Journal of Gastroenterology

, Volume 48, Issue 6, pp 698–705

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


    • Secondary Prevention and ScreeningIRCCS AOU San Martino-IST
  • Matteo Puntoni
    • Office of the Scientific DirectorOspedali Galliera
  • Beatrice Gatteschi
    • AOU San Martino-IST (Unit of Pathology)
  • Paolo Massa
    • Gastroenterology UnitOspedali Galliera
  • Guido Missale
    • Unit of Surgical EndoscopyUniversity of Brescia
  • Francesco Munizzi
    • Endoscopy UnitIRCCS AOU San Martino-IST
  • Laura Turbino
    • Pathology UnitOspedali Galliera
  • Vincenzo Villanacci
    • Pathology UnitSpedali Civili
  • Andrea De Censi
    • Medical Oncology UnitOspedali Galliera
  • Paolo Bruzzi
    • Clinical Epidemiology UnitIRCCS AOU San Martino-IST
Original Article—Alimentary Tract

DOI: 10.1007/s00535-012-0691-z

Cite this article as:
Bonelli, L., Puntoni, M., Gatteschi, B. et al. J Gastroenterol (2013) 48: 698. doi:10.1007/s00535-012-0691-z



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 bowelRecurrent adenomaAntioxidants

Supplementary material

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

Copyright information

© Springer Japan 2012