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ABSTRACT OBJECTIVES: To assess the effects of supplementation with the diastereoisomer of 5-methyltetrahydrofolate ([6_S_]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 [6_S_]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 [6_S_]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

[6_S_]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.

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INFORMATION AUTHORS AND AFFILIATIONS * 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 * Department of Internal Medicine, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands Y M Smulders & C D A

Stehouwer * Institute of Food Research, Norwich, UK J R Dainty & P M Finglas Authors * K de Meer View author publications You can also search for this author inPubMed Google Scholar * Y

M Smulders View author publications You can also search for this author inPubMed Google Scholar * J R Dainty View author publications You can also search for this author inPubMed Google

Scholar * D E C Smith View author publications You can also search for this author inPubMed Google Scholar * R M Kok View author publications You can also search for this author inPubMed 

Google Scholar * C D A Stehouwer View author publications You can also search for this author inPubMed Google Scholar * P M Finglas View author publications You can also search for this

author inPubMed Google Scholar * C Jakobs View author publications You can also search for this author inPubMed Google Scholar 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, _t_lag is the time during which the plasma enrichment remains at baseline. The value of _T_

(ie _t_max−_t_lag) 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 RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE de Meer, K., Smulders, Y., Dainty, J. _et

al._ [6_S_]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 Download citation * Received: 22 October 2004 * Revised: 09 June 2005 * Accepted: 29 June 2005 * Published: 07 September 2005 * Issue Date: 01

December 2005 * DOI: https://doi.org/10.1038/sj.ejcn.1602254 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a

shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * [6_S_]5-methyltetrahydrofolate *

folic acid kinetics * homocysteine * elderly