title: The Effect of Trimethoprim on Serum Folate Levels in Humans: A Randomized, Double-Blind, Placebo-Controlled Trial.
abstract: Trimethoprim antagonize the actions of folate by inhibition of dihydrofolate reductase. This could diminish serum folate levels in humans and causes folate deficiency in some patients. We conducted a randomized, double-blind, placebo-controlled trial, to investigate the effect of trimethoprim on serum folate levels in healthy participants after a 7-day trial period. Thirty young, healthy males were randomly allocated to receive trimethoprim, 200 mg twice daily, and 30 were randomly allocated to placebo. Before trial initiation, participant numbers were given randomly generated treatment allocations within sealed opaque envelopes. Participants and all staff were kept blinded to treatment allocations during the trial. Serum folate was measured at baseline and at end of trial. In the 58 participants analyzed (30 in the trimethoprim group and 28 in the placebo group), 8 had folate deficiency at baseline. Within the trimethoprim group, serum folate was significantly decreased (P = 0.018) after the trial. We found a mean decrease in serum folate among trimethoprim exposed of 1.95 nmol/L, compared with a 0.21 nmol/L mean increase in the placebo group (P = 0.040). The proportion of folate-deficient participants increased significantly within the trimethoprim group (P = 0.034). No serious adverse events were observed. In conclusion, we found that a daily dose of 400 mg trimethoprim for 7 days significantly lowered serum folate levels in healthy study participants.
authors.affiliation: 1Department of Clinical Pharmacology, Copenhagen University Hospital Bispebjerg, Copenhagen NW, Denmark; 2Laboratory of Clinical Pharmacology, Copenhagen University Hospital Rigshospitalet, Copenhagen N, Denmark; 3Department of Clinical Medicine, Faculty of Health and Medical Sciences, Copenhagen N, Denmark; and 4Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N, Denmark.
authors.forename: Kasper
authors.initials: K
authors.lastname: Meidahl Petersen
authors.forename: Kasper
authors.initials: K
authors.lastname: Eplov
authors.forename: Torben
authors.initials: T
authors.lastname: Kjær Nielsen
authors.forename: Espen
authors.initials: E
authors.lastname: Jimenez-Solem
authors.forename: Morten
authors.initials: M
authors.lastname: Petersen
authors.forename: Kasper
authors.initials: K
authors.lastname: Broedbaek
authors.forename: Sara
authors.initials: S
authors.lastname: Daugaard Popik
authors.forename: Lina
authors.initials: L
authors.lastname: Kallehave Hansen
authors.forename: Henrik
authors.initials: H
authors.lastname: Enghusen Poulsen
authors.forename: Jon
authors.initials: J
authors.lastname: Trærup Andersen
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D005492:Folic Acid / Q000097:blood*; D006801:Humans; D008297:Male; D014295:Trimethoprim / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D005492:Folic Acid; D014295:Trimethoprim