have been asked whether the triglyceride (TG) form of omega-3 is superior and
safer than the ethyl ester (EE) form. The following Q/As address these issues.
Summary: A review of the scientific literature in which comparisons between the
EE vs. TG omega-3 forms were assessed in terms of bioavailability, safety, or efficacy indicate
the differences are minor, inconsequential, and cannot be judged to be
physiologically or clinically significant. Results
from comparative studies, in general, suggest that absorption of EPA and DHA from TG or from EE - and the biological outcomes over time-- are similar when
fish oil is routinely supplemented and a steady state has been achieved. Further,
the more sustained uptake of the EE form has been postulated to offer an
advantage in terms of heart health.
In short, the claim that
the TG form is, in any clinically significant way, more advantageous or
beneficial than the EE form is not supported by credible science at this time. In fact, the EE form has been used in
the majority of cardiovascular-related clinical trials showing benefit of
omega-3s, and is the choice for the National Eye Institute’s AREDS 2 trial now
in progress. The EE form enjoys a strong safety profile when taken as directed,
and a more highly concentrated, prescription EE product is approved by the FDA.
are composed of 3 fatty acids bound to a glycerol backbone. Unrefined fish oil
contains TGs with varying amounts of EPA and DHA as the fatty acids attached to
glycerol. One limitation of unrefined fish oil is that its low concentration of
omega-3 can make it impractical to obtain higher doses. Both the EE and commercially available TG forms undergo processing and
purification by various methods.
concentration of omega-3 in fish oil can be increased through ethylation. During
this process, the glycerol backbone of triglycerides is removed from EPA and
DHA and some of the shorter chain fatty acids are also taken out. The DHA and EPA free fatty acids are then esterified to form ethyl esters.
way to increase omega-3 content is to first use ethylation to concentrate DHA and EPA. The resulting ethyl esters are then broken down, and the free fatty
acids are reconverted to triglyceride. It should be
noted that both the EE and TG forms are classified as esters. In EE, the fatty
acids are esterified to an ethanol backbone, while in TG the fatty acids are
esterified to a glycerol alcohol backbone.
Suppliers of high quality fish oil store the oils in sealed containers flushed
with nitrogen to prevent light and oxygen exposure. Under these conditions,
with controlled temperatures, there is no difference in stability between the
EE and TG forms. Similarly, both forms are equally stable once the fish oil is encapsulated
in hermetically sealed softgels, packaged and stored properly.
majority of clinical studies examining supplemental omega-3s for various health
parameters have employed the EE form, according to omega-3 researcher Dr. Jing Xuan Kang, Associate Professor at Harvard, and as reflected
by a recent Mayo Clinic review (1).
The well known ‘GISSI’ secondary prevention trial is one example. In this study
of over 11,300 patients who had experienced recent heart attacks, those receiving
about 850 mg daily of combined EPA and DHA (in
the EE form) for 3 ½ years had a reduced risk of death from all causes plus
nonfatal heart attack and stroke, as well as significant risk reduction for
cardiovascular death, especially sudden death (2,3).
Also notable: the fish oil being administered in
the AREDS-2 trial now underway
contains the EE form of omega-3s (4). This trial will test the effects of 1,000 mg of combined EPA (650 mg) and DHA (350 mg) daily in age-related macular degeneration.
Results from comparative studies in
general suggest that absorption of EPA and DHA from TG or from EE - and the
biological outcomes over time – are similar when fish oil is routinely
supplemented and a steady state has been achieved.
from human studies comparing absorption of omega-3 fatty acids from TG vs. EE
have been somewhat conflicting: Several studies show no difference in
absorption (5-8), while others suggest that absorption of ethyl esters
may be lower (9-11). Differences in test materials, subjects, analyses
and duration make comparisons difficult. In general, however, studies that
found lower absorption rates for ethyl esters tended to be of short duration
(8-12 hours) and provided omega-3 as a single large dose. In studies where
omega-3 supplementation spanned several weeks or more, there were generally no significant differences in
however, reported that the bioavailability was higher for the TG form vs. the
EE form. It should be noted that these conclusions are
based on a relatively short-term (2 week) study at a fixed dose of approximately
3.5 g of EPA + DHA daily. An important point to consider when looking
at short term bioavailability is that the effectiveness of EE omega-3 on
objective health parameters such as lowering elevated blood triglycerides
begins about 1 month after starting supplementation, with maximum effectiveness
observed at about 2-3 months (13). Thus, any short-term differences in
absorption, metabolism, and overall bioavailability do not have a significant clinical impact, and most people taking fish oil supplements do so over the long term
rather than for only a short period of time.
there be a difference between short and longer term study findings regarding
EE? The process of EE hydrolysis appears to be slower than the action of
pancreatic lipase on TGs, which would explain the delayed rise in plasma or
tissue levels seen in some human studies (14).
in the TG form are acted upon by pancreatic lipase enzyme in the gut, while the
EE form is hydrolyzed (the fatty acid separated from its ethyl carrier) only
when taken up by endothelial cells of the intestinal lining.
above, the process of hydrolyzing ethyl esters is slower than that for
triglycerides, which are rapidly acted upon by pancreatic lipase in the gut.
Yet, the slower, more sustained uptake of EPA and DHA from EE could prove to be
advantageous. One way that these fatty acids are believed to help prevent fatal
arrhythmias is by inhibiting myocardial sodium and calcium ion channels, and
possibly certain potassium ion channels (15, 16). To do this, omega-3s must first be released
from tissue stores. One theory is that with ethyl esters, the slow release of
absorbed free fatty acids from lymph tissue means that more of these fatty
acids will already be mobilized and available in serum to help accomplish
electrical stabilization (17,18).
asked whether omega-3s in the EE form might pose more of a risk for free
radical formation than the TG form if the fatty acids from EE are not fully
converted to triglycerides in endothelial cells.
has been demonstrated that EE is fully converted to triglycerides (6). Secondly, dosing with EE has shown clear incorporation of omega-3 fatty acids into both triglycerides and plasma phospholipids within a week (19). Finally, the results from a study using high dose EE form, suggest
that this premise has little merit. Highly purified EPA and DHA as EE (4 grams
daily) led to no significant change in the oxidative status of plasma,
indicating no increase in oxidative stress at the high dose administered (20).
Further, the long term safety profile of EE omega-3 is
excellent (13,21-23). The
EE form (as the Rx product Lovaza®, formerly Omacor) is the
only omega-3 form approved by the FDA, and there was neither concern nor
controversy when the FDA reviewed and approved it.
No! A YouTube circulating
on the internet demonstrates that the EE form of fish oils is able to
dissolve a Styrofoam (polystyrene) cup while the TG form does not. The narrator of the demonstration inaccurately states that the effect of
EE on the Styrofoam is due to the “ethanol” in EE fish oil, and implies that
ingesting the EE form will have detrimental effects on the digestive tract and
in fact, no free ethanol in SBH fish oil softgels, nor does polystyrene in any way
resemble the human digestive tract. One
chemical property of a compound is its polarity (difference
in electrical charge between opposite ends of a molecule). Within the body, our
diet, and the environment, examples of both polar and non-polar natural
compounds abound. Chemistry students learn that polar compounds like ethanol and water will not dissolve non-polar materials like Styrofoam. Only
non-polar compounds can dissolve Styrofoam, which is also non-polar. "Like
dissolves like” as the saying goes.
The observation that the EE form is able to dissolve Styrofoam simply
reflects the fact that the polarity of EE is extremely similar to
Styrofoam. It means nothing more than
that, and it certainly does not suggest a concern for safety or toxicity. The EE
form of omega-3 fish oil has been judged to be very safe by every regulatory
agency that has reviewed the scientific data.
products OmegaAdvance, Macular
Omega-3 Companion, HydroEye and Optic Nerve
Formula include EPA and DHA as ethyl esters. A very small amount of Cod
liver oil is included in HydroEye as
a source of vitamin A, and its omega-3s are in the triglyceride form.
suggests 2 small softgels daily of OmegaAdvance for those who want to meet the American Heart Association’s recommended intake
of approximately 500 mg omega-3s daily. For those who wish to match the level
of 1000 mg combined EPA and DHA that is being examined in AREDS-2 clinical
trial, 2 softgels daily of Macular
Omega-3 Companion provides the required dose. Four softgels daily of OmegaAdvance also provides 1,000 mg of EPA/DHA.
the available evidence does not indicate any compelling difference between the
two forms with consistent intake. If
this changes, SBH will ensure that the form of omega oils in our products
reflect the most current science. The omega-3 fatty acids in SBH products are sourced
from a company providing the only USP-verified fish oil on the market.
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