The Short-Term Bioavailabilities of [6S]-5-Methyltetrahydrofolate and Folic Acid Are Equivalent in Men

Abstract

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 micro g FA capsule; and 3) 500 micro g [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.

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

“…Neither the amount of folate in the standard diet, nor the saturation regimen with supraphysiologic doses of [6S]-5-CH 3 H 4 PteGlu affected the folate response in view of the fact that serum folate concentrations did not differ from baseline during the placebo treatment. In accordance with other studies (Prinz-Langenohl et al, 2003;Pentieva et al, 2004), oral [6S]-5-CH 3 H 4 PteGlu administration resulted in peak serum folate concentrations within 2 h postprandially, which returned to baseline after 4-8 h. Owing to very large inter-method and inter-laboratory differences among serum folate determination methods (Gunter et al, 1996), further comparison of results would require calibration standardization and assessment of interlaboratory variation (that is, it has been shown that the Elecsys assay reads 'low' among the automated methods that are in current usage (Owen and Roberts, 2003)). …”

“…The estimated total folate response of [6S]-5-CH 3 H 4 PteGlu in serum was significantly higher after consumption of treatment 3 or 4 as compared to treatment 2 (respectively 46.574.0 and 53.074.0 vs 34.373.8 h nmol/l, Po0.05), whereas no significant difference was found between treatments 3 and 4 (P ¼ 0.47). Ingestion of [6S]-5-CH 3 H 4 PteGlu with 973.8 and 289.4 mg L-AA resulted in a significant increase of the AUC with 18.7 h nmol/l (95% confidence interval (CI), 9.8-27.6 h nmol/l) and 12.3 h nmol/l (95% CI, 3.3-21.2 h nmol/l), Pentieva et al, 2004), using measurement of serum or plasma folate responses after an oral folate dose to express the AUC relative to an equivalent PteGlu dose. This methodology has been accepted as a valuable indicator for short-term folate bioavailability when the post-dosing measurement period allows adequate characterization of the AUC (X80%) (Cahill et al, 1998).…”

Assessment and interpretation of micronutrient status during pregnancy

“…Postprandial serum tHcy concentrations are generally slightly lower than fasted values but these differences are small compared with the total amount of dayto-day variation (144,145) . Serum folate, on the other hand, can reflect recent intake, especially when consumed in relatively high doses such as those found in antenatal folic acid supplements (146) . During pregnancy the correlation between folate status and tHcy becomes weaker with advancing gestation.…”

Research goals for folate and related B vitamin in Europe

“…The recently available natural folate stereoisomer, [6S]-5-methyltetrahydrofolate, as a potential fortificant or supplement, is a possible alternate to folic acid in some situations (Pentieva et al, 2004). Within the EU project it was demonstrated that it has similar effects on folate status and plasma concentrations of tHcy in humans as folic acid (Lamers et al, 2004) and on theoretical grounds could be used in the elderly as it would not mask vitamin B 12 deficiency.…”