A large clinical trial has found that omega-3 fish oil supplements do not improve memory, cognitive function, or protect against Alzheimer's-related brain changes, despite successfully increasing omega-3 levels in the brain.

Researchers from the Keck School of Medicine of the University of Southern California followed 365 adults aged 55 to 80 who were considered at increased risk of Alzheimer's disease. Participants, all of whom consumed little fish, were randomly assigned to receive either a daily high-dose DHA (2,000 mg) supplement or a placebo over a two-year period.

The study confirmed that DHA, an omega-3 fatty acid essential for brain function, reached the brain. After six months, DHA levels in cerebrospinal fluid increased by an average of 17%, demonstrating that the supplement effectively crossed into the central nervous system.

However, this increase did not translate into measurable health benefits. Participants taking fish oil showed no improvement in memory or cognitive performance compared with the placebo group. Brain scans also revealed no reduction in hippocampal shrinkage, a hallmark of brain aging and Alzheimer's disease.

Nearly half of the participants carried the APOE4 gene, the strongest known genetic risk factor for late-onset Alzheimer's disease, yet even in this high-risk population, fish oil supplementation failed to provide significant protection.

Lead investigator Dr. Hussein Naji Yassine said the findings do not support the use of fish oil supplements as a strategy to prevent Alzheimer's disease. According to the researchers, omega-3 fatty acids may be more beneficial when obtained through an overall Mediterranean-style diet rather than in supplement form.

The team is now investigating why the brain absorbs omega-3 fatty acids without producing measurable cognitive benefits and whether factors such as age, genetics, dietary habits, or overall health influence how the brain utilizes these nutrients.

The researchers emphasize that maintaining a healthy lifestyle—including regular physical activity, quality sleep, and a balanced diet—remains one of the most effective approaches for supporting brain health and reducing the risk of Alzheimer's disease.

The findings were published in the journal eBioMedicine.