The Effect of Folate and Folate Plus Zinc Supplementation on Endocrine Parameters and Sperm Characteristics in Sub-Fertile Men: A Systematic Review and Meta-Analysis

Urol J. 2017 Aug 29;14(5):4069-4078.


Purpose: To evaluate the effect of folate and folate plus zinc supplementation on endocrine parameters and sperm characteristics in sub fertile men.

Materials and methods: We conducted a systematic review and meta-analysis. Electronic databases of Medline, Scopus , Google scholar and Persian databases (SID, Iran medex, Magiran, Medlib, Iran doc) were searched from 1966 to December 2016 using a set of relevant keywords including "folate or folic acid AND (infertility, infertile, sterility)".All available randomized controlled trials (RCTs), conducted on a sample of sub fertile men with semen analyses, who took oral folic acid or folate plus zinc, were included. Data collected included endocrine parameters and sperm characteristics. Statistical analyses were done by Comprehensive Meta-analysis Version 2.

Results: In total, seven studies were included. Six studies had sufficient data for meta-analysis. "Sperm concentration was statistically higher in men supplemented with folate than with placebo (P < .001)". However, folate supplementation alone did not seem to be more effective than the placebo on the morphology (P = .056) and motility of the sperms (P = .652). Folate plus zinc supplementation did not show any statistically different effect on serum testosterone (P = .86), inhibin B (P = .84), FSH (P = .054), and sperm motility (P = .169) as compared to the placebo. Yet, folate plus zinc showed statistically higher effect on the sperm concentration (P < .001), morphology (P < .001), and serum folate level (P < .001) as compared to placebo.

Conclusion: Folate plus zinc supplementation has a positive effect on sperm characteristics in sub fertile men. However, these results should be interpreted with caution due to the important heterogeneity of the studies included in this meta-analysis. Further trials are still needed to confirm the current findings.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Dietary Supplements
  • Folic Acid / blood
  • Folic Acid / pharmacology*
  • Folic Acid / therapeutic use
  • Humans
  • Infertility, Male / drug therapy*
  • Inhibins / blood
  • Male
  • Sperm Count*
  • Sperm Motility / drug effects*
  • Spermatozoa / cytology
  • Testosterone / blood
  • Vitamin B Complex / blood
  • Vitamin B Complex / pharmacology*
  • Vitamin B Complex / therapeutic use
  • Zinc / pharmacology*
  • Zinc / therapeutic use


  • inhibin B
  • Vitamin B Complex
  • Testosterone
  • Inhibins
  • Folic Acid
  • Zinc