signicant treatment eect
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very low certainty evidence relative to a usual diet,
Portfolio might be the most eective (fig 6, appendix
tables S35 and S40).
No popular named diets showed a statistically
significant increase in HDL cholesterol at the six
month follow-up (fig 6, appendix tables S35 and
S40). Similar, but smaller, results were found at the
12 month follow-up for both LDL and HDL cholesterol
(appendix table S41).
C reactive protein
We found no statistically significant dierences bet-
ween popular named diets and usual diet (fig 6,
appendix tables S35 and S42). Similar results were
found at the 12 month follow-up (appendix table S43).
Additional analyses
Appendix figure S7 presents the results of mean
surface under the cumulative ranking curve values
for all outcomes at six months. We did not perform
network meta-regressions and sensitivity analyses for
C reactive protein because of the limited number of
eligible randomised controlled trials. Network meta-
regressions for the other five outcomes showed that
none of the regression factors (behavioural support and
exercise, risk of bias, clinical population, and funding
support) had statistically significant eects. Appendix
tables S44-S57 present the results of network meta-
regressions and sensitivity analyses.
Adverse events
Twenty two (18.2%) of the 121 randomised controlled
trials, of which 12 evaluated low carbohydrate
diets, reported adverse events. One trial reported
a statistically significant higher risk of headaches
at three months (25% v 8%; P=0.03) in the group
receiving a low fat diet (n=73) than in the group with
a low carbohydrate diet (n=75), but no significant
dierences at six and 12 months.34 Another trial
reported a statistically significant increase in the risk
of several adverse eects at six months in the group
assigned to a low carbohydrate diet (n=60) than in
those assigned to a low fat diet (n=60), including
constipation (68% v 35%; P=0.001), headache (60% v
Diet v
usual
diet
Weight
loss
(kilograms)
Systolic
blood
pressure
reduction
(mm Hg)
Diastolic
blood
pressure
reduction
(mm Hg)
Low
density
lipoprotein
reduction
(mg/dL)
High
density
lipoprotein
reduction
(mg/dL)
C-reactive
protein
reduction
(mg/dL)
0.643.41-2.753.305.145.46Atkins
0.27-0.33-2.892.333.464.07Zone
NA-1.903.932.844.683.63DASH
0.25-0.614.591.032.942.87Mediterranean
0.52-2.527.273.8514.565.31Paleolithic
0.33-2.131.922.223.954.87Low fat
0.19-2.850.217.817.867.77Jenny Craig
NA-0.137.131.952.935.95Volumetrics
0.87-0.887.131.032.803.90Weight Watchers
NA-2.047.151.442.393.76Rosemary Conley
1.11-4.874.710.200.693.64Ornish
-0.37-3.2621.293.985.973.64Portfolio
NA-0.013.902.203.172.88Biggest Loser
NANANANANA2.15Slimming World
NA0.36-0.64NANA9.86South Beach
-1.15-1.71-2.010.400.580.31 Dietary advice
“Among the most effective” with moderate to high certainty
“Inferior to the most effective/superior to the least effective” with moderate to high certainty
“Among the least effective” with moderate to high certainty
“Maybe among the most effective” with very low to low certainty
“Inferior to the most effective/superior to the least effective” with very low to low certainty
“Maybe among the least effective” with very low to low certainty
“Maybe worse than usual diet”
Fig6 | Summary of results of popular named diets network meta-analysis for all outcomes at six months. The number
is the point estimates of eect in comparison with usual diet
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40%; P=0.03), halitosis (38% v 8%; P=0.001), muscle
cramps (35% v 7%; P=0.001), diarrhoea (23% v 7%;
P=0.02), general weakness (25% v 8%; P=0.01),
and rash (13% v 0%; P=0.006).35 Study authors did
not assess the likelihood that the diet was plausibly
responsible for the adverse events.
Discussion
Our network meta-analysis quantifies the comparative
eectiveness of three dietary macronutrient patterns
based on 14 popular named dietary programmes for
both weight and related cardiovascular risk factors
at six and 12 months using the GRADE approach.
Evidence of low to moderate certainty showed
that all three dietary macronutrient patterns (low
carbohydrate, low fat, and moderate macronutrient)
were associated with larger reductions in body weight
(fig 3) and blood pressure than a usual diet (fig 4);
reductions with moderate macronutrient diets were
slightly smaller than with the other two macronutrient
patterns. Eects on weight were less at 12 months than
at six months (between 4 and 5 kg reductions relative
to usual diet at six months, about 3 kg at 12 months).
Based on moderate certainty evidence, both low fat
and moderate macronutrient diets are likely to reduce
LDL cholesterol relative to usual diets at six months.
All these changes were potentially important based
on the importance threshold we specified in advance
(weight loss 2 kg, systolic blood pressure 3 mm Hg,
diastolic blood pressure 2 mm Hg, LDL cholesterol
5 mg/dL; appendix text S3). Macronutrient diet related
improvements in both blood pressure and blood lipids
disappeared almost completely at 12 months.
Of the popular named diets, Atkins, DASH, and
Zone had the highest certainty evidence and the most
consistent eects for reduction in weight and blood
pressure at six months; an unnamed diet, low fat,
performed similarly to the named diets (fig 6). Only the
Mediterranean diet showed a statistically significant
dierence compared with usual diet in LDL cholesterol
reduction (fig 6). Estimated eects at the 12 month
follow-up for weight loss and cardiovascular risk factor
improvements diminished for all popular named diets,
except for the Mediterranean diet. None of the diets
were associated with a statistically significant increase
in HDL cholesterol or reduction in C reactive protein at
either the six or 12 month follow-up.
Network meta-analyses showed that although there
were statistically significant dierences between some
dietary patterns, these dierences were generally
small at six months and negligible at 12 months. For
example, low carbohydrate dietary patterns resulted in
an estimated dierence in weight loss of 1.57 kg (95%
credible interval 0.86 to 2.29), a reduction in systolic
blood pressure of 1.66 mm Hg (0.36 to 2.98), and a
reduction in diastolic blood pressure of 1.33 mm Hg
(0.51 to 2.16) compared with moderate macronutrient
dietary patterns at six months (fig 3, fig 4, and fig 5).
The same small dierences between diets at six
months and even smaller and uncertain dierences
at 12 months apply to the popular named diets. For
instance, Atkins resulted in an estimated dierence
in weight loss of only 1.38 kg (95% credible interval
0.15 to 2.62) and an LDL cholesterol reduction of
−0.15 mg/dL (−4.92 to 4.63 mg/dL) compared with the
Zone diet at the six month follow-up (appendix tables
S36 and S40). Figure 6 highlights instances in which
dierences exist, all of which are small or even trivial,
with the corresponding certainty of the underlying
evidence.
Strengths and limitations of this review
Strengths of this review include our use of network
meta-analysis, thus taking advantage of both direct
and indirect comparisons to generate the most robust
estimates possible of weight and cardiovascular risk
factors for both dietary macronutrient patterns and
individual popular named diets. We used explicit
eligibility criteria; conducted a comprehensive lit-
erature search developed with an experienced
librarian; performed duplicate assessment of study
eligibility, risk of bias, and data extraction; sum-
marised the data using a transparent statistical
analysis including network meta-regression accoun-
ting for potential eect modifiers (eg, exercise and
behavioural support); applied the GRADE approach
to rate certainty of evidence; presented tables of
results highlighting certainty of evidence; and used
an innovative classification scheme enhancing the
transparency of the relative eects of the named diets
across multiple outcomes (fig 6). Furthermore, to
reduce the heterogeneity between studies, we used
three categories for control diets: usual diet, dietary
advice, and low fat diet; the low fat diet proved to have
moderate certainty evidence supporting weight and
blood pressure reductions, similar to the named diets.
We conducted sensitivity analyses by restricting them
to studies assessed as low risk of bias, studies focusing
on otherwise healthy populations, and studies without
diet company (industry) support. All analyses provided
results similar to those of our primary analysis, further
supporting the robustness of our results.
Our review has some limitations. Firstly, many
comparisons provided only low certainty evidence,
primarily because of inconsistency and imprecision,
but also because of risk of bias. The paucity of direct
comparisons between popular named diets contributed
to the low certainty evidence: 14 popular named
diet programmes included 407 paired comparisons
across six outcomes, of which only 59 made direct
comparisons, and, of these, only 22 included more
than one study. Secondly, our ability to deal with
publication bias was limited given the paucity of direct
comparisons. For example, only two of 136 comparison
groups (Atkins v low fat, and Zone v low fat) had more
than 10 studies for the outcome weight loss. Thirdly,
we did not involve patients in either the planning or
the conduct of the study. Fourthly, considerably fewer
trials reported our target outcomes at the 12 month
follow-up, and most of the evidence was low to very
low certainty (appendix tables S58-S63). Fifthly,
adherence to diets was generally not reported, and
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could have been low, particularly at 12 months. If this
is the case, our results describe what is likely to happen
for average adherence by patients. Full adherence
would probably yield larger eects in improvement
of weight loss and cardiovascular risk factors. If the
weight loss achieved at six months continued at 12
months, it is uncertain whether the improvements in
cardiovascular risk factors would also be maintained.
Future studies, therefore, could usefully examine
how to achieve longer term adherence to diets. Lastly,
participants in randomised trials are always a select
population. Selection could be more important in
dietary trials than in trials in which eects are less tied
to individual behaviour. Whether trial non-participants
would be more, or less, adherent to the popular named
diets is, however, a matter of speculation.
Comparison with other studies
Our review examined weight loss and cardiovascular
risk factors among dietary macronutrient patterns and
popular named diets using new network meta-analysis
methods and the GRADE approach to summarise
the certainty of evidence. In comparison with our
previous network meta-analysis that examined weight
loss alone,4 we included three additional popular
diets (DASH, Portfolio, Mediterranean). Altogether,
we included 73 additional randomised controlled
trials, resulting in almost three times the number of
participants included in the previous trial.
Consistent with our previous review, results
indicated that almost all dietary patterns and popular
named diets showed a minimally clinical important
weight loss of 2.0 kg compared with a usual diet for
up to 12 months, with the dierences among diets, for
the most part, small and often trivial.4 Our findings are
also consistent with the 2014 joint guidelines from the
American Heart Association, the American College of
Cardiology, and The Obesity Society, concluding that
evidence was inadequate to recommend any particular
diet.3 Similar to another recent review,36 our results
showed that the Atkins diet probably achieves the
largest weight loss, although the gradient of weight or
cardiovascular risk factor improvement relative to other
diets is small. For reduction of cardiovascular risk,
recent dietary guidelines from the US and Canada, and
the EAT Lancet commission have recommended plant
based diets.37-39 To the extent that short term results
might have implications for long term cardiovascular
outcomes, our findings do not support this conclusion:
rather, they suggest that omnivorous based diets (eg,
Atkins, Zone) have a similar eect to diets that tend
to be higher in plant based foods (eg, Ornish, DASH,
Mediterranean).
Conclusions
Compared with usual diet, moderate certainty
evidence supports modest weight loss and substantial
reductions in systolic and diastolic blood pressure
for low carbohydrate (eg, Atkins, Zone), low fat (eg,
Ornish), and moderate macronutrient (eg, DASH,
Mediterranean) diets at six but not 12 months.
Dierences between diets are, however, generally
trivial to small, implying that people can choose the
diet they prefer from among many of the available
diets (fig 6) without concern about the magnitude of
benefits.
AUTHOR AFFILIATIONS
1Evidence Based Social Science Research Centre, School of Public
Health, Lanzhou University, Lanzhou, China
2Department of Social Medicine and Health Management, School of
Public Health, Lanzhou University, Lanzhou, China
3Department of Health Research Methods, Evidence and Impact,
McMaster University, Hamilton, ON, Canada
4Michael G DeGroote Institute for Pain Research and Care,
McMaster University, Hamilton, ON, Canada
5Department of Pediatrics, University of Alberta, Edmonton, AB,
Canada
6Institute of Primary Health Care (BIHAM), University of Bern, Bern,
Switzerland
7Applied Health Research Centre, St Michael’s Hospital, University
of Toronto, Toronto, ON, Canada
8Institute of Health Policy, Management and Evaluation, University
of Toronto, Toronto, ON, Canada
9Department of Community Health and Epidemiology, Faculty of
Medicine, Dalhousie University, Halifax, NS, Canada
10Zucker School of Medicine at HOFSTRA/Northwell Mather
Hospital, Port Jeerson, NY, USA
11School of Medicine, Wayne State University, Detroit, MI, USA
12School of Population and Public Health, University of British
Columbia, Vancouver, BC, Canada
13HIV/STI Surveillance Research Centre, and WHO Collaborating
Centre for HIV Surveillance, Institute for Futures Studies in Health,
Kerman University of Medical Sciences, Kerman, Iran
14Library and Archives Services, The Hospital for Sick Children,
Toronto, ON, Canada
15Department of Medicine, University of Toronto, Toronto, ON,
Canada
16Department of Agricultural, Food, and Nutritional Sciences,
University of Alberta, Edmonton, AB, Canada
17Institute of Social and Preventive Medicine (ISPM), University of
Bern, Bern, Switzerland
18Department of Pharmacology, Faculty of Medicine and Dentistry,
University of Alberta, Edmonton, AB, Canada
19Evidence Based Medicine Centre, School of Basic Medical
Sciences, Lanzhou University, Lanzhou, China
20Department of Nutrition, Texas A&M University, College Station,
TX, 77845, USA
We thank Kristian Thorlund (McMaster University) for supporting the
development of the original statistical code for our analysis, and Bei
Pan (Gansu Provincial Hospital), Liangying Hou (School of Public
Health, Lanzhou University), and Huijuan Li (School of Public Health,
Lanzhou University) for help with cleaning data, data analysis, and
table preparation.
Contributors: BCJ, GDCB, and BS conceived the study. BCJ, GDCB,
CLH, BS, LG, BRdC, RTT, and GHG designed the study protocol. TA-W,
BS, and BCJ designed and performed the search strategy. BS, LG,
CLH, RK, KQ, HYK, MK, WA, SD, DZ, and AN screened abstracts and full
texts, extracted data, or judged risk of bias of included studies. LG,
AS, AN, and BRdC performed the data analysis. LG, BCJ, BS, GHG, JT,
and KY designed and performed the GRADE assessment. LG, BS, and
BCJ wrote the rst dra of the manuscript. LG, BS, GDCB, CLH, RTT,
GHG, and BCJ provided administrative, technical, or material support.
BCJ, GDCB, BS, BRdC, and GHG supervised the study. All authors
interpreted the data analysis and critically revised the manuscript. BCJ
and LG are the guarantors. The corresponding author attests that all
listed authors meet authorship criteria and that no others meeting the
criteria have been omitted.
Funding: This research was not funded by a specic grant from any
funding agency in the public, commercial, or not-for-prot sectors.
It was funded, in part, by internal investigator funds from Dalhousie
University (awarded to BCJ) and the University of Alberta (awarded
to GDCB). SD was supported by a scholarship from Umm AlQura
on 5 April 2020 by guest. Protected by copyright.http://www.bmj.com/BMJ: first published as 10.1136/bmj.m696 on 1 April 2020. Downloaded from
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University, Makkah, Kingdom of Saudi Arabia. GDCB was supported by
an Alberta Health Services Chair in Obesity Research.
Competing interests: All authors have completed the ICMJE uniform
disclosure form at www.icmje.org/coi_disclosure.pdf (available
on request from the rst author) and declare: no support from any
organisation for the submitted work. BS reports funding from Mitacs
Canada in the past three years, and the International Life Sciences
Institute (ILSI), North America to support his graduate work for his
2015 academic year (the ILSI funding is outside the required three
year period requested on the ICJME form). In 2016-17, BS worked for
the Cornerstone Research Group, a contract research organisation.
AS reports personal fees from Dalhousie University. RTT reports
grants from Sano Canada, outside the submitted work. As part of his
recruitment to Texas A&M University, BCJ receives funds from Texas
A&M AgriLife Research to support investigator initiated research
related to saturated and polyunsaturated fats. Support from Texas
A&M AgriLife institutional funds are from interest and investment
earnings, not a sponsoring organisation, industry, or company. BCJ
also received funding in 2015 from ILSI (outside the required three
year period requested on ICJME form) to assess the methodological
quality of nutrition guidelines dealing with sugar intake using
internationally accepted GRADE (grading of recommendations,
assessment, development, and evaluation) and AGREE (appraisal
of guidelines for research and evaluation) guideline standards. The
authors conducted the review of methodological quality of nutrition
guidelines independently without involvement of the funder. No other
relationships or activities that could appear to have influenced the
submitted work.
Ethical approval: Not required.
Data sharing: All data are freely available within the appendices. No
additional data available.
The manuscript’s guarantors (BCJ and LG) arm that the manuscript
is an honest, accurate, and transparent account of the study being
reported; that no important aspects of the study have been omitted;
and that any discrepancies from the study as planned (and, if relevant,
registered) have been explained.
Dissemination to participants and related patient and public
communities: We plan to disseminate the results to relevant patient
communities through the media relations department of our
institutions.
This is an Open Access article distributed in accordance with the
Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license,
which permits others to distribute, remix, adapt, build upon this work
non-commercially, and license their derivative works on dierent
terms, provided the original work is properly cited and the use is non-
commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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