title: Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial.
abstract: OBJECTIVE
  To study the effects of folic acid and zinc sulfate treatment on semen variables in fertile and subfertile men.
  
  
  METHODS
  Double-blind, placebo-controlled interventional study.
  
  
  METHODS
  Two outpatient fertility clinics and nine midwifery practices in The Netherlands.
  
  
  METHODS
  One hundred eight fertile and 103 subfertile men.
  
  
  METHODS
  Both groups were randomly assigned to receive one of four treatments for 26 weeks: folic acid and placebo, zinc sulfate and placebo, zinc sulfate and folic acid, and two placebos. Folic acid was given at a daily dose of 5 mg, and zinc sulfate was given at a daily dose of 66 mg.
  
  
  METHODS
  Before and after treatment, standardized semen and blood samples were obtained for determinations of sperm concentration, motility, and morphology according to World Health Organization guidelines; semen morphology according to strict criteria; and blood folate and zinc concentrations. Effects of the four interventions were evaluated separately in subfertile and fertile men.
  
  
  RESULTS
  Subfertile men demonstrated a significant 74% increase in total normal sperm count and a minor increase of 4% abnormal spermatozoa. A similar trend was observed in fertile men. Pre-intervention concentrations of folate and zinc in blood and seminal plasma did not significantly differ between fertile and subfertile men.
  
  
  CONCLUSIONS
  Total normal sperm count increases after combined zinc sulfate and folic acid treatment in both subfertile and fertile men. Although the beneficial effect on fertility remains to be established, this finding opens avenues of future fertility research and treatment and may affect public health.
authors.affiliation: Department of Obstetrics and Gynecology, University Medical Centre Nijmegen, Nijmegen, The Netherlands.
authors.forename: Wai Yee
authors.initials: WY
authors.lastname: Wong
authors.forename: Hans M W M
authors.initials: HM
authors.lastname: Merkus
authors.forename: Chris M G
authors.initials: CM
authors.lastname: Thomas
authors.forename: Roelof
authors.initials: R
authors.lastname: Menkveld
authors.forename: Gerhard A
authors.initials: GA
authors.lastname: Zielhuis
authors.forename: Régine P M
authors.initials: RP
authors.lastname: Steegers-Theunissen
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D005492:Folic Acid / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D005500:Follow-Up Studies; D006801:Humans; D007248:Infertility, Male / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D012661:Semen / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D018709:Statistics, Nonparametric; D019287:Zinc Sulfate / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D019287:Zinc Sulfate; D005492:Folic Acid