Journal of Gastroenterology

, Volume 48, Issue 6, pp 698–705 | Cite as

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

  • Luigina BonelliEmail author
  • Matteo Puntoni
  • Beatrice Gatteschi
  • Paolo Massa
  • Guido Missale
  • Francesco Munizzi
  • Laura Turbino
  • Vincenzo Villanacci
  • Andrea De Censi
  • Paolo Bruzzi
Original Article—Alimentary Tract



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.


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).


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).


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.


Large bowel Recurrent adenoma Antioxidants 



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.

Supplementary material

535_2012_691_MOESM1_ESM.pdf (38 kb)
Supplementary material 1 (PDF 37 kb)


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Copyright information

© Springer Japan 2012

Authors and Affiliations

  • Luigina Bonelli
    • 1
    Email author
  • Matteo Puntoni
    • 4
  • Beatrice Gatteschi
    • 10
  • Paolo Massa
    • 5
  • Guido Missale
    • 8
  • Francesco Munizzi
    • 2
  • Laura Turbino
    • 6
  • Vincenzo Villanacci
    • 9
  • Andrea De Censi
    • 7
  • Paolo Bruzzi
    • 3
  1. 1.Secondary Prevention and ScreeningIRCCS AOU San Martino-ISTGenoaItaly
  2. 2.Endoscopy UnitIRCCS AOU San Martino-ISTGenoaItaly
  3. 3.Clinical Epidemiology UnitIRCCS AOU San Martino-ISTGenoaItaly
  4. 4.Office of the Scientific DirectorOspedali GallieraGenoaItaly
  5. 5.Gastroenterology UnitOspedali GallieraGenoaItaly
  6. 6.Pathology UnitOspedali GallieraGenoaItaly
  7. 7.Medical Oncology UnitOspedali GallieraGenoaItaly
  8. 8.Unit of Surgical EndoscopyUniversity of BresciaBresciaItaly
  9. 9.Pathology UnitSpedali CiviliBresciaItaly
  10. 10. AOU San Martino-IST (Unit of Pathology)GenoaItaly

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