Increased intake of docosahexaenoic acid may lower the risk of Alzheimer’s and dementia

Several studies have shown that dietary factors, especially the consumption of products containing docosahexaenoic acid (22:6n−3, DHA), influence the risks of Alzheimer’s disease (AD). In addition, DHA has been shown to reduce the risk of several AD-related events, such as brain glucose hypometabolism, aggregations of the amyloid beta peptide in fibrils and oligomers, as well as neuroinflammation.

DHA is an omega-3 fatty acid that is crucial to the structure of the human nervous system, cerebral cortex, retina and skin. DHA can be synthesized from alpha-linolenic acid or obtained from the consumption of human breast milk, fatty fish, fish oil or algae oil.

Study: Red blood cell DHA is inversely related to the risk of Alzheimer’s disease and all-cause dementia incidents: Study of Framingham offspring. Image Credit: NOOMEANG/


Previous studies have shown that increased DHA intake increases the risk of developing AD in carriers of the APOLIPOPROTEIN E (APOE)-ε4 allele. Under natural conditions, the the new DHA synthesis is marginal as the detection of DHA in tissues or blood is mainly attributed to dietary intake.

The lifespan of red blood cells (RBCs) is about 120 days. As a result, researchers assessing long-term intake of DHA are performed more effectively in RBCs compared to other blood lipid pools such as serum/plasma phospholipids and total serum/plasma.

A previous study conducted in Canada, where the study cohort included individuals over the age of 65, reported no association between RBC DHA and the incidence of dementia. This study also reported that higher blood mercury levels, which is a biomarker for fish intake, was associated with a reduced risk of dementia.

Although epidemiological data on RBC DHA status and cognition are widely available, evidence on the relationship between RBC DHA status and the incidence of AD is limited. In addition, the interaction between the APOE genotype and DHA remains unclear.

About the study

Scientists have recently hypothesized that higher RBC levels of DHA are strongly associated with a reduced risk of AD and all-cause dementia. They further hypothesized the existence of an interaction between APOE-ε4 and DHA. Taken together, these hypotheses were tested in a recent nutrients study using the Framingham Offspring Cohort.

The Framingham Health Study is an ongoing population study based in Framingham, Massachusetts. This cohort was first established in 1948 to identify factors associated with the development of cardiovascular disease.

The offspring cohort was developed in 1971 and included the children of the participants of the original cohort. To date, the entire cohort has been examined during nine exam cycles with a frequency of approximately once every 4 years.

The current study was conducted during the eighth exam cycle and included 3,021 participants. The authors collected RBCs from the participants and measured DHA levels.

Participants were excluded from the study if they missed RBC fatty acid measurements, suffered from dementia, were under the age of 65, or had information about their APOE genotype. Finally, 1,531 participants were eligible for the current study and were followed for a median of 7.2 years for a diagnosis of dementia.

Study findings

The present study reported that an increase in the concentration of DHA in RBCs was associated with a reduced risk of AD and all-cause dementia. Participants who were in the top quintile of RBC DHA showed nearly half the risk of developing AD during follow-up compared to those who were in the lower quintile.

The researchers also determined the possible interaction between RBC DHA and APOE-ε4 carrier. To this end, an inverse relationship between RBC DHA and the risk of AD is in ε4 carriers was observed, with ε4 carriers associated with a greater genetic risk of late-onset AD compared to non-carriers. The research results therefore strongly indicate that: ε4 carriers would benefit greatly from higher DHA consumption compared to non-carriers.

The current study supports the existence of a link between diet and brain health. More specifically, an increase in DHA intake appears to increase RBC DHA levels, which is beneficial for brain health. The authors estimate that by delaying the onset of AD by five years, a person could have 2.7 years left to live.

Taken together, the study results are consistent with those of a previous study that uncovered cross-sectional associations between RBC DHA and an individual’s cognitive performance.

In the future, researchers should focus on identifying better markers such as eicosapentaenoic acid (EPA, 20:5n−3) and/or DHA that can be used to predict an individual’s risk of dementia. In addition, an optimal sampling system should be established to analyze omega-3 content in dementia patients.

Strengths and limitations

One of the main strengths of the current study is the large cohort made up of older adults who lived in community settings and were under ongoing dementia monitoring. In addition, because of the continued collection of varied health measures of the participants over the years, scientists could include these data as potential confounders in statistical models.

Nevertheless, the current study had certain limitations. For example, due to its observational nature, the authors have failed to address causality and establish the directionality of associations. Another shortcoming of this study is the low number of ε4 carriers.

An additional limitation is that the scientists were unable to determine whether the single measurement of RBC DHA is appropriate for estimating the risk of AD over a long period of time compared to more frequent measurements.

Reference magazine:

  • Sala-Vila, A., Satizabal, CL, Tintle, N., et al. (2022) Red blood cell DHA is inversely related to the risk of Alzheimer’s disease and all-cause dementia incidents: Study of Framingham offspring. nutrients14(12), 2408. doi: 10.3390/nu14122408

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