Effect of Folate on Colonic and Blood Cells
- To analyze the effects of changes in levels of dietary folate intake on damage to DNA
and repair capacity, mRNA expression, and DNA uracil incorporation in peripheral blood
mononuclear cell and rectal biopsy cell samples from patients at increased risk for
developing colorectal neoplasia.
OUTLINE: Patients are enrolled into 1 of 2 intervention groups..
- Group I (folate depletion [in-patient]): Patients consume a weight-maintaining, average
folate diet with no high folate-containing foods for 8 weeks. Patients are then
admitted to The Rockefeller University Hospital and placed on a weight-maintaining,
low-folate diet for 12 weeks. During the last 4 weeks of the in-patient period,
patients receive oral folic acid supplementation once daily for 4 weeks.
- Group II (folate supplementation [out-patient]): Patients consume a weight-maintaining,
average folate diet with no high folate-containing foods for 16 weeks as an
out-patient. After the first 8 weeks of the diet, patients also receive oral folic acid
supplementation once daily for 8 weeks.
Patients undergo blood sample collection periodically for biomarker correlative studies.
Samples are analyzed for serum and red cell folate and homocystine levels to assess folate
depletion; methylentetrahydrofolate reductase (MTHFR) polymorphism to test for inherited
alterations of folate metabolism; serum and plasma biomarkers; and DNA studies. Patients
also undergo tissue sample collection by sigmoidoscopy and rectal biopsy periodically.
Tissue samples are assessed for mucosal folate concentration and mucosal folic acid
metabolites; DNA methylation; and gene assays by microarray analysis.
After completion of study intervention, patients are followed at 4 weeks.
Masking: Single Blind, Primary Purpose: Prevention
DNA uracil incorporation in peripheral blood mononuclear cells (PBMCs)
Peter R. Holt, MD
United States: Federal Government