The effect of flaxseed supplementation on body weight and body composition: A systematic review and meta-analysis of 45 randomized placebo-controlled trials

Abstract

Flaxseed consumption may be inversely associated with obesity; however, findings of available randomized controlled trials (RCTs) are conflicting. The present study aimed to systematically review and analyse RCTs assessing the effects of flaxseed consumption on body weight and body composition. PubMed, Medline via Ovid, SCOPUS, EMBASE and ISI Web of Sciences databases were searched up to November 2016. Mean changes in body composition indices including body weight, body mass index (BMI) and waist circumference were extracted. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence intervals (CI). Heterogeneity between studies was assessed with the I(2) test. Publication bias and subgroup analyses were also performed. The quality of articles was assessed via the Jadad scale. A total of 45 RCTs were included. Meta-analyses suggested a significant reduction in body weight (WMD: -0.99 kg, 95% CI: -1.67, -0.31, p = 0.004), BMI (WMD: -0.30 kg m(-2) , 95% CI: -0.53, -0.08, p = 0.008) and waist circumference (WMD: -0.80 cm, 95% CI: -1.40, -0.20, p = 0.008) following flaxseed supplementation. Subgroup analyses showed that using whole flaxseed in doses ≥30 g d(-1) , longer-term interventions (≥12 weeks) and studies including participants with higher BMI (≥ 27 kg m(-2) ) had positive effects on body composition. Whole flaxseed is a good choice for weight management particularly for weight reduction in overweight and obese participants.

Full text

Obesity Treatment/Prevention
The effect of flaxseed supplementation on body weight
and body composition: a systematic review and meta-
analysis of 45 randomized placebo-controlled trials
M. Mohammadi-Sartang,
1,2
Z. Mazloom,
1,2
H. Raeisi-Dehkordi,
1,2
R. Barati-Boldaji,
2,3
N. Bellissimo
4
and
J. O. Totosy de Zepetnek
4
1
Department of Clinical Nutrition, School of
Nutrition and Food Sciences, Shiraz University
of Medical Sciences, Shiraz, Iran,
2
Meta-
Research Innovation Office, School of Nutrition
and Food Sciences, Shiraz University of
Medical Sciences, Shiraz, Iran,
3
Department of
Community Nutrition, School of Nutrition and
Food Sciences, Shiraz University of Medical
Sciences, Shiraz, Iran, and
4
School of Nutrition,
Ryerson University, Toronto, Ontario, Canada
Received 3 January 2017; revised 2 March
2017; accepted 9 March 2017
Address for correspondence: Z. Mazloom,
Department of Clinical Nutrition, School of
Nutrition and Food Sciences, Shiraz University
of Medical Sciences, Shiraz, Iran.
Email: zohreh.mazloom@gmail.com
Summary
Flaxseed consumption may be inversely associated with obesity; however,
findings of available randomized controlled trials (RCTs) are conflicting. The
present study aimed to systematically review and analyse RCTs assessing the
effects of flaxseed consumption on body weight and body composition.
PubMed, Medline via Ovid, SCOPUS, EMBASE and ISI Web of Sciences
databases were searched up to November 2016. Mean changes in body
composition indices including body weight, body mass index (BMI) and waist
circumference were extracted. Effect sizes were expressed as weighted mean
difference (WMD) and 95% confidence intervals (CI). Heterogeneity between
studies was assessed with the I
2
test. Publication bias and subgroup analyses
were also performed. The quality of articles was assessed via the Jadad scale.
A total of 45 RCTs were included. Meta-analyses suggested a significant
reduction in body weight (WMD: 0.99 kg, 95% CI: 1.67, 0.31,
p= 0.004), BMI (WMD: 0.30 kg m
2
, 95% CI: 0.53, 0.08, p= 0.008)
and waist circumference (WMD: 0.80 cm, 95% CI: 1.40, 0.20,
p= 0.008) following flaxseed supplementation. Subgroup analyses showed that
using whole flaxseed in doses ≥30 g d
1
, longer-term interventions (≥12 weeks)
and studies including participants with higher BMI (≥27 kg m
2
) had positive
effects on body composition. Whole flaxseed is a good choice for weight
management particularly for weight reduction in overweight and obese
participants.
Keywords: Body mass index, body weight, flax, obesity.
Abbreviations: ALA α-linolenic acid; BMI body mass index; CI confidence
interval; PCOS polycystic ovary syndrome; RCTs randomized controlled trials;
SD standard deviation; SEs standard errors; SDG secoisolariciresinol diglucoside;
WC waist circumference; WMD weighted mean difference.
Introduction
Obesity is a major health concern and an important risk
factor for diabetes, cardiovascular disease and cancer.
According to the World Health Organization in 2014, more
than 1.9 billion adults were overweight (body mass index
[BMI] ≥25 kg m
2
), and 600 million were obese
(BMI ≥30 kg m
2
) (1,2). It is predicted that ~1.12 billion
individuals will be obese by 2030 (2). The increasing
prevalence of obesity and its related metabolic abnormalities
(e.g. dyslipidaemia, insulin resistance and hypertension) has
created an urgent need for finding an effective approach to
obesity reviews doi: 10.1111/obr.12550
© 2017 World Obesity Federation Obesity Reviews

reduce obesity (3). A large body of evidence suggests a
potential of utilizing functional foods or dietary
nutraceuticals for the management of obesity and associated
abnormalities (4–6).
Flaxseed (a.k.a. linseed) is a functional food that is a rich
source of α-linolenic acid (ALA), an omega-3 fatty acid
found in vegetables (7,8). Previous studies have shown
anti-inflammatory, antithrombotic and antiarrhythmic pro-
perties of ALA (9). Flaxseed oil contains 50–62% ALA,
while whole flaxseed contains 22% ALA (10). Further,
flaxseed contains a high quantity of soluble dietary fibre
(11–13) and is a rich food source of lignan, one of the
three major groups of phytoestrogens (14). Flaxseed and
its components have been shown to be beneficial in
reducing risk of cardiovascular diseases, diabetes, blood
pressure and hyperlipidaemia (15–17); its consumption
may also positively influence body weight, and by
extension obesity (18–20).
Despite increased research on flaxseed in the last decade,
there are inconsistencies between trials examining its effects
on body composition indices. Some trials suggest an inverse
association between flaxseed consumption and body
composition indices (21,22), while others show no little or
reduction in body composition compared with control
following flaxseed supplementation (23–25). The present
study performed a comprehensive systematic review and
meta-analyses of available randomized controlled trials
(RCTs) to help quantify the overall effects of flaxseed
products on body composition indices in adults.
Materials and methods
Search strategy
Preferred Reporting Items for Systematic Reviews and
Meta-Analyses statement guidelines were followed as a
framework for reporting meta-analyses of RCTs (26). A
systematic literature search was conducted in medical
databases including PubMed, Medline via Ovid, SCOPUS,
EMBASE and ISI Web of Sciences up to November 2016
using the following subject headings (MeSH) and non-
MeSH keywords: flax* OR flaxseed* OR ‘flax seed*’OR
‘flax-seed*’OR linseed* OR lignan* OR ‘Linum
usitatissimum*’(Supporting Information S1). The search
was confined to RCTs exploring the influence of flaxseed
or its products (whole or ground flaxseed, lignin
supplement and flaxseed oil) using the English language,
and only studies among human participants were included.
The reference list of related articles, reviews and meta-
analyses were hand-searched for additional relevant studies.
Two independent investigators (H. R. D. and R. B. B.)
screened titles and abstracts for relevant studies, and
discrepancies were resolved using a third investigator
(M. M. S.). The PubMed’s‘My NCBI’(National Centre
for Biotechnology Information) email alert service was
created for identifying new articles that may be published
after our search.
Inclusion criteria
Publishes studies were included if they met the following
criteria: (i) full-text articles written in the English
language; (ii) RCTs with either parallel or crossover
design; (iii) conducted among adults (age ≥18 years);
(iv) intervention duration of at least 2 weeks; (v) no use
of hormone replacements, fish oil or ALA in the control
group; and (vi) assessed body weight, BMI and waist
circumference (WC) as outcome measures (sufficient
information including standard deviation [SD], standard
error [SE] or 95% confidence interval [CI] must have been
available at baseline and at end study in both flaxseed
and control group). Studies were not included if we were
unable to extract the net effect of the flaxseed intervention
(i.e. if flaxseed was supplemented as an adjunct to another
supplement, the control group containing that
supplement).
Quality assessment
The quality of eligible studies was evaluated
independently by two investigators (M. M. S. and
Z. M.) using the quantitative 5-point Jadad scale (27).
Articles were assigned 0 or 1 point for each of the
following five criteria: (i) randomization, (ii) suitable
method of randomization, (iii) double blinding, (iv)
suitable method of double blinding and (v) explanation
and reason of withdrawals and dropouts (27). Articles
with scores with ≥3 and ≤2 were considered of high and
low quality, respectively (28).
Data extraction
Eligible RCTs were reviewed independently by two
authors (H. R. D. and R. B. B.), and the following data
were extracted using a standardized electronic form: first
author’s name, publication year, study location, sample
size (enrolment and number completed), type and dose
of intervention and placebo, study design, duration of
the intervention, patient’s status and other information
including age and sex. Mean and SD of outcome
measures at study baseline, post-intervention and/or
change between baseline and post-intervention were
recorded. For studies reporting data at multiple doses
or multiple time points, only the highest dose of
supplementation at end study were extracted. Three
studies included a fish oil arm that we did not assess in
accordance with our inclusion criteria (29–31).
2Flaxseed and body composition M. Mohammadi-Sartang et al.obesity reviews
© 2017 World Obesity FederationObesity Reviews

Quantitative data synthesis and statistical analysis
We evaluated the influence of flaxseed supplementation on
change of the following outcomes: (i) mass (kg); (ii) BMI
(kg m
2
) and (iii) WC (cm). Effect sizes for the meta-
analysis were defined as weighted mean difference (WMD;
value at end trial minus the value at baseline) and 95%
CI. In the event of no reported SD of the mean difference,
it was calculated as follows: SD = ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
SD baselineðÞ2þ½
p
SD end studyðÞ22RSD baselineSD end studyðÞ:
A correlation coefficient of 0.5 was assumed as this R
value is a conservative estimate between 0 and 1 (32). When
SE was reported in place of SD, we converted it SD for
analyses: SD = SE × ffiffiffi
n
p, where nis the number of
participants in each group. If interested outcomes were
reported as median and range, all mean and SD values were
estimated using the method described by Hozo et al. (33).
Plot digitizer software was used to extract data when the
outcome variable was presented in graphic form only. Pre-
defined subgroup analyses were performed on different
types of flaxseed, supplementation duration, participant
BMI, participant sex, type of study and quality assessment
using the Jadad scale. Random-effects meta-regression
analysis was performed using an unrestricted maximum
likelihood method to explore the association between
changes in body composition indices and duration and dose
of flaxseed supplementation.
Statistical heterogeneity between studies was evaluated
using Cochran’sQ-test (significance set at p<0.1) and I
2
(≥50% assumed to indicate substantial heterogeneity
among studies). In the presence of heterogeneity, pooled
effect size was calculated using a random-effects model;
otherwise, we applied a fixed-effects model. Sensitivity
analysis was used to explore the extent to which inferences
might depend on a particular study using the leave-one-
out method (i.e. removing a single trial at a time and
repeating the analyses) (34). Publication bias was assessed
by funnel plot, Begg’s rank correlation and Egger’s weighted
regression tests. In the event of publication bias, the Duval
and Tweedie ‘trim and fill’and ‘fail-safe N’methods were
utilized (35). All statistical analyses were performed using
Comprehensive Meta-Analysis (CMA) V2 software
(Biostat, Englewood, NJ, USA) (36) with a level of
significance of p<0.05.
Results
A total of 2,592 reports were initially identified; after
removing duplicates (n= 1,259), 1,333 articles remained.
Of the 1,333 articles, 1,264 were excluded because they
were either not RCTs in humans or unrelated to our
present meta-analyses according to inclusion criteria. A
total of 69 potentially relevant articles were chosen for
full-text evaluation and detailed examination. Among
the full-text articles evaluated, 24 studies were excluded
for the following reasons: duplicate report (n= 2), not
randomized placebo-controlled studies (n= 2), no
anthropometric measurements performed (n= 17) and
use of flaxseed in combination with other components
without an appropriate control group (n= 3). Forty-five
eligible RCTs with 49 treatment arms were included in
the meta-analyses (21–25,30,31,37–74). Of these, 28
articles reported effects of flaxseed on weight (21–
23,25,31,37,38,40,43–45,47–49,51–54,57,59,62,63,66–
68,71), 35 articles on BMI (21,22,24,25,30,31,37–39,42–
44,46–51,53,55–62,64–66,68–71,74) and 13 articles on
WC (21,22,31,39,41,44,48,55,60,61,66,72,73). The study
selection process is shown in Fig. S1.
Characteristics of the included studies
Study characteristics of the 45 eligible articles are presented
in Table S1. Data were pooled from the 45 studies
comprising 48 treatment arms; sample size ranged from 9
to 277. Overall, 2,789 participants were randomly assigned
in these trials, and 2,561 participants (91.82%) completed
the studies. Mean age of the participants ranged from 25.6
to 67 years. Nine of the 45 trials were performed exclusively
on women (31,38,41,43,45,48,51,57,75) and nine on men
(40,44,46,54,56,63,65,70,74), and the remaining trials
included both sexes; however, three studies did not mention
sex composition of participants (58,67,68). Eligible studies
were published between 1995 and 2016, and most of them
were conducted in the USA (31,37,38,46,52,57,60,61,66,70,75),
Canada (22,23,41–43,48,50,67), Iran (21,59,69,71,73) and
Brazil (24,39,44,45,49). The remaining studies were conducted
in China (62,72), Australia (40,56,63,74), Greece (64,65),
Germany (47), Denmark (51), Romania (58) India (53) and
Japan (54).
Twenty-two treatment arms used whole
(21,22,24,38,42,44,46,48,49,53,57,67,68,71–73), ground
(25,43,45,58,66) or deffated (52) flaxseed for the
intervention. Sunflower seed (38), raw rice (44), collagen
(45), wheat germ (48), manioc flour (49), cassava flour
(24), wheat bran (52,66) and wheat (67) were used for the
control groups. Eighteen treatment arms supplemented
flaxseed oil for the intervention (23,30,31,39,40,47,50,54–
56,59–61,63–65,69,70,74), while the control group was
provided canola oil (50,56), corn oil (54,70), olive oil
(30,40,55,60), soybean oil (31,75), safflower oil (63–65),
sunflower oil (23,47), MCT oil (59), n-6 oil (74) or placebo
(22,39). One study used both whole flaxseed and flaxseed
oil (22), and five studies used flaxseed lignan
(37,41,45,51,62); the controls in these studies were assigned
placebo. Three studies (21,72,73) incorporated lifestyle
advice only for the control group, while the intervention
group was assigned lifestyle advice and 30 g d
1
flaxseed.
Two other studies (46,58) provided a low-fat or regular diet
Flaxseed and body composition M. Mohammadi-Sartang et al.3obesity reviews
© 2017 World Obesity Federation Obesity Reviews

for the control group, and the intervention group was
provided the same diet in combination with additional
flaxseed.
A wide range of flaxseed supplementation doses were
utilized in the study designs: whole flaxseed 13 to
90 g d
1
, flaxseed oil 1 to 15.4 g of ALA per day and lignan
50 to 600 mg d
1
. Supplementation duration varied from 3
to 48 weeks. Participant characteristics also varied between
studies, many focusing on special and diseased populations:
metabolic syndrome (70,72,73), type 2 diabetes
(22,30,41,62), cardiovascular disease (42,44,67), obesity
(24,49,66), hyperlipidaemia (38,47,50,52,58,64,65,68,71),
postmenopausal women (45,57), polycystic ovary
syndrome (31), prostate cancer (46), haemodialysis
(25,59), diabetic nephropathy (69), non-alcoholic fatty liver
disease (21), fire-fighters (23), normolipidaemic men (63),
healthy adults (37,40,48,51,54–56,60,61,74) and older
adults (39).
Data quality
Twenty-nine trials were classified as high quality
(Jadad score ≥3) (23,24,30,31,37–39,41–43,46–
49,51,52,54,55,57,59,60,62,63,65), and 16 trials
were of low quality (Jadad score <3)
(21,22,25,40,44,45,50,53,56,58,61,64,66,68,71,73).
The last column of Table 1 provides the quality
assessment results of the studies.
Three of the 45 included articles did not report
randomization (53,58,68), but excluding these three
studies had no impact on the meta-analyses. Thirty-
two studies did not adequately explain the
randomization procedure (21,22,25,37–41,43–
45,47,49–58,60,61,63,64,66,68,70,71,73,74). Twenty
studies reported double blinding (24,30,31,37–
39,41,43,47–49,51,54,57,59,60,62,67,69,70), but 28
studies did not clearly describe the blinding procedure
(21–23,25,31,38,40,42,44–47,50,53,54,56,58,60,61,64–
66,68,69). Details of dropouts were provided in all the
studies.
Meta-analysis results
Twenty-eight studies with 30 treatment arms including a
total of 1,837 participants reported body weight as an
outcome measure. Pooled results from the random-effects
model showed that a reduction in body weight was
significant following flaxseed consumption (WMD:
0.99 kg, 95% CI: 1.67, 0.31, p= 0.004) with
significant heterogeneity (I
2
= 50.00%, p= 0.001) (Fig. 1A).
Thirty-five trails with 38 treatment arms including a total
of 2,209 participants reported BMI as an outcome measure.
Pooled results from the random-effects model showed that
BMI was reduced in the flaxseed group compared with the
control group (WMD: 0.30 kg m
2
, 95% CI: 0.53,
0.08, p= 0.008), with significant heterogeneity among
the studies (I
2
= 54.93%, p<0.001) (Fig. 1B).
Thirteen studies with 14 treatment arms including a total
of 912 subjects reported WC as an outcome measure.
Pooled results from the random-effects model showed that
WC was reduced following an intervention of flaxseed or
its derivatives (WMD: 0.80 cm, 95% CI: 1.40, 0.20,
p= 0.008), with no significant heterogeneity among the
studies (I
2
= 46.94%, p= 0.027) (Fig. 1C).
Sensitivity analysis
Effect sizes for the influence of flaxseed on body weight
were robust in the sensitivity analysis, suggesting that
omission of each trial did not have a significant effect on
the results (Fig. S2A). However, effects of flaxseed on BMI
and WC were sensitive to studies performed by Yari et al.
(73) and Taylor et al. (22), respectively. Removing these
two studies from the analyses rendered the effect of flaxseed
on BMI and WC non-significant (Fig. S2B–C).
Subgroup analysis
Results of the subgroup analyses are summarized in Table 1.
When stratified on the basis of type of intervention (whole
flax, flaxseed oil and lignan), a significant reduction in body
weight was observed in trials using whole flaxseed (WMD:
1.75 kg, 95% CI: 2.87, 0.63, p= 0.002), but not
flaxseed oil (WMD: 0.37 kg, 95% CI: 1.48, 0.74,
p= 0.514) or lignan extract (WMD: 0.20 kg, 95%
CI:0.23, 0.63, p= 0.363). BMI was also decreased in the
interventions using whole flaxseed (WMD: 0.63 kg m
2
,
95% CI: 1.17 to 0.09, p= 0.021), but not flaxseed oil
(WMD: 0.004 kg m
2
, 95% CI: 0.08, 0.09, p= 0.930)
or lignan extract (WMD: 0.10 kg m
2
, 95% CI: 0.06,
0.26, p= 0.234). Finally, WC decreased in studies using
whole flaxseed (WMD: 1.21, 95% CI 1.96, 0.46,
p= 0.001), but not in flaxseed oil (WMD: 0.05, 95%
CI: 1.06, 0.96, p= 0.921).
The subgroup analyses performed to identify the
effective dose of whole flaxseed on body composition
showed that body weight (WMD: 0.21 kg, 95% CI:
0.34, 0.09, p= 0.001) and BMI (WMD: 0.60 kg m
2
,
95% CI: 0.81, 0.39, p<0.001) were reduced in whole
flaxseed doses ≥30 g d
1
, but not in lower doses. With
regard to duration of supplementation, there was a
reduction in body weight (WMD: 1.50 kg, 95% CI:
2.41, 0.60, p= 0.001), BMI (WMD: 0.44 kg m
2
,
95% CI: 0.73, 0.16, p= 0.002) and WC (WMD:
0.69 cm, 95% CI: 1.61, 0.32, p= 0.003) among
trials with ≥12 weeks of duration, compared with those
lasting <12 weeks.
4Flaxseed and body composition M. Mohammadi-Sartang et al.obesity reviews
© 2017 World Obesity FederationObesity Reviews

Table 1 Results of subgroup analysis of included randomized controlled trials in meta-analysis of flaxseed supplementation and body composition indices
Variables Type of intervention Duration Baseline BMI Gender RCT type Study quality
Body weight WF FXO LIG ≥12 <12 ≥27 <27 F M Both RP RC Low (<3) High (≥3)
No. of comparison 18 7 4 18 12 13 17 7 4 19 22 8 14 16
WMD, 95% CI 1.75, 2.87,
0.63 0.37,
1.48, 0.74
0.20,
0.23, 0.63 1.50, 2.41,
0.0.60
0.138,
0.96, 1.23 1.80,
3.30,
2.35
0.17,
0.46,
0.11
0.46,-
3.04, 2.10
0.72,
6.32,
7.52
1.20,
2.01,
0.39
1.31
2.18,
0.45
0.19,
0.23,
0.62
2.19,
3.68,
0.71
0.15,
0.44,
0.13
pvalue 0.002 0.514 0.363 0.001 0.806 0.019 0.242 0.722 0.610 0.003 0.003 0.378 0.004 0.282
I
2
(%) 61.65 0.00 0.00 69.74 0.00 49.51 0.00 0.00 0.00 68.27 54.69 0.00 50.33 0.00
p-heterogeneity <0.001 0.994 0.944 <0.001 1.00 0.011 0.893 1.00 0.990 <0.001 0.001 1.00 0.016 0.914
BMI WF FXO LIG ≥12 <12 ≥27 <27 F M Both RP RC Low (<3) High (≥3)
No. of comparison 19 15 3 19 18 24 13 6 7 25 18 9 14 23
WMD,95% CI 0.63, 1.17
to 0.09
0.004,
0.08, 0.09
0.10,
0.06, 0.26 0.44,:
0.73, 0.16
0.146,
0.35, 0.61 0.55,
1.04,
0.06
0.02,
0.08.
0.14
0.28,
0.54.
0.03
0.16,
0.87,
0.55
0.36,
0.65,
0.07
0.43,
0.73,
0.12
1.00,
0.06,
0.26
0.66,
1.23,
0.08
0.004,
0.07,
0.08
pvalue 0.021 0.925 0.234 0.002 0.565 0.028 0.633 0.028 0.660 0.015 0.005 0.232 0.025 0.918
I
2
(%) 50.24 0.00 0.00 76.46 0.00 66.04 0.00 0.00 18.54 66.34 64.04 0.00 47.26 0.00
p-heterogeneity 0.007 0.548 0.950 <0.001 1.00 <0.001 0.690 0.997 0.288 <0.001 <0.001 0.999 0.026 0.864
WC WF FXO LIG ≥12 <12 ≥27 <27 F M Both RP RC Low (<3) High (≥3)
No. of comparison 7 6 1 9 5 9 5 2 1 11 12 2 7 7
WMD, 95% CI 1.21, 95%
CI 1.96, 0.46 0.05, 95%
CI: 1.06,
0.96
1.50,
12.72,
9.72
0.69, 95%
CI: 1.61,
0.32
0.22, 95%
CI: 1.40,
1.86
1.12,
1.97,
0.26
0.50,
1.34,
0.34
1.44,
3.04,
0.16
1.36,
1.68,
3.68
0.80,
1.47,
0.14
0.83,
1.44,
0.22
0.28,
3.75,
3.94
1.82,
2.92,
0.72
0.37,
1.09,
0.34
pvalue 0.001 0.921 0.793 0.003 0.784 0.010 0.245 0.079 0.465 0.017 0.007 0.878 0.001 0.305
I
2
(%) 70.53 0.00 0.00 63.04 0.00 62.17 0.00 0.00 0.00 54.37 54.24 0.00 64.52 0.00
p-heterogeneity 0.002 0.974 1.00 0.006 0.899 0.007 0.676 0.618 1.00 0.016 0.013 0.741 0.010 0.821
BMI, body mass index; F, female; FXO, flaxseed oil; LIG, lignans; M, male; RC, randomized crossover design; RCT, randomized controlled trial; RP, randomized parallel design; WC, waist circumference; WF,
whole flaxseed; WMD, weight mean difference.
Flaxseed and body composition M. Mohammadi-Sartang et al.5obesity reviews
© 2017 World Obesity Federation Obesity Reviews

Figure 1 Forest plot detailing weighted mean difference and 95% confidence intervals (CIs) for the impact of flaxseed supplementation on body
composition indices. BMI, body mass index. [Colour figure can be viewed at wileyonlinelibrary.com]
6Flaxseed and body composition M. Mohammadi-Sartang et al.obesity reviews
© 2017 World Obesity FederationObesity Reviews

When stratified on the basis of BMI status, flaxseed
consumption reduced body weight, BMI and WC among
participants with BMI ≥27, but not among participants
with BMI <27 (Table 1). We also observed a significant
reduction in BMI in women compared with men, with mean
changes of 0.28 kg m
2
(95% CI: 0.54, 0.03, p= 0.03)
and 0.16 kg m
2
(95% CI: 0.87, 0.55, p= 0.66),
respectively.
A significant reduction in body weight, BMI and WC was
found in studies using a parallel design but not crossover
Figure 2 Meta-regression plots of the association between mean changes in body composition indices and duration of flaxseed supplementation. The
size of each circle is inversely proportional to the variance of change. BMI, body mass index; CI, confidence interval; WC, waist circumference.
Flaxseed and body composition M. Mohammadi-Sartang et al.7obesity reviews
© 2017 World Obesity Federation Obesity Reviews

design when assessing based on the type of RCTs. Finally,
subgroup analyses suggested significant reducing effects of
flaxseed and its derivatives on body weight, BMI and WC
in low-quality studies, but not in high-quality studies.
Meta-regression
The effect of flaxseed intervention on body weight (slope:
0.049; 95% CI: 0.06 to 0.03; p= 0.02), BMI (slope:
0.007; 95% CI: 0.01 to 0.0001; p= 0.046) and WC
(slope: 0.015; 95% CI: 0.11 to 0.04; p= 0.028) were
associated with supplementation duration (Fig. 2A–C).
When assessing the influence of flaxseed and flaxseed
derivatives dose (whole flaxseed or flaxseed oil, expressed
as ALA g d
1
and lignan extract), no association effects
were found with body weight, BMI or WC (Table S2).
Publication bias
Funnel plots revealed asymmetry in the meta-analyses of
flaxseed consumption on body weight and BMI, but there
was no sign of publication bias with respect to WC. Using
the ‘trim and fill’method for adjusting publication bias,
seven and six potentially missing studies were imputed for
the meta-analyses of body weight and BMI, respectively
(Fig. S3). Corrected effect sizes after imputation of
potentially missing studies, as well as results of Egger’s
linear regression, Begg’s rank correlation and ‘fail-safe N’
tests, are summarized in Table S3.
Discussion
The present systematic review and meta-analyses of
RCTs explored the effects of flaxseed product
consumption on body composition indices in adults.
Our major findings indicate that participants ingesting
flaxseed products had lower body weight, BMI and
WC after the intervention than controls. However,
subgroup analyses revealed that body composition
indices were reduced with whole flaxseed consumption
only, in trials lasting ≥12 weeks, and among participants
with BMI ≥27 kg m
2
.
Flaxseed is a rich source of plant lignans (primarily
secoisolariciresinol diglucoside [SDG]) (12,13); in fact,
flaxseed contains more than 100 times higher SDG than
most other foods (76). Purified lignans in the form of SDG
have been shown to reduce visceral (abdominal) fat in mice
compared with those not consuming SDG (77). The authors
suggested that the high content of SDG may contribute to
the overall effects of flaxseed via a reduction of mRNA
levels of sterol regulatory element-binding proteins that
are involved in TAG synthesis (77). SDG may also be useful
in regulating adiponectin levels and can prevent or reduce
obesity through increased fat oxidation in skeletal muscle
(77,78). In the present meta-analyses, five studies used
lignin supplements (37,41,45,51,62), but subgroup analysis
revealed that lignan did not have any benefit for body
composition in adults. The limited data on humans make
it difficult to draw conclusions regarding the effects of
lignan on obesity. Further, flaxseed oil did not significantly
reduce body weight, BMI and WC, supporting previous
studies reporting no effects of ALA on body composition
(40,47,54,59).
We did observe reductions in body composition indices
with whole flaxseed, however, possibly owing to the high
fibre content (25% soluble form) (13,79). Dietary fibre,
particularly soluble fibre, has anti-obesity effects that have
been shown to decrease body weight (80). Dietary fibre
may help prevent weight gain or promote weight loss via
delayed gastric emptying, inducing feelings of fullness by
absorbing large amounts of water (81), and/or increasing
the concentration of short chain fatty acids that act to
enhance satiety by a variety of mechanisms (82). Further,
dietary fibre can induce viscosity and reduce re-uptake of
bile acids, subsequently reducing micelle formation and
lipid uptake (83,84).
The present meta-analysis found that duration of
flaxseed supplementation had an effect on body
composition indices. Subgroup analysis showed a
significant reduction in body weight, BMI and WC
following intervention durations of ≥12 weeks. These
findings may be explained by the subsequent increase in
circulating ALA after flaxseed supplementation. ALA is
converted to eicosapentaenoic acid (20:5 n-3) and
docosahexaenoic acid (22:6 n-3) in the body (85); the
anti-obesity effects of eicosapentaenoic acid and
docosahexaenoic acid have been shown in previous studies
(86–88). In the long-term supplementation, concentrations
of these long chain omega-3 fatty acids are increased (89),
potentiating the anti-obesity effects of flaxseed.
Furthermore, dietary fibre consumption leads to a gradual
increase in intestinal gut flora (90), which may enhance
lignan absorption (91) and result in the formation of the
main component of mammalian lignans, enterolactone
(92). An inverse relationship between enterolactone and
obesity has been observed (93,94).
Positive effects of flaxseed interventions were observed
among participants with BMI ≥27 kg m
2
.These
findings suggest that higher BMI has a potent moderating
impact on the effects of flaxseed consumption on changes
in body composition. In other words, it appears that
individuals with higher BMI were more likely to be
positively affected by the supplementation. Our meta-
analysis also showed that the influence of flaxseed on
BMI was more striking in women than in men; however, as
three articles did not report the sex composition of the
participants, the exact sex-specificity effect of flaxseed
remains unclear.
8Flaxseed and body composition M. Mohammadi-Sartang et al.obesity reviews
© 2017 World Obesity FederationObesity Reviews

Limitations
The present study has several limitations; the findings
should be interpreted with caution. First, our results
showed that body weight, BMI and WC were reduced in
low-quality studies but not in higher-quality studies.
Second, the protocol design differences between studies
may have affected our findings. Crossover trials utilized a
washout period of anywhere between 2 (52) and 12 weeks
(41,62), creating different carry-over effects between trials.
This may, in part, help explain the significant reduction
effect observed in parallel design versus crossover design.
In most of the included crossover studies (seven of 12),
the duration of supplementation was <12 weeks, perhaps
providing explanation as to why we observed a significant
effect of flaxseed on body weight, BMI and WC in studies
lasting ≥12 weeks but not in lower durations. Third,
significant heterogeneity between studies indicates that
the effects of flaxseed on body weight and BMI are not
uniform, likely owing to employing different
methodologies and assessing different populations. Finally,
more than half the eligible studies had a small sample size
(30 of 44 included studies had a sample size lower than 50
participants).
Further, it should be noted that sensitivity analyses
revealed that the results of BMI and WC were highly
determined by the studies of Yari et al. (73) and Taylor
et al. (22), respectively. It is likely that more studies will
help confirm whether flaxseed and its products affect
BMI and WC.
Conclusions
The current meta-analysis pooled results from 45 RCTs
regarding the effects of flaxseed consumption on body
composition indices; we believe that our findings are
valuable for researchers and clinicians. Our findings show
that supplementation of whole flaxseed for more than
12 weeks in individuals with a BMI higher than 27 kg m
2
may reduce body weight, BMI and WC. Flaxseed
consumption may be a valuable dietary approach for the
prevention and treatment of obesity, and many trials have
explored the effects of flaxseed interventions on body
composition. However, more research is needed with larger
sample sizes, adequate durations and well-designed trials
lasting over 12 weeks in order to confirm the beneficial
effects of flaxseed consumption on body composition.
Future research should determine the ideal quantity of
flaxseed for weight loss.
Acknowledgements
The authors’responsibilities were as follows: M. M. S. and
Z. M. conceived the study. M. M. S. carried out the literature
search. H. R. D. and R. B. B. carried out data extraction and
independent reviewing. M. M. S. and Z. M. assessed the
quality of included studies. M. M. S. performed data
analysis and interpretation. M. M. S. wrote the manuscript.
Z. M., N. B. and J. T. revised the manuscript. The
manuscript has been read and approved by all authors.
Conflict of interest statement
The research did not receive any specific grant from funding
agencies in the public, commercial or not-for-profit sectors.
The authors declared that they have no potential conflicts of
interest.
Supporting information
Additional Supporting Information may be found online in
the supporting information tab for this article. http://dx.doi.
org/10.1111/obr.12550
Table S1 Demographic characteristics of the included
studies.
Table S2 Meta-regression between changes in body
composition indices and administered doses of various
flaxseed products.
Table S3 Assessment of publication bias in the impact of
flaxseed supplementation on body composition indices.
Figure S1 Flow diagram of the study selection procedure
showing the number of eligible randomized controlled trials
for the meta-analysis of the impact of flaxseed
supplementation on body composition indices.
Figure S2 Leave-one-out sensitivity analysis of the impact of
flaxseed supplementation on body composition indices.
Figure S3 Funnel plots detailing publication bias in the
studies selected for analysis of flaxseed’s effects on body
composition indices. Trim and fill method was used to
impute for potentially missing studies. Open circles
represent observed published studies; closed circles
represent imputed unpublished studies. BMI, body mass
index; WC, waist circumference.
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