Americans spend more than $1 billion annually on fish oil supplements, in part due to purported cognitive benefits from the omega-3 fatty acids they contain, essential nutrients that help form brain cell connections needed for cognition. 

However, a new Keck Medicine of USC study published today in eBioMedicine suggests that increasing omega-3 levels via supplements has little effect on brain health despite showing evidence that the nutrients directly reach the brain. 

The two-year, placebo-controlled, double-blinded study of older adults with an elevated risk of developing Alzheimer's showed that high doses of omega-3s did not improve memory, cognitive function or brain cell loss in areas of the brain related to Alzheimer's. 

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. 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." 

Hussein Naji Yassine, MD, director of the USC Center for Personalized Brain Health and lead investigator of the study

How the study was conducted 

Researchers recruited 365 adults, ages 55 to 80 who rarely ate fish, which is rich in omega-3s, and who study authors considered at risk for Alzheimer's. About half (47%) carried an APOE4 gene, the strongest genetic risk factor for late-onset Alzheimer's. Participants were randomly chosen to receive either daily fish oil supplements or a placebo. The supplements contained 2,000 mg of docosahexaenoic acid (DHA), a key omega-3 involved in brain function. 

Researchers were first interested to learn whether the omega-3 in the supplement was able to reach the brain. 

They measured DHA levels in cerebrospinal fluid, which surrounds the brain, and found an average 17% increase of DHA levels in patients' brains after six months, confirming the omega-3 reached its intended target. 

Next, researchers tested participants' memory and cognitive abilities at the beginning of the study and again two years later. Study participants who took DHA supplements did no better on the tests than those who took a placebo. Brain scans also showed that supplements did not prevent shrinkage of the hippocampus, a brain region important for memory that is often used as a marker of brain aging and Alzheimer's risk. 

Looking beyond supplements 

Now, Yassine and his team are focused on solving why omega-3 supplements can reach the brain but not affect brain health. Based on their previous research, they believe omega-3s may work better as a part of a Mediterranean-style diet, which is naturally rich in omega-3s and linked with lower Alzheimer's risk, than in 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 

While out of scope of the study, the researchers stress that overall healthy living - rather than relying on fish oil supplements alone -is the best way to protect 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. "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." 

Other USC authors for the study include Lina D'Orazio, PhD, a clinical psychologist and neuropsychology specialist with Keck Medicine; Lon Schneider, PhD, a professor of psychiatry and behavioral sciences at the Keck School of Medicine of USC; Michael Harrington, MD, a professor of research neurology at the Keck School; and Meredith Braskie, PhD, an assistant professor of neurology at the Keck School.