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Jean Mayer-U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111 and * The Framingham Heart Study, Boston University School of Medicine, Framingham, MA 01701
2To whom correspondence should be addressed. E-mail: paul{at}hnrc.tufts.edu.
Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5-methyltetrahydrofolate, the methyl donor for remethylation of homocysteine to methionine. The C677T MTHFR polymorphism is associated with mild hyperhomocysteinemia, but only in the presence of low folate status. Because MTHFR contains flavin adenine dinucleotide (FAD) as a prosthetic group, riboflavin status may also influence homocysteine metabolism. The objective of this study was to examine the association between riboflavin status and fasting plasma total homocysteine (tHcy) concentration while also considering MTHFR C677T genotype and folate status. The study was conducted using fasting plasma samples (n = 450) from the fifth examination of the Framingham Offspring Study cohort. All persons with the TT genotype and age- and sex-matched sets of individuals with the CT and CC genotypes were selected for determination of plasma riboflavin and flavin mono- and dinucleotide levels. Plasma riboflavin was associated with tHcy concentrations, but the association was largely confined to persons with plasma folate <12.5 nmol/L and TT genotype. In these persons, the mean tHcy among individuals with riboflavin levels <6.89 nmol/L was 14.5 µmol/L, whereas the mean tHcy for those with riboflavin 
11 nmol/L was 11.6 µmol/L (P-trend <0.03). Plasma flavin nucleotides were unrelated to tHcy concentrations. Our data suggest that riboflavin status may affect homocysteine metabolism, but only in a small segment of the population who have both low folate status and are homozygotes for the MTHFR C677T mutation.
KEY WORDS: • homocysteine • riboflavin • folate • methylenetetrahydrofolate reductase • humans
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