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Therapeutics

Fiber supplementation increased the risk for recurrent adenomas, and calcium supplementation did not prevent recurrence

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ACP J Club. 2001 May-June;134:104. doi:10.7326/ACPJC-2001-134-3-104


Source Citation

Bonithon-Kopp C, Kronborg O, Giacosa A, Räth U, Faivre J, for the European Cancer Prevention Organisation Study Group. Calcium and fibre supplementation in prevention of colorectal adenoma recurrence: a randomised intervention trial. Lancet. 2000 Oct 14;356:1300-6. [PubMed ID: 11073017] (All 2001 articles were reviewed for relevancy, and abstracts were last revised in 2007.)


Abstract

Question

In patients with colorectal adenomas, does supplementation with ispaghula husk or calcium prevent adenoma recurrence?

Design

Randomized (allocation concealed*), blinded (patients, clinical staff, and investigators),* placebo-controlled trial with 3-year follow-up.

Setting

21 centers in 10 countries (Belgium, Denmark, France, Germany, Ireland, Israel, Italy, Portugal, Spain, and the United Kingdom).

Patients

665 patients who were 35 to 75 years of age, had a complete index colonoscopy showing ≥ 2 adenomas or 1 adenoma of > 5 mm in diameter, and did not have a debilitating or life-threatening disease. Exclusion criteria were history of large-bowel disease, contraindications to calcium or fiber, or inability or unwillingness to stop current fiber or calcium supplementation. 552 patients (83%, mean age 59 y, 64% men) completed the 3-year follow-up.

Intervention

After stratification by center, patients were allocated to 1 of 3 groups: elemental calcium, given at 2 g of calcium gluconolactate and carbonate in a water solution twice daily (n = 176); ispaghula husk, given as 3.5 g of orange-flavored effervescent granules dissolved in water (n = 198); or placebo that either matched the elemental calcium or the ispaghula husk (n = 178).

Main outcome measure

New adenomas at the 3-year colonoscopy.

Main results

Patients in the fiber group had a 45% increase in recurrent adenomas relative to the placebo group at 3 years {P = 0.04}† (Table). The difference between the calcium and placebo groups was not statistically significant (Table).

Conclusions

In patients with adenomas, supplementation with ispaghula husk increased the risk for recurrent adenoma. Calcium supplementation did not prevent adenomas.

*See Glossary.

P value calculated from data in article.

Sources of funding: Europe Against Cancer Programme; Association Contre le Cancer; Association Luxembourgeoise Contre le Cancer; INSERM; French Ministry of Health; Deutsches Krebsforschungzentrum; Danish Cancer Society; FISS; Hospital supplies (Ireland); University of Coimbra; Istituto Tumori Genova.

For correspondence: Professor J. Faivre, Registre Bourguignon des Tumeurs Digestives, Faculté de Médecine de Dijon, BP 87900, 21079 Dijon, France. FAX 33-380-66-8251.


Table. Supplementation with calcium or ispaghula husk (fiber) vs placebo for preventing recurrent adenomas‡

Outcome at 3 y Comparison Event rates RRI (95% CI) NNH (CI)
Recurrent adenomas Fiber vs placebo 29% vs 20% 45% (1 to 109) 12 (6 to 340)
RRR (CI) NNT
Calcium vs placebo 16% vs 20% 21% (-23 to 50) Not significant

‡Abbreviations defined in Glossary; RRI, RRR, NNH, NNT, and CI calculated from data in article.


Commentary

The tendency to develop colorectal cancer is largely acquired, although genes play a role in some people. Age-adjusted incidence rates vary 10 to 15-fold throughout the world, and people who move from low to high-incidence areas, such as North America and Europe, acquire higher rates during their lifetimes. Observational studies suggest that calcium and fiber are protective along with other factors (1), but this has been difficult to confirm because of the limitations of observational studies, especially the lack of ability to measure long-term dietary exposure.

The randomized trial by Bonithon-Kopp and colleagues ought to settle the matter. But does it? The trial has limitations, which are common even in the best preventive trials. The results are imprecise because enrollment was less than the investigators had planned. The main outcome event was recurrence of adenomas, but a different set of factors may govern their growth, evolution to cancer, and distant spread. Many participants did not cooperate with their assigned treatment, leaving room for systematic differences among compared groups despite initial randomization. Finally, 3 years of follow-up is a short time in the natural history of this cancer, which usually takes at least 10 years to develop. With this study, the benefits of calcium supplementation look more promising, whereas fiber supplementation looks less promising. But that is a matter for investigators in this difficult field to tackle. Clinicians should still advise patients to consume ≥ 5 vegetables and fruits, a multivitamin, and calcium supplements each day. This practice not only may help prevent colorectal cancer but also is advisable for many other health reasons.

Robert H. Fletcher, MD, MSc
Harvard Medical School
Boston, Massachusetts, USA


Reference

1. Tomeo CA, Colditz GA, Willett WC, et al. Harvard Report on Cancer Prevention. Volume 3: Prevention of colon cancer in the United States. Cancer Causes Control. 1999;10:167-80. [PubMed ID: 10454062]