LOS ANGELES — A clinical trial conducted by USC Keck Medicine found that high-dose docosahexaenoic acid (DHA) supplementation increased brain DHA levels but did not improve brain volume or cognitive performance in older adults at risk for dementia. The findings were published in eBioMedicine on June 25, 2026, in an article titled "CNS target engagement of high-dose DHA supplementation in older adults at risk for dementia: a randomised, double-blind, placebo-controlled trial."

The randomized, double-blind, placebo-controlled study enrolled 365 adults, aged 55 to 80, who did not have dementia. Participants had low dietary DHA intake and at least one risk factor for dementia at the start of the study. The mean age of participants was 66, with 58% being female and 39% Hispanic. Approximately 47% of the participants were APOE ε4 carriers; the APOE ε4 gene variant is a genetic risk factor for Alzheimer's disease.

Participants were divided into two groups, receiving either 2 grams per day of DHA or a placebo for 24 months. DHA supplementation resulted in an increase in the cerebrospinal fluid DHA to arachidonic acid ratio at six months compared with the placebo group. Cerebrospinal fluid DHA levels rose by 17% in the supplementation group. The red cell omega-3 index also increased from 4.9% to 11% in the supplementation group, and these increases were independent of APOE ε4 status.

Despite the increases in brain DHA levels, the trial showed no difference in brain volumes between the intervention and control groups over the study period. There was also no difference in cognitive performance between the two groups. APOE ε4 non-carriers displayed a mean cognitive score improvement of 3.8, while carriers showed a mean improvement of 1.6, regardless of their treatment group. Both the intervention and control groups experienced comparable adverse events. The study had a dropout rate of 38%.

Docosahexaenoic acid (DHA) is a fatty acid that is part of the nerve cell membrane. Hussein Naji Yassine, MD, director of the USC Center for Personalized Brain Health and the study's lead investigator, stated, "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." He added, "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."