AGE-RAGE Interaction Does Not Explain the Clinical Improvements after Therapeutic Fasting in Osteoarthritis

Complement Med Res. 2018;25(3):167-172. doi: 10.1159/000486237. Epub 2017 Feb 13.

Abstract

Background: Therapeutic fasting improves joint pain in patients with osteoarthritis (OA), but the underlying mechanisms are unknown. Interactions of advanced glycation end products (AGEs) and their receptors (RAGE) play a role in OA pathogenesis. This study aimed to investigate whether the benefits of fasting in OA can be explained by changes in AGEs or RAGE.

Patients and methods: 37 patients with OA underwent fasting for 8 days. Serum levels of an AGE (N-ε-(carboxymethyl)-lysine; CML) and the soluble RAGE (sRAGE) as well as clinical outcome parameters such pain characteristics (measured by visual analogue scale; VAS), joint function (determined by the Western Ontario and McMaster Universities Arthritis Index; WOMAC), and quality of life (via the 36-Item Short-Form Health Survey (SF-36) questionnaire) were assessed. The variables were measured at baseline, the end of fasting, and at follow-up at 4 weeks.

Results: The CML levels did not significantly change from baseline to the end of intervention (Δ = -25.6 ± 92.2 ng/ml; p = 0.10). In contrast, the sRAGE levels (Δ = -182.7 ± 171.4 ng/ml; p < 0.0001) and the sRAGE/CML ratio (Δ = -0.4 ± 0.6; p < 0.001) significantly decreased, but they returned to baseline levels 4 weeks after the end of fasting. The scores for pain, WOMAC, and the physical subscale of the SF-36 significantly improved during fasting. There was no correlation between the clinical outcomes and changes in serum levels of CML, sRAGE, or the sRAGE/CML ratio.

Conclusions: Fasting resulted in a significant but non-sustained reduction of sRAGE levels and the sRAGE/CML ratio in OA, while the CML levels did not change. Improvement in clinical endpoints of OA does not correlate with changes in CML or sRAGE.

Keywords: Advanced glycation end products; Fasting; N-ε-(carboxymethyl)-lysine; Osteoarthritis; Receptor for advanced glycation end products.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Fasting / blood*
  • Female
  • Glycation End Products, Advanced / blood*
  • Humans
  • Lysine / analogs & derivatives
  • Lysine / blood
  • Male
  • Middle Aged
  • Osteoarthritis / blood*
  • Osteoarthritis / therapy*
  • Quality of Life
  • Receptor for Advanced Glycation End Products / blood*
  • Treatment Outcome

Substances

  • Glycation End Products, Advanced
  • Receptor for Advanced Glycation End Products
  • N(6)-carboxymethyllysine
  • Lysine