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Omega-3s Linked to Better Brain and Cognitive Health at Midlife

Omega-3s Linked to Better Brain and Cognitive Health at Midlife

Diet may be a key contributor to brain health in midlife. In particular, omega-3 fatty acids—those highly present in fish and other seafood (especially cold-water fatty fish, such as salmon, mackerel, tuna, herring, and sardines, nuts and seeds (such as flaxseed, chia seeds, and walnuts), and plant oils (such as flaxseed oil)—have been related to better neurological outcomes in older adults. But, studies focusing on midlife are lacking.  

While investigating the effect of omega-3 fatty acids on middle-aged adults, researchers working on the Framingham Heart Study found that the omega-3 index was associated with larger hippocampal volumes—a brain area critical for memory and learning. Out of the 2,183 cognitively healthy participants (mean age 46 years, 53% women), those with higher levels of eicosapentaenoic acid (EPA)—one of several omega-3 fatty acids—saw improved levels of abstract reasoning, suggesting the omega-3’s support cognitive health in middle-aged adults.

“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, Ph.D., assistant professor of population health sciences with the Glenn Biggs Institute at UT Health San Antonio. Satizabal is the lead author of the study.

The Almighty Omega-3

The class of lipids known as omega-3 fatty acids, or omega-3s, is considered essential, meaning that because our systems cannot create them on their own, we must ingest them through diet or supplementation. EPA (eicosapentaenoic acid), DHA (docosahexaenoic acid), and ALA (alpha-linolenic acid) are the three main omega-3 fatty acids. 

We know how important omega-3 fatty acids are to our overall well-being and lifespan. Unfortunately, the composition of the fat ratios we generally consume has been significantly changed by the Western diet of today, so if you don't make an effort to include omega-3 fatty acids in your diet, you're probably not receiving enough.

Omega-3s Linked to Better Brain and Cognitive Health at Midlife

Omega-3 Supports Brain and Cognitive Health

The team divided participants into those who had very little omega-3 red blood cell concentration, those who had at least a little, and more. From their calculations, the researchers found that a higher omega-3 index was associated with larger hippocampal volumes and better abstract reasoning. Similar results were obtained for DHA or EPA concentrations individually. “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.”

The risk of having poor brain health can be increased by specific genes. One such family of genes pertains to APOE, which has three common forms — e2, e3, and e4 — which are linked to good, normal, and poor brain health, respectively. We all have two APOE copies that are some mix of these three forms. A quarter of adults (25%) have one copy of APOE4, and two to three percent have two copies.

In this study, the researchers found that EPA and DHA also protected APOE4 carriers’ brain health. Stratification by APOE-e4 status showed associations between higher DHA concentrations or 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—an indicator of poor hippocampal health—but only in APOE-e4 carriers.

These 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. “It’s genetics, so you can’t change it,” Melo van Lent said, referring to the vulnerability of this risk group. “So, if there is a modifiable risk factor that can outweigh genetic predisposition, that’s a big gain.”

How it works

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 fatty acids, 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,” Satizabal said.

That being said, there are lots of ways to get your fill of omega-3s, from eating foods rich in nutrients to supplements. A common way to get omega-3s—fish oil supplements—can often be high in harmful mercury or other heavy metals and are not typically made sustainably. One solution is krill oil—a highly bioavailable omega-3-rich supplement. So, you don’t have to wait until later in life or when developing omega-3 deficiency to start loading up on DHA and EPA via supplements like krill oil because it seems like you can start seeing effects as early as midlife.


Claudia L. Satizabal, Jayandra Jung Himali, Alexa S. Beiser, et al. Association of Red Blood Cell Omega-3 Fatty Acids With MRI Markers and Cognitive Function in Midlife: The Framingham Heart Study. Neurology Oct 2022, 10.1212/WNL.0000000000201296; DOI: 10.1212/WNL.0000000000201296

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