Folic acid supplementation on inflammation and homocysteine in type 2 diabetes mellitus: systematic review and meta-analysis of randomized controlled trials
What this study found
Folic acid supplementation in adults with type 2 diabetes mellitus reduced homocysteine levels and may modestly reduce C-reactive protein. No significant effects were seen for TNF-alpha or IL-6. The overall certainty of evidence was moderate for homocysteine and low for IL-6, supporting a possible but limited anti-inflammatory benefit.
- Study & population
- Systematic review and meta-analysis of randomized controlled trials in adults with type 2 diabetes mellitus.
- Intervention
- Oral folic acid or folate supplementation was evaluated across randomized trials, with doses ranging from 0.25 mg to 10 mg and treatment durations from 2 weeks to 6 months.
- Key limitation
- The evidence was limited by heterogeneity across trials, small sample sizes, and short intervention periods.
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Open PDFOriginal abstract
Background The beneficial effects of folate have been observed under different conditions, but the available evidence on inflammation and reduction of cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM) is limited. The study aimed to explore the effects of folate on inflammation and homocysteine amongst individuals with T2DM. Methods PubMed, Scopus, and Cochrane Library were used to search for evidence. A random-effect model meta-analysis through Review Manager (version 5.4) and metaHun was performed. Results were reported as standardized mean differences (SMD) and 95% confidence intervals graphically using forest and funnel plots. Results Data from 9 trials with 426 patients living with T2DM were analyzed. Folic acid supplementation significantly revealed a large effect size on homocysteine levels compared to placebo, SMD = −1.53, 95%CI (−2.14,−0.93), p < 0.05. Additionally, we observed a medium marginal effect size on C-reactive protein (SMD = −0.68, 95%CI (−1.34, −0.01), p = 0.05). However, no significant effect on tumor necrosis factor-α (SMD = −0.86, 95%CI (−2.65, 0.93), p = 0.34), and interleukin-6 (SMD = −0.04, 95%CI (−1.08, 1.01), p = 0.95) was observed. Conclusion Evidence analyzed in this study suggests that folic acid supplementation in T2DM reduces homocysteine and may mitigate CVDs. However, its effect on inflammation is inconclusive.