Fish oil supplements may not work for certain cancer patients

About 19 million American adults consume dietary fish oil supplements.

These supplements, which primarily consist of the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid, are widely used as a remedy for chronic diseases.

However, the effects of EPA and DHA supplementation on cancer risk have been inconsistent.

In a study, a team of researchers from the University of Michigan and University of Texas MD Anderson Cancer Center have shown that the gene 15-lipoxygenase-1, or ALOX15, is essential for helping EPA and DHA suppress colorectal cancer.

The results, published in Cellular and Molecular Gastroenterology and Hepatology, emphasize the need to screen for the presence of ALOX15 in cancer patients when developing prevention strategies using EPA and DHA supplements.

Large clinical studies focusing on the association between fish oil, EPA, DHA and cancer have largely been inconclusive.

While some have shown that these supplements can reduce cancer risk, others have shown no benefit or even an increase in cancer incidence.

In the current study, researchers first compared the response of mice given a diet supplemented with fish oil to a control diet.

To their surprise, fish oil increased the number of colon tumors in mice exposed to chemicals that cause inflammation and accelerated colon tumor formation.

When DHA and EPA are consumed, they are broken down into molecules called resolvins that prevent chronic inflammation, a key feature in cancer formation.

This metabolism of DHA and EPA depends on the enzyme ALOX15, which is usually turned off in various cancers.

The team tested whether mice lacking ALOX15 responded differently to fish oil supplements compared to control mice.

They found that the loss of ALOX15 increased colorectal tumors when the mice were fed fish oil, although the degree differed based on the type of omega-3 acid.

There were fewer tumors in mice that were fed EPA diets compared to DHA.

The commonly used forms of EPA and DHA include free fatty acids, ethyl esters and triglycerides.

Lovaza, which contains the ethyl ester forms of EPA and DHA, is approved by the Food and Drug Administration to treat high levels of triglycerides in the blood.

Overall, Lovaza and the ethyl ester and free forms of EPA reduced the tumor numbers and volumes, especially when the mice contained ALOX15.

On the other hand, the different variants of DHA were unable to inhibit tumor development in mice lacking ALOX15. The presence of ALOX15, however, reduced tumor growth.

“Not all fish oil supplements are the same,” said Imad Shureiqi, professor of internal medicine at the University of Michigan and a member of Rogel Cancer Center.

“It is also important to ask whether the person who is taking the supplement has the required enzymes to metabolize these products to prevent chronic inflammation and subsequently cancer development.”

Although the reported results were from studies mostly done on animals, the findings suggest that having colon polyps without ALOX15 will make EPA and DHA less effective in stopping tumor growth.

Shureiqi recommends that people talk to their physicians before they take fish oil supplements.

The team is now working on developing drugs that can help increase ALOX15 expression in cancer cells.

They hope that by doing so, these new drugs will aid the supplementation of EPA and DHA for preventing colon cancer development.

Additional authors: Xiangsheng Zuo, Yoshiyuki Kiyasu, Yi Liu, Yasunori Deguchi, Fuyao Liu, Micheline Moussalli, Lin Tan, Bo Wei, Daoyan Wei and Peiying Yan.

Funding/disclosures: This work was supported by National Cancer Institute grants: R01CA137213, R01CA195686, R01CA206539 R01CA266223, R01CA236905 and R03CA235106; an Rogel Cancer Center Innovation grant 2022 and Cancer Prevention and Research Institute of Texas grant RP150195.

Paper cited: "Colorectal ALOX15 as a host factor determining the effects of EPA and DHA on colorectal tumorigenesis in mice,” Cellular and Molecular Gastroenterology and Hepatology. DOI: 10.1016/j.jcmgh.2025.101607 

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