Abstract
CONTEXT: There are various therapeutic approaches available to reduce homocysteine (Hcy) levels. However, it remains unclear which intervention is more effective for healthy adults. OBJECTIVES: A systematic review and network meta-analysis (NMA) were conducted to comprehensively investigate the efficacy of different nutritional supplements in reducing Hcy levels in healthy adults. DATA SOURCES: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to July 2023. DATA EXTRACTION: The lead author, year of publication, sample size, population characteristics, intervention measures, duration, and mean difference of Hcy levels from baseline to endline were extracted. DATA ANALYSIS: Data were pooled using a random-effects model. Network meta-analysis was conducted by integrating direct and indirect evidence. A total of 16 studies were included in this analysis. The nutritional supplement combination that achieved the highest ranking (surface under the cumulative ranking curve [SUCRA] = 75.8) was superior compared with a single supplement. Among similar or closely dosed folic acid (FA) supplements, 800 μg FA (SUCRA = 93.7) was the most effective option. When comparing various doses of different supplements, 1 mg of FA plus 7.2 mg of vitamin B6 (B6) plus 20 μg of vitamin B12 (B12; SUCRA = 83.9) ranked first and 800 μg of FA (SUCRA = 78.3) ranked second. In comparison with placebo or no-treatment control groups, interventions such as 1 mg of FA plus 7.2 mg of B6 plus 20 μg of B12 (mean difference [MD] = -1.03; 95% CI -1.71 to -0.36), 400 μg of FA plus 400 μg of B12 (MD = -0.87; 95% CI -1.46 to -0.27), and 800 μg of FA (MD = -0.84; 95% CI -1.12 to -0.56) were more effective in reducing Hcy levels. The random-effects summary MD for all interventions compared with placebo was -0.59 (95% CI -0.71 to -0.48; P < .0001). CONCLUSIONS: The NMA demonstrated that the combination of FA with other vitamins is more effective in reducing Hcy levels, particularly when the dose of FA is close to 800 μg. The combination of 1 mg of FA, 7.2 mg of B6, and 20 μg of B12 is considered the most favorable option. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42023453123.