Green-lipped mussel extract (Perna canaliculus) and glucosamine sulphate in patients with knee osteoarthritis: therapeutic efficacy and effects on gastrointestinal microbiota profiles

Inflammopharmacology. 2013 Feb;21(1):79-90. doi: 10.1007/s10787-012-0146-4. Epub 2012 Jul 22.


Objective: To investigate how changes in the gastrointestinal tract (GIT) microbiota profile may influence nutraceutical efficacy in osteoarthritis (OA) and allow the formulation of a hypothesis that explains in part the inconsistent and contentious findings from OA clinical studies with green-lipped mussel (GLM) and glucosamine.

Methods: A non-blinded randomised clinical trial was conducted with 38 subjects diagnosed with knee OA. Each participant received either 3,000 mg/day of a whole GLM extract or 3,000 mg/day of glucosamine sulphate (GS), p.o. for 12 weeks. Faecal microbial analyses were carried out after collecting stools at T (0) and T (12) weeks. Additional pharmacometric measures were obtained from changes in arthritic scores in the Western Ontario McMaster Universities Arthritis Index (WOMAC) and the Lequesne algofunctional indices and the Gastrointestinal Symptom Rating Scale (GSRS). An intention-to-treat analysis was employed and participant data collected at T (0), T (6) and T (12) weeks.

Results: There were no statistically significant changes in bacterial growth patterns determined by the Wilcoxon test. In both groups there was a trend towards a decrease in Clostridium and Staphylococcus species and increase in Lactobacillus, Streptococcus and Eubacterium species. In the GLM group Bifidobacterium tended to increase and Enterococcus and yeast species to decrease. The GS-treated group demonstrated a trend towards a decrease in Bacteroides and an increase in yeasts and Coliforms species, most notably Escherichia coli. We further confirm significant improvement (p < 0.05) in all OA outcome measures from T (0) to T (12) weeks for both the GLM and GS groups. The GSRS scores indicated that GIT function significantly improved over the 12 weeks duration with GLM and GS supplementation.

Conclusion: Both GLM and GS reduced OA symptoms and non-significantly altered the gut microbiota profile from baseline. Changes in the microbiota profiles occurred in both treatment groups; the most notable being a reduction in the Clostridia sp. This study suggests that nutritional supplements such as GLM and GS may regulate some of the metabolic and immunological activities of the GIT microbiota. The decrease in Clostridia, a potent modulator of colonic Th17 and CD4+ regulatory T cells, was consistent with a decrease in inflammation; improved GSRS scores and OA symptoms for these OA participants. The GIT microbiota may be important factor in the first-pass metabolism of these nutraceuticals.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Animals
  • Feces / microbiology
  • Female
  • Gastrointestinal Tract / microbiology*
  • Glucosamine / pharmacology*
  • Humans
  • Male
  • Middle Aged
  • Osteoarthritis, Knee / drug therapy*
  • Osteoarthritis, Knee / pathology
  • Perna / chemistry*
  • Prospective Studies
  • Time Factors
  • Tissue Extracts / isolation & purification
  • Tissue Extracts / pharmacology*
  • Treatment Outcome


  • Tissue Extracts
  • Glucosamine