Growth and recurrence of colorectal polyps: a double-blind 3-year intervention with calcium and antioxidants

Digestion. 1998;59(2):148-56. doi: 10.1159/000007480.


Background: Dietary calcium and antioxidants have been suggested as protective agents against colorectal cancer. This has been supported by animal experimental studies, case control and cohort studies.

Materials and methods: In a prospective intervention study of colorectal adenomas, and intermediary stage in colorectal carcinogenesis, 116 polyp-bearing patients received a placebo-controlled daily mixture of beta-carotene 15 mg, vitamin C 150 mg, vitamin E 75 mg, selenium 101 microg, and calcium (1.6 g daily) as carbonate for a period of 3 years with annual colonoscopic follow-up to test if the mixture was able to reduce polyp growth or recurrence. All polyps of < 10 mm at enrollment or follow-up were left unresected until the end of the study.

Results: 87-91% of the patients attended the annual endoscopic follow-up investigations, and 19% of the patients dropped out of the medical intervention. The rest consumed 85% of the total amount of tablets over the 3 years. The fecal calcium concentration was 2.3-2.7 times higher in patients taking active medication compared to the placebo group. Diet registration showed that, when adding the intake of antioxidants and calcium from diet and intervention, there was a significant difference between the intake of these substances in the active and the placebo group. No difference was detected in the growth of adenomas between the active and the placebo group from year to year and for the total study period. Moreover, there was no effect on polyps of < 5 or 5-9 mm, or on polyps in the different colonic segments analyzed separately. A reduced growth of adenomas was found in patients <60 years of age taking active medication (n = 8) compared to those taking placebo (n = 6; mean difference 2.3 mm; 95% CI 0.26-4.36). There was a significantly lower number of patients free of new adenomas in the placebo group compared to those taking active medication as tested by logistic regression and Kaplan-Meier analysis (log-rank test p value 0.035). Subgroup analysis showed that only the group of patients with no family history of colorectal cancer, those with only one adenoma at inclusion, and those <65 years benefitted from the intervention medication.

Conclusion: The study did not find an overall effect on polyp growth. Our data, however, may support a protective role of calcium and antioxidants on new adenoma formation.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / drug therapy
  • Aged
  • Antioxidants / administration & dosage
  • Antioxidants / adverse effects
  • Antioxidants / therapeutic use
  • Ascorbic Acid / administration & dosage
  • Calcium, Dietary / administration & dosage
  • Calcium, Dietary / adverse effects
  • Calcium, Dietary / therapeutic use
  • Cell Division / drug effects
  • Colonic Polyps / drug therapy*
  • Colonic Polyps / pathology
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Constipation / chemically induced
  • Diarrhea / chemically induced
  • Diet
  • Double-Blind Method
  • Dyspepsia / chemically induced
  • Energy Intake / drug effects
  • Female
  • Follow-Up Studies
  • Gastrointestinal Diseases / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Patient Compliance
  • Patient Dropouts
  • Prospective Studies
  • Time Factors
  • Vitamin A / administration & dosage


  • Antioxidants
  • Calcium, Dietary
  • Vitamin A
  • Ascorbic Acid