Triglyceride or ethyl ester form of fish oil?

Triglyceride or ethyl ester form of fish oil?

Customers often ask whether the triglyceride (TG) form of omega-3 is better and safer than the ethyl ester form (EE). This is what our article is about.

Summary:   A review of the scientific literature in which comparisons between the EE and TG forms of omega-3 were evaluated in terms of bioavailability, safety, or efficacy shows that the differences are insignificant, insignificant, and cannot be recognized as physiologically or clinically significant. The results of comparative studies show that the absorption of EPA and DHA from TG or EE is identical, especially when fish oil is regularly used for a long time.  

Simply put, the claim that the TG form is more beneficial or useful than the EE form is currently not supported by reliable science. Moreover, the EE form was used in most clinical trials related to cardiovascular diseases showing the benefits of omega-3 , and was the choice for the National eye Institute's AREDS 2 study. The EE form is also safer and more concentrated. EE omega is approved by the FDA. 

What is omega-3 in the form of ethyl ester (EE) and triglycerides (TG)?

Triglycerides consist of 3 fatty acids linked to the main chain of glycerol. Unrefined fish oil contains TG with varying amounts of EPA and DHA as fatty acids. One of the disadvantages of unrefined fish oil is that its low concentration of omega-3 makes it impossible to get higher doses. As the EE and commercially available TG forms undergo processing and purification by various methods. 

The concentration of omega-3 in fish oil can be increased by ethylation. During this process, the glycerol base and some shorter-chain fatty acids are removed from the EPA and DHA. Then the free fatty acids are esterified to form ethyl esters.

Another way to increase the omega-3 content is to first use ethylation to concentrate DHA and EPA . The resulting ethyl esters are then broken down and the free fatty acids are converted to triglyceride. It should be noted that the forms of EE and TG are classified as esters. In the EE form, fatty acids are esterified to the ethanol main chain, whereas in TG, fatty acids are esterified to the glycerol main chain. 

Is one form more stable than the other?

No. Suppliers of high-quality fish oil store the oils in sealed containers filled with nitrogen to prevent exposure to light and oxygen. Under these conditions, at controlled temperatures, there is no difference in stability between the forms of EE and TG. Similarly, both forms are equally stable if fish oil is enclosed in hermetically sealed capsules, packaged, and stored correctly.

Has the EE form been proven to be clinically effective?

The vast majority of clinical studies that examined additional omega-3s for various health parameters used a form of EE, according to omega-3 researcher Dr. Jing Xuan Kang, an assistant Professor at Harvard, and as reflected in a recent review of the Mayo clinic (1) , the Well-known secondary prevention study "GISSI" is one example. In this study of more than 11,300 patients who had suffered recent heart attacks, those who received about 850 mg per day of combined EPA and DHA (in the form of EE) for 3.5 years had a reduced risk of death from all causes plus non-fatal heart attack and stroke. , as well as a significant reduction in the risk of cardiovascular death, especially sudden death (2,3).

Is the TG form better absorbed than the EE form?

The results of comparative studies generally show that the uptake of EPA and DHA from TG or EE - and the biological results over time-are similar when the Supplement is taken regularly and over a long period of time.

One short-term study (12) reported that bioavailability was higher for the TG form compared to the EE form. However, it should be noted that these findings were based on a relatively short-term (2 weeks) study at a fixed dose of approximately 3.5 g of EPA + DHA per day. In contrast, a longer study published in 2016 found no significant differences in bioavailability with forms of TG and EE over a 3-month period (13). An important point to consider when considering short-term bioavailability is that the effectiveness of EE omega-3 on objective health parameters, such as reducing elevated blood triglycerides, begins about 1 month after starting supplementation, with maximum effectiveness observed in about 2-3 months. (14). Thus, any short-term differences in absorption, metabolism, and overall bioavailability do not have a significant clinical impact, and most people who take fish oil supplements do so for a long time, not just for a short period of time.

Why will there be a difference between short-term and long-term research results for EE? The process of hydrolysis of EE appears to be slower than the effect of pancreatic lipase on TG, which explains the slow increase in plasma or tissue levels observed in some human studies (15). The pancreatic lipase enzyme in the gut acts on omega-3 in the form of TG, whereas the EE form is hydrolyzed (the fatty acid is separated from the ethyl carrier) only when it is absorbed by the endothelial cells of the intestinal lining.

Can the form of EE lead to the formation of an excessive amount of free radicals? Is EE safe to take over a long period of time?

Can omega-3s in the form of EE pose a greater risk of free radical formation than the form of TG if the fatty acids from EE are not completely converted to triglycerides in endothelial cells.

First, it has been proven that EE is completely converted to triglycerides (6). Second, the use of EE showed a clear conversion of omega-3 fatty acids to plasma triglycerides and phospholipids within a week (19). Finally, the results of a study using a high-dose EE form showed that this has few benefits. Highly purified EPA and DHA as the EE form (4 grams per day) resulted in no significant change in the oxidative state of plasma, indicating no increase in oxidative stress when taking high dosages of the EE form.

Foam myth: do fish products pose an EE form health risk?

No! There are a lot of materials on YouTube that demonstrate that the EE form of fish oil can dissolve a Cup of Styrofoam (polystyrene), but the TG form can't. The videos say that the effect on the foam is associated with" ethanol " in the EE form of fish oil, and it is assumed that taking the EE form will have a negative effect on the gastrointestinal tract and liver. 

In fact, there is no free ethanol in the EE form of fish oil, and polystyrene does not resemble the human digestive tract in any way. One of the chemical properties of a compound is its polarity (the difference in electric charge between opposite ends of the molecule). There are many examples of both polar and non-polar natural compounds in the body, our diet, and the environment. Chemistry students know that polar compounds such as ethanol and water do not dissolve non-polar materials such as Styrofoam. Only non-polar compounds can dissolve Styrofoam, which is also non-polar.

The observation that the form of EE is capable of dissolving Styrofoam simply reflects the fact that the polarity of EE is extremely similar to Styrofoam. The EE form of omega-3 fish oil has been rated very safe by all regulatory agencies, including the FDA, which has taken into account a huge amount of scientific data.

Related materials:

1. Lee JH, O'Keefe JH, Lavie CJ, Marchioli R, Harris WS. Omega-3 fatty acids for cardioprotection. Mayo Clin Proc 83(3):324-32, 2008.
2. GISSI-Prevenzione. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction. Lancet 354:447-55, 1999.
3. Breslow JL. N-3 fatty acids and cardiovascular disease. Am J Clin Nutr ;83(6 Suppl):1477S-1482S, 2006.
4. AREDS-2 Investigators Brochure, www.areds2.org
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13. West, Annette L., Graham C. Burdge, and Philip C. Calder. "Lipid structure does not modify incorporation of EPA and DHA into blood lipids in healthy adults: a randomised-controlled trial." British Journal of Nutrition 116.5 (2016): 788-797.
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