Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

A diet low in fat and high in fiber, fruits, and vegetables did not reduce the recurrence of colorectal adenomas

PDF

ACP J Club. 2001 Jan-Feb;134:20. doi:10.7326/ACPJC-2001-134-1-020

Related Content in this Issue
• Companion Abstract and Commentary: A high-fiber cereal supplement did not prevent the recurrence of colorectal adenomas


Source Citation

Schatzkin A, Lanza E, Corle D, et al., and the Polyp Prevention Trial Study Group. Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. N Engl J Med. 2000 Apr 20;342:1149-55. [PubMed ID: 10770979] (All 2001 articles were reviewed for relevancy, and abstracts were last revised in 2007.)


Abstract

Question

Does a diet that is low in fat and high in fiber, fruits, and vegetables reduce the rate of recurrent colorectal adenomas?

Design

Randomized {allocation concealed*}†, blinded (outcome assessor),* controlled trial with 4-year follow-up.

Setting

8 clinical centers in the United States.

Patients

2079 adults ≥ 35 years of age who had had ≥ 1 histologically confirmed colorectal adenoma removed in the 6 months before the study. Exclusion criteria were history of colorectal cancer, surgical resection of adenomas, bowel resection, the polyposis syndrome, inflammatory bowel disease, > 150% of recommended weight, use of lipid-lowering drugs, or condition or dietary restrictions that would limit compliance with the protocol. Follow-up was 92%.

Intervention

1037 participants were allocated to an intervention group and were given a diet low in fat (20% of total calories), high in dietary fiber (18 g/1000 kcal), and high in fruits and vegetables (3.5 servings/1000 kcal) and nutrition and behavior-modification counseling by nutritionists. 1042 participants were allocated to a control group and were given a standard brochure on healthy eating; this group was asked to follow their usual diet.

Main outcome measure

The recurrence of colorectal adenomas between 1 and 4 years was identified by colonoscopy. Secondary outcomes were the number, size, and histologic features of the detected adenomas and colorectal cancer.

Main results

Analysis was by intention to treat. Participants in the intervention group had greater reductions in percentage of fat intake as total calories (absolute difference in change between groups, 9.7%; 95% CI 9.0% to 10.3%), greater increases in dietary fiber intake (absolute difference in change between groups, 6.9 g/1000 kcal; CI 6.4 to 7.3 g/1000 kcal), and greater increases in fruit and vegetable intake (absolute difference in change between groups, 1.13 servings/1000 kcal; CI 1.04 to 1.21 servings/ 1000 kcal) than did those in the control group. The intervention and control groups did not differ for rates of having ≥ 1 recurrent colorectal adenoma (39.7% vs 39.5%, P = 0.98), ≥ 1 adenoma with a diameter ≥ 1 cm (4.9% vs 5.6%, P = 0.57), ≥ 1 advanced adenoma (6.3% vs 7.0%, P = 0.60), or colorectal cancer (1% vs 0.4%, P = 0.19). Among those with recurrent colorectal adenomas, no difference existed for the mean number of adenomas in the intervention and control groups (1.85 vs 1.84, P = 0.93).

Conclusion

A diet that is low in fat and high in fiber, fruits, and vegetables did not reduce the rate of recurrent colorectal adenomas.

*See Glossary.

†Information provided by author.

Source of funding: National Cancer Institute.

For correspondence: Dr. A. Schatzkin, Chief, National Cancer Institute, EPS Room 7032, Bethesda, MD 20892-7232, USA. FAX 301-496-6829.


Commentary

In developed countries, colon cancer is a common disease. Observational studies have shown that dietary factors may be causally associated with the risk for colon cancer. Specifically, epidemiologic studies have shown an increased risk for colon cancer with a diet high in fat and red meat and low in fiber, fresh fruits, and vegetables. Insoluble fiber is believed to protect the colon by absorbing carcinogens (1). Therefore, a strong rationale exists to evaluate dietary interventions in persons at risk for colon cancer.

Randomized controlled trials commonly examine the prevention of colonic adenomas (adenomatous polyps). Acceptance of these lesions as a surrogate end point for developing carcinoma is based on the observation that cancer almost always arises from preexisting polyps. Persons with benign polyps, especially those that are > 1 cm in diameter or that show villous architecture, have an increased risk. Use of this outcome is efficient; fewer patients are required to detect a treatment effect than if cancer was selected for evaluation. However, this assumes that interventions that reduce polyp formation necessarily prevent cancer. Although this assumption may not inevitably be the case, the approach is sensible given the existing data. Therefore, the results of the 2 large randomized controlled trials—one by Schatzkin and colleagues and the other by Alberts and colleagues—that evaluated the effect of dietary interventions on the formation of adenomatous polyps are of great interest.

Both studies were meticulously done. Schatzkin and colleagues randomized > 2000 patients, 90% of whom underwent 2 colonoscopies over a 4-year period. Compliance with the low-fat, high-fiber, and high fruit and vegetable intake diet was excellent. Although self-reporting is a subjective measure of dietary compliance, the higher serum carotenoid level and the trend toward lower weight in the intervention group confirm that patients assigned to active treatment were compliant. No beneficial effect of therapy was observed; the lower boundary of the 95% confidence interval for the observed difference in polyp formation (0.2%) was consistent with only a potential 4% improvement over the control group. Moreover, more cases of colon cancer were observed in the intervention group.

Alberts and colleagues evaluated the efficacy of a wheat-bran fiber supplement in 1429 patients who were at risk for polyp recurrence. Again, no beneficial effect of this intervention was identifiable on polyp or cancer formation. Although patients were preselected for tolerance of the fiber supplement, more gastrointestinal symptoms occurred in the intervention group.

Collectively, these 2 studies provide strong evidence that dietary interventions are ineffective in preventing the recurrence of adenomas. Nevertheless, these results do not necessarily mean that diet does not play a role in the development of cancer. Because exposure to carcinogens occurs over years, the experimental paradigm used in these trials may not be adequate to evaluate the role of fiber as a protective factor. Unfortunately, evaluation of long-term dietary interventions by randomized controlled trials is not practical.

Of interest, pharmacologic interventions may succeed where diets fail. Nonsteroidal anti-inflammatory drugs, most notably the cyclooxygenase (COX)-2 inhibitors, have shown promising results in preventing polyp formation in patients with hereditary polyposis (2).

Although high-fiber, low-fat diets may have other benefits, this strategy will not prevent colonic polyp formation in patients who are at risk for recurrence.

Brian Feagan, MD
University of Western Ontario
London, Ontario, Canada


References

1. Kritchevsky D. Protective role of wheat bran fiber: preclinical data. Am J Med. 1999;106:28S-31S. [PubMed ID: 10089112]

2. Stockbrugger RW. Nonsteroidal anti-inflammatory drugs (NSAIDs) in the prevention of colorectal cancer. Eur J Cancer Prev. 1999;9(Suppl 1):S21-5. [PubMed ID: 10772414]

3. Jacobs ET, Lanza E, Alberts DS, et al. Fiber, sex, and colorectal adenoma: results of a pooled analysis. Am J Clin Nutr. 2006;83:343-9. [PubMed ID: 16469993]