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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.

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.