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docosahexaenoic acid (DHA), Omega-3 fatty acids, found abundantly in oily fish such as mackerel and sardines, are thought to improve cognitive function by supporting connections between brain cells. However, it has not been conclusively proven that DHA taken as a supplement actually reaches the brain or provides measurable benefits against disease. Dementia.
Against this backdrop, a research team at the University of Southern California School of Medicine published the results of a large, two-year clinical trial involving older people at increased risk of cancer. Alzheimer’s disease. The study found that although high doses of DHA supplements did reach the brain, they did not improve memory or cognitive function, nor did they slow brain atrophy.
“Everyone is hoping for a magic solution to prevent Alzheimer’s disease, but we can’t say that fish oil supplements protect brain health.” He said Hussein Naji Yassin, director of the Center for Personalized Brain Health at the University of Southern California. “While omega-3 fatty acids play an important role in forming brain cell connections needed for cognition, our results do not support fish oil supplements as a preventative measure against Alzheimer’s disease.”
DHA reached the brain, but…
Yassin and colleagues conducted a randomized, double-blind, placebo-controlled trial including 365 men and women between the ages of 55 and 80 who rarely ate fish. Nearly half of the participants (47%) carried the APOE ε4 allele, the strongest genetic risk factor for late-onset Alzheimer’s disease. All participants consumed less than 200 mg of DHA per day through their diet.
Participants were randomly assigned to one of two groups. One group received a daily supplement containing 2,000 mg of DHA, while the other group received a placebo for 24 months. The placebo is made from a mixture of corn oil and soybean oil and is indistinguishable from a DHA supplement in appearance, taste, and smell. Neither the participants nor the researchers knew what type of treatment each person received.
The researchers first wanted to determine whether DHA actually reached the brain. Measurements of DHA levels in the cerebrospinal fluid, which surrounds the brain and spinal cord, showed that concentrations increased by 17 percent after six months in the DHA group. There was no difference between APOE ε4 allele carriers and non-carriers, providing direct evidence that high-dose DHA supplementation reaches the brains of cognitively healthy older adults regardless of APOE ε4 status.
However, the results were very different when it came to cognitive function and brain structure. After 24 months, participants completed the Repeated Neuropsychological Status Battery, a standardized test of memory and cognitive performance. No significant differences were found between the DHA and placebo groups. Likewise, there were no significant differences in changes in hippocampal volume, a brain region important for memory and an early biomarker of Alzheimer’s disease.
Why didn’t it work?
Researchers suggest several possible explanations for why DHA reaches the brain but fails to produce measurable clinical benefits. One possibility involves an enzyme that disrupts DHA metabolism in the brain. When an enzyme known as calcium-dependent phospholipase A2 (cPLA2) is activated, it may break down DHA before it can be incorporated into synaptic membranes, the structures where DHA is thought to play its most important role in supporting cognitive function.
Another possible explanation is that many participants had cardiovascular risk factors such as obesity, high blood pressure, and physical inactivity. The chronic inflammation associated with these conditions may have blunted the effects of supplements, making it difficult for a single nutrient to produce measurable benefits.
The researchers also noted that the participants were relatively young, with an average age of 66, and experienced only minimal cognitive decline over the course of the two-year study. As a result, there may have been too little reduction during the trial to detect any protective effect from DHA supplementation.
