The polyp prevention trial II: dietary intervention program and participant baseline dietary characteristics. A randomized trial of a low fat high fibre diet in the recurrence of colorectal polyps. Toronto Polyp Prevention Group. Randomized trial of intake of fat, fiber, and beta carotene to prevent colorectal adenomas. The polyp prevention trial I: rationale, design, recruitment, and baseline participant characteristics. Implementation of a 4-y, high-fiber, high-fruit-and-vegetable, low-fat dietary intervention: results of dietary changes in the Polyp Prevention Trial. Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas. Phoenix Colon Cancer Prevention Physicians' Network. Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. Polyp Prevention Trial Study Group. Calcium and fibre supplementation in prevention of colorectal adenoma recurrence: a randomised intervention trial. European Cancer Prevention Organisation Study Group. A randomized trial of vitamins C and E in the prevention of recurrence of colorectal polyps.
The Polyp Prevention Trial (PPT) is a multicenter randomized controlled trial to evaluate whether a low-fat, high-dietary fiber, high-fruit and -vegetable eating pattern will reduce the recurrence of adenomatous polyps of the large bowel. Men and women who had one or more adenomas removed recently were randomized into either the intervention (n = 1037) or control (n = 1042) arms. Food frequency questionnaire data indicate that PPT participants at the beginning of the trial consumed 36.8% of total energy from fat, 9.7 g of dietary fiber/1000 kcal, and 3.8 daily servings of fruits and vegetables. Baseline dietary characteristics, including intake of fat, fiber, and fruits and vegetables, as well as other macro- and micronutrients, were similar in the two study groups. The intervention participants receive extensive dietary and behavioral counseling to achieve the PPT dietary goals of 20% of total energy from fat, 18 g/1000 kcal of dietary fiber, and 5-8 daily servings (depending on total caloric intake) of fruits and vegetables. Control participants do not receive such counseling and are expected to continue their usual intake. Dietary intake in both groups is mentioned annually using a 4-day food record (also completed at 6 months by intervention participants only) and a food frequency questionnaire, with a 10% random sample of participants completing an annual unscheduled 24-h telephone recall. Blood specimens are drawn and analyzed annually for lipids and carotenoids. This article provides details on the rationale and design of the PPT dietary intervention program and describes the participant baseline dietary intake data characteristics. After polypectomy for adenomatous colorectal polyps, 201 persons were randomized to receive counselling on a diet low in fat (the lesser of 50 g/day or 20% of energy) and high in fibre (50 g/day) (LFHF), or to follow a normal western diet (ND), high in fat and low in fibre. After 12 months of counselling, fat consumption was about 25% of energy in the LFHF group and 33% in the ND group; fibre consumption was 35 g and 16 g respectively. After an average of two years of follow-up, an intention to treat analysis led to a ratio of cumulative incidence rates of 1.2 (95% CL 0.6-2.2) for recurrence of neoplastic polyps, a finding which suggests no significant difference between dietary groups over the period of observation. An exploratory analysis conducted among 142 persons with substantial diet counselling indicated a reduced risk of neoplastic polyp recurrence in women (RR = 0.5), associated with reduced concentrations of faecal bile acids while on the LFHF diet, but indicated an increased risk of recurrence in men (RR = 2.1), associated with increased faecal bile acids. Although a larger study would be needed to rule out the role of chance, these findings of gender-specific associations between diet counselling and both faecal bile acid concentrations and recurrence of colorectal neoplasia are consistent with recently published evidence of differences between genders. Epidemiologic evidence of associations between the high intake of fat and low intake of dietary fiber, beta carotene, and other dietary constituents and the risk of colorectal neoplasia has been inconsistent and has not provided a sufficient basis for recommendations concerning the dietary prevention of large-bowel cancer in humans.
                We conducted a clinical trial to assess the effects on the incidence 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).
                We performed a randomized, partially double-blinded, placebo-controlled factorial trial in which half the patients were assigned to each intervention, resulting in seven intervention groups and one control group. Eligibility criteria included histologic confirmation of at least one colorectal adenoma and confidence expressed by the colonoscopist that all polyps had been removed. Dietary changes were individually initiated and monitored by dietitians and research nurses. At surveillance colonoscopy, the size and location of all polyps were recorded, and their histology was later centrally reviewed. Among 424 patients who were randomly assigned in the trial, 13 were found to be ineligible upon histologic review. Among the remaining 411, complete outcome data were collected from 390 at 24 months and from 306 at 48 months. All P values are from two-sided tests of statistical significance.
                There was no statistically significant prevention of total new adenomas with any of the interventions. We found a statistically non-significant reduced risk of large adenomas (> or = 10 mm) with the low-fat intervention: At 24 months, the odds ratio (OR) adjusted for potential confounders = 0.4 and 95% confidence interval (CI) = 0.1-1.1; at 48 months, OR = 0.3 and 95% CI = 0.1-1.0. Less and statistically nonsignificant reductions in the 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 bran had zero large adenomas at both 24 and 48 months, a statistically significant finding (P = .03).
                Because only small numbers of patients were studied, our finding that the combination of fat reduction and a supplement of wheat bran reduced the incidence of large adenomas in this randomized, controlled trial must be treated with caution. The results do suggest, however, that these interventions may reduce the transition from smaller to larger adenomas, a step that may critically define those adenomas most likely to progress to malignancy. The Polyp Prevention Trial (PPT) is a multicenter randomized controlled trial examining the effect of a low-fat (20% of total energy intake), high-fiber (18 g/1000 kcal), high-vegetable and -fruit (5-8 daily servings) dietary pattern on the recurrence of adenomatous polyps of the large bowel, precursors of most colorectal malignancies. Eligibility criteria include one or more adenomas removed within 6 months of randomization; complete nonsurgical polyp removal and complete colonic examination to the cecum at the qualifying colonoscopy: age 35 years of more; no history of colorectal cancer, inflammatory bowel disease, or large bowel resection; and satisfactory completion of a food frequency questionnaire and 4-day food record. Of approximately 38,277 potential participants with one or more polyps recently resected, investigators at eight clinical centers randomized 2,079 (5.4%; 1,037 in the intervention and 1,042 in the control arm) between June 1991 and January 1994, making the PPT the largest adenoma recurrence trial ever conducted. Of PPT participants, 35% are women and 10% are minorities. At study entry, participants averaged 61.4 years of age; 14% of them smoked, and 22% used aspirin. At the baseline colonoscopy, 35% of participants had two or more adenomas, and 29% had at least one large (> of = 1 cm) adenoma. Demographic, behavioral, dietary, and clinical characteristics are comparable across the two study arms. Participants have repeat colonoscopies after 1 (T(1)) and 4 (T(4)) years of follow-up. The primary end point is adenoma recurrence; secondary end points include number, size, location, and histology of adenomas. All resected lesions are reviewed centrally by gastrointestinal pathologists. The trial provides 90% power to detect a reduction of 24% in the annual adenoma recurrence rate. The primary analytic period, on which sample size calculations were based is 3 years (T(1) to T(4)), which permits a 1-year lag time for the intervention to work and allows a more definitive clearing of lesions at T(1), given that at least 10-15% of polyps may be missed at baseline. The final (T(4)) colonoscopies are expected to be completed in early 1998. The Polyp Prevention Trial (PPT) was a multicenter randomized clinical trial designed to determine the effects of a high-fiber (4.30 g/MJ), high-fruit-and-vegetable (0.84 servings/MJ), low-fat (20% of energy from fat) diet on the recurrence of adenomatous polyps in the large bowel.
                Our goal was to determine whether the PPT intervention plan could effect change in 3 dietary goals and to examine the intervention's effect on the intake of other food groups and nutrients.
                Participants with large-bowel adenomatous polyps diagnosed in the past 6 mo were randomly assigned to either the intervention (n = 1037) or the control (n = 1042) group and remained in the trial for 4 y. Three dietary assessment instruments were used to measure dietary change: food-frequency questionnaires (in 100% of the sample), 4-d food records (in a 20% random cohort), and 24-h dietary recalls (in a 10% random sample).
                Intervention participants made and sustained significant changes in all PPT goals as measured by the dietary assessment instruments; the control participants' intakes remained essentially the same throughout the trial. The absolute differences between the intervention and control groups over the 4-y period were 9.7% of energy from fat (95% CI: 9.0%, 10.3%), 1.65 g dietary fiber/MJ (95% CI: 1.53, 1.74), and 0.27 servings of fruit and vegetables/MJ (95% CI: 0.25, 0.29). Intervention participants also reported significant changes in the intake of other nutrients and food groups. The intervention group also had significantly higher serum carotenoid concentrations and lower body weights than did the control group.
                Motivated, free-living individuals, given appropriate support, can make and sustain major dietary changes over a 4-y period. The risks of colorectal cancer and adenoma, the precursor lesion, are believed to be influenced by dietary factors. Epidemiologic evidence that cereal fiber protects against colorectal cancer is equivocal. We conducted a randomized trial to determine whether dietary supplementation with wheat-bran fiber reduces the rate of recurrence of colorectal adenomas.
                We randomly assigned 1429 men and women who were 40 to 80 years of age and who had had one or more histologically confirmed colorectal adenomas removed within three months before recruitment began to a supervised program of dietary supplementation with either high amounts (13.5 g per day) or low amounts (2 g per day) of wheat-bran fiber. The primary end point was the presence or absence of new adenomas at the time of follow-up colonoscopy. Subjects and physicians, including colonoscopists, were unaware of the group assignments.
                Of the 1303 subjects who completed the study, 719 had been randomly assigned to the high-fiber group and 584 to the low-fiber group. The median times from randomization to the last follow-up colonoscopy were 34 months in the high-fiber group and 36 months in the low-fiber group. By the time of the last follow-up colonoscopy, at least one adenoma had been identified in 338 subjects in the high-fiber group (47.0 percent) and in 299 subjects in the low-fiber group (51.2 percent). The multivariate adjusted odds ratio for recurrent adenoma in tile high-fiber group, as compared with the low-fiber group, was 0.88 (95 percent confidence interval, 0.70 to 1.11; P=0.28), and the relative risk of recurrence according to the number of adenomas, in the high-fiber group as compared with the low-fiber group, was 0.99 (95 percent confidence interval, 0.71 to 1.36; P=0.93).
                As used in this study, a dietary supplement of wheat-bran fiber does not protect against recurrent colorectal adenomas. We tested the hypothesis that dietary intervention can inhibit the development of recurrent colorectal adenomas, which are precursors of most large-bowel cancers.
                We randomly assigned 2079 men and women who were 35 years of age or older and who had had one or more histologically confirmed colorectal adenomas removed within six months before randomization to one of two groups: an intervention group given intensive counseling and assigned to follow a diet that was low in fat (20 percent of total calories) and high in fiber (18 g of dietary fiber per 1000 kcal) and fruits and vegetables (3.5 servings per 1000 kcal), and a control group given a standard brochure on healthy eating and assigned to follow their usual diet. Subjects entered the study after undergoing complete colonoscopy and removal of adenomatous polyps; they remained in the study for approximately four years, undergoing colonoscopy one and four years after randomization.
                A total of 1905 of the randomized subjects (91.6 percent) completed the study. Of the 958 subjects in the intervention group and the 947 in the control group who completed the study, 39.7 percent and 39.5 percent, respectively, had at least one recurrent adenoma; the unadjusted risk ratio was 1.00 (95 percent confidence interval, 0.90 to 1.12). Among subjects with recurrent adenomas, the mean (+/-SE) number of such lesions was 1.85+/-0.08 in the intervention group and 1.84+/-0.07 in the control group. The rate of recurrence of large adenomas (with a maximal diameter of at least 1 cm) and advanced adenomas (defined as lesions that had a maximal diameter of at least 1 cm or at least 25 percent villous elements or evidence of high-grade dysplasia, including carcinoma) did not differ significantly between the two groups.
                Adopting a diet that is low in fat and high in fiber, fruits, and vegetables does not influence the risk of recurrence of colorectal adenomas. Some epidemiological studies have suggested that high dietary intake of calcium and fibre reduces colorectal carcinogenesis. Available data are not sufficient to serve as a basis for firm dietary advice. We undertook a multicentre randomised trial to test the effect of diet supplementation with calcium and fibre on adenoma recurrence.
                We randomly assigned 665 patients with a history of colorectal adenomas to three treatment groups, in a parallel design: calcium gluconolactate and carbonate (2 g elemental calcium daily), fibre (3.5 g ispaghula husk), or placebo. Participants had colonoscopy after 3 years of follow-up. The primary endpoint was adenoma recurrence. Analyses were by intention to treat.
                23 patients died, 15 were lost to follow-up, 45 refused repeat colonoscopy, and five developed severe contraindications to colonoscopy. Among the 552 participants who completed the follow-up examination, 94 stopped treatment early. At least one adenoma developed in 28 (15.9%) of 176 patients in the calcium group, 58 (29.3%) of 198 in the fibre group, and 36 (20.2%) of 178 in the placebo group. The adjusted odds ratio for recurrence was 0.66 (95% CI 0.38-1.17; p=0.16) for calcium treatment and 1.67 (1.01-2.76, p=0.042) for the fibre treatment. The odds ratio associated with the fibre treatment was significantly higher in participants with baseline dietary calcium intake above the median than in those with intake below the median (interaction test, p=0.028)
                Supplementation with fibre as ispaghula husk may have adverse effects on colorectal adenoma recurrence, especially in patients with high dietary calcium intake. Calcium supplementation was associated with a modest but not significant reduction in the risk of adenoma recurrence. Because supplements of vitamins C and E had been associated with reduction of fecal mutagen levels, a double-blind randomized trial was designed to examine the effects of these vitamins on the rate of recurrence of colorectal polyps, presumed precursors for colorectal cancer. Two hundred patients believed to be free of polyps after removal of at least one colorectal polyp were randomized to receive a supplement of 400 mg each of ascorbic acid and alpha-tocopherol, or a placebo. Fifteen patients had to be excluded because a review of pathology indicated that their polyps were not adenomatous. A second colonoscopic examination was planned after 2 yr of supplementation. One hundred thirty-seven people (75% of eligible subjects) completed the study; polyps were observed in the second colonoscopy in 41.4% of 70 subjects on vitamin supplements and in 50.7% of 67 subjects on placebos. After adjustment for differences between groups in demographic and dietary factors before study entry, the relative risk of polyp occurrence was 0.86, with 95% confidence limits from 0.51 to 1.45, in an analysis of 129 subjects with complete information on demographic and dietary factors who had completed the trial. Of the 48 patients who had not completed the study, 7 had died, 33 had not returned to their physician for an examination, and 8 had had a follow-up colonoscopy or sigmoidoscopy. Inclusion of the three polyps found in these eight examinations led to an estimate of relative risk of 0.86 (95% confidence limits, 0.51 to 1.43). The findings of this investigation suggest that any reduction in the rate of polyp recurrence associated with vitamin supplementation is small, and a larger study would be required to ensure that an effect of this size was not a chance finding.
There is currently no evidence from RCTs to suggest that increased dietary fibre intake will reduce the incidence or recurrence of adenomatous polyps within a two to four year period.