Loss of ALOX15, which frequently occurs in colorectal tumors, reduces the cancer-preventive benefits of fish oil.
An estimated 19 million adults in the United States regularly take fish oil supplements in hopes of improving their health. These popular supplements are rich in omega-3 fatty acids, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which have long been promoted for their potential to reduce inflammation and protect against chronic diseases.
However, the relationship between omega-3 intake and cancer prevention has been far from clear.
In a recent study, scientists from the University of Michigan and the University of Texas MD Anderson Cancer Center discovered that a specific gene, known as 15-lipoxygenase-1 (ALOX15), plays a crucial role in enabling EPA and DHA to help prevent colorectal cancer.
The findings, published in Cellular and Molecular Gastroenterology and Hepatology, suggest that identifying whether cancer patients have the ALOX15 gene could be important when designing preventive strategies that involve EPA and DHA supplements.
Despite years of investigation, large-scale clinical trials examining links between fish oil, omega-3 fatty acids, and cancer have yielded uncertain outcomes. Some studies report that these supplements may help lower cancer risk, while others find little benefit—or even a potential increase in cancer incidence.
Surprising Results in Animal Models
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.
Different Forms, Different Effects
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.
Reference: “Colorectal 15-Lipoxygenase-1 as a Host Factor Determining the Effects of Eicosapentaenoic Acid and Docosahexaenoic Acid on Colorectal Tumorigenesis in Mice” by Xiangsheng Zuo, Yoshiyuki Kiyasu, Yi Liu, Yasunori Deguchi, Fuyao Liu, Micheline Moussalli, Lin Tan, Bo Wei, Daoyan Wei, Peiying Yang and Imad Shureiqi, 14 August 2025, Cellular and Molecular Gastroenterology and Hepatology.
DOI: 10.1016/j.jcmgh.2025.101607
Funding: National Cancer Institute, Rogel Cancer Center, Cancer Prevention and Research Institute of Texas
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2 Comments
Every meta-analysis I’ve come across concluded that omega 3 supplements are ineffective at everything assessed including heart disease, depression, arthritis, cognition, and dementia. They’re a complete waste of money.
I stopped buying them. I eat fish 3 times a week instead.