Elsevier

The Lancet

Volume 356, Issue 9238, 14 October 2000, Pages 1300-1306
The Lancet

Articles
Calcium and fibre supplementation in prevention of colorectal adenoma recurrence: a randomised intervention trial

https://doi.org/10.1016/S0140-6736(00)02813-0Get rights and content

Summary

Background

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.

Methods

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 followup. The primary endpoint was adenoma recurrence. Analyses were by intention to treat.

Findings

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)

Interpretation

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.

Introduction

There is clear evidence that diet has a major role in colon carcinogenesis. Some experimental and analytical studies have suggested that the consumption of dietary fibre, vegetables, whole-grain cereals, and calcium may have a protective effect against colorectal cancer1 and adenomas, 2 but results from epidemiological studies have been inconsistent.3, 4, 5, 6 Adenomas are thought to be precursors of most colorectal cancers in more developed countries and could be a target for primary prevention. Several arguments support the notion that the adenomacarcinoma sequence is a multistep process.7 Cancer could be prevented at the stage of adenoma appearance, growth, or transformation into carcinoma. Attractive carcinogenesis hypotheses can be tested in intervention studies, the most appropriate way to assess the feasibility and efficacy of preventive measures. Two intervention studies have provided some evidence of a protective effect of calcium alone or with antioxidants on adenoma recurrence,8, 9 but findings of trials on the effects of a low-fat, high-fibre diet10 and wheat-bran supplementation have been disappointing.11 No intervention study has investigated the effects in human beings of soluble fibre such as ispaghula husk, a mucilaginous substance, which has potent antitumour activity in animal models of colon carcinogenesis. The European Cancer Prevention Organisation (ECP) Intervention Study, started in 1991, was a placebo-controlled trial aimed at assessing the efficacy of ispaghula husk and calcium supplementation in the prevention of adenoma recurrence over 3 years.

Section snippets

Participants

The ECP Intervention Study involved 21 centres from ten countries (Belgium, Denmark, France, Germany, Ireland, Israel, Italy, Portugal, Spain, and the UK). Between 1991 and 1994, we enrolled patients with colorectal polyps who met the inclusion and exclusion criteria.12 The inclusion criteria were: a complete index colonoscopy showing at least two adenomas or one adenoma of diameter more than 5 mm, based on the diagnosis of the local pathologist; age between 35 and 75 years; no debilitating or

Results

Among the 640 patients who had histologically confirmed adenomas at inclusion, 13 underwent interim colonoscopy (five calcium group, six fibre group, two placebo group) and 552 underwent the 3-year colonoscopy (figure). A complete colon examination was obtained in 539 patients, of whom 21 had undergone a control colonoscopy. In 13 other patients (2·3%), only a limited examination could be obtained. This examination reached at least to the transverse colon for eight patients. The proportion with

Discussion

This randomised intervention study showed that calcium supplementation for 3 years had a slight but not significant beneficial effect on adenoma recurrence, whereas fibre supplementation by a mucilaginous substance resulted in a significant increase in the recurrence rate.

The rate of final colonoscopy was high and similar in all treatment groups, and the baseline characteristics of the patients who completed the study did not differ between treatment groups. We do not believe, therefore, that

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