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Better Brain Health in Midlife Linked to Omega-3 Levels

Fish are a rich source of Omega-3 fatty acids.
Fish are a rich source of Omega-3 fatty acids. Credit: Diane Helentjaris on Unsplash.
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Scientists have discovered an association between brain structure, cognitive function and Omega-3 concentration in red blood cells. The study is published in the journal Neurology.

All about Omega-3

Polyunsaturated fatty acids (PUFAs) are fatty acids that possess more than one double bond in their chemical backbone. The most widely recognized and studied PUFAS include Omega-3 and Omega-6, which are critical components of the phospholipid cell membrane.


Examples of omega-3 PUFAS include: 

  • Alpha-linolenic acid (ALA)
  • Eicosapentaenoic acid (EPA)
  • Docosahexaenoic acid (DHA)


An increasing amount of research is demonstrating that intake of Omega-3 PUFAs is associated with beneficial effects on the brain. DHA, in particular, is considered important for:

  • Brain and eye development
  • Playing a role in mental health through childhood and early adulthood
  • The fluidity and function of cellular membranes, and neurotransmitter release

Fish – such as salmon, sardines and tuna – are a rich source of omega-3 PUFAS, therefore earning them the nickname “brain food”. 

Benefits of Omega-3 PUFAS identified in old age populations

The apparent beneficial effects of Omega-3 PUFAS are derived from studies conducted primarily in older populations. Researchers from the Faculty of The University of Texas Health Science Center at San Antonio (UT Health San Antonio) and other investigators from the Framingham Heart Study wanted to explore whether Omega-3 fatty acid concentrations in the blood are associated with better neurological outcomes in midlife. Dr. Claudia Satizabal, assistant professor of population health sciences with the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at UT Health San Antonio, is the lead author of the new publication.

Measuring Omega-3 concentrations, MRI and cognitive aging markers

Using data from 2,183 participants recruited to the Third-Generation and Omni 2 cohorts of the Framingham Heart Study, the researchers conducted a cross-sectional analysis of omega-3 fatty acid concentrations in red blood cells with MRI scans and cognitive markers of brain aging. The average age of participants was 46 years old, and the cohort comprised 53% women and 47% men.


“DHA and EPA concentrations were measured from RBC using gas chromatography, and the Omega-3 index was calculated as EPA + DHA,” the authors write. “We 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.”


In addition, the team explored the effects of Omega-3 concentration in volunteers carrying a genetic mutation linked with increased risk of developing Alzheimer’s disease, known as APOE4.

A little bit of Omega-3 is better than none at all

The researchers found that a higher Omega-3 index was associated with larger hippocampal volumes, a brain structure that plays an integral role in memory and learning. This association was statistically significant.


In addition, consuming more Omega-3s was associated with better abstract reasoning, the ability to understand complex concepts via logical thinking. “We saw the worst outcomes in the people who had the lowest consumption of Omega-3s,” Satizabal said. “So, that is something interesting. Although the more Omega-3 the more benefits for the brain, you just need to eat some to see benefits.”


Participants that carried the APOE4 mutation were also found to have less small-vessel disease.


“Omega-3 fatty acids such as EPA and DHA are key micronutrients that enhance and protect the brain,” said study coauthor Dr. Debora Melo van Lent, PhD, postdoctoral research fellow at the Biggs Institute. “Our study is one of the first to observe this effect in a younger population. More studies in this age group are needed.”


The biological mechanisms by which DHA and EPA seemingly protect the brain remain to be understood, and the researchers acknowledge their work as “exploratory” due to the observational nature of the study design. However, they propose one theory as to how this association may occur: the importance of DHA and EPA in neuronal membranes. When these fatty acids are replaced by other types of fatty acids, neurons seem to become unstable. “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,” Satizabal said.


This article is a rework of a press release issued by the University of Texas Health Science Center at San Antonio. Material has been edited for length and content.


Reference: Satizabal CL, Himali JJ, Beiser AS, et al. Association of red blood cell Omega-3 fatty acids with MRI markers and cognitive function in midlife: The Framingham Heart Study. Neurology. 2022:10.1212/WNL.0000000000201296. doi:10.1212/WNL.0000000000201296.