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Shirley A.A. Beresford, PhD, Department of Epidemiology, University of Washington, Box 357236, Seattle, WA 98195-7236, 206-543-9512, beresfrd@u.washington.edu, Johanna W Lampe, PhD, Cancer Prevention Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, P.O. Box 19024, Seattle, WA 98109, Cheryl A.M. Anderson, PhD, MPH, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, 8th Floor Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104, Arno G. Motulsky, MD ScD, School of Medicine, University of Washington, Box 357730, Seattle, WA 98195-7730, and Dale F. McLerran, MS, Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave., N., MP-702, Seattle, WA 98109-1024.
There is continuing controversy surrounding the optimal level of folate fortification of flour and grain products. In general, increased folate intake is needed to normalize homocysteine (tHcy), but the minimum necessary level of folate supplementation is not known. We therefore undertook a study of different doses of added folic acid to evaluate their effect on levels of homocysteine, recruiting individuals within broad level of homocysteine and 5, 10-methylene tetrahydrofolate reductase (MTHFR) C677T genotype. We conducted a randomized cross-over trial in which each participant was his or her own control. Two treatment periods of 12 weeks each were separated by a washout period of 30 weeks. Adherence to the study protocol was high, and nearly 80% of those randomized completed the 54 week study. The measure of folate requirement that we used was plasma homocysteine (tHcy). Based on prior literature, we hypothesized that tHcy responds to increased folate intake until a lower bound of tHcy is approached, at which point additional folic acid intake does not result in any further lowering of tHcy. The doses of folic acid we examined were 0 µg , 200 µg and 400 µg. For the dose of 400 µg, the average additional effect, beyond that of 200 µg, was essentially zero, consistent with a lower bound. The average effect of 200 µg folic acid was a differential reduction in tHcy of 0.42 µmol/L (p<0.05). The hypothesis that TT homozygotes might require a higher dose of additional folic acid could not be resolved definitively with the sample size available. It is concluded that in this era of fortification of enriched flour and grain products with folic acid, additional homocysteine lowering can be achieved among individuals not taking daily folic acid supplements.
Learning Objectives: At the end of this session, the participant will be able to
Keywords: Food and Nutrition, Genetics
Presenting author's disclosure statement:
I do not have any significant financial interest/arrangement or affiliation with any organization/institution whose products or services are being discussed in this session.