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A new study of over 2000 men and women in good cognitive health shows that higher Omega-3 fatty acid concentrations may preserve brain health and enhance cognition in middle age. The study was one of the first to observe this effect on a younger population.

Key Highlights From the Omega-3 study

The Faculty of The University of Texas Health Science Center San Antonio (UT Health San Antonio) and other investigators from the Framingham Heart Study conducted the research. Details were published online on Oct. 5 in Neurology®, the medical journal of the American Academy of Neurology.

Diet may be a key contributor to brain health in midlife. Omega-3 fatty acids are particularly related to better neurological outcomes in older adults.

Eating cold-water fish and other sources of omega-3 fatty acids may preserve brain health and enhance cognition in middle age.

Better brain structure

Having at least some omega-3s in red blood cells was associated with better brain structure and cognitive function among healthy study volunteers in their 40s and 50s.

“Studies have looked at this association in older populations. The new contribution here is that, even at younger ages, if you have a diet that includes some omega-3 fatty acids, you are already protecting your brain for most of the indicators of brain aging that we see at middle age,” said Claudia Satizabal, PhD, assistant professor of population health sciences with the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at UT Health San Antonio. Satizabal is the lead author of the study.

Background and objectives

Studies focusing on midlife are lacking, which is why this study is important. The researchers investigated the cross-sectional association of red blood cell (RBC) Omega-3 fatty acid concentrations with MRI and cognitive markers of brain aging in a community-based sample of predominantly middle-aged adults, and further explore effect modification by APOE genotype.


Participants were derived from the Third-Generation and Omni 2 cohorts of the Framingham Heart Study attending their second examination. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentrations were measured from RBC using gas chromatography, and the Omega-3 index was calculated as EPA + DHA.

The researchers used linear regression models to relate Omega-3 fatty acid concentrations to brain MRI measures (i.e., total brain, total gray matter, hippocampal, and white matter hyperintensity volumes) and cognitive function (i.e., episodic memory, processing speed, executive function, and abstract reasoning) adjusting for potential confounders.  They tested for interactions between omega-3 fatty acid levels and APOEgenotype (e4 carrier vs. non-carrier) on MRI and cognitive outcomes.

Key Findings

The study included 2,183 dementia- and stroke-free participants (mean age 46 years, 53% women, 22% APOE-e4 carriers).

In multivariable models, a higher Omega-3 index was associated with larger hippocampal volumes (standard deviation unit beta ±standard error; 0.003 ±0.001, p=0.04), and better abstract reasoning (0.17 ±0.07, p=0.013).

Similar results were obtained for DHA and EPA concentrations individually. Stratification by APOE-e4 status showed associations between higher DHA concentrations and Omega-3 index and larger hippocampal volumes in APOE-e4 non-carriers, whereas higher EPA concentrations were related to better abstract reasoning in APOE-e4 carriers.

Finally, higher levels of all Omega-3 predictors were related to lower white matter hyperintensity burden but only in APOE-e4 carriers. 

Summary of findings:

  • A higher omega-3 index was associated with larger hippocampal volumes. The hippocampus, a structure in the brain, plays a major role in learning and memory.
  • Consuming more omega-3s was associated with better abstract reasoning, or the ability to understand complex concepts using logical thinking.
  • APOE4 carriers with a higher omega-3 index had less small-vessel disease. The APOE4 gene is associated with cardiovascular disease and vascular dementia.


The study highlighted the importance of Omega-3 fatty acids such as EPA and DHA are key micronutrients to enhance and protect the brain,

The study results, albeit exploratory, suggest that higher Omega-3 fatty acid concentrations are related to better brain structure and cognitive function in a predominantly middle-aged cohort free of clinical dementia.

According to Science Daily, “Researchers don’t know how DHA and EPA protect the brain. One theory is that, because those fatty acids are needed in the membrane of neurons when they are replaced with other types of fatty acids, that’s when neurons (nerve cells) become unstable. Another explanation may have to deal with the anti-inflammatory properties of DHA and EPA.”

“It’s complex. We don’t understand everything yet, but we show that, somehow, if you increase your consumption of omega-3s even by a little bit, you are protecting your brain.”  – Claudia Satizabal

These associations differed by APOE genotype, suggesting potentially different metabolic patterns by APOE status.

Closing remarks

Study co-author Debora Melo van Lent, Ph.D., a postdoctoral research fellow at the Biggs Institute, said the study was one of the first to observe this effect on a younger population. Additional studies on middle-age populations are warranted to confirm these findings.


Association of Red Blood Cell Omega-3 Fatty Acids With MRI Markers and Cognitive Function in Midlife: The Framingham Heart Study. Satizabal CL, Himali JJ, Beiser AS, et al. Neurology. 2022 Oct 5:10.1212/WNL.0000000000201296.

Staff Writer

This post was written by a staff writer on Longevity, the bio for which will be included in the post for more information.

The content in this editorial is for general information only and is not intended to provide medical or other professional advice. For more information on your medical condition and treatment options, speak to your healthcare professional.

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