Omega-3 Fatty Acids
Contains or consists of following acids/esters
Docosahexaenoic Acid
Docosahexaenoic Acid Ethyl Ester
DOCOSAPENTAENOIC ACID
Eicosapentaenoic Acid
Eicosapentaenoic Acid Ethyl Ester
Linolenic Acid(ALA; Alpha-linolenic Acid)
Omega-3-acid Ethyl Esters
Omega-3 Marine Triglycerides
They are obtained by esterification of concentrated
and purified omega-3 acids with glycerol or by transesterification
of the omega-3 acid ethyl esters with glycerol. The omega-
3 acids are from the body oil of fatty fish species coming from
families such as Engraulidae, Carangidae, Clupeidae, Osmeridae,
Salmonidae, and Scombridae. The acids consist of alphalinolenic
acid, moroctic acid, eicosatetraenoic acid, eicosapentaenoic
acid (timnodonic acid), heneicosapentaenoic acid,
clupanodonic acid, and docosahexaenoic acid (cervonic acid).
Adverse Effects and Precautions
The most common adverse effects of omega-3 fatty
acid preparations are gastrointestinal disturbances, particularly
at high doses, including nausea, eructation,
vomiting, abdominal distension, diarrhoea, and constipation.
There have been rare reports of acne and eczema.
Moderate increases in hepatic transaminases have
been reported in patients with hypertriglyceridaemia.
Preparations vary widely in concentration and purity.
Some preparations contain significant amounts of vitamins
A and D and long-term use could cause toxicity.
There is a theoretical possibility of vitamin E deficiency
with long-term use, although many preparations
contain vitamin E as an antoxidant. Concern has been
expressed over the high calorific value and cholesterol
content of some preparations.
Omega-3 fatty acids have antithrombotic activity and
should be given with caution to patients with haemorrhagic
disorders or to those receiving anticoagulants or
other drugs affecting coagulation. Hepatic function
should be monitored in patients with hepatic impairment,
particularly if receiving high doses. Caution may
also be required in asthmatic patients sensitive to aspirin
since omega-3 fatty acids may affect prostaglandin
synthesis
Effects on the blood. Omega-3 fatty acids have antithrombotic
effects and may increase bleeding. In a study1 in adolescents
with familial hypercholesterolaemia, epistaxis occurred in 8 of
11 patients treated with a fish oil supplement; prolonged bleeding
time was noted in 3 patients. There have also been case reports
of INR elevation and haematoma in patients taking fish oil preparations
with antithrombotics, although controlled studies
have failed to show an effect.
Effects on glucose metabolism. Although a deterioration in
glycaemic control has been reported in diabetic patients taking
omega-3 fatty acids and fish oil preparations, a meta-analysis1 of
studies in type 1 and type 2 diabetics, and a systematic review
of controlled studies in type 2 diabetics, both concluded that fish
oils effectively lowered triglycerides without a deleterious effect
on glycaemic control.
Uses and Administration
Omega-3 fatty acids are long-chain polyunsaturated
fatty acids containing 18 to 22 carbon atoms and a varying
number of double bonds, the first of which is in
the n-3 position. They are essential fatty acids and must
be obtained from the diet. They have an important role
as eicosanoid precursors and as components of cell
membranes; in humans, they compete with arachidonic
acid, an omega-6 fatty acid precursor. Their actions
in humans include a hypolipidaemic action (especially
a reduction in plasma triglycerides), an anti-inflammatory
action, and an antiplatelet effect. The main dietary
omega-3 fatty acids are eicosapentaenoic acid and docosahexaenoic
acid and are derived from marine fish;
other omega-3 fatty acids found in fish oils (defined in
terms of number of carbon atoms and number of double
bonds) include alpha-linolenic acid, moroctic acid, eicosatetraenoic acid, heneicosapentaenoic
acid, and clupanodonic acid.
Alpha-linolenic acid is also found in some plant sources
and is converted to a limited extent in the body to
eicosapentaenoic acid and docosahexaenoic acid.
Fish oils and purified omega-3 fatty acid preparations
are used in patients with severe hypertriglyceridaemia
and for secondary prevention after myocardial infarction. They are also marketed as dietary supplements, and are used in preparations for parenteral nutrition.
The preparations available vary widely in purity and
omega-3 fatty acid content, usually expressed in terms
of eicosapentaenoic acid and docosahexaenoic acid;
the fatty acids may be present as triglycerides or as
ethyl esters. Typical oral doses of fish oil for the treatment
of hypertriglyceridaemia are 5 g twice daily of a
preparation containing 17% eicosapentaenoic acid and
11.5% docosahexaenoic acid, or 2 to 4 g daily of a
preparation containing 46% eicosapentaenoic acid and
38% docosahexaenoic acid. For the secondary prevention
of myocardial infarction, 1 g daily of a preparation
containing 46% eicosapentaenoic acid and 38% docosahexaenoic
acid may be given. Eicosapentaenoic
acid ethyl ester may also be used alone in the treatment
of hyperlipidaemia, and to improve the symptoms associated
with arteriosclerosis obliterans.
Action. Interest in omega-3 fatty acids arose from observations
that populations with a diet rich in marine fish oils generally have
a low incidence of cardiovascular disease, while the incidence of
asthma, psoriasis, and auto-immune diseases appears to be lower
among Eskimos (Inuit) than in populations consuming a typical
western diet (although the incidence of haemorrhagic stroke and
epilepsy may be higher). Increased omega-3 fatty acid intake has
been suggested to underlie these differences, and fish oil and other
omega-3 preparations have therefore been promoted as dietary
supplements, with benefit suggested for many conditions.
The beneficial health effects of omega-3 fatty acids have been
attributed to their effects on eicosanoid balance, lipid metabolism,
and cell membranes. Essential fatty acids of both the omega-
3 and omega-6 series have an important role as components
of cell membranes and as precursors of eicosanoids (prostaglandins,
leukotrienes, and thromboxanes). Eicosanoids derived
from omega-3 fatty acids generally have anti-inflammatory,
antithrombotic, antiarrhythmic, and vasodilator effects, while
those derived from omega-6 fatty acids tend to be pro-inflammatory
and prothrombotic. Since omega-3 and omega-6 fatty acids
compete for the same enzymatic pathways, increasing the intake
of omega-3 fatty acids promotes the formation of anti-inflammatory
and antithrombotic eicosanoids, and may have beneficial effects.
Production of inflammatory cytokines such as interleukins
and tumour necrosis factor alpha may also be affected.
Cardiovascular disorders. Omega-3 fatty acids have a
number of actions that are potentially beneficial for patients at
risk of cardiovascular disease. They have a hypolipidaemic effect
due to inhibition of very-low-density lipoprotein (VLDL)
synthesis in the liver, and this particularly reduces triglyceride
concentrations. Heart rate may be reduced, and they also have
an antiarrhythmic effect, possibly due to a direct action on myocardial cells. Omega-3 fatty acids may also reduce blood pressure
in hypertensive patients, as well as increasing erythrocyte
deformability and decreasing blood viscosity. They appear to stabilise
atherosclerotic plaques, and may reduce progression of
atherosclerosis and of restenosis after percutaneous coronary
intervention.
Despite these benefits, the role of dietary or supplementary omega-
3 fatty acids for cardiovascular risk reduction remains
controversial. Epidemiological studies have suggested
that increased dietary fish intake is associated with a reduced risk
of fatal coronary events, and possibly also ischaemic
stroke, and there is also evidence for benefit with omega-3
fatty acid supplements, particularly for secondary prevention.
In the GISSI-Prevenzione study,long-term use of
omega-3 fatty acid supplements reduced the risk of fatal cardiovascular
events in a large group of Italian post-infarction patients
studied for 3.5 years, while the JELIS investigators reported
a reduction in primary and secondary cardiovascular events in
Japanese patients with hypercholesterolaemia. However, a systematic
review found no clear benefit from omega-3 fatty
acids, whether dietary or supplemental, in people with or without
cardiac risk factors.
Inflammatory and auto-immune disorders. Omega-3 fatty
acids have effects on several immunological and inflammatory
mediators and have been tried in a number of inflammatory
and auto-immune disorders. Beneficial effects have been reported
in rheumatoid arthritis and in glomerular kidney
disease, but results in kidney transplantation
have been mixed, and systematic reviews suggest no significant
effect on rejection episodes or graft survival. Some studies
have shown benefit in psoriasis, both with oral and
with intravenous dosage, but other studies found neither the
oral nor the topical route to be effective. Variable benefit has
been seen in inflammatory bowel disease although
this may relate to the different formulations used. In Crohn's disease,
a systematic review found that enteric-coated formulations
helped to maintain remission, but a subsequent randomised
study using a gelatin capsule formulation found no benefit.
Similarly, a systematic review found that conventional formulations
were not of benefit in patients with ulcerative colitis. Fish
oils have also been tried in lung disorders, although systematic
reviews have found little evidence of benefit in asthma; in
cystic fibrosis, limited benefit has been reported, with one
study reporting that fish oil supplementation reduced the need
for antibacterial treatment. Preliminary evidence also suggests
that omega-3 supplementation may reduce inflammatory markers
and improve dyspnoea in chronic obstructive pulmonary disease.
Malignant neoplasms. There is some evidence that the incidence
of cancer may be lower in populations with a high fish
intake, and animal studies have suggested that omega-3 fatty
acids may slow the progression of some cancers. However,
studies of omega-3 fatty acid intake and cancer incidence in humans
have given conflicting results, and systematic reviews
have found no evidence of a beneficial effect. It has also been
suggested that omega-3 fatty acids might be beneficial in patients
with cancer cachexia, but a randomised study found that eicosapentaenoic
acid supplementation was less effective than megestrol
acetate, and a systematic review found insufficient evidence
to establish whether eicosapentaenoic acid was more effective
than placebo.
Neurological and psychiatric disorders. Omega-3 fatty
acids concentrate in neuronal membranes and appear to have an
important role in brain development and function. Supplementation
during pregnancy and in infants has been investigated, but
there is little evidence that maternal supplements improve neonatal
outcomes, and only limited evidence of a benefit on growth
and neurodevelopment in preterm infants given milk formulas
supplemented with both omega-3 and omega-6 fatty acids.
However, in older children with phenylketonuria treated with dietary
restriction, omega-3 fatty acid supplements may improve
motor skills.
Omega-3 fatty acids have also been tried in the treatment of neurological
and psychiatric disorders. There appears to be a link
between deficient fatty acid intake and mood disorders, and
there is reasonable evidence to support the use of omega-3 fatty
acids as adjuncts in the treatment of depression, including possible
benefit in the depressive symptoms of bipolar disorder, but
further studies are needed to confirm this. Benefit has been
shown in schizophrenia, but results have been mixed and the role
of omega-3 fatty acids is not established. Some positive results
have been reported in hyperactivity and in autism, but further
studies are needed. Omega-3 fatty acids have also been tried in
dementia, but there is not yet sufficient evidence to recommend
them for prevention.
Eicosapentaenoic acid ethyl ester has been tried in Huntington's
disease, and may improve motor function, but this remains to
be confirmed.
SUMMARY
These promote foetal growth
Ensure optimal maturation of visual and cortical functions.
Improve cognitive function during lactation
Help improve birthweight
Reduce the risk of premature births
These give critical support in last trimester
Prolong gestation and reduces risk of pre-eclampsia.
Lipid lowering effects. these reduce Triglyceride synthesis and chylomicron secretion from intestinal cells and suppress hepatic fatty acid synthesis and triglyceride production, thereby limiting VLDL secretion.
These improve endothelial dysfunction by decreasing production of a growth factor by endothelial cells, resulting in diminished recruitment ,proliferation and formation of foam cells.
It reduces platelet activation ,aggregation and deposition of platelet antigens by reducing production of thromboxane.
It exerts anti-inflammatory effect through modulation of proinflammatory cytokine synthesis.
Treatment for 6 weeks reduced proteinuria in non-dialysed patients with chronic glomerular disease and improved renal functions in patients with IgA nephropathy ,thus retarding the chronic renal failure.
These reduce cardiovascular mortality in high risk haemodialysis patients by showing beneficial effects on lipids,platelets and blood pressure and may help to protect against atheroma.