Omega-3 Fatty Acids Linked to Brain Volume

January 23, 2014

Total normal brain and hippocampus volumes were directly associated with levels of omega-3 fatty acids in a study of more than 1000 postmenopausal women.

The study, published online in Neurology on January 22, was conducted by a team led by James Pottala, PhD, University of South Dakota, Sioux Falls.

"These results are consistent with the idea that higher omega-3 levels may slow the loss of brain volume that occurs as we age," senior author, William Harris, PhD, also from the University of South Dakota, told Medscape Medical News.

Women's Health Initiative Memory Study

To examine the association between the amount of omega-3 fatty acids in the body and brain volume, Dr. Pottala, Dr. Harris, and colleagues used data from the Women's Health Initiative Memory Study Magnetic Resonance Imaging (WHIMS-MRI) that evaluated the effects of hormone therapy in postmenopausal women in which blood samples had been frozen and brain MRI scans recorded.

"The blood samples were taken at the start of the study and the MRI scans were performed 8 years later. While this is not necessarily the perfect design, that's what was available," Dr. Harris noted.

They used the red blood cell omega-3 index as a measure of omega-3 status. This index is the percentage of omega-3 fatty acids — eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) — of the total fatty acids in red blood cell membranes.

Results showed that overall brain size was slightly but significantly smaller in the women in the lowest quartile of omega-3 index compared with those in the highest quartile. And specifically, the hippocampus, which is the area of the brain related to cognitive function, was also significantly smaller in the lowest vs the highest quartile of omega-3 index. This was after controlling for age, lipid levels, glucose, blood pressure, education, and hormone therapy.

The hippocampal volume difference between the highest and lowest quartiles of omega-3 levels was about 2.5%. For comparison, other studies have shown that patients with fairly severe Alzheimer's disease have hippocampus volumes about 40% smaller than people without dementia, Dr. Harris said. "So it is a small effect but it is interesting that there was any detectable effect at all."

The women in the lowest omega-3 quartile had an omega-3 index of 3.4% compared with 7% for those in the highest quartile. "For reference, Japanese people, who generally eat a lot of fish, have an omega-3 index of around 10%," Dr. Harris noted. "It would be possible to move from an index of 3% to one of 7% by taking about 1000 mg of EPA + DHA every day or by eating a small portion of salmon or sardines every day. So it's not difficult to do."

In the paper the researchers write, "Changes in the omega-3 index that can be achieved through diet modification and/or supplementation are similar to those associated with 1 to 2 years of normal, age-related brain atrophy."

Another Piece of the Puzzle

Dr. Harris commented: "This is another piece of the puzzle, but this is a difficult puzzle to put together. There have now been many studies showing an association of omega-3 fatty acids with brain health but also some that have not found such a link. However, the weight of the evidence is in favor of a positive association."

He cautions that there is not yet enough evidence to say that this association is causal.

"It could be something else that is causing both omega-3 levels to go up and benefiting the brain — perhaps some other constituent of fish, and omega-3 could be just be a marker of how much fish you eat. Or people who eat more fish may not be eating so much of something else that is harmful," he said.

People who eat high quantities of fish may lead healthier lifestyles in general, he added. "But then when we look at the whole picture, omega-3 fatty acids are a major component of brain tissue and they are metabolized to anti-inflammatory compounds that could reduce brain cell death. We can certainly make a good story to support the idea that omega-3 fatty acids are good for the brain."

He notes that a previous study using Framingham data suggested that low levels of omega-3 fatty acids were associated with deficits in cognitive function, and some studies have suggested a benefit in cognitive performance of supplementing with omega 3 fatty acids. But these have been quite small so far, and larger studies are needed.

Some larger studies are now underway. One in the United States — called VITAL — is looking at the effect of supplementing with omega-3 fatty acids and vitamin D on heart health and brain health in 20,000 individuals, with results due in 2016/2017.

In the meantime, is there enough evidence to support supplementation? Dr. Harris says there may be.

"I do think you could make a case for omega-3 supplementation," he said. "There is the issue of cost, but this isn't massive and if everyone decided to take supplements there may be a resource issue as this would challenge fish stocks. But there is no evidence for harm and certainly some suggestion for benefit so the risk/benefit ratio is good."

The study was supported by the National Heart, Lung, and Blood Institute. Dr. Harris owns OmegaQuant Analytics, LLC, and is a senior research scientist at Health Diagnostic Laboratory Inc, both of which offer red blood cell fatty acid tests. He is also a scientific advisor to Omthera Pharmaceuticals and Aker BioMarine Antarctic.

Neurology. 2014;82:435-442. Published online January 22, 2014. Abstract

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