Effect of Supplementation With Marine ω-3 Fatty Acid on Risk of Colorectal Adenomas and Serrated Polyps in the US General Population: A Prespecified Ancillary Study of a Randomized Clinical Trial

JAMA Oncol. 2020 Jan 1;6(1):108-115. doi: 10.1001/jamaoncol.2019.4587.


Importance: Marine ω-3 fatty acid has been suggested to protect against colorectal cancer.

Objective: To assess the effect of daily marine ω-3 fatty acid supplementation on the risk of colorectal cancer precursors, including conventional adenomas and serrated polyps.

Design, setting, and participants: This study was a prespecified ancillary study of the placebo-controlled randomized clinical trial VITAL (Vitamin D and Omega-3 Trial). An intention-to-treat analysis was used to examine the effect of daily marine ω-3 supplements among 25 871 adults in the US general population (including 5106 African American persons) free of cancer and cardiovascular disease at enrollment. Randomization was from November 2011 to March 2014, and intervention ended as planned on December 31, 2017.

Interventions: Marine ω-3 fatty acid, 1 g daily (which included eicosapentaenoic acid, 460 mg, and docosahexaenoic acid, 380 mg) and vitamin D3 (2000 IU daily) supplements.

Main outcomes and measures: Risk of conventional adenomas (including tubular adenoma, tubulovillous adenoma, villous adenoma, and adenoma with high-grade dysplasia) or serrated polyps (including hyperplastic polyp, traditional serrated adenoma, and sessile serrated polyp). In a subset of participants who reported receiving a diagnosis of polyp on follow-up questionnaires, endoscopic and pathologic records were obtained to confirm the diagnosis. Odds ratios (ORs) and 95% CIs were calculated using logistic regression, after adjusting for age, sex, vitamin D treatment assignment, and use of endoscopy. Secondary analyses were performed according to polyp features and participants' characteristics.

Results: The demographic characteristics of participants at randomization were well balanced between the treatment and placebo groups; for example, 50.6% vs 50.5% were women, and 19.7% vs 19.8% were African American persons were included in each group. The mean (SD) age was 67.1 (7.1) years in the placebo group and 67.2 (7.1) in the ω-3 treatment group. During a median follow-up of 5.3 years (range, 3.8-6.1 years), 294 cases of conventional adenomas were documented in the ω-3 group and 301 in the control group (multivariable OR, 0.98; 95% CI, 0.83-1.15) (1:1 ratio between number of cases and number of participants). In addition, 174 cases of serrated polyps were documented in the ω-3 group and 167 in the control group (OR, 1.05; 95% CI, 0.84-1.29). Null associations were found for polyp subgroups according to size, location, multiplicity, or histology. In secondary analyses, marine ω-3 treatment appeared to be associated with lower risk of conventional adenomas among individuals with low plasma levels of ω-3 index at baseline (OR, 0.76; 95% CI, 0.57-1.02; P = .03 for interaction by ω-3 index). A beneficial association of supplementation was also noted in the African American population (OR, 0.59; 95% CI, 0.35-1.00) but not in other racial/ethnic groups (P = .11 for interaction).

Conclusions and relevance: Supplementation with marine ω-3 fatty acids, 1 g per day, was not associated with reduced risk of colorectal cancer precursors. A potential benefit of this supplementation for individuals with low baseline ω-3 levels or for African American persons requires further confirmation.

Trial registration: ClinicalTrials.gov identifier: NCT01169259.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma* / epidemiology
  • Adenoma* / prevention & control
  • Adult
  • Aged
  • Colonic Polyps* / epidemiology
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / epidemiology
  • Colorectal Neoplasms* / prevention & control
  • Dietary Supplements
  • Fatty Acids, Omega-3* / therapeutic use
  • Female
  • Humans


  • Fatty Acids, Omega-3

Associated data

  • ClinicalTrials.gov/NCT01169259