Omega-3 Fish Oil Bioavailability: EE vs TG vs rTG

🧠Article Difficulty: Moderate
🕒12 minute read

This article directly examines the current science on the bioavailability of the 3 most common forms of Omega-3 fish oil used in supplements: Triglyceride (TG), re-esterified triglyceride (rTG), and ethyl esters (EE).

There are various opinion pieces online regarding potential bioavailability differences between the forms; therefore, in this article, I present all of the scientific literature that I was able to find on the topic to give you a clear idea of whether there is a meaningful difference between the different chemical forms found in supplements.

Navigation

• The different chemical forms
• How the different forms are digested
• Bioavailability of EE Omega-3
• TG vs EE bioavailability
• rTG bioavailability
• Importance of concentration
• Side effects between the different forms
• Why TG vs EE differences are overstated
• Summary
• Finding the right Omega-3

The different chemical forms

TG: Triglycerides are the natural fat form found in fish oil, consisting of three fatty acids attached to a glycerol backbone. This is the same structure as most dietary fats and the primary form in which fat is stored in the human body.

EE: Ethyl esters (EE) are produced by chemically converting natural fish oil triglycerides during purification, binding EPA and DHA to ethanol. This process allows omega-3s to be concentrated to high levels, after which they may be used as-is or converted back into triglycerides (rTG).

rTG (TGE): rTG are made by converting ethyl ester omega-3s back onto a glycerol backbone after concentration, resulting in a high-strength oil that is structurally a triglyceride again.

How the different forms are digested

TG and rTG are digested via pancreatic lipase, the same enzyme used to digest most dietary fats, producing free fatty acids and monoacylglycerols that are absorbed and metabolised by the body.

EE are digested differently and rely more on bile salt-stimulated pathways (carboxyl ester lipase). Because they rely more on bile salts, they are best taken alongside a fat-containing meal, as this stimulates the release of bile into the small intestine. This is why you will commonly see the recommendation on Omega-3 supplements saying ‘take with food’.

Bioavailability of EE Omega-3

The most heavily researched form of omega-3 supplements is the ethyl ester (EE), largely due to its use in prescription products and clinical trials. Clinical data show that EE-supplemented omega-3s are effective at increasing plasma EPA and DHA levels (1) and at reducing blood triglycerides, supporting cardiovascular health (2).

Because EPA and DHA are the biologically active components of omega-3s, increases in their plasma levels are consistent with the broader health benefits associated with omega-3 supplementation, including support for eye health, cognitive function, inflammatory regulation, and pregnancy, when taken at appropriate doses.

TG vs EE bioavailability

A large-scale systematic review concluded that the proposed hierarchy of rTG>TG>EE is not as meaningful as some authors have stated it to be, and may lack practical significance (3). More meaningful was the importance of consuming the Omega-3 supplements with a meal. 

When looking at the direct bioavailability comparison studies (of which there are few), these are the findings:

Yurko-Mauro et al., 2015 compared the effect of EPA and DHA matched TG fish oil and EE fish oil on blood plasma levels and red blood cell levels over a 4-week period, and found no significant difference between the types (4).

Similarly, a study from Nordøy et al., 1991 also compared blood plasma EPA and DHA levels between EE and TG omega-3 fish oils and also found no significant difference between the forms (5).

A third study from Chevalier et al., 2021, also monitoring blood plasma levels following EE and TG supplementation also found no significant difference (7).

The three studies above all directly compared EE with TG, and all three conclude no significant difference between the forms. So to answer the question, are EE omega-3’s inferior to TG, the answer is no they are not.

However, the three studies did not compare rTG. I was able to locate two studies that did directly compare rTG with EE and TG. 

rTG bioavailability

One study found that following 2 weeks of supplementation, rTG was more effective at raising plasma EPA and DHA levels than EE and TG (8).

Similarly, a 6-month trial found that rTG was more effective than EE for lowering blood triglycerides in patients who were prescribed statins (those with or at risk of cardiovascular disease) (9).

A third study reported that rTG increased the omega-3 index (EPA+DHA stored in red blood cell membranes) by approximately 15% more than EE at both 3 and 6 months, although both forms produced large and clinically meaningful increases in EPA and DHA (10).

Therefore, based on the three studies above, there is moderate evidence to suggest that rTG may have bioavailability benefits beyond EE and TG forms. However, the number of direct comparison studies is limited, and the existing studies were conducted in different populations and measured different outcomes. Therefore, while these findings suggest that rTG may offer some bioavailability advantages over EE and TG, more evidence is required to establish consistency and to what degree the difference exists.

For most typical supplement users, any difference is unlikely to be meaningful. However, rTG may be preferred for individuals requiring higher doses of Omega-3, such as those targeting reductions in blood triglycerides or cardiovascular risk. 

Importance of concentration

A potential confound with the first rTG vs EE study above is that the concentration of the EE omega-3 used to compare rTG against was only 50% (i.e., 50% of the total fish oil in the capsule was EPA and DHA). Interestingly, research has shown that stronger EE concentrations (i.e, greater EPA and DHA relative to the total oil in the capsule) significantly increase the bioavailability of EE fish oil supplements (11) and better reduce blood triglycerides than lower concentrations. Therefore, it’s advised you seek a fish oil with 60%+ EPA and DHA concentration. This is due to the non EPA and DHA oil in the supplement competing for limited enzyme availability. 

It is also important to note that the chemical form of omega-3 does not determine oxidation stability. Oxidation is primarily influenced by raw material quality, processing, antioxidant protection, and third-party testing rather than whether the oil is EE, TG, or rTG. It is worth selecting an Omega-3 that undergoes oxidation testing to ensure stability, as oxidation can degrade EPA and DHA and reduce the effective dose delivered to the body.

Side effects between the different forms

Research has found no difference in burping, altered taste, digestive discomfort, nausea, or bloating between EE and TG Omega-3 supplements (12).

Why the difference between TG and EE is overstated online

While there may be some difference between rTG compared to EE and TG, there appears to be no meaningful difference between TG and EE. A possible reason why this has become common in articles and marketing copy, is that there are a lot of studies on FFA (free fatty acids) vs. EE, which may then be misconstrued as TG vs EE. FFA is the actual fatty acid molecule, how it would appear after being broken down from a triglyceride. However, supplements can not be made of FFAs as they are chemically unstable, unpleasant to take, can cause digestive issues, and can not be suitably formulated into supplement form, so they are impractical as commercial omega-3 supplements. 

Summary

To summarize, all three chemical types of Omega-3 fish oil found in supplements effectively raise blood plasma EPA and DHA, and therefore are bioavailable. EE omega-3’s are the most common form of chemical oil in Omega-3 supplements as they represent an easy form of highly concentrated EPA and DHA. The claim that TG is superior to EE is largely not supported by bioavailability data. However, rTG may offer some bioavailability benefits beyond both TG and EE, which may be particularly suitable for those requiring higher doses of Omega-3’s such as for the treatment of cardiovascular disease. However, total EPA and DHA potency and concentration are more important than chemical form, so regardless of form, it’s worth selecting an Omega-3 with a high dose of EPA and DHA. For example, a 750 mg EPA and DHA EE or TG capsule will outperform a 400 mg EPA and DHA rTG capsule. Therefore, it’s best to focus predominantly on EPA and DHA content, third-party testing, cost, and product origin rather than simply the chemical form. To learn more about exactly how much EPA and DHA you should be consuming each day, read this article.

Thrive Ultra Strength Omega-3

At Thrive, we offer a highly potent 750 mg EPA & DHA per capsule Omega-3, using EE form at 63% concentration. This offers a very high dose of Omega-3, with 1 capsule per day being suitable for most people’s needs. Our Ultra Strength Omega-3 is designed for high potency while also offering good value to consumers. We also conduct rigorous third party testing for potency, heavy metals, oxidation, and contaminants, and publish the results for our customers so that you know you're getting the best possible Omega-3 available. For more on how Thrive Omega-3 compares to the best Omega-3 supplements in Canada, view our detailed comparison article.

Thrive Ultra Strength Omega-3

We are also currently working on an rTG formula, for those with very high Omega-3 requirements. This product will likely be launched at a higher cost to the consumer and is ideally meant for those with higher Omega-3 needs - such as for lower blood triglycerides. For most people, our Ultra Strength Omega-3 is the right choice.   

Finding the right Omega-3

If you're seeking the best possible Omega-3 for your needs, check out our detailed science-based comparison (currently being written).

Learn more about Omega-3's

For a deep dive into the science of Omega-3's, including daily target intake for EPA and DHA read this article

For a quick look at the science of EPA and DHA daily intake, read this article

About the Author:

Joe is a certified trainer, strength and conditioning coach, and nutrition coach. He holds a Bachelor of Science with Honours in Sport and Exercise Science, graduating with First Class standing. During his studies, Joe focused on human physiology and performance, and he applies this knowledge of exercise science to his work with Thrive. Joe is the co-founder of Thrive Protein, a Canadian family-run supplement company focused on clean, scientifically backed nutrition products, including protein powders, greens, and electrolytes.