Glucosamine Sulphate : Scientific articles and information from journals
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Glucosamine is a substance synthesized in the body.
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Glucosamine sulfate is an artificially synthesized salt of glucsamine. This compound has been used for many years as a natural treatment for arthritis and in particular, osteoarthritis. STATUS HEALTH
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Osteoarthritis is a form of degenerative arthritis occurring when the cartilage that cushions the ends of bone joints breaks down, causing pain, stiffness and deformity.  
In animal models of arthritis, glucosamine sulfate was reported to have the potential to slow the degradation of cartilage. Its mode of action is believed to involve stimulation of cartilage cells to synthesize the building blocks of cartilage - called glycosaminoglycans and proteoglycans. It also has been reported to have anti-inflammatory properties through a mechanism that inhibits the activity of proteolytic enzymes. In the early 1980s, a number of small, controlled human trials were conducted in Europe and Asia to study the clinical use of glucosamine sulfate in the treatment of osteoarthritis.  

Small trials were then done in the early 1990's. These studies all showed that glucosamine sulphate had a benefit when used as a sulphate.

Chloride did not help. Glucosamine chloride was tested in a large study by the USA National institutre of health and again confirmed that Glucosamine Chloride does not work.

However early and more recent studies show that Glucosamine SULPHATE works.


Therefore in my personal opinion there is fairly good evidence that there is benefit in osteoarthritis.

I have therefore prescribed it for many years.

Use in other Arthritis types such as Rheumatoid arthritis has not been fully tested, but there is certainly no harm in using it as a cartilage protector.

Publication in the Lancet Vol 357 Jan 2001 showed optimistic results with an increase in joint space (cartilage) when used over 3 years.  
This suggests a fairly definite positive response  


K.K. Förster1, K. Schmid1, G. Giacovelli2, L.C. Rovati2 1Dept. of Clinical Research, Opfermann Arzneimittel, Wiehl; 2Dept. of Clinical Pharmacology, Rotta Research Lab., Monza (I), Germany

Objective: Control of symptoms of cervical and/or lumbar spondylarthrosis in comparison with placebo Six weeks of treatment plus four weeks of follow-up. 160 patients were enrolled, randomly assigned to either the verum group (80 patients: 66 women, 14 men; mean age of 64.2 years) or to the placebo group (80 patients: 65 women, 15 men; mean age of 62.0 years).

Results: 52.5% GS patients showed either "definitely improved" or "improved" symptoms, versus 33.7% placebo group patients (p = 0.034).

Global assessment, figures were higher: 67.5 versus 58.8% (not significant, n.s.). Conclusions: GS has a significantly better symptomatic efficacy than placebo in controlling pain and movement limitation in spondylarthrosis. This effect lasts on after the end of treatment, whereby safety of GS is very good and comparable to that of placebo.



T.E. Towheed

Rheumatic Diseases Unit, Queen's University, Canada

Glucosamine sulphate (GS) has been proposed as a slow acting drug in osteoarthritis (OA). Randomized controlled trials (RCTs) evaluating the efficacy of GS in the management of OA were systematically reviewed. A MEDLINE search strategy, supplemented by a review of reference lists, was used to help identify English language RCTs published between 1966 and 1997. Quantitative review of the efficacy of GS in OA was performed by meta-analysis. Effect sizes were used to synthesize quantitative data that were measured with different scales, and P Odds Ratios (OR) were used for pooling dichotomous data. The search strategy identified a total of 9 RCTs. The average duration of the RCTs was 5.4 weeks. The mean number of subjects randomized subjects was 97. GS was administered orally in 5 RCTs, parenterally in 2, and a combined oral/parenteral route was used in 2 RCTs. 6 RCTs included subjects with only OA of the knee, 2 did not state the location of the OA, and 1 included subjects with OA at multiple sites. In the 7 RCTs that compared GS versus placebo, GS was always superior. 2 RCTs: compared GS versus ibuprofen;GS was superior in 1 and equivalent in 1. There were methodological problems with these RCTs, including a lack of standardization of the case definition of OA, and a lack of standardization of outcome assessment. The combined effect size for pain relief, comparing GS vs placebo (n = 5 studies) was 1.23 (95% CI, .93 to 1.53). The P OR, for overall favorable response comparing GS versus placebo (n = 2 studies) was 2.04 (95% CI, 1.38 to 3.02).

GS was found to be extremely safe and superior to placebo, and at least similar in efficacy to ibuprofen. Further studies are needed to determine whether the route of administration of GS is clinically important, and whether the therapeutic effect of GS in OA is site specific.


Adv Ther. 2009 Sep;26(9):858-71. Epub 2009 Sep 4.  
Effect of glucosamine sulfate with or without omega-3 fatty acids in patients with osteoarthritis.   Gruenwald J, Petzold E, Busch R, Petzold HP, Graubaum HJ.

INTRODUCTION: A total of 177 patients with moderate-to-severe hip or knee osteoarthritis (OA) were tested over a period of 26 weeks in a two-center, two-armed, randomized, double-blind, comparison study.

The aim was to see if a combination of glucosamine sulfate (1500 mg/day) and the omega-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (group A), showed equivalence (noninferiority) or superiority as opposed to glucosamine sulfate alone (group B).

METHODS: The primary therapy evaluation was performed using the Western Ontario and McMaster Universities Arthrosis index (WOMAC) score. At the end of the study, a reduction in the pain score of > or =20% was required (primary target criterion) and the quantitative difference in the WOMAC subscores pain, stiffness, and function were analyzed (secondary target criteria).

RESULTS AND CONCLUSION: When a minimal pain reduction of > or =20% was chosen, there was no statistically significant difference in the number of responders between the two groups (92.2% group A, 94.3% group B). A higher responder criterion (> or =80% reduction in the WOMAC pain score) was chosen. Therefore, the frequency of responders showed a therapeutic and statistical superiority for the combination product of glucosamine sulfate and the omega-3 polyunsaturated fatty acids in patients who complied with the study protocol (group A 44%, group B 32%; P=0.044).

OA symptoms (morning stiffness, pain in hips and knees) were reduced at the end of the study: by 48.5%-55.6% in group A and by 41.7%-55.3% in group B. The reduction was greater in group A than in group B.

There was a tendency toward superiority shown in the secondary target criteria and concurrent variables. In the global safety evaluation, both products have been demonstrated to be very safe in long-term treatment over 26 weeks.

To our knowledge, this is the first clinical trial in which glucosamine was given in combination with omega-3 fatty acids to patients with OA.


Int J Clin Pract. 2010 May;64(6):756-62.  
Glucosamine sulphate in the treatment of knee osteoarthritis: cost-effectiveness comparison with paracetamol.

Scholtissen S, Bruyère O, Neuprez A, Severens JL, Herrero-Beaumont G, Rovati L, Hiligsmann M, Reginster JY.  
Department of Public Health, University of Liege, Liege, Belgium.  

INTRODUCTION: The aim of this study was to explore the cost-effectiveness of glucosamine sulphate (GS) compared with paracetamol and placebo (PBO) in the treatment of knee osteoarthritis. For this purpose, a 6-month time horizon and a health care perspective was used.

MATERIAL AND METHODS: The cost and effectiveness data were derived from Western Ontario and McMaster Universities Osteoarthritis Index data of the Glucosamine Unum In Die (once-a-day) Efficacy trial study by Herrero-Beaumont et al. Clinical effectiveness was converted into utility scores to allow for the computation of cost per quality-adjusted life year (QALY) For the three treatment arms Incremental Cost-Effectiveness Ratio were calculated and statistical uncertainty was explored using a bootstrap simulation. RESULTS: In terms of mean utility score at baseline, 3 and 6 months, no statistically significant difference was observed between the three groups. When considering the mean utility score changes from baseline to 3 and 6 months, no difference was observed in the first case but there was a statistically significant difference from baseline to 6 months with a p-value of 0.047.

When comparing GS with paracetamol, the mean baseline incremental cost-effectiveness ratio (ICER) was dominant and the mean ICER after bootstrapping was -1376 euro/QALY indicating dominance (with 79% probability). When comparing GS with PBO, the mean baseline and after bootstrapping ICER were 3617.47 and 4285 euro/QALY, respectively.

CONCLUSION: The results of the present cost-effectiveness analysis suggested that GS is a highly cost-effective therapy alternative compared with paracetamol and PBO to treat patients diagnosed with primary knee OA.

Rheumatol Int. 2010 Jan;30(3):357-63. Epub 2009 Jun 21.  

Effect of glucosamine or chondroitin sulfate on the osteoarthritis progression: a meta-analysis.  
Lee YH, Woo JH, Choi SJ, Ji JD, Song GG.   Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine

The aim of this study was to assess the structural efficacies of daily glucosamine sulfate and chondroitin sulfate in patients with knee osteoarthritis (OA). The authors surveyed randomized controlled studies that examined the effects of long-term daily glucosamine sulfate and chondroitin sulfate on joint space narrowing (JSN) in knee OA patients using the Medline and the Cochrane Controlled Trials Register, and by performing manual searches.

Meta-analysis was performed using a fixed effect model because no between-study heterogeneity was evident. Six studies involving 1,502 cases were included in this meta-analysis, which consisted of two studies on glucosamine sulfate and four studies on chondroitin sulfate. Glucosamine sulfate did not show a significant effect versus controls on minimum JSN over the first year of treatment (SMD 0.078, 95% CI -0.116 to -0.273, P = 0.429).
However, after 3 years of treatment, glucosamine sulfate revealed a small to moderate protective effect on minimum JSN (SMD 0.432, 95% CI 0.235-0.628, P < 0.001). The same was observed for chondroitin sulfate, which had a small but significant protective effect on minimum JSN after 2 years (SMD 0.261, 95% CI 0.131-0.392, P < 0.001).
This meta-analysis of available data shows that glucosamine and chondroitin sulfate may delay radiological progression of OA of the knee after daily administration for over 2 or 3 years.


T.E. McAlindon, J. Gulin, D.T. Felson

Arthritis Ctr., Boston Univ., MA 02118, USA

 OA is a major cause of pain and disability in the population for which effective treatment is badly needed. GL and CH have been used for over 10 years in Europe, yet have been neglected as credible OA therapies in the US. Because of their safety, GL and CH would be of value even if only modestly effective. We performed a meta-analysis and quality assessment of clinical trials to evaluate their efficacy, and the quality of the evidence.

Studies eligible for inclusion were double-blind placebo-controlled trials of ³4 weeks duration, testing oral or parenteral GL or CH for knee or hip OA, which reported p values and size of treatment effect. Studies were sought using MEDLINE, manual searches of manuscripts and journal supplements, and by contacting authors of published manuscripts and content experts. Study quality was scored independently by two observers using a validated inventory with range 0-65, in which scores £ 33 are considered poor, 34-45 moderate, ³46 good (JAMA 1994; 272: 108). Disagreements were treated by adjudication, and by taking averages.

We decided a priori to (i) treat the global pain score in the index joint (or, if unavailable, the Lequesne Index) as the study 1° outcome (ii) classify a trial as positive if the score in the treated group at completion was ³25% lower than the placebo group and significant [p < .05]. We then computed the probability that the observed number of positive studies might have occurred by chance if the treatments were in fact ineffective using the sign test, and the number of negative studies which would be required to make this result null (p » .5).

13 trials met eligibility criteria: GL (4 papers, 2 abstracts), CH (5 papers, 2 abstracts). Inter-rater ICC for quality scoring was 0.87, p = .0001. Quality scores ranged 8-36, mean 21.1, 95% CI 16.9-25.2, and were substantially lower for abstracts compared with manuscripts (12.2 vs 25.0, p = .001). Deficiencies related to description of randomization, blinding, and completion rates. Only 2 included an intent-to-treat analysis. 5 of the 6 GS studies received industrial support. All studies were classified as positive, and demonstrated large effects - mean score reduction compared to placebo 39.5% (sd 21.9) for GS, 40.2% (6.4) for CS. The probabilities for this outcome in the absence of any true effect are p = .016 (GS), p = .008 (CS). The numbers of negative studies required to nullify these probabilities are 45 (GS) & 62 (CS).

Clinical trials of GL and CH show substantial benefits in the treatment of OA, but provide insufficient information about study design and conduct to allow definitive evaluation. We conclude that further studies are needed to test the efficacy of GS and CS.



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