Folic acid supplementation and blood pressure: a GRADE-assessed systematic review and dose-response meta-analysis of 41,633 participants.

Hypertension is a predisposing factor for cardiovascular disease (CVD). The extant literature regarding the effects of folic acid supplementation on blood pressure (BP) is inconsistent. Therefore, this systematic review and meta-analysis of randomized controlled trials was conducted to summarize the effects of folic acid supplementation on BP. A systematic search was carried out in PubMed, Scopus, ISI Web of Science, and Cochrane library, from database inception to August 2021. Data were pooled using the random-effects method and were expressed as weighted mean difference (WMD) and 95% confidence intervals (CI). The pooled results of 22 studies, including 41,633 participants, showed that folic acid supplementation significantly decreased systolic BP (SBP) (WMD: -1.10 mmHg; 95% CI: -1.93 to -0.28; p = 0.008). Subgroup analysis showed that the results remained significant when baseline SBP was ≥120 mmHg, intervention duration was ≤6 weeks, intervention dose was ≥5 mg/d, in patients with CVD, males and females, and overweight participants, respectively. Furthermore, the changes observed in diastolic BP (DBP) (WMD: -0.24 mmHg; 95% CI: -0.37 to -0.10; p < 0.001) were also statistically significant. However, subgroup analysis showed that the results remained significant in subject with elevated DBP, long term duration of intervention (>6 weeks), low dose of folic acid (<5 mg/day), CVD patients, both sexes and male, and participants with normal BMI. Dose-response analysis showed that folic acid supplementation changed SBP and DBP significantly based on dose and duration. However, meta-regression analysis did not reveal any significant association between dose and duration of intervention with changes in SBP. The present study demonstrates the beneficial effects of folic acid supplementation on BP by decreasing both SBP and DBP.

The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines.

The current study was performed to evaluate the effects of alpha-lipoic acid (ALA) supplementation on lactate, nitric oxide (NO), vascular cell adhesion molecule-1 (VCAM-1) levels, and clinical symptoms in women with episodic migraines. Considering the inclusion and exclusion criteria, ninety-two women with episodic migraines participated in this randomized, double-blind, placebo-controlled, parallel-design trial. The participants were randomly assigned to receive either 300 mg/day ALA or placebo, twice per day for 12 weeks. The primary outcomes included headache severity, headache frequency per month, and duration of attacks and the secondary outcomes included lactate (a marker of mitochondrial function), NO, and VCAM-1 serum levels were measured at baseline and the end of the intervention. At the end of the study, there was a significant decrease in lactate serum levels (- 6.45 ± 0.82 mg/dl vs - 2.27 ± 1.17 mg/dl; P = 0.039) and VCAM-1 (- 2.02 ± 0.30 ng/ml vs - 1.21 ± 0.36 ng/ml; P = 0.025) in the ALA as compared to the placebo group. In addition, the severity (P < 0.001), frequency (P = 0.001), headache impact test (HIT-6) (P < 0.001), headache dairy results (HDR) (P = 0.003), and migraine headache index score (MHIS) (P < 0.001) had significantly decreased in the intervention as compared to the control group. No significant changes were observed for NO levels and duration of migraine pains. ALA supplementation can be considered a potential adjunct treatment in patients with migraine due to its improving mitochondrial and endothelial functions and clinical symptoms.

Beneficial effects of folic acid supplementation on lipid markers in adults: A GRADE-assessed systematic review and dose-response meta-analysis of data from 21,787 participants in 34 randomized controlled trials.

Folic acid supplementation has received considerable attention in the literature, yet there is a large discrepancy in its effects on lipid markers in adults. Therefore, this systematic review and meta-analysis of 34 randomized controlled trials (RCTs) evaluated the effects of folic acid supplementation on triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol concentrations in a cohort of 21,787 participants. A systematic search current as of March 2021 was performed in PubMed/Medline, Scopus, Web of Science, and Embase using relevant keywords to identify eligible studies. A fix or random-effects model was used to estimate the weighted mean difference (WMD) and 95% confidence intervals (CIs). Thirty-four RCTs were included in this meta-analysis. The pooled analysis revealed that serum TG (WMD: -9.78 mg/dL; 95% CI: -15.5 to -4.00; p = 0.001, I2=0.0%, p = 0.965) and TC (WMD: -3.96 mg/dL; 95% CI: -6.71 to -1.21; p = 0.005, I2=46.9%, p = 0.001) concentrations were significantly reduced following folic acid supplementation compared to placebo. However, folic acid supplementation did not affect serum concentrations of LDL (WMD: -0.97 mg/dL; 95% CI: -6.82 to 4.89; p = 0.746, I2=60.6%, p < 0.001) or HDL cholesterol (WMD: 0.44 mg/dL; 95% CI: -0.53 to 1.41; p = 0.378, I2= 0.0%, p = 0.831). A significant dose-response relationship was observed between the dose of folic acid supplementation and serum concentrations of HDL cholesterols (r = 2.22, p = 0.047). Folic acid supplementation reduced serum concentrations of TG and TC without affecting LDL or HDL cholesterols. Future large RCTs on various populations are needed to show further beneficial effects of folic acid supplementation on lipid profile.

Effects of chromium supplementation on blood pressure, body mass index, liver function enzymes and malondialdehyde in patients with type 2 diabetes: A systematic review and dose-response meta-analysis of randomized controlled trials.

BACKGROUND: Several studies reported beneficial effects of chromium supplementation for management of type 2 diabetes mellitus (T2DM). The present study aimed to provide a systematic review and meta-analysis of randomized controlled trials (RCTs) examining the effects of chromium supplementation on blood pressure, body mass index (BMI), liver function enzymes and malondialdehyde (MDA) in patients with T2DM. METHODS: PubMed, Scopus, and Embase were searched up to 15 November 2020 with no language and time restriction. RCTs that reported the effects of chromium supplementation on blood pressure, BMI, liver function enzymes and MDA in patients with T2DM were included. A random-effects model was used to compute weighted mean differences (WMDs) with 95 % confidence intervals (CIs). Between-study heterogeneity was assessed by Cochran's Q test and quantified by I2 statistic. RESULTS: Of 3586 publications, 15 RCTs were included for the meta-analysis. Pooled effect sizes indicated that chromium significantly reduced diastolic blood pressure (DBP) (WMD): -2.36 mmHg, 95 % CI: -4.14, -0.60; P = 0.008), and MDA (WMD: -0.55 umol/l, 95 % CI: -0.96, -0.14; P = 0.008). However, chromium supplementation did not significantly affect BMI, systolic blood pressure (SBP), alanine aminotransferase (ALT), aspartate aminotransferase (AST). Meta-regression analysis did not show significant linear relationship between dose of chromium and change in BMI (p = 0.412), SBP (p = 0. 319), DBP (p = 0.102), ALT (p = 0.923), AST (p = 0.986) and MDA (p = 0.055). CONCLUSION: The present systematic review and meta-analysis shows that supplementation with chromium at dose of 200-1000 µg/day may reduce DBP and MDA in T2DM patients.

Effects of chromium supplementation on lipid profile in patients with type 2 diabetes: A systematic review and dose-response meta-analysis of randomized controlled trials.

BACKGROUND: The purpose of this study was to determine the influence of chromium supplementation on lipid profile in patients with type 2 diabetes mellitus (T2DM). METHODS: A systematic search was performed in Scopus, Embase, Web of Science, the Cochrane library and PubMed databases to find randomized controlled trials (RCTs) related to the effect of chromium supplementation on lipid profile in patients with T2DM, up to June 2020. Meta-analyses were performed using the random-effects model, and I2 index was used to evaluate heterogeneity. RESULTS: The primary search yielded 725 publications. 24 RCTs (with 28 effect size) were eligible. Our meta-analysis indicated that chromium supplementation resulted in a significant decrease in serum levels of triglyceride (TG) (MD: -6.54 mg/dl, 95 % CI: -13.08 to -0.00, P = 0.050) and total cholesterol (TC) (WMD: -7.77 mg/dl, 95 % CI: -11.35 to -4.18, P < 0.001). Furthermore, chromium significantly increases high-density lipoprotein (HDL) (WMD: 2.23 mg/dl, 95 % CI: 0.07-4.40, P = 0.043) level. However, chromium supplementation did not have significant effects on low-density lipoprotein (LDL) (WMD: -8.54 mg/dl, 95 % CI: -19.58 to 2.49, P = 0.129) level. CONCLUSION: Chromium supplementation may significantly improve lipid profile in patients with T2DM by decreasing TG and TC and increasing HDL. However, based on our analysis, chromium failed to affect LDL. It should be noted that the lipid-lowering properties of chromium supplementation were small and may not reach clinical importance.

Vitamin B12 and Folate Status in Patients with Epilepsy Under Levetiracetam Monotherapy.

BACKGROUND: Antiepileptic drugs (AEDs) may lead to an increase in the plasma concentration of homocysteine. There is limited information, especially from Iran, regarding the risk in patients who are treated with levetiracetam as a new type of AED. The aim of the present study was to investigate the effect of levetiracetam on plasma homocysteine, vitamin B12, and folate levels in adult patients with epilepsy. METHODS: We conducted a case-control study and enrolled adult patients with epilepsy who had received monotherapy with levetiracetam for at least 6 months at some time prior to the study. homocysteine serum, vitamin B12, and folate were measured, and folate and vitamin B12 intake was determined by the food frequency questionnaire (FFQ). RESULTS: Thirty-three patients on levetiracetam and 35 control subjects aged between 18 and 60 years were enrolled. No statistically significant differences in the means of the serum markers of vitamin B12, FA, and homocysteine levels were found between the two groups. In the first model, i.e., the crude model, no significant differences were observed in the serum concentrations of homocysteine, vitamin B12, and folate. In the second model, education was considered, and body mass index and folate intake was controlled with no significant difference being observed in the mean homocysteine serum level. CONCLUSIONS: Treatment with levetiracetam in patients with epilepsy has no effect on the serum levels concentrations of homocysteine, vitamin B12, and folate. This medication is suggested for patients who use AEDs on a long-term basis and at high dosages.