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. © 2019, Springer Nature B.V

The effects of vitamin D and probiotic co-supplementation on mental health parameters and metabolic status in type 2 diabetic patients with coronary heart disease: A randomized, double-blind, placebo-controlled trial

Abstract Background: This study was carried out to evaluate the effects of vitamin D and probiotic co-supplementation on mental health parameters and metabolic status in diabetic people with coronary heart disease (CHD). Methods: This randomized, double-blind, placebo-controlled trial was carried out among 60 diabetic people with CHD, aged 45–85 years old. Subjects were randomly allocated into two groups to receive either 50,000 IU vitamin D every 2 weeks plus 8 × 109 CFU/g probiotic of Lactocare Zisttakhmir Co (n = 30) or placebo (n = 30) for 12 weeks. Fasting blood samples were obtained at baseline and after the 12-week intervention to determine metabolic profiles. Results: After the 12-week intervention, compared with the placebo, vitamin D and probiotic co-supplementation resulted in significant improvements in beck depression inventory total score (−2.8 ± 3.8 vs. −0.9 ± 2.1, P = 0.01), beck anxiety inventory scores (−2.1 ± 2.3 vs. −0.8 ± 1.4, P = 0.009) and general health questionnaire scores (−3.9 ± 4.1 vs. −1.1 ± 3.4, P = 0.005). Compared with the placebo, vitamin D and probiotic co-supplementation resulted in significant reductions in serum insulin levels (−2.8 ± 3.8 vs. +0.2 ± 4.9 μIU/mL, P = 0.009), homeostasis model of assessment-estimated insulin resistance (−1.0 ± 1.6 vs. −0.1 ± 1.5, P = 0.02), and a significant increase in serum 25-OH-vitamin D (+11.8 ± 5.9 vs. +0.1 ± 1.4 ng/mL, P < 0.001), the quantitative insulin sensitivity check index (+0.03 ± 0.04 vs. −0.001 ± 0.01, P = 0.003) and serum HDL-cholesterol levels (+2.3 ± 3.5 vs. −0.5 ± 3.8 mg/dL, P = 0.004). In addition, changes in serum high sensitivity C-reactive protein (hs-CRP) (−950.0 ± 1811.2 vs. +260.5 ± 2298.2 ng/mL, P = 0.02), plasma nitric oxide (NO) (+1.7 ± 4.0 vs. −1.4 ± 6.7 μmol/L, P = 0.03) and plasma total antioxidant capacity (TAC) (+12.6 ± 41.6 vs. −116.9 ± 324.2 mmol/L, P = 0.03) in the supplemented group were significantly different from the changes in these indicators in the placebo group. Conclusions: Overall, vitamin D and probiotic co-supplementation after 12 weeks among diabetic people with CHD had beneficial effects on mental health parameters, serum hs-CRP, plasma NO, TAC, glycemic control and HDL-cholesterol levels. Keywords: Vitamin D Probiotic Mental health Inflammation Oxidative stress Type 2 diabetes mellitus Coronary heart diseas

The effects of alpha-lipoic acid supplementation on glucose control and lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials

Abstract Objective This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to summarize the effect of alpha-lipoic acid (ALA) supplementation on glycemic control and lipid profiles among patients with metabolic diseases. Methods We searched the following databases till October 2017: MEDLINE, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials. The relevant data were extracted and assessed for quality of the studies according to the Cochrane risk of bias tool. Data were pooled using the inverse variance method and expressed as standardized mean difference (SMD) with 95% confidence intervals (95% CI). Heterogeneity between studies was assessed by the Cochran Q statistic and I-squared tests (I2). Twenty-four studies were included in the meta-analyses. Results The findings of this meta-analysis showed that ALA supplementation among patients with metabolic diseases significantly decreased fasting glucose (SMD -0.54; 95% CI, −0.89, –0.19; P = 0.003), insulin (SMD –1.01; 95% CI, −1.70, −0.31; P = 0.006), homeostasis model assessment of insulin resistance (SMD -0.76; 95% CI, −1.15, –0.36; P < 0.001) and hemoglobin A1c (SMD –1.22; 95% CI, −2.01, –0.44; P = 0.002), triglycerides (SMD –0.58; 95% CI, −1.00, −0.16; P = 0.006), total- (SMD –0.64; 95% CI, −1.01, −0.27; P = 0.001), low density lipoprotein-cholesterol (SMD –0.44; 95% CI, −0.76, −0.11; P = 0.008). We found no detrimental effect of ALA supplementation on high density lipoprotein-cholesterol (HDL-cholesterol) levels (SMD 0.57; 95% CI, −0.14, 1.29; P = 0.11). Conclusions Overall, the current meta-analysis demonstrated that ALA administration may lead to an improvement in glucose homeostasis parameters and lipid profiles except HDL-cholesterol levels. Keywords: Meta-analysis Lipid profiles Glycemic control Alpha-lipoic acid

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 � 10 9 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 β (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 (β - 0.93; 95% CI, - 1.78, - 0.08; P = 0.03) and depression, anxiety and stress scale scores (β - 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 (β - 0.19 ng/mL; 95% CI, - 0.28, - 0.10; P &lt; 0.001), hirsutism (β - 0.95; 95% CI, - 1.39, - 0.51; P &lt; 0.001), high-sensitivity C-reactive protein (hs-CRP) (β - 0.67 mg/L; 95% CI, - 0.97, - 0.38; P &lt; 0.001) and malondialdehyde (MDA) levels (β - 0.25 μmol/L; 95% CI, - 0.40, - 0.10; P = 0.001), and a significant increase in total antioxidant capacity (TAC) (β 82.81 mmol/L; 95% CI, 42.86, 122.75; P &lt; 0.001) and total glutathione (GSH) levels (β 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). © 2019 The Author(s)

Melatonin administration lowers biomarkers of oxidative stress and cardio-metabolic risk in type 2 diabetic patients with coronary heart disease: A randomized, double-blind, placebo-controlled trial

Background & aims: Melatonin may benefit diabetic people with coronary heart disease (CHD) through its beneficial effects on biomarkers of oxidative stress and cardio-metabolic risk. This investigation evaluated the effects of melatonin administration on metabolic status in diabetic patients with CHD. Methods: This randomized, double-blind, placebo-controlled trial was conducted and involved 60 diabetic patients with CHD. Subjects were randomly allocated into two groups to receive either 10 mg melatonin (2 melatonin capsules, 5 mg each) (n = 30) or placebo (n = 30) once a day for 12 weeks. Results: Compared with the placebo, melatonin supplementation resulted in significant increases in plasma glutathione (GSH) (+64.7 ± 105.7 vs. �11.1 ± 137.6 μmol/L, P = 0.02) and nitric oxide (NO) (+0.9 ± 4.7 vs. �3.3 ± 9.6 μmol/L, P = 0.03), and significant decreases in malondialdehyde (MDA) (�0.2 ± 0.3 vs. +0.1 ± 0.5 μmol/L, P = 0.007), protein carbonyl (PCO) (�0.12 ± 0.08 vs. +0.03 ± 0.07 mmol/mg protein, P < 0.001) and serum high sensitivity C-reactive protein (hs-CRP) levels (�1463.3 ± 2153.8 vs. +122.9 ± 1230.4 ng/mL, P = 0.001). In addition, taking melatonin, compared with the placebo, significantly reduced fasting plasma glucose (�29.4 ± 49.0 vs. �5.5 ± 32.4 mg/dL, P = 0.03), serum insulin concentrations (�2.2 ± 4.1 vs. +0.7 ± 4.2 μIU/mL, P = 0.008), homeostasis model of assessment-estimated insulin resistance (�1.0 ± 2.2 vs. +0.01 ± 1.6, P = 0.04), total-/HDL-cholesterol ratio (�0.18 ± 0.38 vs. +0.03 ± 0.35, P = 0.02) and systolic (�4.3 ± 9.6 vs. +1.0 ± 7.5 mmHg, P = 0.01) and diastolic blood pressure (�2.8 ± 7.3 vs. +0.1 ± 3.6 mmHg, P = 0.04). Melatonin treatment also significantly increased quantitative insulin sensitivity check index (+0.006 ± 0.01 vs. �0.004 ± 0.01, P = 0.01) and serum HDL-cholesterol (+2.6 ± 5.5 vs. �0.01 ± 4.4 mg/dL, P = 0.04). Supplementation with melatonin had no significant effect on other metabolic parameters. Conclusions: Overall, melatonin intake for 12 weeks to diabetic patients with CHD had beneficial effects on plasma GSH, NO, MDA, PCO, serum hs-CRP levels, glycemic control, HDL-cholesterol, total-/HDL-cholesterol ratio, blood pressures and parameters of mental health. Registered under ClinicalTrials.gov Identifier no. http://www.irct.ir: IRCT2017051333941N1. © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolis

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. © 2019 John Wiley & Sons, Ltd

Correction: The Effects of Melatonin Supplementation on Glycemic Control: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

his systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to clarify the effect of melatonin supplementation on glycemic control. Databases including PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials were searched until July 30th, 2018. Two reviewers independently assessed study eligibility, extracted data, and evaluated the risk of bias for included trials. Heterogeneity among included studies was assessed using Cochran’s Q test and I-square (I2) statistic. Data were pooled using random-effect models and mean difference (MD) was considered as the overall effect size. Twelve trials out of 292 selected reports were identified eligible to be included in current meta-analysis. The pooled findings indicated that melatonin supplementation significantly reduced fasting glucose (MD=–6.34; 95% CI, –12.28, –0.40; p=0.04; I2: 65.0) and increased the quantitative insulin sensitivity check index (QUICKI) (MD=0.01; 95% CI, 0.00, 0.02; p=0.01; I2: 0.0). However, melatonin administration did not significantly influence insulin levels (MD=–1.03; 95% CI, –3.82, 1.77; p=0.47; I2: 0.53), homeostasis model assessment of insulin resistance (HOMA-IR) (MD=–0.34; 95% CI, –1.25, 0.58; p=0.37; I2: 0.37) or HbA1c levels (MD=–0.22; 95% CI, –0.47, 0.03; p=0.08; I2: 0.0). In summary, the current meta-analysis showed a promising effect of melatonin supplementation on glycemic control through reducing fasting glucose and increasing QUICKI, yet additional prospective studies are recommended, using higher supplementation doses and longer intervention period, to confirm the impact of melatonin on insulin levels, HOMA-IR and HbA1c. Key words: melatonin - glycemic control - insulin resistance - meta-analysi

The effects of inositol supplementation on lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials

Background Several studies have evaluated the effect of inositol supplementation on lipid profiles among population with metabolic diseases; however, the findings are controversial. This review of randomized controlled trials (RCTs) was performed to summarize the evidence of the effects of inositol supplementation on lipid profiles among population with metabolic diseases. Methods Relevant RCTs studies were searched in Cochrane Library, EMBASE, MEDLINE, and Web of Science until October 2017. Two researchers assessed study eligibility, extracted data, and evaluated risk of bias of included primary studies, independently. To check for the heterogeneity among included studies Q-test and I2 statistics were used. Data were pooled by using the random-effect model and standardized mean difference (SMD) was considered as summary of the effect size. Results Overall, 14 RCTs were included into meta-analysis. Pooled results showed that inositol supplementation among patients with metabolic diseases significantly decreased triglycerides (SMD − 1.24; 95% CI, − 1.84, − 0.64; P < 0.001), total- (SMD − 1.09; 95% CI, − 1.83, − 0.55; P < 0.001), and LDL-cholesterol levels (SMD − 1.31; 95% CI, − 2.23, − 0.39; P = 0.005). There was no effect of inositol supplementation on HDL-cholesterol levels (SMD 0.20; 95% CI, − 0.27, 0.67; P = 0.40). Conclusions Inositol supplementation may result in reduction in triglycerides, total- and LDL-cholesterol levels, but did not affect HDL-cholesterol levels among patients with metabolic diseases. Additional prospective studies regarding the effect of inositol supplementation on lipid profiles in patients with metabolic diseases are necessary. Keywords: Inositol Lipid profiles Metabolic diseases Meta-analysi

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 (β �2.15; 95 CI, �3.62, �0.68; P = 0.005), Beck Depression Inventory index (β �3.62; 95 CI, �5.53, �1.78; P<0.001) and Beck Anxiety Inventory index (β �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 (β �1.20 µIU/mL; 95 CI, �2.14, �0.26; P = 0.01), homeostasis model of assessment-insulin resistance (HOMA-IR) (β �0.28; 95 CI, �0.50, �0.05; P = 0.01), serum total- (β �7.96 mg/dL; 95 CI, �13.75, �2.17; P = 0.008) and LDL-cholesterol levels (β �5.88 mg/dL; 95 CI, �11.42, �0.33; P = 0.03), and significantly increased the quantitative insulin sensitivity check index (QUICKI) (β 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. © 2019 Elsevier B.V

The effects of melatonin supplementation on inflammatory markers among patients with metabolic syndrome or related disorders: a systematic review and meta-analysis of randomized controlled trials

Abstract Objective This systematic review and meta-analysis of randomized controlled trials (RCTs) was carried out to determine the effect of melatonin supplementation on the inflammatory markers among individuals with metabolic syndrome (MetS) and related disorders. Methods We searched the following databases up to March 2018: PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. Three reviewers independently assessed study eligibility, extracted data, and evaluated risk of bias of included primary studies. Statistical heterogeneity was assessed using Cochran’s Q test and I-square (I2) statistic. Data were pooled using the random effect model and standardized mean difference (SMD) was considered as the summary effect size. Results Six trials of 317 potential reports were identified to be suitable for our meta-analysis. The pooled results using random effects model indicated that melatonin supplementation significantly reduced C-reactive protein (CRP) (SMD = − 1.80; 95% CI − 3.27, − 0.32; P = 0.01; I2: 95.2) and interleukin 6 (IL-6) concentrations (SMD = − 2.02; 95% CI − 3.57, − 0.47; P = 0.01; I2: 91.2) among patients with MetS and related disorders; however, it did not affect tumor necrosis factor-α (TNF-α) concentrations (SMD = − 1.87; 95% CI − 3.81, 0.07; P = 0.05; I2: 94.4). Conclusions In summary, the current meta-analysis showed the promising effect of melatonin administration on reducing CRP and IL-6, but not TNF-α levels among patients with MetS and related disorders. Additional prospective studies are recommended using higher supplementation doses and longer intervention period. Keyword Melatonin Inflammatory markers Meta-analysi