DIJON, FranceIn patients with a history of colorectal adenomas, use of a soluble fiber supplement (ispaghula husk) appears to have an adverse effect on recurrence, said Jean Faivre, MD, of the European Cancer Prevention Organi-sation (ECP) Study Group. The study also showed that calcium supplementation produced a modest but not significant reduction in the risk of adenoma recurrence.
665 Patients Randomized
Between 1991 and 1994, 665 patients with a history of colorectal adenomas were enrolled in the study at 21 centers in 9 European countries and Israel, said Professor Faivre, of Registre Bourguignon des Tumeurs Digestives, Faculté de Médicine de Dijon. They were randomly assigned to three groups: fiber supplement (3.5 g of ispaghula husk daily), calcium supplement (2 g of elemental calcium daily), or placebo. Ispaghula husk is a mucilaginous substance used as an ingredient in some laxatives.
The calcium was administered twice daily in the form of two sachets diluted in water; the fiber was given as one sachet of orange-flavored effervescent granules diluted in water.
Colonoscopy was performed after 3 years. Of the 552 subjects who completed the follow-up colonoscopic examination, 94 had stopped treatment early, but the proportions who stopped prematurely did not differ significantly between the treatment groups. A complete colon exam was obtained in 539 patients.
During the 3 years of follow-up, at least one adenoma developed in 28 (15.9%) of the 176 participants receiving calcium, 58 (29.3%) of the 198 receiving fiber, and 36 (20.2%) of the 178 on placebo (Lancet 356:1300-1306, 2000). One person, receiving placebo, was diagnosed with an invasive adenocarcinoma.
The risk of recurrence was significantly increased in patients receiving the fiber treatment, Professor Faivre said, with an odds ratio of 1.63. There was a nonsignificant risk reduction in the calcium group (odds ratio, 0.75). Adjustment for age, sex, history of adenoma, and number and location of adenomas at inclusion had little effect on the results (adjusted odds ratio, 0.66 for calcium and 1.67 for fiber).
The adverse effect of the ispaghula fiber supplementation was observed overall and in most subgroups of patients, which suggests that it cannot be attributed to chance alone, he said.
The odds ratio for recurrence for those receiving fiber was significantly higher in participants whose baseline dietary calcium intake was above the median, compared with those with low calcium intake (P = .028). This finding was unexpected, and we cannot rule out that it was due to chance alone, he said.
The increased risk of recurrence with fiber supplementation was seen for both small and larger adenomas, with no significant variations according to the colon subsite. Professor Faivre noted, however, that since very few patients developed large adenomas, we cannot exclude the possibility of a beneficial effect of ispaghula husk on later stages of carcinogenesis, such as adenoma growth and malignant transformation.
Finally, he said, there was no evidence that the adverse effect of fiber could be explained by differential changes in dietary intake by treatment groups during the trial.
Professor Faivre concluded that the findings do not accord with the hypothesis of a protective effect of fiber on the risk of colon cancer. He cited five previous studies showing no benefit for fiber supplementation or a high-fiber diet.
He added, however, that the findings should not prevent recommendations for high consumption of vegetables, fruits, and cereals, because this approach has potentially beneficial effects on other chronic diseases, especially coronary heart disease.