Omega-3 Fish Oil: Could Supplements Backfire Without Key Enzyme?

For the nearly 19 million adults in the United States who take fish oil supplements, a new understanding of how the body processes omega-3 fatty acids is emerging. Research published February 13, 2026, suggests that the benefits of these supplements – often taken to reduce inflammation and lower the risk of chronic diseases – may depend on the presence of a specific enzyme, ALOX15.

The study, conducted by researchers at the University of Michigan and the University of Texas MD Anderson Cancer Center, focused on the impact of omega-3s, specifically EPA and DHA, on colorectal cancer. The findings, published in Cellular and Molecular Gastroenterology and Hepatology, reveal that these fatty acids only appear to curb the growth of colorectal cancer when ALOX15 is present. In fact, in mice lacking the enzyme, fish oil – particularly DHA – sometimes increased tumor growth.

The Role of ALOX15

ALOX15, or 15-lipoxygenase-1, acts as a crucial catalyst in the process of activating the protective effects of omega-3 fatty acids. Without this enzyme, the body struggles to utilize EPA and DHA effectively, potentially negating any cancer-fighting benefits. This discovery helps explain the mixed results seen in previous clinical trials investigating the link between omega-3 supplementation and cancer risk. Some trials have suggested a protective effect, while others have shown no benefit or even a potential increase in cancer cases.

“Fish oil’s cancer-fighting reputation may hinge on a little-known gene,” researchers stated. The study highlights the complex interplay between genetics, diet and health outcomes. It suggests that a one-size-fits-all approach to supplementation may not be effective, and that individual genetic profiles could determine who truly benefits from taking fish oil.

Implications for Supplement Use

The findings don’t necessarily mean that fish oil supplements are ineffective for everyone. Rather, they underscore the importance of understanding individual biological differences. The presence or absence of ALOX15 could be a key factor in determining whether someone will experience a positive, neutral, or even adverse effect from omega-3 supplementation.

Currently, there is no readily available test to determine an individual’s ALOX15 status. However, researchers note that loss of ALOX15 frequently occurs in colorectal tumors. This suggests that individuals with a history of colorectal cancer, or those at high risk, might be particularly susceptible to the potential downsides of fish oil supplementation if they lack sufficient ALOX15 activity.

Beyond Colorectal Cancer

While this study specifically focused on colorectal cancer, the role of ALOX15 in mediating the effects of omega-3 fatty acids may extend to other conditions as well. Inflammation is a common underlying factor in many chronic diseases, and omega-3s are often touted for their anti-inflammatory properties. If ALOX15 is indeed a critical enzyme in this process, its absence could limit the benefits of omega-3s in a wider range of health contexts.

The research team emphasizes that more studies are needed to fully elucidate the role of ALOX15 and to identify potential strategies for enhancing omega-3 metabolism in individuals who lack the enzyme. This could involve exploring alternative forms of omega-3s, or developing therapies that boost ALOX15 activity.

A Broader Perspective on Supplements

This study serves as a reminder that dietary supplements are not always a simple solution to complex health problems. The effectiveness of any supplement can be influenced by a multitude of factors, including genetics, lifestyle, and overall health status. It also highlights the importance of rigorous scientific research to understand the true benefits and risks of these products.

It’s important to note that while approximately 19 million adults in the U.S. Take fish oil supplements, the evidence supporting their widespread use for heart health has been questioned. A December 1, 2023 review from Harvard Health Publishing indicated that multiple randomized trials have shown no evidence of heart-related benefits from fish oil supplements, suggesting that obtaining omega-3s through diet – from fatty fish like salmon, tuna, and sardines – may be a more reliable approach.

As research continues to unravel the intricacies of omega-3 metabolism, a more personalized approach to supplementation may become increasingly important. For now, individuals considering taking fish oil supplements should discuss their options with a healthcare professional, taking into account their individual health history and genetic predispositions.