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OBJECTIVE: To investigate effects of short-term oral treatment with seal oil in patients with psoriatic arthritis (PsA). METHODS: Forty-three patients with polyarticular PsA were randomized to receive oral treatment for 2 weeks with either seal oil or soy oil in a double blind controlled trial. Clinical and biochemical variables were assessed at baseline, after treatment, and 4 weeks post-treatment. Patients were allowed to continue nonsteroidal antiinflammatory drugs (NSAID) and disease modifying antirheumatic drugs (DMARD) during the study. RESULTS: Forty patients completed the study, 20 in each treatment group. Patients in the seal oil group reported a significant improvement in global assessment of the disease 4 weeks post- treatment (p < 0.01), and both groups showed a trend toward improvement in tender joint count, but the differences between the groups were not significant. There was a fall in the ratio of n-6 to n-3 fatty acids and in arachidonic acid (AA) to eicosapentaenoic acid (EPA) in serum after treatment with seal oil (p < 0.01). Twenty-one percent of all patients had elevated values of calprotectin in feces suggestive of asymptomatic colitis. CONCLUSION: Treatment with seal oil was followed by a modest improvement in patient's global assessment of the disease and a trend towards a decrease in number of tender joints. There was a shift in fatty acid composition in serum toward a putative antiinflammatory profile. Oral treatment with seal oil may have NSAID-like effects in PsA.