Journal of Human Nutrition and Dietetics

RESEARCH PAPER
The effect of dietary soy intake on weight loss, glycaemic
control, lipid profiles and biomarkers of inflammation and
oxidative stress in women with polycystic ovary syndrome:
a randomised clinical trial
M. Karamali,1 M. Kashanian,1 S. Alaeinasab2 & Z. Asemi3
1
Department of Gynecology and Obstetrics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
2
Imam Sajad Hospital, Shahriyar, Tehran, Iran
3
Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran

Keywords
soy diet, weight loss, metabolic status, polycystic
ovary syndrome.
Correspondence
Z. Asemi, Research Center for Biochemistry and
Nutrition in Metabolic Diseases, Kashan University
of Medical Sciences, Kashan, Iran.
Tel.: +98 31 55463378
Fax: +98 31 55463377
E-mail: asemi_r@yahoo.com
How to cite this article
Karamali M., Kashanian M., Alaeinasab S., Asemi
Z. (2018). The effect of dietary soy intake on
weight loss, glycaemic control, lipid profiles and
biomarkers of inflammation and oxidative stress
in women with polycystic ovary syndrome: a
randomised clinical trial. J Hum Nutr Diet.
https://doi.org/10.1111/jhn.12545
Clinical trial registration number http://www.
irct.ir: IRCT201701295623N104.
Abstract
Background: The present study aimed to evaluate the effects of dietary soy
intake on weight loss and metabolic status of patients with polycystic ovary
syndrome (PCOS).
Methods: A randomised clinical trial was conducted among 60 women with
PCOS. Participants were randomly assigned into two groups to receive
either a test diet (n = 30) or a control diet (n = 30) for 8 weeks. Partici-
pants in the test group consumed a diet containing 0.8 g protein kg–1 body
weight (35% animal proteins, 35% soy protein and 30% vegetable proteins)
and participants in the control group consumed a similar diet containing
70% animal proteins and 30% vegetable proteins.
Results: Adherence to the test diet, compared with the control diet, resulted
in significant decreases [mean (SD)] in body mass index (BMI) [ 0.3 (0.6)
versus +0.1 (0.5) kg m–2, P = 0.02], fasting plasma glucose [ 0.2 (0.5) ver-
sus +0.1 (0.3) mmol L 1, P = 0.01], total testosterone [ 0.3 (0.7) versus
+0.3 (0.3) mmol L 1, P < 0.001], insulin [ 15.0 (18.0) versus +4.8
(18.6) pmol L 1, P < 0.001] and insulin resistance [ 0.6 (0.6) versus
+0.2 (0.7), P < 0.001], as well as a significant increase in quantitative insulin
sensitivity check index [+0.01 (0.01) versus 0.002 (0.02), P = 0.01]. In
addition, significant decreases in triglycerides [ 0.1 (0.4) versus
+0.2 (0.3) mmol L 1, P = 0.01] and malondialdehyde (MDA) [ 1.2 (1.0)
versus +0.2 (1.2) lmol L 1, P < 0.001] and significant increases in nitric
oxide (NO) [+13.6 (14.1) versus +0.9 (24.3) lmol L 1, P = 0.01] and glu-
tathione (GSH) [+170.1 (175.5) versus +24.2 (168.7) lmol L 1, P = 0.002]
were seen in the test group compared to the control.
Conclusions: Adherence to test diet among subjects with PCOS significantly
decreased BMI, glycaemic control, total testosterone, triglycerides and MDA,
and significantly increased NO and GSH compared to the control diet.

reproductive-aged women, depending on the diagnostic

Introduction
Polycystic ovary syndrome (PCOS) is a prevalent hetero-
geneous disorder associated with disturbances of repro-
ductive, endocrine and metabolic function (1). The
prevalence of PCOS was reported as 6–25% for
criteria used (2). The prevalence of being overweight and
obese and that of insulin resistance in PCOS patients was
reported as 61% (3) and 44–70% (4), respectively. Insulin
resistance appears to be central to the pathogenesis of
hyperandrogenism in women with PCOS and contributes

ª 2018 The British Dietetic Association Ltd. 1

 Soy diet and polycystic ovary syndrome
to dyslipidaemia and endothelial dysfunction (5).
Increased inflammatory cytokines such as C-reactive pro-
tein (CRP) are associated with the incidence of cardiovas-
cular disease and metabolic syndrome, as well as type 2
diabetes mellitus (T2DM) in women with PCOS (6).
Weight loss and lifestyle changes, including increased
physical activity, are the first-line treatment in the man-
agement of PCOS (7). In addition, previous studies have
reported that a healthy dietary pattern may be associated
with the metabolic profiles and inflammatory cytokines in
diseases related to metabolic syndrome (8,9). Earlier, it was
reported that not only the quantity, but also the type of
protein has important implications in patients with meta-
bolic diseases (10). The ingestion of vegetable proteins in
place of animal proteins appears to be correlated with a
lower risk of coronary heart disease as a result of
decreased cholesterol concentrations (11,12). One specific
type of dietary protein that has received increased atten-
tion in recent years is soy protein. In a study by Sathya-
palan et al.(13), it was observed that the consumption of
50 g day 1 of soy protein for 12 weeks in men with
T2DM and subclinical hypogonadism decreased glycaemic
control, triglycerides and CRP levels. We have previously
shown that soy isoflavone intake (50 mg day 1) for
12 weeks in subjects with PCOS significantly decreased
insulin resistance, triglycerides and malondialdehyde
(MDA), and also significantly increased total glutathione
(GSH) levels, although it did not affect weight, body mass
index (BMI), other lipid profiles and inflammatory fac-
tors (14). In addition, another study showed that adher-
ence to the soy protein for 4 years significantly decreased
lipid profiles and inflammatory markers among patients
with diabetic nephropathy (DN) (15). A previous meta-
analysis demonstrated that soy isoflavones significantly
decreased total- and low-density lipoprotein (LDL)-cho-
lesterol, but did not affect high-density lipoprotein
(HDL)-cholesterol levels (16). However, a 24-week soy-
based supplementation was reported not to affect lipid
profiles and insulin sensitivity in hypercholesterolaemic
participants (17).
The effects of a soy diet on metabolic profiles may be a
result of activating peroxisome proliferator-activated
receptors and nuclear receptors that participate in cellular
lipid homeostasis and the action of insulin (18), the inhi-
bition of intestinal glucose absorption (19) and the
increase in the abundance of hepatic messenger RNA for
cholesterol 7a-hydroxylase (20). These mechanisms might
suggest the importance of soy intake in subjects with
PCOS. However, whether soy intake has direct benefits
on weight loss, glucose metabolism, lipid profiles,
biomarkers of inflammation and oxidative stress in sub-
jects with PCOS has not been assessed to date. The pre-
sent study aimed to assess the effects of a test diet
2 ª 2018 The British Dietetic Association Ltd.
M. Karamali et al.
containing soy on weight loss and metabolic status in
these subjects.
Materials and methods
Trial design
The present study comprised a parallel randomised con-
trolled clinical trial.
Participants
The present study was carried out among 60 patients aged
18–40 years old with PCOS who were referred to the
Research and Clinical Center for Infertility at the Akbara-
badi clinic affiliated to Iran University of Medical
Sciences (IUMS), Tehran, Iran, from January 2017 to
March 2017. The diagnosis of PCOS was made in accor-
dance with the Rotterdam criteria (21). All subjects attend-
ing the centre were first evaluated by the study
gynaecologist and, after the diagnosis of PCOS in all sub-
jects, they were instructed to complete a hirsutism or
modified Ferriman Gallwey (mF-G) scoring form vali-
dated for the Iranian population (22). We did not include
pregnant women and women who had hyperprolacti-
naemia, thyroid dysfunction, endocrine diseases including
diabetes or impaired glucose tolerance or gastrointestinal
problems, as well as women who took medications, such
as hormonal contraceptives, insulin sensitising agents,
anti-inflammatory or antidiabetic and lipid lowering
drugs, or any other medications that might affect repro-
ductive physiology during the 8-week intervention.
Ethics statements
The present study was conducted in accordance with the
Declaration of Helsinki and written informed consent was
obtained from all participants prior to the intervention.
The research was approved by the Ethics Committee of
IUMS and was registered in the Iranian website for regis-
tration of clinical trials (http://www.irct.ir:
IRCT201701295623N104).
Study design
At baseline, subjects were matched according to BMI
(<25 and ≥25 kg m–2), age (<30 and ≥30 years), and phe-
notypes A (14 subjects in each group) and D (16 subjects
in each group) of PCOS. Then, participants were ran-
domly assigned into two groups to receive either a test
diet (n = 30) or a control diet (n = 30) for 8 weeks. As a
result of a lack of evidence regarding the appropriate val-
ues of soy intake for women with PCOS, we used the
above-mentioned values based on a previous study in
 M. Karamali et al.
among patients with DN (15). All subjects were taking
metformin tablet at the initial dose of 500 mg, which was
increased in a stepwise manner during the first 3 weeks
to a total of 1500 mg day 1 (23). Participants were
requested not to change their routine physical activity
and not to take any nutritional supplements during the
8-week treatment. All subjects completed the 3-day food
records and three physical activity records at baseline, as
well as at weeks 2 and 5 and the end-of-the trial. Daily
macro- and micronutrient intakes were analysed using NU-
TRITIONIST IV (First Databank, San Bruno, CA, USA). Phys-
ical activity was described as metabolic equivalents
(METs) in hours per day (24).
Intervention
Participants in the test group consumed a diet containing
0.8 g protein kg 1 body weight (35% animal proteins,
35% textured soy protein and 30% vegetable proteins)
and participants in the control group consumed a similar
diet containing 70% animal proteins including meats,
poultry, fish and dairy, and 30% vegetable proteins
including grains and vegetables. Both diets were equicalo-
ric. Participants in the test group received textured soy
protein (Sobhan, Behshahr, Iran). In addition, all partici-
pants received education regarding the preparation of
their meals with soy protein. Based on our analysis, the
nutrient composition (per 30 g) of soy protein consumed
by the study participants comprised: protein (15.6 g), fat
(0.3 g), fibre (1.4 g), total phyto-oestrogen (75 mg), mag-
nesium (89 mg), calcium (85 mg) and potassium (1 mg).
The protein content of soy was 52% of the dry weight.
The soy protein used in the present study was a commer-
cially available product.
Treatment adherence
Compliance with the consumption of the diets was moni-
tored once a week via telephone interviews. The compli-
ance was also double-checked by the use of 3-day dietary
records completed throughout the study.
Assessment of anthropometric measures
The weight and height of subjects were each determined in
a fasting status using a standard scale (Seca, Hamburg,
Germany) at baseline and after the 8-week intervention.
BMI was calculated as weight in kg divided by height in
metres squared. Waist circumference (WC) was assessed at
the minimum circumference between the iliac crest and the
last rib. Hip circumference (HC) was quantified at the
maximum protuberance of the buttocks. All anthropomet-
ric measures were conducted by a trained midwife.
ª 2018 The British Dietetic Association Ltd.
Soy diet and polycystic ovary syndrome
Assessment of outcomes
Markers of insulin metabolism [insulin levels, homeostasis
model of assessment-insulin resistance (HOMA-IR) and
quantitative insulin sensitivity check index (QUICKI)]
were considered as the primary outcome and lipid pro-
files, and biomarkers of inflammation and oxidative stress
were considered as the secondary outcomes.
Clinical assessments
Clinical assessments included determinations of hirsutism
using a mFG scoring system, of acne score (25) and of
alopecia based on assessment guidelines collated by Olsen
et al. (26). Acne was marked by a four-point scale: 0, no
acne; 1, minor acne on face; 2, moderate acne on face only;
and 3, severe acne, face and back or chest (25). The taking of
a medical history, focusing on symptoms of PCOS, specifi-
cally menstrual irregularities (21) and clinical hyperandro-
genism (21), was conducted by a trained midwife.
Biochemical assessment
Serum insulin values were quantified using an enzyme-
linked immunosorbent assay (ELISA) kit (DiaMetra,
Milano, Italy) with inter- and intra-assay coefficient vari-
ances (CVs) of 3.5–5.1%, respectively. The HOMA-IR
and QUICKI were determined in accordance with the
suggested formulas (27). HOMA-IR was calculated as
(fasting insulin in mU L 1) 9 (fasting plasma glucose
in mmol L 1)/22.5 (27). QUICKI was calculated as 1/(log
(fasting insulin lU mL 1) + log(fasting glucose
mg dL 1)) (27). Enzymatic kits (Pars Azmun, Tehran,
Iran) were applied to determine fasting plasma glucose
(FPG), serum triglycerides, very low-density lipoprotein
(VLDL)-, total-, LDL- and HDL-cholesterol concentra-
tions. Serum high sensitivity C-reactive protein (hs-CRP)
values were determined using a commercial ELISA kit
(LDN, Nordhorn, Germany) with inter- and intra-assay
CVs of 4.3–6.1%, respectively. Plasma nitric oxide (NO)
using the Griess method, total antioxidant capacity
(TAC) by the method of ferric reducing antioxidant
power developed by Benzie and Strain (28), GSH using
the method of Beutler et al. (29) and MDA levels using
the thiobarbituric acid reactive substances spectrophoto-
metric test (30) were all determined with inter- and intra-
assay CVs <5%. Commercial kits were used to determine
serum follicle-stimulating hormone (FSH) and luteinising
hormone (LH) levels (Pars Azmun, Tehran, Iran) with
inter- and intra-assay CVs <7%. Serum total testosterone
concentrations were determined using an Elisa kit
(Monobind, California, USA) with inter- and intra-assay
CVs <7%.
3
 Soy diet and polycystic ovary syndrome M. Karamali et al.

Sample size anthropometric measures as well as in macro- and

To estimate the sample size, we used a randomised clinical
trial sample size formula where type one (a) and type two
errors (b) were 0.05 and 0.20 (power = 80%), respectively.
Based on a previous study (14), we used an SD of 1.0 and a
difference in mean (d) of 0.8, considering HOMA-IR as
the primary outcome. The calculation indicated that 25
individuals were needed in each group. Assuming a drop-
out of five persons per group, the final sample size was
determined to be 30 individuals per group.
Randomisation
Randomisation assignment was conducted using com-
puter-generated random numbers. Randomisation and
allocation were carried out by a trained midwife and the
outcome was masked from the researcher and subjects
until the main analyses were completed.
Statistical analysis
The normality of the data was assessed using the
Shapiro–Wilk test. To detect differences in
micronutrient intakes between the two groups, we applied
independent-samples t-test. The Pearson chi-square test
was used to compare categorical variables. To determine
the effects of the test diet on glucose homeostasis, lipid
profiles, biomarkers of inflammation and oxidative stress,
we used a two-way repeated measures analysis of vari-
ance. In this analysis, the treatment (test versus control)
was regarded as the between-subject factor and time with
two time-points (baseline and week 8 of intervention)
was considered as the within-subject factor. Adjustment
for changes in baseline values of biochemical parameters,
age and baseline BMI was performed by analysis of
covariance. P < 0.05 was considered statistically signifi-
cant. All statistical analyses were conducted using SPSS,
version 18 (SPSS Inc., Chicago, Illinois, USA).
Results
In the present study, all 60 participants [test (n = 30) and
control diets (n = 30)] completed the trial (Fig. 1). No
side effects were reported following the consumption of
the test diet in women with PCOS throughout the study.

Assessed for eligibility (n = 75)

Enrollment

Excluded (n = 15)
- Not meeting inclusion criteria (n = 7)
- Not living in Tehran (n = 8)

Randomised (n = 60)
Allocation

Allocated to placebo (n = 30) Allocated to intervention (n = 30)

Follow-up

Lost to follow-up (n = 0) Lost to follow-up (n = 0)

Analysis

Analysed (n = 30) Analysed (n = 30)

Figure 1 Summary of patient flow diagram.

4 ª 2018 The British Dietetic Association Ltd.

 M. Karamali et al. Soy diet and polycystic ovary syndrome

Mean age, height, weight, BMI, WC, HC and METs at Table 2 Dietary intake of women with polycystic ovary syndrome
baseline and end-of-trial were not statistically different throughout the present study
between the two groups (Table 1). After the 8-week inter- Control group Soy protein
vention, the test diet significantly [mean (SD)] decreased (n = 30) group (n = 30) P*
weight [ 0.7 (1.5) versus +0.1 (1.2) kg, P = 0.02], BMI 1
Energy (kcal day ) 2084.3 (191.8) 2136.6 (191.2) 0.29
[ 0.3 (0.6) versus +0.1 (0.5) kg m–2, P = 0.02], WC
Carbohydrates 327.5 (29.8) 333.3 (30.5) 0.46
[ 1.2 (1.7) versus +0.1 (1.3) cm, P = 0.002] and HC (g day 1)
[ 1.6 (1.8) versus +0.2 (1.4) cm, P < 0.001] compared Protein (g day 1) 58.1 (5.6) 59.0 (4.4) 0.49
to the control diet. In addition, alopecia rate (42.9 versus Fat (g day 1) 69.9 (6.4) 71.4 (6.9) 0.39
12.5%, P = 0.04) decreased following the consumption of SFAs (g day 1) 18.5 (1.7) 13.1 (1.2) <0.001
the test diet compared to the control diet, although acne PUFAs (g day 1) 24.4 (2.1) 30.4 (2.5) <0.001
MUFA (g day 1) 21.2 (1.5) 22.1 (1.9) 0.06
unchanged (16.7 versus 15.4%, P = 0.93).
TDF (g day 1) 25.1 (2.2) 29.4 (3.4) <0.001
Based on the 3-day dietary records that patients com-
Soy (g day 1) – 39.1 (2.4) –
pleted throughout the study, no statistically significant Soy protein (g day 1) – 20.3 (1.2) –
difference was seen between the two groups in terms of
dietary intakes of energy, carbohydrates, proteins and fats; All values are the mean (SD). MUFAs, monounsaturated fatty acids;
PUFAs, polyunsaturated fatty acids; SFAs, saturated fatty acids; TDF,
however, significant differences were observed in dietary
total dietary fibre.
intakes of saturated fatty acids (SFA) (P < 0.001),
*Obtained from an independent t-test.
polyunsaturated fatty acids (PUFA) (P < 0.001) and total
dietary fibre (P < 0.001) between the two groups
(Table 2). versus +0.2 (1.2) lmol L 1, P < 0.001], as well as signifi-
Adherence to the test diet, compared to the control cant increases in plasma NO [+13.6 (14.1) versus +0.9
diet, resulted in significant decreases in serum insulin (24.3) lmol L 1, P = 0.01] and GSH [+170.1 (175.5) ver-
levels [ 15.0 (18.0) versus +4.8 (18.6) pmol L 1, P < sus +24.2 (168.7) lmol L 1, P = 0.002], were seen in the
0.001], HOMA-IR [ 0.6 (0.6) versus +0.2 (0.7), P < test group compared to the control group (Table 3). We
0.001] and a significant increase in QUICKI [+0.01 (0.01) did not observe any significant effect of test diet on other
versus 0.002 (0.02), P = 0.01] (Fig. 2). lipid profiles, FSH, LH, biomarkers of inflammation and
Significant decreases in FPG [ 0.2 (0.5) versus oxidative stress.
+0.1 (0.3) mmol L 1, P = 0.01], serum total testosterone There was a significant difference in baseline levels of
[ 0.3 (0.7) versus +0.3 (0.3) mmol L 1, P < 0.001], tri- plasma NO (P < 0.001) between the two groups. There-
glycerides [ 0.1 (0.4) versus +0.2 (0.3) mmol L 1, P = fore, we adjusted the analysis for baseline of biochemical
0.01], VLDL-cholesterol [ 0.1 (0.1) versus +0.02 (0.06) variables. When we controlled the analysis for baseline
mmol L 1, P = 0.01] and plasma MDA [ 1.2 (1.0) values of biochemical variables, the difference in changes
in plasma NO (P = 0.46) between the two groups became
nonsignificant, whereas other findings did not alter (data
not shown). In addition, when we adjusted the analysis
Table 1 General characteristics of the study participants
for baseline values of biochemical parameters, age and
Control diet Soy diet baseline BMI, plasma NO levels (P = 0.45) became non-
(n = 30) (n = 30) P*
significant and other findings did not alter (Table 4).
Age (years) 25.9 (5.0) 25.0 (5.7) 0.53 Additional adjustment for baseline values of insulin
Height (cm) 161.9 (5.0) 161.2 (6.7) 0.64 serum, HOMA-IR and QUICKI did not affect our find-
Weight at study baseline (kg) 72.8 (9.5) 74.4 (15.5) 0.64 ings except for plasma NO levels (P = 0.28; data not
Weight at end-of-trial (kg) 72.9 (9.3) 73.7 (15.2) 0.81 shown).
BMI at study baseline (kg m–2) 27.8 (3.9) 28.7 (6.1) 0.50
BMI at end-of-trial (kg m–2) 27.9 (3.8) 28.4 (6.0) 0.63
WC at study baseline (cm) 80.8 (10.3) 85.0 (13.5) 0.17 Discussion
WC at end-of-trial (cm) 80.9 (10.4) 83.9 (12.9) 0.32
HC at study baseline (cm) 97.1 (9.8) 100.1 (13.7) 0.34 To our knowledge, the present study is the first report of
HC at end-of-trial (cm) 97.3 (9.8) 98.5 (13.2) 0.69 soy intake on weight loss and metabolic status among
MET-h day 1 at study baseline 27.5 (1.5) 27.8 (1.7) 0.39 women with PCOS. Previously, the beneficial effects of
MET-h day 1 at end-of-trial 27.6 (1.6) 28.0 (1.9) 0.38 different diet compositions on anthropometric, reproduc-
Data are the mean (SD). HC, hip circumference; METs, metabolic
tive, metabolic and psychological outcomes have been
equivalents; WC, waist circumference. reported in women with PCOS (31,32). Adherence to the
*Obtained from an independent-samples t-test. combination of high-protein and low glycaemic load

ª 2018 The British Dietetic Association Ltd. 5

 Soy diet and polycystic ovary syndrome
Insulin
P < 0.001
40
20
Mean changes (pM)
Mean changes
0
–20
Study groups
–40
Figure 2 Changes [means (SD)] in markers of insulin metabolism after 8 weeks of intervention. HOMA-IR, homeostasis model of assessment-
insulin resistance; QUICKI, quantitative insulin sensitivity check index.
foods in a modified diet in women with PCOS resulted
in a significant increase in insulin sensitivity compared to
a conventional diet. In addition, in a systematic review, a
low-carbohydrate or low glycaemic index diet in women
with PCOS led to greater reductions in insulin resistance,
fibrinogen, and total- and HDL-cholesterol levels. We
have previously shown that soy isoflavone intake
(50 mg day 1) for 12 weeks in women with PCOS signif-
icantly decreased insulin metabolism, hormonal profiles,
triglycerides and MDA, and significantly increased GSH
levels, although it did not affect weight, BMI, other lipid
profiles and inflammatory factors (14). In our previous
study, the effects of soy isoflavone intake in women with
PCOS were examined after 12 weeks (14), whereas, in the
present study, we evaluated the effects of a soy diet in
women with PCOS after 8 weeks. In the previous study,
weight, BMI, WC, HC and plasma NO levels unchanged,
whereas, in the present study, weight, BMI, WC, HC and
FPG significantly decreased and plasma NO levels signifi-
cantly increased. Finally, in the previous study, we used
50 mg day 1 of soy isoflavone, whereas, in the present
study, we used a soy diet containing 75 mg day 1 of total
phyto-oestrogen and other compositions, including fibre,
magnesium and potassium. We found that the adherence
to test diet for 8 weeks among women with PCOS signifi-
cantly decreased weight, BMI, WC, HC, parameters of
glucose homeostasis, triglycerides, VLDL-cholesterol and
MDA, and significantly plasma NO and GSH levels com-
pared to the control diet, although it did not affect other
metabolic profiles.
Patients with PCOS are susceptible to several disorders
including metabolic disorders, increased inflammation and
oxidative stress (14). Although several strategies have been
suggested, weight loss and lifestyle change are the first-line
therapy for PCOS management (7). Our findings showed
that the test diet for 8 weeks in women with PCOS
resulted in significant decreases in weight, BMI, WC and
HC compared to the control diet. Animal studies (33) and
6 ª 2018 The British Dietetic Association Ltd.
M. Karamali et al.
HOMA-IR QUICKI
P < 0.001 0.03
P = 0.01 Control diet
1.0
0.02 Soy diet
0.5
0.01
Mean changes
0.0 0.00
–0.5 –0.01
Study groups
Study groups
–1.0 –0.02
–1.5 –0.03
few cross-sectional studies have supported the effects of
soy and soy products on adipose weight and adipocyte cir-
cumference. Deibert et al. (34) demonstrated that a high-
soy-protein and low-fat diet for 6 months significantly
decreased weight and fat mass in overweight and obese
subjects. Adherence to a soy-based low-calorie diet com-
pared to a traditional low-calorie diet among overweight
subjects for 8 weeks also had a greater effect on decreasing
the body fat percentage (35). Several studies in rodents have
shown that dietary isoflavones intake decreased body
weight and adipose tissue (33,36) and, in particular,
could prevent body weight gain and increase in serum
lipids as a consequence of a decline in oestrogen after
ovariectomy (37). The underlying mechanisms by which
soy protein exert its beneficial effects on obesity are not
yet fully understood. Beside biological effects via oestrogen
receptor-mediated mechanisms, isoflavones have also
direct effects on lipid metabolism in liver and adipose tis-
sue by affecting both de novo lipogenesis (38) and lipolysis
(39)
. Isoflavone intake decreases the expression of hepatic
sterol regulatory element-binding transcription factor 1
(SREBP-1c), acetyl-CoA carboxylase (ACC), and fatty acid
synthase (FAS) of intact rats fed a control diet. The sup-
pression of de novo lipid synthesis may be caused by tar-
geting SREBP-1c, which regulates downstream fatty acid
synthetic pathways, such as FAS and ACC (40).
The present study demonstrated that the consumption
of test diet for 8 weeks in women with PCOS resulted in
significant decreases in FPG, serum total testosterone,
insulin values, HOMA-IR, serum triglycerides and VLDL-
cholesterol levels, as well as a significant increase in
QUICKI compared to the control diet, although it did
not affect other lipid profiles. Similarly, supplementation
with soy phyto-oestrogens for 12 weeks decreased insulin
resistance in postmenopausal women with T2DM (41). A
significant decrease of insulin levels was also seen follow-
ing supplementation with a soy food containing
50 mg day 1 of isoflavones for 8 weeks in
 M. Karamali et al.

ª 2018 The British Dietetic Association Ltd.

Table 3 Metabolic profiles at baseline and after the 8-week intervention in subjects with polycystic ovary syndrome

Control diet (n = 30) Soy diet (n = 30) P*

Study baseline End-of-trial Change Study baseline End-of-trial Change Time Group Time 9 Group

FPG (mmol L 1) 5.1 (0.4) 5.2 (0.4) 0.1 (0.3) 5.0 (0.7) 4.8 (0.5) 0.2 (0.5) 0.08 0.04 0.01
mF-G scores 8.6 (6.6) 8.4 (6.6) 0.2 (0.8) 8.4 (3.2) 8.1 (3.0) 0.3 (1.2) 0.09 0.84 0.80
FSH (IU L 1) 8.0 (1.6) 7.8 (1.7) 0.2 (1.5) 7.7 (3.4) 7.5 (3.0) 0.2 (2.5) 0.62 0.62 0.98
LH (IU L 1) 9.0 (4.3) 9.6 (4.5) 0.6 (3.3) 10.3 (5.0) 9.4 (5.6) 0.9 (5.1) 0.75 0.57 0.14
Total testosterone (nmol L 1) 4.9 (1.7) 5.2 (1.7) 0.3 (0.3) 5.2 (2.4) 4.9 (2.4) 0.3 (0.7) 0.18 0.83 <0.001
Triglycerides (mmol L 1) 1.3 (0.6) 1.5 (0.7) 0.2 (0.3) 1.3 (0.5) 1.2 (0.5) 0.1 (0.4) 0.92 0.40 0.01
VLDL-cholesterol (mmol L 1) 0.3 (0.1) 0.3 (0.1) 0.02 (0.06) 0.3 (0.1) 0.2 (0.1) 0.1 (0.1) 0.92 0.40 0.01
Total cholesterol (mmol L 1) 4.5 (0.8) 4.3 (0.8) 0.2 (0.7) 4.5 (0.9) 4.4 (0.8) 0.1 (0.4) 0.05 0.70 0.56
LDL-cholesterol (mmol L 1) 2.3 (0.6) 2.0 (0.7) 0.3 (0.6) 2.4 (0.7) 2.3 (0.6) 0.1 (0.4) 0.007 0.28 0.15
HDL-cholesterol (mmol L 1) 1.5 (0.2) 1.6 (0.4) 0.1 (0.3) 1.5 (0.2) 1.5 (0.2) 0.05 (0.2) 0.13 0.54 0.95
hs-CRP (ng mL 1) 2463.5 (1944.9) 2907.2 (2320.3) 443.6 (1802.4) 2153.3 (2458.0) 2209.1 (2172.9) 55.8 (1512.7) 0.25 0.35 0.37
NO (lmol L 1) 57.3 (18.1) 58.2 (16.9) 0.9 (24.3) 40.2 (12.0) 53.8 (10.2) 13.6 (14.1) 0.006 <0.001 0.01
TAC (mmol L 1) 794.7 (184.0) 786.0 (177.3) 8.7 (219.7) 836.9 (133.2) 843.9 (122.3) 6.9 (135.7) 0.97 0.13 0.74
GSH (lmol L 1) 473.3 (152.2) 497.7 (169.2) 24.2 (168.7) 516.4 (126.9) 686.5 (148.6) 170.1 (175.5) <0.001 0.001 0.002
MDA (lmol L 1) 3.3 (0.9) 3.5 (1.5) 0.2 (1.2) 3.8 (0.9) 2.6 (0.7) 1.2 (1.0) 0.001 0.34 <0.001

All values are the mean (SD). FPG, fasting plasma glucose; FSH, follicle-stimulating hormone; GSH, total glutathione; hs-CRP, high-sensitivity C-reactive protein; LH, luteinising hormone; mF-G,
modified Ferriman Gallwey; MDA, malondialdehyde; NO, nitric oxide; TAC, total antioxidant capacity.
*P values represent the two-way repeated measures analysis of variance.
Soy diet and polycystic ovary syndrome

7
 Soy diet and polycystic ovary syndrome M. Karamali et al.

Table 4 Adjusted changes in metabolic profile of the patients with inhibiting glucose uptake in the intestine and regulating
polycystic ovary syndrome insulin production in pancreatic islet b cells via the cyclic
Control diet Soy diet adenosine monophosphate pathway (47). In addition, the
(n = 30) (n = 30) P* test diet may decrease triglycerides and VLDL-cholesterol
1
levels via changes in mRNA abundances of key hepatic
FPG (mmol L ) 0.06 (0.06) 0.26 (0.06) 0.002
enzymes and receptors (48), accelerating b-oxidation, as
FSH (IU L 1) 0.04 (0.3) 0.2 (0.3) 0.71
LH (IU L 1) 0.06 (0.06) 0.26 (0.06) 0.41 well as inhibiting fatty acid synthase and increasing its
Free testosterone 0.3 (0.1) 0.3 (0.1) <0.001 faecal excretion (49). In the present study, the decrease in
(nmol L 1) SFA intake and increase in fibre and PUFA intake in the
Insulin (pmol L 1) 4.8 (3.0) 14.4 (3.0) <0.001 test group may have direct/indirect impacts on body
HOMA-IR 0.2 (0.1) 0.5 (0.1) <0.001 weight and the measured biochemical indices. In a study
QUICKI 0.002 (0.004) 0.01 (0.004) 0.01
by Shab-Bidar et al. (50), a positive trend over successive
mF-G scores 0.2 (0.2) 0.3 (0.2) 0.76
quartiles of SFA intake with LDL-cholesterol and triglyc-
Triglycerides (mmol L 1) 0.13 (0.07) 0.12 (0.07) 0.01
VLDL-cholesterol 0.02 (0.01) 0.02 (0.01) 0.01 erides levels, as well as PUFA/SFA ratio intake with HDL-
(mmol L 1) cholesterol levels, was reported. Furthermore, an inverse
Total cholesterol 0.18 (0.09) 0.09 (0.09) 0.52 association between HDL-cholesterol with SFA and PUFA
(mmol L 1) intake and a positive association with MUFA and the
LDL-cholesterol 0.30 (0.09) 0.09 (0.09) 0.11 PUFA/SFA ratio was found (50).
(mmol L 1)
The present study indicated that the test diet for 8 weeks in
HDL-cholesterol 0.05 (0.05) 0.05 (0.05) 0.96
women with PCOS led to a significant increase in plasma NO
(mmol L 1)
hs-CRP (ng mL 1) 520.6 (286.7) 21.0 (286.7) 0.19 and GSH values, and a significant decrease in plasma MDA
NO (lmol L 1) 8.8 (2.8) 5.6 (2.8) 0.45 levels compared to the control diet, although it did not influ-
TAC (mmol L 1) 20.5 (26.5) 18.7 (26.5) 0.30 ence serum hs-CRP and plasma TAC values. In an animal
GSH (lmol L 1) 11.5 (28.3) 183.0 (28.3) <0.001 study by Trujillo et al. (51), soy protein intake in obese rats
MDA (lmol L 1) 0.1 (0.2) 1.1 (0.2) <0.001 resulted in a significant increase in NO availability. Further-
All values are the mean (SE). Values are adjusted for baseline values,
more, both soy nuts and soy protein intake for 8 weeks
age and BMI at baseline. FPG, fasting plasma glucose; FSH, follicle- decreased MDA levels significantly compared to the control
stimulating hormone; GSH, total glutathione; hs-CRP, high-sensitivity diet in postmenopausal women with the metabolic syndrome
(52)
C-reactive protein; LH, luteinising hormone; mF-G, modified Ferriman . Supporting our findings, soy milk intake for 4 weeks had
Gallwey; MDA, malondialdehyde; NO, nitric oxide; TAC, total antioxi- no affect on inflammatory cytokines in patients with DN (53).
dant capacity.
However, soy diet intake for 4 weeks in animal models had
*Obtained from an analysis of covariance.
no effect on vascular NO production (54). The conflicting
results obtained in different studies may be a result of the dif-
postmenopausal women (42). In a meta-analysis study ferent study designs, the intake of phyto-oestrogen or a soy
conducted by Liu et al. (43), the intake of genistein diet, the different types and durations of phytoestrogen sup-
resulted in significant effects with respect to decreasing plementation, and the general characteristics of the study par-
fasting glucose, insulin concentrations and HOMA-IR ticipants. Increased inflammatory markers in subjects with
values. Furthermore, triglycerides levels significantly PCOS results in an increased risk for the development of
decreased following supplementation with 300 mg day 1 atherosclerosis, infertility and other comorbidities (55). Soy is
of isoflavone for 6 months in healthy postmenopausal rich in L-arginine, a NO precursor, which may increase NO
women (44). In a meta-analysis study by Anderson et al. (12), levels (56). In addition, a soy diet may decrease biomarkers of
soy protein consumption at a median of 30 g day 1 was oxidative stress by inhibiting oxidative modification of LDL,
associated with a significant effect in lipoprotein risk fac- and increasing the activity of NAD(P)H quinone oxidoreduc-
tors for coronary heart disease. In another meta-analysis tase 1 and glutathione S-transferase (57).
study, the intake of soya products led to a significant The present study has a few limitations. First, the eval-
decrease in serum total- and LDL-cholesterol, as well as a uation of insulin resistance was only based on HOMA-IR.
significant increase in serum HDL-cholesterol concentra- We did not use a direct dynamic test, such as the glucose
tions (45). The soyamilk-kefir diet for 8 weeks also tolerance test or a hyperinsulinaemic euglycaemic clamp.
resulted in a significant decrease in non-HDL-/HDL-cho- Therefore, this should be taken into account in the inter-
lesterol ratio in cholesterol-fed hamsters (46). Soy products pretation of our findings. As a result of funding limita-
are rich sources of various nutrients, including plant pro- tions, we did not assess other hormonal profiles,
tein, fibre, vitamins, minerals and phyto-oestrogens (iso- including free testosterone, prolactin and 17-OH proges-
flavones), which may improve glycaemic control via terone. In addition, we did not assess compliance with

8 ª 2018 The British Dietetic Association Ltd.

 M. Karamali et al.
the test diet by use of a biomarker. Finding appropriate
biomarkers for dietary patterns is a new field of research
and we are not aware of any definite biomarker that can
reflect adherence to the test diet.
In conclusion, the results of the present study demon-
strate that, compared to a control diet, adherence to test
diet for 8 weeks among PCOS subjects significantly
decreased weight, BMI, WC, HC, FPG, total testosterone,
insulin, HOMA-IR, triglycerides, VLDL-cholesterol and
MDA, and also significantly increased QUICKI, NO and
GSH, although it did not affect other metabolic profiles.
This suggests that the test diet containing soy with high
unsaturated and low saturated fat may have an advanta-
geous therapeutic potential for patients with PCOS. Fur-
ther research is needed in other patients and for longer
periods to determine the safety of this dietary approach.
Transparency declaration
The lead author affirms that this manuscript is an honest,
accurate and transparent account of the study being
reported. The reporting of this work is compliant with
CONSORT1 guidelines. The lead author affirms that no
important aspects of the study have been omitted and that
any discrepancies from the study as planned in the Iranian
website for registration of clinical trials (http://www.irct.
ir: IRCT201701295623N104) have been explained.
Acknowledgments
The present study was funded by a grant from the Vice-
chancellor for Research, IUMS, and Iran. We thank the
staff of Akbarabadi Clinic (Tehran, Iran) for their assis-
tance with this project.
Conflict of interests, source of funding and
authorship
None of the authors had any personal or financial
conflict of interest.
No funding declared.
ZA contributed to the conception, design and statisti-
cal analysis of the study, as well as the drafting of the
manuscript. MK, MK and SA contributed to the data
collection and drafting of the manuscript. All of the
authors approved the final version of the manuscript
submitted for publication. ZA supervised the study.
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