Triglycerides versus ethyl esters

It took some time and effort before scientists finally established that there is a difference in the ‘speed’ at which the two most consumed types of Omega-3 fatty acids, i.e. ethyl esters and triglycerides, are absorbed from the intestine.

If the type of Omega-3 fatty acids is significant in the absorption process we would obviously like to take the most easily absorbed form. Hence the intensive research into the biological availability of Omega-3 fatty acids in the form of triglycerides on the one hand and ethyl esters on the other hand.

Omega-3 supplements such as triglycerides and ethyl esters: characteristics

Triglycerides consist of three fatty acids bonded to a single glycerol molecule (see figure 1).

.

Figure 1. General triglyceride structure (three fatty acids linked to a single glycerol molecule)

In chemical terms this is referred to as the esterification of these fatty acids with a glycerol molecule. This is how Omega-3 fatty acids such as EPA and DHA are present in fish. A triglyceride derived from fish usually contains 1 EPA molecule (eicosapentaenoic acid) or 1 DHA molecule (docosahexaenoic acid) and 2 other fatty acids. Consequently, on average the Omega-3 content (EPA + DHA) derived from fish oil never exceeds 33%, the other 67% consists of other fatty acids.

Figure 2. Triglyceride consisting of three fatty acids (top: EPA; centre and bottom: palmitic acid, a saturated fatty acid)

The ethyl esters in Omega-3 fatty acids originate from triglycerides. They are formed as follows. The three fatty acids are separated from the glycerol molecule using ethanol (pure alcohol). This creates free, non-bound fatty acids that are able to react with ethanol. This reaction results in a new ester compound. Instead of being esterified to glycerol, the fatty acids are now esterified to ethanol and produce so called ethyl esters (see figure 3).
This method is applied to obtain fish oil with a high concentration (in excess of 33%) of Omega-3 fatty acids. In view of the fact that all fatty acids are separated from their glycerol molecule through the addition of ethanol, it is possible to separate the individual free fatty acid chains (EPA, DHA and the other non-Omega-3 fatty acids). This makes it possible to supply fish oil that contains up to 95% Omega-3 fatty acids and to produce 50%-90% pure EPA or DHA.

Figure 3. Ethyl ester from EPA (eicosapentaenoic acid)

Absorption of Omega-3 from the intestine

The absorption of triglycerides derived from fish or food supplements by the cells of the intestinal wall is not straightforward. These fats first need to be digested in the gut by enzymes such as lipases and hydrolases (see figure 2). The digestion process produces free fatty acids and monoglycerides (= glycerol molecules with 1 bound fatty acid). The intestinal wall cells easily absorb this type of fatty acid. Fatty acids in the form of ethyl esters also need to be digested by an enzyme called hydrolase (see figure 2). This enzyme ensures that the free fatty acids derived from ethyl esters are also absorbed by the intestinal wall cells.
During the next phase each intestinal cell creates new molecules with the help of monoglycerides and free fatty acids. These new chemical compounds are part of the triglyceride and phospholipid group. The latter are fats, which are part of the basic structure of each cell membrane.
During the last phase the intestinal cell gives the new fats a special coating so that they are ready to be transported in the bloodstream. The compound fats are referred to as chylomicrones. Chylomicrones contain both cholesterol and newly formed triglycerides and phospholipids. Once they have arrived in the bloodstream, long-chain fatty acids (such as Omega-3 fatty acids) are transported to their destination, i.e. the tissues.

Biological availability of Omega-3

Various conflicting theories on the absorption rate of Omega-3 fatty acids have been published. Some studies point to an improved biological availability (absorption rate) of Omega-3 fatty acids in the form of triglycerides. Other studies report that, with the same dose of Omega-3 fatty acids, the ethyl ester types produce equally high EPA and DHA plasma concentrations as Omega-3 fatty acids in the form of triglycerides.
But the matter has now been settled, as the scientific community has recently come to the conclusion that the conflicting data on the absorption of Omega-3 fatty acids is entirely due to the time at which the tests are carried out.1
There is, in fact, a difference in absorption speed between Omega-3 fatty acids derived from triglycerides and Omega-3 fatty acids derived from ethyl esters. Figure 3 provides a summary of the various studies during which this absorption speed was evaluated. Figure 3 proves beyond doubt that the type of Omega-3 fatty acids defines the speed at which they are absorbed.1
Figure 3a shows the EPA and DHA lymph concentration (triglyceride and ethyl ester form) in function of time in rats.2 Three hours after administration the EPA and DHA lymph concentration is highest for the triglyceride form. However, 24 hours after administration the amount of EPA and DHA in the form of ethyl esters is approximately twice as high as EPA and DHA administered as triglycerides. This absorption pattern is identical in humans. Within a period of 8 hours the amount of EPA in the blood (after a 1 g intake of EPA) is 7 times higher following the consumption of EPA as triglycerides, compared to the consumption of EPA as ethyl esters (figure 3b).3 After 24 hours, however, a comparable quantity of Omega-3 fatty acids as triglycerides or as ethyl esters is found in the blood. This points to equivalent biological availability. Figures 3c and 3d confirm this hypothesis. Volunteers who participated in these studies consumed 1.26 g EPA and 660 mg DHA per day as triglycerides and 1.06 g EPA and 640 mg DHA per day as ethyl esters.4

Omega-3 consumed as triglycerides or as ethyl esters does not have any effect on biological availability (absorption rate) after 24 hours. After that time the same amount of Omega-3 fatty acids is available to the body irrespective of the origin of these fatty acids, triglycerides or ethyl esters.


Figure 4. Absorption speed and biological availability of EPA and/or DHA after the consumption of these fatty acids as triglycerides and ethyl esters.

Finally:

During the initial 12 hours following the intake of Omega-3 fatty acids the EPA and DHA plasma concentration is the highest for Omega-3 fatty acids in the form of triglycerides, as opposed to the consumption of Omega-3 fatty acids as ethyl esters, in which the high plasma concentration is only reached, at the earliest, 12 hours after intake. This is a significant factor if these fatty acids are to be used for the prevention of heart failure.
Literature on the subject is quite clear and indicates that DHA in particular is important in the treatment of cardiac arrhythmia. Furthermore, the risk of heart failure is higher in the early hours of the morning. It is important, therefore, to have sufficient DHA in the bloodstream at this time of the day. This implies that Omega-3 fatty acids are best taken at bedtime (as a preventive measure against heart failure) and are preferable in the form of ethyl esters. Peak concentrations are reached approximately 12 hours later (early hours of the morning), the time at which a sufficiently high DHA concentration is indispensable. There is, however, another reason why ethyl esters are more beneficial for heart patients. It is a generally accepted fact that the amount of LDL cholesterol defines the risk of arteriosclerosis (atherosclerosis). If the heart patient is free from hypertriglyceridemy, the intake of Omega-3 fatty acids as ethyl esters will not lead to an increased LDL cholesterol level, whereas Omega-3 fatty acids as triglycerides would have that effect.5

This document is published by Verno Scientific

Literature:
1. Rupp H, Wagner D, Rupp T, Schulte LM, Maisch B. Risk Stratification by the “EPA+DHA Level” and the “EPA/AA Ratio” - Focus on anti-inflammatory and antiarrhythmogenic effects of long-chain omega-3 fatty acids. Herz 2004; 29:673–85.
2. Ikeda I, Imasato Y, Nagao H, Sasaki E, Sugano M, Imaizumi K, Yazawa K. Lymphatic transport of eicosapentaenoic and docosahexaenoic acids as triglyceride, ethyl ester and free acid, and their effect on cholesterol transport in rats. Life Sci. 1993;52(16):1371-9.
3. Lawson LD, Hughes BG. Human absorption of fish oil fatty acids as triacylglycerols, free acids, or ethyl esters. Biochem Biophys Res Commun. 1988 Apr 15;152(1):328-35.
4. Luley C, Wieland H, Grünwald J. Bioavailability of omega-3 fatty acids: ethylester preparations are as suitable as triglyceride preparations. Akt Ernährungsmed 1990;15:123–5.
5. Reis GJ, Silverman DI, Boucher TM, Sipperly ME, Horowitz GL, Sacks FM, Pasternak RC. Effects of two types of fish oil supplements on serum lipids and plasma phospholipid fatty acids in coronary artery disease. Am J Cardiol 1990; 66(17):1171-5.