Pro- and anti-inflammatory cytokines in healthy volunteers fed various doses of fish oil for 1 year

Dietary supplementation with n-3 fatty acids from fish oil alleviates inflammation in various chronic inflammatory disease states. Reductions in the produc- tion of pro-inflammatory cytokines interleukin 1 b (IL- 1b), tumour necrosis factor alpha (TNF-a), and inter- leukin 6 (IL-6) have been seen in humans after short-term n-3 fatty acid supplementation. We investigated long- term effects of dietary n-3 fatty acids on circulating cytokine concentrations and on ex vivo stimulated whole-blood production of IL-1b, TNF-a and interleukin 1 receptor antagonist (IL-1Ra), the naturally occurring antagonist of IL-1. A total of 58 monks with a mean age of 56 years were randomized into four groups and their diets were supplemented with 0, 3, 6, or 9 g of fish oil, providing 0, 1·06, 2·13 or 3·19 g of n-3 fatty acids per day. Subjects received equal amounts of saturated fatty acids, vitamin E and cholesterol. Compliance was excel- lent and erythrocyte fatty acid profiles closely reflected the amounts of n-3 fatty acids ingested. In the group receiving 9 g of fish oil per day, no influence of n-3 fatty acids on circulating cytokine concentrations was observed relative to placebo. Endotoxin-stimulated whole-blood cytokine production was measured at 26 and 52 weeks after the start and at 4, 8 and 26 weeks after cessation of supplementation. In all groups, the production of IL-1b and IL-1Ra was higher during supplementation than afterwards. However, no differences in cytokine production were noted between the placebo group and the various treatment groups at any point in time. Our results suggest that long-term supplementation of fish oil does not affect ex vivo cytokine production in man.