Higher Doses of Omega-3 Supplements May be Needed for Reduced Cognitive Decline

Higher Doses of Omega-3 Supplements May be Needed for Reduced Cognitive Decline

For years, a scientific puzzle has challenged researchers attempting to fight and potentially reduce Alzheimer's disease, a common and incurable form of dementia.

The outcomes of numerous laboratory investigations and population studies support the preventive potential of omega-3 fatty acids found abundantly in various fish species. However, to date the majority of studies evaluating omega-3s for averting or curtailing cognitive decline in humans have failed to show significant benefits. We now know that a genetic marker in people with a high risk to dementia, APOE4, may have a reduced capacity to absorb and utilize omega-3 fatty acids that can improve brain function and reduce dementia risk.

A small clinical trial from the University of Southern California provides important clues about potential genetic influence by comparing levels of omega-3s in the blood with those in the central nervous system. Among participants who carry a specific mutation that heightens risk for Alzheimer's, taking the supplements raised levels of a key fatty acid far less compared to those without the mutation. The findings suggest that higher doses of omega-3 supplements may be needed in order to make a difference in this at-risk population group, because dramatic increases in blood levels of omega-3s are accompanied by far smaller increases within the brain.

"Trials have been built on the assumption that omega-3s get into the brain," said senior author Dr. Hussein Yassine, associate professor of medicine and neurology at the Keck School of Medicine of USC. "Our study was specifically designed to address this question."

The researchers recruited 33 participants who had risk factors for Alzheimer's but were not cognitively impaired. All participants had a family history of the disease, a sedentary lifestyle, and a diet low in fatty fish. Fifteen carried the gene variant APOE4, which is linked to inflammation in the brain and increases Alzheimer's risk by a factor of four or more; the other 18 were noncarriers.

Participants were randomly assigned to a treatment group or control group. Members of the treatment group were asked to take supplements containing more than 2 grams of an omega-3 called docosahexaenoic acid (DHA) daily for six months. Control group members took placebos each day over the same period. Participants in both groups also were asked to take daily B-complex vitamins, which help the body process omega-3s.

Dr. Yassine and his colleagues gathered samples of blood plasma and cerebrospinal fluid, a gauge for whether the omega-3s reached the brain, from participants at the beginning and at the end of the study period. The scientists looked at levels of two omega-3 fatty acids: DHA and eicosapentaenoic acid (EPA), a potent anti-inflammatory that the body can construct from the longer chain DHA.

Higher doses for omega-3s to be effective?

The researchers found that at the end of the six months, participants who took omega-3 supplements had 200 percent more DHA in their blood compared to those who took placebos. In contrast, the DHA found in cerebrospinal fluid was only 28 percent higher in the treatment group than the control group. This result hints that measuring omega-3 levels in the blood may not indicate how much is reaching the brain.

Dr. Yassine and his co-authors also report that, within the treatment group, those without the risk-inflating APOE4 mutation showed an increase of EPA (anti-inflammatory omega-3 fatty acid) in their cerebrospinal fluid three times greater than what was seen in carriers of the gene.

This study indicates that APOE4 carriers, despite taking the same dose, ended up with less omega-3s in their brains. The findings suggest that omega-3 fatty acids are either getting metabolized or are not getting absorbed into the brain as efficiently in people with the APOE4 gene, which again, makes people more vulnerable to developing Alzheimer’s disease. It seems safe to infer that people with the APOE4 variant will benefit from higher levels of omega-3 which is known to reduce inflammation, a driving force behind Alzheimer’s development.

Notably, the two-gram dose of DHA in this study far exceeded what has been used in major clinical trials testing the protective power of omega-3s, which in previous trials has been typically administered at one gram or less daily.

The preliminary data from the current study was intriguing enough that the scientists were able to attract funding for a larger trial for which recruitment is underway. Following 320 participants over two years, it will examine whether high doses of omega-3s can slow cognitive decline in carriers of the APOE4 gene.