Americans spend more than $1 billion each year on fish oil supplements, largely due to claims that the omega-3 fatty acids they contain can support brain health. These essential nutrients help build and maintain connections between brain cells that are important for thinking and memory.
But new research from Keck Medicine of USC suggests that increasing omega-3 levels through supplements may not provide the brain benefits many people expect. The study, published in eBioMedicinefound that although omega-3s from fish oil successfully reached the brain, they did not improve measures of brain health in older adults at higher risk for Alzheimer’s disease.
Over the course of a two-year, double-blind, placebo-controlled 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 to prevent Alzheimer’s, but our findings showed that fish oil supplements do not appear to protect brain health,” said Dr. Hussein Naji Yassine, director of the USC Center for Personalized Brain Health and principal investigator of the study. “While omega-3s play an important role in forming brain cell connections necessary for cognition, our results do not support fish oil supplementation as a preventative measure against Alzheimer’s.”
Fish oil reached the brain
The study included 365 adults ages 55 to 80 who rarely consumed fish, an important dietary source of omega-3 fatty acids. The researchers considered all participants to be at high 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 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 supplements could actually reach the brain.
To answer that question, they measured DHA levels in the 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.
There is no improvement in memory or brain aging
Although DHA reached the brain, that did not translate into measurable cognitive benefits.
The researchers tested the participants’ memory and thinking abilities at the beginning of the study and again two years later. Those who took DHA supplements did no better on cognitive tests than participants who received a placebo.
The brain imaging results told a similar story. The scans showed that fish oil supplements did not slow the 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 led researchers to investigate why omega-3s can reach the brain without producing noticeable improvements in brain health.
Based on previous research, Yassine and his colleagues suspect that omega-3s may be more effective when consumed as part of an overall Mediterranean-style dietary pattern rather than as a stand-alone supplement. The Mediterranean diet is naturally rich in omega-3s and has been associated with a lower risk of Alzheimer’s disease.
“We are focused on better understanding how the brain processes omega-3s and whether factors such as poor health, dietary pattern, genetic risk and age can change the brain’s ability to absorb and effectively use omega-3s,” Yassine said. “We are working to develop drugs that can help the brain better use these nutrients to preserve cognitive function.”
A healthy life is still the most important thing
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 the risk of Alzheimer’s.
“Staying healthy throughout life remains the most powerful tool we have to reduce the risk of Alzheimer’s, including regular exercise, quality sleep and a balanced diet,” Yassine said. “Living a healthy lifestyle is the brain equivalent of receiving regular car maintenance and high-quality oil changes. The brain is more likely to lose function if health problems in other parts of the body are not addressed, just as car engines stop working if regular maintenance is skipped.”
Other USC authors who participated in the study include Lina D’Orazio, PhD, a clinical psychologist and neuropsychology specialist at Keck Medicine; Lon Schneider, PhD, professor of psychiatry and behavioral sciences at the Keck School of Medicine of USC; Michael Harrington, MD, professor of research neurology at the Keck School; and Meredith Braskie, PhD, assistant professor of neurology at the Keck School.