Comparison of myo-inositol and metformin on glycemic control, lipid profiles, and gene expression related to insulin and lipid metabolism in women with polycystic ovary syndrome: a randomized controlled clinical trial.

This investigation was conducted to evaluate comparison of myo-inositol and metformin on glycemic control, lipid profiles, and gene expression related to insulin and lipid metabolism in women with polycystic ovary syndrome (PCOS). This randomized controlled trial was conducted on 53 women with PCOS, aged 18-40 years old. Subjects were randomly allocated into two groups to take either myo-inositol (n = 26) or metformin (n = 27) for 12 weeks. Myo-inositol supplementation, compared with metformin, significantly reduced fasting plasma glucose (FPG) (ß -5.12 mg/dL; 95% CI, -8.09, -2.16; p=.001), serum insulin levels (ß -1.49 µIU/mL; 95% CI, -2.28, -0.70; p<.001), homeostasis model of assessment-insulin resistance (ß -0.36; 95% CI, -0.55, -0.17; p<.001), serum triglycerides (ß 12.42 mg/dL; 95% CI, -20.47, -4.37; p=.003) and VLDL-cholesterol levels (ß -2.48 mg/dL; 95% CI, -4.09, -0.87; p=.003), and significantly increased the quantitative insulin sensitivity check index (ß 0.006; 95% CI, 0.002, 0.01; p=.006) compared with metformin. Moreover, myo-inositol supplementation upregulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (p=.002) compared with metformin. Overall, taking myo-inositol, compared with metformin, for 12 weeks by women with PCOS had beneficial effects on glycemic control, triglycerides and VLDL-cholesterol levels, and gene expression of PPAR-γ.

The influences of vitamin D and omega-3 co-supplementation on clinical, metabolic and genetic parameters in women with polycystic ovary syndrome.

OBJECTIVE: The aim of this study was to evaluate the effect of the co-administration of vitamin D and omega-3 fatty acid on clinical, metabolic and genetic parameters in women with polycystic ovary syndrome (PCOS). METHODS: This randomized, double-blinded, placebo-controlled clinical trial was conducted on 60 subjects, aged 18-40 years old with PCOS. Subjects were randomly allocated to take either 50,000 IU vitamin D every 2 weeks plus 2000 mg/day omega-3 fatty acid from fish oil (n = 30) or placebo (n = 30) for 12 weeks. Gene expression analysis of inflammatory cytokines was conducted on peripheral blood mononuclear cells (PBMCs) of PCOS women using RT-PCR method. RESULTS: Vitamin D and omega -3 fatty acid co-supplementation significantly decreased serum total testosterone levels (-0.2 ±â€¯0.5 vs. + 0.1 ±â€¯0.4 ng/mL, P = 0.02) compared with the placebo. In addition, vitamin D and omega-3 fatty acid co-supplementation resulted in a significant improvement in beck depression inventory (-1.4 ±â€¯1.6 vs. -0.5 ±â€¯0.6, P = 0.01), general health questionnaire scores (-4.5 ±â€¯4.3 vs. -1.9 ±â€¯2.3, P = 0.005) and depression anxiety and stress scale scores (-5.0 ±â€¯5.1 vs. -2.3 ±â€¯3.5, P = 0.01) compared with the placebo. Additionally, vitamin D and omega-3 fatty acid co-administration significantly decreased serum high-sensitivity C-reactive protein (hs-CRP) (-1.2 ±â€¯1.9 vs. + 0.1 ±â€¯0.7 mg/L, P = 0.001) and malondialdehyde (MDA) levels (-0.4 ±â€¯0.4 vs. + 0.2 ±â€¯0.6 µmol/L, P < 0.001), and significantly increased plasma total antioxidant capacity (TAC) levels (+ 114.6 ±â€¯122.2 vs. -2.4 ±â€¯168.2 mmol/L, P = 0.003) compared with the placebo. Results of RT-PCR demonstrated that vitamin D and omega-3 fatty acid co-supplementation significantly downregulated gene expression of interleukin-1 (IL-1) (P = 0.03), and upregulated vascular endothelial growth factor (VEGF) (P = 0.004) in PBMCs of subjects with PCOS, when compared with placebo. CONCLUSIONS: Overall, the co-administration of vitamin D and omega-3 fatty acid for 12 weeks had beneficial effects on mental health parameters, serum total testosterone, hs-CRP, plasma TAC and MDA levels, and gene expression of IL-1 and VEGF among women with PCOS.

A Randomized Double-Blinded, Placebo-Controlled Trial Investigating the Effect of Fish Oil Supplementation on Gene Expression Related to Insulin Action, Blood Lipids, and Inflammation in Gestational Diabetes Mellitus-Fish Oil Supplementation and Gestational Diabetes.

Gestational diabetes mellitus (GDM) is a common complication of pregnancy, and it is mostly associated with postpartum diabetes, insulin resistance, and dyslipidemia. Fish oil (omega-3) supplementation has been shown to reduce the risk of different chronic diseases such as cardiovascular disease, type 2 diabetes, and cancers, though the evidence of its impact on gestational diabetes is scarce. Our goal in this study was to determine the effect of fish oil administration on gene expression related to insulin action, blood lipids, and inflammation in women with GDM. Participants with GDM (n = 40), aged 18-40 years, were randomized to take either 1000 mg fish oil capsules, containing 180 mg eicosapentaenoic acid and 120 mg docosahexaenoic acid (n = 20), or placebo (n = 20) twice a day for 6 weeks. Gene expression related to insulin, lipids, and inflammation was quantified in peripheral blood mononuclear cells (PBMCs) of GDM women using Reverse Transcription Polymerase Chain Reaction (RT-PCR) method. Results of RT-PCR indicated that omega-3 supplementation upregulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (P = 0.04) in PBMCs of patients with GDM, compared with the placebo. In addition, gene expression of the low-density lipoprotein receptor (LDLR) (P < 0.001), interleukin-1 (IL-1) (P = 0.007), and tumor necrosis factor alpha (TNF-α) (P = 0.01) was downregulated in PBMCs of women with GDM, following omega-3 supplementation. No significant effect of omega-3 supplementation was indicated on gene expression of IL-8 in PBMCs of patients with GDM. Overall, fish oil supplementation for 6 weeks in women with GDM significantly improved gene expression of PPAR-γ, IL-1, and TNF-α, but not gene expression of IL-8.

The effects of omega-3 and vitamin E co-supplementation on parameters of mental health and gene expression related to insulin and inflammation in subjects with polycystic ovary syndrome.

OBJECTIVE: The aim of this study was to evaluate the effects of omega-3 and vitamin E co-supplementation on parameters of mental health and gene expression related to insulin and inflammation in subjects with polycystic ovary syndrome (PCOS). METHODS: Forty PCOS women were allocated into two groups and treated with 1000mg omega-3 fatty acids plus 400 IU vitamin E supplements (n = 20) or placebo (n = 20) per day for 12 weeks. Parameters of mental health were recorded at baseline and after the 12-week intervention. Gene expression related to insulin and inflammation were measured in blood samples of PCOS women. RESULTS: After the 12-week intervention, compared with the placebo, omega-3 and vitamin E co-supplementation led to significant improvements in beck depression inventory total score (- 2.2 ± 2.0 vs. - 0.2 ± 1.3, P = 0.001), general health questionnaire scores (- 5.5 ± 4.6 vs. - 1.0 ± 2.3, P < 0.001) and depression anxiety and stress scale scores (- 7.2 ± 5.2 vs. - 1.3 ± 1.3, P < 0.001). Compared with the placebo, omega-3 and vitamin E co-supplementation could up-regulate peroxisome proliferator-activated receptor gamma (PPAR-γ) expression (P = 0.04) in peripheral blood mononuclear cells (PBMC) of PCOS women. In addition, compared with the placebo, omega-3 and vitamin E co-supplementation down-regulated interleukin-8 (IL-8) (P = 0.003) and tumor necrosis factor alpha (TNF-α) expression (P = 0.001) in PBMC of PCOS women. There were no significant difference between-group changes in glucose transporter 1 (GLUT-1), IL-6 and transforming growth factor beta (TGF-ß) in PBMC of PCOS women. CONCLUSION: Omega-3 and vitamin E co-supplementation was effective in improving parameters of mental health, and gene expression of PPAR-γ, IL-8 and TNF-α of women with PCOS.

The Effects of Magnesium and Zinc Co-Supplementation on Biomarkers of Inflammation and Oxidative Stress, and Gene Expression Related to Inflammation in Polycystic Ovary Syndrome: a Randomized Controlled Clinical Trial.

Magnesium and zinc are known to exert multiple beneficial effects including anti-inflammatory and antioxidant actions. To our knowledge, data on the effects of magnesium and zinc co-supplementation on biomarkers of inflammation and oxidative stress and gene expression related to inflammation in subjects of polycystic ovary syndrome (PCOS) are scarce. This study was conducted to evaluate the effects of magnesium and zinc co-supplementation on biomarkers of inflammation and oxidative stress and gene expression related to inflammation in subjects with PCOS. This randomized double-blind, placebo-controlled trial was conducted among 60 subjects with PCOS diagnosed according to the Rotterdam criteria, aged 18-40 years old. Participants were randomly assigned into two groups to take either 250 mg of magnesium oxide plus 220 mg of zinc sulfate (containing 50 mg zinc) supplements (n = 30) or placebo (n = 30) twice a day for 12 weeks. Biomarkers of inflammation and oxidative stress were assessed at baseline and at end of treatment. Gene expression related to inflammatory cytokines was assessed in peripheral blood mononuclear cells (PBMCs) of PCOS women with RT-PCR method. After the 12-week intervention, compared with the placebo, magnesium and zinc co-supplementation significantly decreased serum high-sensitivity C-reactive protein (hs-CRP) (- 1.6 ± 2.4 vs. + 0.1 ± 0.7 mg/L, P = 0.001) and protein carbonyl (PCO) (- 0.14 ± 0.28 vs. + 0.02 ± 0.07 mmol/mg protein, P = 0.002) and significantly increased plasma total antioxidant capacity (TAC) levels (+ 60.7 ± 69.4 vs. - 1.5 ± 141.5 mmol/L, P = 0.03). Results of RT-PCR demonstrated that compared with the placebo, magnesium and zinc co-supplementation downregulated gene expression of interleukin-1 (IL-1) (P = 0.007) and tumor necrosis factor alpha (TNF-α) (P = 0.03) in PBMCs of subjects with PCOS. Overall, magnesium and zinc co-supplementation, compared with the placebo, for 12 weeks among PCOS women had beneficial effects on serum hs-CRP, plasma PCO, TAC, and gene expression of IL-1 and TNF-α. CLINICAL TRIAL REGISTRATION NUMBER: http://www.irct.ir : IRCT201706075623N121.

Effects of Selenium Supplementation on Gene Expression Levels of Inflammatory Cytokines and Vascular Endothelial Growth Factor in Patients with Gestational Diabetes.

Selenium is known to exert multiple beneficial effects including anti-inflammatory actions. The aim of the study was to evaluate the effects of selenium supplementation on gene expression levels of inflammatory cytokines and vascular endothelial growth factor (VEGF) in women with gestational diabetes (GDM). This randomized double-blind, placebo-controlled trial was carried out among 40 subjects diagnosed with GDM aged 18-40 years old. Subjects were randomly allocated into two groups to receive either 200 µg/day selenium supplements (n = 20) or placebo (n = 20) for 6 weeks. Gene expression of inflammatory cytokines and VEGF were assessed in lymphocytes of GDM women with RT-PCR method. Results of RT-PCR indicated that after the 6-week intervention, compared with the placebo, selenium supplementation downregulated gene expression of tumor necrosis factor alpha (TNF-α) (P = 0.02) and transforming growth factor beta (TGF-ß) (P = 0.01), and upregulated gene expression of VEGF (P = 0.03) in lymphocytes of patients with GDM. There was no statistically significant change following supplementation with selenium on gene expression of interleukin (IL)-1ß and IL-8 in lymphocytes of subjects with GDM. Selenium supplementation for 6 weeks in women with GDM significantly decreased gene expression of TNF-α and TGF-ß, and significantly increased gene expression of VEGF, but did not affect gene expression of IL-1ß and IL-8. Clinical trial registration number http://www.irct.ir : IRCT201612045623N95.

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.

INTRODUCTION: Data on comparison of myo-inositol and metformin on mental health parameters and biomarkers of oxidative stress in subjects with polycystic ovary syndrome (PCOS) are scarce. This purpose of this study was to compare of myo-inositol and metformin on mental health parameters and biomarkers of oxidative stress in subjects with PCOS. METHODS: This randomized controlled trial was conducted among 60 subjects diagnosed with PCOS according to the Rotterdam criteria. Subjects were randomly assigned into two groups to intake either myo-inositol (n = 30) or metformin (n = 30) for 12 weeks. Parameters of mental health were recorded at baseline and after the 12-week intervention. Fasting blood samples were obtained at baseline and the end of the study to determine biomarkers of biomarkers of 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 = 0.03), general health questionnaire scores (-1.7 ± 2.9 vs. -0.5 ± 1.2, p = 0.02), depression anxiety and stress scale scores (-3.9 ± 6.4 vs. -0.9 ± 1.9, p = 0.01) and plasma total antioxidant capacity (TAC) concentrations (+106.1 ± 69.6 vs. +2.1 ± 132.4 mmol/L, p < 0.001) in the myo-inositol group were significantly different from the changes in these indicators 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.

Comparison of myo-inositol and metformin on clinical, metabolic and genetic parameters in polycystic ovary syndrome: A randomized controlled clinical trial.

OBJECTIVE: To our knowledge, data on comparison of myo-inositol and metformin on clinical, metabolic and genetic parameters in subjects with polycystic ovary syndrome (PCOS) are limited. This study was carried out to compare myo-inositol and metformin on clinical, metabolic and genetic parameters in subjects with PCOS. DESIGN, PATIENTS AND MEASUREMENTS: This randomized controlled trial was conducted among 60 subjects with PCOS aged 18-40 years. Subjects were randomly allocated into two groups to receive either myo-inositol (N=30) or metformin (N=30) for 12 weeks. Gene expression of inflammatory cytokines was assessed in peripheral blood mononuclear cells (PBMCs) of PCOS women by RT-PCR. RESULTS: After the 12-week intervention, compared with metformin, myo-inositol intake significantly decreased serum total testosterone (-1.4±4.2 vs +0.7±1.4 nmol/L, P=.03), modified Ferriman-Gallwey (mF-G) scores (-1.1±0.7 vs -0.5±0.8, P=.01) and serum high-sensitivity C-reactive protein (hs-CRP) levels (-2.6±3.9 vs +0.2±1.5 mg/L, P<.001). RT-PCR demonstrated that compared with metformin, myo-inositol downregulated gene expression of interleukin-1 (IL-1) (P=.02) in PBMCs of subjects with PCOS. We did not observe any significant effect of myo-inositol intake compared with metformin on other hormonal profiles, plasma nitric oxide (NO) or gene expression of IL-8 and tumour necrosis factor alpha (TNF-α). CONCLUSIONS: Overall, taking myo-inositol, compared with metformin, for 12 weeks in patients with PCOS with hyperinsulinism and normoinsulinism had beneficial effects on total testosterone, mFG scores, serum hs-CRP levels and gene expression of IL-1, but did not affect other hormonal profiles, NO levels or gene expression of IL-8 and TNF-α.

Oral carnitine supplementation influences mental health parameters and biomarkers of oxidative stress in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Limited data are available assessing the effects of oral carnitine supplementation on mental health parameters and biomarkers of oxidative stress of women with polycystic ovary syndrome (PCOS).This study was designed to determine the effects of oral carnitine supplementation on mental health parameters and biomarkers of oxidative stress in women with PCOS. METHODS: In the current randomized, double-blind, placebo-controlled trial, 60 patients diagnosed with PCOS were randomized to take either 250 mg carnitine supplements (n = 30) or placebo (n = 30) for 12 weeks. RESULTS: After 12 weeks' intervention, compared with the placebo, carnitine supplementation resulted in a significant improvement in Beck Depression Inventory total score (-2.7 ± 2.3 versus -0.2 ± 0.7, p < 0.001), General Health Questionnaire scores (-6.9 ± 4.9 versus -0.9 ± 1.5, p < 0.001) and Depression Anxiety and Stress Scale scores (-8.7 ± 5.9 versus -1.2 ± 2.9, p = 0.001). In addition, changes in plasma total antioxidant capacity (TAC) (+84.1 ± 151.8 versus +4.6 ± 64.5 mmol/L, p = 0.01), malondialdehyde (MDA) (-0.4 ± 1.0 versus +0.5 ± 1.5 µmol/L, p = 0.01) and MDA/TAC ratio (-0.0005 ± 0.0010 versus +0.0006 ± 0.0019, p = 0.003) in the supplemented group were significantly different from the changes in these indicators in the placebo group. CONCLUSIONS: Overall, our study demonstrated that carnitine supplementation for 12 weeks among patients with PCOS had favorable effects on parameters of mental health and biomarkers of oxidative stress.

The effects of vitamin D and omega-3 fatty acids co-supplementation on biomarkers of inflammation, oxidative stress and pregnancy outcomes in patients with gestational diabetes.

BACKGROUND: This study was carried out to determine the effects of vitamin D and omega-3 fatty acids co- supplementation on biomarkers of inflammation, oxidative stress and pregnancy outcomes in gestational diabetes (GDM) patients. METHODS: This randomized, double-blind, placebo-controlled trial was conducted among 120 GDM women. Participants were randomly divided into four groups to receive: 1) 1000 mg omega-3 fatty acids containing 180 mg eicosapentaenoic acid (EPA) and 120 mg docosahexaenoic acid (DHA) twice a day + vitamin D placebo (n = 30); 2) 50,000 IU vitamin D every 2 weeks + omega-3 fatty acids placebo (n = 30); 3) 50,000 IU vitamin D every 2 weeks + 1000 mg omega-3 fatty acids twice a day (n = 30) and 4) vitamin D placebo + omega-3 fatty acids placebo (n = 30) for 6 weeks. RESULTS: Subjects who received vitamin D plus omega-3 fatty acids supplements compared with vitamin D, omega-3 fatty acids and placebo had significantly decreased high-sensitivity C-reactive protein (-2.0 ± 3.3 vs. -0.8 ± 4.4, -1.3 ± 2.4 and +0.9 ± 2.7 mg/L, respectively, P = 0.008), malondialdehyde (-0.5 ± 0.5 vs. -0.2 ± 0.5, -0.3 ± 0.9 and +0.5 ± 1.4 µmol/L, respectively, P < 0.001), and increased total antioxidant capacity (+92.1 ± 70.1 vs. +55.1 ± 123.6, +88.4 ± 95.2 and +1.0 ± 90.8 mmol/L, respectively, P = 0.001) and glutathione (+95.7 ± 86.7 vs. +23.0 ± 62.3, +30.0 ± 66.5 and -7.8 ± 126.5 µmol/L, respectively, P = 0.001). In addition, vitamin D and omega-3 fatty acids co-supplementation, compared with vitamin D, omega-3 fatty acids and placebo, resulted in lower incidences of newborns' hyperbilirubinemiain (P = 0.037) and newborns' hospitalization (P = 0.037). CONCLUSION: Overall, vitamin D and omega-3 fatty acids co-supplementation for 6 weeks among GDM women had beneficial effects on some biomarkers of inflammation, oxidative stress and pregnancy outcomes.