The role of fatty acids in the management of osteoarthritis

Oct 01, 2004

Osteoarthritis is a chronic and potentially debilitating disease involving the disruption of metabolic homeostasis within the articular chondrocyte. Specifically, osteoarthritis involves an increased ratio of cartilage-degrading enzymes (matrix metalloproteinases, or MMPs) to their normal inhibitors, tissue inhibitors of metalloproteinases (TIMPs). It is the imbalance of TIMPs and MMPs that contributes to the pathologic breakdown of cartilage. Dietary fatty acids can help to correct this imbalance by modulating the production of inflammatory mediators.

N-3 fatty-acid types

Dietary fats are an important component of canine diets. They supply a concentrated source of energy as well as essential fatty acids, such as linoleic acid and α-linolenic acid. Due to dogs' inability to produce these fatty acids and their metabolic need for them, linoleic acid and α-linolenic acid must be supplied in the diet. Furthermore, these fatty acids serve as substrates for further desaturation and chain elongation to longer 20- and 22-carbon fatty acids.

Vegetable oils—such as flaxseed, soybean, and canola oils—contain amounts of α-linolenic acid ranging from 7% to more than 50% of the oil's total fatty-acid content. Alpha-linolenic acid can be metabolized into the long-chain n-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid. However, the conversion rate of α-linolenic acid to eicosapentaenoic acid and docosahexaenoic acid is low. In dogs fed diets containing α-linolenic acid or fish oil at the same n-6:n-3 fatty-acid ratio, fish oil supplementation resulted in significantly greater eicosapentaenoic acid and docosahexaenoic acid enrichment in both the plasma and neutrophils than the group consuming the α-linolenic acid supplemented diet.1 Furthermore, even when α-linolenic acid was fed at levels of more than 20% of total energy, there was no docosahexaenoic acid enrichment in the plasma or neutrophils.1 The findings are similar in primates and people—studies reveal inefficient conversion of dietary α-linolenic acid to eicosapentaenoic acid.2-4 Even though α-linolenic acid and eicosapentaenoic acid are both n-3 fatty acids, they need to be considered separately because they're metabolized differently. The dietary n-6:n-3 fatty-acid ratio or the total n-3 fatty-acid content does not include the possible anti-inflammatory potential of a diet.5

Fatty acids and eicosanoid synthesis

Figure 1. Eicosanoid formation from 20-carbon chain n-6 (arachidonic acid) and n-3 (eicosapentaenoic acid) fatty acids. (Abbreviations: COX = cyclooxygenase, 5-LO = 5-lipoxygenase, PGE = prostaglandin E, and LTB = leukotriene B.)
The 20-carbon fatty acids—eicosapentaenoic acid and arachidonic acid—serve as precursors for biologic mediators, including the prostaglandins and leukotrienes (Figure 1). Most cells in the body produce prostaglandins, including chondrocytes and synoviocytes. Inflammatory cells, polymorphonuclear leukocytes, macrophages, and mast cells produce leukotrienes primarily. The arachidonic-acid-derived prostaglandin E2 (PGE2), which is normally present in small amounts, serves important physiologic roles. However, its production increases in inflammatory conditions such as osteoarthritis. PGE2 stimulates pain receptors and promotes additional inflammation. Leukotriene B4 (LTB4), also derived from arachidonic acid, promotes inflammation as well. On the other hand, prostaglandin E3 (PGE3) and leukotriene B5 (LTB5), the eicosanoid products of eicosapentaenoic acid, have markedly less biologic activity than those derived from arachidonic acid and are considered anti-inflammatory.