Gene Discovery Could Explain Why Fish Oil’s Cancer Benefits Remain Elusive
Nearly 19 million U.S. adults rely on fish oil supplements, hoping to harness the power of omega-3 fatty acids – specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) – to combat inflammation and reduce chronic disease risk. However, the link between these supplements and cancer prevention has been frustratingly inconsistent. New research identifies a key gene that may explain why.
The conflicting results from previous studies – some suggesting a benefit, others showing no effect, and even a few hinting at increased cancer risk – have prompted scientists to dig deeper. A collaborative effort between researchers at the University of Michigan and the University of Texas MD Anderson Cancer Center has pinpointed a gene, 15-lipoxygenase-1 (ALOX15), as a critical determinant in whether EPA and DHA can effectively suppress colorectal cancer. The study, published in Cellular and Molecular Gastroenterology and Hepatology, suggests that assessing a patient’s ALOX15 status could be crucial when considering omega-3 supplementation as a preventative measure.
Surprising Findings in Animal Models
Initial investigations involved comparing mice fed diets enriched with fish oil to those on standard diets. The results were unexpected: in mice exposed to chemicals that promote inflammation and accelerate tumor growth, fish oil actually increased the number of colon tumors. This counterintuitive finding underscored the complexity of the relationship between omega-3s and cancer.
The body typically converts EPA and DHA into resolvins, molecules known for their anti-inflammatory properties, which play a protective role against cancer development. This conversion is dependent on the enzyme ALOX15. However, researchers discovered that ALOX15 is frequently inactive in various types of cancer.
Further experiments revealed that mice genetically engineered to lack ALOX15 experienced a surge in colorectal tumors when given fish oil. The impact varied depending on whether the supplement contained EPA or DHA.
EPA Outperforms DHA, and Form Matters
Notably, mice consuming EPA-rich diets developed fewer tumors than those receiving DHA. Both EPA and DHA are available in different forms – free fatty acids, ethyl esters, and triglycerides – and the study explored their varying effects.
Lovaza, an FDA-approved prescription medication containing ethyl ester forms of EPA and DHA, is currently used to treat high triglyceride levels. The research team found that Lovaza, along with the ethyl ester and free fatty acid forms of EPA, significantly reduced both the number and size of tumors, but only in mice with active ALOX15. In contrast, DHA variants failed to inhibit tumor growth in mice lacking the enzyme. When ALOX15 was present, tumor growth was reduced.
“Not all fish oil supplements are the same,” stated a senior researcher involved in the study. “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.”
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 do not have active ALOX15 may not experience the same protective benefits from EPA and DHA, rendering the supplements less effective in slowing tumor growth.
A leading physician involved in the study advises patients to consult with their doctors before initiating fish oil supplementation.
Looking ahead, the research team is actively developing medications aimed at boosting ALOX15 levels within cancer cells. Their ultimate goal is to enhance the body’s ability to process EPA and DHA, potentially strengthening efforts to prevent colon cancer. This research highlights the importance of personalized approaches to cancer prevention, recognizing that a one-size-fits-all strategy may not be effective for everyone.
