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Jamilian Et Al. (2018) Comparison of Myo-Inositol and Metformin On Mental Health Parameters and Biomarkers of Oxidative Stress in Women With PCOS-A Randomized, Double-Blind, Placebo-Controlled Trial
Jamilian Et Al. (2018) Comparison of Myo-Inositol and Metformin On Mental Health Parameters and Biomarkers of Oxidative Stress in Women With PCOS-A Randomized, Double-Blind, Placebo-Controlled Trial
To cite this article: Hamidreza Jamilian, Mehri Jamilian, Fatemeh Foroozanfard, Faraneh Afshar
Ebrahimi, Fereshteh Bahmani & Zatollah Asemi (2017): Comparison of myo-inositol and metformin
on mental health parameters and biomarkers of oxidative stress in women with polycystic ovary
syndrome: a randomized, double-blind, placebo-controlled trial, Journal of Psychosomatic
Obstetrics & Gynecology, DOI: 10.1080/0167482X.2017.1383381
ORIGINAL ARTICLE
Introduction: Data on comparison of myo-inositol and metformin on mental health parameters Received 7 July 2017
and biomarkers of oxidative stress in subjects with polycystic ovary syndrome (PCOS) are scarce. Revised 3 September 2017
This purpose of this study was to compare of myo-inositol and metformin on mental health Accepted 15 September 2017
parameters and biomarkers of oxidative stress in subjects with PCOS.
Methods: This randomized controlled trial was conducted among 60 subjects diagnosed with KEYWORDS
PCOS according to the Rotterdam criteria. Subjects were randomly assigned into two groups to Myo-inositol; metformin;
intake either myo-inositol (n ¼ 30) or metformin (n ¼ 30) for 12 weeks. Parameters of mental polycystic ovary syndrome;
health were recorded at baseline and after the 12-week intervention. Fasting blood samples mental health; oxidative
were obtained at baseline and the end of the study to determine biomarkers of biomarkers of stress
oxidative stress.
Results: After the 12-week intervention, changes in beck depression inventory total score
(1.0 ± 1.7 vs. 0.3 ± 0.7, p ¼ 0.03), general health questionnaire scores (1.7 ± 2.9 vs. 0.5 ± 1.2,
p ¼ 0.02), depression anxiety and stress scale scores (3.9 ± 6.4 vs. 0.9 ± 1.9, p ¼ 0.01) and
plasma total antioxidant capacity (TAC) concentrations (þ106.1 ± 69.6 vs. þ2.1 ± 132.4 mmol/L,
p < 0.001) in the myo-inositol group were significantly different from the changes in these indi-
cators in the metformin group. Myo-inositol supplementation for 12 weeks among patients with
PCOS did not affect plasma glutathione and malondialdehyde levels.
Conclusions: Overall, our data supported that myo-inositol supplementation for 12 weeks among
patients with PCOS had favorable effects on parameters of mental health and plasma TAC levels.
CONTACT Zatollah Asemi asemi_r@yahoo.com Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical
Sciences, Kashan, Iran
ß 2017 Informa UK Limited, trading as Taylor & Francis Group
2 H. JAMILIAN ET AL.
resistance such as PCOS, gestational diabetes, and and was recorded in the Iranian website for registra-
metabolic syndrome [13–14]. In addition, other studies tion of clinical trials (http://www.irct.ir:
underlined the importance of two inositol isoforms, IRCT201706065623N118).
myo- and D-chiro-, in metabolism and ovarian function
in PCOS women [15,16]. In a study by Chengappa
Study design
et al. [17] it observed that inositol intake at a dosage
of 12 g/day for six weeks in patients with bipolar Participants were randomly assigned into two groups
depression improved Hamilton Depression Rating to intake either 500 mg of metformin three times a
Scale and Clinical Global Improvement scores. In add- day (n ¼ 30) or myo-inositol containing 2 g of myo-
ition, the beneficial effects of folate supplementation inositol plus 200 mg of folate twice a day (n ¼ 30) for
on biomarkers of oxidative stress in patients with 12 weeks. Myo-inositol and metformin were manufac-
PCOS [18] and type 2 diabetes mellitus [19] have pre- tured by LO.LI. Pharma (Rome, Italy) and Tehran Darou
viously reported. Pharma (Tehran, Iran), respectively. Participants were
Although there is evidence to indicate that myo- asked not to alter their routine physical activity or
inositol intake may improve mental health parameters usual dietary intakes during the study and not to con-
and biomarkers of oxidative stress in PCOS women, sume any supplements and medications that might
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the beneficial effects of myo-inositol intake in PCOS influence related markers during the study or the pre-
women on these variables compared with the metfor- vious three months (wash-out). All participants pro-
min, to our knowledge, has not yet been firmed. vided three-day dietary records and three physical
Therefore, we hypothesized that myo-inositol intake activity records. Both dietary records and physical
might improve mental health parameters and bio- activity were taken at baseline, weeks of 3, 6, 9 and 12
markers of oxidative stress of PCOS women. The pur- of the intervention. To obtain information on partici-
pose of this study was to compare myo-inositol and pant nutrient intake based on these three-day food
metformin on mental health parameters and bio- diaries, we used Nutritionist IV software (First
markers of oxidative stress among women with PCOS. Databank, San Bruno, CA, USA) modified for Iranian
foods.
baseline and the end of treatment. BDI is a self-com- sample t-test was used to establish changes in
piled questionnaire of 21 items in multiple choice for- anthropometric measures and dietary intakes between
mat [21]. The GHQ-28 comprises 28-item consisting of the two groups. To compare the effects of myo-inosi-
four subscales: somatic symptoms, anxiety and insom- tol and metformin on mental health and oxidative
nia, social dysfunction and severe depression [22]. stress parameters, we used one-way repeated meas-
DASS questionnaire consists of three 14-item self- ures analysis of variance. Adjustment for changes in
report scales that measure depression, anxiety and baseline values of biochemical parameters, age and
stress [23]. baseline BMI was conducted by analysis of covariance.
p < 0.05 were considered statistically significant. All
statistical analyzes conducted using the Statistical
Biochemical assessment
Package for Social Science version 18 (SPSS Inc.,
Ten milliliters fasting blood samples were taken at Chicago, IL, USA).
baseline and after the 12-week intervention at Arak
reference laboratory, Arak, Iran. Serum high sensitivity
Results
C-reactive protein (hs-CRP) levels were assessed using
available ELISA kits (LDN, Nordhorn, Germany). Thirty participants in both groups completed the trial
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Spectrophotometric methods were used to assess out of 65 subjects which were recruited in our study
nitric oxide (NO) [24]. Plasma total antioxidant capacity (five subjects were excluded from the study because
(TAC) by the method of ferric reducing antioxidant of not meeting inclusion criteria) (Figure 1). On aver-
power developed by Benzie and Strain [25], total age, higher than 90% of myo-inositol and metformin
glutathione (GSH) using the method of Beutler et al. were taken in both groups.
[26] and malondialdehyde (MDA) concentrations by Mean age, height, weight and BMI at baseline and
the thiobarbituric acid reactive substances spectro- end-of-trial were not statistically different between the
photometric test [27] were determined. two groups (Table 1).
Considering the three-day dietary records obtained
at baseline, weeks of 3, 6, 9 and 12 of the intervention,
Sample size
there was no statistically significant difference in terms
Considering the following values: effect size ¼ 0.5, of dietary macro- and micro-nutrient intakes between
a ¼ 0.05, b ¼ 0.20, to the power of 80% and using a myo-inositol and metformin groups (data not shown).
formula suggested for clinical trials, the sample size After the 12-week intervention, compared with met-
was estimated at 25 subjects in each group. formin, myo-inositol supplementation led to significant
Considering the possible losses, the sample size was improvements in BDI score (1.0 ± 1.7 vs. 0.3 ± 0.7,
set at 30 subjects in each group finally. p ¼ 0.03), GHQ scores (1.7 ± 2.9 vs. 0.5 ± 1.2, p ¼ 0.02)
and DASS scores (3.9 ± 6.4 vs. 0.9 ± 1.9, p ¼ 0.01)
(Table 2). In addition, change in plasma TAC concentra-
Randomization
tions (þ106.1 ± 69.6 vs. þ2.1 ± 132.4 mmol/L, p < 0.001)
Randomization assignment was conducted using com- in myo-inositol group were significantly different from
puter-generated random numbers. At the time of ran- the change in this indicator in metformin group. Myo-
domization, sequentially numbered, sealed envelopes inositol supplementation for 12 weeks among patients
were opened. Allocation to study group was concealed with PCOS did not affect plasma GSH and MDA levels.
until consent was obtained and inclusion/exclusion cri- Baseline levels of MDA (p ¼ 0.01) were significantly
teria verified. Allocation of the subjects was conducted different between the two groups. Therefore, we con-
by a trained staff at the gynecology clinic that was trolled the analyzes for the baseline values of bio-
blinded to the randomization schedule. Because com- chemical parameters, age and baseline BMI. When we
mercially available myo-inositol and metformin were adjusted the analysis for baseline values of biochem-
used, there was no blinding after randomization; con- ical variables, age and baseline BMI, BDI scores
sequently, researchers and participants could identify (p ¼ 0.05) and GHQ scores (p ¼ 0.06) became non-sig-
the actual treatment. nificant, and other findings did not alter (Table 3).
Enrollment
Excluded (n=5)
- Not meeting inclusion criteria (n=5)
Randomized (n=60)
Allocation
Analysis
Table 2. Parameters of mental health and biomarkers of oxidative stress at baseline and after the 12-week intervention in sub-
jects with polycystic ovary syndrome that received either myo-inositol or metformina.
Metformin group (n ¼ 30) Myo-inositol group (n ¼ 30)
Baseline End-of-trial Change p b
Baseline End-of-trial Change pb pc
BDI total scores 15.1 ± 3.9 14.8 ± 3.9 0.3 ± 0.7 0.04 15.4 ± 5.2 14.4 ± 5.1 1.0 ± 1.7 0.004 0.03
GHQ scores 49.7 ± 8.4 49.2 ± 8.6 0.5 ± 1.2 0.02 50.2 ± 6.2 48.5 ± 6.6 1.7 ± 2.9 0.004 0.04
DASS scores 86.6 ± 15.7 85.7 ± 15.7 0.9 ± 1.9 0.01 89.1 ± 16.6 85.2 ± 15.8 3.9 ± 6.4 0.002 0.01
TAC (mmol/L) 823.0 ± 152.0 825.1 ± 166.0 2.1 ± 132.4 0.93 868.5 ± 56.2 974.6 ± 60.6 106.1 ± 69.6 <0.001 <0.001
GSH (mmol/L) 586.5 ± 112.9 591.6 ± 143.4 5.1 ± 138.5 0.84 631.3 ± 79.9 663.9 ± 88.0 32.7 ± 80.1 0.03 0.35
MDA (mmol/L) 2.5 ± 0.6 2.8 ± 1.2 0.3 ± 1.4 0.21 2.8 ± 0.3 2.7 ± 0.3 0.1 ± 0.4 0.11 0.10
a
Data are means ± SDs.
b
Obtained from paired-samples t-test.
c
p Values represent the time group interaction (computed by analysis of the one-way repeated measures ANOVA).
BDI: beck depression inventory; DASS: depression anxiety and stress scale; GHQ: general health questionnaire; GSH: total glutathione; MDA: malondialde-
hyde; TAC: total antioxidant capacity.
Table 3. Mean adjusted changes in parameters of mental psychological disturbances [44,45]. Inositol intake may
health and biomarkers of oxidative stress in patients with improve mental health parameters through to control
polycystic ovary syndrome that received either myo-inositol or intracellular calcium concentration and modulates
metformina.
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