Er is een groot verschil in kwaliteit van visolie die te koop is.

Goede visolie bevat de natuurlijke vetzuren, trilgyceriden (TG)  en/of fosfolipiden zoals die in vis zitten.

De meest verkochte visolie bevat echter veresterde vetzuren (EE). Door Transesterificatie (of omestering genoemd), waarbij de glycerolen in de triglyceriden vervangen worden door ethanol (alcohol) ontstaan uit natuurlijke visolie de ethyl esters. Dan wordt door moleculaire distillatie de hoeveelheden EPA en DHA vergroot. De nu verkregen visolie, bevat alleen ethyl esters en zeker geen vetzuren en wordt daarom ten onrechte visolie of geconcentreerde visolie (Fish oil concentrate) genoemd.

Uit verschillende onderzoeken (zie beneden) blijkt dat de EE aanzienlijk slechter opgenomen in het lichaam dan de TG.

Er is ook al onderzoek dat laat zien dat EE niets doet voor een betere bloeddruk in tegenstelling tot TG.

Een ander groot nadeel van EE is dat deze vetzuren ook veel sneller kunnen oxideren bij blootstelling aan licht, warmte of zuurstof dan de triglyceriden.

Volgens onderzoek zijn de meeste van deze producten die verkocht worden al geoxideerd en kunnen de voordelen van inname hiervan wel eens nadelen worden.

Als niets op de verpakking van het supplement vermeld staat weet u bijna zeker dat het EE betreft, triglyceriden of fosfolipiden zal zeker vermeld staan.

Hoe u zelf kunt controleren of het EE of TG zijn? Doe wat visolie in een polystyreen (piepschuim) potje. Als het EE's zijn ziet u binnen 10 minuten dat al redelijk wat van de olie door het potje heen lekt. Bij TG's of fosfolipiden gebeurt dat niet, hooguit minieme lekkage na 2-3 uur.

Inmiddels bestaat er ook een milieuvriendelijker algenolie, rijk aan omega-3 vetzuren, waarbij geen vissen gebruikt worden. Doch nergens is de juiste samenstelling van algenolie te vinden m.b.t. de omega-3 vetzuren die er in zitten. Gelet op het productieproces zullen dat dan bijna zeker ethyl esters zijn.

Fish Oil Triglycerides vs. Ethyl Esters: A comparative review of absorption, stability and safety concerns

Media exposure, scientific findings, and word of mouth have lead to a significant increase in fish oil supplementation over the past five years. The popularity of these supplements has also lead to an increased concern over product quality. The term “pharmaceutical quality” is typically associated with fish oils that are highly refined; however, the use of this term is not regulated and can be freely used by any branded fish oil product. Most experts associate pharmaceutical quality with products that comply with a fish oil monograph developed by the Council for Responsible Nutrition (CRN). The CRN Monograph established strict limits for environmental contaminants and oxidative quality parameters. Although the CRN Monograph represents an important step forward in the standardization of high quality fish oil it does not address every issue relating to quality. In particular the monograph does not differentiate between lipid classes (molecular forms). Although a product label may say “Fish Oil”, the chances are the product is not an oil at all, rather it is an alternate lipid class called a fatty acid ethyl ester (FAEE) or just EE for short. This differs in molecular structure from authentic fish oil which has a chemical structure known as a triglyceride (TG).

What are triglycerides?

The National Academy of Sciences defines fats and oils as “complex organic molecules that are formed by combining three fatty acids with one molecule of glycerol”. Triglycerides, or triacylglycerols, are the terms used to define this molecular structure combining three fatty acids (i.e. EPA and DHA) esterified (bonded) to a glycerol backbone. TGs are the natural molecular form that make up virtually all fats and oils in both animal and plants species. The omega-3 fats present in fish are almost exclusively TGs¹. Because free fatty acids are rapidly oxidized the TG structure offers greater stability to the fatty acids and prevents breakdown and oxidation².

What are ethyl esters, and how are they produced?

Fatty acid ethyl esters are a class of lipids that are derived by reacting free fatty acids with ethanol (alcohol)³. Called trans-esterification, the process involves a reaction whereby the glycerol backbone of a TG is removed and substituted with ethanol⁴. The resulting EE allow for the fractional distillation (concentration) of the long chain fatty acids at lower temperatures. Commonly referred to as molecular distillation in the fish oil industry this step allows for the selective concentration of the EPA and DHA fatty acids to levels greater than found naturally in fish3. The resulting EPA and DHA concentrate is typically the end product that is subsequently marketed and sold as “Fish Oil concentrate”. This situation presents several issues. Because the term fat or oil refers only to TG the EPA and DHA ethyl ester concentrate is, by definition, no longer a fat or oil and is incorrectly marketed as fish oil. Because EEs rarely occur in nature this affects the way they are digested and absorbed in the body.

Are all fish oil concentrates ethyl esters?

The vast majority of fish oil concentrates sold globally; including those sold in North America are EPA and DHA EE concentrates. A small percentage of fish oil concentrates on the market are natural TGs. In the manufacturing of EE concentrates it is possible to convert the fatty acids back to TGs using food grade enzymes. This process, called glycerolysis, removes the ethanol molecule and re-esterifies the EPA and DHA fatty acids to a glycerol backbone. These are commonly referred to as re-esterfied or concentrated triglycerides (rTGs). The process of converting EE to TG is uncommon due to cost constraints adding 30-40 % to the end bulk oil cost. Therefore, the only rationale for omitting the glycerolysis step is cost cutting.

Absorption and metabolism of natural triglycerides vs. ethyl esters

Dietary fish oil (triglycerides) is digested in the small intestine by the emulsifying action of bile salts and the hydrolytic activity of pancreatic lipase^1,5. The hydrolysis of a TG molecule produces two free fatty acids (FFA) and a monoglyceride (one fatty acid combined to glycerol)^1,5. These metabolic products are then absorbed by intestinal enterocytes and reassembled again as TGs^1,5. Carrier molecules called chylomicrons then transport the TGs into the lymphatic channel and finally into the blood⁶. The digestion of EEs is slightly different due to the lack of a glycerol backbone¹. In the small intestine it is again the pancreatic lipase that hydrolyzes the fatty acids from the ethanol backbone, however; the fatty acid-ethanol bond is up to 50 times more resistant to pancreatic lipase as compared to hydrolysis of TGs^7,8. The EEs that get hydrolyzed produce FFA plus ethanol. The FFA’s are taken up by the enterocytes and must be reconverted to TGs to be transported in the blood¹. The TG form of fish oil contains its own monoglyceride substrate; whereas EE fish oils, coupled to ethanol, do not. EE must therefore obtain a glycerol substrate from another source. Without a glycerol or monoglyceride substrate TG re-synthesis is delayed, suggesting that transport to the blood is more efficient in natural TG fish oils in comparison to EEs. Furthermore, this delay of TG re-synthesis in EE fish oils could cause an increase in free fatty acids and subsequent oxidation of those free fatty acids.

Bioavailability of triglycerides vs. ethyl ester fish oils

Numerous studies have assessed the absorption and bioavailability of EE fish oils. Most studies have measured the amount of EPA and DHA in blood plasma after ingestion of fatty acids as either TG or EE. Although a few studies have found that the absorption rate is similar between the two types of oils, the overall evidence suggests that TG fish oils are better absorbed in comparison to EE. Natural TG fish oil results in 50 % more plasma EPA and DHA after absorption in comparison to EE oils¹¹, TG forms of EPA and DHA were shown to be 48 % and 36 % better absorbed than EE forms¹², EPA incorporation into plasma lipids was found to be considerably smaller and took longer when administered as an EE¹³, plasma lipid concentrations of EPA and DHA were significantly higher with daily portions of salmon in comparison to 3 capsules of EE fish oil¹⁴ and in the rat, DHA TG supplementation led to higher plasma and erythrocyte DHA content than did DHA EE¹⁵ and a higher lymphatic recovery of EPA and DHA¹⁶.

One of the causative factors for the poor bioavailability of EE is a much greater resistance to digestive enzymes. As previously mentioned, during the digestive process, pancreatic lipase enzymes hydrolyse (cleave) the oils to liberate the fatty acids and EEs are much more resistant to this enzymatic process than the natural TG form⁷. A recent study assessed the specificity of five lipases towards EPA and DHA in TG and EE forms. All of the investigated lipases discriminated against both EPA and DHA more in EE than in the natural TG oils. In other words, both EPA and DHA were more easily hydrolysed from a TG than from an EE. EPA and DHA hydrolysis would be further compromised in individuals who suffer from a digestive disorder, such as pancreatic insufficiency. EEs should be avoided in such populations as they would likely cause malabsorption of EPA and DHA. Review of the existing literature provides evidence which, suggests that omega-3 fatty acids in the natural form of TGs are more efficiently digested and significantly better incorporated into plasma lipids in comparison to EE forms. Recently, two clinical trials have settled the debate of which fish oil form is more bio-available in humans; the ethyl ester (EE) versus the triglyceride (TG) form. The Dyerberg et al., 2010 study was done to demonstrate the differences in absorption levels of plasma EPA+DHA following consumption of various fish oil forms including EE and TG. They noticed that with about the same grand total of EPA+DHA administered to the EE and TG group compared to the placebo group, the EE form was given the lowest assimilation as a measure of bioavailability⁹. The mechanism of action was simple, in that, pancreatic lipase breaks down EE to a lesser extent than TG⁹. Since, the omega 3 fatty acid plasma profile can significantly be elevated with the consumption of TG versus EE fish oil; then clearly TG fish oil can be more effective. In another more recent study done by Neubronner et al., 2010 a similar comparison was made utilizing a different study design. A unique method of bio-availability was used (Omega 3 index) this method looks at the omega 3 FA (EPA+DHA) incorporated into the RBC membranes¹⁰. In comparison to the plasma levels measured in the Dyerberg et al., study, this method is even more specific because it can measure EPA+DHA at the level of the tissues¹⁰. Therefore, the outcome of this study showed a statistically significant incorporation of EPA+DHA in the RBC membranes via TG over EE by over 25 percent¹⁰. Therefore, in both of the above studies the overall bioavailability of omega 3 fatty acids with equal EPA+DHA in the form of TG showed to be more effective.

Ethyl ester fish oils are less stable, and readily oxidize

Omega-3 fatty acids in the form of EEs are much less stable than those in the natural TG form and readily oxidize. The oxidation kinetics of DHA as an EE or as a TG was assessed by measuring the concentration of oxygen found in the head space of a reaction vessel with both TG and EE forms¹⁷. The EE form of DHA was more reactive, and quickly oxidized, demonstrating that EEs are far less stable and can more readily produce harmful oxidation products¹⁷. Furthermore, the stability of phospholipid, triglyceride and EEs containing DHA has been assessed¹⁸. After a ten-week oxidation period, the EE DHA oil decayed 33 % more rapidly¹⁸.

Ethyl ester fish oil safety

During the digestive process, EEs are converted back to TGs by intestinal enterocytes1 which, results in the release of ethanol. Although the amount of ethanol released in a typical dose of fish oil is small, those with sensitivities to alcohol or those who are alcoholics should refrain from the consumption of EEs. Young children may also be more vulnerable to the toxic effects of ethanol even in small quantities. The exact amount of ethanol released from the EE fish oil is dependent on the exact profile of the fatty acids. For a typical 60 % omega-3 EE concentrate the amount of ethanol would be approximately 15 % by weight (see Figure 1). Additional concern exists regarding whether a small portion of EE is absorbed directly into the body¹⁹. Unlike TGs, the presence of EEs in the body has been found to potentiate cytotoxicity¹⁹. Several in vitro studies using purified lysosomes²⁰, purified mitochondria¹⁹ or intact Hep G2 cells²² have provided evidence for toxicity of EEs. Studies in animals have shown that ethanol released into the liver and pancreas can result in severe organ damage²³. Post mortem organ analysis has demonstrated that EEs are toxic mediators of ethanol induced cellular injury²⁴, and have been shown to induce pancreatic injuries when infused in vivo into rats²⁵. It is possible that efficient EE digestion in the GI tract could prevent toxicity³, but until further studies carefully examine EE oxidation, the potential for direct uptake of EEs, or EE absorption into the circulation via the stomach, EEs should be consumed with caution.

How can I determine if my fish oil is a natural triglyceride or an ethyl ester?

There is a simple, inexpensive and rapid method to determine if a fish oil supplement is in the TG or EE form by using polystyrene (Styrofoam) cups.

Method

Measure and place 20 ml of fish oil in a polystyrene cup. Place the cup on a plate to avoid any mess. Observe the cup after 10 minutes. If the fish oil has leaked significantly through the cup it contains EE. Due to their chemical composition, EE will actually eat straight through the polystyrene cup. This effect will become evident after just a few minutes; however, significant leakage is seen after 10 minutes. Natural TG fish oils placed in the same cup will not show leakage after 10 minutes. Natural TG fish oils may show leakage through the cup in very small amounts after 2-3 hours.

Conclusion

Fish oil supplements in the natural TG form offer numerous advantages when compared to those in the EE form: oils in a TG form are completely safe to consume, are naturally occurring, provide increased absorption, and are much more stable. Therefore, since TG fish oil can be more effectively absorbed then it can be potentially better at reaching therapeutic ranges in comparison to EE fish oil. While EEs are a source of omega-3 fatty acids, research shows that they are not as beneficial as TGs and additional research is required to fully assess potential toxicity. While some countries (e.g. Australia) have gone as far as banning the sale of EEs, other countries such as the US, Canada, and the UK allow the sale of the EE form and furthermore do not require any additionally labeling. These supplements are therefore often incorrectly labeled as “Fish Oil” and pose a risk to those who must avoid ingestion of alcohol.

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(25-09-2018)