Osteoarthritis (OA), the most common form of joint disease known, is characterized by articular cartilage abrasion, cartilage proteoglycan loss, joint space narrowing, and osteophyte formation. Studies in man and guinea pig have suggested a beneficial role for vitamin C (ascorbic acid:​ AA) in slowing OA progression, but the mechanism of this action is unknown. The goals of this study were to determine the transcriptional and post-transcriptional effects of AA on cartilage metabolism in vitro and in vivo, and to determine the cumulative effects of increased intake of this nutrient on OA. We hypothesized that increased dietary intake of AA would result in decreased histologic OA severity.

Tibiofemoral cartilage from Hartley guinea pigs was cultured with L-ascorbic acid or various forms of AA to allow the isolation and determination of the effects of antioxidant, acid, and nutrient components of the vitamin on cartilage metabolism. Additionally, 46 Hartley guinea pigs were placed on a low (2.5 mg), medium (30 mg), or high (150 mg) daily AA diet for 8 months to determine the effects of long-term regulated AA dosing on histologic and biochemical markers of OA.

Scurvy preventing (or nutrient forms) of AA increased collagen II, prolyl 4- hydroxylase, and aggrecan transcript levels relative to untreated controls in culture. Non-acidic nutrient forms of L-ascorbic acid also increased new collagen synthesis. Additionally, the non-nutrient and high dose acidic forms increased levels of oxidative damage to collagen over the untreated control.

In vivo, AA levels correlated positively with all histologic characteristics quantified, including cartilage damage, proteoglycan loss, and osteophyte number and severity. Total histology scores correlated significantly with average animal mass and femoral bone mineral density.

In summary, although AA stimulated synthesis of articular cartilage matrix components in vitro, the daily intake of large amounts of the nutrient did not lead to an OA resistant tissue. In fact, AA in this animal model system appears to accelerate OA, with higher AA intake being associated with increased osteophyte formation. Whether this is due to increased oxidative damage such as the ability of AA to enhance nonenzymatic glycation of proteins, remains to be determined.