Osteoarthritis (OA) is a painful and life-altering disease that severely limits the daily activities of millions of Americans, and it is one of the most common causes of disability in the world. With obesity on the rise and the world’s population living longer, the prevalence of OA is expected to increase dramatically in the coming decades, generating burdensome socioeconomic costs. This review summarizes current pharmaceutical, non-pharmaceutical, and prospective new treatments for OA, with primary focus on the dietary supplement avocado/soybean unsaponifiables (ASU). ASU modulates OA pathogenesis by inhibiting a number of molecules and pathways implicated in OA. Anticatabolic properties prevent cartilage degradation by inhibiting the release and activity of matrix metalloproteinases and increasing tissue inhibitors of these catabolic enzymes. ASU also inhibits fibrinolysis by stimulating the expression of plasminogen activator inhibitor. Anabolic properties promote cartilage repair by stimulating collagen and aggrecan synthesis via inhibition of inflammatory cytokines such as interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor, ERK, and prostaglandin E2. Chondroprotective effects are mediated by correcting growth factor abnormalities, increasing TGF-β, and decreasing vascular endothelial growth factor (VEGF) in synovial fluid. ASU also inhibits cholesterol absorption and endogenous cholesterol biosynthesis, which mediate reactive oxygen species pathology in chondrocytes. At the clinical level, ASU reduces pain and stiffness while improving joint function, resulting in decreased dependence on analgesics.
Avocado and soybean oils are used for manufacturing soap and the unsaponifiables fraction from these oils is termed avocado/soybean unsaponifiables (ASU). ASU has been tested in the management of OA. ASU contains phytosterols, β-sitosterol, campesterol, and stigmasterol, fat soluble vitamins, triterpene fatty acids and possibly furan fatty acids, but the identity of the active components in it is unknown . Several formulations of ASU are available on the market as supplements. Piascledine, which contains the unsaponifiables as one part from avocado and two from soybean, is a unique patented preparation . In articular chondrocyte cultures ASU may modulate NFκβ levels to inhibit inflammatory cytokines and stimulate collagen synthesis . Animal studies also support its benefits in OA.
A PubMed search in August 2015 with the words “avocado/ASU” and “osteoarthritis” and “knee” showed 25 entries of which five were human clinical trials on pain and function of OA in hip and knee (Table 1) . Literature on the human trials of ASU in hip and knee OA, and for the rationale of this therapy has been reviewed recently . It is pointed out that there may be a conflict of interest in these studies. Also, one should consider that soybean protein alone may be beneficial for OA and this complicates the interpretation of the benefits of ASU .
The effect of ASU on patients with hip (n = 50) or knee (n = 114) OA was examined in a randomised, double blind, placebo controlled, multicenter trial with a 6 month treatment period (Table 1) . After the 6 months its efficacy was greater than that of the placebo (P <0.001 for intergroup difference at month 6). The decrease in the Lequesne index (from 9.7 ± 0.3 to 6.8 ± 0.4) was significantly greater in the ASU group than in the placebo group (from 9.4 ± 0.3 to 8.9 ± 0.4). Fewer patients treated with ASU required NSAIDs (48 %) than those in the placebo group (63 %) (p = 0.054). The improvements appeared to be more marked in patients with hip than those with knee OA. Another similar study confirmed these findings . In yet another study, the effects of two doses (300 or 600 mg daily) of ASU were compared in patients with knee OA over 3 months (Table 1) . Both doses were effective. At day 90, NSAIDs and analgesics intake decreased to less than half in 71 % patients receiving ASU (300 mg or 600 mg) compared to 36 % in the placebo group (p <0.01). The Lequesne’s index dropped by 3.9, 2.9 and 1.9 points with 600 mg ASU, 300 mg ASU and placebo, respectively (p <0.01).
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