British Journal of Nutrition

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British Journal of Nutrition (2010), 103:724-729 Cambridge University Press
Copyright © The Authors 2009
doi:10.1017/S0007114509992339

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Human and Clinical Nutrition

Comparison of (6S)-5-methyltetrahydrofolic acid v. folic acid as the reference folate in longer-term human dietary intervention studies assessing the relative bioavailability of natural food folates: comparative changes in folate status following a 16-week placebo-controlled study in healthy adults


Anthony J. A. Wrighta1 c1, Maria J. Kinga1, Caroline A. Wolfea1, Hilary J. Powersa2 and Paul M. Finglasa1

a1 Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK
a2 Human Nutrition Unit, University of Sheffield, The School of Medicine, Sheffield S10 2RX, UK
Article author query
wright aja [PubMed]  [Google Scholar]
king mj [PubMed]  [Google Scholar]
wolfe ca [PubMed]  [Google Scholar]
powers hj [PubMed]  [Google Scholar]
finglas pm [PubMed]  [Google Scholar]

Abstract

Folic acid (pteroylmonoglutamic acid) has historically been used as the reference folate in human intervention studies assessing the relative bioavailability of dietary folate. Recent studies using labelled folates indicated different plasma response kinetics to folic acid than to natural (food) folates, thus obviously precluding its use in single-dose experiments. Since differences in tissue distribution and site of biotransformation were hypothesised, the question is whether folic acid remains suitable as a reference folate for longer-term intervention studies, where the relative bioavailability of natural (food) folate is assessed based on changes in folate status. Healthy adults aged 18–65 years (n 163) completed a 16-week placebo-controlled intervention study in which the relative bioavailability of increased folate intake (453 nmol/d) from folate-rich foods was assessed by comparing changes in plasma and erythrocyte folate concentration with changes induced by an equal reference dose of supplemental (6S)-5-methyltetrahydrofolic acid or folic acid. The relative increase in plasma folate concentration in the food group was 31 % when compared with that induced by folic acid, but 39 % when compared with (6S)-5-methyltetrahydrofolic acid. The relative increase in erythrocyte folate concentration in the food group when compared with that induced by folic acid was 43 %, and 40 % when compared with (6S)-5-methyltetrahydrofolic acid. When recent published observations were additionally taken into account it was concluded that, in principle, folic acid should not be used as the reference folate when attempting to estimate relative natural (food) folate bioavailability in longer-term human intervention studies. Using (6S)-5-methyltetrahydrofolic acid as the reference folate would avoid future results' validity being questioned.

(Received April 01 2009)

(Revised July 28 2009)

(Accepted July 28 2009)

(Online publication October 26 2009)

Key Words:Human nutrition; (6S)-5-methyltetrahydrofolic acid; Folic acid; Plasma homocysteine; Folate; Bioavailability; Intervention studies

Correspondence:

c1 Corresponding author: Dr Anthony J. A. Wright, fax +44 1603 507723, email tony.wright@bbsrc.ac.uk

Footnotes

Abbreviations: 5-CH3H4PteGlu, (6S)-5-methyltetrahydrofolic acid; RNI, UK reference nutrient intake


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