Daily supplementation of 1 g marine ω-3 fatty acid did not reduce risk for conventional adenomas or serrated polyps, according to a study published by JAMA Oncology.

Although epidemiologic data remain unclear, several prospective studies have indicated that a putative chemopreventive benefit of marine ω-3 fatty acids may act in the early stage of colorectal cancer (CRC) development. In this ancillary study of the placebo-controlled, randomized, clinical vitamin D and omega-3 trial (VITAL), adults in the US general population without cancer or cardiovascular disease (N=25,871) were randomized to receive either 1 g marine ω-3 (n=12,933) or placebo (n=12,938) daily, for a median treatment period of 5.3 years. This study followed the CONSORT reporting guideline for randomized clinical trials. Participants were required to forgo the use of fish-oil supplements, to limit use of vitamin D from all supplemental sources, including multivitamins to 800 IU per day, and to complete a 3-month placebo run-in phase. Participants completed questionnaires and indicated whether they had received a diagnosis of any colorectal polyp in the prior 4 years; researchers acquired medical records only for patients who confirmed the diagnosis. Low-and high-risk subgroups were classified on the basis of the size and histologic features of polyps.

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The researchers collected medical records from 35.0% of participants who reported diagnoses of colorectal polyps by the end of the study period (n=999). Diagnosis of conventional adenomas was confirmed in the patients receiving marine ω-3 fatty acids (n=294) and in the placebo group (n=301). Serrated polyp diagnoses were confirmed in patients in the ω-3 group (n=174) and in the placebo group (n=167). Marine ω-3 fatty acid treatment was not associated with risk for either conventional adenomas (multivariable odds ratio 1.05; 95% CI, 0.83-1.15) or serrated polyps (odds ratio 1.05; 95% CI, 0.84-1.29). Null results were found in sensitivity analyses when excluding participants with colorectal polyps that occurred within the first 2 years after the beginning of the trial.

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This study was limited by the potential for undiagnosed polyps because the protocol did not mandate regular screening endoscopy. Medical record reviews were possible for only a subset of participants with reported polyps whose physicians recommended surveillance colonoscopy within 5 years. Researchers were also unable to assess a dose-response relationship because only single-dose levels of marine ω-3 fatty acid were used in the trial.

Overall, the researchers discovered thatω-3 supplementation of 1 g per day was not associated with risk of a colorectal premalignant lesion.  However, the findings did not rule out a potential benefit of marine ω-3 fatty acid either at higher doses or in high-risk populations, as reported in previous studies of patients with familial adenomatous polyposis14 or with established CRC.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Song M, Lee IM, Manson JE, et al. 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 [published online November 21, 2019]. JAMA Oncol. doi: 10.1001/jamaoncol.2019.4587