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

Publication ,  Journal Article
Kraus, VB; Huebner, JL; Stabler, T; Flahiff, CM; Setton, LA; Fink, C; Vilim, V; Clark, AG
Published in: Arthritis Rheum
June 2004

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 beta (TGF beta) 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 beta. Prolonged intraarticular exposure to TGF beta has been shown to cause OA-like changes. We found expression of active TGF beta 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 beta. 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).

Duke Scholars

Published In

Arthritis Rheum

DOI

ISSN

0004-3591

Publication Date

June 2004

Volume

50

Issue

6

Start / End Page

1822 / 1831

Location

United States

Related Subject Headings

  • Weight Gain
  • Transforming Growth Factor beta
  • Synovial Fluid
  • Severity of Illness Index
  • Scurvy
  • Osteoarthritis, Knee
  • Matrilin Proteins
  • Male
  • Least-Squares Analysis
  • Guinea Pigs
 

Citation

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ICMJE
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Kraus, V. B., Huebner, J. L., Stabler, T., Flahiff, C. M., Setton, L. A., Fink, C., … Clark, A. G. (2004). Ascorbic acid increases the severity of spontaneous knee osteoarthritis in a guinea pig model. Arthritis Rheum, 50(6), 1822–1831. https://doi.org/10.1002/art.20291
Kraus, Virginia B., Janet L. Huebner, Thomas Stabler, Charlene M. Flahiff, Lori A. Setton, Christian Fink, Vladimir Vilim, and Amy G. Clark. “Ascorbic acid increases the severity of spontaneous knee osteoarthritis in a guinea pig model.Arthritis Rheum 50, no. 6 (June 2004): 1822–31. https://doi.org/10.1002/art.20291.
Kraus VB, Huebner JL, Stabler T, Flahiff CM, Setton LA, Fink C, et al. Ascorbic acid increases the severity of spontaneous knee osteoarthritis in a guinea pig model. Arthritis Rheum. 2004 Jun;50(6):1822–31.
Kraus, Virginia B., et al. “Ascorbic acid increases the severity of spontaneous knee osteoarthritis in a guinea pig model.Arthritis Rheum, vol. 50, no. 6, June 2004, pp. 1822–31. Pubmed, doi:10.1002/art.20291.
Kraus VB, Huebner JL, Stabler T, Flahiff CM, Setton LA, Fink C, Vilim V, Clark AG. Ascorbic acid increases the severity of spontaneous knee osteoarthritis in a guinea pig model. Arthritis Rheum. 2004 Jun;50(6):1822–1831.
Journal cover image

Published In

Arthritis Rheum

DOI

ISSN

0004-3591

Publication Date

June 2004

Volume

50

Issue

6

Start / End Page

1822 / 1831

Location

United States

Related Subject Headings

  • Weight Gain
  • Transforming Growth Factor beta
  • Synovial Fluid
  • Severity of Illness Index
  • Scurvy
  • Osteoarthritis, Knee
  • Matrilin Proteins
  • Male
  • Least-Squares Analysis
  • Guinea Pigs