[6S]5-methyltetrahydrofolate or folic acid supplementation and absorption and initial elimination of folate in young and middle-aged adults

Abstract

Objectives: To assess the effects of supplementation with the diastereoisomer of 5-methyltetrahydrofolate ([6S]5-methylTHF), as an alternative supplement for folic acid, on folate absorption and elimination, in two age groups. Design: A randomized, double-blind intervention study. Subjects: A total of 12 young (o30 y) and 12 middle-aged (Z50 y) healthy volunteers were recruited. Methods: Volunteers were randomized to receive daily supplementation with 400 mg folic acid or equimolar amounts of [6S]5-methylTHF during 5 weeks. Before and after supplementation, absorption and initial elimination were calculated following oral [ 2 H 2 ]folic acid test doses using isotope kinetics in plasma. Results: Folic acid absorption was lower in the middle-aged as compared to the young adults, both before (P ¼ 0.03) and after (P ¼ 0.05) supplementation. In the young adults, absorption decreased by 22% after [6S]5-methylTHF and increased by 21% after folic acid (P ¼ 0.02). In the other age group, no such changes were found. The folate rate constant of elimination increased after folic acid supplementation in the young ( þ 50%; P ¼ 0.05) but not in the middle-aged ( þ 18%; P ¼ 0.5) adults. Conclusions: Young adults show increased folate turnover after folic acid supplementation relative to the effect of [6S]5-methylTHF supplementation. Similar differences are not observed in middle-aged adults, in whom folic acid absorption was found to be lower as compared to the young adults.

Circulating Unmetabolized Folic Acid: Relationship to Folate Status and Effect of Supplementation

“…One possible mechanism for the observed decline in plasma concentrations of unmetabolized folic acid is upregulation of folic acid metabolism [9, 50]. Kamen and colleagues found that, as compared to human liver cells in situ , the expression and activity of DHFR was 100- to 200-times higher in human cell lines in vitro and fresh rat liver cells.…”

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

“…Despite this general acceptance, recent reports have questioned the validity of PteGlu as reference in AUC protocols Melse-Boonstra et al, 2004;Wright et al, 2005) since a substantial portion of the plasma response after consumption of 13 C 5 -PteGlu or 13 C 5 -5-formyltetrahydrofolate does not originate from the test dose, and secondly since plasma response kinetics among PteGlu and natural folates largely differ (Wright et al, 2003(Wright et al, , 2005. Alternatively, we considered [6S]-5-CH 3 H 4 PteGlu since its appearance in circulation is unlikely to depend on interconversion reactions (de Meer et al, 2005). It should be noted that using 'unlabeled' [6S]-5-CH 3 H 4 PteGlu did not allow a distinction between the response originating from the dose and the endogenous response caused by displacement of folate from body pools (Wright et al, 2003) and that interpretation of the current results is hence somewhat challenging.…”

The Bioavailability of Various Oral Forms of Folate Supplementation in Healthy Populations and Animal Models: A Systematic Review

“…A total of 23 studies out of the original 5226 articles identified fit the full inclusion criteria and were appraised in this review. All studies provided quantitative data with 4 trials [19][20][21][22] using animal models and 19 studies [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] conducting human trials.…”