Potential role of serum vitamin D as a risk factor in pediatric acute lymphoblastic leukemia.

Vitamin D deficiency/insufficiency (VDD, VDI) is common in children yet limited experience exists on the association of VDD and hematologic malignancies amongst this population. Therefore, this study aimed to compare serum vitamin D levels in children with acute lymphoblastic leukemia (ALL) and controls. Moreover, vitamin D levels is compared in subjects with and without relapse and evaluated as a prognostic factor for relapse-free survival (RFS). Children with newly diagnosed ALL were recruited as case group. Data on demographic variables as well as the dietary habits were collected by interview. In addition, serum 25(OH)D3 was measured. The case group was followed up for 36 months to assess RFS. Overall, 358 subjects were included in the study (n = 169 cases, n = 189 controls). The mean levels of 25(OH)D3 were 28.05 ± 18.87 and 28.76 ± 12.99 in cases and controls, respectively (p = .68). VDD was found in 15.4% (n = 26) and 4.2% (n = 8) of the case and control groups, respectively (p < .001). Relapse was seen in 18.34% of patients and vitamin D levels of 20 ng/mL or above were associated with longer RFS (p = .044 by log-rank test). In this study, VDD and VDI amongst children with ALL were significantly higher than controls. In addition, lower levels of Vitamin D were associated with increased risk of relapse.

The Effect of Garlic (Allium Sativum) on Polycystic Ovary Syndrome Related Hormones and Glycemic Parameters: A Randomized, Double-Blinded Clinical Trial.

Background: The purpose of the present study was to investigate the effect of garlic supplementation on androgen levels and glycemic-related markers in patients with PCOS. Methods: In these 8 weeks of randomized double-blinded control trial, 80 women were randomly assigned into two groups in which patients were asked to intake either 800 mg/day garlic or an identical placebo. A blood sample was obtained pre- and post-trial to assess androgens and glycemic-related parapets. A 3-days- food record and a short form of international physical activity questionnaires (IPAQ) were also evaluated at the beginning and end of the trial. Results: All participants completed the trial. Garlic supplementation resulted in significant reduction in fasting plasma glucose (-3.22 ± 7.41 vs. 0.72 ± 5.37; P = 0.008) and homeostatic model assessment for insulin resistance (HOMA-IR) (-0.29 ± 1.45 vs. 0.28 ± 1.20; P = 0.02). In addition, a trend to a significant improvement was detected in free androgen index (FAI) (P = 0.09), insulin levels (P = 0.07), and quantitative insulin sensitivity check index (QUICKI) (P = 0.06). However, no significant difference was found in testosterone and sex hormone-binding globulin (SHBG) (P > 0.05). Conclusions: Present study indicates that garlic supplementation could be beneficial for FPG and insulin resistance improvement. However, garlic supplementation does not show remarkable efficacy on androgens. Further studies are warranted to confirm the results.

The Therapeutic Impact of Garlic (Allium Sativum) on Oxidative Stress Markers among Polycystic Ovary Syndrome Patients: A Randomized, Double-Blinded Clinical Trial.

Background: The present study aimed to investigate the effect of garlic supplementation on oxidative stress markers in patients with polycystic ovary syndrome (PCOS). Methods: Eighty patients with PCOS were randomized and instructed to consume either garlic supplementation (800 mg/day) or a placebo (starch) for 8 weeks. They were also asked to avoid intake of any other supplement during the study. Oxidative stress-related markers including total antioxidant capacity, catalase, glutathione, malondialdehyde concentrations, and anthropometric measures were assessed at baseline and end of the trial. Results: Garlic supplementation resulted in significant improvement in catalase concentration (1.82 ± 9.28 vs. -1.55 ± 8.66; P value: 0.03), glutathione levels (29.15 ± 57.53 vs. 2.42 ± 77.51; P value: 0.048) as well as weight (-0.64 ± 1.94 vs. 0.11 ± 0.82; P value: 0.04), body mass index (BMI; -0.25 ± 0.75 vs. 0.05 ± 0.61; P value: 0.04), and waist circumference (-0.21 ± 0.77 vs. 0.02 ± 0.65; P value: 0.01). However, we failed to detect any significant change in hip circumference, waist to hip circumference ratio, total antioxidant capacity, and malondialdehyde levels between the two groups. Conclusions: The present study indicates that garlic supplementation could be beneficial in improving oxidative stress and weight loss among PCOS women.

The effect of garlic (Allium sativum) supplementation on the lipid parameters and blood pressure levels in women with polycystic ovary syndrome: A randomized controlled trial.

Polycystic ovary syndrome (PCOS) is the most prevalent female endocrine-related disorder in reproductive ages. The aim of the study was to investigate the effect of garlic on the lipid parameters and blood pressure levels in women with PCOS. The present study was a randomized, double-blinded control trial, conducted on 80 PCOS patients. Participants were taught to intake either a total 800 mg/day garlic supplement or an identical placebo (starch) after lunch for 8 weeks. Physical activity, diet intake, anthropometric measures, and blood pressure were evaluated at baseline and end of the study. The blood sample was also taken to assess the change in outcomes of interest at the pre- and post-intervention. Garlic supplementation significantly reduced serum total cholesterol (change mean difference: -8.05, 95% CI: -15.47, -0.62) and LDL-C (change mean difference: -7.67, 95%CI: -14.64, -0.70) levels in comparison to the control group. In addition, a trend to a significant decrease was found in serum triglyceride levels and Systolic blood pressure; however, no significant difference was observed between two groups in HDL-C and diastolic blood pressure levels. The present study suggested that garlic supplementation might be effective on lipid markers improvement. Further studies are needed to confirm our findings.

Effects of Folic Acid Supplementation on Inflammatory Markers: A Grade-Assessed Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials.

It has been theorized that folic acid supplementation improves inflammation. However, its proven effects on inflammatory markers are unclear as clinical studies on this topic have produced inconsistent results. To bridge this knowledge gap, this systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of folic acid supplementation on serum concentrations of the inflammatory markers C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Methods: To identify eligible RCTs, a systematic search up to April 2021 was completed in PubMed/Medline, Scopus, Web of Science, EMBASE, Cochrane databases, and Google Scholar using relevant keywords. A fix or random-effects model was utilized to estimate the weighted mean difference (WMD) and 95% confidence interval (95% CI). Results: Twelve RCTs were included in the present meta-analysis. The pooled analysis revealed that serum concentrations of CRP (WMD: -0.59 mg/L, 95% CI -0.85 to -0.33, p < 0.001) were significantly reduced following folic acid supplementation compared to placebo, but did not affect serum concentrations of IL-6 (WMD: -0.12, 95% CI -0.95 to 0.72 pg/mL, p = 0.780) or TNF-α (WMD: -0.18, 95% CI -0.86 to 0.49 pg/mL, p = 0.594). The dose-response analysis demonstrated a significant relationship between an elevated dosage of folic acid supplementation and lower CRP concentrations (p = 0.002). Conclusions: We found that folic acid supplementation may improve inflammation by attenuating serum concentrations of CRP but without significant effects on IL-6 and TNF-α. Future RCTs including a larger number of participants and more diverse populations are needed to confirm and expand our findings.

Folic Acid Supplementation Improves Glycemic Control for Diabetes Prevention and Management: A Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: There is a growing interest in the considerable benefits of dietary supplementations, such as folic acid, on the glycemic profile. We aimed to investigate the effects of folic acid supplementation on glycemic control markers in adults. METHODS: Randomized controlled trials examining the effects of folic acid supplementation on glycemic control markers published up to March 2021 were detected by searching online databases, including Scopus, PubMed, Embase, and ISI web of science, using a combination of related keywords. Mean change and standard deviation (SD) of the outcome measures were used to estimate the mean difference between the intervention and control groups at follow-up. Meta-regression and non-linear dose-response analysis were conducted to evaluate the association between pooled effect size and folic acid dosage (mg/day) and duration of the intervention (week). From 1814 detected studies, twenty-four studies reported fasting blood glucose (FBG), fasting insulin, hemoglobin A1C (HbA1C), and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) as an outcome measure. RESULTS: Results revealed significant reductions in FBG (weighted mean difference (WMD): -2.17 mg/dL, 95% CI: -3.69, -0.65, p = 0.005), fasting insulin (WMD: -1.63 pmol/L, 95% CI: -2.53, -0.73, p < 0.001), and HOMA-IR (WMD: -0.40, 95% CI: -0.70, -0.09, p = 0.011) following folic acid supplementation. No significant effect was detected for HbA1C (WMD: -0.27%, 95% CI: -0.73, 0.18, p = 0.246). The dose-response analysis showed that folic acid supplementation significantly changed HOMA-IR (r = -1.30, p-nonlinearity = 0.045) in non-linear fashion. However, meta-regression analysis did not indicate a linear relationship between dose, duration, and absolute changes in FBG, HOMA-IR, and fasting insulin concentrations. CONCLUSIONS: Folic acid supplementation significantly reduces some markers of glycemic control in adults. These reductions were small, which may limit clinical applications for adults with type II diabetes. Further research is necessary to confirm our findings.

Effects of Folic Acid Supplementation on Oxidative Stress Markers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

(1) Background: This systematic review and meta-analysis aimed to assess the effects of folic acid supplementation on oxidative stress markers. (2) Methods: Online database including PubMed, Scopus, Web of Science, and Cochrane were searched up to January 2021, to retrieve randomized controlled trials (RCTs) which examined the effect of folic acid supplementation on markers of oxidative stress. Meta-analyses were carried out using a random-effects model. I2 index was used to evaluate the heterogeneity of RCTs. (3) Results: Among the initial 2322 studies that were identified from electronic databases search, 13 studies involving 1013 participants were eligible. Pooled effect size from 13 studies indicated that folic acid supplementation elicits a significant rise in serum concentrations of glutathione (GSH) (WMD: 219.01 umol/L, 95% CI 59.30 to 378.71, p = 0.007) and total antioxidant capacity (TAC) (WMD: 91.70 umol/L, 95% CI 40.52 to 142.88, p < 0.001) but has no effect on serum concentrations of nitric oxide (NO) (WMD: 2.61 umol/L, 95% CI -3.48 to 8.72, p = 0.400). In addition, folic acid supplementation significantly reduced serum concentrations of malondialdehyde (MDA) (WMD: -0.13 umol/L, 95% CI -0.24 to -0.02, p = 0.020). (4) Conclusions: This meta-analysis study suggests that folic acid supplementation may significantly improve markers within the antioxidative defense system by increasing serum concentrations of GSH and TAC and decreasing serum concentrations of MDA.

The efficacy of alpha-lipoic acid in improving oxidative, inflammatory, and mood status in women with episodic migraine in a randomised, double-blind, placebo-controlled clinical trial.

AIM: Migraine is a common neurovascular disorder, which is associated with severe to moderate disabling headaches. Oxidative stress and inflammation might play a role in migraine pathogenesis and the mood disorders. Considering the antioxidant and anti-inflammatory properties of alpha-lipoic acid (ALA), this study was designed to investigate its effect on oxidative, inflammatory, and mood conditions in women with episodic migraine. METHODS: In total, 92 women with episodic migraine participated in the study. The patients were randomly divided into two groups, receiving a 300-mg capsule of ALA or placebo twice daily for 3 months. To assess the oxidative and inflammatory status, the serum levels of total antioxidant capacity (TAC), total oxidant status (TOS), glutathione (GSH), malondialdehyde (MDA), oxidative stress index (OSI), and C-reactive protein (CRP) were determined at the beginning and at the end of the intervention. A depression, anxiety, stress scale (DASS-21-items) questionnaire was used to evaluate mood status. RESULTS: Finally, 79 patients reached the final analysis stage. At the end of the intervention, a significant decrease in the serum levels of MDA (means difference [MD]: -0.83, 95% confidence intervals (CI): -1.04, -0.62 nmol/mL vs MD: -0.32, CI: -0.48, -0.15 nmol/mL; P < .001) and CRP (MD: -0.78, CI: -1.17, -0.39 mg/L vs MD: -0.63, CI: -1.80, 0.52 mg/L; P < .001) was observed in the ALA as compared with the placebo group, but changes in serum GSH (P = .086), TAC (P = .068), TOS (P = .225), and OSI (P = .404) were not statistically significant. In addition, depression, anxiety, and stress (with P < .001, in all cases) had significantly decreased in the intervention as compared with the control group. CONCLUSION: The results of this study suggest that ALA supplementation for 3 months has beneficial effects on improving the oxidative, inflammatory, and mood conditions of patients suffering from episodic migraine.

The Relationship Between Antioxidants and Inflammation in Children With Attention Deficit Hyperactivity Disorder.

INTRODUCTION: Recent studies have identified Attention Deficit Hyperactivity Disorder (ADHD) as an inflammatory condition associated with immunological and oxidative responses. Therefore, it is necessary to examine these processes in these patients. The present study aimed at investigating the relationship between the dietary intake of antioxidants, Superoxide Dismutase (SOD) activity, and the serum levels of inflammatory factors in ADHD students. METHODS: This retrospective case-control study was conducted on 64 ADHD children aged 6 - 13 years. The demographic questionnaire, Food Frequency Questionnaire, and Baecke Physical Activity Questionnaire were used for data collection. SOD activity and the serum level of inflammatory factors (homocysteine, interleukin-6, and C-reactive Protein (CRP)) were measured in all patients. According to the CRP values, 32 patients were included in the case group (CRP≥1 mg/L) and 32 patients in the control group (0≤CRP<1 mg/L). RESULTS: There was no significant difference between the two groups in age, sex, weight, height, and body mass index. In the case group, the mean SOD activity (P=0.034), the physical activity (P=0.04), zinc intake (P=0.02), and homocysteine levels were higher than the control group (P=0.001). Of all studied variables, the best predictors were homocysteine (OR: 1.34, 95% CI: 1.082-1.670, P=0.029) and physical activity (OR: 0.85, 95% CI: 0.761-0.952, P=0.022) respectively, whereas other variables were not significant predictors. CONCLUSION: The present study showed that the level of inflammatory factors in the case group was significantly higher than the control group. Homocysteine and physical activity can predict the inflammation status induced by CRP.

Assessment and comparison of the antioxidant defense system in patients with type 2 diabetes, diabetic nephropathy and healthy people: A case-control study.

INTRODUCTION: Findings of previous studies in the field of antioxidant defense system in patients with type 2 diabetes (T2DM), diabetic nephropathy (DM) are limited and conflicting. Therefore, we evaluated the antioxidant defense system status in type 2 diabetes patients, diabetic nephropathy and healthy subjects in Iranian population. METHODS: This population-based case-control study was conducted in 2019 and included 30 individuals with T2DM and 30 patients with DN, as the case groups and 30 healthy subjects for the control group. Individuals entered to the study for case group were diagnosed as T2DM patients based on fast glucose blood tests (FGB) (≥126 mg/dL) and HbA1 (≥6.5%). DN was defined based on these tests and macroalbuminuria (>300 mg/day). Serum was carefully separated and antioxidant defense system status was estimated. Dietary intakes were evaluated by using a food frequency questionnaire (FFQ). RESULTS: Energy intake in control group was higher than case groups; BMI was higher in the DN group compared to the other groups. Significantly higher levels of MDA were observed in T2DM patients compared to control group in crude model (1.255 vs. 1.079 nmol/L; P = 0.006). The same results were shown after adjustment for potential confounders (1.256 vs. 1.085 nmol/L; P = 0.022). Total antioxidant capacity (TAC) was less in case groups compared with control group; level of catalase (CTL) and superoxide dismutase enzymes comparisons showed that DN patients had higher level than control group, but these associations were not significant. CONCLUSIONS: We found that MDA levels were significantly higher in T2DM patients compared to control group. Level of TAC was less in case groups in comparison to controls. SOD and CTL levels were higher in DN compared to controls; these associations were not significant.

Omega-3 and vitamin E co-supplementation can improve antioxidant markers in obese/overweight women with polycystic ovary syndrome.

Background: Polycystic ovary syndrome is one of the most important factors in female infertility. Oxidative stress is likely to contribute to increased insulin and androgen production in the ovaries, as well as probably impairing follicle production. Aims: This study aims to determine the complementary effects of omega-3 and vitamin E supplements on certain oxidative stress indices in obese and overweight women with polycystic ovary syndrome. Materials and Methods: This double-blind, randomized clinical trial was performed on polycystic ovary syndrome subjects with BMI > 25. Patients were randomly allocated into two groups to receive either 2 g of omega-3 plus 400 IU of vitamin E, or a placebo, for 8 weeks. At the beginning and the end of the study, total antioxidant capacity, glutathione levels, catalase activity, malondialdehyde concentrations, as well as dietary intake and physical activity were evaluated. Statistical analysis was performed using SPSS. Results: 32 patients in the intervention group and 30 patients in the placebo group completed the study. Co-supplementation of omega-3 and vitamin E significantly increased total antioxidant capacity (mg/dl) (1.15 ± 0.93 vs -0.6 ± 0.72; P < 0.001), catalase activity (IU/L) (1.19 ± 1.06 vs 0.12 ± 0.36; P < 0.001) and glutathione levels (µmol/L) (1.5 ± 1.06 vs 0.23 ± 1.43; P = 0.028). Additionally, a significant reduction of malondialdehyde levels (nmol/L) (-0.34 ± 0.32 vs 0.57 ± 2.20; P = 0.008) was observed, in comparison with placebo. Conclusion: Co-supplementation with omega-3 and vitamin E had beneficial effect on total antioxidant capacity, malondialdehyde concentrations, glutathione levels and catalase activity.