Abstract Body (Do not enter title and authors here): Introduction: Cardiovascular diseases are among the leading causes of morbidity and mortality worldwide. A key component is arteriopathy due to oxidative stress, involving homocysteine as a modifiable risk factor by supplementing folic acid.
Hypothesis: This meta-analysis hypothesizes that folic acid supplementation reduces the risk of cardiovascular diseases by lowering homocysteine levels.
Methods: Following PRISMA guidelines, a systematic search was conducted in PubMed, Cochrane, Scopus, Web of Science, CINAHL, and EMBASE databases up to March 18, 2024. Randomized controlled trials (RCTs) were included, comparing folic acid supplementation with placebo or alternative treatments in adult patients. The primary outcomes were impact on cardiovascular diseases, stroke, coronary heart disease, peripheral arterial disease, and mortality. Data were extracted and analyzed using random-effects models to calculate risk ratios (RR) and 95% confidence intervals (CI).
Results: Our analysis included 16 studies with 39,034 participants meeting the inclusion criteria. The meta-analysis found a statistically significant reduction in stroke risk [RR: 0.87; 95%CI: 0.79, 0.96; P = 0.004] and mortality [RR: 0.92; 95%CI: 0.85, 0.99; P = 0.01]. It showed no statistically significant risk reduction in cardiovascular disease, coronary heart disease, or peripheral arterial disease. Additionally, when evaluating its effectiveness on HDL and LDL, folic acid supplementation showed no statistically significant difference in any of these values between the studies.
Conclusions: Folic acid supplementation showed efficacy in reducing the risk of stroke and mortality. However, future research is necessary to investigate homocysteine's role in cardiovascular diseases and events. Systematic review registration number: PROSPERO registry— CRD42024525945.