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

• Published in: Molecular nutrition & food research 2020-05, Vol.64 (9), p.e1900696-n/a
• Main Authors: Hoek, Jeffrey, Steegers‐Theunissen, Régine P. M., Willemsen, Sten P., Schoenmakers, Sam
• Format: Article
• Language: English
• Subjects: Animals; Confidence intervals; Congenital defects; congenital malformations; Dietary Supplements; Epigenesis, Genetic; Epigenetics; Female; Fertility; folate; Folic acid; Folic Acid - blood; Folic Acid - pharmacology; folic acid supplements; Humans; Male; Meta-analysis; Methylation; Placenta; Pregnancy; Pregnancy Outcome; Review; Reviews; Risk reduction; Sperm; sperm quality; Spermatozoa - drug effects; Spermatozoa - physiology; Systematic review; Vitamin B
• ISSN: 1613-4125; 1613-4133; 1613-4133
• DOI: 10.1002/mnfr.201900696

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. The aim of this study is to investigate and provide an overview of the evidence of associations between the periconceptional paternal folate status and folic acid supplement use and sperm quality, sperm epigenome, and pregnancy outcomes in both human and animal studies. It is concluded that more research is necessary into the periconceptional roles of paternal micronutrients.