docosahexaenoic acid (DHA), Omega-3 fatty acid, found in enormous amounts in oily fish such as mackerel and sardines, is thought to improve cognitive function by supporting connections between brain cells. However, it has never been clearly demonstrated that DHA taken as a dietary supplement actually reaches the brain or provides any material benefits in the fight against dementia.
In this context, a research team from the USC School of Medicine published the results of a enormous, two-year clinical trial involving older adults at increased risk of developing Alzheimer’s disease. The study found that while high-dose DHA supplements do reach the brain, they do not improve memory or cognitive function, nor do they tardy brain atrophy.
“Everyone is hoping for a silver bullet to prevent Alzheimer’s disease, but we can’t say that fish oil supplements protect brain health.” he said Hussein Naji Yassine, director of the Personalized Brain Health Center at USC. “Although omega-3 fatty acids play an important role in creating connections between brain cells needed for cognitive processes, our results do not support that fish oil supplements can provide a preventive measure against Alzheimer’s disease.”
DHA reached the brain, but…
Yassine and his colleagues conducted a randomized, double-blind, placebo-controlled study of 365 men and women aged 55 to 80 who rarely ate fish. Nearly half of the participants (47 percent) 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 in 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 received a placebo for 24 months. The placebo consisted of a mixture of corn oil and soybean oil and did not differ from the DHA supplement in appearance, taste and smell. Neither participants nor researchers knew what treatment each person received.
Scientists first wanted to determine whether DHA actually reached the brain. Measurements of DHA levels in the cerebrospinal fluid surrounding the brain and spinal cord showed that after six months of DHA utilize, the concentration increased by 17 percent. There was no difference between carriers and noncarriers of the APOE ε4 allele, providing direct evidence that high-dose DHA supplementation reaches the brains of cognitively hearty 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 Repeatable Neuropsychological Assessment Battery, a standardized test of memory and cognitive performance. No significant differences were found between the DHA and placebo groups. Similarly, there were no significant differences in changes in the volume of the hippocampus, a brain region crucial for memory and an early biomarker of Alzheimer’s disease.
Why didn’t it work?
Scientists suggest several possible explanations for why DHA reached the brain but provided no material clinical benefit. One possibility involves an enzyme that interferes with DHA metabolism in the brain. When an enzyme called calcium-dependent phospholipase A2 (cPLA2) is activated, it can break down DHA before it can be incorporated into synaptic membranes – the structures where DHA is thought to play its most significant role in supporting cognitive function.
Another possible explanation is that many participants had cardiovascular risk factors such as obesity, hypertension and physical inactivity. The chronic inflammation associated with these conditions may have weakened the effect of supplementation, making it arduous for any single nutrient to provide material benefits.
The researchers also note that the participants were relatively teenage (average age was 66) and experienced only minimal cognitive decline over the course of the two-year study. As a result, there may simply have been too little of a decline during the study to detect any protective effect of DHA supplementation.