Selenium Supplementation for Prevention of Colorectal Adenomas and Risk of Associated Type 2 Diabetes

Abstract

Background: Selenium supplementation may help to prevent colorectal cancer; as precursors of colorectal cancer, colorectal adenomas are a surrogate for colorectal cancer. Selenium supplementation may increase risk of type 2 diabetes (T2D).

Methods: The Selenium and Celecoxib (Sel/Cel) Trial was a randomized, placebo controlled trial of selenium 200 µg daily as selenized yeast and celecoxib 400 mg once daily, alone or together, for colorectal adenoma prevention. Men and women between age 40 and 80 years were eligible following colonoscopic removal of colorectal adenomas. The primary outcome was adenoma development. Celecoxib was suspended because of cardiovascular toxicity in other trials, but accrual continued to selenium and placebo. A total of 1621 participants were randomly assigned to selenium or placebo, of whom 1374 (84.8%) were available for analysis. All statistical tests were two-sided.

Results: In the respective placebo and selenium arms of 689 and 685 participants, adenoma detection after medians of 33.6 (range = 0.0-85.1 months) and 33.0 months (range = 0.0-82.6 months) were 42.8% and 44.1% (relative risk [RR] = 1.03, 95% confidence interval [CI] = 0.91 to 1.16, P = .68). In participants with baseline advanced adenomas, adenoma recurrence was reduced by 18% with selenium (RR = 0.82, 95% CI = 0.71 to 0.96, P = .01). In participants receiving selenium, the hazard ratio for new-onset T2D was 1.25 (95% CI = 0.74 to 2.11, P = .41), with a statistically significantly increased risk of selenium-associated T2D among older participants (RR = 2.21; 95% CI = 1.04 to 4.67, P = .03).

Conclusions: Overall, selenium did not prevent colorectal adenomas and showed only modest benefit in patients with baseline advanced adenomas. With limited benefit and similar increases in T2D to other trials, selenium is not recommended for preventing colorectal adenomas in selenium-replete individuals.

Figure 1.

Patient flow diagram – original cohort. *Not eligible per protocol includes medical conditions (n = 484), medication use (n = 178), regular high-dose aspirin/NSAID use (n = 333), clinical lab results (n = 21), supplemental selenium use (n = 76), other (n = 174). †Other includes 16 lost to follow-up or moved, one deceased, five toxicity during placebo run-in. ‡Includes some participants with no follow-up colonoscopy at the close of the trial who agreed to participate in long-term follow-up and provide colonoscopy results in the future, participants lacking insurance coverage, etc. §The colonoscopy report indicated that either a polyp was destroyed in vivo or lost during the retrieval process, or a polyp was removed but there is no histological analysis on the pathology report, and no other polyp information was available. Without histological analysis, presence of adenomatous tissue cannot be determined.

Figure 2.

Patient flow diagram – Advanced Adenomas–Only cohort. *Not eligible per protocol includes medical conditions (n = 37), medication use (n = 50), regular high-dose aspirin/NSAID use (n = 1), clinical lab results (n = 2), supplemental selenium use (n = 20), other (n = 9). †Includes some participants with no follow-up colonoscopy at the close of the trial who agreed to participate in long-term follow-up and provide colonoscopy results in the future, participants lacking insurance coverage, etc. ‡The colonoscopy report indicated that either a polyp was destroyed in vivo or lost during the retrieval process, or a polyp was removed but there is no histological analysis on the pathology report, and no other polyp information was available. Without histological analysis, presence of adenomatous tissue cannot be determined.