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

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.

The Association of Blood Biomarkers and Body Mass Index in Knee Osteoarthritis: A Cross-Sectional Study

“…A study on fasting in KOA also found no association of changes in pain and function scores and AGE/sRAGE. 37 oxLDL, the oxidized form of LDL-cholesterol, is a significant regulator of cartilage degeneration 10 : In KOA, oxLDL levels are higher compared with controls. Furthermore, in another study, oxLDL was found to be positively correlated with KOA severity.…”

“…A study on fasting in KOA also found no association of changes in pain and function scores and AGE/sRAGE. 37 …”

Unravelling the health effects of fasting: a long road from obesity treatment to healthy life span increase and improved cognition

“…The safety of this programme has been recently documented in large cohort studies [15,24]. This type of LF, generally lasting from 4 to 21 days, has been studied in various clinical conditions: chronic inflammatory disorders [92,93] and rheumatoid arthritis [59,94], hypertension [95], irritable bowel syndrome [96], insulin resistance, type 2 diabetes and metabolic syndrome [97,98], fibromyalgia [99], breast and ovarian cancer [100], osteoarthritis [101], obesity [102], and fatty liver [103]. Furthermore, MRI evaluation documented significant changes in body composition after 14 days of fasting [104].…”

The role of AGEs in pathogenesis of cartilage destruction in osteoarthritis

“…In addition, high molecular weight AGEs that are bound to proteins from foreign substances can be detected. 90,91 Combining the correct choice of food and cooking methods together with physical exercise can avoid the harmful effects of a high-AGEs diet on the body. 33,92 Studies on endogenous AGEs have shown that substances such as aminoguanidine, pyridoxamine, and monomer amino acids (such as lysine and arginine) can effectively inhibit AGEs formation, AGEs-induced protein cross-linking, and tissue collagen accumulation and hardening.…”