The objective of this study is to characterize the relationship between change in folic acid and change in plasma homocysteine for modest changes in folic acid intake. The dose-response relationship of folic acid and plasma homocysteine will be estimated separately for each gender, each genotype for the thermolabile variant of 5,10-methylenetetrahydrofolate reductase (MTHFR), and with elevated plasma homocysteine levels or homocysteine levels in the normal range.
Male and female volunteers, aged 18-69 were screened for genotype of MTHFR and basal level of homocysteine. Within genotype, gender, and broad homocysteine level, 160 volunteers were randomly selected for study enrollment. Because of reported differences in efficiency of homocysteine metabolism in people of African descent, an additional 40 African-American volunteers were enrolled. Selected volunteers were randomized using a Latin square design to received three different doses of folic acid in random order for twelve weeks. The doses of folic acid include: 0 mcg, 200 mcg, and 400 mcg. There was a 30-week washout period between the two treatment periods. Blood samples were taken at baseline, then every six weeks for the 54-week study period. Samples were analyzed for plasma homocysteine, red cell folate, serum folate, and serum B12.
The data from this study will provide information about the dose-response relationship of folic acid and plasma homocysteine in the context of folic acid-fortified flour and grain products. The extent of interaction between MTHFR genotype and intake of folic acid supplements will also be determined. Additionally, these data will provide much needed information regarding the response of plasma homocysteine and red cell folate to stopping folate supplementation.
