There are three main forms of omega-3 fat found in supplements, including triglycerides (TG, the natural form of fish oil), ethyl-esters (EE, the concentrated form of fish oil) and phospholipids (PL, derived from krill oil). There are numerous studies comparing the absorption of these different forms, measured by their ability to raise the omega-3 index (the % of EPA and DHA in our red blood cell membranes) based on a standard manufacturer-recommended dose. rTG has proven to be the most effective, followed by EE, then TG and finally PL from krill oil.
The process of breaking down and utilising the fatty acids found in fish oil can be varied, depending on the type of fat consumed. The absorption of dietary fats is a complicated process that requires many steps including the transport of fat from the diet into the intestine cell, and then from the intestine cell to the lymphatic system and then to the blood.
Triglycerides from standard fish oil
Typically, fats in most food sources are found in their natural triglyceride (TG) form. TGs are generally associated with standard fish body or fish liver oil. These fats are comprised of three fatty acids (such as omega-3 EPA and DHA) linked to a molecule of glycerol. Without glycerol, free fatty acids can rapidly oxidise and therefore the glycerol backbone helps to naturally stabilise the fat molecules and prevent breakdown and oxidation. The addition of antioxidants such as vitamin E and encapsulation of oils also prevent fatty acids from oxidising.
Digestion of triglycerides
Digestion of fats requires the chemical breakdown of large molecules to smaller molecules. As TG molecules are too big to travel across cell membranes into the cells of the intestine, after consumption, bile and the enzyme lipase breakdown dietary fat in the small intestine. The lipase enzyme breaks the TG molecule into two free fatty acids and a monoglyceride (one fatty acid combined to the glycerol), which are then able to cross the membrane and enter the cells of the small intestine where they are reassembled again as TGs.
Once the TGs are reformed, they join with other fats and proteins to form carrier molecules called chylomicrons. Chylomicrons enable fats to move within the water-based solution of the bloodstream, allowing the TGs to be transported out of the cells of the small intestine through the lymphatic system (a transport network of clear fluid called lymph) and finally into the blood, where they are then delivered to various part of the body. The type of protein present in the outer lipid layer of these structures determines which cells in the body they will be delivered to.
The more recently developed re-esterified triglyceride (rTG) takes the EE form of omega-3 and reconverts it back to its natural TG form. This not only allows the delivery of concentrated omega-3, but ensures that absorption is optimised.
Fatty acids in ethyl-ester form are used to deliver high concentrations of omega-3 in a smaller volume of oil, to achieve therapeutic doses in fewer capsules. Ethyl esters are derived by reacting free fatty acids (such as omega-3 EPA) with ethanol. The fatty acids are removed from their natural glycerol backbone and then linked (esterified) with a molecule of ethanol.
Once this high concentration of omega-3 is achieved, it is also then possible to restructure the fat back to the natural triglyceride form, by re-attaching the fatty acids to the glycerol backbone, called re-esterified triglycerides.
Digestion of ethyl-esters
The digestion of ethyl-EPA fish oils is slightly different to TG due to the lack of a glycerol backbone. In the small intestine, it is again the pancreatic enzyme lipase that breaks the fatty acids from the ethanol backbone; the fatty acid-ethanol bond is more resistant to lipase compared to TGs, therefore slowing this process, and producing free fatty acids plus ethanol. The free fatty acids are then taken up by the cells of the small intestine but must then be reconverted to TGs in order to form chylomicrons, then leave the cell, enter the lymphatic system and then the blood.
As a result, the bioavailability may be compromised unless the supplement is taken with a fatty meal to ensure the presence of a glycerol ‘pool’ required for the free fatty acids to reform as TG; taking EE supplements with a high fat meal can improve bioavailability by as much as 13 fold. In addition, without glycerol, EE are more susceptible to oxidation than TG, so it is important to include an antioxidant such as vitamin E to protect the oil.
Whist at first glance, EE supplements may sound like they have potential absorption complications, it is worth noting that EE is most commonly used in large intervention studies and the generic form of choice for pharmaceutical products such as Vascepa (the pure EPA product used in the USA for triglyceride management). Although it is now recognised that rTG has superior bioavailability and is more stable than EE, the pharmaceutical forms of EE can take several years to bring to market and cannot simply be modified once they are licensed medicines.
After absorption, EPA is used by the body for a variety of functions including being used directly as energy, to help form lipoproteins (fat molecule transporters which carry cholesterol), to be made into the phospholipids that form cell membranes, to form fatty acid esters or remain as triglycerides stored in fat (adipose) tissue.
A major component of the structure of cell membranes, phospholipids are both water- and fat-soluble. One of the richest sources of phospholipids is from krill oil.
Phospholipids are comprised of two fatty acids joined to a phosphate group (such as choline) and a glycerol molecule. The fatty acid positioning (or ‘space’) is limited on the glycerol molecule. Generally, one of the fatty acids will be a saturated fat and the other an unsaturated fat such as a monounsaturated fat, or a polyunsaturated fat such as EPA or DHA. Simply put, EPA and DHA have to compete with other fatty acids, including omega-6 fats, for this space. As such, omega-3 in phospholipid form results in a low concentration of omega-3 EPA.
Digestion of phospholipids
As phospholipids are hydrophilic (water-soluble), the digestion of phospholipids (PL) does not fully depend on the bile and pancreatic enzymes. Individuals with digestive malabsorption issues may therefore be able to digest phospholipids more easily.
Whilst the structure of the fatty acids in krill are the key feature attributed to its high bioavailability, the amount of EPA and DHA provided by krill oil is in fact the lowest of all the omega-3 sources! Indeed, the concentration of omega-3 as both EPA and DHA found in krill oil is so low, that taking omega-3 in the form of krill oil does not effectively increase the omega-3 index and nor is it suitable for increasing EPA levels.
Which omega-3 form works best?
Using a triglyceride fish oil is adequate for anyone looking for general wellbeing support, but since the concentrations of EPA and DHA are not high, standard fish oil does not raise the omega-3 index sufficiently to offer significant health benefits. For more intensive support, an ethyl-ester form of omega-3 will allow very high doses of EPA and DHA to be achieved as concentration can be as high as 90% (compared to 18% in a standard triglyceride fish oil). High concentration is important because this influences absorption and increases the omega-3 index (% of EPA + DHA in red blood cells) and the targeting of benefits specific to a certain active (for example EPA). Purification and esterification also reduce to a minimum the volume of unnecessary fatty acids, waste products and impurities within the oil. Re-esterified triglyceride omega-3 concentrates the oil to a very pure form, like ethyl-ester, but mimics the natural triglyceride form to offer both high concentration and superior bioavailability.
Unlike lower concentration standard fish oil supplements, Igennus 70-90% EE and rTG supplements enable therapeutic blood plasma levels of omega-3 to be achieved. When taking EE omega-3, absorption can be enhanced by taking capsules with foods containing fat. For therapeutic use in specific health conditions, rTG is the gold standard – thus, it is also more expensive but has been proven to raise the omega-3 index to a greater extent and more rapidly than any other form of omega-3 – as with Pharmepa Restore.