High dose of EPA/DHA omega-3s benefit group at high risk of dementia

A high dose of omega-3s restricted the growth of cerebral white matter lesions in a group of subjects at highest risk of dementia. The effects for the rest of the subjects were not statistically significant, which could be due to the smaller size of the study.

The new research was published in the journal JAMA Network Open. It was the work of a group of researchers associated with universities and medical schools in Alabama, Massachusetts and Oregon.

The researchers used 975 mg EPA and 650 mg DHA. This dosage level can be found in certain high-concentrate omega-3 supplements if an extra capsule is taken.

Cerebral white matter lesions (WML) are knots of abnormal myelin tissue that can be seen on MRI scans. Myelin is the sheath that surrounds nerve cells. WML accumulation is a known risk factor for the development of Alzheimer’s disease and other forms of dementia.

The authors said that past research has shown that omega-3s is associated with a reduced WML burden. The metabolism of these fatty acids into lipophilic inflammation-resolving metabolites is postulated as one of the mechanisms of action for this effect. The authors also said that omega-3s have been associated with a downregulation of adhesion molecules in the brain.  Higher adhesion activity is thought to be associated with greater WML activity.

The present study is a further analysis of data derived from the Polyunsaturated Fatty Acids for the Prevention of Cerebral Small Vessel Disease and Inflammation in Aging (PUFA trial).  Baseline results of the first trial were first reported in 2019.

Study was moderate sized, but longer term

For the original trial, the researchers recruited 102 subjects for the quadruple blinded, placebo-controlled trial. The subjects were 75 years old or older at the start of the 3-year trial and were living in community settings. They ranged from cognitively intact to exhibiting mild cognitive impairment. A bit more than half of the participants were women.

The subjects took 3 softgels daily that contained a total dose 975 mg of EPA and 675 mg of DHA. The placebo group received 3 softgels containing soybean oil.

The subjects, who were all recruited in the Portland, Ore. area, visited the clinic once every three months during the study, primarily to ensure compliance with the study protocols.

The subjects underwent MRI scans at baseline and then annually during the study to measure WML progression.

The subjects were also divided into those who were apolipoprotein E ε4 allele (APOE*E4) carriers and those who were not. About 25% of the general population carries at least one ε4 allele of the Apolipoprotein E (APOE ε4). This is the strongest genetic risk factor for late onset Alzheimer’s disease. 

Best results seen in highest risk group

The results showed a general trend toward less WML accumulation among the omega-3s group than in the placebo group. However, the differences were not statistically significant, the authors said. 

The authors noted that overall, the WML accumulation was less than anticipated, which means the study may have been underpowered to achieve statistical significance. But they did see a very promising trend for benefit in the highest risk group.

“The significant reduction in neuronal integrity breakdown among APOE*E4 carriers suggests that the effects of ω-3 may be amplified for these individuals. These results will enable improved study design and sample size calculations for future efforts of a relatively cheap, safe, and well-tolerated therapy for primary and secondary dementia prevention,” the authors concluded.