Ascorbic acid increases the severity of spontaneous knee osteoarthritis in a guinea pig model

Abstract

Objective. To determine whether ascorbic acid might be of benefit for the treatment of spontaneous osteoarthritis (OA) when administered over a long period of time.Methods. We investigated the effects of 8 months' exposure to low, medium, and high doses of ascorbic acid on the in vivo development of histologic knee OA in the male Hartley guinea pig. The low dose represented the minimum amount needed to prevent scurvy. The medium dose was the amount present in standard laboratory guinea pig chow and resulted in plasma levels comparable with those achieved in a person consuming 200 mg/day (5 fruits and vegetables daily). The high dose was the amount shown in a previous study of the guinea pig to slow the progression of surgically induced OA.Results. We found an association between ascorbic acid supplementation and increased cartilage collagen content but, in contrast to findings in a previous study of surgically induced OA in the guinea pig, ascorbic acid worsened the severity of spontaneous OA. Active transforming growth factor ␤ (TGF␤) was expressed in marginal osteophytes, whose size and number were significantly increased with increasing intake of ascorbic acid. Synovial fluid levels of cartilage oligomeric matrix protein, a biomarker of cartilage turnover, corroborated the histologic findings.Conclusion. Ascorbic acid has been shown to activate latent TGF␤. Prolonged intraarticular exposure to TGF␤ has been shown to cause OA-like changes. We found expression of active TGF␤ in osteophytes, a prominent feature of the joint histology seen in association with ascorbic acid treatment. Thus, the deleterious effects of prolonged ascorbic acid exposure may be mediated in part by TGF␤. This worsening of OA with ascorbic acid supplementation suggests that ascorbic acid intake should not be supplemented above the currently recommended dietary allowance (90 mg/day for men and 75 mg/day for women).

Dietary vitamin C requirement and its effects on tissue antioxidant capacity of juvenile largemouth bass, Micropterus salmoides

“…Ascorbic acid (ASA) is a water soluble vitamin, acting as a cosubstrate for hydroxylase and oxygenase enzymes involved in the biosynthesis of pro-collagen, carnitine and neurotransmitters, which is necessary for the skin, cartilage and bone formation, growth, and reproduction (Darias et al, 2011;Kraus et al, 2004;Tolbert, 1979). ASA is also a powerful antioxidant which protects low density lipoproteins from oxidation, reduces harmful oxidants in the stomach and promotes iron absorption (Padayatty and Levine, 2001).…”

The effects of vitamin C supplementation on incident and progressive knee osteoarthritis: a longitudinal study

“…Although this was a rigorous 6-month, double-blind placebo-controlled trial, study limitations (including trace amounts of selenium found in the placebo), as well as low power due to small sample size (n 30) should be considered. In contradiction to all other published findings, a 2004 study conducted on guinea pigs observed a dose-dependent, positive association between ascorbic acid supplementation and the severity of spontaneous OA (24) . In addition, Kraus et al (24) noted a correlation between the knee joint histological severity scores and plasma ascorbate concentration (r 5 0?38, P 5 0?01) and concluded that osteoarthritic patients should not consume above the Recommended Daily Value for vitamin C. The present study highlights the complexity of the relationship between the pathogenesis of OA and dietary antioxidant consumption and underscores the need for related, rigorous clinical research investigations.…”

Production and Enrichment of Chironomid Larva with Different Levels of Vitamin C and Effects on Performance of Persian Sturgeon Larvae

“…Much focus has been put on this vitamin due to involvement in the biosynthesis of carnitine, neurotransmitters, and collagen (Terova et al 2001;Kraus et al 2004;Darias et al 2011), and ascorbic acid has also shown a specific role in mineral metabolism (Sandnes 1991), the stress response (Ren et al 2010), immunity (Waagbø 2006), and wound healing (Wahli et al 2003). Consequently, an appropriate amount of ascorbic acid should be supplied in fish feed from exogenous sources to ensure their normal growth and health (Pitaksong et al 2013).…”