EPA & DHA: Key to Brain Structure and Performance

Original publication: von Schacky C. Importance of EPA and DHA Blood Levels in Brain Structure and Function. Nutrients. 2021 Mar 25;13(4):1074. doi: 10.3390/nu13041074. PMID: 33806218; PMCID: PMC8066148. Link to the article

Why Your Brain Runs on Omega-3s—and What Happens If You’re Low

Think of Omega-3s as brain fuel. Without enough EPA and DHA in your bloodstream, your brain starts to slow—structurally and functionally. Memory fades, thinking gets foggy, and risks like depression, stroke, or dementia rise. And yet, most people are running on empty.

The Scientific Wake-Up Call: What the Study Found

A landmark review by Dr. Clemens von Schacky, published in Nutrients (2021), connects the dots between blood levels of EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) and nearly every function in the human brain—from infancy through old age. Epidemiological studies have shown that a low Omega-3 Index—compared to the optimal range—is associated with increased risks of all-cause mortality, ischemic stroke, reduced brain volume, cognitive decline, faster progression to dementia, psychiatric disorders, and impairments in complex brain functions.

The Omega-3 Index, a validated blood test that measures the percentage of EPA + DHA in red blood cells, reveals it all. The optimal range is 8–11%. But here’s the problem: most people fall between 2–6%—far below what’s needed.

Many intervention studies and their meta-analyses have treated EPA and DHA as pharmaceutical agents with good bioavailability. This approach often yields significant results in populations with low baseline levels (e.g., individuals with major depression) but has also contributed to numerous neutral findings and widespread confusion.

However, when study outcomes were analyzed based on measured blood levels of EPA and DHA, rather than comparing supplement groups to placebos, the observed effects were more pronounced and aligned more closely with epidemiological evidence. These findings underscore the importance of incorporating blood level measurements in future clinical trial designs and support the targeted use of EPA and DHA based on an individual’s Omega-3 Index.

Brain function depends on factors like blood glucose, brain structure, perfusion, and inflammation. The fatty acid composition of cell membranes—especially EPA and DHA—affects membrane stability, signaling, and other functions. This review highlights the role of EPA and DHA in brain health, focusing on blood levels measured via the Omega-3 Index, a reliable long-term marker of EPA and DHA status.

What Happens When Omega-3 Levels Are Low?

Across every life stage, low EPA + DHA is linked to:

• Shrinking brain volume

• Slower thinking and poor memory

• Higher risk of depression, ADHD, and dementia

• Increased stroke and mortality risk

• Pregnancy complications and developmental issues in babies

This isn’t theory—it’s backed by both epidemiological data and blood-based clinical trials.

The role of the EPA and DHA in brain health falls into three main areas:

1. Brain Development and Maintenance:
   Humans convert little ALA (plant-based omega-3) to DHA, so direct DHA intake is crucial, especially during pregnancy and brain development into early adulthood. DHA is also needed lifelong to maintain brain structure due to ongoing cell turnover.
2. Brain Perfusion:
   Brain function relies on blood flow, which is influenced by vasoactive compounds derived from EPA and DHA. A higher Omega-3 Index is linked to better cerebral blood flow and reduced risk of stroke, as these fatty acids lower blood pressure and stabilize blood vessels.
3. Inflammation in the Brain:
   Inflammatory processes, such as those involved in depression, are mitigated by EPA and DHA, which help both reduce and resolve inflammation.

Why Most Omega-3 Research Got It Wrong (and How to Get It Right)

A major flaw in past studies? They only looked at supplement use, not actual blood levels. And here’s why that matters:

• Absorption varies—up to 13x between individuals

• Fatty meals are needed to absorb Omega-3 properly

• Placebo and supplement groups often overlapped in blood values

• Timing, dosing, and capsule form were often inconsistent

When trials actually measured blood levels of EPA and DHA, the results were strikingly clearer: higher Omega-3 Index = better brain health. Many past studies linked dietary intake of EPA and DHA to brain health but often relied on food frequency questionnaires and outdated nutrient databases, leading to unreliable data. Blood levels, particularly in erythrocytes, provide stronger and more accurate associations with clinical outcomes.

It often comes down to what researchers measure and whom they study. Many older trials didn’t account for critical variables that can influence results, such as:

• Genetic factors like the ApoE4 gene, which affects fat metabolism and Alzheimer’s risk

• Vitamin B levels, which work together with Omega-3s in brain health

• Homocysteine levels, an inflammation marker linked to cognitive decline

These factors can dramatically influence how individuals absorb, process, and benefit from EPA and DHA.

Some large intervention trials overlooked the bioavailability of EPA and DHA. Participants were often instructed to take supplements with breakfast—a meal typically low in fat—despite the fact that fat is necessary for proper absorption. This reduced the effectiveness of supplementation. Additionally, individual differences in absorption are large (up to 13-fold), and baseline Omega-3 levels were usually not considered. As a result, EPA and DHA blood levels often overlapped between the supplement and placebo groups, making it difficult to detect clinical effects. Many reviews and meta-analyses ignored these design flaws, leading to potentially misleading conclusions.

Research across generations

In every period of human life (early life, childhood and adolescence, and adulthood), the importance of Omega 3 fatty acids was studied. During pregnancy, the placenta prioritizes the transfer of AA and DHA to the fetus, aiming for just over 8% DHA in fetal red blood cells—a likely natural target. This comes at the expense of the mother’s DHA levels. A German study found that most pregnant women had an Omega-3 Index below the recommended 8–11%, which dropped further after birth. Only 11.5% supplemented with omega-3s, and while this raised their average levels slightly, most remained below target with wide individual variation. Low Omega-3 Index in pregnancy is linked to complications like premature birth, infant mortality, maternal ICU needs, perinatal depression, and impaired brain development in the child.

Mothers with a low Omega-3 Index are more likely to have preterm births. Since the brain develops rapidly in the last trimester—especially accumulating DHA—preterm babies are often born with lower Omega-3 levels and may need extra DHA and possibly AA for healthy brain development. A meta-analysis confirmed that DHA and AA supplementation benefits brain function in preterm infants aged 12–24 months.

What do recent studies say?

A recent review of 33 trials found that daily supplementation with at least 450 mg DHA + EPA, leading to an Omega-3 Index above 6%, is more likely to improve cognition in individuals aged 4–25, including those with conditions like ADHD or autism. Supporting this, a 23-week trial in undernourished children under and over 4 years showed that a supplement containing 255 mg DHA and 171 mg EPA improved brain blood flow and executive function. These findings highlight the benefits of EPA and DHA, especially in children with a low Omega-3 Index.

Across all ages—from childhood to old age—higher Omega-3 Index levels are consistently linked to better cognitive function, including memory, executive function, and problem-solving. A low Omega-3 Index is associated with faster cognitive decline and earlier dementia. While reaction time, a simple measure of brain performance, improved in most trials, results across studies on omega-3 supplementation and cognition have been mixed.

Some clinical studies report noticeable brain benefits—especially in people with early-stage Alzheimer’s disease or when DHA intake exceeds 600 mg/day. In fact, multiple trials show that when EPA and DHA levels in the blood go up, so does brain performance.

One striking study even found that omega-3 supplementation cut age-related gray matter loss by two-thirds, pointing to a powerful protective effect.

Why Blood Testing (Not Just Supplementing) Matters

More recent trials that measured and analyzed blood levels of EPA and DHA showed stronger and clearer effects, aligning with epidemiological findings. However, proper sample handling and use of validated testing methods (like the Omega-3 Index) are essential for reliable data.
In short, trial design must prioritize blood level-based inclusion criteria, dosing strategies that ensure absorption, and validated blood tests to accurately assess the true impact of EPA and DHA.

Since the brain gets EPA and DHA only from the bloodstream, and factors like genetics (e.g., ApoE4) influence their uptake, measuring blood levels—rather than dietary intake—is key to understanding their impact on brain health.

Clinical trials show clearer results when EPA and DHA blood levels—especially in erythrocytes—are measured and used as endpoints, aligning with findings from epidemiological studies like Framingham. This underscores the importance of assessing blood levels rather than just dietary intake in research and meta-analyses.

Correcting low Omega-3 Index levels significantly reduces risks of mortality, stroke, heart attacks, and mental health issues like depression and dementia. Populations such as vegans, vegetarians, athletes, pregnant women, and individuals with mental health disorders often have deficits.
Given the public health impact, countries should follow Canada’s example by assessing national Omega-3 Index levels. Since food sources like farmed fish are declining in EPA and DHA content, supplements—shown to be safe and effective—are a practical solution. The threshold for supplementation should be low due to the high potential benefit and minimal risk.

Bottom line:

Your brain can only use the EPA and DHA that actually reach your bloodstream. So measuring blood levels—not just tracking supplement use—is the only way to know if you’re getting enough.

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From Science to Supplement: What MVS Pharma Has Done Differently

Thanks to the study by Clemens von Schacky Importance of EPA and DHA Blood Levels in Brain Structure and Function. MVS Pharma received a broad and complete confirmation about the benefits of using Omega 3 fatty acids as a supplement in each stage of human life. That not only motivated but inspired the team to set a new standard among the Omega 3 supplements.

Inspired by this research, MVS Pharma developed a new gold standard in Omega-3 supplementation—backed by blood science and optimized for absorption, protection, and real-world results.

Here’s what sets our product (MVS Omega-3) apart:

1. Superior Omega-3 Content

• 860 mg/g Omega-3 fatty acids

• Balanced EPA:DHA ratio — 480 mg/g : 320 mg/g

• Delivered in re-esterified triglyceride (rTG) form for maximum absorption

rTG is absorbed up to 70% more effectively than ethyl ester forms used in many generic supplements.

2. Unmatched Capsule Technology

• Ultra-thin hardgel capsules (only 70 mg) vs. standard 200 mg softgels

• 10:1 oil-to-shell ratio (vs. 3.5:1 in softgels)

• No plasticizers—only pure gelatin

• Oxygen permeability: 0.0014 cc/m²/24h

  • That’s 50x more protective than HPMC capsules commonly used in “vegan” formats

On top of that, adding antioxidants prevents the oxidation processes, but the capsule itself has a crucial influence on these processes. The capsule we use is hardgel and ultra-thin, made of gelatin with no other plasticizers. That makes it much lighter (70 mg) than the standard softgel capsules, which are approximately. 200 mg. These thin, stable, pure, and clean capsules have an oil-to-shell ratio of 10:1 compared to the 3,5:1 ratio of softgel capsules.

But the feature that makes our product unique is the very low oxygen shell permeability of 0.0014 cc/m²/24 hours. If we compare it with a regular HPMC capsule value of 0.069 cc/m²/24 hours, it’s approximately. 50-fold difference, for example.

3. Dual Protective Packaging

Oxidation is the enemy of Omega-3 potency. That’s why we use a two-tiered defense system:

1. Capsule-level protection (low-permeability shell)

2. Outer packaging designed to block oxygen, moisture, and light

   • Maintains freshness over 3-year shelf life

This dual-layer strategy means no fishy aftertaste, no oxidation, and no compromise on quality.