The effects of quercetin supplementation on lipid profiles and inflammatory markers among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials.

Aims: This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to determine the effect of quercetin administration on lipid profiles and inflammatory markers among patients with metabolic syndrome (MetS) and related disorders.Methods: We searched systematically online databases including Cochrane Library, EMBASE, MEDLINE, and Web of Science to identify the relevant RCTs until November 2018. Q-test and I2 statistics were applied to assess heterogeneity among included studies. Data were combined using fixed- or random-effects model and presented as standardized mean difference (SMD) with 95% confidence interval (CI).Results: Out of 591 citations, 16 RCTs were included in the meta-analysis. The pooled findings showed that quercetin consumption significantly decreased total-cholesterol (SMD = -0.98; 95% CI, -1.48, -0.49; p < 0.001; I2: 94.0), LDL-cholesterol (SMD = -0.88; 95% CI, -1.35, -0.41; p < 0.001; I2: 92.7) and C-reactive protein (CRP) levels (-0.64; 95% CI, -1.03, -0.25; p = 0.001; I2: 90.2). While, quercetin supplementation did not significantly affect triglycerides (TG) (SMD = -0.32; 95% CI, -0.68, 0.04; p = 0.08; I2: 84.8), HDL-cholesterol (SMD = 0.20; 95% CI, -0.20, 0.24; p = 0.84; I2: 70.6), interleukin 6 (IL-6) (SMD = -0.69; 95% CI, -1.69, 0.31; p = 0.17; I2: 94.5) and tumor necrosis factor-alpha (TNF-α) levels (SMD = -0.06; 95% CI, -0.25, 0.14; p = 0.58; I2: 35.6)Conclusions: In summary, the current meta-analysis demonstrated that quercetin supplementation significantly reduced total-cholesterol, LDL-cholesterol, and CRP levels, yet did not affect triglycerides, HDL-cholesterol, IL-6 and TNF-α among patients with MetS and related disorders.

Melatonin and pancreatic cancer: Current knowledge and future perspectives.

Pancreatic cancer has a high mortality rate due to the absence of early symptoms and subsequent late diagnosis; additionally, pancreatic cancer has a high resistance to radio- and chemotherapy. Multiple inflammatory pathways are involved in the pathophysiology of pancreatic cancer. Melatonin an indoleamine produced in the pineal gland mediated and receptor-independent action is the pancreas and other where has both receptors. Melatonin is a potent antioxidant and tissue protector against inflammation and oxidative stress. In vivo and in vitro studies have shown that melatonin supplementation is an appropriate therapeutic approach for pancreatic cancer. Melatonin may be an effective apoptosis inducer in cancer cells through regulation of a large number of molecular pathways including oxidative stress, heat shock proteins, and vascular endothelial growth factor. Limited clinical studies, however, have evaluated the role of melatonin in pancreatic cancer. This review summarizes what is known regarding the effects of melatonin on pancreatic cancer and the mechanisms involved.

Melatonin, a calpain inhibitor in the central nervous system: Current status and future perspectives.

Dysregulation of neuronal Ca2+ and oxidative stress plays an important role in the activation of cysteine proteases including calpains and caspases that contribute to neuronal death. In neurodegenerative diseases, traumatic brain injury, stroke, and neuropathic pain calpain activities are markedly increased. Melatonin is a beneficial supplement in the treatment of central nervous system (CNS) disorders. Melatonin is a potent antioxidant and works as a free-radical scavenger to regulate a large number of molecular pathways, including oxidative stress, inflammation, apoptosis, and cell death under different pathological conditions. However, limited studies have evaluated the inhibitory effect of melatonin on calpains. This review summarizes the current knowledge related to the effects of melatonin on calpains in some of the common CNS disorders.

The effects of microRNAs in activating neovascularization pathways in diabetic retinopathy.

Diabetic retinopathy (DR) is one of the major complications of diabetes mellitus that causes diabetic macular edema and visual loss. DR is categorized, based on the presence of vascular lesions and neovascularization, into non-proliferative and proliferative DR. Vascular changes in DR correlate with the cellular damage and pathological changes in the capillaries of blood-retinal barrier. Several cytokines have been involved in inducing neovascularization. These cytokines activate different signaling pathways which are mainly responsible for the complications of DR. Recently; microRNAs (miRNAs) have been introduced as the key factors in the regulation of the cytokine expression which plays a critical role in neovascularization of retinal cells. Some studies have demonstrated that changing levels of miRNAs have essential role in the pathophysiology of vascular changes in patients with DR. The aim of this study is to identify the effects of miRNAs in the pathogenesis of DR via activating neovascularization pathways.

Could circRNA be a new biomarker for pre-eclampsia?

Pre-eclampsia is a devastating complication of pregnancy which is characterized by hypertension and proteinuria in pregnant women. Pre-eclampsia is important as it is the leading cause of death. Moreover, untreated pre-eclampsia might lead to other lethal complications, for both fetus and mother. Pre-eclampsia can also affect the quality of life in affected women. Despite a large number of risk factors for pre-eclampsia, these risk factors are able to detect just 30% of women who are susceptible to pre-eclampsia. Heterogeneous manifestations of pre-eclampsia necessitate the discovery of potential biomarkers required for its early detection. Circular RNAs (circRNAs) are a type of RNA which are more abundant, specific, and highly organized compared with other types of RNA. Accordingly, circRNAs have been suggested as one of the potential biomarkers for different diseases. Recently, researchers have shown interest in the effects of circRNAs in pre-eclampsia, although the current evidence is limited. The majority of obstetricians are probably not aware of circRNAs as a useful biomarker. Here, we aimed to summarize recent supporting evidence and assess the mechanisms by which circRNAs are involved in pre-eclampsia.

The effects of statin use on inflammatory markers among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials.

Current evidence suggests that statin use decreases the incidence of cardiovascular diseases (CVD) through reducing LDL cholesterol and decreasing inflammation. Metabolic syndrome (MetS) is usually associated with increased inflammatory markers and increased risk of CVD. We conducted a systematic review and meta-analysis to determine the effect of statin use on inflammatory markers including C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1 (IL-1) among patients with MetS and related disorders. PubMed, EMBASE, Web of Science databases, and Cochrane Library were searched for randomized controlled trials (RCTs) through April 2018. Three independent investigators evaluated study eligibilities, extracted data, and assessed study quality using the Cochrane Collaboration risk of bias tool and Jadad's quality scales. Heterogeneity was determined using Cochran's Q statistic and I-square (I2) test. Based on the heterogeneity results, we pooled data using random-effect or fixed effect models presented as standardized mean differences (SMD) and corresponding 95% confidence intervals (CI). One hundred thirteen RCTs (19,644 patients) were included in our meta-analysis. The pooled results using random effects model showed that statin use statistically significantly decreased CRP level (SMD= -0.97; 95% CI, -1.10, -0.85; P < 0.001; I2: 95.1%), TNF-α (SMD= -1.88; 95% CI, -2.40, -1.38; P < 0.001; I2: 97.2%), IL-6 (SMD= -1.67; 95% CI, -1.98, -1.34; P < 0.001; I2: 96.5%), and IL-1 concentrations (SMD= -8.35; 95% CI, -10.49, -6.22; P < 0.001; I2: 98.4%) among patients with MetS and related disorders. Our meta-analysis showed beneficial effects of statin use on reducing inflammatory markers in patients with MetS and related disorders.

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.

Effects of magnesium supplementation on carotid intima-media thickness and metabolic profiles in diabetic haemodialysis patients: a randomised, double-blind, placebo-controlled trial.

This study evaluated the effects of Mg administration on carotid intima-media thickness (CIMT), glycaemic control and markers of cardio-metabolic risk in diabetic haemodialysis (HD) patients. This randomised, double-blind, placebo-controlled clinical trial was conducted in fifty-four diabetic HD patients. Participants were randomly divided into two groups to take either 250 mg/d Mg as magnesium oxide (n 27) or placebo (n 27) for 24 weeks. Mg supplementation resulted in a significant reduction in mean (P<0·001) and maximum levels of left CIMT (P=0·02) and mean levels of right CIMT (P=0·004) compared with the placebo. In addition, taking Mg supplements significantly reduced serum insulin levels (ß=-9·42 pmol/l; 95% CI -14·94, -3·90; P=0·001), homoeostasis model of assessment-insulin resistance (ß=-0·56; 95 % CI -0·89, -0·24; P=0·001) and HbA1c (ß=-0·74 %; 95 % CI -1·10, -0·39; P<0·001) and significantly increased the quantitative insulin sensitivity check index (ß=0·008; 95 % CI 0·002, 0·01; P=0·002) compared with the placebo. In addition, Mg administration led to a significant reduction in serum total cholesterol (ß=-0·30 mmol/l; 95% CI -0·56, -0·04; P=0·02), LDL-cholesterol (ß=-0·29 mmol/l; 95% CI -0·52, -0·05; P=0·01), high-sensitivity C-reactive protein (hs-CRP) (P<0·001) and plasma malondialdehyde (MDA) (P=0·04) and a significant rise in plasma total antioxidant capacity (TAC) levels (P<0·001) compared with the placebo. Overall, we found that taking Mg for 24 weeks by diabetic HD patients significantly improved mean and maximum levels of left and mean levels of right CIMT, insulin metabolism, HbA1c, total cholesterol and LDL-cholesterol, hs-CRP, TAC and MDA levels.

Clinical and metabolic response to vitamin D plus probiotic in schizophrenia patients.

BACKGROUND: This study determined the effects of a novel combination of vitamin D and probiotic on metabolic and clinical symptoms in chronic schizophrenia. METHODS: This trial was conducted among 60 patients with chronic schizophrenia to receive either 50,000 IU vitamin D3 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 was associated with a significant improvement in the general (- 3.1 ± 4.7 vs. + 0.3 ± 3.9, P = 0.004) and total PANSS scores (- 7.4 ± 8.7 vs. -1.9 ± 7.5, P = 0.01). Vitamin D and probiotic co-supplementation also significantly increased total antioxidant capacity (+ 51.1 ± 129.7 vs. -20.7 ± 53.3 mmol/L, P = 0.007), and significantly decreased malondialdehyde (- 0.3 ± 0.9 vs. + 0.2 ± 0.4 µmol/L, P = 0.01) and high sensitivity C-reactive protein levels (- 2.3 ± 3.0 vs. -0.3 ± 0.8 mg/L, P = 0.001) compared with the placebo. Moreover, taking vitamin D plus probiotic significantly reduced fasting plasma glucose (- 7.0 ± 9.9 vs. -0.2 ± 9.9 mg/dL, P = 0.01), insulin concentrations (- 2.7 ± 2.3 vs. + 0.4 ± 2.0 µIU/mL, P < 0.001), homeostasis model of assessment-estimated insulin resistance (- 0.8 ± 0.7 vs. + 0.1 ± 0.7, P < 0.001), triglycerides (- 7.8 ± 25.2 vs. + 10.1 ± 30.8 mg/dL, P = 0.01) and total cholesterol levels (- 4.9 ± 15.0 vs. + 5.9 ± 19.5 mg/dL, P = 0.04) and total-/HDL-cholesterol ratio (- 0.1 ± 0.6 vs. + 0.3 ± 0.8, P = 0.04). CONCLUSION: Probiotic and vitamin D for 12 weeks to chronic schizophrenia had beneficial effects on the general and total PANSS score, and metabolic profiles. TRIAL REGISTRATION: This study was retrospectively registered in the Iranian website ( www.irct.ir ) for clinical trials registration ( http://www.irct.ir : IRCT2017072333551N2). 07-31-2017 2.

The effects of magnesium-zinc-calcium-vitamin D co-supplementation on biomarkers of inflammation, oxidative stress and pregnancy outcomes in gestational diabetes.

BACKGROUND: Diabetes is the most common medical condition in pregnant women and its complications affect both mother and fetus. The beneficial effects of vitamin D on gestational diabetes have been shown, though data on the effects of co-administration of vitamin D with other nutrients on pregnancy outcomes in gestational diabetes (GDM) are scarce. This study was aimed to determine the effects of magnesium-zinc-calcium-vitamin D co-supplementation on parameters of inflammation and oxidative stress, and pregnancy outcomes among women with GDM. METHODS: This randomized, double-blinded, placebo-controlled trial was conducted on 60 women with GDM not taking oral hypoglycemic agents. Patients were randomly assigned to take magnesium-zinc-calcium-vitamin D supplements (n = 30) or placebo (n = 30) for 6 weeks. Fasting blood samples were collected from participants at baseline and after the 6-week intervention to measure related biomarkers. RESULTS: Magnesium-zinc-calcium-vitamin D co-supplementation resulted in a significant reduction in serum high-sensitivity C-reactive protein (- 1.2 ± 3.5 vs. + 0.8 ± 2.0 mg/L, P = 0.01) and plasma malondialdehyde concentrations (- 0.3 ± 0.3 vs. + 0.3 ± 1.1 µmol/L, P = 0.003), as well as a significant increase in total antioxidant capacity levels (+ 38.2 ± 76.5 vs. -16.3 ± 93.5 mmol/L, P = 0.01), compared to placebo. We found a decreasing trend in newborns' weight (3089.8 ± 519.9 vs. 3346.3 ± 411.1 g, P = 0.05) and the rate of macrosomia (3.3% vs. 16.7%, P = 0.08) in the magnesium-zinc-calcium-vitamin D supplemented women. CONCLUSIONS: Overall, the findings of this study have demonstrated that magnesium-zinc-calcium-vitamin D co-supplementation for 6 weeks to women with GDM may reduce biomarkers of inflammation and oxidative stress. This study was retrospectively registered on 25 April 2017 in the Iranian website ( www.irct.ir ) for clinical trials registration ( http://www.irct.ir : IRCT201704225623N109).

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 effects of curcumin-containing supplements on biomarkers of inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials.

Besides other benefits, curcumin is getting more recognized for its antioxidant and anti-inflammatory properties, highlighting the importance of curcumin application for chronic disease prevention. This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to assess the influence of curcumin-containing supplements on biomarkers of inflammation and oxidative stress. MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials were searched till January 2018 for eligible studies. The selected studies were evaluated for their quality using the Cochrane risk of bias tool and relevant data were extracted from included studies. Data were pooled using the inverse variance method and expressed as standardized mean difference (SMD) with 95% confidence intervals (95% CI). Fifteen RCTs were included in the final analysis. The meta-analysis indicated that curcumin supplementation significantly decreased interleukin 6 (IL-6) (SMD -2.08; 95% CI [-3.90, -0.25]; p = 0.02), high-sensitivity C-reactive protein (hs-CRP) (SMD -0.65; 95% CI [-1.20, -0.10], p = 0.02), and malondialdehyde (MDA) concentrations (SMD -3.14; 95% CI [-4.76, -1.53], p < 0.001). Though, curcumin supplementation had no significant effect on tumor necrosis factor-alpha (SMD -1.62; 95% CI [-3.60, 0.36]; p = 0.10) and superoxide dismutase levels (SMD 0.34; 95% CI [-1.06, 1.74], p = 0.63). Overall, this meta-analysis suggests that taking curcumin-containing supplements may exert anti-inflammatory and antioxidant properties through a significant reduction in IL-6, hs-CRP, and MDA levels.

A comparison between the effects of flaxseed oil and fish oil supplementation on cardiovascular health in type 2 diabetic patients with coronary heart disease: A randomized, double-blinded, placebo-controlled trial.

This study compared the effects of flaxseed and fish oil supplementation on cardiovascular risk parameters in diabetic patients with coronary heart disease. Participants were randomly allocated into three intervention groups to receive either 1,000 mg of omega-3 fatty acids from fish oil or 1,000 mg of omega-3 fatty acids from flaxseed oil or placebo (n = 30 each group) twice a day for 12 weeks. A significant reduction in insulin levels (.04) was observed following flaxseed oil and fish oil supplementation compared with the placebo. In addition, a significant reduction in high-sensitivity C-reactive protein (.02) was seen after flaxseed oil supplementation compared with the placebo and a significant increase in total nitrite (.001) was seen after flaxseed oil and fish oil intake compared with placebo. Additionally, a significant increase in total antioxidant capacity (p < .001) after consuming flaxseed oil and fish oil compared with placebo and glutathione levels (.001) after consuming fish oil compared with flaxseed oil and placebo was observed. Overall, our study revealed the beneficial effects of flaxseed oil and fish oil supplementation on few metabolic profiles. This study suggests that the effect of flaxseed oil in reducing insulin and increasing total nitrite and total antioxidant capacity is similar to fish oil.

The effects of expression of different microRNAs on insulin secretion and diabetic nephropathy progression.

MicroRNAs (miRNAs) have recently become well-known efficacious biomarkers for the diagnosis of diabetic nephropathy (DN). MiRNAs, short noncoding RNAs, are posttranscriptional regulators of gene expression, which regulate several biological cell functions, including insulin production and secretion, as well as insulin resistance in tissues. Today, the focus of the medical world is centered on the role of miRNAs as mediators for different diseases, such as DN and end-stage renal diseases (ESRD). MiRNAs are stable and detectable in human biological fluids, so their detection for early diagnosis of different diseases is highly sensitive and specific. Previous reports have shown that the alteration of miRNA profiles significantly correlates with specific stages of DN, kidney fibrosis, and renal dysfunction. This review was aimed at assessing the pathway of different miRNA expressions responsible for insulin secretion disorder and DN progression.

The effects of vitamin D supplementation on metabolic profiles and gene expression of insulin and lipid metabolism in infertile polycystic ovary syndrome candidates for in vitro fertilization.

BACKGROUND: Vitamin D deficiency in women diagnosed with polycystic ovary syndrome (PCOS) remarkably decreases the chance of pregnancy, which might be related to its impact on metabolic abnormalities in these patients. It is hypothesized that vitamin D supplementation influences metabolic profile of these patients and indirectly might affect fertility and the outcomes. Therefore, this study was conducted to determine the effects of vitamin D supplementation on the levels of anti-Müllerian hormone (AMH), metabolic profiles, and gene expression of insulin and lipid metabolism in infertile women with PCOS who were candidate for in vitro fertilization (IVF). METHODS: This study was a randomized, double-blinded, placebo-controlled trial conducted among 40 infertile women, aged 18-40 years, diagnosed with PCOS and was candidate for IVF. Participants were randomly assigned into two intervention groups for receiving either 50,000 IU vitamin D or placebo (n = 20 each group) every other week for 8 weeks. Gene expression for insulin and lipid metabolism was conducted using peripheral blood mononuclear cells (PBMCs) of women with PCOS, via RT-PCR method. RESULTS: Vitamin D supplementation led to a significant reduction in serum AMH (- 0.7 ± 1.2 vs. - 0.1 ± 0.5 ng/mL, P = 0.02), insulin levels (- 1.4 ± 1.6 vs. -0.3 ± 0.9 µIU/mL, P = 0.007), homeostatic model of assessment for insulin resistance (- 0.3 ± 0.3 vs. -0.1 ± 0.2, P = 0.008), and a significant increase in quantitative insulin sensitivity check index (+ 0.009 ± 0.01 vs. + 0.001 ± 0.004, P = 0.04), compared with the placebo. Moreover, following vitamin D supplementation there was a significant decrease in serum total- (- 5.1 ± 12.6 vs. + 2.9 ± 10.9 mg/dL, P = 0.03) and LDL-cholesterol levels (- 4.5 ± 10.3 vs. + 2.5 ± 10.6 mg/dL, P = 0.04) compared with the placebo. CONCLUSION: Overall, the findings of this trial supported that 50,000 IU vitamin D supplementation every other week for 8 weeks had beneficial effects on insulin metabolism, and lipid profile of infertile women with PCOS who are candidate for IVF. These benefits might not be evident upon having sufficient vitamin D levels. TRIAL REGISTRATION: This study was retrospectively registered in the Iranian website ( www.irct.ir ) for clinical trials registration ( http://www.irct.ir : IRCT20170513033941N27).

High-dose ω-3 Fatty Acid Plus Vitamin D3 Supplementation Affects Clinical Symptoms and Metabolic Status of Patients with Multiple Sclerosis: A Randomized Controlled Clinical Trial.

Background: Combined omega-3 fatty acid and vitamin D supplementation may improve multiple sclerosis (MS) by correcting metabolic abnormalities and attenuating oxidative stress and inflammation. Objective: This study aimed to determine the effects of ω-3 fatty acid and vitamin D cosupplementation on the disability score and metabolic status of patients with MS. Methods: This was a randomized, placebo-controlled clinical trial with Expanded Disability Status Scale (EDSS) score and inflammation as primary outcomes and oxidative stress biomarkers and metabolic profile as secondary outcomes. Patients, aged 18-55 y, were matched for disease EDSS scores, gender, medications, BMI, and age (n = 53) and randomly received a combined 2 × 1000 mg/d ω-3 fatty acid and 50,000 IU/biweekly cholecalciferol supplement or placebo for 12 wk. The placebos were matched in colour, shape, size, packaging, smell, and taste with supplements. Fasting blood samples were collected at baseline and end of intervention to measure different outcomes. Multiple linear regression models were used to assess treatment effects on outcomes adjusting for confounding variables. Results: Patients taking ω-3 fatty acid plus vitamin D supplements showed a significant improvement in EDSS (ß -0.18; 95% CI: -0.33, -0.04; P = 0.01), compared with placebo. Serum high-sensitivity C-reactive protein (ß -1.70 mg/L; 95% CI: -2.49, -0.90 mg/L; P < 0.001), plasma total antioxidant capacity (ß +55.4 mmol/L; 95% CI: 9.2, 101.6 mmol/L; P = 0.02), total glutathione (ß +51.14 µmol/L; 95% CI: 14.42, 87.87 µmol/L; P = 0.007), and malondialdehyde concentrations (ß -0.86 µmol/L; 95% CI: -1.10, -0.63 µmol/L; P < 0.001) were significantly improved in the supplemented group compared with the placebo group. In addition, ω-3 fatty acid and vitamin D cosupplementation resulted in a significant reduction in serum insulin, insulin resistance, and total/HDL-cholesterol, and a significant increase in insulin sensitivity and serum HDL-cholesterol concentrations. Conclusion: Overall, taking ω-3 fatty acid and vitamin D supplements for 12 wk by patients with MS had beneficial effects on EDSS and metabolic status. This trial was registered at the Iranian website (www.irct.ir) for registration of clinical trials as IRCT2017090133941N20.

The Effects of Vitamin D Supplementation on Markers Related to Endothelial Function Among Patients with Metabolic Syndrome and Related Disorders: A Systematic Review and Meta-Analysis of Clinical Trials.

This systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted to summarize the effect of vitamin D supplementation on endothelial function among people with metabolic syndrome and related disorders. Cochrane library, Embase, PubMed, and Web of Science database were searched to identify related RCTs published up 20th May 2018. To check heterogeneity a 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 effect size. Twenty-two trials of 931 potential citations were found to be eligible for current meta-analysis. The pooled findings by using random effects model indicated that vitamin D supplementation to individuals with MetS and related disorders significantly increased flow-mediated dilatation (FMD) (SMD=1.10; 95% CI, 0.38, 1.81, p=0.003). However, it did not affect pulse-wave velocity (PWV) (SMD=0.04; 95% CI, -0.25, 0.33, p=0.80) and augmentation index (AI) (SMD=0.07; 95% CI, -0.25, 0.40; p=0.65). Overall, this meta-analysis demonstrated that vitamin D supplementation to patients with metabolic syndrome and related disorders resulted in an improvement in FMD, but did not influence PWV and AI.

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

In the article, the name of the co-author was given incorrectly. The correct name of the author is Mohammad Ali Mansournia. In the abstract section the correct abbreviation of "mean difference" is MD.

The Effects of Vitamin D Supplementation on Biomarkers of Inflammation and Oxidative Stress Among Women with Polycystic Ovary Syndrome: 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 summarize the effect of vitamin D supplementation on biomarkers of inflammation and oxidative stress among women with polycystic ovary syndrome (PCOS). Cochrane library, Embase, PubMed, and Web of Science database were searched to identify related randomized-controlled articles (RCTs) published up to November 2017. Two researchers assessed study eligibility, extracted data, and evaluated risk of bias of included RCTs, independently. To check heterogeneity 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 effect size. Seven RCTs were included into our meta-analysis. The findings showed that vitamin D supplementation in women with PCOS significantly decreased high-sensitivity C-reactive protein (hs-CRP) (SMD -1.03; 95% CI, -1.58, -0.49; p <0.001) and malondialdehyde (MDA) (SMD -1.64, 95% CI -2.26 to -1.02, p <0.001), and significantly increased total antioxidant capacity (TAC) levels (SMD 0.86, 95% CI 0.08 to 1.64, p=0.03). Vitamin D supplementation had no significant effect on nitric oxide (NO) (SMD 0.11, 95% CI -0.44 to 0.66, p=0.69) and total glutathione (GSH) levels (SMD 0.54, 95% CI -0.20 to 1.28, p=0.15). Overall, the current meta-analysis demonstrated that vitamin D supplementation to women with PCOS resulted in an improvement in hs-CRP, MDA and TAC, but did not affect NO and GSH levels.

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

This 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 standardized 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 (SMD=-6.34; 95% CI, -12.28, -0.40; p=0.04; I2: 65.0) and increased the quantitative insulin sensitivity check index (QUICKI) (SMD=0.01; 95% CI, 0.00, 0.02; p=0.01; I2: 0.0). However, melatonin administration did not significantly influence insulin levels (SMD=-1.03; 95% CI, -3.82, 1.77; p=0.47; I2: 0.53), homeostasis model assessment of insulin resistance (HOMA-IR) (SMD=-0.34; 95% CI, -1.25, 0.58; p=0.37; I2: 0.37) or HbA1c levels (SMD=-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.