Choline, a dietary component, is a precursor for a variety of compounds including the methyl donor, betaine and is a possible determinant of chronic/developmental disease risk. The choline-adequate intake (AI) for men is 550 mg/d, about half the amount normally consumed in the diet. Choline requirements may be higher in persons with a common genetic variant in the folate-metabolizing enzyme, methylenetetrahydrofolate reductase (MTHFR C677T). We propose to investigate the response of traditional and novel functional indices of choline and folate status to controlled choline [225, 550 (AI), 1100 (typical intake) and 2200 mg/d] and folate (400 mcg/d) intakes in young Mexican American men (18-45 y; n=56) grouped according to their MTHFR genotype with n=28 677 TT and n=28 of the more prevalent CC form. Further, we will employ a stable isotope tracer protocol to assess the fate of exogenous choline and the influence of MTHFR C->T genotype and levetof choline intake on that rate and extent of isotopic labeling of choline metabolites and other intermediates or products of one-carbon metabolism. A low choline diet (225 mg/d) will be consumed for 2 wk followed by randomization to supplemental choline or placebo for total choline intakes of 225 (7 TT and 7 CC); 550 (7 TT and 7 CC); 1100 (7 TT and 7 CC) and 2200 (7 CC and 7 TT) mg/d for 12wk. Throughout the study duration, the men will receive the 1998 folate RDA, 400 mcg/d as dietary folate equivalents and all other nutrients in adequate amounts. In addition, subjects (n=20) in the 550 and 2200 mg/d will consume 15% of their total choline intake as D13-choline from wk 12 to wk 14. The response of folate and choline nutritional status to vadous levels of controlled choline intake with constant folate intake will be assessed by several response variables (i.e, plasma folate, choline, betaine, homocysteine). Further, isotopic enrichment of choline metabolites or other one-carbon intermediates/products (i.e, choline, betaine, methionine and serine) will be measured in wk 14 plasma from subjects consuming the tracer.