Cytokines and matrix metalloproteinases

The proinflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), are known to have long-term deleterious effects on bone and cartilage.⁶ IL-1β stimulates PGE₂ production, and both IL-1β and TNF-α activate MMPs, the enzymes responsible for cartilage degradation. Furthermore, both IL-1β and TNF-α concentrations are elevated in canine osteoarthritis.^7,8 A number of in vitro and ex vivo studies demonstrate long-chain n-3 supplementation's ability to reduce the production of these proinflammatory cytokines. In vitro studies have shown that n-3 fatty-acid supplementation reduces MMP production.^9,10 Further- more, ex vivo studies demonstrate that dietary fish oil supplementation reduces TNF-α and IL-1β production in stimulated whole blood or polymorphonuclear leukocytes.^11-13 Long-chain n-3 fatty-acid supplementation's ability to suppress IL-1β and TNF-α synthesis is important because of these cytokines' roles in the inflammatory process.

Fish oil supplementation and arthritis

In addition, fish oil supplementation has been shown to improve the biochemical parameters associated with osteoarthritis.^21,22 These studies demonstrated that long-chain n-3 fatty acids reduced the inflammation associated with osteoarthritis and decreased the production of MMP, IL-1, 5-lipoxygenase, and cyclooxygenase-2, with no reduction in TIMP production. Similar findings have been observed in rodent studies in which osteoarthritis was induced.^23,24

Fish oil supplementation in canine osteoarthritis

A study recently conducted at the Colorado State University Veterinary Teaching Hospital evaluated the effects of fish oil on key biochemical markers in dogs with osteoarthritis.²⁵ Twenty-four dogs with confirmed osteoarthritis were referred for cruciate ligament repair. They were randomly assigned to one of two groups—a group receiving fish oil supplements or a control group. Beginning on day –7, the dogs were fed the specified diets until day 56 (63 days total). Plasma and synovial fluid samples were collected on days –7, 0, 14, 28, and 56. Samples were assayed for fatty-acid composition, MMP-2 and MMP-9, TIMP-2, and bicyclo-PGE₂ (the stable metabolite of PGE₂).

Numerous significant differences were observed. As expected, fish oil supplementation had significant effects on eicosapentaenoic acid and docosahexaenoic acid enrichment in plasma and synovial fluid as well as a corresponding reduction in arachidonic acid. A significant increase in TIMP-2 and significant reductions in MMP-2 and MMP-9 were also observed. Furthermore, plasma bicylco-PGE₂ was significantly reduced from point of entry due to diet (P = 0.0195). The study demonstrated that fish oil supplementation improves the biochemical parameters associated with canine osteoarthritis.