Omega-3 fatty acids play critical roles in maintaining brain health and function, potentially reducing the risk of developing Alzheimer’s disease. People who carry the APOE4 gene variant and those with obesity have a higher risk of developing the disease, suggesting that differences in metabolism could be a factor. A 2022 study found that obesity influenced the amount of omega-3 in plasma phospholipid form that is important for brain transport.

Fifty people (half of whom carried the APOE4 gene) took 2.5 grams of combined docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) daily for six months. Because omega-3 fatty acids must be in the free fatty acid form or phospholipid form to cross the blood-brain barrier, researchers measured these forms of the fatty acids in the participants' plasma before and after the intervention. They also investigated whether APOE genotype or body mass index (BMI, a proxy for overweight and obesity) influenced these measures.

They found that supplemental omega-3s increased by up to fourfold in all participants, regardless of APOE status. However, participants with a high BMI experienced lower plasma phospholipid omega-3 increases than those with a low BMI. Having a high BMI is a well-established risk factor for Alzheimer’s disease. Interestingly, APOE4 did not influence the amount of plasma phospholipid omega-3.

They also lend support to evidence suggesting that APOE4 carriers do not respond to lower dose omega-3 supplementation as well as non carriers possibly because they do not transport DHA in free fatty acid form across the blood-brain barrier as well. However, the transport of the phospholipid form of DHA across the blood-brain barrier bypasses the default in tight junctions, potentially providing a better means of DHA transport for people with the APOE4 gene and lowering their risk of developing the disease. Learn more about APOE4 and DHA transport in this peer-reviewed article by Dr. Rhonda Patrick.