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

Kraus VB, Huebner JL, Stabler T, Flahiff CM, Setton LA, Fink C, Vilim V, Clark AG · Arthritis and Rheumatism

The result that stops the cofactor story from running unopposed. Over eight months ascorbic acid raised cartilage collagen content, as the mechanism predicts — and worsened the severity of spontaneous osteoarthritis, with osteophyte size and number rising as intake rose, active TGF-beta expressed in those osteophytes, and synovial fluid cartilage oligomeric matrix protein corroborating the histology. It also contradicts an earlier study by the same group in SURGICALLY induced osteoarthritis, where ascorbate slowed progression. The authors' stated conclusion is that ascorbic acid should not be supplemented above the recommended dietary allowance.

Population

Male Hartley guinea pigs, which develop osteoarthritis spontaneously and cannot synthesise ascorbate

Intervention

Low, medium and high dietary ascorbic acid for 8 months; the medium dose gives plasma levels equivalent to a person taking 200 mg/day

Comparator

Low dose, the minimum needed to prevent scurvy

Limitations

Guinea pigs, and a spontaneous model whose osteophyte-heavy phenotype may not mirror human post-traumatic cartilage loss. The opposite result in the same species under a surgical model is unexplained and means the direction of effect may depend on the type of joint damage. Eight months is long for an animal study and short for human osteoarthritis. NIH-funded, no commercial interest.