Americans spend more than $1 billion annually on fish oil supplements, partly due to claims about their cognitive benefits. A new Keck Medicine of USC study published in eBioMedicine on June 18 suggests that increasing omega-3 levels through supplements has little effect on brain health, despite evidence that these nutrients reach the brain.
The two-year, placebo-controlled, double-blinded study involved 365 adults aged 55 to 80 who rarely ate fish and were considered at risk for Alzheimer's disease. Nearly half of the participants carried an APOE4 gene, which is recognized as a strong genetic risk factor for late-onset Alzheimer's. Participants were randomly assigned to receive either daily fish oil supplements containing 2,000 mg of docosahexaenoic acid (DHA) or a placebo.
Researchers first sought to determine if the omega-3 from the supplement could reach the brain by measuring DHA levels in cerebrospinal fluid. After six months, they found an average increase of 17% in DHA levels among those taking the supplement. Despite this increase, memory and cognitive tests conducted at both the start and end of the two-year period showed no improvement among those taking DHA compared to those given a placebo. Brain scans also indicated that supplementation did not prevent shrinkage of the hippocampus—a region important for memory and often used as a marker for brain aging and Alzheimer's risk.
Hussein Yassine and his team are now working to understand why omega-3s can reach the brain but do not affect its health when taken as supplements. They believe that omega-3s may be more effective when consumed as part of a Mediterranean-style diet rather than as standalone supplements.
"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." While this was outside their study's scope, researchers emphasized healthy living overall—rather than relying solely on fish oil supplements—as key for protecting brain health.
"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.
