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Antioxidant supplement and long-term reduction of recurrent adenomas of the large bowel. A double-blind randomized trial

  • Original Article—Alimentary Tract
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Abstract

Background

Patients who undergo polypectomy are at increased risk of adenoma recurrence. The preventive potential of vitamins (A, C and E) and selenium supplementation represent an interesting opportunity for colorectal cancer prevention.

Methods

To assess the efficacy of a combination of these micronutrients in reducing the incidence of recurrent adenomas in subjects on post-polypectomy endoscopic follow-up, a double-blind placebo-controlled randomized trial was started in Italy in 1988. A total of 411 patients were randomized to receive either an active compound (200 μg selenium, 30 mg zinc, 2 mg vitamin A, 180 mg vitamin C, 30 mg vitamin E) or a placebo daily for 5 years. Of them, 330 had follow-up colonoscopy (164 in the intervention and 166 in the placebo group).

Results

After a median follow-up of 4 years (range 1–15 years), 100 patients had recurrence: 38 in the intervention and 62 in the placebo arm. The 15-year cumulative incidence of recurrence was 48.3 % in the intervention and 64.5 % in the placebo arm (HR = 0.59; log-rank P = 0.009). A 39 % reduction of the risk of recurrence was observed in the intervention compared to the placebo group (adjusted HR = 0.61; 95 % CI 0.41–0.92): the risk reduction was similar for small tubular (adjusted HR = 0.61; 95 % CI 0.37–0.99) and advanced adenomas (adjusted HR = 0.50; 95 % CI 0.24–1.01).

Conclusions

Our study showed a statistically significant effect of antioxidant supplementation on adenoma recurrence. Further clinical trials are needed to address the role of antioxidants in subgroups of subjects at increased risk for colorectal cancer.

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Acknowledgments

The authors are grateful to Mrs. Alessandra Guelfi for data management. The study was partially supported by the Italian League Against Cancer (grant Y. 2006) and by the Compagnia di San Paolo (grant no. 2007.0267) to Luigina Bonelli. Pharma Nord provided both the multiagent antioxidant selenium-based compound (Bio-Selenium) and the placebo.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Secondary Prevention and Screening, IRCCS AOU San Martino-IST, Largo R. Benzi, 10, 16132, Genoa, Italy

    Luigina Bonelli

  2. Endoscopy Unit, IRCCS AOU San Martino-IST, Genoa, Italy

    Francesco Munizzi

  3. Clinical Epidemiology Unit, IRCCS AOU San Martino-IST, Genoa, Italy

    Paolo Bruzzi

  4. Office of the Scientific Director, Ospedali Galliera, Genoa, Italy

    Matteo Puntoni

  5. Gastroenterology Unit, Ospedali Galliera, Genoa, Italy

    Paolo Massa

  6. Pathology Unit, Ospedali Galliera, Genoa, Italy

    Laura Turbino

  7. Medical Oncology Unit, Ospedali Galliera, Genoa, Italy

    Andrea De Censi

  8. Unit of Surgical Endoscopy, University of Brescia, Brescia, Italy

    Guido Missale

  9. Pathology Unit, Spedali Civili, Brescia, Italy

    Vincenzo Villanacci

  10. AOU San Martino-IST (Unit of Pathology), Genoa, Italy

    Beatrice Gatteschi

Authors
  1. Luigina Bonelli
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  2. Matteo Puntoni
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  3. Beatrice Gatteschi
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  4. Paolo Massa
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  5. Guido Missale
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  6. Francesco Munizzi
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  7. Laura Turbino
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  8. Vincenzo Villanacci
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  9. Andrea De Censi
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  10. Paolo Bruzzi
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Corresponding author

Correspondence to Luigina Bonelli.

Additional information

B. Gatteschi: retired.

ClinicalTrials.gov Identifier: NCT01437826.

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Bonelli, L., Puntoni, M., Gatteschi, B. et al. Antioxidant supplement and long-term reduction of recurrent adenomas of the large bowel. A double-blind randomized trial. J Gastroenterol 48, 698–705 (2013). https://doi.org/10.1007/s00535-012-0691-z

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  • DOI: https://doi.org/10.1007/s00535-012-0691-z

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