Fish Oil Triglycerides
vs. Ethyl Esters
by
Michael Gross, MD, and Susan Klein, ND December 2009
Omega-3s from fish oil, eicosapantaeonic acid (EPA) and
docosahexaenoic acid (DHA) come to consumers in one of two forms:
triglycerides or ethyl esters. One of the most controversial and debated
quality issues surrounding fish oil is which form of fish oil 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 triglyceride. Over 98% of
all fats ingested are in triglyceride form.
Cost vs. Absorption
Ethyl ester forms of omega-3 fatty acid supplements are becoming more
prevalent in the market because of the cost: they are cheaper to produce
than triglyceride forms. The industry created ethyl ester because they
are a more malleable form than triglycerides. They have a much higher
boiling point, and are 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 concentrate the
omega-3 molecules, EPA and DHA. In this model sterility overshadows
efficacy
Studies have shown that ethyl esters are the least bio-available forms
of omega-3’s compared to TG forms and/or whole fish.(1) Once
purification is complete through the micro distillation process why
would the manufacturer leave them in an EE form – COST.
The process to convert fish oil EEs back to TGs is costly. Bulk oil
costs for TG concentrates are typically 30-40% higher than 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 the omega-3 fatty acid depends on the variables of the
distillation process but normally results in a 50-70% omega-3 solution.
(2)
The process of converting TGs to EEs is necessary from a technical
standpoint in the production of fish oil concentrates to purify the oil.
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).
Metabolism
While in the EE form, the glycerol backbone is missing. Therefore, the
fatty acids will find an available triglyceride backbone or 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 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.(4)
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 certainly a less efficient
absorption process compared with the direct intake of a natural form
triglyceride because the EE form must be reconverted in the body back to
a TG form. The delay in TG re-synthesis suggests that transport to the
blood is more efficient in natural TG fish oils in comparison to
EE.(5)(6)(7) 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.(8)
Just the Science
A bioavailability of different omega-3 formulations was reported by
Dyerberg (the father of fish oil), 95 et al. Seventy-two healthy
subjects were allocated to be given a reesterified 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. (9)
A similar study also concluded that only 20 percent of the omega-3s in
the standard ethyl ester from were absorbed, unless they were taken with
a high-fat meal, which raised the absorption level three-fold, to 60
percent.(10) In contrast, the absorption of other fish derived omega-3s
(EPA and DHA) in their natural triglyceride from 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
percent to 90 percent when taken with a high-fat meal.(11)
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 shown to be 48% and 36% better absorbed than EE forms, EPA
incorporation into plasma lipids was found to be considerably smaller
and took longer when administered as an EE.(12)
Omega-3 fish oils 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
forms. (13) The EE form of DHA was more reactive, and quickly oxidized,
demonstrating that EE fish oils are far less stable and more readily
product harmful oxidation products. (14) Furthermore, the stability of
oil containing DHA in phospholipid triglyceride, and EE form has been
assessed. After a 10-week oxidation period, the EE DHA oil decayed 33%
more rapidly. (15)
Side Effects: Ethyl Ester vs. Triglyceride
Ethyl Ester Form:
The ethanol in EE form MUST be filtered through the liver. As we have
just discussed, 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. Any
form of alcohol filtering through the liver runs the risk of side
effects.
The most common side effects: burping (thus the need for enteric
coating), infection, flu symptoms, upset stomach, a change in your sense
of taste, back pain, and skin rash. Indeed, the impact of ethanol
release from ethyl ester forms of fish oil can be 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 is paradoxically the clinical issue for
which this drug is prescribed). All of these side effects are a result
of the toxicity of the ethanol released form this highly concentrated EE
form.
Triglyceride Form:
NONE
Almost all Clinical Evidence showing Omega-3 benefits relate to fish
consumption. Fish are in a TG form. There are NO ethyl ester fish in
nature. Humans must consume fish oil in the same form as the fish to
receive the maximum benefits.
Ethyl esters have been in the human food chain approximately 20 years.
Triglyceride fatty acids have been eaten safely, and for great benefit,
for an estimated 600 million years.