High doses of docosahexaenoic acid (DHA) supplements may help prevent progression to dementia in people who carry the apolipoprotein ε4 allele (APOE4), a new review published online January 17, 2017 in JAMA Neurology.
DHA (docosahexaenoic acid), found almost exclusively in marine organisms living in cold water, is an essential long-chain omega-3 polyunsaturated fatty acid. As one of the primary components of cell membranes, DHA is a key building block in every cell in a human body. Notably, DHA is a major structural fatty acid in the brain and eyes, representing approximately 97% of all omega-3 fats in the brain and 93% of all omega-3 fats in the retina. It plays a role in the formation of synapses and indirectly limits the production of amyloid deposition and helps cells clear toxic amyloid peptides.
Having the APOE4 allele is one of the strongest risk factors for developing Alzheimer’s disease. This allele is present in 20% of the general population but in about 50% of patients with Alzheimer’s disease.
Animal studies have shown that mice or rats given enough DHA over at least 10% of their lifespan don’t develop Alzheimer’s disease pathology (amyloid) in the brain. Observational studies in humans further suggested the link between DHA consumption and lower risk for Alzheimer’s disease. A meta-analysis published in the American Journal of Clinical Nutrition summarized 21 studies of 181,580 participants with 4,438 dementia cases identified during a follow-up ranging from 2.1 to 21 years.2 The analysis found that compared with not eating fish, consuming 1 serving of fish per week was associated with a significantly lower risk for Alzheimer’s disease dementia. Additional epidemiologic studies and clinical trials further suggested a trend of cognitively healthy APOE4 carriers benefiting from taking fish oil supplements over an extended period of time. In the Rush Memory and Aging Project, participants free of dementia underwent annual clinical neurologic evaluations and brain autopsy at death. After a mean follow-up of 8 years, the study showed APOE4 carriers who consumed at least one meal of seafood per week had fewer Alzheimer’s disease neuropathologic changes compared with those who consumed less fish.3
Scientists hypothesized several possible mechanisms that might link APOE4 with DHA metabolism. These include accelerated liver catabolism of DHA; defective DHA transfer across the blood-brain barrier; and hypolipidated or decreased APOE4 particle numbers, resulting in less efficient brain DHA metabolism. The conclusion from these scientific studies suggests that supplementing DHA may reduce Alzheimer’s disease risk.
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- Yassine, HN et al.; Association of Docosahexaenoic Acid Supplementation With Alzheimer Disease Stage in Apolipoprotein E ε4 Carriers, JAMA Neurol. Published online January 17, 2017. doi:10.1001/jamaneurol.2016.4899
- Zhang, Y et al.; Intakes of fish and polyunsaturated fatty acids and mild-to-severe cognitive impairment risks: a dose-response meta-analysis of 21 cohort studies, American Journal of Clinical Nutrition 2016; 103(2): 330-340
- Bennett, DA et al.; Overview and Findings from the Rush Memory and Aging Project, Curr Alzheimer Res. 2012 Jul 1; 9(6): 646-663
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