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Unmetabolized folic acid and total folate concentrations in breast milk are unaffected by low-dose folate supplements^1,2,3

¹ From Physiology & Experimental Medicine, The Hospital for Sick Children, Toronto, Canada (LAH, JY, and DLO), and the Department of Nutritional Sciences, University of Toronto, Toronto, Canada (LAH and DLO).

² Supported by Merck Eprova AG (Schaffhausen, Switzerland) and the Natural Sciences & Engineering Research Council of Canada. LAH received a student stipend to carry out this work from the Canadian Institute of Health Research Training Grant in Clinical Nutrition (STP-53889) and from the Ontario Student Opportunity Trust Fund, The Hospital for Sick Children Foundation Scholarship Program.

³ Reprints not available. Address correspondence to LA Houghton, Department of Human Nutrition, University of Otago, PO Box 56, Dunedin, New Zealand. E-mail: lisa.houghton{at}otago.ac.nz.

ABSTRACT

Background: Many lactating women in North America are exposed to high synthetic folic acid intakes because of food fortification and vitamin supplement use. Few data exist on the potential long-term effect of high folic acid intakes on milk folate concentrations, whereas no data are available on the effect of supplemental [6S]-5-methyltetrahydrofolate ([6S]-5-methylTHF).

Objective: The aim of the present study was to investigate the effect of 3 treatments (placebo, folic acid, and [6S]-5-methylTHF) on milk folate and folate-binding protein (FBP) concentrations and to determine whether unmetabolized folic acid is present in milk.

Design: In this 16-wk randomized, placebo-controlled intervention, 69 lactating women were randomly assigned to receive [6S]-5-methylTHF (416 µg/d, 906 nmol/d) or a placebo, or were assigned to receive folic acid (400 µg/d, 906 nmol/d) within 1 wk postpartum. Total milk folate, FBP, and unmetabolized folic acid concentrations were measured at 16 wk.

Results: Unmetabolized folic acid was detected in 96% of milk samples tested representing 8% of total milk folate concentrations. Total milk folate, FBP, and the proportion of unmetabolized milk folic acid did not differ between treatments; however, FBP concentrations were significantly lower than those published before mandatory folic acid fortification of the food supply.

Conclusion: Maternal intake of synthetic folic acid leads to the appearance of unmetabolized folic acid in milk and, seemingly, a down-regulation of milk FBP synthesis. The impact of these changes on the bioavailability of folate in infants requires further exploration.

Received for publication June 20, 2008. Accepted for publication October 6, 2008.