Effects of folic acid with vitamin B12/vitamin B6 intervention on serum homocysteine metabolism and complications in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials

作者：Yaqi Yin, Ziming Zhao, Xu Wang, Qibiao Wu · 发表于：Frontiers in Nutrition · 年份：2025 · DOI：10.3389/fnut.2025.1701310 · 被引用次数：2 · 研究领域：Folate and B Vitamins Research、Liver Disease Diagnosis and Treatment、Alcoholism and Thiamine Deficiency

Aims Folic acid and B vitamins play key roles in regulating serum homocysteine metabolism. Elevated homocysteine levels have been associated with insulin resistance and diabetes-related complications in patients with type 2 diabetes mellitus. This study evaluated the effects of folic acid supplementation combined with B vitamins (B12 and B6) on homocysteine levels and complication risk in adults with type 2 diabetes mellitus. Methods We conducted a systematic search of eight databases from inception through August 30, 2025. The primary efficacy outcome was serum homocysteine level, while safety outcomes included the overall incidence and specific types of diabetes-related complications. Meta-analyses were performed using R version 4.5.0 with the meta package (version 8.1-0), employing random-effects models. Results are presented as standardized mean differences (SMDs) with 95% confidence intervals (CIs) for continuous outcomes and risk ratios (RRs) with 95% CIs for dichotomous outcomes. Results Twenty-nine studies met the inclusion criteria: 26 investigated folic acid plus vitamin B12, one examined folic acid plus vitamin B6, and two evaluated folic acid in combination with both vitamins B12 and B6. Supplementation with folic acid plus vitamin B12 (SMD = −2.77, 95% CI [−3.23, −2.30], P < 0.0001) significantly reduced serum homocysteine levels and decreased the incidence of total complications (RR = 0.30, 95% CI [0.24, 0.38], P < 0.0001). Similar results were als...