The bioactive lipids responsible for the signs and symptoms of inflammation belong mainly to the omega-6 family and are represented by prostaglandins and leukotrienes. Antagonism of inflammation by omega-3 fatty acids has been demonstrated in animal models. Studies have shown that omega-3 fatty acids, particularly those in fish oil, can decrease leukocyte production of omega-6 prostaglandins and leukotrienes, as well as cytokines.1

In humans, there is evidence for preventive and therapeutic effects of fish-derived fats. For example, in Japan, a country where levels of fish consumption are considerably higher than in Australia and the United States, the prevalence of rheumatoid arthritis is about 0.4%, compared with about 1% in Australia and the US. This lower disease prevalence in Japan occurs in the context of higher prevalence of a genotype associated with increased susceptibility to rheumatoid arthritis.2

The association of decreased emergence of rheumatoid arthritis with increased fish intake is supported by results of a case–control study of women with the disease. Results indicated that fish consumption was higher in healthy controls than in the women with rheumatoid arthritis. Dietary estimations indicated that being in the top 10% of omega-3 fat intake (> 1.6 g daily) was associated with an approximate 70% decreased probability of having (seropositive) rheumatoid arthritis.3

Ecological and case–control studies provide evidence of associations between dietary fish intake and decreased disease occurrence. Only dietary intervention studies can provide direct evidence of a protective or therapeutic effect of omega-3 fatty acids. Therefore, it is significant that 13 double-blind, placebo-controlled studies with rheumatoid arthritis patients have found benefits from ingestion of fish oil. Not all outcome measures improved in all studies. Tender joint count was the measure which improved in most studies (9 of 11 studies), but other measures to improve were the duration of morning stiffness, grip strength, and time to fatigue.4 Also, there was an indication of an anti-inflammatory drug-sparing effect. It was apparent that 12 weeks was the minimum time at which effects were seen. The finding of a beneficial effect on tender joint count is supported by a meta-analysis.4

An assessment of the value of these results can be made from several viewpoints. When one considers that the median intake of the omega-3 fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) in these studies was 3.3 g daily, the therapeutic effect may seem modest. On the other hand, the subjects had long-standing disease (mean duration, more than 10 years) and the fish oils were taken in addition to a full range of anti-inflammatory and antirheumatic medication. Overall, it is clear that the effect is genuine and it is possible that the effect size may be larger in more favourable conditions such as early-onset disease, where there is little or no joint damage.

When considering whether subjects with rheumatoid arthritis may benefit from fish oil ingestion, an important consideration additional to arthritis therapy is the potential for collateral health benefits. Rheumatoid arthritis has a standardised mortality ratio ≥ 2, which is attributable mainly to increased cardiovascular mortality, and this has led to the conclusion that prevention of cardiovascular disease must be added to one of the aims of rheumatoid arthritis treatment.5 Thus, recommending use of dietary omega-3 fats in rheumatoid arthritis treatment is well justified for preventive effects in cardiovascular disease.