Content uploaded by Mohammad Jalali
Author content
All content in this area was uploaded by Mohammad Jalali on Jun 04, 2021
Content may be subject to copyright.
Available via license: CC BY-NC-ND 4.0
Content may be subject to copyright.
Complementary Therapies in Medicine 59 (2021) 102692
Available online 24 February 2021
0965-2299/© 2021 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Soy intake is associated with lowering blood pressure in adults: A
systematic review and meta-analysis of randomized double-blind
placebo-controlled trials
Zahra Mosallanezhad
a
,
b
,
1
, Marzieh Mahmoodi
a
,
b
,
1
, Sara Ranjbar
a
,
b
, Razieh Hosseini
c
, Cain C.
T. Clark
d
, Kristin Carson-Chahhoud
e
,
f
, Zahra Norouzi
g
, Ali Abbasian
h
, Zahra Sohrabi
i
,
Mohammad Jalali
a
,
*
a
Nutrition Research Center, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
b
Student Research Committee, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
c
Student Research Committee, Department of Nutrition, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
d
Centre for Sport, Exercise and Life Sciences, Coventry University, Coventry CV15FB, UK
e
Australian Centre for Precision Health, School of Health Sciences, University of South Australia, Australia
f
School of Medicine, the University of Adelaide, South Australia, Australia
g
Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
h
Department of Physical Education & Sport Sciences, Masjed-Soleiman Branch, Islamic Azad University, Masjed-Soleiman, Iran
i
Department of Community Nutrition, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
ARTICLE INFO
Keywords:
Soy
Blood pressure
Hypertension
Review
Meta-analysis
ABSTRACT
Background: Soy has several benecial effects on cardiovascular disease (CVD); however, results of clinical trial
studies are equivocal. Thus, the present study sought to discern the efcacy of soy intake on blood pressure.
Methods: The search process was conducted in PubMed, Scopus, Web of Science, and Cochrane Library, to
ascertain studies investigating the efcacy of soy intake on blood pressure in adults, published up to June 2020.
A random-effects model was applied to pool mean difference and 95 % condence interval (CI). Begg’s and
Egger’s methods were conducted to assess publication bias.
Results: Pooled effects from 17 effect sizes revealed a signicant improvement in systolic blood pressure (SBP)
(−1.70; −3.34 to −0.06 mmHg; I
2
=45.4 %) and diastolic blood pressure (DBP) (−1.27; −2.36 to −0.19 mmHg,
I
2
=43.9 %) following soy consumption, in comparison with controls. Subgroup analysis demonstrated a
reduction in both SBP and DBP in younger participants with lower baseline DBP and intervention durations of
<16 weeks.
Conclusion: Our results suggest that soy intake is associated with an ameliorating effect on blood pressure in
adults.
1. Introduction
Soy is a traditional food that is globally popular, especially in Asia, and
is widely used to produce various food products, such as soybean oil, soy
milk, soy our, and many retail food products.
1
Utilizing soy products in
the food processing industry makes it possible to achieve signicant
economic effects by reducing production costs and standardizing qual-
ity.
2,3
Soybean contains compounds such as protein, ber, vitamins,
minerals, and phytochemicals, which has led to considerable research
interest regarding its effects on various diseases.
1,4
Accordingly, previous
studies have reported protective features of soy in diabetes, cancer,
osteoporosis, and menopausal problems,
3
with further studies conrming
its benecial effects on cardiovascular disease (CVD).
5
One of the most important risk factors of CVD is hypertension, which
represents one of the most prevalent non-communicable diseases,
worldwide.
6
Several strategies, including medication and lifestyle
* Corresponding author at: Nutrition research Center, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Razi Ave, Shiraz, 7153675541,
Iran.
E-mail address: Mj.artak@gmail.com (M. Jalali).
1
These authors contributed equally to the work and should be regarded as equal rst authors.
Contents lists available at ScienceDirect
Complementary Therapies in Medicine
journal homepage: www.elsevier.com/locate/ctim
https://doi.org/10.1016/j.ctim.2021.102692
Received 17 January 2021; Accepted 20 February 2021
Complementary Therapies in Medicine 59 (2021) 102692
2
modication are recommended to manage the disorder,
7
whilst
numerous studies have been performed to investigate the effects of nu-
trients on blood pressure.
8
For instance, the Dietary Approaches to Stop
Hypertension (DASH) diet has been advocated as part of the treatment
protocol for hypertensive patients.
9
Moreover, there are several studies
demonstrating the effectiveness of macronutrients on blood pres-
sure.
10,11
In the case of total protein intake, however, the results man-
ifest in the literature are contradictory, although the positive effect of
plant based protein on blood pressure has been conrmed.
12
In addition,
although observational studies
13,14
have conrmed the efcacy of soy
as a vegetable protein on blood pressure, the results of clinical trial
studies are equivocal.
15,16
Due to the limited number of participants in previous clinical trial
studies,
17,18
as well as differences in intervention duration,
19,20
age,
21,22
and baseline blood pressure,
18,21,23
it is not possible to draw any rm
conclusion regarding the effect of soy on blood pressure. Therefore, in
this study we aimed to identify the effect of soy intake on blood pressure
by performing a systematic review and meta-analysis of randomized
clinical trials.
2. Methods
We undertook our study in accordance with guidelines proposed by
the Preferred Reporting Items for Systematic reviews and Meta-Analyses
(PRISMA).
24
The review protocol was registered with PROSPERO
(CRD42020214728).
2.1. Search process
To identify relevant papers investigating the effect of soy on blood
pressure, we undertook a systematic search in PubMed, Embase, Scopus,
Web of Science, and Cochrane Library, for all available publications up
to June 2020, using a combination the relevant terms in titles and ab-
stracts, without making any restrictions (Supplementary material 1). In
some cases, we used the wildcard term “*” to increase sensitivity and
checked the reference lists of the relevant reviews and Google Scholar to
supplement the database search strategy, which was prepared with in-
group consensus. After loading retrieved records into EndNote, dupli-
cates were removed.
2.2. Inclusion and exclusion criteria
Four authors independently assessed the records retrieved from the
database search. Randomized controlled trials (RCTs) investigating the
association of soy intake and blood pressure in adults (>18 years of age)
were identied for inclusion. To maximize methodological rigor, only
double-blind placebo-controlled trials were then shortlisted for inclu-
sion, to increase quality of evidence, and reduce potential bias in the
meta-analysis. Review articles, dissertations, brief reports, observation-
designed and non-English language studies were excluded, as were those
lacking clinical information or statistical data required for analysis (e.g.
baseline of blood pressure, standard deviation (SD), standard error (SE),
95 % condence intervals (CIs) and interquartile (IQR)). Disagreements
in the inclusion or exclusion of any study were resolved by group dis-
cussion. For example, one study did not clearly mention term “placebo”
Fig. 1. The process of study selection.
Z. Mosallanezhad et al.
Complementary Therapies in Medicine 59 (2021) 102692
3
Table 1
Characteristics of the included RCTs.
Study Country Type of study Population Age
group
(C vs.
I)
Body
weight
(C vs. I)
BMI (C
vs. I)
Intervention
type
Sample
size
Duration
(weeks)
Baseline
SBP
(mmHg)
Baseline
DBP
(mmHg)
Teede
(2001)
Australia Randomized,
double-blind,
placebo-
controlled trial
Men and
Postmenopausal
Women
60 vs.
61
74 vs.
72
26 vs.
25
Soy protein 179 12 130 76
Sagara
(2004)
Scotland Randomized,
double-blind,
placebo-
controlled trial
Hypercholesterolemic
and / or hypertensive
52.2
vs.
52.2
83.8 vs.
85.1
27.2
vs.
27.6
Soy protein 50 5 142 87.1
He (2005) China Randomized,
double-blind,
controlled
trial.
Healthy 51.4
vs.
50.8
70.6 vs.
70
26.8
vs.
26.9
Soybean
protein
276 12 134.7 84.7
Kim (2005) Korea Randomized,
double-blind,
placebo-
controlled trial
T2DM 61.7
vs.
59.9
61.1 vs.
64.1
23.8
vs.
24.4
Soybean 30 13 137.5 86.6
Hermansen
(2005)
Denmark Randomized,
double-blind,
placebo-
controlled trial
Hypercholesterolemic 58 vs.
60.6
75.3 vs.
77.1
25.6
vs.
26.4
Soy protein 100 24 133 80.2
Aubertin-
Leheudre
(2008)
Canada Randomized,
double-blind,
placebo-
controlled trial
Obese Postmenopausal
Women
57.7
vs.
57.1
82.5 vs.
79.6
32.8
vs.
31.2
Soy
isoavone
39 25 125.1 79
Chan (2008) China Randomized,
double-blind,
placebo-
controlled trial
Ischaemic stroke 65.8
vs.
66.8
NR* 25 vs.
26.2
Soy
isoflavone
102 12 141 77
Kwak
(2010)
Korea Randomized,
double-blind,
placebo-
controlled trial
Prediabetes and newly
diagnosed T2DM
57.6
vs.
56.8
65.8 vs.
62.6
24.8
vs.
24.1
Black soy
peptide
42 12 125.1 73.6
Wong
(2012)
Netherlands Randomized,
double-blind,
placebo-
controlled trial
Menopausal women
with high or normal
blood pressure
55.5
vs.
55.8
68.9 vs.
67.6
25.4
vs.
25.3
Soy
hypocotyl
isoflavones
24 6 140.1 82.8
Liu 1 (2013) China Randomized,
double-blind,
placebo-
controlled trial
Postmenopausal
women with mild
hyperglycemia
54.8
vs.
54.3
54.4
vs.56.1
22.6
vs.
23.6
Soy protein
and
isoavones
180 25 127.9 77
Liu 2 (2013) China Randomized,
double-blind,
placebo-
controlled trial
Postmenopausal
women with mild
hyperglycemia
54.8
vs.
56.3
54.4 vs.
56.8
22.6
vs.23.9
Soy
isoavones
180 25 125.9 78.2
Kim (2013) Korea Randomized,
double-blind,
placebo-
controlled trial
Postmenopausal
women
53.5
vs.
53.7
56.5 vs.
57.7
23.3
vs.
23.2
Soy
isoflavone
85 12 116.1 74.6
Squadrito
(2013)
Italy Randomized,
double-blind,
placebo-
controlled trial
Postmenopausal
women with metabolic
syndrome
55.4
vs.
55.6
NR 31.8
vs.
31.8
Soy
isoflavone
108 51 135.7 78.7
Cheng
(2013)
Taiwan Randomized,
double-blind,
placebo-
controlled trial
Healthy
postmenopausal
women
56.1
vs. 57
55.1 vs.
55.1
22.9
vs.
23.1
Soy
isoflavone
82 52 119 77.3
Husain
(2015)
Iran Randomized,
double-blind,
placebo-
controlled trial
Postmenopausal
women
50.32
vs.
50.93
NR NR Soy 61 8 125.77 81.77
Liu 1 (2015) China Randomized,
double-blind,
placebo-
controlled trial
Postmenopausal
women with
prehypertension
58.5
vs.
57.6
57.6 vs.
56.5
NR Soy 180 24 130.7 81.6
Liu 2 (2015) China Randomized,
double-blind,
placebo-
controlled trial
Postmenopausal
women with
prehypertension
58.5
vs.
57.7
57.6 vs.
56.5
NR Soy
isoflavone
180 24 131.9 81.6
C (control group); I (intervention group); BMI (body mass index); T2DM (type 2 diabetes mellitus), NR (not reported).
Z. Mosallanezhad et al.
Complementary Therapies in Medicine 59 (2021) 102692
4
as the control,
21
however, the study-design was comparable to a
placebo-controlled design. Following discussion with clinical and sta-
tistical experts, this study was included. In addition, studies were
excluded if the control group was not clinically comparable with the
intervention, and therefore inclusion would have biased the results.
Trials that prescribed effective nutrients, diet, medicines, or other
combinations concomitant to soy, in comparison with controls were also
excluded.
2.3. Data extraction
After identifying studies for inclusion, a combination of four authors
extracted clinical and statistical data, including: rst authors last name,
corresponding author’s e-mail, publication year, country, population,
participants’ characteristics, intervention and control type, dose and
type of supplement, treatment duration, sample size, methodological
quality, mean change of interested outcome from baseline at the end of
trial, related SD, SE, 95 % CI or IQR. Where required appropriate
transformations were undertaken to calculate the SD from studies
reporting: SE (SD =SE ×√n), 95 % CI (SD =√n ×(upper limit −lower
limit)
∕
3.92) or IQR (SD =IQR / 1.35).
25
In addition, WebPlotDigitizer
(https://automeris.io/WebPlotDigitizer) was used to derive the mean
change and the corresponding SD when the data were plotted, but not
reported. In the case of an article with two different intervention groups
and one control group, the intervention groups were considered as
different studies, and to avoid giving more weight to them; number of
participants in the control group was divided by 2.
2.4. Quality appraisal
Two authors independently assessed quality in the included studies
using the Cochrane Collaboration risk of bias assessment tool,
26
which is
scored across seven domains being: random sequence generation (se-
lection bias), allocation concealment (selection bias), blinding of par-
ticipants and personnel (performance bias), blinding of outcome
assessment (detection bias), incomplete outcome data (attrition bias),
selective reporting (reporting bias), and other sources of bias. Each
included study also received an overall grading of Good (>2 low risk
domains), Fair (=2 low risk domains), or Poor (<2 low risk domains).
2.5. Statistical analysis
Weighted mean difference (WMD) and 95 % CI was calculated in
Stata v.13, applying a random-effects method. Inter-study heterogeneity
was evaluated by checking I
2
index (low: <50%, hight: >50%).
27
Sub-
group analyses were planned by effective clinical covariates i.e. age (>
56, <56 years old), baseline blood pressure (SBP: >130, <130 mmHg;
DBP: >80, <80 mmHg), and intervention duration (<16, >16 weeks).
Table 2
The methodological quality of included RCTs on effect of soy intake on blood pressure based on review authors’ judgments about each risk of bias item for each
included study.
Z. Mosallanezhad et al.
Complementary Therapies in Medicine 59 (2021) 102692
5
Fig. 2. Forest plot detailing WMDs and 95 % CIs for the meta-analyses of SBP (A) and DBP (B).
Z. Mosallanezhad et al.
Complementary Therapies in Medicine 59 (2021) 102692
6
Mean changes and their SDs of relevant outcomes were obtained by
using the following equations: [mean-post – mean-baseline] and [(√
([(SD pre)
2
+(SD post)
2
] – [2 r ×SD pre ×SD post]))],
28,49,50
respec-
tively. In addition, a sensitivity analysis was applied by discarding each
trial in turn, to ensure robustness of results. A Begg’s rank-correlation
29
and Egger’s regression asymmetry
30
were performed to evaluate po-
tential publication bias. P-values of less than 0.05 represented statistical
signicance.
3. Results
3.1. Results of the search and study characteristics
From 3163 records, 15 RCTs with 17 effect sizes were identied for
inclusion, all of which were able to be included in the meta-analysis
(Fig. 1). These studies were published between 2001 and 2015. Ten
were conducted in Asia,
17,19,20,21,22,31,32,33,34,35
four in Europe,
18,23,36,37
and another one in the United States of America.
38
Participant age
ranged from 50.32–66.8 years. Intervention durations were less than 16
weeks
17,18,20,21,22,23,31,32,33
or more than 16 weeks
19,34,35,36,37,38
in
nine and six trials, respectively (Table 1).
Baseline blood pressure across studies was reported as SBP <130
mmHg
17,20,33,34,35,38
and >130 mmHg
18,19,21,22,23,31,32,36,37
in six and
nine RCTs, respectively. In addition, enrolled participants of seven and
eight studies had >80 mmHg
18,19,20,21,23,32,36
and <80 mmHg
17,22,31,33,34,35,37
DBP, respectively.
3.2. Quality assessment for included studies
Results of the quality assessment are shown in Table 2. Overall, study
quality was assessed as good, with a low risk of bias the dominant
classication across all domains. All studies were assessed as having low
risk of bias for sequence generation and blinding of participants. Six
studies were assessed as having unclear risk of bias for allocation
concealment, ve had unclear risk for blinding of outcome assessment,
one had unclear risk for selective reporting and three had unclear risk for
other potential sources of bias. Two studies were assessed as having high
risk of bias for incomplete outcome data, with three assessed as unclear
and the remaining 10 studies as low risk.
3.3. Meta-analysis of blood pressure outcomes
A signicant reduction in both SBP (WMD = − 1.70 mmHg, 95 % CI
=[−3.34, −0.06], P =0.04, I
2
=45.4 %) and DBP (WMD = − 1.27
Fig. 3. Findings from subgroup analysis based on age (<56, >56 years old) (A), baseline blood pressure (<130, >130 mmHg) (B), duration (<16, >16 weeks) (C)
and region (Asia, Europe, America) (D) regarding the effect of soy consumption on SBP.
Z. Mosallanezhad et al.
Complementary Therapies in Medicine 59 (2021) 102692
7
mmHg, 95 % CI =[−2.36, -0.19], P =0.02, I
2
=43.9 %) were observed
in the soy intake group when compared with controls (Fig. 2).
Subgroup analyses, identied a greater reduction in blood pressure
for participants aged younger than 56 years (Fig. 3, A and Fig. 4, A) and
lower baseline diastolic blood pressure (Fig. 4, B). In addition, both
systolic (Fig. 3, C) and diastolic (Fig. 4, C) blood pressure were signi-
cantly reduced when soy intake duration was <16 weeks.
3.4. Publication bias and sensitivity analysis
Egger’s regression and Begg’s rank-correlation tests indicated that
there was no signicant publication bias for SBP (P for Egger’s test =
0.71 and Begg’s test =0.99) (Fig. 5, A) or DBP (P for Egger’s test =0.94
and Begg’s test =0.51) (Fig. 5, C). According to the ndings from
sensitivity analysis, pooled eff ;ect sizes obtained for the effect of soy
intake on SBP (Fig. 5, B) and DBP (Fig. 5, D) were not sensitive to any
particular study or group of studies.
4. Discussion
Data from 17 effect sizes were available to examine efcacy of soy
consumption on blood pressure in adults. Our results showed that soy
consumption signicantly improves SBP and DBP. Subgroup analyses
identied a greater reduction in blood pressure among younger partic-
ipants with lower baseline diastolic blood pressure, and in trials lasting
for <16 weeks duration.
The effect of soy consumption on blood pressure has been previously
assessed in several RCTs. A study by Washburn et al. indicated that 40 g
of soy protein containing 68 mg of phytoestrogens, improved blood
pressure abnormality.
39
In Teede et al., it was demonstrated that
administration of 40 g of soy protein containing 118 mg of isoavones,
improved blood pressure in healthy men and women.
31
Furthermore,
Welty et al. showed that a soy nut diet (containing 25 g of soy protein
and 101 mg of aglycone isoavones) lowered systolic blood pressure in
hypertensive and normotensive patients
40
; whilst, Rivas et al. reported
that a 3-month intervention with soymilk reduced blood pressure in men
and women with mild-to-moderate hypertension, and that this hypo-
tensive effect was related to urinary excretion of the isoavonoid gen-
istein.
41
Indeed, it has been shown that the BP-lowering effect of soy
might be related to isoavones,
42
the suspected active ingredients in
soy, via the activation of endothelial nitric oxide (NO) synthase (eNOS)
and stimulation of NO production. Genistein is one of the soy isoavones
that can result in activation of eNOS and NO synthesis.
43
This is
conrmed in another study where it was demonstrated that higher soy
Fig. 4. Findings from subgroup analysis based on age (<56, >56 years old) (A), baseline blood pressure (<130, >130 mmHg) (B), duration (<16, >16 weeks) (C)
and region (Asia, Europe, America) (D) regarding the effect of soy consumption on DBP.
Z. Mosallanezhad et al.
Complementary Therapies in Medicine 59 (2021) 102692
8
consumption is related to higher plasma concentrations of NO.
44
It has been shown that oxidative stress and inammation play a
potential role in the development of hypertension
45
; thereby suggesting
that soy isoavones might lower BP through antioxidant and
anti-inammatory effects.
46,47
In line with the meta-analysis by Liu
et al.,
48
it is unsurprising that we did not observe an inverse relationship
of soy consumption with BP among older people, largely due to the
adverse structural changes in the vessel wall among this group.
5
It is
known that BP increases with enhancing arterial stiffness, concomitant
to aging, and the consumption of phytoestrogens have been inversely
related to arterial stiffness.
5
Moreover, soy consumption also reduces BP
through its natriuretic effect, which is similar to furosemide.
13
In the present study, we found that soy intake led to a higher
reduction in blood pressure in participants with lower baseline systolic
and diastolic BP, which is in contrast with result of the meta-analysis
conducted by Liu et al
48
One reason that should be noted for this
inconstancy is the difference in inclusion criteria regarding study design,
inter-study heterogeneity, and risk of bias, which was lower across our
pooled included studies.
4.1. Strengths and limitations
The present meta-analysis is the rst comprehensive study to have
assessed the inuence of soy intake on BP from randomized double-blind
placebo-controlled trials. We used a comprehensive and accurate sys-
tematic search strategy, that allowed us to examine both indexed and
non-indexed trials. To reduce between-study heterogeneity and
potential bias, and also enhance the power of results, we only included
studies in which the control group received a placebo and where a
double-blind design was employed. This approach improved quality of
pooled analyses and subsequently permitting more rigorous insights in
the effect of soy intake on BP. In addition, based on risk of bias assess-
ment using Cochrane methodology, the quality of all studies was
assessed overall as low risk. Subgroup analysis according to covariates
that have clinical importance regarding soy intake and blood pressure
improvements were pre-specied and provided additional insights to
inform subsequent recommendations. It should be noted that there was
no signicant publication bias found, whilst pooled results were not
sensitive to any individual study. Also, low amount of inter-study het-
erogeneity empowered the results. However, despite the clear novelty of
this work, our study has some limitations that should be noted. First, as
some included trials only reported dose of isoavones, whilst others only
reported soy, we were not able to apply a dose-response analysis. Sec-
ond, we could not conduct subgroup analysis for baseline BMI and body
weight of participants, which could be clinically important markers
related to the change of BP, because of their absence in some included
trials. Moreover, due to a variety of diseases among included study
participants and lack of essential clinical data about their metabolic
markers, we were not able to conduct additional subgroup analysis
based on type of diseases and different health conditions without
reducing the power of the analysis. Finally, although we contacted some
corresponding authors to request missing essential data, in most cases,
we received no response, or unsatisfactory responses.
Fig. 5. The funnel plot and the result of sensitivity analysis for SBP (A, B) and DBP (C, D).
Z. Mosallanezhad et al.
Complementary Therapies in Medicine 59 (2021) 102692
9
4.2. Conclusion
In the present study, pooled effect sizes from 17 studies revealed a
signicant improvement in SBP and DBP in adults following soy con-
sumption, in comparison with controls. In addition, subgroup analysis
indicated a further reduction in both SBP and DBP in younger partici-
pants with lower baseline DBP and intervention durations <16 weeks.
Thus, increases to soy consumption could be considered as an alterna-
tive or complementary approach to improving BP outcomes among
adults, and particularly among younger adults.
Authors contribution
All named authors meet the International Committee of Medical
Journal Editors (ICMJE) criteria for authorship for this article, take re-
sponsibility for the integrity of the work as a whole, and have given their
approval for this version to be published.
Funding
None.
Ethics approval and consent to participate
Not applicable.
Declaration of Competing Interest
The authors report no declarations of interest.
Acknowledgements
We thank Morteza Zare (https://www.researchgate.net/prole/Mor
teza_Zare), the expert statistician and head of Meta-Research Innovation
ofce (METRIO), Shiraz University of Medical Sciences, Iran.
Appendix A. Supplementary data
Supplementary material related to this article can be found, in the
online version, at doi:https://doi.org/10.1016/j.ctim.2021.102692.
References
1 Zeng J, Feng Y, Feng J, et al. The effect of soy intervention on insulin-like growth
factor 1 levels: a meta-analysis of clinical trials. Phytother Res. 2020;34(July(7)):
1570–1577. https://doi.org/10.1002/ptr.6630. PubMed PMID: 32072706.
2 Balla F. Nutritional value and economic aspects of fortication of foods of plant
origin with soy protein. J Am Oil Chem Soc. 1974;51(January(1)):156A–158A.
https://doi.org/10.1007/BF02542121. PubMed PMID: 4856014.
3Endres JG. Soy protein products: Characteristics, nutritional aspects, and utilization. The
American Oil Chemists Society; 2001.
4Sugano M. Soy in health and disease prevention. CRC Press; 2005.
5 Man B, Cui C, Zhang X, et al. The effect of soy isoavones on arterial stiffness: a
systematic review and meta-analysis of randomized controlled trials. Eur J Nutr.
2020;11(June):1–12. https://doi.org/10.1007/s00394-020-02300-6. PubMed PMID:
32529287.
6 Schwingshackl L, Chaimani A, Schwedhelm C, et al. Comparative effects of different
dietary approaches on blood pressure in hypertensive and pre-hypertensive patients:
a systematic review and network meta-analysis. Crit Rev Food Sci Nutr. 2019;59(16):
2674–2687. https://doi.org/10.1080/10408398.2018.1463967. PubMed PMID:
29718689.
7Miller 3rd ER, Erlinger TP, Young DR, et al. Results of the Diet, E xercise, and W eight
Loss I ntervention T rial (DEW-IT). Hypertension. 2002;40(5):612–618.
8 Schwingshackl L, Chaimani A, Hoffmann G, et al. Impact of different dietary
approaches on blood pressure in hypertensive and prehypertensive patients: protocol
for a systematic review and network meta-analysis. BMJ Open. 2017;7(April (4)):
e014736. https://doi.org/10.1136/bmjopen-2016-014736. PubMed PMID:
28446526; PubMed Central PMCID: PMCPMC5566592.
9Moore TJ, Conlin PR, Ard J, et al. DASH (Dietary Approaches to stop Hypertension)
diet is effective treatment for stage 1 isolated systolic hypertension. Hypertension.
2001;38(2):155–158.
10 Zhao L, Stamler J, Yan LL, et al. Blood pressure differences between northern and
southern Chinese: role of dietary factors: the International Study on Macronutrients
and Blood Pressure. Hypertension. 2004;43(6):1332–1337.
11 Miller 3rd ER, Erlinger TP, Appel LJ. The effects of macronutrients on blood pressure
and lipids: an overview of the DASH and OmniHeart trials. Curr Atheroscler Rep.
2006;8(November(6)):460–465. https://doi.org/10.1007/s11883-006-0020-1.
PubMed PMID: 17045071.
12 Katherine L, Ziegler TR. Modern nutrition in health and disease. 2012.
13 Yang G, Shu X-O, Jin F, et al. Longitudinal study of soy food intake and blood
pressure among middle-aged and elderly Chinese women. Am J Clin Nutr. 2005;81
(5):1012–1017.
14 Nagata C, Shimizu H, Takami R, et al. Association of blood pressure with intake of
soy products and other food groups in Japanese men and women. Prev Med. 2003;36
(June(6)):692–697. https://doi.org/10.1016/s0091-7435(03)00052-5. PubMed
PMID: 12744912.
15 Maleki Z, Jazayeri S, Eslami O, et al. Effect of soy milk consumption on glycemic
status, blood pressure, brinogen and malondialdehyde in patients with non-
alcoholic fatty liver disease: a randomized controlled trial. Complement Ther Med.
2019;44(June):44–50. https://doi.org/10.1016/j.ctim.2019.02.020. PubMed PMID:
31126574; eng.
16 Sedaghat A, Shahbazian H, Rezazadeh A, et al. The effect of soy nut on serum total
antioxidant, endothelial function and cardiovascular risk factors in patients with type
2 diabetes. Diabetes Metab Syndr. 2019;13(Mar-Apr(2)):1387–1391. https://doi.org/
10.1016/j.dsx.2019.01.057. PubMed PMID: 31336497; eng.
17 Kim J, Lee H, Lee O, et al. Isoavone supplementation inuenced levels of
triglyceride and luteunizing hormone in Korean postmenopausal women. Arch Pharm
Res. 2013;36(March(3)):306–313. https://doi.org/10.1007/s12272-013-0059-9.
PubMed PMID: 23475289; eng.
18 Wong WW, Taylor AA, Smith EO, et al. Effect of soy isoavone supplementation on
nitric oxide metabolism and blood pressure in menopausal women. Am J Clin Nutr.
2012;95(June(6)):1487–1494. https://doi.org/10.3945/ajcn.111.032045. PubMed
PMID: 22552034; PubMed Central PMCID: PMCPMC3349458. eng.
19 Liu ZM, Ho SC, Chen YM, et al. Effect of whole soy and puried daidzein on
ambulatory blood pressure and endothelial function–a 6-month double-blind,
randomized controlled trial among Chinese postmenopausal women with
prehypertension. Eur J Clin Nutr. 2015;69(October(10)):1161–1168. https://doi.org/
10.1038/ejcn.2015.24. PubMed PMID: 25782428; eng.
20 Husain D, Khanna K, Puri S, et al. Supplementation of soy isoavones improved sex
hormones, blood pressure, and postmenopausal symptoms. J Am Coll Nutr. 2015;34
(1):42–48. https://doi.org/10.1080/07315724.2013.875434. PubMed PMID:
25648211; eng.
21 He J, Gu D, Wu X, et al. Effect of soybean protein on blood pressure: a randomized,
controlled trial. Ann Intern Med. 2005;143(July (1)):1–9. https://doi.org/10.7326/
0003-4819-143-1-200507050-00004. PubMed PMID: 15998749; eng.
22 Chan YH, Lau KK, Yiu KH, et al. Reduction of C-reactive protein with isoavone
supplement reverses endothelial dysfunction in patients with ischaemic stroke. Eur
Heart J. 2008;29(November(22)):2800–2807. https://doi.org/10.1093/eurheartj/
ehn409. PubMed PMID: 18812325.
23 Sagara M, Kanda T, M NJ, et al. Effects of dietary intake of soy protein and
isoavones on cardiovascular disease risk factors in high risk, middle-aged men in
Scotland. J Am Coll Nutr. 2004;23(February(1)):85–91. https://doi.org/10.1080/
07315724.2004.10719347. PubMed PMID: 14963058; eng.
24 Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews
and meta-analyses: the PRISMA statement. PLoS Med. 2009;151(4):264–269.
25 Follmann D, Elliott P, Suh I, et al. Variance imputation for overviews of clinical trials
with continuous response. J Clin Epidemiol. 1992;45(July(7)):769–773. https://doi.
org/10.1016/0895-4356(92)90054-q. PubMed PMID: 1619456.
26 Higgins JP, Altman DG, Gøtzsche PC, et al. The cochrane collaboration’s tool for
assessing risk of bias in randomised trials. 343. 2011, d5928.
27 Higgins J, Thomas J, Chandler J, et al. Cochrane handbook for systematic reviews of
interventions version 6.0 (updated July 2019). Cochrane. 2019.
28 Borenstein M, Hedges LV, Higgins JP, et al. Introduction to meta-analysis. John Wiley
& Sons; 2011.
29 Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for
publication bias. Biometrics. 1994;50(December(4)):1088–1101. PubMed PMID:
7786990.
30 Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a
simple, graphical test. BMJ. 1997;315(September (7109)):629–634. https://doi.org/
10.1136/bmj.315.7109.629. PubMed PMID: 9310563; PubMed Central PMCID:
PMCPMC2127453.
31 Teede HJ, Dalais FS, Kotsopoulos D, et al. Dietary soy has both benecial and
potentially adverse cardiovascular effects: a placebo-controlled study in men and
postmenopausal women. J Clin Endocrinol Metab. 2001;86(July(7)):3053–3060.
https://doi.org/10.1210/jcem.86.7.7645. PubMed PMID: 11443167; eng.
32 Kim JI, Kim JC, Kang MJ, et al. Effects of pinitol isolated from soybeans on glycaemic
control and cardiovascular risk factors in Korean patients with type II diabetes
mellitus: a randomized controlled study. Eur J Clin Nutr. 2005;59(March(3)):
456–458. https://doi.org/10.1038/sj.ejcn.1602081. PubMed PMID: 15536472; eng.
33 Kwak JH, Lee JH, Ahn CW, et al. Black soy peptide supplementation improves
glucose control in subjects with prediabetes and newly diagnosed type 2 diabetes
mellitus. J Med Food. 2010;13(December(6)):1307–1312. https://doi.org/10.1089/
jmf.2010.1075. PubMed PMID: 21091245.
34 Liu ZM, Ho SC, Chen YM, et al. Effect of soy protein and isoavones on blood
pressure and endothelial cytokines: a 6-month randomized controlled trial among
postmenopausal women. J Hypertens. 2013;31(February(2)):384–392. https://doi.
org/10.1097/HJH.0b013e32835c0905. PubMed PMID: 23203140; eng.
Z. Mosallanezhad et al.
Complementary Therapies in Medicine 59 (2021) 102692
10
35 Cheng WC, Lo SC, Tsai KS, et al. Effects of high-dose phytoestrogens on circulating
cellular microparticles and coagulation function in postmenopausal women. J Formos
Med Assoc. 2015;114(August(8)):710–716. https://doi.org/10.1016/j.
jfma.2013.11.001. PubMed PMID: 24360978; eng.
36 Hermansen K, Hansen B, Jacobsen R, et al. Effects of soy supplementation on blood
lipids and arterial function in hypercholesterolaemic subjects. Eur J Clin Nutr. 2005;
59(July(7)):843–850. https://doi.org/10.1038/sj.ejcn.1602151. PubMed PMID:
15900307; eng.
37 Squadrito F, Marini H, Bitto A, et al. Genistein in the metabolic syndrome: results of a
randomized clinical trial. J Clin Endocrinol Metab. 2013;98(Augu (8)):3366–3374.
https://doi.org/10.1210/jc.2013-1180. PubMed PMID: 23824420.
38 Aubertin-Leheudre M, Lord C, Khalil A, et al. Isoavones and clinical cardiovascular
risk factors in obese postmenopausal women: a randomized double-blind placebo-
controlled trial. J Womens Health (Larchmt). 2008;17(October(8)):1363–1369.
https://doi.org/10.1089/jwh.2008.0836. PubMed PMID: 18788990.
39 Washburn S, Burke GL, Morgan T, et al. Effect of soy protein supplementation on
serum lipoproteins, blood pressure, and menopausal symptoms in perimenopausal
women. Menopause. 1999;6(1):7–13. Spring PubMed PMID: 10100174.
40 Welty FK, Lee KS, Lew NS, et al. Effect of soy nuts on blood pressure and lipid levels
in hypertensive, prehypertensive, and normotensive postmenopausal women. Arch
Intern Med. 2007;167(May(10)):1060–1067. https://doi.org/10.1001/
archinte.167.10.1060. PubMed PMID: 17533209.
41 Rivas M, Garay RP, Escanero JF, et al. Soy milk lowers blood pressure in men and
women with mild to moderate essential hypertension. J Nutr. 2002;132(July(7)):
1900–1902. https://doi.org/10.1093/jn/132.7.1900. PubMed PMID: 12097666;
eng.
42 Zarei A, Stasi C, Mahmoodi M, et al. Effect of soy consumption on liver enzymes,
lipid prole, anthropometry indices, and oxidative stress in patients with non-
alcoholic fatty liver disease: a systematic review and meta-analysis of clinical trials
%. J Iranian J Basic Med Sci. 2020;23(10):1245–1250. https://doi.org/10.22038/
ijbms.2020.46854.10797.
43 Richardson SI, Steffen LM, Swett K, et al. Dietary total isoavone intake is associated
with lower systolic blood pressure: The Coronary Artery Risk Development in Young
Adults (CARDIA) study. J Clin Hypertens. 2016;18(8):778–783.
44 Hallund J, Bugel S, Tholstrup T, et al. Soya isoavone-enriched cereal bars affect
markers of endothelial function in postmenopausal women. Br J Nutr. 2006;95(June
(6)):1120–1126. https://doi.org/10.1079/bjn20061734. PubMed PMID: 16768834.
45 Jalali M, Karamizadeh M, Ferns GA, et al. The effects of cashew nut intake on lipid
prole and blood pressure: a systematic review and meta-analysis of randomized
controlled trials. Complement Ther Med. 2020;50(May):102387. https://doi.org/
10.1016/j.ctim.2020.102387. PubMed PMID: 32444052.
46 Panneerselvam S, Packirisamy R, Bobby Z, et al. Protective effect of soy isoavones
(from Glycine max) on adipose tissue oxidative stress and inammatory response in
an experimental model of post-menopausal obesity: the molecular mechanisms.
Biochem Anal Biochem. 2016;5(266), 2161-1009.1000266.
47 Yoon GA, Park S. Antioxidant action of soy isoavones on oxidative stress and
antioxidant enzyme activities in exercised rats. Nutr Res Pract. 2014;8(December(6)):
618–624. https://doi.org/10.4162/nrp.2014.8.6.618. PubMed PMID: 25489400;
PubMed Central PMCID: PMCPMC4252520.
48 Liu XX, Li SH, Chen JZ, et al. Effect of soy isoavones on blood pressure: a meta-
analysis of randomized controlled trials. Nutr Metab Cardiovasc Dis. 2012;22(June
(6)):463–470. https://doi.org/10.1016/j.numecd.2010.09.006. PubMed PMID:
21310599.
49 Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. Introduction to meta-analysis.
John Wiley & Sons; 2011.
50 Follmann D, Elliott P, Suh IL, Cutler J. Variance imputation for overviews of clinical
trials with continuous response. J clin epidemiol. 1992;45(7):769–773.
Z. Mosallanezhad et al.