Osteoarthritis (OA) is a degenerative joint disease that affects more than 60% of older individuals. OA has been associated with an inflammatory response. Certain inflammatory signaling pathways may become activated in the presence of OA, including nuclear factor-kappa B (NF-κB). Pro-inflammatory cytokines, including interleukin (IL)-1 beta and tumor necrosis factor alpha (TNF-α), have been shown to participate in the activation of osteoclasts, which are the primary cells responsible for bone resorption. 

Oxidative stress has also been linked to OA. The presence of reactive oxygen species has been shown to alter chondrocyte homeostasis, cause a reduction in glycosaminoglycans, and has been linked to cartilage matrix degradation. Nitric oxide (NO) is produced by chondrocytes by inducible NO synthase (iNOS); this may lead to cellular damage and changes to surrounding cartilage. Concentrations of NO and expression of iNOS may be higher in the chondrocytes of individuals with OA. 

Polyunsaturated fatty acids (PUFAs) have two or more carbon-to-carbon double bonds. Their nomenclature is based on the position of where the first double bond is located. Omega-3 (n-3) PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA), have been shown to support a healthy response to inflammation and oxidative stress. Alternatively, omega-6 (n-6) PUFAs participate in pro-inflammatory processes in the body. Typical Western diets contain a higher amount of n-6 than n-3 PUFAs. 

A recently published review article by Oppedisano and colleagues explored the relationship between n-3 PUFAs and OA. An animal study investigated the effects of DHA supplementation on bone quality. Results indicated that in the initial phase of OA, DHA may play a protective role in the microstructure of subchondral bone. DHA was also shown to inhibit the protein expression of certain markers related to osteoclasts, including Cathepsin K and tartrate-resistant acid phosphatase. 

Oppedisano and colleagues also described studies that evaluated the effects of n-3 PUFAs on certain molecules, including IL-1 beta and matrix metallopeptidase 13 (MMP-13). The MMP-13 expression has been associated with increases in OA. One animal study showed that supplementation with an equal ratio of n-6 and n-6 PUFAs inhibited MMP-13 expression. A laboratory study showed that increasing concentrations of DHA inhibited both IL-1 beta and MMP-13 messenger RNA expression in a dose-dependent manner. 

Human studies outlined by Oppedisano and colleagues also indicated that supplementation with PUFA may influence markers related to OA. Several clinical trials have explored the impact of supplementation with n-3 PUFAs on pain associated with OA. The quality of OA was assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). The WOMAC scores were shown to be lower in the presence of n-3 PUFAs, along with analgesic use and overall pain scores. 

The authors of the study conclude that the potential protective role of n-3 PUFAs related to OA may be associated with their support of the body’s response to oxidative stress and inflammation. In addition, the ratio between n-3 and n-6 PUFAs may be of importance. N-3 PUFAs (such as DHA and EPA) are present in fatty fish. ALA can be found in beans, nuts, and flax seeds. 

By Colleen Ambrose, ND, MAT