The Fat You Actually Want: Powered by Omega-3

In this Nexus:

💡 Different Omega's

🐟 Dietary Sources and Bioavailability of Omega-3

🔬 Omega-3 Fatty Acids' Mechanisms of Action

✅ Clinical Benefits of Omega-3 Fatty Acids

🧬 Clinical Trial Data on EPA and DHA

‼️ Dosage and Safety Considerations

💊 Omega-3 Stability and the Risk of Oxidation

📊 How Much Omega-3 Is in Your Supplement?

📈 My Omega-3 Index Results

After recently speaking at several conferences for physicians and pharmacists on the topic of Omega-3 polyunsaturated fatty acids, I finally found time to put my thoughts and the clinical trials that I have analysed into an article. Excited to share it with a wider audience. Omega-3 fatty acids are essential nutrients with wide-ranging effects on human health. These fatty acids play critical role in cardiovascular function, brain development, inflammation modulation, and cellular homeostasis. An increasing body of evidence also supports their contribution to healthy aging. In this Nexus I discuss different omega fatty acids, dietary sources, therapeutic efficacy, dosage recommendations, safety concerns, and also disclose my omega-3 index results. Happy reading!

Different Omega's

Lets start from the essentials. Omega fatty acids are classified based on where their first double bond is located, with the most well-known types being omega-3, omega-6, and omega-9. Omega-3s are known for their anti-inflammatory, heart- and brain-protective effects. Omega-6s (like linoleic and arachidonic acid) are essential for health but can promote inflammation when consumed in excess. Omega-9s, such as oleic acid in olive oil, support heart health and are not essential because the body can produce them. Less common types like omega-7 and omega-5 are also being studied for potential anti-inflammatory and antioxidant benefits.

The diagram below shows how omega-6 and omega-3 fatty acids affect inflammation in the body (1). Omega-6 fats, commonly found in vegetable oils, eggs, and red meat, are turned into substances that promote inflammation, in particular - arachidonic acid. While omega-6 fatty acids are important in small amounts, they are harmful when overconsumed. In contrast, omega-3 fats found in flaxseeds or fish oil are converted into compounds that help reduce or resolve inflammation. Most people today consume too much omega-6 and not enough omega-3 (spoiler alert - including myself), tipping the balance toward chronic inflammation. I will be discussing the importance of this balance later in this article.

Omega-3 polyunsaturated fatty acids (PUFAs) are a group of essential long-chain polyunsaturated fats that play a crucial role in human physiology. The three most well-studied forms are (1):

• Plant origin - alpha-linolenic acid (ALA), found primarily in plant sources such as flaxseeds, chia seeds, and hemp seeds;
• Animal origin - eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both of which are found in marine sources such as oily fish and fish oils.

While ALA can be enzymatically converted into EPA and DHA in the body, the conversion rate is highly inefficient - estimated at only 5–10% in healthy individuals. This means that people who do not consume fish (meaning EPA and DHA) are at risk for omega-3 deficiency and the imbalance between omega fatty acids, as only a small amount of ALA in the body will be converted to EPA and DHA.

Dietary Sources and Bioavailability of Omega-3

EPA and DHA are most effectively obtained from animal-based sources, particularly oily fish and marine oils, which provide readily bioavailable forms of these fatty acids. In contrast, plant-based sources are rich in ALA but require metabolic conversion to produce the active EPA and DHA forms.

Animal-based sources (high in bioavailable EPA/DHA) (2):

• Anchovy oil: ~7.5 g EPA/DHA per 100 g
• Mackerel: ~5 g EPA/DHA per 100 g
• Cod liver oil: ~7 g EPA/DHA per 100 g
• Sardines: ~1.5 g EPA/DHA per 100 g

Plant-based sources (rich in ALA, but requires conversion to EPA/DHA) (2):

• Flaxseed: ~23 g ALA per 100 g
• Chia seeds: ~18 g ALA per 100 g
• Hemp seeds: ~10 g ALA per 100 g

For therapeutic purposes (such as improving lipid profiles or reducing cardiovascular events) marine-derived EPA and DHA are the preferred sources due to their superior bioavailability and direct incorporation into cell membranes, where they exert anti-inflammatory and lipid-modulating effects.

What Does Science Say?

Omega-3 Fatty Acids' Mechanisms of Action

Omega-3 fatty acids exhibit a wide array of biological effects that make them beneficial in both the prevention and management of chronic diseases. Mechanistically, these fatty acids modulate membrane fluidity, inhibit the synthesis of pro-inflammatory eicosanoids, reduce platelet aggregation, and influence gene expression related to lipid metabolism and inflammation. These interconnected biological mechanisms are described in slightly more details below:

• Membrane structure and communication. When omega-3s are built into cell membranes, they make the membranes more flexible and influence “lipid rafts” — small areas that help organize how cell surface receptors and proteins interact (3). This can change how cells respond to signals, including hormones and immune triggers.
• Regulating genes. Omega-3s activate specific receptors in the cell nucleus, such as PPAR-α and PPAR-γ (4). These receptors control the activity of genes involved in fat metabolism and inflammation, helping to shift the body toward a healthier, less inflammatory state.
• Cell signaling. EPA and DHA (key omega-3s) influence major cell signaling pathways like MAPK, NF-κB, and JAK/STAT (5). These are systems cells use to respond to stress, inflammation, and other stimuli - and omega-3s help calm excessive inflammatory responses.
• Reducing oxidative stress. Omega-3s also enhance the body’s antioxidant defences, reducing the production of reactive oxygen species (ROS) and supporting enzymes that neutralize oxidative damage (6).

Clinical Benefits of Omega-3 Fatty Acids

EPA and DHA have demonstrated a wide range of clinically beneficial effects across multiple body systems (7):

• They support cardiovascular health by lowering triglyceride levels, stabilizing heart rhythm, and reducing blood pressure and arterial inflammation.
• Omega-3s exhibit anti-inflammatory properties that are valuable in managing conditions such as rheumatoid arthritis and Crohn’s disease.
• Their neuroprotective effects contribute to improved cognitive function and may slow neurodegenerative processes.
• In the metabolic domain, omega-3s show anti-hyperglycaemic and anti-hyperlipidemic actions, helping regulate blood sugar and lipid profiles.
• They also enhance skin health, reduce joint pain, and bolster the immune system.
• Emerging evidence suggests roles in cancer prevention and adjunctive treatment, particularly through modulation of cell signaling and inflammation.

Collectively, these effects make omega-3s a valuable component of preventive and therapeutic strategies in longevity.

Clinical Trial Data on EPA and DHA

While many longevity food supplements lack reliable data from robust clinical trials, the situation with omega-3 fatty acids is quite different. There has been a number of clinical studies, investigating the effects of EPA and DHA which included large sample sizes (thousands of participants), they were multicenter, double-blinded, placebo-controlled and randomized. Everything you would expect from clinical trials investigating new medicinal products. So let's check what this data reveals.

Cardiovascular Diseases

Omega-3 supplementation has demonstrated substantial benefits in cardiovascular health. The ASCEND clinical trial was conducted in the UK and included over 15,000 patients with Type 2 diabetes (8). These patients were given either EPA/DHA 840 mg daily or placebo and followed-up for over 7 years.

The core finding of ASCEND study was 19% decrease in cardiovascular mortality among patients using EPA/DHA.

Another clinical trial VITAL was conducted in the United States and included over 25,000 of older adults without history of cardiovascular disease or cancer (8). These patients were given either EPA/DHA 840 mg daily or placebo and followed-up for over 5 years.

VITAL study reported a 28% reduction in myocardial infarction risk, and a 17% reduction in ischemic heart disease.

A meta-analysis summarizing data from recent randomized trials provided below (8):

One of the most robust clinical trials in this field is the REDUCE-IT trial, a double-blind, placebo-controlled, randomized study involving over 8,000 high-risk patients with elevated triglyceride levels and established cardiovascular disease or diabetes (9). Patients received 4 g/day of EPA only in addition to statin therapy. Over a median follow-up of 4.9 years, REDUCE-IT trial demonstrated a significant reduction in cardiovascular death, nonfatal myocardial infarction, stroke, coronary revascularization, or unstable angina. This chart below shows that EPA significantly reduced the risk of major cardiovascular events compared to placebo in high-risk patients. These results underscore the importance of EPA at pharmacologic doses for cardioprotection.

Cognitive Function

DHA is particularly concentrated in the brain and is vital for neuronal structure and function. A randomized controlled trial conducted in New Zealand in healthy young adults whose habitual diets were low in DHA, showed that DHA supplementation improved memory and reaction times, supporting its role in cognitive health even in non-demented populations (10).

Metabolic Effects

Recent studies have also highlighted the potential of omega-3 fatty acids in improving insulin sensitivity. A 2023 study found that omega-3 supplementation led to measurable improvements in insulin resistance, suggesting utility in the prevention or management of type 2 diabetes and metabolic syndrome (11).

Cancer Prevention

Although still an emerging area, omega-3 fatty acids have shown promise in reducing inflammation and modulating cell proliferation pathways relevant to cancer (12). For instance, data suggest a potential role in improving outcomes among breast cancer survivors and possibly reducing the incidence of hormone-responsive tumors.

Dosage and Safety Considerations

For the general adult population the European Food Safety Authority (EFSA) recommend a daily intake of 250–500 mg of combined EPA and DHA to maintain cardiovascular health (13). Clinical trials often use higher doses, up to 4 g/day for therapeutic purposes, particularly in managing hypertriglyceridemia (high cholesterol) or reducing residual cardiovascular risk.

Doses up to 5 g/day are considered safe for long term use and well-tolerated, though higher intake may lead to modest increases in low-density lipoprotein cholesterol and a potential reduction in blood coagulation capacity, which could increase bleeding risk in susceptible individuals. Furthermore, high doses of DHA have been linked to improvements in cognitive performance, providing a rationale for higher supplementation in older adults or those with early cognitive decline.

Omega-3 Stability and the Risk of Oxidation

A significant but underappreciated concern with omega-3 supplementation is the risk of lipid oxidation. Oxidized omega-3s lose their beneficial bioactivity and can form harmful byproducts such as lipid peroxides and aldehydes, which may damage cellular membranes, induce oxidative stress, and promote atherosclerosis and neurodegeneration. Key factors accelerating oxidation include:

• Exposure to oxygen
• Heat during storage or processing
• Light (particularly UV rays)
• Metal contaminants such as iron or copper

To mitigate these risks, high-quality omega-3 products are typically encapsulated in opaque packaging, fortified with antioxidants (e.g., vitamin E), and stored under refrigeration. Products with a strong fishy odor or taste are often indicative of oxidation and should be avoided.

Market analyses reveal alarming trends in product quality. A study evaluating 171 omega-3 supplements sold in North America found that over 50% exceeded permissible oxidation limits. Additionally, products designed for children were found to have significantly higher oxidation levels (14).

This means that formulation matters. Pick products which are formulated as capsules (not liquid) and without any taste or smell additives.

How Much Omega-3 Is in Your Supplement?

Omega-3 dietary supplements and prescription medications differ substantially in terms of regulatory oversight, manufacturing standards, and clinical validation. In the EU and U.S., dietary supplements are not required to demonstrate clinical efficacy or undergo rigorous quality control before market release, provided their labelling complies with food supplement regulations. This regulatory gap allows variability in composition, oxidation levels, and efficacy among omega-3 products.

The significant variability in the actual omega-3 content of commercially available dietary supplements were demonstrated in a study conducted in 2020 (15). As shown in the graph below, each bar represents a different product, showing what percentage of the labeled omega-3 amount it truly contains.

Only 3 out of 32 supplements meet or even exceed their stated content, the majority fall short, many delivering only 50% to 70% of what the label promises.

Such inconsistency raises concerns about quality control and consumer transparency in the supplement industry. For individuals relying on these products for cardiovascular or anti-inflammatory benefits, the discrepancy could mean subtherapeutic dosing and reduced clinical effectiveness.

My Omega-3 Index Results

In Lithuania we have a saying Batsiuvys be batų which very much compares to the English version - The cobbler's children have no shoes. That is how I felt when I saw my omega-3 index results shown below. This was the first time I have done this test, and now I wish I have performed it sooner.

My omega-3 index is 5.67%, which falls below the optimal range of 8–12%. While not critically low, it suggests suboptimal levels of EPA and DHA. My omega-6 to omega-3 ratio is 7:1, higher than the ideal range of 3:1 to 5:1. The arachidonic acid (AA) to EPA ratio is 14.1:1, once again above the recommended range of 2.5:1 to 11:1. On a positive note, my trans fat index is 0.64%, which is within the optimal range <1% —a sign of a diet low in industrial trans fats, which is beneficial for heart health.

I really thought I consume sufficient amount of omega-3 fatty acids... But as I always say during my lectures - if there is a laboratory test that you can do to check any parameters of your health - do it, and base your decisions on precise data, not on assumptions. Now I started using EPA/DHA at higher doses and trying to incorporate more fatty fish in my meals. Will check the progress in 2-3 month time. Highly recommend to check your omega-3 index as well!

Omega-3 fatty acids provide a range of scientifically proven health benefits, particularly in cardiovascular and cognitive domains. However, the efficacy and safety of supplementation depend heavily on the source, formulation, and manufacturing quality of the product. As you can see - I need it myself, will share some updates how are things going with my omegas in the near future. In the meantime, more on longevity coming soon, stay tuned!