Fish oil supplements are widely used for their omega-3 fats, but new research suggests they could have very different effects on colon tumor growth depending on whether a key enzyme—ALOX15—is active. Researchers say the findings may help explain why studies of omega-3 supplements and cancer risk have produced mixed results.
Nearly 19 million adults in the United States take fish oil supplements, which are rich in omega-3 fatty acids—mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Many people use these products in hopes of lowering inflammation and reducing the risk of chronic disease, but evidence related to cancer has been inconsistent.
What the study found
In the new study, researchers from the University of Michigan and the University of Texas MD Anderson Cancer Center investigated why omega-3 results in cancer research can look so different from one study to another. The work, published in Cellular and Molecular Gastroenterology and Hepatology, points to a gene called 15-lipoxygenase-1—also known as ALOX15—as a major factor in whether EPA and DHA help suppress colorectal cancer.
To test fish oil’s effects on tumor development, the researchers compared mice fed a fish oil–enriched diet with mice fed a standard diet. In mice exposed to chemicals that cause inflammation and accelerate colon tumor formation, fish oil unexpectedly increased the number of colon tumors.
Why the ALOX15 enzyme matters
The study links the different outcomes to how the body processes EPA and DHA after they are consumed. According to the report, EPA and DHA can be converted into molecules called resolvins, which help prevent chronic inflammation—an important feature in cancer development—and this metabolism depends on the enzyme ALOX15.
A key complication is that ALOX15 is often “switched off” or “turned off” in various types of cancer, which could limit the body’s ability to generate those potentially helpful byproducts from omega-3 fats. When researchers tested mice that lacked ALOX15, they found that loss of the enzyme was associated with increased colorectal tumors when the animals were fed fish oil, though the effect varied depending on the omega-3 fatty acid involved.
EPA vs. DHA and supplement forms
The results also differed between the two major omega-3s found in fish oil. Mice fed diets rich in EPA developed fewer tumors than mice given DHA, according to the findings.
The researchers also highlighted that EPA and DHA come in multiple supplement forms, including free fatty acids, ethyl esters, and triglycerides. The study noted that Lovaza, a prescription product containing ethyl ester forms of EPA and DHA, is approved by the U.S. Food and Drug Administration to treat high triglyceride levels in the blood. In the experiments, Lovaza as well as ethyl ester and free fatty acid forms of EPA reduced tumor number and size (or volume), especially when ALOX15 was active, while DHA variants did not stop tumor development in mice lacking ALOX15.
Imad Shureiqi, a professor of internal medicine at the University of Michigan and a member of Rogel Cancer Center, said, “Not all fish oil supplements are the same.” He added that it is important to ask whether the person taking a supplement has the enzymes needed to metabolize these products to prevent chronic inflammation and, subsequently, cancer development.
What this means for patients
Both reports emphasize that the findings mainly come from animal studies, but they raise practical questions for people considering omega-3 supplements as part of colon cancer prevention. The researchers suggest that screening or testing for the presence of ALOX15 could matter when developing prevention strategies that involve EPA and DHA supplementation. The reports also say the results imply that people with colon polyps who do not have active ALOX15 may not get the same protective effects from EPA and DHA, making the supplements less effective at slowing tumor growth.
At a broader level, other research has also pointed to genetics as a reason omega-3 supplement trials can produce different outcomes in different groups. A review in Frontiers in Nutrition describes how variation in genes such as FADS1 and FADS2 can affect how the body converts dietary omega-6 and omega-3 fats into longer-chain fatty acids that influence inflammation, and it argues that ancestry and genetic variability should be factored into future omega-3 clinical trial designs.
Shureiqi recommends that people speak with their physicians before taking fish oil supplements. The team also reported it is developing drugs intended to increase ALOX15 expression in cancer cells, with the aim of improving how the body processes EPA and DHA in colon cancer prevention efforts.
