Different Types of Omega-3

When purchasing a fish oil supplement, there are several things that should be considered: the amount of omega-3 fatty acids EPA+DHA, the source of the fish oil (sustainability), quality of the experience (taste) and whether the fish oil is in triglyceride or ethyl ester form. In this article, you’ll learn:

  • What triglycerides and ethyl esters are
  • What the differences are between the two
  • How producing fish oils as triglycerides is costlier, but improves the final product
  • And more!

Isn’t all fish oil the same?
Let’s say you have two fish oil products and they have the same amount of EPA+DHA per serving and same flavour. How might they differ? They may differ in the chemical structure of that oil. Perhaps you’ve heard someone ask, “Is that fish oil in the triglyceride or ethyl ester form?”

Fish oil is in one of two forms; triglyceride or in the ethyl ester form.

What are triglycerides?
Triglycerides are made of three fatty acids (e.g. EPA and DHA) attached to a glycerol backbone. This is the molecular form that makes up virtually all fats and oils in both animal and plant species.
What are ethyl esters?
Ethyl esters are made of one fatty acid attached to one ethanol molecule. Generally, ethyl esters are not found in nature, and are only created through chemical synthesis.
How are triglycerides and ethyl esters different?
EPA and DHA in ethyl ester form have different chemical properties than EPA and DHA provided in the natural triglyceride form of fish oil. Both triglycerides and ethyl esters are “esterified forms,” which means that an ester link/bond holds the fatty acids onto their chemical backbone. The fatty acids in triglycerides are esterified to a glycerol backbone, whereas the fatty acids in ethyl esters are esterified to an ethanol (alcohol) backbone. This may seem inconsequential, but it is important.
If the oil in fish is naturally in the triglyceride form how are ethyl esters produced?
When fish is caught and the oil extracted, it is in the triglyceride form. To concentrate the amount of EPA and DHA the oil undergoes a conversion step in which the oil is changed from its natural triglyceride form into the ethyl ester form, this step is referred to as trans-esterification. During this process, the glycerol backbone of the fish oil (in the triglyceride form), is removed resulting in free fatty acids (FFA’s) and a free glycerol molecule. An ethanol molecule is then attached to each of the FFA’s, creating ethyl esters.
The resulting ethyl esters allow for the concentration of the omega-3 long chain fatty acids. This process ( called molecular distillation) allows for the selective concentration of EPA and DHA to levels greater than found naturally in fish The resulting ethyl ester concentrate of EPA and DHA is subsequently marketed and sold as “fish oil concentrate.”[1]. Most of the fish oil products on the market are in the ethyl ester form.
But, are all fish oil concentrates ethyl esters?
Manufactured ethyl ester concentrates can be converted back to the natural triglyceride form using enzymes in a process called glycerolysis. Food-grade enzymes separate the ethanol molecule from the fatty acid, creating a FFA and a free ethanol molecule.
When glycerol is reintroduced to the solution, the enzymes then re-esterify the fatty acids back onto a glycerol backbone, creating triglyceride oil. These oils are commonly referred to as re-esterfied (or reformed) triglycerides, which have the same structure to natural triglycerides but with higher concentrations of the desired fatty acids, EPA and DHA.
The process of converting ethyl esters back to triglycerides is costly, and is therefore bypassed by many fish oil manufacturers. In fact, the vast majority of fish oil concentrate softgels sold globally—including those sold in North America—are ethyl ester concentrates. Only a small percentage of fish oil concentrate softgels on the market are true triglyceride oils.
While most capsules sold on the market use oil in the ethyl ester form, liquid ethyl ester products are not as widely used. This may be due to the fact that it has been suggested that the ethyl ester oil has a more intense fishy flavour and may oxidize more rapidly when exposed to air compared to oil in the triglyceride form [2].

How do triglycerides work in my body, compared to ethyl esters?
While converting concentrated ethyl ester fish oil back to its natural triglyceride form increases manufacturing costs, clinical research suggests it may improves its bioavailability [3, 4].

Dietary fats are digested in the small intestine by the action of bile salts and pancreatic lipase. Bile salts break up fat globules into much smaller emulsion droplets, which increase the surface area where lipase can work to liberate two of the three fatty acids from the triglyceride, resulting in two FFA and a monoglyceride (one fatty acid attached to glycerol) [4].

FFA and monoglycerides then form micelles (fat droplets), which are absorbed by intestinal enterocytes, the absorptive cells lining the intestines.  Once inside the enterocyte, the FFA and monoglycerides are reassembled back into triglycerides. Carrier molecules called chylomicrons then transport the triglycerides into the lymphatic channel and finally into the blood [5].

The digestion of ethyl ester is slightly different, because they lack a glycerol backbone. In the small intestine, ethyl esters are emulsified by bile salts and hydrolyzed by pancreatic lipase. This hydrolysis releases the fatty acid from the ethanol backbone resulting in a FFA and an ethanol molecule.

Similar to triglycerides, the FFA liberated from ethyl esters are absorbed by enterocytes where they are converted to triglycerides so they can be transported in the blood. This step is straightforward with triglycerides, since they already contain a glycerol molecule that can be used to re-esterify the FFA back to triglycerides within intestinal enterocytes.

Ethyl esters contain ethanol and not glycerol, which means that the FFA must obtain a glycerol molecule from another source (such as dietary fat) within the enterocyte to become transformed into a triglyceride.

Once transformed, triglycerides are packaged into chylomicrons that transport the triglycerides into the lymphatic channel and subsequently into the blood.

It has been suggested that the metabolism of ethyl esters is less efficient than triglycerides. Pancreatic lipase hydrolyzes ethyl esters to a lesser degree and at a slower rate than triglycerides [6-9].

Which form of omega-3 fish oil is better absorbed by my body?
There is considerable debate about whether different molecular forms of EPA and DHA are similarly absorbed. Of course, fish contains omega-3 fatty acids in the natural triglyceride form—however, the vast majority of studies demonstrating the clinical efficacy of fish oil have used ethyl ester fish oil. Importantly though, most of these studies have not directly compared ethyl esters versus triglycerides in terms of clinical efficacy or absorption.

There have been several studies that have directly compared the absorption or bioavailability of ethyl ester and triglyceride oils. The longest study that’s been conducted to date is a 6 month long study in which the objective was to study the difference in bioavailability of fish oil in the triglyceride form vs fish oil in the ethyl ester form [4].

The study was a double-blind placebo-controlled trial involving 150 subjects investigating the effect of EPA and DHA given as a triglyceride concentrate, ethyl ester concentrate, or a corn placebo oil on the omega-3 index, a measure of red blood cell EPA and DHA levels [4].

After three months, the omega-3 index increased by 186% in the triglyceride group compared to 161% in the ethyl ester group, with the difference being statistically significant [4]. After six months, the omega-3 index increased by 197% in the triglyceride group compared to 171% in the ethyl ester group [4]. Furthermore, in a subset of these subjects, fasting serum triacylglycerol levels were found to be significantly reduced from baseline in the triglyceride group (but not the ethyl ester group) after three and six months of supplementation [4]. These results are extremely valuable, because they suggest that not only are cellular levels of EPA and DHA raised about 15% more effectively when consumed as a triglyceride concentrate versus an ethyl ester concentrate, but also that the bioavailability difference translates into more desirable biological effects [4].

How do I know if my omega-3 fish oil is an ethyl ester or a triglyceride?
Fish oil products available in Canada do not require labels to state whether they are in triglyceride or ethyl ester form. Since this information may not be easily accessible, the best way to find out what form your oil is in is to ask the manufacturer.
Fish oil in the triglyceride form offers numerous advantages over ethyl ester fish oil.  First, triglyceride oils are the molecular form found naturally in fish, and based on the longest study to date, a triglyceride fish oil is metabolized and absorbed more efficiently than an oil in the ethyl ester form [4].

You can rest assured that all NutraSea products are in the triglyceride form.

1. Breivik, H., H. G.G., and B. Kristinsson, Preparation of highly purified concentrates of eicosapentaenoic acid and docosahexaenoic acid. JAOCS, 1997. 74(11): p. 1425-29.

2. Sullivan Ritter, J.C., S.M. Budge, and F. Jovica, Oxidation rates of triglyceride and ethyl ester fish oils. Submitted to Food Chem (in review), 2014.

3. Dyerberg, J., et al., Bioavailability of marine n-3 fatty acid formulations. Prostaglandins Leukot Essent Fatty Acids, 2010. 83(3): p. 137-41.

4. Neubronner, J., et al., Enhanced increase of omega-3 index in response to long-term n-3 fatty acid supplementation from triacylglycerides versus ethyl esters. Eur J Clin Nutr, 2011. 65(2): p. 247-54.

5. Carlier, H., A. Bernard, and C. Caselli, Digestion and absorption of polyunsaturated fatty acids. Reprod Nutr Dev, 1991. 31(5): p. 475-500.

6. Lawson, L.D. and B.G. Hughes, Human absorption of fish oil fatty acids as triacylglycerols, free acids, or ethyl esters. Biochem Biophys Res Commun, 1988. 152(1): p. 328-35.

7. el Boustani, S., et al., Enteral absorption in man of eicosapentaenoic acid in different chemical forms. Lipids, 1987. 22(10): p. 711-4.

8. Krokan, H.E., K.S. Bjerve, and E. Mork, The enteral bioavailability of eicosapentaenoic acid and docosahexaenoic acid is as good from ethyl esters as from glyceryl esters in spite of lower hydrolytic rates by pancreatic lipase in vitro. Biochim Biophys Acta, 1993. 1168(1): p. 59-67.

9. Ikeda, I., et al., Digestion and lymphatic transport of eicosapentaenoic and docosahexaenoic acids given in the form of triacylglycerol, free acid and ethyl ester in rats. Biochim Biophys Acta, 1995. 1259(3): p. 297-304.