Past clinical trials have tried to determine whether or not taking DHA supplements, or omega-3 supplements could help prevent Alzheimer’s disease. Many studies using low DHA doses have shown no effect. In this study, we hypothesized that larger doses of current DHA formulations were necessary to get into the brain and that APOE4, a known risk gene of AD, may make DHA supplementation less effective by reducing its brain delivery.

In a placebo-controlled randomized clinical trial, 33 healthy individuals with a family history of dementia, were provided vitamin B complex and randomly assigned them to take either placebo (corn/soy oil pills) or over 2g of DHA supplements for 6 months. Cerebrospinal fluid was obtained from participants at the beginning and end of the study. Almost half of the participants carried the APOE4 gene variant.

We found a modest increase in DHA and EPA levels in the cerebrospinal fluid of those who took the DHA supplements compared to placebo. However, the changes in spinal fluid were much lower than blood. Those with the APOE4 risk gene showed a 3 times lower increase in brain omega-3 levels. These findings suggest that DHA supplementation under 1g per day (what was used in many past trials) may be ineffective in delivering  omega-3 fatty acids to the brain to protect against Alzheimer’s disease, particularly in those most at risk such as APOE4 carriers.

We thank our study volunteers for being so generous! Without their help, we would not know how much of DHA can get into the human brain.

A big question remains: can high doses of DHA slow memory decline or preserve brain volumes? To answer this question, we are actively conducting a large trial, PreventE4. You can help us by participating!

APOE4 reduces omega-3 fatty acid brain delivery. Those carrying the APOE4 risk gene have a harder time getting omega-3 (DHA and EPA) into their brains, possibly because their brain cells may be breaking down DHA to produce energy instead of using it in synapses to help make new memories. This process may contribute to the increased risk of Alzheimer’s disease in those carrying the APOE4 gene variant.

See the full publication in EBioMedicine.

More information can also be found in USC’s press release