The effectiveness and safety of the active form of folate on biochemical parameters in women of childbearing age: A systematic review and meta-analysis

source extracted confidence: high 2026-04-09
#humans #female #folic-acid #pregnancy #dietary-supplements

The effectiveness and safety of the active form of folate on biochemical parameters in women of childbearing age: A systematic review and meta-analysis

Xie et al., 2025 | Medicine (Baltimore) | Meta Analysis

Citation

Xie Min, Qing Xuemei, ... Zhang Jing. The effectiveness and safety of the active form of folate on biochemical parameters in women of childbearing age: A systematic review and meta-analysis. Medicine (Baltimore). 2025-Dec-12;104(50):e46564. doi:10.1097/MD.0000000000046564

Abstract

BACKGROUND: Low folate levels in women of childbearing age can cause various health issues. Additionally, low perinatal folate concentrations are a significant cause of neural tube defects. Currently, folic acid supplements mainly consist of folic acid and the active form of folate. Therefore, this systematic review and meta-analysis aimed to evaluate the effectiveness and safety of the active form of folate in women of childbearing age. METHODS: We searched the published literature in PubMed, Medline, EMBASE, The Cochrane Library, China National Knowledge Infrastructure, and Wanfang. Randomized controlled trials (RCTs) were obtained to assess the effects of the active form of folate versus folic acid in women of childbearing age. The random or fixed effects model was used to analyze the data in meta-analysis. The results were expressed as standardized mean differences or risk ratios along with their corresponding 95% confidence intervals. RESULTS: Eleven RCTs were identified in our systematic review. The results indicated that the active form of folate supplementation might significantly increase plasma folate (P = .04), increase erythrocyte folate (P = .01), and decrease unmetabolized folic acid (P < .0001). Supplementation with the active form of folate might increase the subsequent pregnancy rates (P = .0005) and might decrease the incidence of adverse pregnancy outcomes (P = .0003) in women with a history of adverse pregnancy outcomes. However, there were no significant differences in homocysteine, vitamin B12, and betaine. In addition, subgroup analyses showed a significant increase in plasma folate and erythrocyte folate in the active form of folate supplementation group, specifically in subgroups with dosage ≥0.4 mg, intervention of the active form of folate supplementation versus the equimolar mass of folic acid, and intervention duration ≥12 weeks. CONCLUSION: Active form of folate supplementation might contribute to higher plasma folate, erythrocyte folate, and subsequent pregnancy rates, lower unmetabolized folic acid, and lower incidence of adverse pregnancy outcomes in women of childbearing age. Due to the limitation in the quality of involved studies and the short duration of treatment, more RCTs with high-quality, long-term duration and pregnancy outcomes are needed for further validation.

Key Findings

Eleven RCTs were identified in our systematic review. The results indicated that the active form of folate supplementation might significantly increase plasma folate (P = .04), increase erythrocyte folate (P = .01), and decrease unmetabolized folic acid (P < .0001). Supplementation with the active form of folate might increase the subsequent pregnancy rates (P = .0005) and might decrease the incidence of adverse pregnancy outcomes (P = .0003) in women with a history of adverse pregnancy outcomes

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size See abstract
Age Range See abstract
Condition See abstract

MeSH Terms

  • Humans
  • Female
  • Folic Acid
  • Pregnancy
  • Dietary Supplements
  • Randomized Controlled Trials as Topic
  • Pregnancy Outcome
  • Adult

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Systematic Review, Meta-Analysis
  • Vertical: folate

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09