Failure of Omega-3s to Prevent, Slow Alzheimer’s Explained? – Brain Health Education and Research Institute

Much higher doses of docosahexaenoic acid (DHA) than initially thought may be required to effectively fight Alzheimer’s disease (AD), new research suggests. In results that could explain why the omega-3 fatty acid has failed to prevent AD or slow its progression, investigators found that among individuals who took omega-3 supplements, DHA blood plasma levels were high, but cerebrospinal fluid (CSF) levels were relatively low. The researchers hypothesized that larger doses of DHA are required for adequate brain bioavailability. They also theorized that the APOE4 gene variant is associated with reduced delivery of both DHA and eicosapentaenoic acid (EPA) to the brain before the onset of cognitive impairment.To test their hypotheses, the investigators conducted a randomized placebo-controlled pilot study that included 33 individuals, all of whom had AD risk factors but were without cognitive impairment.

Results showed that among participants in the DHA supplement group (n = 13), blood plasma DHA levels were 200% higher than for patients in the placebo group (n = 13). In contrast, CSF levels were only 28% higher in the intervention group vs the placebo group (mean difference, 0.08 μg/mL; P < .0001). The researchers also found that among carriers of the APOE4 mutation in the active intervention group, DHA levels in CSF were lower, despite the fact that these patients received the same dose as noncarriers (mean difference, 0.02 μg/mL; P = .08). Similarly, there was a 43% increase in CSF EPA levels in the patients in the active intervention arm compared with patients in the placebo arm (mean difference, 0.008 μg/mL; P < .0001). The increase in CSF EPA in non-APOE4 carriers after supplementation was three times greater than in APOE4 carriers (mean difference, 0.006 μg/mL; P = .001). “E4 carriers, despite having the same dose, had less omega-3s in the brain. This finding suggests that EPA is either getting consumed, getting lost, or not getting absorbed into the brain as efficiently with the E4 gene,” Yassine said in a release.