Nearly 19 million adults in the United States regularly take fish oil supplements, drawn by the promise of reduced inflammation and a lower risk of chronic diseases. However, emerging research suggests that the benefits of these supplements, rich in omega-3 fatty acids like eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), aren’t universal. A growing body of evidence indicates that the effectiveness of fish oil hinges on an individual’s genetic makeup, specifically the presence of a little-known enzyme called ALOX15.
For years, clinical trials investigating the link between omega-3 supplementation and cancer prevention have yielded conflicting results. Some studies have pointed to a potential reduction in cancer risk, while others have shown no benefit, and a concerning few have even suggested a possible increase in cancer cases. Researchers at the University of Michigan and the University of Texas MD Anderson Cancer Center sought to resolve this discrepancy, focusing on colorectal cancer.
The Role of ALOX15 in Omega-3 Metabolism
Their study, published in Cellular and Molecular Gastroenterology and Hepatology, identified 15-lipoxygenase-1 (ALOX15) as a critical factor determining whether EPA and DHA can effectively suppress colorectal cancer. The enzyme acts as a key catalyst in converting EPA and DHA into resolvins – molecules that actively reduce chronic inflammation, a known driver of cancer development. Without sufficient ALOX15 activity, this conversion process is impaired, diminishing the potential anti-cancer effects of omega-3s.
The findings suggest a potential future where genetic testing for ALOX15 activity could become a standard part of assessing the suitability of omega-3 supplementation as a preventative measure, particularly for individuals with a history of colon polyps or increased cancer risk. “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,” explained Imad Shureiqi, professor of internal medicine at the University of Michigan and a member of Rogel Cancer Center.
Surprising Findings from Mouse Studies
To investigate the impact of fish oil on tumor development, researchers conducted experiments on mice. Surprisingly, they found that a fish oil-enriched diet actually increased the number of colon tumors in mice exposed to chemicals designed to induce inflammation and accelerate tumor growth. This counterintuitive result underscored the importance of ALOX15.
Further investigation revealed that the impact of fish oil varied significantly depending on the specific omega-3 fatty acid used. Mice fed diets rich in EPA developed fewer tumors compared to those given DHA. This difference highlights the distinct metabolic pathways and effects of these two common omega-3s.
EPA, DHA, and Different Supplement Formulations
The study also examined the effects of different formulations of EPA and DHA, including free fatty acids, ethyl esters, and triglycerides. Lovaza, an FDA-approved prescription medication containing ethyl ester forms of EPA and DHA used to treat high triglyceride levels, was included in the analysis.
The results showed that Lovaza, along with the ethyl ester and free fatty acid forms of EPA, reduced both the number and size of tumors, but only in mice with active ALOX15. DHA variants, however, did not demonstrate the same tumor-suppressing effect in mice lacking the enzyme. When ALOX15 was present, DHA did contribute to tumor growth reduction.
This distinction is crucial, as it suggests that the form of omega-3 consumed, and the individual’s ability to metabolize it, are both critical determinants of efficacy. “Not all fish oil supplements are the same,” Shureiqi emphasized.
Implications for Patients and Future Research
While the majority of the data originates from animal studies, the findings raise important questions for human health. The research suggests that individuals with colon polyps who lack active ALOX15 may not experience the same protective benefits from EPA and DHA supplementation, rendering the supplements less effective in slowing tumor growth.
Shureiqi advises patients to consult with their physicians before initiating fish oil supplementation. This is particularly important for those with a personal or family history of colorectal cancer, or those currently undergoing treatment for the disease.
Looking ahead, the research team is focused on developing medications designed to boost ALOX15 levels within cancer cells. The goal is to enhance the body’s natural ability to process EPA and DHA, potentially strengthening preventative efforts against colon cancer. This approach represents a shift towards personalized medicine, tailoring preventative strategies to an individual’s genetic profile and metabolic capabilities. The findings underscore the complexity of nutritional supplementation and the need for a more nuanced understanding of how these compounds interact with our individual biology.
