Written by Joyce Smith, BS. This study suggests that a minimum dose of two grams per day of docosahexaenoic acid (DHA) is required to ensure adequate delivery to the brain, particularly for those individuals who carry the APOE4 allele.
Many studies have extolled the health benefits of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) omega-3 fatty acids (n-3 FA). Higher blood levels of n-3 FA have shown a risk reduction for Alzheimer’s disease 1 while PET scans have detected lower cognitive function, smaller brain volume and amyloid plaque accumulation in patients with lower levels 2. Ranking high among DHA and EPA benefits are their strong antioxidant and anti -amyloidogenic properties that promote brain plasticity and inhibit synaptic loss 3-5. Lower doses (less than 1 g per day) of DHA supplementation for the primary prevention of AD have shown no cognitive function benefit in the cognitively unimpaired elderly 6. It is also known that aging, the presence of the APOE4 allele, a positive family history of dementia 7 and sedentary lifestyles 8 all contribute to the risk of developing dementia. (APOE4 is an allele of the APOE gene and is associated with the transportation of cholesterol and other fats via the bloodstream).
Given the amount of DHA supplementation required for DHA brain delivery is unknown, researchers hypothesized 9 that larger doses of DHA are needed to provide adequate brain levels and that the presence of the APOE4 allele reduces the delivery of DHA and EPA to the brain, thus contributing to the onset of cognitive impairment. In a double-blind trial, 33 participants were assigned to a six-month supplementation of either 2,152 mg per day of DHA (n=18), of which eight participants carried the APOE4 allele or a placebo (n=15), of which seven were APOE4 carriers. All participants were instructed to limit their intake of polyunsaturated fatty acids (PUFAs) and to take vitamin B complex supplements twice daily during that time. All had AD risk factors but were not cognitively impaired, had a family history of the disease, a sedentary lifestyle, and a diet low in n-3FA. Plasma blood and cerebrospinal fluid (CSF) levels of DHA and EPA, brain MRIs and cognitive function tests were all completed at baseline and repeated at six months to detect any changes in brain DHA and EPA levels, brain volume or cognitive function.
- After six months, those who supplemented with DHA had a significant increase in both CSF DHA and CSF EPA compared to placebo (p<0.0001 for both).
- CSF DHA of APOE4 non-carriers increased compared to carriers (p = 0.08) but not significantly; however, change in CSF EPA levels was significantly greater in APOE4 non-carriers compared to carriers (p = 0.001) in both treatment and placebo groups.
- Both plasma DHA and EPA levels also significantly increased after 6 months of supplementation and did not differ between APOE4 carriers and non-carriers.
- When comparing plasm DHA levels to CSF DHA levels, participants who took DHA for 6 months had a 200% increase in plasma DHA but only a 28% increase in CSF DHA.
- Brain volume and cognitive scores did not change significantly.
Researchers concluded that an association, independent of APOE4 status, exists between greater brain amyloid accumulation and lower brain DHA levels and that both an increase in amyloid deposition and lower DHA levels precede the onset of cognitive impairment.
Study limitations include the use of a disproportionately higher number of female to male participants. Also, the study was not able to determine whether the low DHA and EPA levels in CSF of the APOE4 carriers was due to their lower uptake across the blood brain barrier or to their greater utilization within the brain cells.
Source: Arellanes, Isabella C., Nicholas Choe, Victoria Solomon, Xulei He, Brian Kavin, Ashley E. Martinez, Naoko Kono et al. “Brain delivery of supplemental docosahexaenoic acid (DHA): A randomized placebo-controlled clinical trial.” EBioMedicine (2020): 102883.
© 2020 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Click here to read the full text study.
Posted August 4, 2020.
Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.
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- Arellanes IC, Choe N, Solomon V, et al. Brain delivery of supplemental docosahexaenoic acid (DHA): A randomized placebo-controlled clinical trial. EBioMedicine. 2020:102883.
