*Arthritic Diseases*

Based on pre-clinical studies carried out on mice experimental models of inflammatory arthritis, krill oil was supposed to have a positive effect in reducing joint inflammation more so than fish oil. In a rodent model of rheumatoid arthritis, mice fed with a krill oil diet, in which EPA and DHA were 0.44 g/100 g of krill oil diet, exhibited a decreased infiltration of inflammatory cells at the joint level, and decreased hyperplasia at the synovial layer, compared to controls [132]. Moreover, in mice transgenic for human TNF-α, while the fish oil and krill oil had a similar effect on cholesterol levels, only krill oil reduced markers of fatty acid oxidation [133]. This is consistent with the observation that fish oil and krill oil are both rich in EPA and DHA, but only krill oil naturally contains antioxidants agents like astaxanthin [134].

In a previous randomized, double blind, placebo controlled clinical trials carried out on 90 patients affected by cardiovascular diseases and/or osteoarthritis and/or rheumatoid arthritis, the effect of krill oil on C-reactive protein (CRP) and on arthritic symptoms were evaluated. Patients received krill oil 300 mg/day or placebo for 30 days and CRP and osteoarthritis symptoms were recorded at baseline and at days 7, 14 and 30. Despite the short treatment, krill oil significantly reduced CRP levels even after 7 days (about 20% of CRP reduction versus an increase of about 16% in the placebo group), reaching a higher reduction (about 30% versus an increase of CRP levels of about 25% in the placebo arm) after 30 days. Moreover, krill oil significantly reduced symptoms such as pain by about 29%, stiffness by about 20% and functional impairment by about 23%, suggesting that a 300 mg daily dose of krill oil could represent a good strategy to counteract arthritic symptoms and inflammation period [135].

In a more recent randomized, double-blind, parallel-group, placebo-controlled study, 50 adult patients affected by mild knee pain received 2 g/day of krill oil or placebo for 30 days. After 30 days of treatment, patients treated with krill oil exhibited a significant reduction of knee pain both in sleeping and in standing and the range of motion in both knees was improved [136].

These promising pre-clinical and clinical studies led Laslett and co-workers to design and start a clinical trial named "KARAOKE" (Krill oil for OA of the knee), focused on the use of krill oil to improve knee osteoarthritis (OA). This study is currently ongoing and 260 Australian patients affected by knee OA characterized by pain, synovitis and effusion will be recruited and randomized to receive 2 g/day of krill oil or placebo every day for six months. Symptoms, functionality and knee structural abnormalities will be monitored at the beginning of the study and after 6 months using validated clinical methods and magnetic resonance imaging. In particular, the primary outcomes of this study are change in knee pain and in size of knee synovitis/effusion over 24 weeks. The secondary outcomes are improvement in knee pain over 4, 8, 12, 16 and 20 weeks [11].
