Research & Education

Fish Oil Triglycerides vs Ethyl Esters

Omega-3s from fish oil are made up of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and are available to consumers either as triglycerides or ethyl esters. One of the most frequently debated quality issues surrounding fish oil is which form is best triglyceride (TG) or ethyl ester (EE)? What form are the long-chain omega-3 fatty acids (EPA and DHA) in when we absorb them from eating fish? The answer is the triglyceride form. In fact over 98% of all fats ingested from foods are in the triglyceride form.

Cost vs. Absorption

Ethyl ester forms of omega-3 fatty acid supplements are the more prevalent form on today's market because they are cheaper to produce than their triglyceride counterparts. The industry actually created ethyl esters because they are a more malleable form than triglycerides. This EE form has a much higher boiling point and is easier to work with when processing for supplement distribution. The main purpose of molecular distillation is to remove the industrial contaminants (e.g. heavy metals dioxins and PCBs) present in the commodity fish oils most supplement makers use and also to concentrate the EPA and DHA. In this model sterility overshadows efficacy. Studies have shown that ethyl esters are the least bioavailable forms of omega-3s as compared to TG forms and/or those of whole fish.1 Once purification is complete through the distillation process manufacturers leave them in an EE form due to cost. The process to convert fish oil EEs back to TGs is costly; with bulk oil costs for TG concentrates typically 30-40% higher than those of EE concentrates.

Micro Distillation

Ethyl esters are produced by reacting crude fish oil in a free fatty acid form with ethanol (an industrial alcohol) to form a synthetic substrate. Under a vacuum the mix is then heat distilled and the resulting condensate is a concentrated omega-3 ethyl ester solution. The concentration of omega-3s in the solution depends on variables within the distillation process but it is normally 50-70% omega-3.2 In the production of fish oil concentrates the process of converting TGs to EEs is necessary to purify the oil from a technical standpoint. However once this molecular distillation process is completed there is an option to leave the fatty acids in free form attached to an ethyl alcohol backbone or to reattach them to a glycerol backbone (triglyceride).


While in the EE form the glycerol backbone is missing. Therefore the fatty acids will find an available triglyceride backbone or they will take one from an existing molecule. If the latter occurs the molecule missing the backbone will look for another backbone and so on creating a domino effect. The free fatty acids are taken up by the enterocytes (gut epithelium) and must be reconverted to TGs in order to be transported in the blood.3

Fats are stored and transported in the body in triglyceride form. Research shows that after ingestion of an omega-3 fatty acid molecule in triglyceride form the fatty acids are cut from the glycerol backbone then the backbone and fatty acids are absorbed via the gut epithelial cells and immediately reattached to form the natural triglyceride.2 This is supported by our own understanding of human physiology; when ethyl esters are consumed they are processed in the liver where the ethanol is drawn off and the body must then rebuild the resulting free fatty acids back into a triglyceride. The EEs that get digested produce free fatty acids plus ethanol. This is a less efficient absorption process compared with the direct intake of a natural form triglyceride because the EE form must be reconverted back to a TG form in the body. The delay in TG re-synthesis suggests that transport to the blood is more efficient in natural TG fish oils as compared to EE.245 Furthermore this delay of TG re-synthesis in EE fish oils causes a release of ethyl alcohol and may subsequently produce oxidative stress by releasing free radicals in addition to releasing the ethanol.6

Just the Science

The bioavailability of different omega-3 formulations was reported by Dyerberg known as the father of fish oil. In his study 72 healthy subjects were given a re-esterified TG EE-free fatty acid fish oil or cod liver oil preparation for two weeks. The concentration of EPA and DHA was highest in the re-esterified TG group and lowest in the cod liver oil group.2 A similar study also concluded that only 20% of the omega-3s in the standard ethyl ester  form were absorbed unless they were taken with a high-fat meal which raised the absorption level three-fold to 60%.1 In contrast the absorption of EPA and DHA in their natural triglyceride form was substantially greater in either context (high fat or low fat): absorption of DHA was equally superior with either low-fat meals or high-fat meals while participants absorption of EPA increased from an already-high 69%to 90% when taken with a high-fat meal.1 Thus the evidence suggests that triglyceride (TG) fish oils are better absorbed in comparison to EEs. Natural TG fish oil results in 50% more plasma EPA and DHA after absorption in comparison to EE oils. TG forms of EPA and DHA were also shown to be 36% - 48% better absorbed than EE forms; EPA incorporation into plasma lipids was found to be considerably smaller and took longer when administered as an EE.7

EEs are more resistant to hydrolysis by pancreatic lipase than natural TG forms so patients with compromised digestive function would likely reap more benefits from the TG form than from EEs. Omega-3 fish oils in the form of EEs are much less stable than those in the natural TG form and readily oxidize. In a comparison of the oxidation kinetics of DHA as an EE or as a TG the EE form of DHA was more reactive and more quickly oxidized demonstrating that EE fish oils are far less stable and more readily produce harmful byproducts.4 Furthermore in a study that assessed the stability of oil containing DHA during a 10-week oxidation period the EE form decayed 33% more rapidly than the TG form.4

Side Effects: Ethyl Ester vs. Triglyceride

The ethanol in the EE form must be filtered through the liver where the ethanol is drawn off and the body must then rebuild the resulting free fatty acids back into a triglyceride. Any form of alcohol filtering through the liver runs the risk of side effects. The most common side effects are burping infection flu-like symptoms upset stomach alterations in sense of taste back pain and skin rash. In fact the impact of ethanol released from ethyl ester forms of fish oil is documented under the adverse events section in the prescribing information for Lovaza -the EE prescription form of fish oil. Some of these adverse events include body odor vomiting gastrointestinal disorder pancreatitis cardiac impact and hypertriglyceridemia (which ironically is the clinical issue for which this drug is prescribed). All of these side effects are a result of the toxicity of the ethanol released from this highly concentrated EE form.

On the other hand there are virtually no negative side effects resulting from the triglyceride form of fish oils. Almost all clinical evidence showing omega-3 benefits relates to whole food fish consumption with fats occurring naturally in the TG form. To receive maximum benefit from the crucial omega-3 fats humans should consume fish oils as close to their naturally occurring state as possible. Research shows that the TG form is more readily digested and assimilated than the ethyl esters which are a very recent addition to the food supply.

Michael Gross MD Susan Klein ND