Millions of people swallow fish oil capsules hoping they're doing something beneficial for their brains, but a new study shows the connection is questionable.

High doses of DHA, an omega-3 fatty acid important to brain function, successfully reached the brains of older adults at risk for dementia in the study by researchers at the University of Southern California's Keck School of Medicine. But there was a Catch-22 when it came to protection from the brain changes related to Alzheimer's. After two years of use, the supplements did not improve memory or thinking skills, or protect against changes in brain structure associated with aging and Alzheimer's disease.

Although they were cognitively unimpaired when the study began, forty-seven percent of the people in the study carried APOE4, the strongest known genetic risk factor for late-onset Alzheimer's disease.

“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,” lead author Hussein Naji Yassine, MD, professor of neurology, physiology and neuroscience at the Keck School Medicine of USC, and director of the USC Center for Personalized Brain Health, said in press release. “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 preventative measure against Alzheimer's.”

The study included 365 adults between the ages of 55 and 80 who rarely ate fish, one of the richest dietary sources of omega-3 fatty acids. All were considered at increased risk for Alzheimer's disease. Although they were cognitively unimpaired when the study began, forty-seven percent of the people in the study carried APOE4, the strongest known genetic risk factor for late-onset Alzheimer's disease.

The research was randomized, double-blind and placebo-controlled, which is considered the gold standard for testing an intervention. Participants were randomly assigned to take either a daily supplement containing 2,000 milligrams of DHA, or an identical-looking placebo. Neither the participants nor the researchers assessing them knew who was talking which.

The first question the researchers explored was surprisingly basic: Could DHA from a supplement get into the brain? To find out, the team measured DHA in cerebrospinal fluid, the clear liquid that surrounds the brain and spinal cord. After six months, DHA levels had increased by an average of 17 percent in participants taking the supplement. The capsules, in other words, were delivering DHA where researchers wanted it to go. But getting there did not translate into better brain health.

Participants were randomly assigned to take either a daily supplement containing 2,000 milligrams of DHA, or an identical-looking placebo. Neither the participants nor the researchers assessing them knew who was talking which.

Participants underwent tests of memory and other thinking abilities when the study began and again two years later. Those who took DHA performed no better than those who took the placebo.

Brain imaging told a similar story. The supplements did not prevent shrinkage of the hippocampus, a region essential to memory and often examined as a marker of brain aging and Alzheimer's risk. Nor did researchers find meaningful protection in other measures of brain structure.

The findings are especially intriguing because they challenge one common explanation for the disappointing results of earlier fish oil studies: perhaps the omega-3s were simply not reaching the brain. In this trial, they clearly did. Yet, there was still no measurable cognitive benefit.

That does not mean omega-3 fatty acids are unimportant. DHA is a critical component of brain cell membranes and plays a role in the connections brain cells use to communicate. The unanswered question is why increasing DHA levels through a high-dose supplement did not produce better results.

The capsules were delivering DHA where researchers wanted it to go. But getting there did not translate into better brain health.

Yassine and his colleagues now want to understand how the aging brain processes and uses omega-3s. Health, age, genetic risk and overall dietary patterns may all influence whether these nutrients can do their job once they arrive.

The researchers also point to an important distinction between taking one nutrient in a capsule and getting nutrients through food. Nutrition research suggests that omega-3s may be more beneficial when consumed as part of a Mediterranean-style diet, which includes fish along with vegetables, fruits, whole grains legumes, nuts and olive oil, as well as healthy lifestyle choices.

For people taking fish oil solely to protect their memory, the new findings are worth discussing with a healthcare professional. Fish oil may be recommended for other medical reasons, however, so stopping a supplement without medical advice is not always the answer.

The study is published in The Lancet.