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Colonic Mucosal Concentrations of Folate Are Accurately Predicted by Blood Measurements of Folate Status among Individuals Ingesting Physiologic Quantities of Folate¹

Departments of Medicine [Y-I. K.] and Nutritional Sciences [Y-I. K.], Division of Gastroenterology, University of Toronto and St. Michael’s Hospital, Toronto, Ontario, M5S 1A8 Canada; Divisions of Clinical Nutrition [J. B. M.] and Gastroenterology [K. F., T. K., Y-M. L., R. N., E. L., J. B. M.], Department of Internal Medicine, New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts; and Vitamin Metabolism Laboratory, Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts 02111 [J. B. M.]

Folate status is inversely related to the risk of colorectal cancer. Whether conventional blood measurements of folate status accurately reflect folate concentrations in the colorectal mucosa has been a controversial topic. This is an important issue because accurate measures of folate status in the colorectal mucosa are important for ascertaining the risk of colorectal cancer in epidemiological studies and for determining the effects of folate supplementation in clinical trials. We examined whether conventional blood measurements of folate and a more sensitive, inverse indicator of systemic folate status, serum homocysteine, accurately reflect folate concentrations in human colonic mucosa obtained by endoscopic biopsy. Study subjects (n = 20) were participants in a randomized trial that investigated the effect of folate supplementation (5 mg daily for 1 year) on provisional molecular markers of colon cancer. Blood samples and biopsies of normal rectosigmoid mucosa were obtained at baseline, at 6 months, and at 1 year. Serum, RBC, and colonic mucosal folate and serum homocysteine concentrations were determined. Colonic mucosal folate concentrations correlated directly with serum folate concentrators at each time point (r = 0.572–0.845; P < 0.015) and with RBC folate concentrations at 6 months and 1 year (r = 0.747–0.771; P < 0.001). Colonic mucosal folate concentrations correlated inversely with serum homocysteine concentrations at each time point (r = -0.622–0.666; P < 0.008). Systemic measures of folate status did not correlate with colonic mucosal folate concentrations among individuals receiving supplemental folate. Our observations indicate that colonic mucosal concentrations of folate may be predicted accurately by blood measurements of folate status only among individuals not ingesting supraphysiological quantities of folate.

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