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.