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Proposed Mechanism of Action:
Through recent research fish oil has
shown evidence of anti-inflammatory, antithrombotic, anitarrhythmic, and
anitatherogenic effects. This is most likely due to fish oil’s high dietary
composition of Ω-3 FA.
Arachadonic acid (AA) is converted into
the proinflammatory mediators prostaglandins and leukotrienes via the enzymes
cyclooxygenase (COX) and lipoxygenase (LOX), respectively. Ω-3 FA is
preferentially incorporated into cell membranes during high dietary intake,
competitively inhibiting the uptake of arachadonic acid into cell membranes. In
particular, EPA has close homology with AA, differing only in the presence or
absence of the n-3 double bond. This leads to decreased production of
AA-derived mediators, including decreased availability of AA for COX and LOX
enzymes and decreased expression of COX-2 and 5-LOX. This is responsible for
Ω-3 anti-inflammatory effect. Other hypothesized downstream effects include
suppressed production of proinflammatory cytokines and modulation of adhesion
molecule expression via alteration of gene expression.
Adapted from:
Practical Applications
of Fish Oil (Ω-3 Fatty Acids) in Primary Care
Research has given credence to this
mechanism by showing significantly decreased potent inflammatory markers, such
as leukotrienes, prostaglandins, interleukins, and tumor necrosis factor during
fish oil supplementation. The additional n-3 double bond can affect biological
activity, with EPA-derived leukotriene B5 possessing little of the
chemotactic or stimulatory effect on leucocytes of LTB4. Similarly,
thromboxane (TX)-A3 has little of the activity of TXA2 as
a vasoconstrictor and platelet aggregator.
Adapted
from:
Fatty Acids and Rheumatoid Arthritis
The main effect of Ω-3 FA in RA has been suggested to be
the reduction of tumor necrosis factor, interleukin levels, and other
anti-inflammatory mediators. Ω-6 on the other hand is a precursor to
prostaglandins, leukotrienes, and related compounds that have important roles in
inflammation and in the regulation of immunity. This effect is best exploited
through the synergistic effects of a higher intake of Ω-3 FA in conjunction with
lower dietary intake of Ω-6 FA so that the Ω-6 to Ω-3 balance approaches 1.
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