Omega-3 fats have been well studied for their numerous health benefits, including their impact on brain health. However, as research evolves, it’s clear that not everyone will benefit from omega-3s similarly. Recent research suggests that individual genetics may affect how effectively one processes and utilizes omega-3 fatty acids.

Understanding how genetics can affect omega-3 levels is crucial for developing personalized and effective omega-3 strategies to optimize brain health and reduce the risk of cognitive decline. This article will explore the latest research on this topic and discuss what it means for individuals hoping to improve their cognitive health.

 

It’s Time to Get Ahead of Dementia

Dementia affects more than 55 million people worldwide. Alzheimer’s disease, the most common form of dementia, contributes to over 60% of those cases. Furthermore, the elderly population is expected to double in size by 2050 in the United States, which could lead to significant public health issues if dementia incidence remains the same.

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It is believed that the pathology of dementia and other neurodegenerative diseases occurs years before signs and symptoms present, and that by the time symptoms are noticed, it might be too late for intervention. Therefore, prevention strategies have become a research focus. Healthy diets have been associated with improved brain health, and omega-3 fatty acids are one of the critical nutrients thought to contribute to cognitive longevity.

 

Omega-3’s Role in Cognitive Decline

Omega-3 fatty acids are a type of polyunsaturated fatty acid. After consumption, omega-3s are incorporated into cell membranes, where they exert their actions. According to a 2023 review on polyunsaturated fats as bioactive molecules in neurodegenerative diseases, these actions include, but are not limited to, maintaining cell membrane fluidity, decreasing levels of inflammatory cytokines, modulating gene expression, and inhibiting platelet aggregation.

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It’s well-documented that inflammation is involved in neurodegenerative disorders and cognitive decline. The relationship between inflammation and oxidative stress is bi-directional. Therefore, agents that reduce oxidative stress are considered anti-inflammatory. Omega-3 fatty acids are precursors to several molecules that actively resolve inflammation. Evidence indicates that dietary intake of omega-3s alters the composition of fatty acids in the brain’s membranes and plays a role in brain pathophysiology.

 

Omega-3 Consumption and Brain Health Research

The research on omega-3 fats and cognitive decline has been conflicting. However, several recent publications have noted the positive effects of omega-3s on cognition.

A 2023 study assessed the longitudinal relationships of omega-3 intake with the risk of Alzheimer’s disease, dementia, or cognitive decline among 1,135 participants who were without dementia at baseline. The researchers found that long-term users of omega-3 fatty acid supplements exhibited a 64% reduced risk of Alzheimer’s disease.

The authors then took their findings, and along with 48 other longitudinal studies involving over 103,000 participants, they performed a meta-analysis to test the longitudinal relationships of omega-3 intake with all-cause dementia or cognitive decline. They reported a moderate-to-high level of evidence suggesting that omega-3 intake could lower all-cause dementia or cognitive decline by ~20%.

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A 2021 review of 33 studies concluded that dietary and supplemental omega-3s have protective effects against cognitive impairment and Alzheimer’s disease and are most effective when consumed before or in the early stages of cognitive decline. The authors also assessed the studies that adjusted for the ApoEe4 gene and found that metabolic effects of different omega-3 fats differ between e4 carriers and non-carriers.

As studies evolve, researchers point out that assessing omega-3 intake might not be adequate and that measuring the Omega-3 Index of subjects will help explain the inconsistent results.

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Omega-3 Index and Brain Health Research

The Omega-3 Index is a measurement that represents the EPA and DHA content of red blood cells expressed as a percent of total fatty acids. Originally linked to cardiovascular risk, the Omega-3 Index is now recognized as the benchmark for whole-body omega-3 status, including brain health. Optimal levels appear to be 8% or greater. However, some evidence indicates that increasing levels by 5% from baseline, regardless of the absolute value, can also provide health benefits.

A 2023 meta-analysis aimed to uncover the role of baseline Omega-3 Index levels by evaluating the effect of omega-3 fats on cognitive function in elderly populations. After assessing 15 randomized controlled trials, they found that omega-3 supplementation did not significantly improve changes in the mini-mental state examination (MMSE) scores to measure cognition. However, out of the 15 trials, only 7 reported Omega-3 Index at baseline and outcome.

In a subgroup analysis using the seven trials that assessed Omega-3 Index levels, researchers found that the MMSE scores were significantly improved in the higher baseline Omega-3 Index subgroup and higher Omega-3 Index increment subgroup. Therefore, the researchers concluded that omega-3 supplementation did not significantly impact cognitive function; a higher baseline Omega-3 Index and higher Omega-3 Index increment were associated with improved cognitive function in older adults.

Another prospective study published in 2020 searched for associations between plasma omega-3 levels and several dementia-related outcomes in older adults. The study included over 1,200 non-demented participants at baseline, and incidents of dementia were systematically detected over a 17-year follow-up. The researchers found that higher plasma omega-3 levels were consistently associated with a lower risk of dementia and a lower decline in global cognition, memory, and medial temporal lobe volume. However, while these studies are promising, there are still mixed results.

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The variability of individual responses to the same intervention has long been explored among the explanations for the mixed results reported on this topic. An individual’s genetic expression might provide information on those most likely to have a beneficial response to increasing omega-3 consumption.

There is some evidence that individuals carrying the APOEe4 allele (who are at higher risk for developing Alzheimer’s disease) may benefit more from increasing DHA than non-carriers. Furthermore, genome-wide association studies have found specific genes associated with cognitive outcomes. Therefore, can a person’s genetic sequence be used to determine if increasing omega-3 intake could impact cognitive metric outcomes?

 

New Study Investigates How Genetics May Impact Omega-3 Response

A December 2023 study published in the Journal of Nutrition was conducted to determine if specific genetic markers might moderate the effect of omega-3 fats on an individual’s risk of cognitive decline. A total of 1600 people from the Framingham Heart Study Offspring Cohort were enrolled in this cross-sectional study, where people underwent Omega-3 Index and genetic testing simultaneously. The researchers wanted to determine if there were any genetic mutations where having a low Omega-3 Index was associated with a higher risk for cognitive decline, which could be minimized by raising Omega-3 Index levels.

Each person’s genetic profile was scanned for minor mutations to see if there were any relationships between certain mutations combined with the cognitive test scores. Second, they looked to see if there were relationships between the person’s red blood cell omega-3 level and cognitive test scores. And finally, they put these together and looked to see if there were certain genetic mutations where having a low omega-3 level was associated with higher risk for cognitive decline but having a high omega-3 level erased that higher risk. This would be called a ‘gene-nutrient interaction.’ The point was to see if a particular genetic makeup rendered a person more or less likely to benefit from higher omega-3 levels when it comes to slowing cognitive decline.

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According to Dr. William S. Harris, an author on this study paper, and president of the Fatty Acid Research Institute (FARI), founder of OmegaQuant Analytics, LLC, and Professor at Sanford School of Medicine, “There indeed were several instances where a given mutation in a gene was associated with higher or lower cognitive performance, BUT the effect on performance was related to how high their omega-3 levels were. In some cases, the effects of a ‘bad’ mutation were erased by having a higher omega-3 score. It is these people who might especially benefit from more omega-3.  Additionally, there were some genes in which higher omega-3 levels were only beneficial for people without mutations,”

With an eye toward the future, Dr. Harris added, “It is a little early to directly apply these findings to health care, primarily because we are not yet routinely testing people for genetic mutations, but the time when this will enter standard practice is not far off. To get there more quickly, it’s important to know WHICH genetic mutation to search for (since there could be up to 3 BILLION places to look in the human genome!). Someday your doctor will be able to run a genetic panel that just focuses on a few important mutations (those associated with increased risk for cognitive decline) and if the patient has some, then the doctor could prescribe a higher omega-3 intake to help blunt the possible effects of the mutations on mental decline.”

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Summary

Cognitive impairment and Alzheimer’s disease present significant public health challenges and include complex etiology. Yet, there does appear to be an association with dietary lifestyle, including intake of omega-3 fats and cognitive health. Several reviews on the topic conclude that individuals consuming higher amounts of omega-3s are less likely to develop cognitive impairment and that omega-3s are most effective as a preventative strategy against Alzheimer’s disease when consumed before or early in stages of cognitive decline.

Furthermore, emerging evidence indicates that supplementing with omega-3 fats to prevent cognitive decline may not be equally effective among all individuals based on individual genetic makeup. While more research is needed before precision nutrition recommendations can be made based on personal genetics, preliminary studies are promising. Maybe one day, scientists will be able to effectively slow the development of cognitive decline by identifying, through genetic testing, who will benefit the most from increased omega-3 intake.

These statements have not been evaluated by the Food and Drug Administration. This test is not intended to diagnose, treat, cure, prevent or mitigate any disease. This site does not offer medical advice, and nothing contained herein is intended to establish a doctor/patient relationship. OmegaQuant, LLC is regulated under the Clinical Laboratory improvement Amendments of 1988 (CLIA) and is qualified to perform high complexity clinical testing. The performance characteristics of this test were determined by OmegaQuant, LLC. It has not been cleared or approved by the U.S. Food and Drug Administration.

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