The response of blood folate levels to folic acid supplementation: Results from a crossover trial

Monitoring changes in folate levels in response to folic acid supplementation is important for gauging the initial effect of folic acid fortification on red cell and serum folate levels. Adequate folate levels are important in preventing neural tube defect affected pregnancies, and in reducing risk for cardiovascular disease and certain cancers. Enzymes in the folate metabolic pathway may affect availability of the primary circulatory form of folate. A common mutation in the enzyme, methylenetetrahydrofolate reductase (MTHFR), 677C → T reduces enzyme activity, leading to lower levels of circulating folate.; This study aims to assess the effect of folic acid, during and post supplementation, on red blood cell and serum folate. A secondary aim is to identify demographic correlates of the MTHFR thermolabile allele in this double-blind, controlled study with a crossover design.; Volunteers, aged 18–69 were screened for factors including genotype of MTHFR. Selected volunteers were randomized to receive two of three different doses of folic acid in random order for twelve weeks. The doses include 0 μg, 200 μg, and 400 μg. There was a 30-week washout period between the treatment periods. Blood samples were taken at baseline, then every six weeks for the 54-week study period.; Red cell and serum folate levels increased with increasing folic acid supplementation. Clearance of folic acid was seen during washout and the time in which blood folate levels returned to baseline, depended on the dose given. The thermolabile allele of MTHFR is less common among Blacks than it is among whites and Asian Americans, and is also less common in women than men.; Information provided regarding the relationship of folic acid intake with blood folate levels will be helpful in monitoring folate intake, defining optimal folate intake, and designing folate studies with crossover designs. Identification of subgroups with a high prevalence of the MTHFR thermolabile allele (i.e. white men) enables the characterization of populations who may be at increased risk for developing cardiovascular diseases when folate consumption is low.