Low seminal plasma folate concentrations are associated with low sperm density and count in male smokers and nonsmokers

Fertil Steril. 2001 Feb;75(2):252-9. doi: 10.1016/s0015-0282(00)01697-6.


Objective: To measure folate levels in seminal plasma from smokers and nonsmokers and to evaluate relationships between seminal plasma folate levels and both folate nutriture and semen quality measures.

Design: Observational study.

Setting: United States Department of Agriculture, Western Human Nutrition Research Center, Presidio of San Francisco, San Francisco, California.

Patient(s): Healthy male smokers (n=24) and nonsmokers (n=24).

Main outcome measure(s): Blood levels of plasma folate and homocysteine, seminal plasma total, non-methyl- and 5-methyltetrahydrofolate concentrations, and total sperm count and density.

Results: Total seminal plasma folate concentrations were on average 1.5 times higher than blood plasma folate concentrations in all men. Seminal plasma folates contained 5-methyltetrahyrdofolate (74% of total) and non-methyltetrahydrofolates (26% of total); all samples had less than four glutamyl residues. Total and 5-methyltetrahydrofolate concentrations correlated significantly with blood plasma folate and homocysteine concentrations. Seminal plasma non-methyltetrahydrofolate levels correlated significantly with sperm density and total sperm count. Seminal plasma of smokers contained a proportionally lower concentration of non-methyltetrahydrofolates compared with nonsmokers.

Conclusion(s): Seminal plasma total folate and 5-methyltetrahydrofolate concentrations reflect folate nutriture. The non-methyltetrahydrofolate fraction of seminal plasma may be important for male reproductive function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Diet
  • Folic Acid / analysis*
  • Folic Acid / blood
  • Genotype
  • Homocysteine / blood
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Mutation
  • Oxidoreductases Acting on CH-NH Group Donors / genetics*
  • Semen / chemistry*
  • Smoking*
  • Sperm Count*
  • Spermatozoa / chemistry
  • Tetrahydrofolates / blood
  • Vitamin B 12 / blood
  • Vitamins / administration & dosage


  • Tetrahydrofolates
  • Vitamins
  • Homocysteine
  • Folic Acid
  • Oxidoreductases Acting on CH-NH Group Donors
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Vitamin B 12
  • 5-methyltetrahydrofolate