Effect of an oral preparation containing hyaluronic acid, chondroitin sulfate, hydrolyzed collagen type II and hydrolyzed keratin on synovial fluid features and clinical indices in knee osteoarthritis. A pilot study

Reumatismo. 2020 Nov 19;72(3):125-130. doi: 10.4081/reumatismo.2020.1272.


The aim of this study was to evaluate the effect of an oral preparation containing a naturally occurring matrix of hydrolyzed collagen type II, chondroitin sulfate (CS), and hyaluronic acid (HA), and bioactive oligopeptides of natural hydrolyzed keratin (K) in patients affected by knee OA through the evaluation of synovial fluid (SF) and clinical changes before and after treatment. Thirty patients with knee OA and swollen joint were included in the study and submitted to arthrocentesis. Patients were randomized in two groups: 1) the treatment group (N.15) took a dietary supplement containing 120 mg HA, 240 mg CS and 300 mg K once a day for 4 weeks; 2) the control group (N.15) was only submitted to arthrocentesis. Patient symptoms were evaluated at the beginning and at the end of the study by the WOMAC self-assessment questionnaire, the Lequesne algofunctional index, and the VAS forms. SF changes were evaluated by measuring local inflammatory indices, cytokines IL-1β, IL-8, IL-6, IL-10 and GM-CSF. The group of patients treated with the oral supplement showed an improvement in the clinical indices WOMAC (p<0.01), Lequesne (p=0.014) and VAS pain (p<0.01). On the contrary, no significant changes were found in the control group. The SF collected from the treated group showed a reduction of IL-8 (p=0.015), IL-6 and IL-10 levels, while no changes in cytokines were observed in the control group. This pilot study suggests that an oral administration of a preparation containing a combination of HA, CS and K can improve some clinical parameters and affect cytokine concentrations in SF in patients with knee OA.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Arthrocentesis
  • Chondroitin Sulfates / administration & dosage*
  • Collagen Type II / administration & dosage*
  • Drug Combinations
  • Granulocyte-Macrophage Colony-Stimulating Factor / analysis
  • Humans
  • Hyaluronic Acid / administration & dosage*
  • Interleukin-10 / analysis
  • Interleukin-1beta / analysis
  • Interleukin-6 / analysis
  • Interleukin-8 / analysis
  • Keratins / administration & dosage*
  • Middle Aged
  • Osteoarthritis, Knee / drug therapy*
  • Pilot Projects
  • Symptom Assessment / methods
  • Synovial Fluid / chemistry*
  • Synovial Fluid / drug effects


  • CSF2 protein, human
  • Collagen Type II
  • Drug Combinations
  • IL1B protein, human
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • Interleukin-10
  • Keratins
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Hyaluronic Acid
  • Chondroitin Sulfates