Effects of vitamin D supplementation on liver fibrogenic factors, vitamin D receptor and liver fibrogenic microRNAs in metabolic dysfunction-associated steatotic liver disease (MASLD) patients: an exploratory randomized clinical trial.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global metabolic problem which can lead to irreversible liver fibrosis. It has been shown that vitamin D and its receptors contribute to fibrogenic pathways in the liver. However, the effect of vitamin D supplementation on liver fibrosis related factors have not been examined. This double blinded placebo controlled clinical trial was designed to investigate the effects on vitamin D supplementation on serum levels of VDR, fibrogenic factors and fibrogenic MicroRNAs in MASLD patients. METHODS: Forty six MASLD patients after block matching for sex and BMI were randomly assigned to receive 4000 IU/d vitamin D or placebo for 12 weeks. Weight, height and waist circumference were measured. Serum fibrogenic microRNAs, laminin, collagen type IV, hyaluronic acid, vitamin D, VDR, PTH, blood fasting glucose, serum fasting insulin, lipid profile, ALT and AST were determined at the baseline and at the end of the trial. Insulin resistance and insulin sensitivity were calculated using the HOMA-IR and QUICKI equation. RESULTS: Supplementation with vitamin D for 12 weeks led to the significant increases in serum 25(OH) vitamin D, VDR and HDL-C compared to placebo (P < 0.001, P = 0.008 and P < 0.001). There were significant decreases in ALT, AST, FBS and LDL-C levels in the vitamin D group as compared to the placebo (P < 0.05). Laminin and hyaluronic acid concentrations were significantly decreased in the vitamin D group as compared to the placebo group, by -10.6 and - 28.7 ng/mL, respectively. Supplementation with vitamin D for 12 weeks resulted in a significant lower MiR-21 and MiR-122 gene expressions compared to the placebo group (P = 0.01 and P < 0.001, respectively). DISCUSSION: As the first randomized controlled trial on the effect of vitamin D supplementation on serum levels of VDR, fibrogenic factors and fibrogenic MicroRNAs in MASLD patients, we found a significant reduction in some liver fibrogenic factors, in liver transaminases and corresponding changes in some fibrosis-related MiRs and some metabolic factors. Further clinical trials with larger sample sizes and direct measures of liver fibrosis are needed to confirm these findings. TRIAL REGISTRATION NUMBER: (available at: http://www.irct.ir , identifier: IRCT201405251485N13), Registration date: 14-03-2017.

The effect of vitamin C on oxidative stress indices and skin regimentation of vitiligo patients.

It has been suggested that vitamin C is involved in suppressing stress oxidation signaling in vitiligo disease. However, the effect of vitamin C supplementation on stress oxidative factors has not been investigated in vitiligo subjects. This study was designed to examine the effects on vitamin C supplementation on serum levels of stress oxidative factors and regimentation in vitiligo patients. Forty-four vitiligo patients will be recruited in this study. After block matching for sex and number of phototherapy sessions, they will be randomly assigned to receive 1000 mg/d vitamin C or placebo for 8 weeks. The weight, height, and waist circumference of participants will be measured. Determination of serum stress oxidative indices (CAT, SOD, GPX, MDA, TOS, TAC) will be done at study baseline and at the end of the trial. Also, the regimentation will be determined using the VASI score. This is the first randomized controlled trial that will determine the effect of vitamin C supplementation on serum levels of stress oxidative indices and regimentation in vitiligo patients. The results of this trial will provide clinical evidence on the effectiveness of vitamin C supplementation in controlling oxidative stress in vitiligo patients. Trial registration number: This study is registered in the Iranian Registry of Clinical Trials website (available at http://www.irct.ir , identifier: IRCT20230123057193N1), Registration date: 2023/04/17.

The Effect of Zinc Supplementation on Lipid Profiles in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Dose-Response Meta-Analysis of Randomized Clinical Trials.

Research on the effects of zinc supplementation on lipid profiles in people with type 2 diabetes mellitus (T2DM) has been inconsistent. This systematic review and meta-analysis was performed to summarize the current data on the effects of zinc supplementation on lipid profiles in patients with T2DM. Three online databases including PubMed, Scopus, and Web of Science were searched to find relevant studies published until September 2022. The exposure was zinc supplementation, and the outcomes were low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), and total cholesterol (TC). Fourteen randomized clinical trials consisting of 1067 patients were included in the statistical analysis. Significant improvement was observed in all 4 lipid profile components. Following zinc supplementation, a significant decrease was observed in TC (weighted mean difference [WMD]: -16.16; 95% confidence interval [CI]: -26.43, -5.89; P = 0.002), LDL (WMD: -6.18; 95% CI: -9.35, -3.02; P < 0.001), and TG (WMD: -13.08; 95% CI: -21.83, -4.34; P = 0.003). After analyzing 13 studies reporting HDL, a significant increase was seen (WMD: 3.76; 95% CI: 1.30, 6.22; P = 0.003). In a nonlinear dose-response analysis, a significant inverse association was observed between <12 wk zinc supplementation and TC, LDL, and TG (TC: WMD: -5, Pnonlinearity < 0.001; LDL: WMD: -5, Pnonlinearity = 0.07, TG: WMD: -16.5, Pnonlinearity = 0.006). Nonlinear dose-response analysis shows that the optimum elemental zinc dosage for the best response to the supplementation for TC, LDL, and TG are 120, 100, and 140 mg/d, respectively (TC: WMD: -5, Pnonlinearity < 0.001; LDL: WMD: -10, Pnonlinearity = 0.006, TG: WMD: -50, Pnonlinearity = 0.031). In conclusion, we found significant changes in all 4 components of the lipid profile through zinc supplementation in T2DM patients. Based on our findings, zinc supplementation may have profound favorable consequences on the lipid profile of T2DM patients, especially in the zinc-deficient group.

The effect of zinc supplementation on anthropometric measurements in healthy children over two years: a systematic review and meta-analysis.

BACKGROUND: Zinc deficiency is one of the most important micronutrient deficiencies in children that can affect the children's growth pattern. In this regard, different studies were conducted to assess the effect of zinc supplementation on growth patterns in healthy children. To the best of our knowledge, no systematic review has summarized the results of these studies. So, in the present study, we systematically reviewed the result of the studies that assessed the effect of zinc supplementation on anthropometric parameters in healthy, over 2-year-old children. METHODS: A systematic search was carried out in PubMed, Scopus, and Web of Science from inception to November 2021. Data were pooled using the random-effects method and were expressed as weighted mean difference (WMD) and 95% confidence intervals (CI). RESULTS: The pooled results of eight studies, including 1586 participants, showed that zinc supplementation significantly increases height [(WMD): 0.9, 95% CI: (0.27, 1.52), p < 0.001], weight [(WMD): 0.51, 95% CI: (0.06, 0.97), p < 0.001], height for age (HAZ) [(WMD): 0.07, 95% CI: (0.03, 0.10), p < 0.001]. Also, meta-regression analysis did not reveal any significant association between dose and duration of intervention and anthropometric parameters. CONCLUSION: The present study demonstrates the beneficial effects of zinc supplementation on weight, height, and HAZ.

Effects of Fish-Oil Consumption on Psychological Function Outcomes in Psychosis: A Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials.

Research on the effects of fish oil on clinical symptoms and psychosocial functioning in people with psychosis has been inconsistent. We conducted this systematic review and meta-analysis to summarize the available data on the effects of oral intake of fish oil on psychological functioning in patients with psychosis. Three online databases including PubMed, Scopus, and Web of Science were searched to identify relevant studies published by April 2021. The exposure was oral fish-oil supplementation. The Positive and Negative Syndrome Scale (PANSS), the Brief Psychiatric Rating Scale (BPRS), and the Global Assessment of Functioning (GAF) were our outcome measures. Seventeen randomized clinical trials involving 1390 patients were included. No change in PANSS was observed following oral fish-oil intake [weighted mean difference (WMD): -0.87; 95% CI: -16.99, 15.26; P = 0.92]. In a nonlinear dose-response analysis, a significant inverse association was observed between <10 wk of fish-oil supplementation and PANSS (WMD: -10; P-nonlinearity = 0.02). Although analysis of 4 studies showed a nonsignificant reduction in BPRS after fish-oil intake (WMD: -2.990; 95% CI: -6.42, 0.44; P = 0.08), a nonlinear dose-response analysis revealed significant inverse associations between dose (>2200 mg/d) and duration of fish-oil supplementation (<15 wk) with BPRS score (WMD: -8; P-nonlinearity = 0.04). Combined effect sizes from 6 randomized clinical trials showed significant increases in GAF after oral administration of fish oil (WMD: 6.66; 95% CI: 3.39, 9.93; P < 0.001). In conclusion, we did not find any significant changes in PANSS and BPRS scores following fish-oil supplementation. Nevertheless, oral fish-oil intake significantly contributed to improvement in GAF scores. This is the first meta-analysis to examine the effects of fish oil on the psychological functioning scores of PANSS, BPRS, and GAF simultaneously.

Effects of Alpha Lipoic Acid Supplementation on Serum Levels of Oxidative Stress, Inflammatory Markers and Clinical Prognosis among Acute Ischemic Stroke Patients: A Randomized, Double Blind, TNS Trial.

Purpose: Stroke is one of the most common conditions causing death. There have been few studies examining the effects of alpha lipoic acid (ALA) on stroke patients. In this regard, the present randomized controlled clinical trial was conducted to examine the effects of ALA supplementation on serum albumin, and inflammatory and oxidative stress markers in stroke patients. Methods: The present paralleled randomized controlled clinical trial involved 42 stroke patients who were over 40 years and under enteral feeding. The participants were randomly assigned into two groups and finally 40 patients completed the study. Patients in alpha lipoic acid group (n=19) took 1200 mg ALA supplement daily along with their meal, and participants in control group (n=21) underwent the routine hospital diet for 3 weeks. Fasting blood samples were obtained and albumin, oxidative stress, and inflammatory indices were assessed at baseline, as well as at the end of the trial. Results: After 3 weeks, treatment of patients with ALA led to a significant decrease in tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) levels (P=0.01) compared to baseline. But serum levels of albumin, total antioxidant capacity (TAC), malondialdehyde (MDA), highsensitivity C-reactive protein (hs-CRP), IL-6 and TNF-α did not change significantly vs. control group (P>0.05). Conclusion: ALA did not significantly change the serum levels of albumin and inflammatory as well as antioxidant capacity indices in stroke patients compared with the control group. More clinical trials with large sample sizes and long duration are needed to clarify the effects of ALA on these patients.

The effect of vitamin E supplementation on biomarkers of endothelial function and inflammation among hemodialysis patients: A double-blinded randomized clinical trial.

OBJECTIVES: The present study was aimed to investigate the effect of alpha-tocopherol supplementation on biomarkers of endothelial function (Intercellular Adhesion Molecule 1 and Vascular Cell Adhesion Protein 1) and inflammatory markers (Interleukin 6 and high-sensitivity C-reactive protein) among the hemodialysis patients. METHODS: To conduct this randomized, double-blinded, and placebo-controlled clinical trial, 49 hemodialysis patients, aged 20-60 years, were recruited and randomly divided into the intervention and control groups. The intervention group (n = 25) received 600 IU alpha-tocopherol soft gels (200 IU three times daily), while the controls (n = 24) consumed the identical placebo soft gels for 10 weeks. At the baseline and end of the study, 7 ml pre-dialysis blood samples were taken from all participants to measure their serum concentrations of ICAM-1, VCAM-1, IL-6, and hs-CRP. RESULTS: Alpha-tocopherol supplementation reduced the serum levels of ICAM-1 and VCAM-1 significantly (-140.67 ± 57.25 ng/ml vs. -15.97 ± 79.19 ng/ml, P = 0.001 for ICAM-1 and --6.79 ± 4.76 ng/ml vs. 1.02 ± 3.22 ng/ml, P = 0.019 for VCAM-1). However, no significant difference was observed between the two groups regarding the serum levels of hs-CRP (-0.15 ± 0.19 mg/l vs. 0.02 ± 0.12 mg/l; P = 0.32) and IL-6 (-0.03 ± 0.1 pg/ml vs. - 0.06 ± 0.11 pg/ml; P = 0.65). CONCLUSIONS: Our results showed that 10 weeks of supplementation with 600 IU alpha-tocopherol improved ICAM-1 and VCAM-1 levels, but did not have any effect on the serum concentration of IL-6 and hs-CRP in hemodialysis patients. Further studies are required to confirm these findings.

Effects of vitamin D supplementation on liver fibrogenic factors in non-alcoholic fatty liver patients with steatohepatitis: study protocol for a randomized clinical trial.

BACKGROUND: It has been suggested that vitamin D and its receptors involve in suppressing fibrogenic signaling in non-alcoholic fatty liver disease (NAFLD). However, the effect of vitamin D supplementation on fibrogenic factors has not been investigated in NAFLD individuals with steatohepatitis. This study was designed to examine the effects on vitamin D supplementation on serum levels of vitamin D receptor (VDR), fibrogenic factors, and fibrogenic microRNAs (MiR) in NAFLD patients. METHODS: Forty-six NAFLD patients will be recruited in this study. After block matching for sex and BMI, they will be randomly assigned to receive 4000 IU/day vitamin D or placebo for 12 weeks. Weight, height, and waist circumference will be measured. Determination of serum fibrogenic MiRs, laminin, collagen type IV, hyaluronic acid, vitamin D, VDR, calcium, blood glucose, serum insulin, lipid profile, liver markers (ALT, AST, total, direct, and indirect bilirubin) will be done at study baseline and at the end of the trial. Insulin resistance and insulin sensitivity will be determined using the HOMA-IR and QUICKI equation. DISCUSSION: This is the first randomized controlled trial that will determine the effect of vitamin D supplementation on serum levels of VDR, fibrogenic factors, and fibrogenic MiRs in NAFLD patients. The results of this trial will provide clinical evidence on the effectiveness of vitamin D supplementation in controlling liver fibrosis in NAFLD patients. TRIAL REGISTRATION: Iranian Registry of Clinical Trials, IRCT201405251485N13 . Registered on 14 March 2017.

Lower glycemic indices and lipid profile among type 2 diabetes mellitus patients who received novel dose of Silybum marianum (L.) Gaertn. (silymarin) extract supplement: A Triple-blinded randomized controlled clinical trial.

OBJECTIVE: This randomized clinical trial was conducted to evaluate the effects of silymarin supplementation on glycemic indices and serum lipid profile in type 2 diabetes mellitus (T2DM) patients. METHODS: 40 T2DM patients (twenty male and twenty female), 25-50 years of age and on stable medication, were recruited for the present paralleled, randomized, triple-blinded, placebo-controlled clinical trial. The participants were randomly assigned to the silymarin or placebo groups, in which the patients either received 140 mg of silymarin, thrice daily (n = 20) or placebo (n = 20) for 45 days. Anthropometric and dietary intake data were collected at the baseline and end of the trial. Fasting blood samples were collected, and glycemic indices and lipid profile were determined at baseline, as well as the end of the study. RESULTS: Silymarin supplementation led to significant reduction in fasting blood sugar, serum insulin, homeostatic model assessment for insulin resistance, serum triglyceride and triglyceride to high-density lipoprotein cholesterol ratio as compared to the placebo, by 11.01, 14.35, 25.92, 23.7 and 27.67% respectively. There was significant increase in high-density lipoprotein cholesterol levels and quantitative insulin sensitivity check index in the silymarin group as compared to the placebo group, by 6.88 and 5.64% respectively, (p < 0.05). Total cholesterol and low-density lipoprotein cholesterol concentrations significantly decreased in the silymarin group as compared to the baseline, by 7.93 (p = 0.001) and 7.15% (p = 0.02), respectively. CONCLUSION: Silymarin supplementation may improve the glycemic indices and lipid profiles of T2DM patients. More studies are needed to validate the adjunct use of silymarin for metabolic control of T2DM patients.

Effects of Silybum marianum (L.) Gaertn. (silymarin) extract supplementation on antioxidant status and hs-CRP in patients with type 2 diabetes mellitus: a randomized, triple-blind, placebo-controlled clinical trial.

AIM: Diabetes is a serious metabolic disorder and oxidative stress and inflammation contribute to its pathogenesis and complications. Since Silybum marianum (L.) Gaertn. (silymarin) extract is an antioxidant with anti-inflammatory properties, this randomized clinical trial was conducted to evaluate the effects of silymarin supplementation on oxidative stress indices and hs-CRP in type 2 diabetes mellitus patients. METHODS: For the present paralleled, randomized, triple-blinded, placebo-controlled clinical trial, 40 type 2 diabetes patients aged 25-50 yr old and on stable medication were recruited from the Iranian Diabetes Society and endocrinology clinics in East Azarbayjan (Tabriz, Iran) and randomly assigned into two groups. Patients in the silymarin treatment group received 140 mg, thrice daily of dried extracts of Silybum marianum (n = 20) and those in the placebo group (n = 20) received identical placebos for 45 days. Data pertaining to height, weight, waist circumference and BMI, as well as food consumption, were collected at base line and at the conclusion of the study. Fasting blood samples were obtained and antioxidant indices and hs-CRP were assessed at baseline, as well as at the end of the trial. RESULTS: All 40 patients completed the study and did not report any adverse effects or symptoms with the silymarin supplementation. Silymarin supplementation significantly increased superoxide dismutase (SOD), glutathione peroxidase (GPX) activity and total antioxidant capacity (TAC) compared to patients taking the placebo, by 12.85%, 30.32% and 8.43%, respectively (p < 0.05). There was a significant reduction in hs-CRP levels by 26.83% (p < 0.05) in the silymarin group compared to the placebo group. Malondialdehyde (MDA) concentration significantly decreased by 12.01% (p < 0.05) in the silymarin group compared to the baseline. CONCLUSIONS: Silymarin supplementation improves some antioxidant indices (SOD, GPX and TAC) and decrease hs-CRP levels in T2DM patients.