Omega-3 supplements: better triglycerides, ethyl esters or phospholipids?

Not all marine-derived Omega 3 supplements contain the same ingredients. The differences are not limited to the concentration and percentages of bioactive Omega 3 (EPA and DHA), but also concern the chemical form in which they are present-a characteristic on which the human body's ability to absorb them and get them there, where it needs them most, depends. Which to prefer among triglycerides, ethyl esters and phospholipids? Better fish oil, krill oil or microalgae oil?Let's find out!

Omega 3 EPA and DHA supplements occupy a not insignificant share of the market. The ingredients with which they can be produced meet different consumer needs; alongside the more traditional fish oil products we find, in fact, supplements with krill oil (useful, for example, in case of fish allergy) or with microalgae oil (potentially suitable for vegans).

But the source of EPA and DHA can also do more than meet the demands of those taking them, because the bioavailability of the Omega 3s in the supplement that ends up on the market also depends on the source (and the processes it undergoes).

Unfortunately, this characteristic has not always been given due consideration. Yet, the absorption of polyunsaturated fats is a complex phenomenon, and on the bioavailability of EPA and DHA might depend the benefits obtained from supplementation.  

On what does the bioavailability of Omega 3 depend?

In fact, bioavailability is one of the factors on which the amount of a nutrient actually available to the body depends, and this principle also applies to Omega 3.

Understood in a narrow sense, bioavailability is the rate at which a substance is absorbed in the gut and enters the bloodstream. In a narrower sense, on the other hand, it is the amount of the substance that reaches the bloodstream or the site where it is supposed to perform its action.

Of the two, the second definition is the more interesting one when one wants to understand how much of the ingested Omega 3 can perform the function for which it was taken. This is why the parameter that is often measured to evaluate it is the so-called Omega-3 Index, i.e., the percentage of EPA and DHA out of the total fats in the membranes of red blood cells; it is from the cell membranes, in fact, that Omega-3s perform many of their renowned biological functions.

In turn, the bioavailability of a nutrient varies depending on several factors. In the case of Omega 3 found in dietary supplements, it is their chemical form that plays an important role.

Triglycerides, ethyl esters and phospholipids: EPA and DHA in dietary supplements

Yes, because, within their sources, Omega 3s can be found bound to different molecules.

As mentioned, the main raw materials for the production of EPA and DHA supplements are oils obtained from fish (in particular, from cod liver and fatty fish, such as salmon and sardines), Antarctic krill(Euphausia superba), and microalgae (particularly from Schizochytrium species).

These sources differ in both the amount and the form of Omega 3 present within them:

• Innatural fish oil, EPA and DHA are present mainly as triglycerides(TG) and, to a lesser extent, as free fatty acids( FFA);
  
  
• inconcentrated fish oil (widely used to produce sufficiently concentrated EPA and DHA supplements) are present in the form of ethyl esters(EE) or re-esterified triglycerides(rTG, a form similar to the TGs found in natural fish oil, but more concentrated in Omega 3). Concentrated and re-esterified fish oil may also contain a proportion of EPA and DHA in the form of diglycerides(Diacylglycerides, DGA) and monoglycerides(Monoacylglycerides, MGA). In addition, while natural fish oils contain about 18 percent EPA and 12 percent DHA, concentrated fish oils contain up to 90 percent EPA and DHA;
  
  
• Inkrill oil, EPA and DHA are present as TG, FFA, DGA, MGA, and, to a large extent, phospholipids(Phospholipids, PL);
  
  
• microalgal oils may contain FFA and TG, and cases are reported where they have been enriched with EE, rTG, and PL.
  
  

The different bioavailability of these molecules depends on how they are processed and absorbed in the gut.

After intake, all these oils are reduced into small droplets that are emulsified with bile acids to facilitate the work of digestive enzymes, which are thus able to detach the Omega 3s from the molecules to which they are bound. This allows the absorption of EPA and DHA in the intestines, which is followed by the re-assembly of the Omega 3 in the form of triglycerides and the formation of chylomicrons that will transport them into the bloodstream.

Krill oil PLs appear to be the most bioavailable form. Their dual nature-part fat-soluble and part water-soluble- facilitates their emulsification, while their ability to form mixed fat particles would facilitate their absorption. It also appears that PL-bound omega-3s are more easily incorporated at the tissue level than triglyceride-bound omega-3s.

They are followed, in order of decreasing bioavailability, byre-esterified triglycerides and natural TGs. Probably natural TGs are more difficult to "cut" than re-esterified TGs. In addition, the absorption of rTGs seems to be favored by association with DAG and MAG.

EEs are last in order of bioavailability. In vitro studies suggest that this is due at least in part to lower efficiency of the enzyme that processes them prior to absorption, which would slow the latter. But not only that, the EE form would also make it more difficult to reassemble Omega 3 in TG form after absorption.

Free fatty acids also appear to be more bioavailable than EE; this would account for the higher bioavailability of krill oil compared with fish oil found in some studies. However, these are easily oxidized forms and, therefore, at risk of gastrointestinal disturbances; therefore, they are generally eliminated during manufacturing processes.

The health effects

All this information seems to lead to one suggestion: better to prefer oils in which Omega 3s are present in forms other than ethyl esters and, among these, to prefer phospholipids or re-esterified triglycerides.

However, there is another aspect to be tested: whether the increased bioavailability of phospholipids also corresponds to increased benefits.

There is no shortage of studies that have investigated this, so much so that a group of experts led by Myeong Gyu Kim of CHA University (Pocheon, South Korea) was able to conduct a meta-analysis in which the effects of krill oil and fish oil were compared in terms of their ability to change blood triglyceride levels (one of the main benefits obtainable with Omega 3 intake).

The 64 randomized controlled trials included in the analysis found that the net difference in levels of triglycerides, "bad" cholesterol (LDL), "good" cholesterol (HDL) and total cholesterol was not significantly different depending on whether krill oil or fish oil was taken.

Based on these findings, published in Nutrition Review in 2020, Kim and colleagues concluded that rather than chemical form, "triglyceride reduction depends on the dose of omega-3 fatty acids taken in."

Thus, it appears that bothfish oil andkrill oil are viable ingredients for producing quality Omega 3 products with which to achieve the hoped-for benefits of supplementing these valuable polyunsaturated fats.

What aboutmicroalgae oil? It is often presented as an alternative to fish or krill oil for those who do not consume animal products, but according to a study published in theEuropean Journal of Nutrition in 2023, it is also a viable option for omnivores.

Bibliographic 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