The importance of adequate folate is unequivocal. Sub-optimal folate status is associated with increased risk for cardiovascular disease, neural tube defects and certain types of cancer. Methylene tetrahydrofolate reductase (MTHFR) is a critical enzyme that regulates folate metabolism. A common polymorphism (677 C->T) in the MTHFR gene is associated with decreased enzyme activity, lower concentrations of plasma folate, higher concentrations of plasma total homocysteine (tHcy) and increased risk for neural tube defects and possibly cardiovascular disease. Conversely, the same mutation is associated with decreased risk of certain forms of cancer providing that folate status is adequate. Observational data suggest decreased risk of certain forms of cancer providing that folate status is adequate. Observational data suggest that individual homozygous for the MTHFR mutation (T/T), approximately 12% of the population, may have higher folate requirements compared to individuals with either heterozygous (C/T) or homozygous wild-type (C/C) genotype. Potential differences in folate metabolism/requirements between racial or ethnic groups have also been described, although not under controlled conditions. The purpose of this study is to determine if the 1998 RDA for folate, 400 mug/d as dietary folate equivalents (DFE), is sufficient to maintain normal folate status in pre-menopausal women (18-45 yo) representing different ethnic/racial groups and different MTHFR genotypes. Mexican American (n=12; C/C genotype), African American (n=12; C/C genotype) and Caucasian women (n=36; C/C, C/T and T/T genotypes) will be randomly assigned to consume controlled folate intakes of either 400 or 800 mug/d as DFE and the remainder will be provided as synthetic folic acid. Folate status response will be assessed by baseline and thereafter weekly measures of serum and red cell folate, plasma tHcy, lymphocyte DNA methylation, lymphocyte deoxynucleotide content as well as urinary excretion of folic acid and 5- methyl-tetrahydrofolate. We hypothesize that the folate needed to satisfy the pathways of homocysteine metabolism and deoxynucleotide synthesis will differ among ethnic/racial groups as well as MTHFR genotypes.
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