CARDIOVASCULAR JOURNAL OF AFRICA • Volume 25, No 2, March/April 2014
86
AFRICA
Letter to the Editor
Adverse effects of ethyl esters or oxidation products in
omega-3 preparations?
Dear Sir
We read with interest the article by Opperman and Benade, titled
Analysis of the omega-3 fatty acid content of South African fish
oil supplements: a follow-up study.
1
We make the following
comments.
In humans, long-chain omega-3 fatty acids are required
in numerous cellular mechanisms and are converted in small
amounts from the plant-based precursor alpha-linolenic acid.
It therefore seemed paradoxical when we found that in patients
with dilative heart failure, the blood levels of eicosapentaenoic
acid (EPA) and docosahexaenoic acid (DHA) were reduced.
2,3
We concluded that a deficiency in highly unsaturated fatty
acids (HUFA) represents a key defect contributing to the rapid
progression of heart failure requiring replacement therapy.
4
It is
therefore important to assess whether dietary supplement and
pharmaceutical-grade omega-3 preparations vary not only in
environmental pollutants,
5
but also in adverse oxidation products.
Opperman and Benade
1
assessed differences in dietary
supplement fish oils available on the South African market.
Compared with their 2009 survey, almost a third of the
supplements contained ethyl esters (EEs), which appeared to be
associated with higher EPA and DHA levels. Although we share
their contention that the presence of EEs should be declared
on the supplement label, we do not see the evidence for their
statement that the safety of a daily intake of EEs has not been
confirmed in humans.
In a major prospective, randomised clinical trial by the
Gissi-Hf investigators,
6
EPA/DHA was administered as EEs
(omega-3-acid ethyl esters 90, Omacor
®
) manufactured as a drug
according to FDA and EMA regulations. Adverse drug reactions
did not differ from the placebo olive oil. Also the rate of
discontinuation was not different from a vitamin E supplement.
7
EEs are split in the gastrointestinal tract. When the intake of
EEs and triglycerides was examined in humans, no differences in
serum EPA and DHA levels were observed.
8
EEs can therefore
not accumulate in organs, as mentioned by Opperman and
Benade.
1
However, since EPA/DHA in the form of EEs appear to
be more prone to autoxidation, the safety of dietary supplements
containing EEs needs greater attention.
Did the authors find differences in the levels of peroxides
and conjugated dienes depending on the ester form? Did
they calculate the intake of peroxides and conjugated dienes
associated with a given EPA/DHA intake?
According to our recent study on 63 dietary supplement fish
oils from 13 countries,
9
the peroxide intake for 1 g of EPA +
DHA would be 8.6
±
6.1 times higher compared with omega-3-
acid ethyl esters 90. The intake of secondary oxidation products
measured as aldehydes would be 10.9
±
4.4 times higher. In
this context it is important to note that the ingestion of less
oxidised omega-3 supplements reduced circulating triglyceride
and cholesterol levels, as opposed to highly oxidised omega-3
capsules, which had a negative effect on cholesterol levels.
10
In view of the increasing evidence that the oxidation level of
omega-3 fatty acid supplements can be a health risk, we consider
it timely to change the perception that EPA/DHA is beneficial,
irrespective of the source and the presence of oxidation products.
Of particular concern is that the majority of fish oils exhibit a
peroxide content above the recommended level of the Global
Organisation for EPA and DHA Omega-3 (GOED), i.e.
>
80%
(South African market, photometric method),
1
89% (market
of 13 countries, photometric method),
9
and 93% (Norwegian
market, AOCS official method).
11
Heinz Rupp,
Karin G Rupp,
Experimental Cardiology Laboratory, Department of Internal
Medicine – Cardiology, Philipps University, Marburg, Germany
References
1.
Opperman M, Benade S. Analysis of the omega-3 fatty acid content of
South African fish oil supplements: a follow-up study.
Cardiovasc J
Afr
2013;
24
: 297
–
302.
2.
Rupp H, Rupp TP, Alter P, Maisch B. N-3 polyunsaturated fatty acids
and statins in heart failure.
Lancet
2009;
373
: 378
–
379.
3.
Rupp H, Rupp TP, Alter P, Maisch B. Inverse shift in serum polyun-
saturated and monounsaturated fatty acids is associated with adverse
dilatation of the heart.
Heart
2010;
96
: 595
–
598.
4.
Rupp H, Rupp TP, Alter P, Maisch B. Mechanisms involved in the
differential reduction of omega-3 and omega-6 highly unsaturated fatty
acids by structural heart disease resulting in “HUFA deficiency”.
Can
J Physiol Pharmacol
2012;
90
: 55
–
73.
5.
Bourdon JA, Bazinet TM, Arnason TT, Kimpe LE, Blais JM, White PA.
Polychlorinated biphenyls (PCBs) contamination and aryl hydrocarbon
receptor (AhR) agonist activity of omega-3 polyunsaturated fatty acid
supplements: implications for daily intake of dioxins and PCBs.
Food
Chem Toxicol
2010;
48
: 3093
–
3097.
6.
Gissi-Hf investigators. Effect of n-3 polyunsaturated fatty acids in
patients with chronic heart failure (the GISSI-HF trial): a randomised,
double-blind, placebo-controlled trial.
Lancet
2008;
372
: 1223
–
1230.
7.
GISSI-Prevenzione investigators. Dietary supplementation with n-3
polyunsaturated fatty acids and vitamin E after myocardial infarc-
tion: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo
Studio della Sopravvivenza nell’Infarto miocardico.
Lancet
1999;
354
:
447
–
455.
8.
Luley C, Wieland H, Grünwald J. Bioavailability of omega-3 fatty
acids: ethylester preparations are as suitable as triglyceride prepara-
