In the absence of the ALOX15 enzyme, EPA and DHA are ineffective at inhibiting colon tumor growth.
Approximately 19 million American adults take dietary fish oil supplements to support health and manage chronic conditions such as cancer. Rich in omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—these supplements have shown significant potential in suppressing colorectal cancer (1✔ ✔Trusted Source
Colorectal 15-Lipoxygenase-1 as a Host Factor Determining the Effects of Eicosapentaenoic Acid and Docosahexaenoic Acid on Colorectal Tumorigenesis in Mice
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Still, the efficiency of EPA and DHA on cancer prevention is undetermined. The specific enzyme ‘ALOX15’ (15-lipoxygenase-1) affects the metabolism of EPA and DHA, that contribute to control colon cancer.
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.
Fish Oil Supplements May Accelerate Colon Tumor Growth
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.
The Role of the ALOX15 Enzyme in Tumor Response to Fish Oil
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.
Effectiveness of Different Fish Oil Formulations
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.”
Future Research on ALOX15 Enzyme to Enhance Fish Oil’s Efficacy
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 – (https://www.cmghjournal.org/article/S2352-345X(25)00148-1/fulltext)
Source-News Wise