Effects of Zinc Supplementation on Inflammatory Status and Nonalcoholic Steatohepatitis in Overweight or Obese Children: a Randomized Clinical Trial.

The purpose of the present clinical trial was to determine the impact of zinc supplementation on serum liver enzymes, steatosis severity, lipid profile, and inflammatory status in overweight or obese children with nonalcoholic steatohepatitis (NASH). This randomized controlled trial was conducted by enrolling 60 children with NASH, aged 10-18 years old. The participants were randomly assigned to two groups that received either 30 mg/day of elemental zinc or placebo for 16 weeks. The severity of liver steatosis was evaluated using liver ultrasonography. Fasting blood samples were collected from each patient at the beginning and after 16 weeks of intervention to measure biochemical parameters. Following a 16-week intervention, zinc supplementation compared with placebo significantly decreased serum alanine aminotransferase (ALT) concentrations and high-sensitivity C-reactive protein and considerably enhanced HDL-cholesterol values. However, zinc intake had no considerable impact on aspartate aminotransferase, the severity of liver steatosis, anthropometric parameters, and other lipid indices versus the placebo group. Overall, zinc supplementation showed a promising impact on serum ALT, HDL-cholesterol, and inflammatory status in overweight or obese children suffering from NASH. Zinc supplementation may be a new strategy for the amelioration of NASH in overweight or obese children. This trial has been registered on the Iranian website for registration of clinical trials with the special ID of IRCT20200531047614N1 ( https://www.irct.ir/trial/48543 ).

Effects of Isoflavone Supplementation on the Response to Medroxyprogesterone in Premenopausal Women with Nonatypical Endometrial Hyperplasia: A Randomized, Double-Blind, Placebo-Controlled Trial.

Objective: The purpose of this study was to evaluate the impact of isoflavone supplementation compared with placebo on endometrial histology and serum estradiol levels in premenopausal women with nonatypical endometrial hyperplasia. Materials and Methods: The present double-blindplacebo-controlled clinical trial was conducted on 100 women with nonatypical endometrial hyperplasia in the age range of 30 to 45 years. Participants were randomly assigned to receive 50 mg of isoflavone (n = 50) or placebos (n = 50) daily for three months. Both groups received the standard treatment of nonatypical endometrial hyperplasia. Endometrial biopsy and blood samples were taken at the baseline and three months after the intervention. The incidence of drug side effects was assessed as well. Results: After three months, 88.4% of isoflavone-administered subjects had a significant histological improvement compared to 68.9% subjects in the placebo group (P=0.02). There were no significant differences between the two groups in the changes of serum estradiol levels and the incidence of drug side effects. Conclusion: The findings of the present study demonstrated that the coadministration of 50 mg of isoflavones and medroxyprogesterone acetate increases the treatment efficacy in women with nonatypical endometrial hyperplasia. Clinical Trial Registration. This trial was registered on the Iranian website for clinical trial registration (https://www.irct.ir/trial/53553).

Alpha-lipoic acid administration affects psychological status and markers of inflammation and oxidative damage in patients with type 2 diabetes and coronary heart disease.

Background: This investigation was performed to assess the effects of alpha-lipoic acid (ALA) supplementation on psychological status and markers of inflammation and oxidative damage in patients with type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). Methods: This randomized, double-blind, placebo-controlled trial was performed in 60 patients with T2DM and CHD, aged 45-85 years. Patients were randomized into two groups to receive either 600 mg/day ALA (n = 30) or placebo (n = 30) for 12 weeks. Results: ALA supplementation significantly decreased Beck Depression Inventory index (BDI) (-5.1 ± 3.5 vs. -1.1 ± 4.8, P = 0.001) when compared with the placebo. ALA supplementation resulted also in a significant reduction of serum high sensitivity C-reactive protein (hs-CRP) (-0.8 ± 1.4 vs. +0.5 ± 0.6 mg/L, P < 0.001) and malondialdehyde (MDA) (-0.3 ± 0.2 vs. -0.1 ± 0.3 µmol/L, P = 0.003), and a significant increase in plasma total antioxidant capacity (TAC) levels (+ 26.8 ± 36.0 vs. -4.6 ± 43.4 mmol/L, P = 0.007) when compared with the placebo. ALA intake upregulated transforming growth factor beta (TGF-ß) (P = 0.03) and downregulated gene expression of interleukin-1 (IL-1) (P = 0.001) in peripheral blood mononuclear cells of patients with T2DM and CHD as well. Conclusions: ALA supplementation for 12 weeks in patients with T2DM and CHD had beneficial effects on BDI, hs-CRP, TAC, MDA values, and gene expression of IL-1 and TGF-ß. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01031-1.

The Effects of Probiotic Supplementation on Clinical Symptom, Weight Loss, Glycemic Control, Lipid and Hormonal Profiles, Biomarkers of Inflammation, and Oxidative Stress in Women with Polycystic Ovary Syndrome: a Systematic Review and Meta-analysis of Randomized Controlled Trials.

The purpose of this systematic review and meta-analysis of randomized controlled trials (RCTs) is to determine the effectiveness of probiotic supplementation on clinical symptoms, weight loss, glycemic control, lipid and hormonal profiles, and biomarkers of inflammation and oxidative stress in women with polycystic ovary syndrome (PCOS). Eligible studies were systematically searched from Cochrane Library, Embase, Medline, and Web of Science databases until January 2019. Cochran (Q) and I-square statistics were used to measure heterogeneity among included studies. Data were pooled by using random-effect model and expressed as standardized mean difference (SMD) with 95% confidence interval (CI). Eleven articles were included in this meta-analysis. Probiotic supplementation significantly decreased weight (SMD - 0.30; 95% CI, - 0.53, - 0.07; P = 0.01), body mass index (BMI) (SMD - 0.29; 95% CI, - 0.54, - 0.03; P = 0.02), fasting plasma glucose (FPG) (SMD - 0.26; 95% CI, - 0.45, - 0.07; P < 0.001), insulin (SMD - 0.52; 95% CI, - 0.81, - 0.24; P < 0.001), homeostatic model assessment for insulin resistance (HOMA-IR) (SMD - 0.53; 95% CI, - 0.79, - 0.26; P < 0.001), triglycerides (SMD - 0.69; 95% CI, - 0.99, - 0.39; P < 0.001), VLDL-cholesterol (SMD - 0.69; 95% CI, - 0.99, - 0.39; P < 0.001), C-reactive protein (CRP) (SMD - 1.26; 95% CI, - 2.14, - 0.37; P < 0.001), malondialdehyde (MDA) (SMD - 0.90; 95% CI, - 1.16, - 0.63; P < 0.001), hirsutism (SMD - 0.58; 95% CI, - 1.01, - 0.16; P < 0.001), and total testosterone levels (SMD - 0.58; 95% CI, - 0.82, - 0.34; P < 0.001), and also increased the quantitative insulin sensitivity check index (QUICKI) (SMD 0.41; 95% CI, 0.11, 0.70; P < 0.01), nitric oxide (NO) (SMD 0.33; 95% CI 0.08, 0.59; P = 0.01), total antioxidant capacity (TAC) (SMD 0.64; 95% CI, 0.38, 0.90; P < 0.001), glutathione (GSH) (SMD 0.26; 95% CI, 0.01, 0.52; P = 0.04), and sex hormone binding globulin (SHBG) levels (SMD 0.46; 95% CI, 0.08, 0.85; P = 0.01). Probiotic supplementation may result in an improvement in weight, BMI, FPG, insulin, HOMA-IR, triglycerides, VLDL-cholesterol, CRP, MDA, hirsutism, total testosterone, QUICKI, NO, TAC, GSH, and SHBG but did not affect dehydroepiandrosterone sulfate levels, and total, LDL, and HDL cholesterol levels in patients with PCOS.

Melatonin supplementation and the effects on clinical and metabolic status in Parkinson's disease: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: This study was performed to evaluate the impact of melatonin supplementation on clinical and metabolic profiles in people with Parkinson's disease (PD). METHODS: This randomized, double-blind, placebo-controlled clinical trial was conducted among 60 patients with PD. Participants were randomly divided into two groups to intake either 10 mg melatonin (two melatonin capsules, 5 mg each) (n = 30) or placebo (n = 30) once a day, 1 h before bedtime for 12 weeks. RESULTS: Melatonin supplementation significantly reduced the Unified Parkinson's Disease Rating Scale (UPDRS) part I score (ß -2.33; 95% CI, -3.57, -1.09; P < 0.001), Pittsburgh Sleep Quality Index (PSQI) (ß -1.82; 95% CI, -3.36, -0.27; P = 0.02), Beck Depression Inventory (BDI) (ß -3.32; 95% CI, -5.23, -1.41; P = 0.001) and Beck Anxiety Inventory (BAI) (ß -2.22; 95% CI, -3.84, -0.60; P = 0.008) compared with the placebo treatment. Compared with the placebo, melatonin supplementation resulted in a significant reduction in serum high sensitivity C-reactive protein (hs-CRP) (ß -0.94 mg/L; 95% CI, -1.55, -0.32; P = 0.003) and a significant elevation in plasma total antioxidant capacity (TAC) (ß 108.09 mmol/L; 95% CI, 78.21, 137.97; P < 0.001) and total glutathione (GSH) levels (ß 77.08 µmol/L; 95% CI, 44.29, 109.86; P < 0.001). Additionally, consuming melatonin significantly decreased serum insulin levels (ß -1.79 µIU/mL; 95% CI, -3.12, -0.46; P = 0.009), homeostasis model of assessment-insulin resistance (HOMA-IR) (ß -0.47; 95% CI, -0.80, -0.13; P = 0.007), total- (ß -13.16 mg/dL; 95% CI, -25.14, -1.17; P = 0.03) and LDL- (ß -10.44 mg/dL; 95% CI, -20.55, -0.34; P = 0.04) compared with the placebo. CONCLUSIONS: Overall, melatonin supplementation for 12 weeks to patients with PD had favorable effects on the UPDRS part I score, PSQI, BDI, BAI, hs-CRP, TAC, GSH, insulin levels, HOMA-IR, total-, LDL-cholesterol, and gene expression of TNF-α, PPAR-γ and LDLR, but did not affect other metabolic profiles.

Correction: The effects of melatonin supplementation on blood pressure in patients with metabolic disorders: a systematic review and meta-analysis of randomized controlled trials.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The Effects of Melatonin Supplementation on Parameters of Mental Health, Glycemic Control, Markers of Cardiometabolic Risk, and Oxidative Stress in Diabetic Hemodialysis Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: This study evaluated the effects of melatonin supplementation on parameters of mental health, glycemic control, markers of cardiometabolic risk, and oxidative stress in diabetic hemodialysis (HD) patients. DESIGN: A randomized, double-blind, placebo-controlled clinical trial was conducted in 60 diabetic HD patients, 18-80 years of age. Participants were randomly divided into 2 groups to take either melatonin (2 x 5mg/day) (n = 30) or placebo (n = 30) 1 hour before bedtime for 12 weeks. The effects of melatonin on mental health, metabolic status, and gene expression related to metabolic status were assessed using multiple linear regression adjusting for age and BMI. RESULTS: Melatonin supplementation significantly decreased Pittsburgh Sleep Quality Index (P = .007), Beck Depression Inventory index (P = .001), and Beck Anxiety Inventory index (P = .01) compared with the placebo. Additionally, melatonin administration significantly reduced fasting plasma glucose (ß = -21.77 mg/dL, 95% CI -33.22 to -10.33, P < .001), serum insulin levels (ß = -1.89 µIU/mL, 95% CI -3.34 to -0.45, P = .01), and homeostasis model of assessment-insulin resistance (ß = -1.45, 95% CI -2.10 to -0.80, P < .001), and significantly increased the quantitative insulin sensitivity check index (ß = 0.01, 95% CI 0.007-0.02, P < .001) compared with placebo treated subjects. In addition, melatonin administration resulted in a significant reduction in serum high sensitivity C-reactive protein (ß = -1.92 mg/L, 95% CI -3.02 to -0.83, P = .001) and plasma malondialdehyde (ß = -0.21 µmol/L, 95% CI -0.36 to -0.06, P = .005); also, significant rises in plasma total antioxidant capacity (ß = 253.87 mmol/L, 95% CI 189.18-318.56, P < .001) and nitric oxide levels (ß = 2.99 µmol/L, 95% CI 0.71-5.28, P = .01) were observed compared with the placebo. CONCLUSION: Overall, melatonin supplementation for 12 weeks to diabetic HD patients had beneficial effects on mental health, glycemic control, inflammatory markers, and oxidative stress.

Effects of Carnitine Administration on Carotid Intima-media Thickness and Inflammatory Factors in Patients with Polycystic Ovary Syndrome: A Randomized, Double-blind, Placebo-controlled Trial.

BACKGROUND: This study was performed to evaluate the effects of carnitine administration on carotid intima-media thickness (CIMT) and inflammatory markers in women with polycystic ovary syndrome (PCOS). METHODS: This randomized, double-blind, placebo-controlled trial was conducted among 60 women diagnosed with PCOS according to the Rotterdam criteria, aged 18-40 years. Participants were randomly allocated into two groups to intake either 250 mg/day carnitine (n = 30) or placebo (n = 30) for 12 weeks. High-resolution carotid ultrasonography was conducted at baseline and after the 12-week intervention. RESULTS: After the 12-week intervention, compared with the placebo, carnitine supplementation resulted in a significant decrease in maximum levels of the left CIMT (-0.01 ± 0.02 vs. +0.002 mm ± 0.006 mm, P = 0.001), mean levels of the left CIMT (-0.01 ± 0.02 vs. +0.001 mm ± 0.01 mm, P = 0.001), maximum levels of the right CIMT (-0.01 ± 0.02 vs. +0.006 mm ± 0.01 mm, P < 0.001), and mean levels of the right CIMT (-0.01 ± 0.02 vs. +0.002 mm ± 0.01 mm, P = 0.001). Change in plasma nitric oxide (NO) (+2.4 ± 3.6 vs. +0.2 ± 2.3 µmol/L, P = 0.007) was significantly different between the supplemented patients and placebo group. We did not see any significant effect in serum high sensitivity C-reactive protein (hs-CRP) following the supplementation of carnitine compared with the placebo. CONCLUSIONS: Overall, carnitine administration for 12 weeks to participants with PCOS had beneficial effects on CIMT and plasma NO, but did not affect serum hs-CRP levels.

Long-term vitamin D and high-dose n-3 fatty acids' supplementation improve markers of cardiometabolic risk in type 2 diabetic patients with CHD.

This study was performed to evaluate the effects of vitamin D and n-3 fatty acids' co-supplementation on markers of cardiometabolic risk in diabetic patients with CHD. This randomised, double-blinded, placebo-controlled trial was conducted among sixty-one vitamin D-deficient diabetic patients with CHD. At baseline, the range of serum 25-hydroxyvitamin D levels in study participants was 6·3-19·9 ng/ml. Subjects were randomly assigned into two groups either taking 50 000 IU vitamin D supplements every 2 weeks plus 2× 1000 mg/d n-3 fatty acids from flaxseed oil (n 30) or placebo (n 31) for 6 months. Vitamin D and n-3 fatty acids' co-supplementation significantly reduced mean (P = 0·01) and maximum levels of left carotid intima-media thickness (CIMT) (P = 0·004), and mean (P = 0·02) and maximum levels of right CIMT (P = 0·003) compared with the placebo. In addition, co-supplementation led to a significant reduction in fasting plasma glucose (ß -0·40 mmol/l; 95 % CI -0·77, -0·03; P = 0·03), insulin (ß -1·66 µIU/ml; 95 % CI -2·43, -0·89; P < 0·001), insulin resistance (ß -0·49; 95 % CI -0·72, -0·25; P < 0·001) and LDL-cholesterol (ß -0·21 mmol/l; 95 % CI -0·41, -0·01; P = 0·04), and a significant increase in insulin sensitivity (ß +0·008; 95 % CI 0·004, 0·01; P = 0·001) and HDL-cholesterol (ß +0·09 mmol/l; 95 % CI 0·01, 0·17; P = 0·02) compared with the placebo. Additionally, high-sensitivity C-reactive protein (ß -1·56 mg/l; 95 % CI -2·65, -0·48; P = 0·005) was reduced in the supplemented group compared with the placebo group. Overall, vitamin D and n-3 fatty acids' co-supplementation had beneficial effects on markers of cardiometabolic risk.

The effects of vitamin D treatment on glycemic control, serum lipid profiles, and C-reactive protein in patients with chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Insulin resistance, dyslipidemia and increased systemic inflammation are important risk factors for chronic kidney disease (CKD). Hence, vitamin D administration might be an appropriate approach to decrease the complications of CKD. Randomized controlled trials assessing the effects of vitamin D supplementation or treatment on glycemic control, lipid profiles, and C-reactive protein (CRP) among patients with CKD were included. METHODS: Two independent authors systematically searched online databases including EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science in November 2018 with no time restriction. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of included trials. Between-study heterogeneity was estimated using the Cochran's Q test and I-square (I2) statistic. Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size. RESULTS: Of the 1358 citations identified from searches, 17 full-text articles were reviewed. Pooling findings from five studies revealed a significant reduction in fasting glucose (WMD: - 18.87; 95% CI: - 23.16, - 14.58) and in homeostatic model assessment of insulin resistance (HOMA-IR) through three studies (WMD: - 2.30; 95% CI: - 2.88, - 1.72) following the administration of vitamin D. In addition, pooled analysis revealed a significant reduction in triglycerides (WMD: - 32.52; 95% CI: - 57.57, - 7.47) through six studies and in cholesterol concentrations (WMD: - 7.93; 95% CI: - 13.03, - 2.83) through five studies, following vitamin D supplementation or treatment, while there was no effect on insulin, HbA1c, LDL and HDL cholesterol, and CRP levels. CONCLUSIONS: This meta-analysis demonstrated the beneficial effects of vitamin D supplementation or treatment on improving fasting glucose, HOMA-IR, triglycerides and cholesterol levels among patients with CKD, though it did not influence insulin, HbA1c, LDL and HDL cholesterol, and CRP levels.

Effects of Melatonin Supplementation on Hormonal, Inflammatory, Genetic, and Oxidative Stress Parameters in Women With Polycystic Ovary Syndrome.

Purpose: The aim of the current study was to evaluate the effect of melatonin administration on clinical, hormonal, inflammatory, and genetic parameters in women with polycystic ovarian syndrome (PCOS). Methods: The present randomized, double-blinded, placebo-controlled clinical trial was conducted among 56 patients with PCOS, aged 18-40 years old. Subjects were randomly allocated to take either 5 mg melatonin supplements (n = 28) or placebo (n = 28) twice a day for 12 weeks. Results: Melatonin administration significantly reduced hirsutism (ß -0.47; 95% CI, -0.86, -0.09; P = 0.01), serum total testosterone (ß -0.11 ng/mL; 95% CI, -0.21, -0.02; P = 0.01), high-sensitivity C-reactive protein (hs-CRP) (ß -0.61 mg/L; 95% CI, -0.95, -0.26; P = 0.001), and plasma malondialdehyde (MDA) levels (ß -0.25 µmol/L; 95% CI, -0.38, -0.11; P < 0.001), and significantly increased plasma total antioxidant capacity (TAC) levels (ß 106.07 mmol/L; 95% CI, 62.87, 149.28; P < 0.001) and total glutathione (GSH) (ß 81.05 µmol/L; 95% CI, 36.08, 126.03; P = 0.001) compared with the placebo. Moreover, melatonin supplementation downregulated gene expression of interleukin-1 (IL-1) (P = 0.03) and tumor necrosis factor alpha (TNF-α) (P = 0.01) compared with the placebo. Conclusions: Overall, melatonin administration for 12 weeks to women with PCOS significantly reduced hirsutism, total testosterone, hs-CRP, and MDA, while increasing TAC and GSH levels. In addition, melatonin administration reduced gene expression of IL-1 and TNF-α. Clinical Trial Registration: www.irct.ir, identifier IRCT2017082733941N9, Available online at: https://www.irct.ir/trial/26051.

The Effects of Vitamin D Supplementation on Glycemic Control, Lipid Profiles and C-Reactive Protein Among Patients with Cardiovascular Disease: a Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Insulin resistance, dyslipidemia and chronic inflammation are important risk factors for cardiovascular diseases (CVD). Hence, vitamin D supplementation might be an appropriate approach to decrease the complications of CVD. This systematic review and meta-analysis aimed to determine the effects of vitamin D supplementation on glycemic control, lipid profiles, and C-reactive protein among patients with coronary artery disease. METHODS: Two independent authors systematically searched online databases including EMBASE, Scopus, Pub- Med, Cochrane Library, and Web of Science until 20th September 2018. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of included trials. The heterogeneity among the included studies was assessed using Cochran's Q test and I-square (I2) statistic. Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size. RESULTS: A total of eight trials (305 participants in the intervention group and 325 in placebo group) were included in the current meta-analysis. Pooling effect sizes from studies revealed a significant reduction in fasting glucose (WMD): -15.67; 95% CI: -29.32, -2.03), insulin concentrations (WMD: -3.53; 95% CI: -4.59, -2.46) and homeostatic model assessment of insulin resistance (WMD: -1.07; 95% CI: -1.49, -0.66), and significant increase in the quantitative insulin-sensitivity check index (WMD: 0.02; 95% CI: 0.01, 0.03) following the administration of vitamin D. In addition, pooled analysis revealed a significant increase in serum HDL-cholesterol concentrations following vitamin D therapy (WMD: 3.08; 95% CI: 1.42, 4.73). Additionally, vitamin D supplementation significantly reduced C-reactive protein (CRP) levels (WMD: -0.75; 95% CI: -1.28, -0.23). CONCLUSION: This meta-analysis demonstrated the beneficial effects of vitamin D supplementation on improving glycemic control, HDL-cholesterol and CRP levels among patients with CVD, though it did not affect triglycerides, total- and LDL-cholesterol levels.

Effects of melatonin administration on mental health parameters, metabolic and genetic profiles in women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: The aim of this study was to evaluate the effect of melatonin supplementation on mental health parameters, metabolic and genetic parameters in women suffering from polycystic ovary syndrome (PCOS). METHODS: This randomized, double-blinded, placebo-controlled clinical trial was performed on 58 subjects, aged 18-40 years old. Subjects were randomly allocated to take either 10 mg melatonin (2 melatonin capsules, 5 mg each) (n = 29) or placebo (n = 29) once a day 1 h before bedtime for 12 weeks. Glycemic control and lipid profiles were measured at baseline and after the 12-week intervention. Using RT-PCR method, gene expression related to insulin and lipid metabolism was conducted on peripheral blood mononuclear cells (PBMCs) of PCOS women. RESULTS: Melatonin supplementation significantly decreased Pittsburgh Sleep Quality Index (ß -2.15; 95% CI, -3.62, -0.68; P = 0.005), Beck Depression Inventory index (ß -3.62; 95% CI, -5.53, -1.78; P<0.001) and Beck Anxiety Inventory index (ß -1.95; 95% CI, -3.41, -0.48; P = 0.01) compared with the placebo. In addition, melatonin administration, compared with the placebo, significantly reduced serum insulin (ß -1.20 µIU/mL; 95% CI, -2.14, -0.26; P = 0.01), homeostasis model of assessment-insulin resistance (HOMA-IR) (ß -0.28; 95% CI, -0.50, -0.05; P = 0.01), serum total- (ß -7.96 mg/dL; 95% CI, -13.75, -2.17; P = 0.008) and LDL-cholesterol levels (ß -5.88 mg/dL; 95% CI, -11.42, -0.33; P = 0.03), and significantly increased the quantitative insulin sensitivity check index (QUICKI) (ß 0.008; 95% CI, 0.002, 0.014; P = 0.007). Moreover, melatonin supplementation upregulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (P = 0.004) and low-density lipoprotein receptor (LDLR) (P = 0.01) compared with the placebo. CONCLUSIONS: Overall, melatonin administration for 12 weeks had beneficial effects on mental health parameters, insulin levels, HOMA-IR, QUICKI, total- and LDL-cholesterol levels, and gene expression of PPAR-γ and LDLR among women with PCOS.

Effects of quercetin supplementation on glycemic control among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials.

This systematic review and meta-analysis of randomized controlled trials was performed to determine the effect of quercetin supplementation on glycemic control among patients with metabolic syndrome and related disorders. Databases including PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials were searched until August 30, 2018. Nine studies with 10 effect sizes out of 357 selected reports were identified eligible to be included in current meta-analysis. The pooled findings indicated that quercetin supplementation did not affect fasting plasma glucose (FPG), homeostasis model of assessment-estimated insulin resistance, and hemoglobin A1c levels. In subgroup analysis, quercetin supplementation significantly reduced FPG in studies with a duration of ≥8 weeks (weighted mean difference [WMD]: -0.94; 95% confidence interval [CI; -1.81, -0.07]) and used quercetin in dosages of ≥500 mg/day (WMD: -1.08; 95% CI [-2.08, -0.07]). In addition, subgroup analysis revealed a significant reduction in insulin concentrations following supplementation with quercetin in studies that enrolled individuals aged <45 years (WMD: -1.36; 95% CI [-1.76, -0.97]) and that used quercetin in dosages of ≥500 mg/day (WMD: -1.57; 95% CI [-1.98, -1.16]). In summary, subgroup analysis based on duration of ≥8 weeks and used quercetin in dosages of ≥500 mg/day significantly reduced FPG levels.

The effects of melatonin supplementation on blood pressure in patients with metabolic disorders: a systematic review and meta-analysis of randomized controlled trials.

The current systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the potential effect of melatonin supplementation on blood pressure in patients with metabolic disorders. The following databases were searched until June 2018: PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. Two reviewers independently assessed the eligibility of retrieved studies, extracted data from included trials, and evaluated the risk of bias of included studies. Statistical heterogeneity was tested using Cochran's Q test and I-square (I2) statistic. Data were pooled using random-effect models and standardized mean difference (SMD) was considered as the effect size. Eight RCTs, out of 743 potential citations, were eligible to be included in the current meta-analysis. The pooled findings indicated a significant reduction in systolic (SBP) (SMD = -0.87; 95% CI, -1.36, -0.38; P = 0.001; I2: 84.3) and diastolic blood pressure (DBP) (SMD = -0.85; 95% CI, -1.20, -0.51; P = 0.001; I2: 68.7) following melatonin supplementation in individuals with metabolic disorders. In summary, the current meta-analysis demonstrated that melatonin supplementation significantly decreased SBP and DBP in patients with metabolic disorders. Additional prospective studies are recommended using higher supplementation doses and longer intervention periods to confirm our findings.

Vitamin D and probiotic co-supplementation affects mental health, hormonal, inflammatory and oxidative stress parameters in women with polycystic ovary syndrome.

OBJECTIVE: The aim of this study was to determine the effect of vitamin D and probiotic co-administration on mental health, hormonal, inflammatory and oxidative stress parameters in women with polycystic ovary syndrome (PCOS). METHODS: This randomized, double-blinded, placebo-controlled clinical trial was carried out on 60 subjects, aged 18-40 years old. Subjects were randomly allocated to take either 50,000 IU vitamin D every 2 weeks plus 8 × 109 CFU/day probiotic (n = 30) or placebo (n = 30) for 12 weeks. RESULTS: Vitamin D and probiotic co-supplementation, compared with the placebo, significantly improved beck depression inventory [ß (difference in the mean of outcomes measures between treatment groups) - 0.58; 95% CI, - 1.15, - 0.02; P = 0.04], general health questionnaire scores (ß - 0.93; 95% CI, - 1.78, - 0.08; P = 0.03) and depression, anxiety and stress scale scores (ß - 0.90; 95% CI, - 1.67, - 0.13; P = 0.02). Vitamin D and probiotic co-supplementation was associated with a significant reduction in total testosterone (ß - 0.19 ng/mL; 95% CI, - 0.28, - 0.10; P < 0.001), hirsutism (ß - 0.95; 95% CI, - 1.39, - 0.51; P < 0.001), high-sensitivity C-reactive protein (hs-CRP) (ß - 0.67 mg/L; 95% CI, - 0.97, - 0.38; P < 0.001) and malondialdehyde (MDA) levels (ß - 0.25 µmol/L; 95% CI, - 0.40, - 0.10; P = 0.001), and a significant increase in total antioxidant capacity (TAC) (ß 82.81 mmol/L; 95% CI, 42.86, 122.75; P < 0.001) and total glutathione (GSH) levels (ß 40.42 µmol/L; 95% CI, 4.69, 76.19; P = 0.02), compared with the placebo. CONCLUSIONS: Overall, the co-administration of vitamin D and probiotic for 12 weeks to women with PCOS had beneficial effects on mental health parameters, serum total testosterone, hirsutism, hs-CRP, plasma TAC, GSH and MDA levels. TRIAL REGISTRATION: This study was retrospectively registered in the Iranian website ( www.irct.ir ) for registration of clinical trials ( IRCT20170513033941N37 ).

The Effects of Synbiotic Supplementation on Metabolic Status in Diabetic Patients Undergoing Hemodialysis: a Randomized, Double-Blinded, Placebo-Controlled Trial.

This study was conducted to evaluate the effects of synbiotic supplementation on metabolic profiles in diabetic patients undergoing hemodialysis (HD). This randomized, double-blinded, placebo-controlled clinical trial was performed in 60 diabetic HD patients. Participants were randomly assigned into two groups to receive either synbiotic capsule, containing Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium bifidum (2 × 109 CFU/g each), plus 0.8 g/day of inulin (n = 30) or placebo (n = 30) for 12 weeks. Synbiotic supplementation significantly decreased fasting plasma glucose (ß - 13.56 mg/dL; 95% CI, - 23.82, - 3.30; P = 0.01), insulin levels (ß - 5.49 µIU/mL; 95% CI, - 6.92, - 4.05; P < 0.001), and insulin resistance (ß - 2.25; 95% CI, - 3.02, - 1.48; P < 0.001), while increased the quantitative insulin sensitivity check index (ß 0.02; 95% CI, 0.01, 0.02; P < 0.001) compared with the placebo. Additionally, synbiotic intake resulted in a significant reduction in high-sensitivity C-reactive protein (ß - 2930.48 ng/mL; 95% CI, - 3741.15, - 2119.80; P < 0.001) and malondialdehyde levels (ß - 0.60 µmol/L; 95% CI, - 0.99, - 0.20; P = 0.003). Moreover, we found a significant increase in total antioxidant capacity (ß 142.99 mmol/L; 95% CI, 61.72, 224.25; P = 0.001) and total glutathione levels (ß 131.11 µmol/L; 95% CI, 89.35, 172.87; P < 0.001) in the synbiotic group compared with the placebo group. Overall, synbiotic supplementation for 12 weeks had beneficial effects on glycemic control, biomarkers of inflammation, and oxidative stress in diabetic patients under HD. This study was registered in the Iranian website (www.irct.ir) for registration of clinical trials (http://www.irct.ir: IRCT2017090133941N17). http://www.irct.ir: IRCT2017090133941N17.