The Protective Effects of Securigera securidaca Seed Extract on Liver Injury Induced by Bile Duct Ligation in Rats.

This study is aimed at evaluating the effects of Securigera securidaca (SS) seed extract on cholestatic liver injury induced by bile duct ligation (BDL) in rats. Total polyphenols and flavonoids in SS seed extract were determined using a colorimetric assay, and their components were quantified using HPLC. Rats in four groups underwent BDL at the common bile duct and were treated for 21 days with either oral distilled water as vehicle, vitamin C, 100 mg/kg SS seed extract, or 200 mg/kg SS seed extract. Rats in the fifth group underwent abdominal incision without BDL and were treated with distilled water, and rats in the sixth group were healthy and received nothing. Finally, rats were sacrificed, blood samples were analyzed through biochemical methods, liver tissues were histologically assessed, and the expression of the TGFß-1, iNOS, caspase-3, and α-SMA genes in the liver was assessed through real-time PCR. BDL significantly increased, and SS seed extract significantly decreased the serum levels of bilirubin and liver function enzymes. Moreover, SS seed extract suppressed the expression of the TGFß-1, iNOS, caspase-3, and α-SMA genes, reduced the levels of nitric oxide, malondialdehyde, and protein carbonyl, and increased the levels of glutathione, total antioxidant capacity, and SOD and catalase enzyme activity in the serum and liver. Extract at a dose of 100 mg/kg had significant positive effects on liver morphology and parenchyma structure in a dose-dependent manner.

Anti-inflammatory and antioxidative effects of thiamin supplements in patients with gestational diabetes mellitus.

OBJECTIVE: The aim of this study was to evaluate the effects of thiamin supplementation on biomarkers of inflammation and oxidative stress in patients with gestational diabetes mellitus (GDM). METHODS: This randomized, double-blind, placebo-controlled trial was conducted among 60 patients with GDM. Patients were randomly allocated into two groups to receive either 100 mg/day thiamin supplements (n = 30) or placebo (n = 30) for 6 weeks. RESULTS: Thiamin supplementation significantly decreased serum high-sensitivity C-reactive protein (hs-CRP) (ß - 0.98 mg/L; 95% CI, -1.54, -0.42; p = .001) and plasma malondialdehyde (MDA) levels (ß - 0.86 µmol/L; 95% CI, -1.15, -0.57; p < .001) when compared with the placebo. In addition, thiamin supplementation downregulated gene expression of tumor necrosis factor-alpha (TNF-α) (p = .002) in peripheral blood mononuclear cells of patients with GDM. Thiamin supplementation did not affect other biomarkers of inflammation and oxidative stress. CONCLUSION: Overall, thiamin supplementation for 6 weeks to patients with GDM significantly reduced hs-CRP and MDA levels, and gene expression of TNF-α, but did not affect other biomarkers of inflammation and oxidative stress. CLINICAL TRIAL REGISTRATION NUMBER: Clinical Trials.govIdentifier no. http://www.irct.ir: IRCT20170513033941N58.

Metabolic and Anti-inflammatory Response to Melatonin Administration in Patients with Diabetic Nephropathy.

INTRODUCTION: Data on the effects of melatonin administration on metabolic parameters in patients with diabetic nephropathy (DN) is limited and controversial. This study was performed to analyze the effects of melatonin administration on metabolic status in patients with DN. METHODS: This randomized, double blind, placebo-controlled clinical trial was performed on 60 patients with DN. Patients were randomly assigned into two groups to take either 10 mg/d of melatonin (n = 30) or placebo (n = 30) for 12 weeks. Fasting blood samples were taken at baseline and 12 weeks after intervention to quantify metabolic parameters. RESULTS: Melatonin administration significantly reduced plasma fasting glucose (ß = -10.64 mg/dL; 95% CI: -20.37 to -0.90; P < .05), insulin (ß = -2.37 µIU/mL, 95% CI: -3.33 to -1.41; P < .001), insulin resistance (ß = -0.67, 95% CI: -0.98 to -0.35; P < .001), significantly increased insulin sensitivity (ß = 0.01, 95% CI: 0.006 to 0.01; P < .05), and plasma HDL-cholesterol levels (ß = 2.75 mg/dL, 95% CI: 0.75 to 4.75; P < .05) when compared with the placebo. Melatonin also caused a significant increase in total antioxidant capacity (TAC) (ß = 140.45 mmol/L; 95% CI: 80.48 to 200.41; P < .001), and glutathione (GSH) levels (ß = 50.36 µmol/L, 95% CI: 94.08 to 0.02; P < .05) when compared with placebo. Ultimately, melatonin could upregulate gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (P < .05) in comparison with placebo. CONCLUSION: Results of this study indicated that melatonin administration for 12 weeks in DN patients had beneficial effects on glycemic control, HDL-cholesterol, TAC and GSH levels, and gene expression of PPAR-γ, but did not affect other metabolic parameters.

The Effects of Nano-curcumin on Metabolic Status in Patients With Diabetes on Hemodialysis, a Randomized, Double Blind, Placebo-controlled Trial.

INTRODUCTION: This study evaluated the effects of nano-curcumin intake on metabolic status in patients with diabetes on hemodialysis (HD). METHODS: This randomized, double-blind, placebo-controlled clinical trial was performed on 60 patients with diabetes on HD. Participants were randomly divided into two groups to take either 80 mg/d nano-curcumin (n = 30) or placebo (n = 30) for 12 weeks. RESULTS: Nano-curcumin significantly decreased fasting plasma glucose (ß = -19.68 mg/dL, 95% CI: -33.48 to -5.88; P < .05) and serum insulin levels (ß = -1.70 µIU/mL, 95% CI: -2.96 to -0.44; P < .05) when compared with patients who received placebo. Nanocurcumin treatment was associated with a significant reduction in triglycerides (ß = -16.13 mg/dL, 95% CI: -31.51 to -0.75; P < .05), VLDL-cholesterol (ß = -3.22 mg/dL, 95% CI: -6.30 to -0.15; P < .05), total cholesterol (ß = -17.83 mg/dL, 95% CI: -29.22 to -6.45; P < .05), LDL-cholesterol (ß = -15.20 mg/dL, 95% CI: -25.53 to -4.87; P < .05), and total-cholesterol/HDL-cholesterol ratio (ß = -1.15, 95% CI: -0.2.10 to -0.21; P < .05) when compared with the placebo. Nanocurcumin also resulted in a significant reduction of serum high sensitivity CRP (ß = -0.78 mg/L, 95% CI: -1.41 to -0.15; P < .05), and plasma malondialdehyde (ß = -0.25 µmol/L, 95% CI: -0.45 to -0.04; P < .05); but also with a significant increase in plasma total antioxidant capacity (ß = 52.43 mmol/L; 95% CI: 4.52 to 100.35; P < .05) and total nitrite levels (ß = 3.62 µmol/L, 95% CI: 2.17 to 5.08; P < .001) when compared with placebo. CONCLUSION: Nano-curcumin intake for 12 weeks had beneficial effects on metabolic profile in patients with diabetes on HD.

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.

The effects of n-3 fatty acids from flaxseed oil on genetic and metabolic profiles in patients with gestational diabetes mellitus: a randomised, double-blind, placebo-controlled trial.

The present study was performed to evaluate the effects of n-3 fatty acids from flaxseed oil on genetic and metabolic profiles in patients with gestational diabetes mellitus (GDM). This randomised, double-blind, placebo-controlled clinical trial was performed in sixty women with GDM. Participants were randomly divided into two groups to intake either 2 × 1000 mg/d n-3 fatty acids from flaxseed oil containing 400 mg α-linolenic acid in each capsule (n 30) or placebo (n 30) for 6 weeks. n-3 Fatty acid intake up-regulated PPAR-γ (P < 0·001) and LDL receptor (P = 0·004) and down-regulated gene expression of IL-1 (P = 0·002) and TNF-α (P = 0·001) in peripheral blood mononuclear cells of subjects with GDM. In addition, n-3 fatty acid supplementation reduced fasting plasma glucose (P = 0·001), insulin levels (P = 0·001) and insulin resistance (P < 0·001) and increased insulin sensitivity (P = 0·005) when compared with the placebo. Additionally, n-3 fatty acid supplementation was associated with a decrease in TAG (P < 0·001), VLDL-cholesterol (P < 0·001), total cholesterol (P = 0·01) and total cholesterol:HDL-cholesterol ratio (P = 0·01) when compared with placebo. n-3 Fatty acid administration was also associated with a significant reduction in high-sensitivity C-reactive protein (P = 0·006) and malondialdehyde (P < 0·001), and an increase in total nitrite (P < 0·001) and total glutathione levels (P = 0·006) when compared with the placebo. n-3 Fatty acid supplementation for 6 weeks to women with GDM had beneficial effects on gene expression related to insulin, lipid and inflammation, glycaemic control, lipids, inflammatory markers and oxidative stress.

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.

The Effects of Selenium Supplementation on Clinical Symptoms and Gene Expression Related to Inflammation and Vascular Endothelial Growth Factor in Infertile Women Candidate for In Vitro Fertilization.

This study was performed to determine the effects of selenium supplementation on clinical symptoms and gene expression related to inflammatory markers in infertile women with polycystic ovary syndrome (PCOS) who were candidate for in vitro fertilization (IVF). Thirty-six women candidate for IVF were recruited in this randomized double-blinded, placebo-controlled trial. They (n = 18/group) were randomly assigned into intervention groups to take either 200 µg/day of selenium or placebo for 8 weeks. RT-PCR findings indicated that selenium supplementation downregulated gene expression of interleukin-1 (IL-1) (P < 0.004) and tumor necrosis factor alpha (TNF-α) (P = 0.02) in lymphocytes of patients with PCOS compared with the placebo. In addition, selenium supplementation upregulated gene expression of vascular endothelial growth factor (VEGF) (P = 0.001) in lymphocytes of patients with PCOS compared with the placebo. Selenium supplementation had no significant effect on clinical symptoms and gene expression of IL-8 (P = 0.10) and transforming growth factor beta (TGF-ß) (P = 0.63). Overall, our findings documented that selenium supplementation for 8 weeks to infertile women candidate for IVF improved IL-1, TNF-α, and VEGF gene expression, though selenium had no effect on clinical symptoms and, IL-8 and TGF-ß gene expression. Clinical trial registration number: http://www.irct.ir: IRCT20170513033941N23.

Effects of Chromium and Carnitine Co-supplementation on Body Weight and Metabolic Profiles in Overweight and Obese Women with Polycystic Ovary Syndrome: a Randomized, Double-Blind, Placebo-Controlled Trial.

The primary aim of our study was to determine the influence of taking chromium plus carnitine on insulin resistance, with a secondary objective of evaluating the influences on lipid profiles and weight loss in overweight subjects with polycystic ovary syndrome (PCOS). In a 12-week randomized, double-blind, placebo-controlled clinical trial, 54 overweight women were randomly assigned to receive either supplements (200 µg/day chromium picolinate plus 1000 mg/day carnitine) or placebo (27/each group). Chromium and carnitine co-supplementation decreased weight (- 3.6 ± 1.8 vs. - 1.0 ± 0.7 kg, P < 0.001), BMI (- 1.3 ± 0.7 vs. - 0.3 ± 0.3 kg/m2, P < 0.001), fasting plasma glucose (FPG) (- 5.1 ± 6.0 vs. - 1.1 ± 4.9 mg/dL, P = 0.01), insulin (- 2.0 ± 1.4 vs. - 0.2 ± 1.2 µIU/mL, P < 0.001), insulin resistance (- 0.5 ± 0.4 vs. - 0.04 ± 0.3, P < 0.001), triglycerides (- 18.0 ± 25.2 vs. + 5.5 ± 14.4 mg/dL, P < 0.001), total (- 17.0 ± 20.3 vs. + 3.6 ± 12.0 mg/dL, P < 0.001), and LDL cholesterol (- 13.3 ± 19.2 vs. + 1.4 ± 13.3 mg/dL, P = 0.002), and elevated insulin sensitivity (+ 0.007 ± 0.005 vs. + 0.002 ± 0.005, P < 0.001). In addition, co-supplementation upregulated peroxisome proliferator-activated receptor gamma (P = 0.02) and low-density lipoprotein receptor expression (P = 0.02). Overall, chromium and carnitine co-supplementation for 12 weeks to overweight women with PCOS had beneficial effects on body weight, glycemic control, lipid profiles except HDL cholesterol levels, and gene expression of PPAR-γ and LDLR. Clinical trial registration number: http://www.irct.ir: IRCT20170513033941N38.

The effects of resveratrol on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease.

This study was performed to investigate the effects of resveratrol on metabolic status in patients with type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). This randomized, double-blind, placebo-controlled trial was performed with 56 patients having T2DM and CHD. The patients were randomly divided into two groups to receive either 500 mg resveratrol per day (n = 28) or placebo (n = 28) for 4 weeks. Resveratrol reduced fasting glucose (ß-10.04 mg dL-1; 95% CI, -18.23, -1.86; P = 0.01), insulin (ß-1.09 µIU mL-1; 95% CI, -1.93, -0.24; P = 0.01) and insulin resistance (ß-0.48; 95% CI, -0.76, -0.21; P = 0.001) and significantly increased insulin sensitivity (ß 0.006; 95% CI, 0.001, 0.01; P = 0.02) when compared with the placebo. Resveratrol also significantly increased HDL-cholesterol levels (ß 3.38 mg dL-1; 95% CI, 1.72, 5.05; P < 0.001) and significantly decreased the total-/HDL-cholesterol ratio (ß-0.36; 95% CI, -0.59, -0.13; P = 0.002) when compared with the placebo. Additionally, resveratrol caused a significant increase in total antioxidant capacity (TAC) (ß 58.88 mmol L-1; 95% CI, 17.33, 100.44; P = 0.006) and a significant reduction in malondialdehyde (MDA) levels (ß-0.21 µmol L-1; 95% CI, -0.41, -0.005; P = 0.04) when compared with the placebo. Resveratrol upregulated PPAR-γ (P = 0.01) and sirtuin 1 (SIRT1) (P = 0.01) in the peripheral blood mononuclear cells (PBMCs) of T2DM patients with CHD. Resveratrol supplementation did not have any effect on inflammatory markers. Four-week supplementation of resveratrol in patients with T2DM and CHD had beneficial effects on glycemic control, HDL-cholesterol levels, the total-/HDL-cholesterol ratio, TAC and MDA levels. Resveratrol also upregulated PPAR-γ and SIRT1 in the PBMCs of T2DM patients with CHD.

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.

Carnitine and chromium co-supplementation affects mental health, hormonal, inflammatory, genetic, and oxidative stress parameters in women with polycystic ovary syndrome.

OBJECTIVE: The aim of this study was to evaluate the effect of the co-administration of carnitine and chromium on mental health, hormonal, inflammatory and genetic parameters in women with PCOS. METHODS: This randomized, double-blinded, placebo-controlled clinical trial was conducted on 54 subjects, aged 18-40 years old. Subjects were randomly allocated to take either 1000 mg/d carnitine plus 200 µg/d chromium as chromium picolinate (n = 26) or placebo (n = 27) for 12 weeks. RESULTS: Carnitine and chromium co-supplementation, compared with the placebo, significantly improved beck depression inventory (ß - 0.84; 95% CI, -1.51, -0.17; p = 0.01), general health questionnaire scores (ß - 1.13; 95% CI, -2.13, -0.14; p = 0.02) and depression anxiety and stress scale scores (ß - 0.96; 95% CI, -0.78, -0.14; p = 0.02). Participants who received carnitine plus chromium supplements had significantly lower total testosterone (ß - 0.15 ng/mL; 95% CI, -0.24, -0.06; p = 0.002), hirsutism (ß - 0.48; 95% CI, -0.91, -0.06; p = 0.02), high-sensitivity C-reactive protein (hs-CRP) (ß - 1.02 mg/L; 95% CI, -1.79, -0.25; p = 0.01), and malondialdehyde (MDA) levels (ß - 0.38 µmol/L; 95% CI, -0.56, -0.20; p < 0.001), and higher total antioxidant capacity (TAC) levels (ß 107.18 mmol/L; 95% CI, 44.24, 170.12; p = 0.001) compared with the placebo. Moreover, carnitine and chromium co-supplementation upregulated gene expression of interleukin-6 (IL-6) (p = 0.02) and tumor necrosis factor alpha (TNF-α) (p = 0.02) compared with the placebo. CONCLUSION: Overall, the co-administration of carnitine and chromium for 12 weeks to women with PCOS had beneficial effects on mental health parameters, serum total testosterone, mF-G scores, hs-CRP, TAC and MDA levels, and gene expression of IL-6 and TNF-α.

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.

Probiotic and selenium co-supplementation, and the effects on clinical, metabolic and genetic status in Alzheimer's disease: A randomized, double-blind, controlled trial.

BACKGROUND AND AIMS: Combined probiotic and selenium supplementation may improve Alzheimer's disease (AD) by correcting metabolic abnormalities, and attenuating inflammation and oxidative stress. This study aimed to determine the effects of probiotic and selenium co-supplementation on cognitive function and metabolic status among patients with AD. METHODS: This randomized, double-blind, controlled clinical trial was conducted among 79 patients with AD. Patients were randomly assigned to receive either selenium (200 µg/day) plus probiotic containing Lactobacillus acidophilus, Bifidobacterium bifidum, and Bifidobacterium longum (2 × 109 CFU/day each) (n = 27), selenium (200 µg/day) (n = 26) or placebo (n = 26) for 12 weeks. RESULTS: Selenium supplementation, compared with the placebo, significantly reduced serum high sensitivity C-reactive protein (hs-CRP) (P < 0.001), insulin (P = 0.001), homeostasis model of assessment-insulin resistance (HOMA-IR) (P = 0.002), LDL-cholesterol (P = 0.04) and total-/HDL-cholesterol ratio (P = 0.004), and significantly increased total glutathione (GSH) (P = 0.001) and the quantitative insulin sensitivity check index (QUICKI) (P = 0.01). Compared with only selenium and placebo, probiotic and selenium co-supplementation resulted in a significant increase in mini-mental state examination score (+1.5 ± 1.3 vs. +0.5 ± 1.2 and -0.2 ± 1.1, respectively, P < 0.001). Probiotic plus selenium intake resulted in a significant reduction in hs-CRP (-1.6 ± 1.4 vs. -0.8 ± 1.0 and +0.1 ± 0.5 mg/L, respectively, P < 0.001), and a significant increase in total antioxidant capacity (+89.4 ± 129.6 vs. +20.0 ± 62.5 and -0.7 ± 27.2 mmol/L, respectively, P = 0.001) and GSH (+122.8 ± 136.5 vs. +102.2 ± 135.2 and +1.5 ± 53.2 µmol/L, respectively, P = 0.001) compared with only selenium and placebo. In addition, subjects who received probiotic plus selenium supplements had significantly lower insulin levels (-2.1 ± 2.5 vs. -1.0 ± 1.3 and +0.7 ± 2.0 µIU/mL, respectively, P < 0.001), HOMA-IR (-0.5 ± 0.6 vs. -0.2 ± 0.3 and +0.1 ± 0.4, respectively, P < 0.001), and higher QUICKI (+0.01 ± 0.01 vs. +0.005 ± 0.007 and -0.002 ± 0.01, respectively, P < 0.006) compared with only selenium and placebo. Additionally, probiotic and selenium co-supplementation resulted in a significant reduction in serum triglycerides (-17.9 ± 26.1 vs. -3.5 ± 33.9 and +0.3 ± 9.3 mg/dL, respectively, P = 0.02), VLDL- (-3.6 ± 5.2 vs. -0.7 ± 6.8 and +0.05 ± 1.8 mg/dL, respectively, P = 0.02), LDL- (-8.8 ± 17.8 vs. -8.1 ± 19.2 and +2.7 ± 19.0 mg/dL, respectively, P = 0.04) and total-/HDL-cholesterol (-0.3 ± 0.7 vs. -0.4 ± 0.9 and +0.3 ± 0.6, respectively, P = 0.005) compared with only selenium and placebo. CONCLUSIONS: Overall, we found that probiotic and selenium co-supplementation for 12 weeks to patients with AD improved cognitive function and some metabolic profiles. This study was registered in the Iranian website (www.irct.ir) for registration of clinical trials (http://www.irct.ir: IRCT20170612034497N5).

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 effects of vitamin E supplementation on endometrial thickness, and gene expression of vascular endothelial growth factor and inflammatory cytokines among women with implantation failure.

OBJECTIVE: Data on the effects of vitamin E supplementation on endometrial thickness, and gene expression of vascular endothelial growth factor (VEGF) and inflammatory cytokines among women with implantation failure are limited. This research was performed to determine the effects of vitamin E supplementation on endometrial thickness, and gene expression of VEGF and inflammatory cytokines among women with implantation failure. METHODS: A randomized clinical trial was done among 40 women with implantation failure aged 18-37 years old. Participants were randomly divided into two groups: group A (n = 20) received 400-IU vitamin E supplements and group B (n = 20) received placebo for 12 weeks. Fasting blood samples were taken at baseline and after the 12-week treatment to determine biomarkers of oxidative stress, and gene expression of VEGF and inflammatory cytokines. RESULTS: After the 12-week intervention, compared with the placebo, women with implantation failure who consumed vitamin E supplements had significantly increased serum vitamin E levels (+18.6 ± 15.0 versus -1.5 ± 1.0 nmol/mL, p < .001) and endometrial thickness (+1.1 ± 0.9 versus -0.5 ± 0.3 mm, p = .01), and significantly decreased plasma malondialdehyde (MDA) concentrations (-0.4 ± 0.3 versus +0.4 ± 0.3 µmol/L, p < .004). In addition, results of RT-PCR demonstrated that compared with the placebo, vitamin E intake downregulated gene expression of low-density lipoprotein receptor (LDLR) (p = .008), interleukin-1 (IL-1) (p = .02), and tumor necrosis factor alpha (TNF-α) (p = .007) in peripheral blood mononuclear cells of women with implantation failure. CONCLUSIONS: Overall, vitamin E supplementation for 12 weeks among women with implantation failure had beneficial effects on endometrial thickness, MDA values, and gene expression of LDLR, IL-1, and TNF-α.

The effects of melatonin supplementation on mental health, metabolic and genetic profiles in patients under methadone maintenance treatment.

This investigation was designed to determine the effect of melatonin supplementation on mental health parameters, metabolic and genetic profiles in patients under methadone maintenance treatment (MMT). This randomized, double-blind, placebo-controlled, clinical trial was conducted among 54 patients under MMT. Participants were randomly allocated to receive either 10 mg melatonin (2 melatonin capsules, 5 mg each) (n = 26) or placebo (n = 28) once a day, 1 hour before bedtime for 12 weeks. Melatonin supplementation significantly decreased Pittsburgh Sleep Quality Index (ß -4.08; 95 percent CI, -5.51, -2.65; P < 0.001), Beck Depression Inventory index (ß -5.46; 95% CI, -8.92, -2.00; P = 0.003) and Beck Anxiety Inventory index (ß -3.87; 95% CI, -5.96, -1.77; P = 0.001) and significantly increased International Index of Erectile Functions (ß 5.59; 95% CI, 1.76, 9.42; P = 0.005) compared with the placebo. Subjects who received melatonin supplements had significantly lower serum insulin levels (ß -2.53; 95% CI, -4.48, -0.59; P = 0.01), homeostasis model of assessment-insulin resistance (ß -0.56; 95% CI, -1.03, -0.09; P = 0.01) and higher quantitative insulin sensitivity check index (ß 0.01; 95% CI, 0.004, 0.02; P = 0.009) and HDL-cholesterol levels (ß 3.71; 95% CI, 1.77, 5.64; P = 0.002) compared to placebo. Additionally, melatonin intake resulted in a significant reduction in serum high sensitivity C-reactive protein (ß -0.15; 95% CI, -0.27, -0.02; P = 0.02), malondialdehyde (ß -0.31; 95% CI, -0.57, -0.05; P = 0.02) and protein carbonyl (ß -0.06; 95% CI, -0.09, -0.04; P < 0.001). This trial indicated that taking melatonin supplements for 12 weeks by patients under MMT had beneficial effects on their mental health metabolic profiles.

The effect of zinc and vitamin E cosupplementation on metabolic status and its related gene expression in patients with gestational diabetes.

Objective: The aim of this study was to determine the effects of zinc and vitamin E cosupplementation on metabolic status and gene expression related to insulin and lipid metabolism in women with gestational diabetes mellitus (GDM).Methods: Fifty-four women, in the age range of 18-40 years, diagnosed with GDM were recruited for this randomized, double-blinded, placebo-controlled trial. Subjects were randomly allocated into two intervention groups to either taking 233 mg/day Zinc Gluconate plus 400-IU/day vitamin E supplements or placebo (n = 27 each group) for 6 weeks. Gene expression related to insulin and lipid metabolism was evaluated in peripheral blood mononuclear cells (PBMCs) of women with GDM using RT-PCR method.Results: Participants who received zinc plus vitamin E supplements had significantly lower serum insulin levels (ß = -3.81; 95% CI, -5.90, -1.72; p = .001), homeostasis model of assessment-insulin resistance (ß = -0.96; 95% CI, -1.54, -0.38; p = .002), serum total-cholesterol (ß = -8.56; 95% CI, -16.69, -0.43; p = .03) and low density lipoprotein-cholesterol (LDL)-cholesterol (ß = -8.72; 95% CI, -15.27, -2.16; p = .01), and higher quantitative insulin sensitivity check index (ß = 0.01; 95% CI, 0.005, 0.02; p = .007) compared with the placebo. Moreover, zinc and vitamin E cosupplementation upregulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ; p = .03) and low-density lipoprotein receptor (LDLR; p = .04) compared with the placebo. Though, zinc and vitamin E combination did not affect other metabolic parameters.Conclusions: Overall, zinc and vitamin E cosupplementation for 6 weeks in women with GDM significantly improved insulin metabolism, lipid profile, and the gene expression levels of PPAR-γ and LDLR.

The effects of omega-3 fatty acids and vitamin E co-supplementation on gene expression related to inflammation, insulin and lipid in patients with Parkinson's disease: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: This study was conducted to evaluate the effects of omega-3 fatty acids and vitamin E co-supplementation on gene expression related to inflammation, insulin and lipid in subjects with Parkinson's disease (PD). PATIENTS AND METHODS: This randomized, double-blind, placebo-controlled clinical trial was performed in 40 subjects with PD. Participants were randomly allocated into two groups to take either 1000 mg/day of omega-3 fatty acids from flaxseed oil plus 400 IU/day of vitamin E supplements or placebo (n = 20 each group) for 12 weeks. Gene expression related to inflammation, insulin and lipid were quantified in peripheral blood mononuclear cells (PBMC) of PD patients with RT-PCR method. RESULTS: After the 12-week intervention, compared with the placebo, omega-3 fatty acids and vitamin E co-supplementation downregulated gene expression of tumor necrosis factor alpha (TNF-α) (P = 0.002) in PBMC of subjects with PD. In addition, omega-3 fatty acids and vitamin E co-supplementation upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) (P = 0.03), and downregulated oxidized low-density lipoprotein receptor (LDLR) (P = 0.002) in PBMC of subjects with PD compared with the placebo. We did not observe any significant effect of omega-3 fatty acids and vitamin E co-supplementation on gene expression of interleukin-1 (IL-1) and IL-8 in PBMC of patients with PD. CONCLUSIONS: Overall, omega-3 fatty acids and vitamin E co-supplementation for 12 weeks in PD patients significantly improved gene expression of TNF-α, PPAR-γ and LDLR, but did not affect IL-1 and IL-8.