Fiber and Prevention of Colonic Adenomas: The Rough Data
ABSTRACTs & COMMENTARY
Synopsis: Epidemiological studies have suggested that dietary supplementation with either fiber or calcium may have protective effects in the bowel, with possibly less adenoma and adenocarcinoma outcomes. The European Cancer Prevention Organization Study group performed a randomized study in which patients who had previously had adenomas resected received either supplemental dietary fiber or calcium (or neither) and found that calcium had a modest (albeit, not statistically significant) benefit and that fiber actually increased the risk of recurrent adenoma development. Thus, the recommendation for high-fiber diets should not be based on a notion that this has a protective effect with regard to the development of colon cancer.
Sources: Bonithon-Kopp C, et al. Lancet 2000;356:
1300-1306; Levin B. Lancet 2000;356:1286-1287.
There is laboratory and epidemiological research that suggests a diet high in calcium and fiber reduces the incidence of adenocarcinoma of the colon.1-3 However, the data is not strong enough to formally recommend dietary adjustment. The purpose of this interventional trial was to provide such data, if indeed fiber and calcium were found to prevent adenoma, a known precursor of colorectal cancer.
Bonithon-Kopp and associates performed the trial in which 665 patients with a history of colorectal adenomas were randomly assigned to one of three treatment groups: Calcium supplementation (2 gm elemental calcium daily), fiber (3.5 gm of ispaghula husk daily), or placebo. Participants had colonoscopy after three years on trial and the primary end point was adenoma recurrence. Analyses were by intention to treat.
The analysis was based upon the 552 patients who completed the trial. At least one adenoma developed in 28 (15.9%) of 176 patients in the calcium group, 58 (29.3%) in the fiber group, and in 36 (20.2%) placebo- treated subjects. The adjusted odds ratio for recurrence was 0.66 (95% confidence interval [CI] 0.38-1.17; P = 0.16) for calcium treatment and 1.67 (1.01-2.76; P = 0.042) for the fiber treatment. Bonithon-Kopp et al concluded that supplementation with fiber may have adverse effects on colorectal adenoma recurrence, but that calcium supplementation may be beneficial (although the results from this study with regard to calcium were not statistically significant).
COMMENT by William B. Ershler, MD
The trial highlights the difficulties in doing a multinational interventional trial. For a number of reasons, recruitment was considerably lower than expected. Although compliance was good for those in the fiber group, it was not good for those assigned to receive calcium. As Levin points out in the accompanying editorial, this may be due to the relatively high level of calcium ingested by those in this experimental group (2.0 g/d in addition to an average dietary intake of 918 mg). He points out that in the United States, the recommended dietary allowance for calcium for adults aged 25 or older (except during pregnancy or lactation) is 800 mg/d and the tolerable, upper limit, dietary reference intake is set at 2500 mg. Thus, some of the drop in compliance might have been due to an untoward effect of this increased level of intake. Nonetheless, the modest beneficial effect observed for those receiving calcium is consistent with another trial in which there was a significant reduction in adenoma development after four years of dietary calcium supplementation.4 If calcium does have a protective effect on the development of adenomas and adenocarcinomas, certainly the mechanism is only conjecture at this point. It has been suggested that calcium binds to secondary bile acids and fatty acids and forms insoluble soaps in the bowel lumen, thereby reducing their absorption and limiting colonic cell proliferation.
The increased risk of adenomas in the fiber group was surprising but, as Bonithon-Kopp et al suggest, points out the importance of interventional prospective studies. Certainly a number of epidemiological studies suggested a protective effect of fiber,5 as did a meta-analysis of 13 case-control studies of colon cancer.6 Despite this, when subjected to randomized trial as with this report, or as observed in others, dietary fiber supplementation has had a disappointing effect with regard to adenoma development, either showing no difference or an actual increase in adenomas in the treatment group.7,8 Although it may be time to abandon the high fiber diet as a tool for colon cancer prevention, it should be recalled that such a diet, particularly when combined with low dietary fat, may have a number of salutary effects, particularly on the cardiovascular system.
References
1. Gaard M, et al. Eur J Cancer Prev 1996;5:445-454.
2. Fuchs CS, et al. N Engl J Med 1999;340:169-224.
3. Martinez ME, et al. Cancer Epidemiol Biomarkers Prev 1998;7:163-168.
4. Baron JA, et al. N Engl J Med 1999;340:100-107.
5. Trock B, et al. J Natl Cancer Inst 1990;82:650-666.
6. Howe GR, et al. J Natl Cancer Inst 1992;84:1887-1896.
7. DeCosse JJ, et al. J Natl Cancer Inst 1989;81:
1290-1297.
8. McLennan R, et al. J Natl Cancer Inst 1995;87:
1760-1766.
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