Omega-3 Supplements: Triglycerides, Ethyl Esters, or Phospholipids?
Not all marine-derived Omega-3 supplements contain the same ingredients. The differences go beyond the concentration and percentages of bioactive Omega-3s (EPA and DHA) and also involve their chemical form—a characteristic that determines the human body's ability to absorb them and deliver them where they are most needed. Which is better: triglycerides, ethyl esters, or phospholipids? Should you choose fish oil, krill oil, or microalgae oil? Let's find out!
Omega-3 EPA and DHA supplements occupy a significant share of the market. Their ingredients cater to different consumer needs; alongside traditional fish oil products, there are supplements with krill oil (useful, for example, for those allergic to fish) or microalgae oil (suitable for vegans).
However, the source of EPA and DHA can do more than just meet consumer preferences, as it also affects the bioavailability of the Omega-3s in the final supplement.
Unfortunately, this characteristic hasn’t always been given due consideration. Yet, the absorption of polyunsaturated fats is a complex process, and the benefits of supplementation may depend on the bioavailability of EPA and DHA.
What determines Omega-3 bioavailability?
Bioavailability is one of the factors that determine how much of a nutrient is actually available to the body, and this principle applies to Omega-3s as well.
In a strict sense, bioavailability refers to the speed at which a substance is absorbed in the intestines and enters the bloodstream. More broadly, it refers to the amount of that substance that reaches the bloodstream or its target site of action.
The latter definition is more relevant when assessing how much of the ingested Omega-3s can perform their intended function. This is why the Omega-3 Index—the percentage of EPA and DHA relative to total fats in red blood cell membranes—is often measured. It is from cell membranes that Omega-3s perform many of their renowned biological functions.
Bioavailability, in turn, depends on several factors. For Omega-3s in dietary supplements, their chemical form plays a crucial role.
Triglycerides, Ethyl Esters, and Phospholipids: EPA and DHA in Dietary Supplements
Yes, because within their sources, Omega-3s can be bound to different molecules.
As mentioned, the primary raw materials for EPA and DHA supplements are oils derived from fish (particularly cod liver and fatty fish like salmon and sardines), Antarctic krill (Euphausia superba), and microalgae (especially species of Schizochytrium).
These sources differ in both the quantity and form of Omega-3s they contain:
- In natural fish oil, EPA and DHA are mainly present as triglycerides (TG) and, to a lesser extent, as free fatty acids (FFA);
- In concentrated fish oil (widely used to produce sufficiently concentrated EPA and DHA supplements), they are present as ethyl esters (EE) or re-esterified triglycerides (rTG, a form similar to natural fish oil TG but more concentrated in Omega-3s). Concentrated and re-esterified fish oil may also contain some EPA and DHA as diglycerides (DAG) and monoglycerides (MAG). While natural fish oils contain about 18% EPA and 12% DHA, concentrated oils can contain up to 90% EPA and DHA;
- In krill oil, EPA and DHA are present as TG, FFA, DAG, MAG, and, to a large extent, phospholipids (PL);
- Microalgal oils may contain FFA and TG, with some cases reporting enrichment with EE, rTG, and PL.
The differing bioavailability of these molecules depends on how they are processed and absorbed in the intestines.
After ingestion, these oils are broken down into small droplets and emulsified with bile acids to aid digestive enzymes in detaching Omega-3s from their carrier molecules. This allows EPA and DHA to be absorbed in the intestines, followed by their reassembly into triglycerides and incorporation into chylomicrons for transport into the bloodstream.
PL in krill oil appear to be the most bioavailable form. Their dual nature—partly fat-soluble and partly water-soluble—facilitates emulsification, while their ability to form mixed lipid particles enhances absorption. Omega-3s bound to PL also seem to integrate more easily into tissues than those bound to triglycerides.
Next in descending order of bioavailability are re-esterified triglycerides and natural TGs. Natural TGs are likely harder to break down than re-esterified ones. Additionally, rTG absorption may be aided by the presence of DAG and MAG.
EEs rank last in bioavailability. In vitro studies suggest this is partly due to lower efficiency of the enzyme that processes them before absorption, slowing uptake. Moreover, the EE form makes it harder to reassemble Omega-3s into TGs post-absorption.
Free fatty acids also appear more bioavailable than EEs, which may explain why some studies find krill oil more bioavailable than fish oil. However, FFAs are prone to oxidation and may cause gastrointestinal issues, so they are usually removed during production.
Health Effects
These findings suggest a recommendation: prefer oils where Omega-3s are in forms other than ethyl esters, and among those, prioritize phospholipids or re-esterified triglycerides.
However, another aspect must be verified: whether the higher bioavailability of phospholipids translates to greater health benefits.
Several studies have explored this, allowing a team led by Myeong Gyu Kim of CHA University (Pocheon, South Korea) to conduct a meta-analysis comparing the effects of krill oil and fish oil on blood triglyceride levels (a key benefit of Omega-3 supplementation).
The analysis of 64 randomized controlled trials found no significant difference in triglyceride, "bad" cholesterol (LDL), "good" cholesterol (HDL), or total cholesterol levels between krill oil and fish oil.
Published in 2020 in Nutrition Reviews, Kim and colleagues concluded that, rather than chemical form, “triglyceride reduction depends on the dose of Omega-3 fatty acids consumed.”
Thus, both fish oil and krill oil appear to be valid ingredients for high-quality Omega-3 products that deliver the desired benefits.
And what about microalgae oil? Often presented as an alternative to fish or krill oil for those who avoid animal products, a 2023 study in the European Journal of Nutrition suggests it’s also a viable option for omnivores.
References:
Cholewski M, Tomczykowa M, Tomczyk M. A Comprehensive Review of Chemistry, Sources and Bioavailability of Omega-3 Fatty Acids. Nutrients. 2018 Nov 4;10(11):1662. doi: 10.3390/nu10111662
García-Maldonado E, Alcorta A, Zapatera B, Vaquero MP. Changes in fatty acid levels after consumption of a novel docosahexaenoic supplement from algae: a crossover randomized controlled trial in omnivorous, lacto-ovo vegetarians and vegans. Eur J Nutr. 2023 Jun;62(4):1691-1705. doi: 10.1007/s00394-022-03050-3
Kim MG, Yang I, Lee HS, Lee JY, Kim K. Lipid-modifying effects of krill oil vs fish oil: a network meta-analysis. Nutr Rev. 2020 Sep 1;78(9):699-708. doi: 10.1093/nutrit/nuz102
Schuchardt JP, Hahn A. Bioavailability of long-chain omega-3 fatty acids. Prostaglandins Leukot Essent Fatty Acids. 2013 Jul;89(1):1-8. doi: 10.1016/j.plefa.2013.03.010
