Fish Oil Form. It Matters.
When we first started developing our fish oil product, our main concern was quality and purity of the fish oils used. From catching the fish, getting it pressed for oil, storing it, and then shipping it halfway across the world to be encapsulated, there’s great potential for things to go wrong. It’s no secret that there’s a huge variation in the quality of oils on the market, and we wanted to ensure ours was on the right side of the bell curve.
In performing our competition analysis to see what other companies were up to, we came across the following copy on Nordic Naturals site, a perceived leader in quality and purity in the fish oil industry.
This piqued our interest as we had also heard from others that the triglyceride form of fish oil was more readily absorbed and the “superior” form. Nordic’s website only posted one study, and we took the claims with a grain of salt until we could do our own research. Was there another important characteristic of fish oil besides the quality and purity of the oils? We were going to find out.
TWO TYPES OF FISH OIL SUPPLEMENTS ON THE MARKET
What we found out was that fish oil supplements are generally sold in two different forms on the market. Ethyl Ester (EE) and Triglyceride (TG). The overwhelming majority of fish oil supplements are sold in the ethyl ester form. What’s the difference?
By definition, fats and oils are complex organic molecules formed by combining three fatty acids with one molecule of glycerol. As such, triglycerides are the natural molecular forms that make up virtually all fats and oils in animals and plants. Fish Oil in its natural form is TG.
Ethyl Esters are created by reacting free fatty acids with ethanol. What this does is remove the glycerol backbone referenced earlier and substitute it with an ethanol molecule through a process called transesterification. Once this process occurs, the fish oil isn’t really an “oil” anymore, as the glycerol backbone has been removed. Now that it is bonded to an ethyl ester, it becomes its own lipid class.
By changing the fish oil into EE form, it is now more readily concentrated through the molecular distillation process, which isolates components through heat energy. Once the EE goes through molecular distillation it becomes what is commonly sold as “fish oil concentrate.” Ethyl Esters are so prevalent due to their ability to provide higher concentrations of EPA/DHA relative to the TG form. It’s possible to convert an EE back into triglyceride form through a process called glycerolysis, which removes the ethanol molecule and re-esterifies the EPA/DHA back to a glycerol backbone.
WHICH FORM IS BETTER?
This is the question we wanted an answer to. We understand “better” is relative but we were looking at things like bioavailability and TAG reducing ability. In looking at the research, we found that a large majority used the EE form. This was irrelevant to helping us solve which was better, and we needed to find research directly comparing the two forms. What we found was that although a few studies have showed similar absorption rates (posted below as well) – the overall evidence points to TG fish oils being better absorbed than EE.
MECHANISM OF ACTION
Dietary fish oil (triglycerides) is digested in the small intestine. The breakdown is spurred on by the pancreatic lipase, or enzyme secreted by the pancreas that is the primary lipase that breaks down dietary fat. The resulting hydrolytic activity (breakdown) turns the TG molecule into free fatty acids and a monoglyceride. These metabolic products are absorbed by your intestines which are then turned back into triglycerides in order to be eventually transported into your blood stream.
The breakdown of ethyl esters are slightly different. The action of the pancreatic lipase and resulting hydrolytic activity are still responsible for the breakdown, but the ethanol bond is more resistant to breakdown than the glycerol backbone of triglycerides. After breakdown, the result is fatty acids and an ethanol molecule. These free fatty acids, as mentioned above, need to be reconverted to TG form in order for them to be taken up into the blood stream.
What does this all mean in English?
In simple terms, TG fish breaks down in your body into fatty acids and a monoglyceride and then converted back to TG in order to be taken up into your blood stream. Ethyl esters that are broken down don’t have the resulting monoglyceride molecule that TG’s do. EE must get this glycerol substrate from another source, delaying its conversion to a TG in order for it to be taken up in your blood. The mechanism of action suggests that uptake of dietary fish oil is more efficient in natural TG form than in EE form. Here are some studies that helped us understand this process (as well as digging back into old college texts)
Digestion and absorption of polyunsaturated fatty acids. http://www.ncbi.nlm.nih.gov/pubmed/1768307
Physicochemical properties of lipids: new strategies to manage fatty acid bioavailability. http://www.ncbi.nlm.nih.gov/pubmed/15672466
Modification of the fatty acid composition of dietary oils and fats on incorporation into chylomicrons and chylomicron remnants. http://www.ncbi.nlm.nih.gov/pubmed/8881715
Lipolysis of menhaden oil triacylglycerols and the corresponding faty acid alkyl esters by pancreatic lipase in vitro: a reexamination. http://www.ncbi.nlm.nih.gov/pubmed/2313198
RESEARCH DIRECTLY COMPARING THE TWO FORMS
Research directly comparing the two forms provides the basis of substantiation for our conclusions. Each study below notes a benefit of using TG form over EE unless otherwise noted.
Enhanced increase of omega-3 index in response to long-term n-3 supplementation from triacyglycerides versus ethyl esters. http://www.ncbi.nlm.nih.gov/pubmed/21063431
Enteral absorption in man of eicosapentaenoic acid in different chemical forms. http://www.ncbi.nlm.nih.gov/pubmed/2828810
Bioavailability of marine n-3 fatty acid formulations. http://www.ncbi.nlm.nih.gov/pubmed/20638827
Human absorption of fish oil fatty acids as triacylglycerols, free acids, or ethyl esters. http://www.ncbi.nlm.nih.gov/pubmed/3358766
Comparative bioavailability of eicosapentaenoic acid and docasahexaenoic acid from triglycerides, free fatty acids and ethyl esters in volunteers. http://www.ncbi.nlm.nih.gov/pubmed/2144420
The enteral bioavailability of eicosapentaenoic acid and docasahexaenoic acid is as good from ethyl esters as from glyceryl esters in spite of lower hydrolytic rates by pancreatic lipase in vitro. http://www.ncbi.nlm.nih.gov/pubmed/8504143 (CN note: This study concluded that absorption was similar, but hydrolysis was more efficient with TG)
Dietary intake of fish vs. formulations leads to higher plasma concentrations of n-3 fatty acids. http://www.ncbi.nlm.nih.gov/pubmed/12848287
Absorption of the n-3 eicosapentaenoic and docasahexaenoic acids as ethyl esters and triglycerides by humans. http://www.ncbi.nlm.nih.gov/pubmed/1826985
(CN Note: This study found that absorption of TG vs. EE were similar. One possible reason is the high study dose used (28g) which might nullify absorption kinetic differences)
Moderate doses of EPA and DHA from re-esterified triacylglycerols but not from ethyl-esters lower fasting serum triacylglycerols in statin-treated dyslipidemic subjects: Results from a six month randomized controlled trial.http://www.ncbi.nlm.nih.gov/pubmed/21862301
Autoxidation kinetic analysis of docasahexaenoic acid ethyl ester and docasahexaenoic triglyceride with oxygen sensor. http://www.ncbi.nlm.nih.gov/pubmed/12036046 (For those that want the conclusion in English…omega-3 fatty acids in EE are less stable than in TG form and more readily oxidize)
Fish oil in its Triglyceride form offers clear benefits and advantages over the ethyl ester form.
As always, the work, research, thoughts, and opinions of experts like Alan help validate or reject the conclusions we draw.
Seeing the post below on FB helped us feel more comfortable in the direction we were heading in.