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

European Journal of Clinical Nutrition volume 59, pages 1409–1416 (2005)Cite this article

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 (<30 y) and 12 middle-aged (≥50 y) healthy volunteers were recruited.

Methods:

Volunteers were randomized to receive daily supplementation with 400 μg folic acid or equimolar amounts of [6S]5-methylTHF during 5 weeks. Before and after supplementation, absorption and initial elimination were calculated following oral [2H2]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=0.03) and after (P=0.05) supplementation. In the young adults, absorption decreased by 22% after [6S]5-methylTHF and increased by 21% after folic acid (P=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 (+50%; P=0.05) but not in the middle-aged (+18%; P=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.

Sponsorship:

Financial support was received from the European Union 5th Framework Programme (Grant QLRT-1999-00576).

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Author information

Authors and Affiliations

  1. Department of Clinical Chemistry, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands

    K de Meer, D E C Smith, R M Kok & C Jakobs

  2. Department of Internal Medicine, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands

    Y M Smulders & C D A Stehouwer

  3. Institute of Food Research, Norwich, UK

    J R Dainty & P M Finglas

Authors
  1. K de Meer
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  2. Y M Smulders
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  3. J R Dainty
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  4. D E C Smith
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  5. R M Kok
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  6. C D A Stehouwer
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  7. P M Finglas
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  8. C Jakobs
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Corresponding author

Correspondence to K de Meer.

Additional information

Guarantor: K de Meer.

Contributors: KDM designed the study, developed the experiments, prepared the original draft and wrote the final manuscript; DECS and RMK validated and performed the laboratory measurements; DECS assisted with the experiments; JRD, KDM and JMS analyzed the data; CJ and PMF contributed to the study design and protocol and manuscript; all contributors edited the manuscript.

Appendix A1

Appendix A1

Estimation of in vivo folate absorption and elimination

Changes in 5-methylTHF isotopomer plasma concentrations are approximated in a single-compartment model (Kok et al, 2004). The appearance of labeled folic acid approximates an infusion rate (R) over the absorption period T. The definition of R is

With V the apparent volume of distribution for folate (∼389 ml/kg body weight; Loew et al, 1987), k the rate constant of elimination from the compartment and t the time after ingestion of the test dose (doseoral), the labeled 5-methylTHF concentration (C) can be approximated as

and

Here, tlag is the time during which the plasma enrichment remains at baseline. The value of T (ie tmax−tlag) is established from the plasma 5-methylTHF enrichment curve. M can be calculated by fitting equations (A.2) and (A.3) to the time series of labeled 5-methylTHF concentrations. The apparent absorption can then be calculated as

A first pass effect is present when folate is absorbed. Assuming that in humans it is a fraction of 0.65 of doseoral (Finglas et al, 2002b), true absorption can be estimated as

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de Meer, K., Smulders, Y., Dainty, J. et al. [6S]5-methyltetrahydrofolate or folic acid supplementation and absorption and initial elimination of folate in young and middle-aged adults. Eur J Clin Nutr 59, 1409–1416 (2005). https://doi.org/10.1038/sj.ejcn.1602254

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