Skip to main content

Advertisement

SpringerLink
Log in

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

  • Research Article
  • Published:
Inflammopharmacology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Aghazadeh-Habashi A, Sattari S, Pasutto F, Jamali F (2002) Single dose pharmacokinetics and bioavailability of glucosamine in the rat. J Pharm Pharm Sci 5(2):181–184

    PubMed  CAS  Google Scholar 

  • Altman R, Ach E, Bloch D et al (1986) Development of criteria for the classification and reporting of osteoarthritis: classification of osteoarthritis of the knee. Arthr Rheum 29(8):1039–1049

    Article  CAS  Google Scholar 

  • Atarashi K, Tanoue T, Shima T et al (2011) Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331(6015):337–341

    Article  PubMed  CAS  Google Scholar 

  • Barnes MJ, Powrie F (2011) Immunology. The gut’s Clostridium cocktail. Science 331(6015):289–290

    Article  PubMed  CAS  Google Scholar 

  • Bellamy N (2002) WOMAC: a 20-year experiential review of a patient-centred self-reported health status questionnaire. J Rheumatol 29(12):2473–2476

    PubMed  Google Scholar 

  • Bellamy N, Buchanan W, Goldsmith CH et al (1988) Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to anti-rheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 15:1833–1840

    PubMed  CAS  Google Scholar 

  • Bjordal J, Ljunggren AE, Klovning A, Slordal L (2004) Non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 inhibitors, in osteoarthritis knee: meta-analysis of randomised placebo controlled trials. Br Med J 329(7478):1317–1322

    Article  CAS  Google Scholar 

  • Brien S, Prescott P, Coghlan B et al (2008) Systematic review of the nutritional supplement Perna Canaliculus (green-lipped mussel) in the treatment of osteoarthritis. Q J Med 101(3):167–179

    Article  CAS  Google Scholar 

  • Chitturi S, George J (2002) Hepatotoxicity of commonly used drugs: nonsteroidal anti-inflammatory drugs, antihypertensives, antidiabetic agents, anticonvulsants, lipid-lowering agents, psychotropic drugs. Semin Liver Dis 22(2):169–183

    Article  PubMed  CAS  Google Scholar 

  • Chong V, Wang C (2008) Higher prevalence of gastrointestinal symptoms among patients with rheumatic disorders. Singap Med J 49(5):419–424

    CAS  Google Scholar 

  • Coulson S, Vecchio P, Gramotnev H, Vitetta L (2012) Green-lipped mussel (Perna canaliculus) extract efficacy in knee osteoarthritis and improvement in gastrointestinal dysfunction: a pilot study. Inflammopharmacology 20(2):71–76

    Article  PubMed  Google Scholar 

  • Egert M, de Graaf AA, Smidt H et al (2006) Beyond diversity: functional microbiomics of the human colon. Trends Microbiol 14:86–91

    Article  PubMed  CAS  Google Scholar 

  • Ehrlich G (2003) Global treatment of osteoarthritis. Inflammopharmacology 11(4–6):333–336

    Article  PubMed  Google Scholar 

  • Ernst E (1998) Usage of complementary therapies in rheumatology: a systematic review. Clin Rheumatol 17:301–305

    Article  PubMed  CAS  Google Scholar 

  • Foley S, Stolarczyk E, Mouni F et al (2008) Characterisation of glutamine fructose-6-phosphate amidotransferase (EC 2.6.1.16) and N-acetylglucosamine metabolism in Bifidobacterium. Arch Microbiol 189(2):157–167

    Article  PubMed  CAS  Google Scholar 

  • Gaboriau-Routhiau V, Rakotobe S, Lécuyer E et al (2009) The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 31(4):677–689

    Article  PubMed  CAS  Google Scholar 

  • Garcia Rodriguez LA, Hernandez-Diaz S (2001) Relative risk of upper gastrointestinal complications among users of acetaminophen and nonsteroidal anti-inflammatory drugs. Epidemiology 12(5):570–576

    Article  PubMed  CAS  Google Scholar 

  • Gillett R, Norrell A (2011) Considerations for safe use of statins: liver enzyme abnormalities and muscle toxicity. Am Fam Physician 83(6):711–716

    PubMed  Google Scholar 

  • Guarner F, Malagelada JR (2003) Gut flora in health and disease. Lancet 361(9356):512–519

    Article  PubMed  Google Scholar 

  • Holzapfel W, Haberer P, Snel J et al (1998) Overview of gut flora and probiotics. Int J Food Microbiol 41:85–101

    Article  PubMed  CAS  Google Scholar 

  • Kelly D, Conway S, Aminov R (2005) Commensal gut bacteria: mechanisms of immune modulation. Trends Immunol 26(6):326–333

    Article  PubMed  CAS  Google Scholar 

  • Koser S, Tribby I, Stuedell J (1961) Glucosamine utilization by some lactic acid bacteria. J Infect Dis 108:324–332

    Article  PubMed  CAS  Google Scholar 

  • Laparra JM, Sanz Y (2010) Interactions of gut microbiota with functional food components and nutraceuticals. Pharmacol Res 61(3):219–225

    Article  PubMed  CAS  Google Scholar 

  • Lequesne MG, Mery C, Samson M, Gerard P (1987) Indexes of severity for osteoarthritis of the hip and knee validation-value in comparison with other assessment tests. Scand J Rheumatol 65:85–89

    Article  CAS  Google Scholar 

  • Lutwak-Mann C (1941) Enzymatic decomposition of amino-sugars. Biochem J 35(5):610–626

    PubMed  CAS  Google Scholar 

  • Reginster JY (2002) The prevalence and burden of arthritis. Rheumatology (Oxford) 41(Supp 1):3–6

    Article  Google Scholar 

  • Rutjes A, Nüesch E, Reichenbach S, Jüni P (2008) S-Adenosylmethionine for osteoarthritis of the knee or hip. Cochrane Database Syst Rev 4:CD007321

    Google Scholar 

  • Smith K, McCoy KD, Macpherson AJ (2007) Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota. Semin Immunol 19(2):59–69

    Article  PubMed  CAS  Google Scholar 

  • Stepankova R, Powrie F, Kofronova O et al (2007) Segmented filamentous bacteria in a defined bacterial cocktail induce intestinal inflammation in SCID mice reconstituted with CD45RBhigh CD4+ T cells. Inflamm Bowel Dis 13(10):1202–1211

    Article  PubMed  Google Scholar 

  • Svedlund J, Sjodin I, Dotevall G (1988) GSRS: a clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Dig Dis Sci 33:129–134

    Article  PubMed  CAS  Google Scholar 

  • Tana C, Umesaki Y, Imaoka A et al (2010) Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome. Neurogastroenterol Motil 22(5):512–519, e114–e115

    Google Scholar 

  • Thrupp L (1980) Susceptibility testing of antibiotics in liquid media. In: Lorian V (ed) Antibiotics in laboratory medicine, chap 4. Williams & Wilkins pub, Baltimore, pp 73–113

  • Towheed T, Maxwell L, Anastassiades TP et al (2005) Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev 2:CD002946

    Google Scholar 

  • Tucker G, Adams R, Wilson D (2010) New Australian population scoring coefficients for the old version of the SF-36 and SF-12 health status questionnaires. Qual Life Res 19:1069–1076

    Article  PubMed  Google Scholar 

  • Ulbricht C, Chao W, Costa D et al (2009) An evidence-based systematic review of green-lipped mussel (Perna canaliculus) by the Natural Standard Research Collaboration. J Diet Suppl 6(1):54–90

    Article  PubMed  Google Scholar 

  • Umesaki Y, Setoyama H, Matsumoto S et al (1999) Differential roles of segmented filamentous bacteria and clostridia in development of the intestinal immune system. Infect Immun 67:3504–3511

    PubMed  CAS  Google Scholar 

  • Vitetta L, Briskey D, Hayes E et al (2012) A review of the pharmacobiotic regulation of gastrointestinal inflammation by probiotics, commensal bacteria and prebiotics. Inflammopharmacology (Epub ahead of print)

  • Wandel S, Juni P, Tendal B et al (2010) Effects of glucosamine, chondroitin or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. BMJ 341:c4675

    Article  PubMed  Google Scholar 

  • Ware J, Kosinski M, Keller S (1996) A 12-item short-form health survey: construction of scales and preliminary tests of reliability and validity. Med Care 34(3):220–233

    Article  PubMed  Google Scholar 

  • Willis A (2007) Anaerobic culture methods, in anaerobic microbiology: a practical approach. IRL Press at Oxford University Press, Oxford

    Google Scholar 

  • Wolfe J, Nakada H (1956) Glucosamine degradation by Escherichia coli. II. The isomeric conversion of glucosamine 6-PO4 to fructose 6-PO4 and ammonia. Arch Biochem Biophys 64(2):489–497

    Article  PubMed  CAS  Google Scholar 

  • Wolfe J, Morita R, Nakada H (1956) Glucosamine degradation by Escherichia coli, I. Observations with resting cells and dry-cell preparations. Arch Biochem Biophys 64:480–488

    Article  PubMed  CAS  Google Scholar 

  • Wolfe F, Kong S, Watson D (2000) Gastrointestinal symptoms and health related quality of life in patients with arthritis. J Rheumatol 27(6):1373–1378

    PubMed  CAS  Google Scholar 

  • Woolf AD, Pfleger B (2003) Burden of major musculoskeletal conditions. Bull World Health Organ 81(9):646–656

    PubMed  Google Scholar 

  • Wu H, Ivanov I, Darce J et al (2010) Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32(6):815–827

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Prof Michael Whitehouse for reviewing the manuscript and Christine Downey [from the PA Hospital Rheumatology Clinic] for assisting with patient recruitment and follow-ups.

Conflict of interest

GLM extract capsules were donated by Aroma New Zealand Ltd who had no involvement in the collection, analysis or interpretation of the data, writing the report or the decision to submit the paper for publication.

Ethical approval and clinical trial registration

Approval for this prospective study was obtained from the Ethics Committee of The University of Queensland and Princess Alexandra Hospital Human Research Ethics Committees. The clinical trial was registered with the Australian and New Zealand Clinical Trail Registry [ANZCTRN: 12611000517976].

Author information

Authors and Affiliations

  1. The Centre for Integrative Clinical and Molecular Medicine, The University of Queensland, School of Medicine, Princess Alexandra Hospital, Lvl 2, R Wing, 199 Ipswich Road, Woolloongabba, QLD, 4102, Australia

    Samantha Coulson, Helen Gramotnev & Luis Vitetta

  2. Bioscreen, Bio21, Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Australia

    Henry Butt

  3. Department of Rheumatology, Princess Alexandra Hospital, Brisbane, QLD, Australia

    Phillip Vecchio

Authors
  1. Samantha Coulson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Henry Butt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Phillip Vecchio
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Helen Gramotnev
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Luis Vitetta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Luis Vitetta.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Coulson, S., Butt, H., Vecchio, P. et al. Green-lipped mussel extract (Perna canaliculus) and glucosamine sulphate in patients with knee osteoarthritis: therapeutic efficacy and effects on gastrointestinal microbiota profiles. Inflammopharmacol 21, 79–90 (2013). https://doi.org/10.1007/s10787-012-0146-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10787-012-0146-4

Keywords

Search

Navigation