Omega-3
Fatty Acids in the Prevention and Treatment of Cardiovascular
Disease
10/25/2002
Epidemiological studies have correlated a high intake of
omega-3 fatty acids (FA) with a low incidence of coronary
artery disease (CAD). This has been documented in the Inuit
population of Greenland (1,2) as well as for the coastal
population of Japan (3 ). Furthermore, observations have
been made regarding the effect of increasing the intake
of fish on the risk of developing CAD (4). It has also been
demonstrated that dietary intake of omega-3 FA reduces the
risk of cardiac arrest (5). Controlled intervention trials
using omega-3 supplements have shown both a primary and
a secondary preventive effect in patients with CAD (6,7).
Atherosclerosis is the arterial disease responsible for
the development of cardiovascular disease and the pathophysiological
events leading to this disease are very complex. Indeed,
omega-3 FA have been shown to interfere in several of these
events in a positive way.
Elevated
serum lipids are an important risk factor for CAD, but the
therapeutic concept of cholesterol lowering alone has been
extended to encompass lowering LDL cholesterol and triglycerides,
while increasing the HDL cholesterol that attacks the so-called
lipid triad.
LDL
cholesterol is comprised of the transport particles carrying
cholesterol and triglycerides (TG) to their destinations
in the human body. If their load of triglycerides is high,
the particles become small and dense. These particles are
poorly handled by the LDL receptor mechanism, which keeps
them in circulation for a long time, then eventually makes
them end up in the subendothelial space of the arteries.
There, they become oxidised. This phenomenon initiates the
vascular inflammation process, which is very closely related
not only to the build-up of atherosclerotic plaques, but
also to the rupture of these pathological structures.
Omega-3
FA lower TG very effectively. Since TG themselves constitute
a risk factor and a reduction of the TG load to small, dense
LDL particles could change their physical properties and
re-establish a better affinity to the LDL receptor, this
therapeutic regimen could create a more comprehensive means
of reducing the effects of lipid risk factors. At the same
time, omega-3 FA has been shown to increase HDL cholesterol,
meaning the so-called reverse cholesterol transport system
is promoted at the same time.
The
inflammatory process in the arterial wall caused by oxidised
LDL may be alleviated by omega-3 FA. This is mainly due
to two defined effects of omega-3 FA on the immunological
mechanisms of the cell-mediated system: A reduction of pro-inflammatory
eicosanoids, and the prevention of white cell recruitment
by down-regulating the presentation of cell-adhesion molecules.
The first effect is mediated by a mechanism entailing that
if EPA is used as a substrate for the production of these
eicosanoids, the products will have a lower biological potency
than the substrate had been derived from the omega-6 series.
The net effect on inflammatory parameters will be to prohibit
the release of Interleukin-1 and Tumour necrosis factor,
two cytokines active in the local inflammatory process.
These may be important mechanisms for the long-term prevention
of atherosclerosis, meaning that a diet rich in omega-3
FA may have positive effects on the incidence of CAD.
Meanwhile,
it is well documented that a regular intake of omega-3 FA
reduces thrombocyte adhesion, and thus also aggregation,
preventing the build up of red thrombi. This is, in turn,
explained by the use of EPA as a substrate for eicosanoids,
in this case thromboxane, which is less active than when
omega-6 is used. Another effect is the reduction of vascular
tone, which is often elevated locally in patients with overt
atherosclerosis. Furthermore omega-3 FA also have a moderate
effect on elevated blood pressure, another risk factor for
CAD.
Last
but not least, omega-3 FA have anti-arrhythmic effects that
are probably mediated by the effect of changes in the cell-membrane
on ion channels. This may possibly explain the beneficial
and rapidly occurring effect of omega-3 FA in the DART study
(6). Another related effect is the normalisation of the
so-called heart-rate variability (HRV), which is seen in
patients treated with omega-3 FA (8,9). Decreased HRV is
associated with increased mortality in postmyocardial infarction
patients.
In
conclusion, the intake of omega-3 FA, preferably as fatty
fish or as a dietary supplement, may offer broad-scale protection
against the development of atherosclerosis. Based on a dietary
principle, this prophylaxis has been shown to postpone or
prevent what is usually perceived as normal ageing of the
arteries (10)
REFERENCES:
1. Dyerberg J et al. Eicosapentaenoic acid and prevention
of thrombosis and atherosclerosis. Lancet 1978;2(8081):117-119
2.
Kromann N and Green A. Epidemiological studies in the Upernavik
districts, Greenland. Acta Med Scand 1980;208:401-406
3.
Hirai A et al. Eicosapentaenoic acid and adult diseases
in Japan: epidemiological and clinical aspects. J Intern
Med Suppl 1989,225 (731):69-75
4.
Kromhout D, Bosschieter EB and de Lezenne Coulander C. The
inverse relation between fish consumption and 20-year mortality
from coronary heart disease. N Engl J Med 1985;312:1205-1209
1.
Siscovick DS et al. Dietary intake and cell membrane levels
of long-chain n-3 polyunsaturated fatty acids and the risk
of primary cardiac arrest. J Amer Med Assoc 1995;274:1363-1367
6.
Burr ML et al. Effects of changes in fat, fish, and fibre
intakes on death and myocardial reinfarction: diet and reinfarction
trial (DART). Lancet 1989;2:757-761
7.
Singh RB et al. Randomized, double-blind, placebo-controlled
trial of fish oil and mustard oil in patients with suspected
acute myocardial infarction: the Indian experiment of infarct
survival. Cardiovasc Drugs and Ther 1997;11:485-491
8.
Christensen JH et al. Effect of fish oil on heart rate variability
in survivors of myocardial infarction: a double blind randomised
controlled trial. Br Med J 1996;312:677-678
9.
Christensen JH et al. Heart rate variability and n-3 fatty
acids in patients with chronic renal failure - a pilot study.
Clin Nephrol 1998;49:102-106
10.
Newman WP et al. Atherosclerosis in Alaska natives and non-natives.
Lancet 1993;341:1056-1057
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