CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 8, September 2013
AFRICA
301
supplements from many other countries that do not have to
adhere to such strict regulations.
There was an improvement in the percentage (42% in 2012)
of supplements that met the arbitrary range of 90–110% for
EPA compared to the results of the previous survey (31% in
2009). With regard to DHA, there was a substantial increase in
the percentage of supplements with DHA content
>
110% (13%
in 2009 vs 35% in 2012). This might be attributed to increased
awareness of consumers regarding n-3 fatty acid intake and
the emphasis on the importance of DHA for neural and brain
development.
To increase the level of n-3 fatty acids in the diet with a fish
oil supplement may be expensive for the average South African
consumer. The current analysis shows that the majority of the
surveyed supplements will cost the consumer R60 to R150
(R2.01 to R5.00/day) per person per month to attain the daily
recommendation of 500 mg/day EPA + DHA, as stipulated by
ISSFAL. For a family of four it will cost R240 to R600 per
month, which makes fish oil supplementation unaffordable for
the average South African household.
Rancidity is a concern, especially in polyunsaturated fatty acid
oils such as fish oil. CDs were measured as an early indicator of
rancidity. Almost half of the supplements tested were in the early
stages of rancidity. Another concern is the peroxide levels of
the majority of supplements, which were higher than the levels
recommended by GOED
17
(
≤
5 meq O
2
/kg oil). Peroxide levels
are a measure of the oxidative rancidity of fats by determination
of the lipid peroxides present.
Rancidity or oil degradation occurs when unsaturated fats
are exposed to oxygen and become oxidised.
20
Fish oil is
prone to oxidation because of the presence of very long-
chain polyunsaturated fatty acids compared to saturated fat or
vegetable oils.
21
Research
21-23
has shown that dietary oxidised
fatty acids pose an increased atherogenic risk. According to
Turner
et al.
,
20
the deleterious effects of oxidised fats on lipid
and chylomicron metabolism, oxidative stress, inflammation,
as well as vascular function contribute to the increased risk of
atherosclerosis.
On average, fish oils contain 180 mg EPA and 120 mg
DHA (ratio of 1.5:1) per 1 000 mg. In our previous analysis,
the majority of EPA-to-DHA ratios of oils in the analysed
supplements were 1.51–2.5:1, while in the current analysis
more DHA was included in the supplements to supply oils with
a 1.1–1.5:1 ratio. It is also evident that some of the surveyed
supplements contained substantially more EPA and DHA per
1 000 mg oil compared with the 180 mg EPA + 120 mg DHA
of standard fish oil. These so-called concentrated fish oils
consist of EE which are the esterified products of fatty acids and
ethanol. This chemical process is known as trans-esterification
and involves the removal of the glycerol backbone of the TG in
fish oil by substituting it with ethanol.
By using fractional distillation, which removes short-chain
and saturated fatty acids from fish oil, it is now possible for
manufacturers of supplements to allow for selective concentration
of EPA and DHA to levels in excess of those found in natural fish
oils. Esterification is also applied to deodorise the fish oil. These
preparations are typically marketed as fish oil concentrates.
Through the process of glycerolysis it is possible to convert
EE back to TG. This process removes the ethanol molecule and
re-esterifies the EPA and DHA fatty acids back to a glycerol
backbone, resulting in the formation of re-esterified TG.
The digestion of EE is altered as a result of the absence of a
glycerol backbone. Enzymes such as pancreatic lipase hydrolyse
the fatty acids from the ethanol backbone in the small intestine.
Since the fatty acid–ethanol bond of EE is much more resistant
to hydrolysis by pancreatic lipase compared to the hydrolysis
of TG in the natural form, this may explain the reduced
bioavailability of EE. Because of the resistance to hydrolysis the
digestion and absorption of EE is significantly lower compared
to TG and phospholipids.
It is concerning that about a third of the surveyed n-3 fatty
acid supplements analysed contained EE. Pregnant women are
advised against the use of EE since the safety of EE during
pregnancy has not been established. In this study, we analysed
one supplement containing EE that specifically recommended
it to be used during pregnancy. During the digestion of EE, they
are converted back to TG and alcohol is released. Even though
the quantity of ethanol released in a typical dose of fish oil via
supplementation is small, at-risk groups such as alcoholics,
pregnant women and young children should refrain from using
n-3 fatty acid supplements that contain EE.
EE of fatty acids have shown toxicity
in vivo
24
and
in vitro
25
and are known to accumulate in major organs such as the heart,
liver, pancreas and potentially the placenta.
26
In a rat study,
27
it was observed that efficient fatty acid EE digestion in the
gastrointestinal tract may prevent toxicity, however, this was not
confirmed in humans.
At present no manufacturers indicate the form (EE, TG and or
rTG) in which n-3 fatty acids are present in capsules. The safety
of daily intakes of EE and/or rTG via n-3 fatty acid supplements
has not been confirmed in humans. EE and rTG are synthetic
molecules and are not found naturally in food or the human body.
In some countries (not in South Africa) fatty acid EEs are
used as prescription medication to reduce very high blood TG
levels (
≥
5.65 mmol/l). However, these preparations provide
pharmacological amounts of n-3 fatty acid EE and are used
under strict supervision of a physician who should be well
informed about the adverse effects the medicine might display.
These drugs are also subjected to rigorous testing through
three phases of clinical trials, as specified by the Federal Drug
Administration. However, the same procedures are not applied
to ensure quality, consistency and purity in dietary supplements.
By presenting n-3 fatty acid supplements in the form of EE
or rTG, it enables manufacturers to increase the concentration
of EPA and DHA in supplements. Our analysis has shown
that manufacturers are increasing the DHA content of fish oil
supplements to entertain the consumer’s demands for higher
DHA intakes. The benefit of such higher DHA intakes needs
further investigation.
A recent meta-analysis and systematic review
28
reported that
treatment with EPA or DHA showed diverse effects on high- and
low-density lipoprotein cholesterol (HDL-C and LDL-C). Both
treatments induced lower blood TG levels. However, DHA was
more often associated with both elevated HDL-C levels and
LDL-C levels. The increase in LDL-C is undesirable. On the
other hand, clinical trials elsewhere
29,30
indicated that fish oil
supplementation is associated with increased LDL-C particle
size or a shift in LDL-C particle distribution from small, dense
particles to larger less dense LDL-C particles, which are known
to be less atherogenic.
