But new research from Keck Medicine of USC suggests that boosting omega-3 levels through supplements may not provide the brain benefits many people expect. The study, published in eBioMedicine, found that although omega-3s from fish oil successfully reached the brain, they did not improve measures of brain health in older adults at increased risk of Alzheimer's disease.

Over the course of a two-year, placebo-controlled, double-blinded clinical trial, researchers found that high-dose omega-3 supplements failed to improve memory, cognitive performance, or brain cell loss in regions associated with 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," 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."

Fish Oil Reached the Brain

The study included 365 adults between the ages of 55 and 80 who rarely consumed fish, a major dietary source of omega-3 fatty acids. Researchers considered all participants to be at elevated risk for Alzheimer's disease. Nearly half (47%) 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 or a placebo. Each supplement contained 2,000 mg of docosahexaenoic acid (DHA), an omega-3 fatty acid that plays an important role in brain function.

One of the researchers' first goals was to determine whether DHA from the supplements could actually make its way into the brain.

To answer that question, they measured DHA levels in cerebrospinal fluid, which surrounds the brain and spinal cord. After six months, DHA levels had increased by an average of 17%, confirming that the nutrient had successfully reached its intended destination.

No Improvement in Memory or Brain Aging

Although DHA reached the brain, that did not translate into measurable cognitive benefits.

Researchers assessed participants' memory and thinking abilities at the start of the study and again two years later. Those who took DHA supplements performed no better on cognitive tests than participants who received a placebo.

Brain imaging results told a similar story. The scans showed that fish oil supplements did not slow shrinkage of the hippocampus, a brain region critical for memory that is commonly used as a marker of brain aging and Alzheimer's risk.

Why Didn't Omega-3s Help?

The findings have prompted researchers to investigate why omega-3s can reach the brain without producing noticeable improvements in brain health.

Based on earlier research, Yassine and his colleagues suspect that omega-3s may be more effective when consumed as part of an overall Mediterranean-style eating pattern rather than as a standalone supplement. The Mediterranean diet is naturally rich in omega-3s and has been associated with a lower risk of Alzheimer's disease.

"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."

Healthy Living Still Matters Most

Although lifestyle factors were not directly examined in this study, the researchers emphasize that maintaining overall health remains one of the most effective ways to support brain function and reduce Alzheimer's risk.

"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 on 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.