Omega-3 fish oil supplements could backfire without this key enzyme

When it comes to cancer, however, the evidence has been mixed. Some large clinical trials have suggested omega-3 supplements may lower cancer risk, while others have found no benefit or even a possible increase in cancer cases.

A Key Gene in Colon Cancer Protection

Researchers from the University of Michigan and the University of Texas MD Anderson Cancer Center set out to better understand these conflicting results. Their study, published in Cellular and Molecular Gastroenterology and Hepatology, identified a gene called 15-lipoxygenase-1, or ALOX15, as a crucial factor in whether EPA and DHA can help suppress colorectal cancer.

The findings suggest that testing cancer patients for ALOX15 could be important when considering prevention strategies that involve omega-3 supplements.

Surprising Results in Mice

To explore how fish oil affects tumor development, scientists compared mice fed a fish oil enriched diet with mice given a standard diet. Unexpectedly, fish oil increased the number of colon tumors in mice exposed to chemicals that trigger inflammation and speed up tumor growth.

Normally, when EPA and DHA are consumed, the body converts them into compounds known as resolvins. These molecules help reduce chronic inflammation, which plays a major role in cancer development. This conversion process relies on the enzyme ALOX15. However, ALOX15 is often switched off in several types of cancer.

The researchers then examined what happened when mice lacking ALOX15 were given fish oil. In those animals, the absence of ALOX15 led to a rise in colorectal tumors, although the impact varied depending on which omega-3 fatty acid was used.

EPA vs DHA and Different Supplement Forms

Mice fed diets rich in EPA developed fewer tumors than those given DHA. EPA and DHA are available in several forms, including free fatty acids, ethyl esters and triglycerides.

Lovaza, a prescription medication containing the ethyl ester forms of EPA and DHA, is approved by the Food and Drug Administration to treat high triglyceride levels in the blood.

In this study, Lovaza as well as the ethyl ester and free fatty acid forms of EPA reduced both the number and size of tumors, particularly in mice that had active ALOX15. In contrast, DHA variants did not prevent tumor growth in mice lacking ALOX15. When ALOX15 was present, tumor growth was reduced.

“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.”

What This Means for Patients

Although most of the data come from animal studies, the results raise important questions. They suggest that people with colon polyps who do not have active ALOX15 may not receive the same protective benefits from EPA and DHA, making the supplements less effective at slowing tumor growth.

Shureiqi advises patients to speak with their doctors before starting fish oil supplements.

Meanwhile, the research team is developing medications designed to boost ALOX15 levels in cancer cells. Their goal is to enhance the body’s ability to process EPA and DHA, potentially strengthening efforts to prevent colon cancer.