Americans spend more than $1 billion each year on fish oil supplements, largely because of claims that the omega-3 fatty acids they contain can support brain health and protect against cognitive decline. Omega-3s, particularly docosahexaenoic acid (DHA), are essential nutrients that help build and maintain the connections between brain cells that are critical for memory and thinking. However, a new study from researchers at the Keck School of Medicine of USC suggests that taking fish oil supplements may not provide the cognitive benefits many people hope for, particularly in reducing the risk of Alzheimer’s disease.
The study, published in the journal eBioMedicine, followed 365 adults aged 55 to 80 who rarely consumed fish and were considered at elevated risk for developing Alzheimer’s disease. Nearly half of the participants carried the APOE4 gene, the strongest known genetic risk factor for late-onset Alzheimer’s. Participants were randomly assigned to receive either a daily fish oil supplement containing 2,000 milligrams of DHA or a placebo. The trial was conducted over two years using a placebo-controlled, double-blind design, considered the gold standard for evaluating treatment effectiveness.
One of the researchers’ primary objectives was to determine whether the omega-3 fatty acids in the supplements could actually reach the brain. To answer this question, they measured DHA levels in cerebrospinal fluid, the liquid that surrounds and protects the brain and spinal cord. After six months, participants taking DHA supplements showed an average 17% increase in DHA levels within the brain, confirming that the nutrient successfully crossed into the central nervous system and reached its intended target.
Despite this encouraging biological finding, the supplements did not produce meaningful improvements in brain health. Researchers assessed participants’ memory and cognitive performance at the beginning of the study and again after two years. Those who received DHA performed no better than those taking a placebo. Brain imaging results were equally disappointing. The scans showed no evidence that supplementation slowed shrinkage of the hippocampus, a brain region essential for memory and commonly used as an indicator of brain ageing and Alzheimer’s risk.
According to lead investigator Dr. Hussein Naji Yassine, director of the USC Center for Personalized Brain Health, the findings suggest that fish oil supplements should not be viewed as a preventive strategy against Alzheimer’s disease. While omega-3 fatty acids remain important for maintaining normal brain structure and function, simply increasing their levels through supplements did not translate into measurable cognitive benefits. The researchers are now exploring why omega-3s can reach the brain without producing the expected protective effects. They suspect that factors such as age, genetics, overall health and dietary patterns may influence how effectively the brain absorbs and uses these nutrients.
The team also believes that omega-3s may be more beneficial when consumed as part of a broader Mediterranean-style dietary pattern rather than as a standalone supplement. Although the study did not examine lifestyle interventions directly, the researchers emphasize that healthy living remains the most effective approach for protecting brain health and reducing Alzheimer’s risk. Regular physical activity, adequate sleep, a balanced diet and attention to overall health continue to offer the strongest evidence-based strategies for maintaining cognitive function as people age. Rather than relying on a single supplement, experts recommend a comprehensive approach that supports both brain and body health throughout life.
More information: Hussein Naji Yassine et al, CNS target engagement of high-dose DHA supplementation in older adults at risk for dementia: a randomised, double-blind, placebo-controlled trial, EBioMedicine. DOI: 10.1016/j.ebiom.2026.106316
Journal information: EBioMedicine Provided by University of Southern California – Health Sciences
