RANDOMIZED TRIAL OF INTAKE OF FAT, FIBER, AND BETA-CAROTENE TO PREVENT COLORECTAL ADENOMAS

Background: Epidemiologic evidence of associations between the high in take of fat and low intake of dietary fiber, beta carotene, and other dietary constituents and the risk of colorectal neoplasia has been inc onsistent and has not provided a sufficient basis for recommendations concerning the dietary prevention of large-bowel cancer in humans. Pur pose: We conducted a clinical trial to assess the effects on the incid ence of adenomas of reducing dietary fat to 25% of total calories and supplementing the diet with 25 g of wheat bran daily and a capsule of beta carotene (20 mg daily). Methods: We performed a randomized, parti ally double-blinded, placebo-controlled factorial trial in which half the patients were assigned to each intervention, resulting in seven in tervention groups and one control group, Eligibility criteria included histologic confirmation of at least one colorectal adenoma and confid ence expressed by the colonoscopist that all polyps had been removed, Dietary changes were individually initiated and monitored by dietitian s and research nurses, At surveillance colonoscopy, the size and locat ion of all polyps were recorded, and their histology was later central ly reviewed, Among 424 patients who were randomly assigned in the tria l, 13 were found to be ineligible upon histologic review, Among the re maining 411, complete outcome data were collected from 390 at 24 month s and from 306 at 48 months, All P values are from two-sided tests of statistical significance, Results: There was no statistically signific ant prevention of total new adenomas with any of the interventions, We found a statistically nonsignificant reduced risk of large adenomas ( greater than or equal to 10 mm) with the low-fat intervention: At 24 m onths, the odds ratio (OR) adjusted for potential confounders = 0.4 an d 95% confidence interval (CI) = 0.1-1.1; at 48 months, OR = 0.3 and 9 5% CI = 0.1-1.0, Less and statistically nonsignificant reductions in t he risk of large adenomas were found with wheat bran: At 24 months, OR = 0.8 and 95% CI = 0.3-2.2; at 48 months, OR = 0.8 and 95% CI = 0.3-2 .5, Patients on the combined intervention of low fat and added wheat b ran had zero large adenomas at both 24 and 48 months, a statistically significant finding (P = .03), Conclusions: Because only small numbers of patients were studied, our finding that the combination of fat red uction and a supplement of wheat bran reduced the incidence of large a denomas in this randomized, controlled trial must be treated with caut ion, The results do suggest, however, that these interventions may red uce the transition from smaller to larger adenomas, a step that may cr itically define those adenomas most likely to progress to malignancy.