Decreases in gamma-tocopherol, but not alpha-tocopherol, with a low-fat diet
Authors: Bernard F. Cole, John A. Baron, Robert S. Sandler, Robert W. Haile, Dennis J. Ahnen, Robert S. Bresalier, Gail Mckeown-Eyssen, Robert W. Summers, Richard Rothstein, Carol A. Burke, Dale C. Snover, Timothy R. Church, Tim Byers
Journal: Cancer Research (2005)

4399   Background:Laboratory and epidemiologic data suggest that folic acid supplementation has an antineoplastic effect in the large bowel. The Aspirin-Folate Polyp Prevention Study is a randomized, double-blind, factorial design trial of folic acid and aspirin supplementation as chemoprotective agents against colorectal adenomas. Findings regarding aspirin have been reported; we report here the folic acid results. Methods:Subjects with a recent history of adenomas were randomly assigned to receive placebo (n=505) or 1 mg of folic acid (n=516) daily with or without aspirin. Follow-up colonoscopy was scheduled approximately three years after the qualifying endoscopy (1st follow-up interval), at which point aspirin supplementation was completed. Randomized supplementation with folic acid or placebo continued until the next surveillance exam (2nd follow-up interval) in subjects who re-consented after completing the 1st follow-up interval. The occurrence of one or more adenomas, adenoma multiplicity (number per subject), and the occurrence of advanced lesions (adenomas with any villous features, severe dysplasia, size of 1 cm or larger, or invasive cancer) were compared during follow up of the folic acid and placebo groups. Results:Adherence to study medications and avoidance of folic-acid-containing vitamin supplements were excellent, with compliance rates varying over time between 87% and 96% of subjects. In the 1st follow-up interval, surveillance colonoscopies were performed in 987 subjects (97%). The incidence of one or more colorectal adenomas was 42% in placebo subjects and 44% in folic acid subjects (crude risk ratio [RR]: 1.04; 95% confidence interval [CI]: 0.90 to 1.20). The incidence of advanced lesions in the folic acid group was modestly higher than in placebo (9% vs. 12%; RR: 1.31; 95% CI: 0.90 to 1.89). 925 subjects consented to extended follow-up, with 729 continuing randomized treatment. With the end of funding for continued treatment, the trial was stopped October 1, 2004. Analysis of the 488 subjects who underwent colonoscopic follow-up in the 2nd interval showed RR’s similar to those of the 1st follow-up interval. Subjects in the folic acid group tended to have greater adenoma multiplicity. In the subgroup that continued treatment in the 2nd follow-up interval, the mean (SD) number of adenomas per subject was 0.55 (0.89) in the placebo group and 0.79 (1.40) in the folic acid group (rate ratio: 1.44; 95% CI: 1.03 to 2.02). No other significant adverse effects of folic acid were detected. Conclusions:Folic acid supplementation at 1 mg/day does not reduce the incidence of colorectal adenomas. There was weak evidence that folic acid increases the risk of multiple adenomas.  This trial was conducted by the Polyp Prevention Study Group and was supported by a grant from the National Cancer Institute (CA 59005). Folic acid and placebo tablets were supplied by Wyeth Pharmaceuticals.