Omega-3
Fatty Acids and Rheumatic Disease
11/14/2002
Rheumatoid arthritis (RA) affects about 1% of the population
in the Western World. However, the clinical course of the
disease may be very different. Cold and humid climatic conditions
normally accentuate symptoms. It was therefore astonishing
to find that inhabitants of Greenland and the Faeroe Islands
had less rheumatic problems than one might have expected.
Of course, there may be genetic differences here since the
Greenland Inuits are different in many respects. However,
the people from the Faeroe Islands are certainly Caucasians.
A cohort study of these two populations revealed that RA
occurred with a prevalence similar to what is stated above.
However, the clinical picture and the long-term outcome
of the disease were quite different. Patients with a diagnosis
of rheumatoid arthritis and a history dating 10 to 20 years
back, were working full time in the fishing industry. Even
more interesting, x-rays of their hands did not show extensive
joint deformations as would have been expected in a Danish
population. Furthermore, the patients participating in the
study had only traces of inflammatory cytokines (IL-1 and
TNF) in plasma and very high concentrations of soluble cytokine
receptors. The Greenland inuits having access to virtually
unlimited seafood resources have an average intake of omega-3
FA ranging from 6 to 12 g daily.
The
most abundant polyunsaturated omega-3 fatty acids are EPA
and DHA. These fatty acids compete with the omega-6 arachidonic
acid (AA) for positions in the phospholipid membranes of
human cells. This is the basis for the immuno-suppressive
effects of EPA and DHA. Since EPA has a higher affinity
for the enzymes cyclooxygenase and 5-lipoxygenase, eicosanoids
of the 3- and 5-series will be produced upon stimulation
instead of the AA derived 2- and 4-series, which are potent
immunoactivators. The 3- and 5- eicosanoids are either non-active
or have a low biological potency. AA-derived eicosanoids
increase the immunological response to the same stimuli,
leading to enhanced cytokine production (Il-1 and TNF),
while EPA leads to a reduction (1). Very important for the
activation of the cell-mediated immune system are the so-called
adhesion molecules (ICAM-1 and E-selectin) essential for
the recruitment of inflammatory white blood cells. EPA,
but even more importantly, DHA have been shown to reduce
the presentation of ICAM-1 and E-selectin, probably by interaction
related to transcription.
Several
controlled studies have convincingly demonstrated the positive
effects of omega-3 FA in RA. Two reviews have been published
summing up the data acquired in this field to date (2,3).
Therapeutic
effects of omega-3 FA on RA cannot be achieved merely by
increasing the number of fish meals. A high-quality omega-3
concentrate in a dose of 3g or more should be used daily.
No clinical response will occur immediately, but it will
start after 2 to 3 months and may even increase further
as a result of chronic use (4). At the same time, the intake
of red meat (high in AA and saturates) and vegetable omega-6
oils should be restricted (1). Olive and rape seed oil should
be used instead. One option for reducing concomitantly used
NSAIDs has been documented, which may spare patients from
gastro-intestinal adverse effects (5).
REFERENCES
1) Cleland
LG and James MJ. Rheumatoid arthritis and the balance of
dietary n-6 and n-3 essential fatty acids. Br J Rheumatol
1997;36:513-515
2) Fortin
PR et al. Validation of a meta-analysis: The effects of
fish oil in rheumatoid arthritis. J Clin Epidemiol 1995;48(11):1379-90
3) James
MJ and Cleland LG. Dietary n-3 fatty acids and therapy for
rheumatoid arthritis. Semin Arthritis Rheum 1997;27:85-97
4) Geusens
P et al. Long-term effect of omega-3 fatty acid supplementation
in active rheumatoid arthritis. Arhtr & Rheumat 1994;37:824-829
5) Lau
CS et al. Effects of fish oil supplementation on non-steroidal
anti-inflammatory drug requirement in patients with mild
rheumatoid arthritis - a double-blind placebo controlled
study. Br J Rheumatol 1993;32:982-989
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