Journal of Ethnopharmacology 254 (2020) 112741

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Journal of Ethnopharmacology
journal homepage: www.elsevier.com/locate/jethpharm

Effects of cinnamon on controlling metabolic parameters of polycystic ovary T

syndrome: A systematic review and meta-analysis
Fatemeh Heydarpoura, Niloofar Hematib, Amir Hadic, Sajjad Moradid, Elham Mohammadie,
Mohammad Hosein Farzaeif,∗
a
Social Development and Health Promotion Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
b
Internal Medicine Department, Kermanshah University of Medical Sciences, Kermanshah, Iran
c
Halal Research Center of IRI, FDA, Tehran, Iran
d
Nutritional Sciences Department, School of Nutritional Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
e
R.R College of Pharmacy, Bangalore, India
f
Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

A R T I C LE I N FO A B S T R A C T

Keywords: Ethnopharmacological relevance: Cinnamon as a traditional medicine has been widely used in various disorders
Cinnamon such as headache, toothache, common cold, diarrhea, flatulence, fever, amenorrhea frigidity. However, the
Polycystic ovary syndrome effect of cinnamon supplementation on metabolic parameters of polycystic ovary syndrome (PCOS) patients has
PCOS not been fully assessed.
Systematic review
Aim of the study: Clinical trials have shown contradictory effects of cinnamon supplementation on metabolic
Meta-analysis
parameters of polycystic PCOS patients. Therefore, we evaluated the effect of cinnamon supplementation on
metabolic parameters of PCOS patients through a systematic review and meta-analysis of clinical trials.
Materials and methods: PubMed, Embase, the Cochrane library, Scopus and Web of Science databases (until
August 2019) were searched to identify potential clinical trials with information on cinnamon supplementation
on metabolic parameters among PCOS patients. Weighted Mean Differences was pooled using a random-effects
model. Standard methods were used for assessment of heterogeneity, publication bias and sensitivity analysis.
Results: Pooling five clinical trials (five treatment arms) together did not show any significant effect on body
weight (WMD: -0.74 kg, 95% CI: -3.17 to 1.69) and body mass index (BMI) (WMD: -1.47, 95% CI: -4.07 to 1.12).
Our results illustrated that a significant decrease of fasting blood sugar (WMD: -5.32, mg/dL95% CI: -10.46 to
-0.17), fasting insulin (WMD: -4.10, μIU/dL95% CI: -6.76 to -0.144) and HOMA-IR (WMD: -0.69 95% CI: -1.37 to
-0.004) were observed after cinnamon treatment. Moreover, our findings demonstrated that oral cinnamon
supplementation in PCOS patients led to significant reduction of serum level of LDL-C, total cholesterol, and
triacylglycerol. Besides, an improvement of serum concentration of HDL-C was shown by cinnamon supple-
mentation.
Conclusion: Generally, present study indicated that cinnamon supplementation may help PCOS patients to
manage their metabolic parameters. Future prospective randomized clinical trials with longer intervention
duration are warranted to obtain a precise conclusion.

1. Introduction
Polycystic ovary syndrome (PCOS) is an intricate endocrine disorder
affecting the psychological, reproductive and metabolic health of
women (Fernandez et al., 2018). This age-related disorder with an es-
timated prevalence of 6–26% worldwide can increase the risk of several
chronic diseases such as obesity, metabolic syndrome, diabetes, cardi-
ovascular events, cancer and psychological problems such as
depression, anxiety and stress (Arentz et al., 2017a; Hadi et al., 2019).
Thus, there is no doubt that effective prevention, management, and
treatment of PCOS can help to improve clinical and public health. A
number of methods including lifestyle modification, pharmacological or
pharmaceuticals treatments, and nutraceuticals interventions are con-
sidered beneficial in management and treatment of PCOS (Arentz et al.,
2017b; Escobar-Morreale, 2018). Nowadays, PCOS patients knowing
the possible side-effects of pharmacological therapies, have more

∗
Corresponding author.
E-mail address: mh.farzaei@gmail.com (M.H. Farzaei).

https://doi.org/10.1016/j.jep.2020.112741
Received 17 December 2019; Received in revised form 24 February 2020; Accepted 3 March 2020
Available online 06 March 2020
0378-8741/ © 2020 Published by Elsevier B.V.
F. Heydarpour, et al.
List of abbreviations:
AMH anti-Mullerian hormone
BMI body mass index
FBS fasting blood sugar
FFM Fat Free Mass
FM Fat Mass
HOMA-IR Homeostatic model assessment- Insulin Resistance
HDL-C High-density lipoprotein cholesterol
attention toward alternative or complementary medicines to improve
their fertility, health and wellbeing (Sills et al., 2001).
Recent studies have shown that nutritional supplements and herbal
medicines as complementary or alternative medicines may help to
improve health outcome in women with PCOS (Arentz et al., 2017b;
Pundir et al., 2019). In addition to lifestyle changes and drug treatment,
previous studies suggested that PCOS patients can manage the com-
plications of their disease by omega 3 fish oils, chromium, selenium,
vitamin D, Vitamin B complex, N-acetylcysteine, camellia sinensis, ci-
micifuga racemose, cimicifuga racemose, mentha spicata, probiotics or
synbiotics, and ultimately cinnamomum supplementation (Arentz et al.,
2017a; Hadi et al., 2019; Pundir et al., 2019). Cinnamon as a traditional
medicine has been widely used in Unani, Indian, Chinese and Persian
nations for a long time (Hajimonfarednejad et al., 2019). It has been
traditionally used for various disorders such as headache, toothache,
common cold, diarrhea, flatulence, fever, amenorrhea frigidity, dys-
pnea, eye inflammation, vaginitis, and leukorrhea (Hajimonfarednejad
et al., 2019). In the past decade, especially, more clinical trials assessed
the efficacy of cinnamon toward the obesity (Kaur et al., 2019), me-
tabolic syndrome (Borzoei et al., 2018a), diabetes (Zare et al., 2019),
oxidative stress related diseases (Li et al., 2019) and PICOS patients
(Borzoei et al., 2018b; Hajimonfarednejad et al., 2018).
Several clinical trials reported controversial results about the effi-
cacy of cinnamon supplementation on improvement of body weight and
body mass index (BMI), fertility and hormonal condition, oxidative
stress status and glucose homeostasis parameters of PCOS patients
(Borzoei et al., 2018b; Hajimonfarednejad et al., 2018; Khan and
Begum, 2019; Kort and Lobo, 2014; Parseh et al., 2019; Talaat and
Ammar, 2018; Wang et al., 2007; Wiweko and Susanto, 2017). Some
studies showed that oral cinnamon supplementation in PCOS patients
led to weight loss (Parseh et al., 2019; Talaat and Ammar, 2018). In
contrast, Hajimonfarednejad et al. (2018) reported that cinnamon
supplementation did not show any effect on body weight or BMI. In
addition, these studies indicated that cinnamon supplementation may
improve glucose homeostasis in PCOS patients (Borzoei et al., 2018b;
Hajimonfarednejad et al., 2018). However Kort et al. (Kort and Lobo,
2014) and Parseh et al. (2019) suggested that oral cinnamon supple-
mentation did not show any effect on glucose homeostasis in PCOS
patients.
Due to the interest to the use of herbal medicines by PCOS patients
and the absence of strong evidence, assessment of herbal remedies was
considered as an appropriate research strategy because it may provide
relevant answers to questions of PCOS patients and clinicians.
According to our search in databases and search engine, no article has
been published endeavoring to summarize the effects of cinnamon on
controlling metabolic parameters of polycystic ovary syndrome. On the
other hand, clinical trials have shown contradictory effects of cinnamon
supplementation on metabolic parameters of PCOS patients.
Furthermore, the outcomes from these clinical trials might not be en-
ough to make an exact conclusion in this area. A systematic review and
meta-analysis was carried out to evaluate the effect of cinnamon sup-
plementation on metabolic parameters in PCOS patients.
2
Journal of Ethnopharmacology 254 (2020) 112741
LDL-C Low-density lipoprotein cholesterol
MDA Malondialdehyde
PCOS Polycystic ovary syndrome
QUICKI Quantitative insulin sensitivity check index
TAC Total antioxidant status
TC Total cholesterol TG: triacylglycerol
WC Waist circumference
WHR Waist/Hip ratio
WMD Weighted Mean Differences
2. Methods
2.1. Literature search and selection
Current systematic review and meta-analysis was carried out ac-
cording to the Preferred Reporting Items for Systematic Reviews and
Meta-Analysis (PRISMA) statement (Moher et al., 2009). A compre-
hensive search and systematic literature review was carried out through
the PubMed, Embase, the Cochrane library, Scopus and Web of Science
databases until 18 August 2019. In the search strategy, we used subject
headings, abstract and keywords, without using date and language re-
strictions. Systematic search was conducted using the following search
terms: ((“Cinnamomum zeylanicum”[Mesh] OR “Cinnamomum zeyla-
nicum”[tiab] OR “Cinnamomum verum”[tiab] OR “Cinnamon”[tiab]
OR “Cinnamons”[tiab] OR “Darchini”[tiab] OR “DLBS3233”[tiab])
AND (“Polycystic Ovary Syndrome”[Mesh] OR “Polycystic Ovary Syn-
drome”[tiab] OR “Stein-Leventhal Syndrome”[tiab] OR “Stein Le-
venthal Syndrome”[tiab] OR “Sclerocystic Ovarian Degeneration”[tiab]
OR “Polycystic Ovarian Syndrome”[tiab] OR “Polycystic Ovary Syn-
drome 1”[tiab] OR “Sclerocystic Ovaries”[tiab] OR “Sclerocystic
Ovary”[tiab])). Electronic systematic literature search was completed
along with citation hand searches and reference list. The research
procedure was performed by two authors (SM and M-H F) in-
dependently and in duplicate. Any disagreement in this regard was
resolved through discussion with the third researcher (NH).
2.2. Eligibility criteria
Two authors selected eligible articles separately by reading titles,
abstracts and whenever required the full-text of the publications. All
human Randomized controlled trials (RCTs), (either parallel or cross-
over designs) which reported the effects of cinnamon on controlling
metabolic parameters of polycystic ovary syndrome including Weight,
body mass index (BMI), waist circumference (WC), Waist/Hip ratio
(WHR), Fat Mass (FM) Fat Free Mass (FFM), fasting blood sugar (FBS),
fasting insulin, Homeostatic model assessment-Insulin Resistance
(HOMA-IR), Quantitative insulin sensitivity check index (QUICKI), total
cholesterol (TC), triacylglycerol (TG), high-density lipoprotein choles-
terol (HDL-C), low-density lipoprotein cholesterol (LDL-C), anti-
Mullerian hormone (AMH), serum estrogen or androgen levels were
considered. Following studies were excluded: (1) RCTs with treatment
duration less than 2 weeks, (2) studies without appropriate comparing
control group. To keep away from overlapping, we included studies
with larger participants. Disagreements regarding the study selection
procedure were resolved by face to face discussion.
2.3. Data extraction
The following data were extracted from the full-text of included
studies using a pre-designed abstraction form: first author's specifica-
tion, publication year, location of the study, patients characteristics
(age, gender, and diseases), total sample size, PCOS criteria, study de-
sign and blinding, type and dose of intervention and placebo, study
duration, and the final result of metabolic parameters of PCOS
F. Heydarpour, et al.
comparisons. When the data were demonstrated at multiple assess-
ments, just the outcomes at the end of the intervention were included in
the analysis. In cases of lack of relevant data, we contacted the corre-
sponding authors via e-mail to get their help. The whole process of data
extraction was conducted independently by two authors (SM and MHF)
to minimize possible errors. If there was a disagreement, it was resolved
by consensus.
2.4. Quality assessment of studies
We had used Cochrane Collaboration's tools for quality assessment
of studies (Higgins et al., 2011). Two investigators (SM and MHF) se-
parately evaluated the methods and the quality of the eligible studies
through Cochrane Collaboration's tools, which includes seven criteria:
1) random sequence generation; 2) allocation concealment; 3) blinding
of participants and personnel; 4) blinding of outcome assessment; 5)
incomplete outcome data; 6) selective reporting; and 7) other sources of
bias. For each item in the tool, the assessment of risk of bias is in two
parts. The support for judgment provides a succinct free text description
or summary of the relevant trial characteristic on which judgments of
Fig. 1. PRISMA flowchart describing the study's systematic literature search and study selection.
3
Journal of Ethnopharmacology 254 (2020) 112741
risk of bias are based and aims to ensure transparency on how judg-
ments are reached (Higgins et al., 2011). Moreover, each scope was
further classified into three classes: low risk, high risk, and unclear risk
of bias. According to the guidelines, the general quality of each study
was considered as good (low risk for more than two cases), fair (low risk
for two cases) or weak (low risk for less than two cases) (Higgins et al.,
2011).
2.5. Meta-analysis of data
To analyze the effect size for blood pressure, the mean change and
its standard deviation for intervention and control groups as compar-
ison group were extracted. A random effects model was used to cal-
culate weighted mean differences (WMDs) with 95% confidence inter-
vals (CIs). Between-study heterogeneity was tested by Cochran's Q test
and quantified by I2 statistic. A subgroup analysis based on the duration
of study (under 6 month + 6 month and more) was conducted to detect
potential sources of heterogeneity. Between subgroup heterogeneity
was assessed using a fixed effect model. Just for BMI subgroup analysis
was run based on the weight status including obese, overweight and
 F. Heydarpour, et al.

Table 1
Description of the studies included in systematic review.
First author Country Sample size PCOS criteria Target Mean age (years) Mean BMI (kg/m2) RCT design Duration Intervention Comparison Reported Outcome Results Quality
(publication year) (Intervention/ Population (Blinding) (weeks) Scorea
control)

Kort et al. (2014) USA 45 (23/22) Rotterdam PCOS patients 27.40 ± 3.85 26.86 ± 4.39 Parallel 24 Cinnamon Placebo (NR) Menstrual cyclicity, In patients taking 4
(Double) extract HOMA-IR and cinnamon,
(1500 mg/ QUICK-I menstrual cyclicity
day) improved from
baseline
Hajimonfarednejad Iran 66 (33/33) Rotterdam PCOS patients 27.57 ± 6.13 26.86 ± 4.39 Parallel 12 Cinnamon Placebo (NR) Weight, BMI, WC, Levels of fasting 5
et al. (2017) (Double) capsules FBS, 2-hr insulin, HOMA-IR,
(1500 mg/ postprandial blood LDL,HDL in the
day) glucose, lipid cinnamon group
profile, serum were significantly
androgen levels, lower after the
fasting insulin and intervention
HOMA-IR
Talaat et al (2018) Saudi 233 (117/116) Rotterdam Overweight 23.29 ± 5.10 29.25 ± 4.12 Parallel 24 Cinnamon Placebo (NR) BMI, WHR and LH Significant 3
Arabia or obese (Double) extract reduction was

4
PCOS patients (336 mg/day) observed in BMI
with and WHR
metformin
Borzoei et al. (2018) Iran 84 (42/42) Rotterdam Overweight 29.72 ± 6.41 31.18 ± 5.44 Parallel 8 Cinnamon Placebo (NR) Weight, BMI, LDL, Significant 4
or obese (Double) capsules HDL, TG, TC, reduction was
PCOS patients (1500 mg/ insulin, HOMA-IR observed in LDL,
day) and FBS TC, Insulin,
HOMA-IR and FBS
Significant
increase was
observed in HDL
Parseh et al. (2019) Iran 20 (10/10) Rotterdam PCOS patients 25.37 ± 2.85 27.54 ± 9.21 Parallel 6 Cinnamon Placebo (NR) BMI, HOMA-IR, Significant 3
(Singel) capsules FBS, FM and FFM reduction was
(1500 mg/ observed in fat
day) mass in
comparison to the
placebo group

BMI: body mass index; MDA: Malondialdehyde, TAC: Total antioxidant status; PCOS: Oolycystic ovary syndrome; HOMA-IR: Homeostatic model assessment-Insulin Resistance; QUICKI: Quantitative insulin sensitivity
check index; TC: Total cholesterol; TG: Triacylglycerol; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; FM: Fat Mass; FFM: Fat Free Mass; WC: Waist circumference; WHR: Waist/
Hip ratio; AMH: Anti-Mullerian hormone.
a
Cochrane quality score.
Journal of Ethnopharmacology 254 (2020) 112741
F. Heydarpour, et al.
normal weight. We did not conduct subgroup analysis for other para-
meters because of the small number of trials. Sensitivity analysis was
conducted by removing each study one by one and recalculating the
pooled evaluations. Begg's rank correlation test and Egger's regression
asymmetry test were performed for detecting potential publication bias.
Statistical analysis was conducted using STATA, version 11.2 (Stata
Corp, College Station, TX). The statistical significant value was defined
as P values < 0.05.
3. Results
3.1. Selection and identification of studies
Out of initial 132 studies that were obtained by electronic and hand
search (39 duplicates), 83 were excluded, because they were unrelated
to present meta-analysis according to our inclusion criteria. After
reading the full text of the remaining 10 articles (Borzoei et al., 2018a;
Borzoei et al., 2018b; Hajimonfarednejad et al., 2018; KARTOLO et al.,
2016; Khan and Begum, 2019; Kort and Lobo, 2014; Parseh et al., 2019;
Talaat and Ammar, 2018; Wang et al., 2007; Wiweko and Susanto,
2017), five studies did not meet with the desired criteria (Borzoei et al.,
2018b; KARTOLO et al., 2016; Khan and Begum, 2019; Wang et al.,
2007; Wiweko and Susanto, 2017). These studies were excluded be-
cause of inadequate information (KARTOLO et al., 2016; Wang et al.,
2007), same study participants (Borzoei et al., 2018b) and using met-
formin as comparing control group (Khan and Begum, 2019; Wiweko
and Susanto, 2017).In total, five eligible RCTs with five treatment arms
were included for our final analysis (Borzoei et al., 2018a;
Hajimonfarednejad et al., 2018; Kort and Lobo, 2014; Parseh et al.,
2019; Talaat and Ammar, 2018). A flow chart describing the systematic
search and study selection process is shown in Fig. 1.
3.2. Characteristics of studies
The main characteristics of the included studies in the present meta-
analysis are described in Table 1. Overall, five effect sizes were ex-
tracted from four RCTs which included a total of 448 subjects, of which
226 subjects were in the cinnamon group and 222 belonged to the
control group. The mean age of participants in these studies ranged
from 26 to 31 years. All the RCTs used a parallel study design. These
studies were published between the year 2014 and 2019. The RCTs
were conducted in Iran (Borzoei et al., 2018a; Hajimonfarednejad et al.,
2018; Parseh et al., 2019), USA(Kort and Lobo, 2014) and Saudi Arabia
(Talaat and Ammar, 2018). The dose of cinnamon ranged from 336 to
1500 mg/day. The duration of intervention also varied from 6 to 24
weeks. According to Cochrane scores, all studies were classified as high-
quality studies (score = 3). Furthermore, all studies adequately ex-
plained the randomization and blinding procedures. The result of the
Table 2
Risk of bias assessment for included randomized controlled clinical trial.
Domain Kort et al. (2014) Hajimonfarednejad et al. (2017)
Random sequence generation
(selection bias) + +
Allocation concealment
(selection bias) + +
Blinding of participants and personnel (performance + +
bias)
Blinding of outcome assessment
(detection bias) + +
Incomplete outcome data (attrition bias) – +
Selective reporting (reporting bias) – –
Other sources of bias ? ?
Score 4 5
Overall quality Good Good
5
Journal of Ethnopharmacology 254 (2020) 112741
quality assessment is reported in Table 2.
3.3. Effects of cinnamon on BMI and body weight of PCOS patient
As shown in Fig. 2, pooling four RCTs (four treatment arms) to-
gether did not show any significant BMI change in PCOS patients
(WMD: -1.47, 95% CI: -4.07 to 1.12) after cinnamon treatment com-
paring to that of placebo group. A high heterogeneity was found among
the studies (I2 = 93.7%, P < 0.001). For detecting the potential
sources of heterogeneity, subgroup analysis was run based on the
weight status (obese or overweight and normal weight). In the same
results, cinnamon supplementation did not show any significant change
on patients with normal BMI (WMD: -0.59, 95% CI: -1.81 to 0.62) or on
obese and overweight (WMD: -2.35, 95% CI: -6.56 to 1.87) PCOS pa-
tients (Fig. 3). Also, our results indicated that cinnamon supplementa-
tion did not show any significant effect on PCOS patients body weight
(WMD: -0.74 kg, 95% CI: -3.17 to 1.69), (Fig. 4).
3.4. Effects of cinnamon on glucose homeostasis parameters of PCOS
patient
Our results indicated that a significant decrease of PCOS patients’
FBS was observed after cinnamon treatment comparing to that of the
placebo group (WMD: -5.32, mg/dL95% CI: -10.46 to -0.17), (Fig. 5). In
addition we found a significant decrease in fasting insulin (WMD: -4.10,
μIU/dL95% CI: -6.76 to -0.144) and HOMA-IR (WMD: -0.69 95% CI:
-1.37 to -0.004) of PCOS patients of treatment group in comparison to
that of the placebo group, (Figs. 6 and 7).
3.5. Effects of cinnamon on lipid profile of PCOS patients
As illustrated in Table 3, cinnamon supplementation in PCOS pa-
tients shows a significant reduction of serum LDL-C (WMD: -14.33, mg/
dL95% CI: -19.87 to -8.80), TC (WMD: -12.10, mg/dL 95% CI: -18.21 to
-5.98), and TG (WMD: -13.05, mg/dL 95% CI: -24.11 to -1.99) level
versus placebo group. Moreover, our results suggested that cinnamon
supplementation improved serum concentration of HDL-C in compar-
ison to that of the placebo group (WMD: 3.20, mg/dL 95% CI: 1.74 to
4.65), (Table 3).
3.6. Publication bias and sensitivity analysis
The sensitivity analysis indicated that calculated overall effect sizes
for BMI, body weight, FBS, fasting insulin, HOMA-IR, and lipid profile
were not substantially changed after removing each study. Egger's
weighted regression tests and Begg's rank correlation were used to de-
tect the publication bias. The results of Begg's test demonstrated no
publication bias for BMI (P = 1), body weight (P = 0.311), FBS
Talaat et al. Borzoei et al. (2018) Parseh et al. (2019)
(2018)
+ + +
+ ? +
– + –
– + –
+ + +
– – –
? ? ?
3 4 3
Good Good Good
F. Heydarpour, et al. Journal of Ethnopharmacology 254 (2020) 112741

Fig. 2. Forest plot of the comparison of the effects of cinnamon versus placebo on body mass index in polycystic ovary syndrome patient.

Fig. 3. Subgroup analysis to assess the effects of cinnamon versus placebo on body mass index in polycystic ovary syndrome patient.

Fig. 4. Forest plot of the comparison of the effects of cinnamon versus placebo on body weight in polycystic ovary syndrome patient.

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F. Heydarpour, et al. Journal of Ethnopharmacology 254 (2020) 112741

Fig. 5. Forest plot of the comparison of the effects of cinnamon versus placebo on fasting blood glucose in polycystic ovary syndrome patient.

(P = 0.496), fasting insulin (P = 0.317), HOMA-IR (P = 1), LDL
(P = 0.313), HDL (P = 0.317), total cholesterol (P = 0.314) and
triacylglycerol (P = 0.316). Furthermore, the results of Egger's test
revealed no publication bias for BMI (P = 0.087), body weight
(P = 0.311), FBS (P = 0.602), (P = 0.317), HOMA-IR (P = 0.909) and
LDL (P = 1). However Egger's test showed that there was publication
bias for fasting insulin (P < 0.001), HDL (P = P < 0.001), total
cholesterol (P = P < 0.001) and triacylglycerol (P = P < 0.001).
4. Discussion
Current systematic review and meta-analysis was conducted with
the aim of evaluating the effect of cinnamon supplementation on me-
tabolic parameters in PCOS patients. Meta-analysis of five eligible
clinical trials indicated that oral cinnamon supplementation had no
significant effect on body weight and BMI. In the same results, subgroup
analysis by weight status suggested that cinnamon supplementation did
not show any significant change on BMI of normal, obese and over-
weight PCOS patients. Our results illustrated that a significant decrease
of PCOS patients’ FBS and fasting insulin were observed after cinnamon
treatment compared to that of the placebo group. Moreover, our find-
ings demonstrated that oral cinnamon supplementation in PCOS pa-
tients led to significant reduction of serum LDL, total cholesterol, and
triacylglycerol level versus placebo group. Besides, cinnamon supple-
mentation improved serum concentration of HDL in comparison to that
of the placebo group.
Based on our results, oral cinnamon supplementation had no
significant effect on body weight and BMI among PCOS patients.
Cinnamon may improve weight or BMI through various possible me-
chanisms. Previous studies suggested that oral cinnamon administra-
tion may be associated with weight loss by delaying gastric emptying,
increasing glucosidase enzymes and inhibiting ATPase in intestinal villi
(Hlebowicz et al., 2007; Kirkham et al., 2009). This effect of cinnamon
led to reducing glucose uptake in the small intestine and consequently
decreased postprandial blood glucose concentration (Hlebowicz et al.,
2007; Kirkham et al., 2009). Furthermore, Methylhydroxy-celson
polymers (MHCP) as cinnamon compound increased insulin sensitivity
and body metabolism via inhibiting insulin receptor-phosphatase and
activating insulin receptor kinase (Al Jamal, 2009). Although, our re-
sults indicated that cinnamon supplementation had no effect on BMI or
weight, it seems that longer intervention duration may lead to the ef-
fectiveness of cinnamon on BMI or weight. For example among in-
cluded studies, Talaat et al. (Talaat and Ammar, 2018) had longer
duration and reported that oral cinnamon supplementation sig-
nificantly decreased BMI in compression to that of the placebo group.
Therefore, the longer duration of intervention may lead to the effec-
tiveness of cinnamon on BMI or weight of PCOS patients.
Another important result to take into consideration is the effect of
oral cinnamon supplementation on decrease of FBS, fasting insulin and
HOMA-IR of PCOS patients. Insulin resistance is a main pathophysio-
logical feature of PCOS contributing to both reproductive and metabolic
disturbances. In terms of reproduction, insulin resistance increases
hyperandrogenism, whereby insulin increases the production of ovarian
androgens (BARBIERI et al., 1986) and decreases the production of

Fig. 6. Forest plot of the comparison of the effects of cinnamon versus placebo on fasting insulin in polycystic ovary syndrome patient.

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F. Heydarpour, et al. Journal of Ethnopharmacology 254 (2020) 112741

Fig. 7. Forest plot of the comparison of the effects of cinnamon versus placebo on HOMA-IR in polycystic ovary syndrome patient.

hepatic sex hormones bound to the globulin (PLYMATE et al., 1988).
Women with PCOS usually exhibit greater insulin resistance than the
non-PCOS overweight population (Lim et al., 2019). Decreased insulin
resistance is the most important mechanism for the improvement of
metabolic syndrome in cinnamon which is one of the most important
pathophysiological factors in PCOS patients. Several studies have de-
monstrated the different effects of cinnamon on hypoglycemia (Borzoei
et al., 2018a; Hajimonfarednejad et al., 2018; Kort and Lobo, 2014).
Cinnamon can improve glucose homeostasis parameters of PCOS pa-
tient through various mechanisms. First, cinnamon inhibits alpha-
amylase action as initial carbohydrate digestion enzyme (Sheng et al.,
2008). Secondly, cinnamon improves the activity of pyruvate kinase
(PK) and phosphenol pyruvate carboxykinase (PEPCK) enzymes that
play important roles in regulating hepatic glucose metabolism (Anand
et al., 2010). Thirdly, it regulates glucose transporter 4 (GLUT4) by
activating adenosine mono phosphate (AMP)-kinase (Nikzamir et al.,
2014; Sheng et al., 2008). Fourthly, another possible mechanism of
cinnamon is enhancing the expression of peroxisome proliferator-acti-
vated alpha (PPAR-α) and PPAR-γ by cinnamaldehyde as cinnamon
compound (Nikzamir et al., 2014; Sheng et al., 2008). Lastly, it can
activate insulin-like growth factor-1 (IGF1) signaling in fibroblasts,
which reduces insulin resistance and improves blood glucose control.
Moreover, cinnamon can down-regulate insulin signaling in adipocytes
(Takasao et al., 2012).
Beyond effects on glucose homeostasis, cinnamon has positive ef-
fects on other aspects of PCOS patient health. Our founding suggested
that oral cinnamon supplementation may improve lipid profile in PCOS
patient. The main hypolipidemic mechanisms of cinnamon are inhibi-
tion of hepatic enzyme HMG Co-A reductase, reducing oxidative stress
and lipid peroxidation by inhibiting 5-lipoxygenase (Lee et al., 2003),
decreasing copper-mediated LDL-c oxidation and LDL-c phagocytosis by
macrophages, and reducing cholesterol ester transfer protein (CETP)
activity (Jin and Cho, 2011). Furthermore, fat differentiation can be
inhibited by cinnamon polyphenolic compounds. Polyphenolic com-
pounds reduce lipolysis, lipogenesis or absorption of intestinal lipids
(Uchiyama et al., 2011).
5. Limitations
There are some limitations in our study that should be mentioned.
First, a high statistical heterogeneity was identified among the studies.
However, we carried out a subgroup analysis based on weight status to
find the potential sources of heterogeneity. Second, the results of the
current systematic review and meta-analysis is in agreement with a
small number of clinical trials. Therefore, the outcomes should be in-
terpreted with caution.
6. Conclusion
In conclusion, we examined the impact of the effect of cinnamon
supplementation on metabolic parameters in PCOS patients through a
systematic review and meta-analysis of clinical trials. Our outcomes of
the present systematic review and meta-analysis indicated that cin-
namon supplementation had no significant effect on body weight and
BMI of PCOS patients with normal BMI or patients who are overweight
and obese. Although, our findings demonstrated that cinnamon sup-
plementation has an effective role in improving glucose homeostasis
parameters of PCOS patient. Moreover, our results demonstrated that
oral cinnamon supplementation in PCOS patients led to significant re-
duction of serum LDL, total cholesterol, triacylglycerol level, and it
improved serum concentration of HDL in comparison to that of the
placebo group. Future prospective randomized clinical trials with
longer intervention duration are warranted to obtain a precise con-
clusion. We suggest that future clinical trials should be more focused
on:
• Determining the more effective doses of cinnamon supplementation
on PCOS disease management.
• Clinical trials on the cinnamon supplementation on different phe-
notype of PCOS disease.

Table 3
Effects of cinnamon supplementation on polycystic ovary syndrome patient lipid profile.
Lipids profile No. of studies Intervention dosage Effect size1 95% CI I2 (%) P for heterogeneity

Low-density lipoprotein cholesterol 2 1500 mg/day -14.33 -19.87 to -8.80 0.00% 0.548
High-density lipoprotein cholesterol 2 1500 mg/day 3.20 1.74 to 4.65 0.00% 0.935
Total cholesterol 2 1500 mg/day -12.10 -18.21 to -5.98 0.00% 0.501
Triacylglycerol 2 1500 mg/day -13.05 -24.11 to -1.99 0.00% 0.874

1
Calculated by random-effects model.

8
F. Heydarpour, et al.
• Clinical trials on the cinnamon supplementation on other PCOS
disease parameters including menstrual cyclicity, duration of cycle,
follicle diameter, and related hormonal status.
• Improving the knowledge about possible molecular mechanisms
related to effect of cinnamon supplementation on PCOS disease
parameters
•
Assessing the possible synergist, agonist, antagonist association be-
tween cinnamon supplementation and well-known PCOS disease
drugs or supplements, by both clinical and experimental studies
Authors’ contributions
Sajjad Moradi (SM), and Mohammad Hosein Farzaei (Mh-F), de-
signed the research; SM, Niloofar Hemati (NH), conducted the research;
SM and Amir Hadi performed statistical analysis; SM, Fatemeh
Heydarpour, and Elham Mohammadi wrote the paper; Mh-F had pri-
mary responsibility for final content.
Declaration of competing interest
No potential competing interests.
Acknowledgments
None.
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