L-ascorbic acid improves the serum folate response to an oral dose of [6S]-5-methyltetrahydrofolic acid in healthy men

Eur J Clin Nutr. 2008 Oct;62(10):1224-30. doi: 10.1038/sj.ejcn.1602840. Epub 2007 Jul 11.


Objective: To investigate the effect of simultaneous administration of [6S]-5-methyltetrahydrofolic acid ([6S]-5-CH(3)H(4)PteGlu) with L-ascorbic acid (L-AA) on serum folate concentrations in healthy male subjects.

Subjects and methods: A total of nine healthy male volunteers were recruited. Serum folate concentrations were measured before and up to 8 h after administration of each treatment (1) placebo, (2) 343 microg [6S]-5-CH(3)H(4)PteGlu), (3) 343 microg [6S]-5-CH(3)H(4)PteGlu) with 289.4 mg L-AA and (4) 343 microg [6S]-5-CH(3)H(4)PteGlu) with 973.8 mg L-AA (n=10 samples per treatment).

Results: Serum folate concentrations significantly increased compared with baseline values, starting from 30 min after [6S]-5-CH(3)H(4)PteGlu administration and remained significantly higher than baseline values during the first 6 h for treatments 3 and 4, and during the first 4 h for treatment 2. Maximal serum folate responses were observed between 0.5 and 1.5 h after [6S]-5-CH(3)H(4)PteGlu consumption and significantly differed between treatments 2 and 4 (P<0.05). When [6S]-5-CH(3)H(4)PteGlu was concurrently administered with 289.4 or 973.8 mg L-AA, the total serum folate response, calculated as the area under the curve (AUC), was significantly improved (46.5+/-4.0 and 53.0+/-4.0 vs 34.3+/-3.8 h nmol/l, P<0.05). No significant difference in AUC was found between the 289.4 and the 973.8 mg L-AA treatments.

Conclusions: Administration of a physiological dose of [6S]-5-CH(3)H(4)PteGlu with L-AA significantly improved the measured serum folate response in folate saturated healthy men.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Antioxidants / pharmacology*
  • Area Under Curve
  • Ascorbic Acid / pharmacology*
  • Biological Availability
  • Biomarkers / blood
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Folic Acid / blood
  • Folic Acid / pharmacokinetics*
  • Humans
  • Intestinal Absorption / drug effects*
  • Male
  • Tetrahydrofolates / pharmacokinetics
  • Vitamin B Complex / blood
  • Vitamin B Complex / pharmacokinetics*
  • Young Adult


  • Antioxidants
  • Biomarkers
  • Tetrahydrofolates
  • Vitamin B Complex
  • Folic Acid
  • Ascorbic Acid
  • 5-methyltetrahydrofolate