ArticlePDF AvailableLiterature Review

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

Authors:

Abstract and Figures

Objective To determine the relative effectiveness 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 effects network meta-analyses to estimate the relative effectiveness 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 effect 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 effect 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 effect 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 significantly 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 benefits for cardiovascular risk factors of 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 effects on weight reduction and improvements in cardiovascular risk factors largely disappear. Systematic review registration PROSPERO CRD42015027929.
Content may be subject to copyright.
thebmj
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 eectiveness 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
eects network meta-analyses to estimate the relative
eectiveness 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 eect 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
eect 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 eect 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 signicantly 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 benets for cardiovascular risk factors of
For numbered aliations 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
dierences 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 eectiveness 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
Dierences between diets were typically small to trivial and oen based on low
certainty evidence
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
RESEARCH
2 doi: 10.1136/bmj.m696 |
BMJ
2020;369:m696 | thebmj
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 eects 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 eect 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 dierences 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 eectiveness 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 eect 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 eect of dierent
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 eectiveness 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
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
RESEARCH
thebmj
BMJ
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 eects 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 eects 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 eects, we
used 95% credible intervals, by means of the 2.5 and
97.5 percentiles obtained from the simulations.25 We
Table1 | 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).
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
RESEARCH
4 doi: 10.1136/bmj.m696 |
BMJ
2020;369:m696 | thebmj
used the node splitting method to generate the eect
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 eect 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 coecient
across comparisons to explore the eect 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 eect
estimates were calculated from available “loops” of
evidence, which included first order loops (based on
a single common comparator treatment—that is the
dierence 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 eect modifiers diered 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 eect
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 dierent groups of interventions (from
the most to the least eective) based on the eect
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 dier from the
reference (that is, confidence interval crossed mean
dierence=0), which we refer to as “among the least
eective”. 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 eective, but superior to the least
eective”). Lastly, diets that proved superior to at least
one category 1 diet (which we call “among the most
eective”). 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
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
RESEARCH
thebmj
BMJ
2020;369:m696 | doi: 10.1136/bmj.m696 5
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
Fig1 | 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
Fig2 | Network plots of all included studies for macronutrient patterns and popular named diets
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
RESEARCH
6 doi: 10.1136/bmj.m696 |
BMJ
2020;369:m696 | thebmj
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 dierences 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 eects similar to those of low carbohydrate
diets for weight loss (fig 3) and blood pressure (fig
4), but a greater eect 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 eects than low
carbohydrate diets on weight loss (fig 3), blood pressure
(fig 4), and HDL cholesterol increase (fig 5), but a greater
eect on LDL cholesterol reduction (fig 5). Appendix
table S12 presents the network meta-analysis results for
C reactive protein, showing no statistically significant
dierences 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 dierences 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 eective
popular named diets, whereas Volumetrics, paleolithic,
low fat, Zone, Weight Watchers, Rosemary Conley,
DASH, Ornish, and Mediterranean were inferior to the
most eective but superior to the least eective diet
interventions. The Biggest Loser, Slimming World, and
dietary advice were the least eective 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 eective (fig 6).
All named diets, except a paleolithic diet, decreased
their estimated eects 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 eective, whereas Atkins, DASH, Portfolio, low
fat, Zone, and Mediterranean were probably inferior to
the most eective, but superior to the least eective,
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
Fig3 | 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
dierence 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 signicant treatment eect
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
RESEARCH
thebmj
BMJ
2020;369:m696 | doi: 10.1136/bmj.m696 7
diets. The Biggest Loser and Ornish proved the least
eective diets. Among the diets with only low or very
low certainty evidence relative to usual diet, Jenny Craig
might be the most eective (fig 6, appendix table S35).
Eects for all popular named diet programmes had
decreased at the 12 month follow-up compared with
the six month follow-up. No statistically significant
dierences 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 eective
popular named diet at six months, whereas DASH,
low fat, and Zone were probably inferior to the most
eective, but superior to the least eective, diets.
Paleolithic, Biggest Loser, Mediterranean, and Ornish
proved the least eective diets. Among the diets with
only low or very low certainty evidence relative to
a usual diet, Jenny Craig might be the most eective
(fig 6, appendix tables S35 and S38). We found no
statistically significant dierences 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 eective 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
Fig4 | 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 dierence 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 signicant treatment eect
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
Fig5 | 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
dierence 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 signicant treatment eect
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
RESEARCH
8 doi: 10.1136/bmj.m696 |
BMJ
2020;369:m696 | thebmj
very low certainty evidence relative to a usual diet,
Portfolio might be the most eective (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 dierences 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 eects. 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
dierences at six and 12 months.34 Another trial
reported a statistically significant increase in the risk
of several adverse eects 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”
Fig6 | Summary of results of popular named diets network meta-analysis for all outcomes at six months. The number
is the point estimates of eect in comparison with usual diet
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
RESEARCH
thebmj
BMJ
2020;369:m696 | doi: 10.1136/bmj.m696 9
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
eectiveness 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. Eects 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 eects 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
dierence compared with usual diet in LDL cholesterol
reduction (fig 6). Estimated eects 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 dierences between some
dietary patterns, these dierences were generally
small at six months and negligible at 12 months. For
example, low carbohydrate dietary patterns resulted in
an estimated dierence 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 dierences between diets at six
months and even smaller and uncertain dierences
at 12 months apply to the popular named diets. For
instance, Atkins resulted in an estimated dierence
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
dierences 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 eect 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 eects 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
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
RESEARCH
10 doi: 10.1136/bmj.m696 |
BMJ
2020;369:m696 | thebmj
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 eects 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 eects 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 dierences 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 eect 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.
Dierences 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 Jeerson, 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 specic grant from any
funding agency in the public, commercial, or not-for-prot 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
RESEARCH
thebmj
BMJ
2020;369:m696 | doi: 10.1136/bmj.m696 11
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) arm 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 dierent
terms, provided the original work is properly cited and the use is non-
commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
1 World Health Organization. Obesity and overweight, Fact sheet.
2018. https://www.who.int/mediacentre/factsheets/fs311/en/
2 Freedho Y, Hall KD. Weight loss diet studies: we need help not hype.
Lancet2016;388:849-51. doi:10.1016/S0140-6736(16)31338-1
3 Jensen MD, Ryan DH, Apovian CM, et al, American College of
Cardiology/American Heart Association Task Force on Practice
Guidelines, Obesity Society. 2013 AHA/ACC/TOS guideline for
the management of overweight and obesity in adults: a report of
the American College of Cardiology/American Heart Association
Task Force on Practice Guidelines and The Obesity Society.
Circulation2014;129(Suppl 2):S102-38. doi:10.1161/01.
cir.0000437739.71477.ee
4 Johnston BC, Kanters S, Bandayrel K, et al. Comparison of weight
loss among named diet programs in overweight and obese
adults: a meta-analysis. JAMA2014;312:923-33. doi:10.1001/
jama.2014.10397
5 Mansoor N, Vinknes KJ, Veierød MB, Retterstøl K. Eects of low-
carbohydrate diets v. low-fat diets on body weight and cardiovascular
risk factors: a meta-analysis of randomised controlled trials. Br J
Nutr2016;115:466-79. doi:10.1017/S0007114515004699
6 Naude CE, Schoonees A, Senekal M, Young T, Garner P, Volmink J.
Low carbohydrate versus isoenergetic balanced diets for reducing
weight and cardiovascular risk: a systematic review and meta-
analysis [correction in: PLoS One 2018;13:e0200284]. PLoS
One2014;9:e100652. doi:10.1371/journal.pone.0100652
7 Sackner-Bernstein J, Kanter D, Kaul S. Dietary intervention for
overweight and obese adults: comparison of low-carbohydrate
and low-fat diets. a meta-analysis. PLoS One2015;10:e0139817.
doi:10.1371/journal.pone.0139817
8 Schwingshackl L, Homann G. Long-term eects of low-fat diets
either low or high in protein on cardiovascular and metabolic risk
factors: a systematic review and meta-analysis. Nutr J2013;12:48.
doi:10.1186/1475-2891-12-48
9 Zhong X, Guo L, Zhang L, Li Y, He R, Cheng G. Inflammatory potential
of diet and risk of cardiovascular disease or mortality: a meta-
analysis. Sci Rep2017;7:6367. doi:10.1038/s41598-017-06455-x
10 Bloomeld HE, Koeller E, Greer N, MacDonald R, Kane R, Wilt
TJ. Eects on health outcomes of a mediterranean diet with no
restriction on fat intake: a systematic review and meta-analysis. Ann
Intern Med2016;165:491-500. doi:10.7326/M16-0361
11 Siervo M, Lara J, Chowdhury S, Ashor A, Oggioni C, Mathers JC.
Eects of the Dietary Approach to Stop Hypertension (DASH) diet on
cardiovascular risk factors: a systematic review and meta-analysis. Br
J Nutr2015;113:1-15. doi:10.1017/S0007114514003341
12 Soltani S, Chitsazi MJ, Salehi-Abargouei A. The eect of dietary
approaches to stop hypertension (DASH) on serum inflammatory
markers: A systematic review and meta-analysis of randomized trials.
Clin Nutr2018;37:542-50. doi:10.1016/j.clnu.2017.02.018
13 Huedo-Medina TB, Garcia M, Bihuniak JD, Kenny A, Kerstetter J.
Methodologic quality of meta-analyses and systematic reviews on the
Mediterranean diet and cardiovascular disease outcomes: a review.
Am J Clin Nutr2016;103:841-50. doi:10.3945/ajcn.115.112771
14 Barnard ND, Willett WC, Ding EL. The misuse of meta-analysis
in nutrition research. JAMA2017;318:1435-6. doi:10.1001/
jama.2017.12083
15 Guyatt GH, Oxman AD, Vist GE, et al, GRADE Working Group.
GRADE: an emerging consensus on rating quality of evidence and
strength of recommendations. BMJ2008;336:924-6. doi:10.1136/
bmj.39489.470347.AD
16 Stern L, Iqbal N, Seshadri P, et al. The eects of low-carbohydrate
versus conventional weight loss diets in severely obese adults: one-
year follow-up of a randomized trial. Ann Intern Med2004;140:778-
85. doi:10.7326/0003-4819-140-10-200405180-00007
17 Volek JS, Ballard KD, Silvestre R, et al. Eects of dietary
carbohydrate restriction versus low-fat diet on flow-mediated
dilation. Metabolism2009;58:1769-77. doi:10.1016/j.
metabol.2009.06.005
18 Higgins JPT, Green S (eds). Cochrane handbook for systematic reviews
of interventions. Version 5.1.0 [updated March 2011]. Cochrane
Collaboration, 2011. www.handbook.cochrane.org.
19 Furukawa TA, Barbui C, Cipriani A, Brambilla P, Watanabe N.
Imputing missing standard deviations in meta-analyses can provide
accurate results. J Clin Epidemiol2006;59:7-10. doi:10.1016/j.
jclinepi.2005.06.006
20 Dias S, Sutton AJ, Welton NJ, Ades AE. Evidence synthesis for
decision making 3: heterogeneity--subgroups, meta-regression,
bias, and bias-adjustment. Med Decis Making2013;33:618-40.
doi:10.1177/0272989X13485157
21 Ades AE, Sculpher M, Sutton A, et al. Bayesian methods
for evidence synthesis in cost-eectiveness analysis.
Pharmacoeconomics2006;24:1-19. doi:10.2165/00019053-
200624010-00001
22 Lumley T. Network meta-analysis for indirect treatment comparisons.
Stat Med2002;21:2313-24. doi:10.1002/sim.1201
23 Turner RM, Davey J, Clarke MJ, Thompson SG, Higgins JP. Predicting
the extent of heterogeneity in meta-analysis, using empirical
data from the Cochrane Database of Systematic Reviews. Int J
Epidemiol2012;41:818-27. doi:10.1093/ije/dys041
24 Rhodes KM, Turner RM, Higgins JP. Predictive distributions were
developed for the extent of heterogeneity in meta-analyses of
continuous outcome data. J Clin Epidemiol2015;68:52-60.
doi:10.1016/j.jclinepi.2014.08.012
25 Salanti G, Higgins JP, Ades AE, Ioannidis JP. Evaluation of networks
of randomized trials. Stat Methods Med Res2008;17:279-301.
doi:10.1177/0962280207080643
26 van Valkenhoef G, Dias S, Ades AE, Welton NJ. Automated generation
of node-splitting models for assessment of inconsistency in network
meta-analysis. Res Synth Methods2016;7:80-93. doi:10.1002/
jrsm.1167
27 Veroniki AA, Straus SE, Fyraridis A, Tricco AC. The rank-heat plot is
a novel way to present the results from a network meta-analysis
including multiple outcomes. J Clin Epidemiol2016;76:193-9.
doi:10.1016/j.jclinepi.2016.02.016
28 US Preventive Services Task Force. Screening for obesity in adults:
recommendations and rationale. Ann Intern Med2003;139:930-2.
doi:10.7326/0003-4819-139-11-200312020-00012
29 Chaimani A, Salanti G. Using network meta-analysis to evaluate the
existence of small-study eects in a network of interventions. Res
Synth Methods2012;3:161-76. doi:10.1002/jrsm.57
30 Chaimani A, Higgins JP, Mavridis D, Spyridonos P, Salanti G. Graphical
tools for network meta-analysis in STATA. PLoS One2013;8:e76654.
doi:10.1371/journal.pone.0076654
31 Puhan MA, Schünemann HJ, Murad MH, et al, GRADE Working Group.
A GRADE Working Group approach for rating the quality of treatment
eect estimates from network meta-analysis. BMJ2014;349:g5630.
doi:10.1136/bmj.g5630
32 Brignardello-Petersen R, Bonner A, Alexander PE, et al, GRADE
Working Group. Advances in the GRADE approach to rate the
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
RESEARCH
No commercial reuse: See rights and reprints http://www.bmj.com/permissions Subscribe: http://www.bmj.com/subscribe
certainty in estimates froma network meta-analysis [correction in:
J Clin Epidemiol 2018;98:162]. J Clin Epidemiol2018;93:36-44.
doi:10.1016/j.jclinepi.2017.10.005
33 Florez ID, Veroniki AA, Al Khalifah R, et al. Comparative eectiveness
and safety of interventions for acute diarrhea and gastroenteritis
in children: a systematic review and network meta-analysis. PLoS
One2018;13:e0207701. doi:10.1371/journal.pone.0207701
34 Bazzano LA, Hu T, Reynolds K, et al. Eects of low-carbohydrate and
low-fat diets: a randomized trial. Ann Intern Med2014;161:309-18.
doi:10.7326/M14-0180
35 Yancy WSJr, Olsen MK, Guyton JR, Bakst RP, Westman EC. A low-
carbohydrate, ketogenic diet versus a low-fat diet to treat obesity
and hyperlipidemia: a randomized, controlled trial. Ann Intern
Med2004;140:769-77. doi:10.7326/0003-4819-140-10-
200405180-00006
36 Anton SD, Hida A, Heekin K, et al. Eects of popular diets without specic
calorie targets on weight loss outcomes: systematic review of ndings
from clinical trials. Nutrients2017;9:822. doi:10.3390/nu9080822
37 Canada’s Food Guide. Eat well, live well. Ottawa: Health Canada,
2019. https://food-guide.canada.ca/en/.
38 Willett W, Rockström J, Loken B, et al. Food in the Anthropocene:
the EAT-Lancet Commission on healthy diets from sustainable
food systems. Lancet2019;393:447-92. doi:10.1016/S0140-
6736(18)31788-4
39 Dietary Guidelines Advisory Committee, Scientic Report of the 2015
Dietary Guidelines Advisory Committee. 2015; http://www.health.
gov/dietaryguidelines/2015-scientic-report/.
Web appendix: Supplementary material
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
... The MCID for our outcomes were as follows: weight (2.5 kg), appetite (1.6), fatigue (0.9), and EORTC QLQ-C30 (at least 3-point increment on QLQ-C30 domains). [36][37][38] ...
Article
Full-text available
There is inconsistent evidence relating to the effects of megestrol acetate (MA) supplementation on cancer patients suffering from anorexia–cachexia syndrome. This review aimed to examine the dose–response effect of MA supplementation in patients with cancer‐associated anorexia/cachexia. Relevant keywords were searched in PubMed, Scopus and ISI Web of Science from inception to June 2023 for randomized controlled trials (RCTs) examining the effect of MA on pathologies in patients with cancer‐associated cachexia. Our primary outcomes were changes in body weight and appetite. However, fatigue and quality of life were secondary outcomes. The mean difference (MD) and 95% confidence interval (95% CI) were estimated using the random‐effects method. Thirteen trials comprising 1229 participants (mean age 60 years) were identified. The results of our highest versus lowest analysis revealed that MA supplementation was not associated with any increase in body weight (MD: 0.64 kg, 95% CI [−0.11, 1.38], P = 0.093, I² = 69.1%; GRADE = very low certainty). Twelve trials, including 14 effect sizes derived from 1369 patients (intervention = 689, control = 680), provided data on the effect of MA on body weight. Subgroup analyses showed a significant increase in body weight following short‐term intervention (≤8 weeks) and a combination of radiation/chemotherapy as concurrent treatment. A linear dose–response meta‐analysis indicated that each 200 mg/day increment in MA consumption had a significant increase in weight gain (MD: 0.44; 95% CI [0.13, 0.74], P = 0.005; I² = 97.1%); however, the magnitude of the effect was small. MA administration significantly affected the quality of life based on pooled effect sizes (MD: 1.15, 95% CI [0.76, 1.54], P < 0.001, I² = 0%; n = 2 RCTs including 176 patients; GRADE = very low certainty). However, no significant effect of MA supplementation was observed on appetite (MD: 0.29, 95% CI [−0.05, 0.64], P = 0.096, I² = 18.3%; n = 3 RCTs including 163 patients; GRADE = very low certainty) and fatigue (MD: 0.14, 95% CI [−0.09, 0.36], P = 0.236, I² = 0%; n = 2 RCTs including 300 patients; GRADE = very low certainty). With very low certainty of the evidence, MA supplementation may not lead to a significantly increased weight gain and other outcomes.
... For the general population and those at increased CVD risk, especially at low to moderate risk, the LDL-C reduction by dietary adjustment, and in general lifestyle changes, represents the primary method of CVD risk reduction and therefore deserves special emphasis in the evaluation of lifestyle changes [3,4]. Dietary adjustments, however, achieve a reduction of LDL-C which is insufficient (usually 10-15%) to reach the recommended LDL-C levels in most cases [4,5]. The European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines 2019 as well as some national guidelines recommend lifestyle interventions, which include not only dietary adjustments but also the use of functional foods [4,6]. ...
Article
Full-text available
Introduction Considering lack of a European standardized postmarketing food supplement surveillance system, some member states and companies have developed their own approaches to monitoring potential AEs to secure a high level of product safety. This paper updates 2021 results of the use of a nutrivigilance system in monitoring the incidence of spontaneously reported suspected AEs associated with RYR-containing food supplements. Material and methods We report the data from a product marketed under the trademark Armolipid/Armolipid Plus. Postmarketing information was collected in a voluntary nutrivigilance system established by the manufacturing company (Meda Pharma SpA, a Viatris Company, Monza, Italy). From 1st October 2004-31st December 2023, this system captured cases of suspected AEs spontaneously reported by consumers, healthcare professionals, health authorities, regardless of causality. Results The total number of case reports received mentioning the RYR-food supplement product line increased to 1186, in which 1904 AEs were reported. The total reporting rate of AEs was estimated to be 0.049% of 3,880,865 exposed consumers. Of the 1186 cases, 28 (0.0007%) included suspected SAEs. After careful investigation, 9 cases (0.0002%) and 12 AEs were assessed by the manufacturer as serious and potentially related to exposure to the above-mentioned RYR-based nutraceutical. Off-label reports linked to the newly introduced limitation at 70 years of age were observed, in contrast to the previous analysis. Conclusions These updated results confirm a very low incidence of RYR suspected AEs. Consumer safety of food supplements could be generally improved by raising awareness of the importance of following the indications and warnings detailed in a food supplement’s labelling.
... Various dieting strategies to combat obesity and overweight were extensively investigated. They include low-calorie diet [102,112], low-fat diet [113,114], lowcarbohydrate diet [115][116][117], ketogenic diet [118,119], and high-protein diet [120]. Other dietary management strategies explored include Mediterranean diet [121,122], Paleolithic (Paleo) diet [123,124], low glycemic index diet [125,126], Nordic diet [127], vegetarian diet [128,129], DASH diet [130,131], and portfolio diet [121,132,133]. ...
Article
Full-text available
Purpose of Review Despite the prevalence of weight loss programs, their success rates remain discouraging, with around half of individuals regaining lost weight within two years. The primary objective of this review is to explore the factors contributing to the failure of weight loss programs and to provide insights into effective weight management strategies. Recent Findings Factors contributing to the failure of weight loss programs include the impracticality of restrictive diets, potential metabolic impacts, limited focus on lifestyle changes, genetic predispositions, psychological influences, socioeconomic status, and medical conditions. A holistic approach considering these factors is crucial for safe and sustainable weight loss. Key findings indicate the importance of holistic approaches to weight management, including lifestyle modifications, medical interventions, and behavioral and psychological strategies. Effective weight loss strategies emphasize low-calorie, nutrient-rich diets, regular physical activity, and interventions tailored to individual needs. Combining multiple approaches offers the best chance of successful weight management and improved health outcomes. Summary This review provides insights into the complexities of obesity management and the factors contributing to the failure of weight loss programs. It highlights the necessity of adopting a holistic approach that addresses dietary habits, physical activity, genetic factors, psychological well-being, and socioeconomic influences. Recommendations include implementing lifestyle modifications, medical interventions when necessary, and integrating behavioral and psychological support to achieve sustainable weight loss and mitigate the global health challenge posed by obesity.
... A unique aspect of low-carbohydrate diets is that in many studies they were implemented ad libitum without prescribing an explicit caloric reduction, yet still elicited significant weight loss [181,182]. Without going into detail on the many individuals trials now published, there is generally less of a discrepancy in weight loss among diets of any macronutrient composition the longer the intervention duration [183], emphasizing the need for ongoing support and selecting the most appropriate diet that works for each person. In regard to this idea of personalized or precision nutrition, it is noteworthy that low-carbohydrate diets appear to be especially superior to low-fat diets in individuals who are insulin resistant or have high insulin secretion [42,43,[184][185][186], which is common in people with obesity. ...
Article
Full-text available
Purpose of Review Considering the high prevalence of obesity and related metabolic impairments in the population, the unique role nutrition has in weight loss, reversing metabolic disorders, and maintaining health cannot be overstated. Normal weight and well-being are compatible with varying dietary patterns, but for the last half century there has been a strong emphasis on low-fat, low-saturated fat, high-carbohydrate based approaches. Whereas low-fat dietary patterns can be effective for a subset of individuals, we now have a population where the vast majority of adults have excess adiposity and some degree of metabolic impairment. We are also entering a new era with greater access to bariatric surgery and approval of anti-obesity medications (glucagon-like peptide-1 analogues) that produce substantial weight loss for many people, but there are concerns about disproportionate loss of lean mass and nutritional deficiencies. Recent Findings No matter the approach used to achieve major weight loss, careful attention to nutritional considerations is necessary. Here, we examine the recent findings regarding the importance of adequate protein to maintain lean mass, the rationale and evidence supporting low-carbohydrate and ketogenic dietary patterns, and the potential benefits of including exercise training in the context of major weight loss. Summary While losing and sustaining weight loss has proven challenging, we are optimistic that application of emerging nutrition science, particularly personalized well-formulated low-carbohydrate dietary patterns that contain adequate protein (1.2 to 2.0 g per kilogram reference weight) and achieve the beneficial metabolic state of euketonemia (circulating ketones 0.5 to 5 mM), is a promising path for many individuals with excess adiposity. Graphical Abstract Created with Biorender.com.
... For the DASH pattern, almost all studies have shown its effective role in reducing cardiovascular outcomes [17,18]. However, little evidence of prospective studies is found in diabetes. ...
Article
Full-text available
(1) Background: There is little known about the relationship between Dietary Approaches to Stop Hypertension (DASH) pattern and diabetes in cohort studies, and the dietary patterns in the Chongqing natural population are unknown. (2) Methods: 14,176 Chinese adults, aged 30–79 years old, participated in this prospective study, from September 2018 to October 2023. A dietary assessment was conducted using a food frequency questionnaire, and three main dietary patterns were extracted from the principal component analysis. DASH patterns were calculated by standards. (3) Results: During the 4.64 y follow-up, 875 developed diabetes (11.3/1000 person-years). Each posteriori diet pattern is named after its main dietary characteristics (meat pattern, dairy products–eggs pattern, and alcohol–wheat products pattern). The high consumption of DASH pattern diet reduced the risk of diabetes (Q5 vs. Q1 HR: 0.71; 95% CI: 0.40–0.56) while high consumption of alcohol–wheat product pattern diet was associated with a high risk of diabetes (Q5 vs. Q1 HR: 1.32; 95% CI: 1.04, 1.66). The other two dietary patterns were not associated with diabetes. In subgroup analysis, there was an interaction between DASH pattern and sex (P for interaction < 0.006), with a strong association in females. (4) Conclusions: DASH pattern may be associated with a reduced new-onset diabetes risk and Alcohol-wheat products pattern may be positively associated with new-onset diabetes. These findings may provide evidence for making dietary guidelines in southwest China to prevent diabetes.
... Also, there is a point to evaluate the imprecision, we used as the recently reported minimal clinically important difference (MCID) threshold for anthropometrics measures, lipid profile, and glycemic indices to rate it. The MCID for BW (4.5 kg), BMI (0.95 kg/m 2 ), WC (2 cm), LDL-C (0.10 mmol/l), HDL-C (0.10 mmol/l), TG (0.09 mmol/l), TC (0.26 mmol/l), FBG (1.6 mmol/L), HOMA-IR (0.05), INS (5 pmol/l), was set [50][51][52]. In the case of lack of MCID in the literature, half of baseline SD values were considered as MCID [53]. ...
Chapter
Nutrition and heart healthy quality diets are essential components of prevention and management of cardiovascular disease. In this chapter, the evidence for specific diets, nutrients and dietary patterns is reviewed, and best practices for preventive cardiovascular care around nutrition and across the life course is presented. Aspects of nutrition that contribute to healthy weight and weight management including current understandings of the microbiome are reviewed. Factors associated with quality nutrition and cardiovascular outcomes, including social determinants, and policy to mitigate adverse influences on diet access and costs are explored.
Chapter
Introduction: Obesity is highly prevalent in the U.S. and is associated with an increased risk of major adverse cardiovascular events (MACE). Modalities for the management of obesity include lifestyle intervention, pharmacotherapy, and bariatric surgery. Areas Covered: This review describes the evidence on the effects of weight loss therapies on MACE risk. Lifestyle interventions and older antiobesity pharmacotherapies have been associated with <12% body weight reduction and no clear benefit to reduce MACE risk. Bariatric surgery is associated with substantial weight reduction (20–30%) and markedly lower subsequent risk for MACE. Newer antiobesity pharmacotherapies, particularly semaglutide and tirzepatide, have shown greater efficacy for weight reduction compared with older medications and are being evaluated in cardiovascular outcomes trials. Expert Opinion: Current practice for cardiovascular risk reduction in patients with obesity is lifestyle intervention for weight loss, combined with the treatment of obesity-related cardiometabolic risk factors individually. The use of medications to treat obesity is relatively rare. In part, this reflects concerns about long-term safety and weight loss effectiveness, possible provider bias, as well as lack of clear evidence of MACE risk reduction. If ongoing outcomes trials demonstrate the efficacy of newer agents for reducing MACE risk, this will likely lead to expanded use in obesity management.
Article
Full-text available
Background Many interventions have shown effectiveness in reducing the duration of acute diarrhea and gastroenteritis (ADG) in children. Yet, there is lack of comparative efficacy of interventions that seem to be better than placebo among which, the clinicians must choose. Our aim was to determine the comparative effectiveness and safety of the pharmacological and nutritional interventions for reducing the duration of ADG in children. Methods Data sources included Medline, Embase, CENTRAL, CINAHL, LILACS, and Global-Health up to May 2017. Eligible trials compared zinc (ZN), vitamin A, micronutrients (MN), probiotics, prebiotics, symbiotics, racecadotril, smectite(SM), loperamide, diluted milk, lactose-free formula(LCF), or their combinations, to placebo or standard treatment (STND), or among them. Two reviewers independently performed screening, review, study selection and extraction. The primary outcome was diarrhea duration. Secondary outcomes were stool frequency at day 2, diarrhea at day 3, vomiting and side effects. We performed a random effects Bayesian network meta-analysis to combine the direct and indirect evidence for each outcome. Mean differences and odds ratio with their credible intervals(CrI) were calculated. Coherence and transitivity assumptions were assessed. Meta-regression, subgroups and sensitivity analyses were conducted to explore the impact of effect modifiers. Summary under the cumulative curve (SUCRA) values with their CrI were calculated. We assessed the evidence quality and classified the best interventions using the Grading of Recommendations, Assessment, Development & Evaluation (GRADE) approach for each paired comparison. Results A total of 174 studies (32,430 children) proved eligible. Studies were conducted in 42 countries of which most were low-and middle-income countries (LMIC). Interventions were grouped in 27 categories. Most interventions were better than STND. Reduction of diarrhea varied from 12.5 to 51.1 hours. The combinations Saccharomyces boulardii (SB)+ZN, and SM+ZN were considered the best interventions (i.e., GRADE quality of evidence: moderate to high, substantial superiority to STND, reduction in duration of 35 to 40 hours, and large SUCRA values), while symbiotics (combination of probiotics+prebiotics), ZN, loperamide and combinations ZN+MN and ZN+LCF were considered inferior to the best and better than STND [Quality: moderate to high, superior to STND, and reduction of 17 to 25 hours]. In subgroups analyses, effect of ZN was higher in LMIC and was not present in high-income countries (HIC). Vitamin A, MN, prebiotics, kaolin-pectin, and diluted milk were similar to STND [Quality: moderate to high]. The remainder of the interventions had low to very-low evidence quality. Loperamide was the only intervention with more side effects than STND [Quality: moderate]. Discussion/Conclusion Most interventions analyzed (except vitamin A, micronutrients, prebiotics, and kaolin-pectin) showed evidence of superiority to placebo in reducing the diarrhea. With moderate-to high-quality of evidence, SB+ZN and SM+ZN, demonstrated the best combination of evidence quality and magnitude of effect while symbiotics, loperamide and zinc proved being the best single interventions, and loperamide was the most unsafe. Nonetheless, the effect of zinc, SB+ZN and SM+ZN might only be applied to children in LMIC. Results suggest no further role for studies comparing interventions against no treatment or placebo, or studies testing loperamide, MN, kaolin-pectin, vitamin A, prebiotics and diluted milk. PROSPERO registration CRD42015023778.
Article
Full-text available
The present review examined the evidence base for current popular diets, as listed in the 2016 U.S. News & World Report, on short-term (≤six months) and long-term (≥one year) weight loss outcomes in overweight and obese adults. For the present review, all diets in the 2016 U.S. News & World Report Rankings for “Best Weight-Loss Diets”, which did not involve specific calorie targets, meal replacements, supplementation with commercial products, and/or were not categorized as “low-calorie” diets were examined. Of the 38 popular diets listed in the U.S. News & World Report, 20 met our pre-defined criteria. Literature searches were conducted through PubMed, Cochrane Library, and Web of Science using preset key terms to identify all relevant clinical trials for these 20 diets. A total of 16 articles were identified which reported findings of clinical trials for seven of these 20 diets: (1) Atkins; (2) Dietary Approaches to Stop Hypertension (DASH); (3) Glycemic-Index; (4) Mediterranean; (5) Ornish; (6) Paleolithic; and (7) Zone. Of the diets evaluated, the Atkins Diet showed the most evidence in producing clinically meaningful short-term (≤six months) and long-term (≥one-year) weight loss. Other popular diets may be equally or even more effective at producing weight loss, but this is unknown at the present time since there is a paucity of studies on these diets.
Article
Full-text available
Inconsistent findings have reported on the inflammatory potential of diet and cardiovascular disease (CVD) and mortality risk. The aim of this meta-analysis was to investigate the association between the inflammatory potential of diet as estimated by the dietary inflammatory index (DII) score and CVD or mortality risk in the general population. A comprehensive literature search was conducted in PubMed and Embase databases through February 2017. All prospective observational studies assessing the association of inflammatory potential of diet as estimated by the DII score with CVD and all-cause, cancer-related, cardiovascular mortality risk were included. Nine prospective studies enrolling 134,067 subjects were identified. Meta-analyses showed that individuals with the highest category of DII (maximal pro-inflammatory) was associated with increased risk of all-cause mortality (hazard risk [HR] 1.22; 95% confidence interval [CI] 1.06–1.41), cardiovascular mortality (RR 1.24; 95% CI 1.01–1.51), cancer-related mortality (RR 1.28; 95% CI 1.04–1.58), and CVD (RR 1.32; 95% CI 1.09–1.60) than the lowest DII score. More pro-inflammatory diets, as estimated by the higher DII score are independently associated with an increased risk of all-cause, cardiovascular, cancer-related mortality, and CVD in the general population, highlighting low inflammatory potential diet may reduce mortality and CVD risk.
Article
Full-text available
Background: Mediterranean diets may be healthier than typical Western diets. Purpose: To summarize the literature comparing a Mediterranean diet with unrestricted fat intake with other diets regarding their effects on health outcomes in adults. Data sources: Ovid MEDLINE, CINAHL, and the Cochrane Library from 1990 through April 2016. Study selection: Controlled trials of 100 or more persons followed for at least 1 year for mortality, cardiovascular, hypertension, diabetes, and adherence outcomes, as well as cohort studies for cancer outcomes. Data extraction: Data extracted by 1 investigator was verified by another. Two reviewers assessed risk of bias and strength of evidence. Data synthesis: Two primary prevention trials found no difference in all-cause mortality between diet groups. One large primary prevention trial found that a Mediterranean diet resulted in a lower incidence of major cardiovascular events (hazard ratio [HR], 0.71 [95% CI, 0.56 to 0.90]), breast cancer (HR, 0.43 [CI, 0.21 to 0.88]), and diabetes (HR, 0.70 [CI, 0.54 to 0.92]). Pooled analyses of primary prevention cohort studies showed that compared with the lowest quantile, the highest quantile of adherence to a Mediterranean diet was associated with a reduction in total cancer mortality (risk ratio [RR], 0.86 [CI, 0.82 to 0.91]; 13 studies) and in the incidence of total (RR, 0.96 [CI, 0.95 to 0.97]; 3 studies) and colorectal (RR, 0.91 [CI, 0.84 to 0.98; 9 studies]) cancer. Of 3 secondary prevention studies reporting cardiovascular outcomes, 1 found a lower risk for recurrent myocardial infarction and cardiovascular death with the Mediterranean diet. There was inconsistent, minimal, or no evidence pertaining to any other outcome, including adherence, hypertension, cognitive function, kidney disease, rheumatoid arthritis, and quality of life. Limitations: Few trials; medium risk-of-bias ratings for many studies; low or insufficient strength of evidence for outcomes; heterogeneous diet definitions and components. Conclusion: Limited evidence suggests that a Mediterranean diet with no restriction on fat intake may reduce the incidence of cardiovascular events, breast cancer, and type 2 diabetes mellitus but may not affect all-cause mortality. Primary funding source: Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative. (PROSPERO: CRD42015020262).
Article
This article describes conceptual advances of the Grading of Recommendations Assessments, Development, and Evaluation (GRADE) working group guidance to evaluate certainty of evidence (confidence in evidence, quality of evidence) from network meta-analysis (NMA). Application of the original GRADE guidance, published in 2014, in a number of NMAs has resulted in advances that strengthen its conceptual basis and make the process more efficient. This guidance will be useful for systematic reviewer authors who aim to assess the certainty of all pairwise comparisons from an NMA and who are familiar with the basic concepts of NMA and the traditional GRADE approach for pairwise meta-analysis. Two principles of the original GRADE NMA guidance are that we need to rate the certainty of the evidence for each pairwise comparison within a network separately, and that in doing so we need to consider both the direct and indirect evidence. We present, discuss, and illustrate four conceptual advances: 1) Consideration of imprecision is not necessary when rating the direct and indirect estimates to inform the rating of NMA estimates, 2) There is no need to rate the indirect evidence when the certainty of the direct evidence is high and the contribution of the direct evidence to the network estimate is at least as great as that of the indirect evidence, 3) We should not trust a statistical test of global incoherence of the network to assess incoherence at the pairwise comparison level, and 4) In the presence of incoherence between direct and indirect evidence, the certainty of the evidence of each estimate can help decide which estimate to believe.
Article
Controversial conclusions from meta-analyses in nutrition are of tremendous interest to the public and can influence policies on diet and health. When the results of meta-analyses are the product of faulty methods, they can be misleading and can also be exploited by economic interests seeking to counteract unflattering scientific findings about commercial products.
Article
Background & aims: Dietary approaches to stop hypertension (DASH) diet is associated with improved blood pressure and risk of cardiovascular diseases. It is proposed that DASH might also improve systemic inflammatory markers like highly sensitive C-reactive protein (hs-CRP); however, interventional studies have led to conflicting results. The aim of current systematic review was to summarize results of randomized clinical trials examining the effect of DASH on inflammatory biomarkers. Methods: Randomized trials which assessed the effect of adherence to DASH diet on the circulating inflammatory biomarkers in adults were identified through searching PubMed, EMBASE, Scopus and Google Scholar up to December 2016. Difference in Mean change and its corresponding standard deviation in inflammatory markers between intervention and control groups were calculated to be used as effect size. Random effects model was used to calculate the summary effects. Results: Seven trials were eligible and six studies with 451 participants were included in the meta-analysis which measured hs-CRP as the biomarker of systemic inflammation. The DASH diet significantly decreased serum hs-CRP levels [mean difference (MD) = -1.01, 95% confidence interval (CI): -1.64, -0.38; I-squared (I(2)) = 67.7%] compared to usual diets; however, the effect was not significant when it was compared with healthy diets (MD = 0.10 mg/L; 95%CI: -0.16, 0.37; I(2) = 94.0%). The reduction in serum hs-CRP levels was greater in trials lasted eight weeks or more. Conclusion: Adherence to DASH diet is effective in improving circulating serum inflammatory biomarkers in adults, compared with usual diet; therefore, it could be a valuable strategy to suppress inflammation process.
Article
Objective: To present a novel and simple graphical approach to improve the presentation of the treatment ranking in a network meta-analysis (NMA) including multiple outcomes. Study design and settings: NMA simultaneously compares many relevant interventions for a clinical condition from a network of trials, and allows ranking of the effectiveness and/or safety of each intervention. There are numerous ways to present the NMA results, which can challenge their interpretation by research users. The rank-heat plot is a novel graph that can be used to quickly recognize which interventions are most likely the best or worst interventions with respect to their effectiveness and/or safety for a single or multiple outcome(s), and may increase interpretability. Results: Using empirical NMAs, we show that the need for a concise and informative presentation of results is imperative, particularly as the number of competing treatments and outcomes in a NMA increases. Conclusions: The rank-heat plot is an efficient way to present the results of ranking statistics, particularly when a large amount of data is available, and it is targeted to users from various backgrounds.