Antioxidant supplement and long-term reduction of recurrent adenomas of the large bowel. A double-blind randomized trial.
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.
Secondary Prevention and Screening, IRCCS AOU San Martino-IST, Largo R. Benzi, 10, 16132, Genoa, Italy. luigina.bonelli@istge.it
Luigina
L
Bonelli
Matteo
M
Puntoni
Beatrice
B
Gatteschi
Paolo
P
Massa
Guido
G
Missale
Francesco
F
Munizzi
Laura
L
Turbino
Vincenzo
V
Villanacci
Andrea
A
De Censi
Paolo
P
Bruzzi
D018256:Adenomatous Polyps / Q000517:prevention & control* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000517:prevention & control* / Q000601:surgery; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007420:Intestine, Large; D008297:Male; D018977:Micronutrients / Q000008:administration & dosage; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D012643:Selenium / Q000008:administration & dosage; D014815:Vitamins / Q000008:administration & dosage; D015032:Zinc / Q000008:administration & dosage
D000975:Antioxidants; D018977:Micronutrients; D014815:Vitamins; D012643:Selenium; D015032:Zinc