November 26, 2019
2 min read

Omega-3 supplementation fails to reduce risk for colorectal cancer precursors

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Omega-3 supplementation of 1 g per day did not appear to reduce the risk for colorectal cancer precursors among the average-risk U.S. population, according to results of an ancillary study of the randomized VITAL trial published in JAMA Oncology.

However, daily supplementation might benefit African Americans and those with low plasma levels of omega-3, according to researchers.

“Although epidemiologic data remain inconclusive, several prospective studies have indicated that a putative chemopreventive benefit of marine [omega]-3 fatty acids may act in the early stage of colorectal cancer development,” Mingyang Song, MD, ScD, assistant professor of clinical epidemiology and nutrition at Harvard University, and colleagues wrote. “Some members of our group recently reported the primary findings of a large-scale prevention trial that showed no reduction in the incidence of major cardiovascular events or cancer for [omega]-3 supplement administration, although the number of cases was too small for a well-powered analysis on colorectal cancer risk. Therefore ... we assessed the effect of [omega]-3 supplement administration on the risk [for] colorectal adenomas and serrated polyps.”

The prespecified ancillary study of the placebo-controlled VITAL trial included 25,871 adults randomly assigned to active omega-3 fatty acid (n = 12,933; mean age, 67.2 years; standard deviation [SD], 7.1 years) or placebo (n = 12,938; mean age, 67.1 years; SD, 7.1 years). Omega-3 supplementation consisted of 1 g per day as a fish-oil capsule that contained 460 mg eicosapentaenoic acid and 380 mg docosahexaenoic acid.

Half of patients in each group also received 2,000 IU daily vitamin D supplementation.

Participants had no history of cancer, myocardial infarction, stroke, transient ischemic attack or coronary revascularization.

The omega-3 and placebo groups appeared well-balanced demographically, with nearly equal amounts of women (50.6% vs. 50.5%) and African Americans (19.7% vs. 19.8%).

Risks for conventional adenomas or serrated polyps served as the primary endpoint. Researchers used logistic regression to calculate ORs after adjusting for age, sex, vitamin D assignment and endoscopy use.

Median follow-up was 5.3 years (range, 3.8-6.1).

Results showed 294 cases of conventional adenomas among those who received omega-3 fatty acid supplementation and 301 cases of conventional adenomas among those who received placebo (multivariate OR = 0.98; 95% CI, 0.83-1.15). Additionally, researchers observed 174 cases of serrated polyps in the omega-3 group and 167 cases in the placebo group (OR, 1.05; 95% CI, 0.84-1.29).

Researchers found null associations for polyp subgroups according to size, location, multiplicity or histology.


Secondary analyses showed that marine omega-3 supplementation appeared to be associated with lower risk for conventional adenomas among individuals with low plasma levels of omega-3 index at baseline (OR = 0.76; 95% CI, 0.57-1.02). Supplementation also appeared associated with lower risk for adenomas among African Americans (OR = 0.59; 95% CI, 0.35-1), although this benefit did not extend to other racial or ethnic groups.

Researchers observed no other interaction among subgroups defined by other demographic or colorectal cancer risk factors, endoscopy history, baseline fish intake or vitamin D assignment.

Protocol did not mandate regular screening endoscopy, which researchers acknowledged may have resulted in undiagnosed polyps. Researchers also noted that due to resource constraints, they could review medical records of only a subset of participants with reported polyps.

“Omega-3 supplementation of 1 g per day was not associated with risk [for] a colorectal premalignant lesion,” Song and colleagues wrote. “A potential benefit of omega-3 supplementation among African American persons or individuals with low baseline omega-3 status requires further investigation.” – by John DeRosier

Disclosures: Song reports research funding from American Cancer Society. Please see the study for all other authors’ relevant financial disclosures.