Paternal Folate Status and Sperm Quality, Pregnancy Outcomes, and Epigenetics: A Systematic Review and Meta-Analysis

source extracted confidence: high 2026-04-09
#animals #dietary-supplements #epigenesis-genetic #female #folic-acid

Paternal Folate Status and Sperm Quality, Pregnancy Outcomes, and Epigenetics: A Systematic Review and Meta-Analysis

Hoek et al., 2020 | Mol Nutr Food Res | Meta Analysis

Citation

Hoek Jeffrey, Steegers-Theunissen Régine P M, ... Schoenmakers Sam. Paternal Folate Status and Sperm Quality, Pregnancy Outcomes, and Epigenetics: A Systematic Review and Meta-Analysis. Mol Nutr Food Res. 2020-May;64(9):e1900696. doi:10.1002/mnfr.201900696

Abstract

SCOPE: The effectiveness of maternal folate in reducing the risk of congenital malformations during pregnancy is well established. However, the role of the paternal folate status is scarcely investigated. The aim of this study is to investigate the evidence of associations between the paternal folate status and sperm quality, sperm epigenome, and pregnancy outcomes. METHODS AND RESULTS: Databases are searched up to December 2017 resulting in 3682 articles, of which 23 are retrieved for full-text assessment. Four out of thirteen human and two out of four animal studies show positive associations between folate concentrations and sperm parameters. An additional meta-analysis of four randomized controlled trials in subfertile men shows that the sperm concentration increases (3.54 95% confidence interval (CI) [-1.40 to 8.48]) after 3-6 months of 5 mg folic acid use per day compared to controls. Moreover, two out of two animal and one out of three human studies show significant alterations in the overall methylation of the sperm epigenome. One animal and one human study show associations between low folate intake and an increased risk of congenital malformations. CONCLUSIONS: This systematic review and meta-analysis shows evidence of associations between paternal folate status and sperm quality, fertility, congenital malformations, and placental weight.

Key Findings

Databases are searched up to December 2017 resulting in 3682 articles, of which 23 are retrieved for full-text assessment. Four out of thirteen human and two out of four animal studies show positive associations between folate concentrations and sperm parameters. An additional meta-analysis of four randomized controlled trials in subfertile men shows that the sperm concentration increases (3.54 95% confidence interval (CI) [-1.40 to 8.48]) after 3-6 months of 5 mg folic acid use per day compared

Outcomes Measured

  • Requires manual extraction

Population

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

MeSH Terms

  • Animals
  • Dietary Supplements
  • Epigenesis, Genetic
  • Female
  • Folic Acid
  • Humans
  • Male
  • Pregnancy
  • Pregnancy Outcome
  • Spermatozoa

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, Systematic Review
  • Vertical: folate

Provenance

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