The short-term bioavailabilities of [6S]-5-methyltetrahydrofolate and folic acid are equivalent in men

K Pentieva, H McNulty, R Reichert, M Ward, JJ Strain, D McKillop, JM McPartlin, E Connolly, A Molloy, K Kramer, JM Scott

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The natural folate derivative, 5-methyltetrahydrofolate ([6S]-5-MTHF), could be an option for supplementation and fortification but its bioavailability remains unclear. This study compared the bioavailability of [6S]-5-MTHF with that of folic acid (FA) by measuring plasma folate responses after a single ingestion of equivalent doses of the two folate forms. In a double-blind, crossover study, 13 men (presaturated with FA) received in random order each of the following treatments administered orally at 1-wk intervals: 1) placebo capsule; 2) 500 μg FA capsule; and 3) 500 μg [6S]-5-MTHF capsule. Plasma total folate concentrations were measured before and up to 10 h after each treatment (n = 10 samples per treatment). Plasma folate concentrations increased significantly (compared with baseline) from 0.5 to 5 h after both folate treatments. The maximum plasma folate response did not differ between the two treatments (mean ± SEM, 33.4 ± 3.9 vs. 31.8 ± 3.9 nmol/L, P = 0.7, for FA and [6S]-5-MTHF, respectively) and typically occurred in individuals between 0.5 and 3 h postprandially. The area under the plasma folate response curve was significantly greater after both folate treatments compared with placebo, and the response did not differ between the treatments. These results indicate that the short-term bioavailabilities of [6S]-5-MTHF and FA are equivalent. Supplementation with the natural folate derivative could have all the beneficial effects associated with FA, but without the potential disadvantage of masking the anemia of vitamin B-12 deficiency.
Original languageEnglish
Pages (from-to)580-585
Number of pages6
JournalJournal of Nutrition
Issue number3
Publication statusPublished (in print/issue) - 1 Mar 2004

Bibliographical note

Funded by EU project “Nutraceuticals for a healthier life: n-3 polyunsaturated fatty acids and 5-methyltetrahydrofolate” (QLRT–1999–00888) and supported by Abbot GmbH, Weisbaden-Delkenheim, Germany.


  • [6S]-5-methyltetrahydrofolate
  • folic acid
  • plasma folate
  • short-term folate bioavailability


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