Fish oil supplements delivered omega-3s to the brain, but a new study found that was not enough to improve cognitive health in older adults at risk for Alzheimer’s.
Fish oil supplements have long been viewed as one of the simplest ways to support brain health, thanks to omega-3 fatty acids that are critical for building and maintaining brain cell membranes. But a new study suggests the biology may be far more complicated than simply getting more omega-3s into the brain.
Researchers at Keck Medicine of USC found that although high-dose fish oil supplements successfully increased omega-3 levels in the brain, they failed to improve memory, cognitive function, or brain structure in older adults at elevated risk for Alzheimer’s disease.
The findings, published June 18 in eBioMedicine, suggest scientists may need to better understand how the aging brain processes these nutrients rather than simply increasing their supply.
“We all wish there was a silver bullet for preventing Alzheimer’s, but our findings showed that fish oil supplements do not appear to protect brain health,” said Hussein Naji Yassine, MD, director of the USC Center for Personalized Brain Health and lead investigator of the study. “While omega-3s play an important role in forming brain cell connections needed for cognition, our results do not support fish oil supplements as a preventive measure against Alzheimer’s.”
How the study was conducted
The study included 365 adults ages 55 to 80 who rarely ate fish, a major dietary source of omega-3s, and whom the study authors considered at risk for Alzheimer’s disease. About half (47%) carried an APOE4 gene, the strongest genetic risk factor for late-onset Alzheimer’s.
Participants were randomly assigned to take either daily fish oil supplements or a placebo. The supplements contained 2,000 mg of docosahexaenoic acid (DHA), an important omega-3 involved in brain function.
The first question was whether omega-3 from the supplement could actually enter the brain.
To find out, investigators measured DHA levels in cerebrospinal fluid, the fluid surrounding the brain. After six months, DHA levels in the brain rose by an average of 17%, showing that the omega-3 had reached the intended target.
The next step was to test whether that change made a measurable difference. Participants completed memory and cognitive assessments at the start of the study and again two years later. Those who took DHA supplements performed no better than those who took a placebo. Brain scans also showed that the supplements did not prevent shrinkage of the hippocampus, a memory-related brain region often used as a marker of brain aging and Alzheimer’s risk.
Looking beyond supplements
Yassine and his team are now trying to understand why omega-3 supplements can reach the brain without producing clear benefits for brain health. Based on earlier work, they suspect omega-3s may be more effective when consumed as part of a Mediterranean-style diet, which is naturally rich in omega-3s and has been linked with lower Alzheimer’s risk, rather than taken as a standalone supplement.
“We’re focused on better understanding how the brain processes omega-3s and whether factors, such as poor health, dietary pattern, genetic risk, and age, may change the brain’s ability to effectively absorb and use omega-3s,” said Yassine. “We are working to develop medications that may help the brain better utilize these nutrients to preserve cognitive function.”
Holistic lifestyle remains the best prevention
Although the study did not test broader lifestyle habits, Yassine and his team emphasize that protecting brain health likely depends more on overall healthy living than on fish oil supplements alone.
“Staying healthy throughout life remains the most powerful tool we have for reducing Alzheimer’s risk, including regular exercise, quality sleep, and a balanced diet,” said Yassine. “Living a healthy lifestyle is the brain’s equivalent of getting regular car maintenance and high-quality oil changes. The brain is more likely to lose greater function if health issues in other parts of the body go unaddressed, in the same way that car engines stop working if regular maintenance is skipped.”
Reference: “CNS target engagement of high-dose DHA supplementation in older adults at risk for dementia: a randomised, double-blind, placebo-controlled trial” by Hussein N. Yassine, Sara Ghasem Pour, Marlene Juarez, Isabella C. Arrelanas, Nada Ali, Dante Dikeman, Ashley Sanchez, Jackson Park, Bilal Kerman, Marlon V. Duro, Isaac Asante, Stan Louie, Naoko Kono, Lina M. D’Orazio, Helena Chui, Wendy J. Mack, Michael G. Harrington, Meredith N. Braskie and Lon S. Schneider, 18 June 2026, eBioMedicine.
DOI: 10.1016/j.ebiom.2026.106316
The research was supported by the National Institutes of Health, grant numbers RF1AG076124, R01AG055770, R01AG067063, R01AG054434, R21AG056518, P30AG066530 and R01AG054434 and the Alzheimer’s Drug Discovery Foundation, grant number GC-201711–2014197.
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University of Southern California – Health Sciences
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