Glucosamine Clinical Trial Summaries

A number of glucosamine clinical trials have been summarized from clinical trial results published in peer reviewed journals. The summaries have been selected from what we believe to be methodologically sound trials. The readers, however, are encouraged to read the original papers and form their own opinion. A number of points must be born in mind:
  1. Glucosamine is not under any patent protection and thus there is no world wide sponsoring pharmaceutical organization
  2. Different trials used different glucosamine products sourced from various suppliers
  3. There is no international standard for glucosamine such as the United States Pharmacopeia or the British Pharmacopeia
  4. Trials used products that were not formulated to glucosamine base
The summaries deal primarily with efficacy. In a separate section entitled "How Safe Is Glucosamine And What Are The Typical Side Effects?" there is a listing of the various side effects that have been reported in these trials.
The trials range from glucosamine treatment in musculoskeletal pain to Crohn's Disease. This range may stretch credibility but for the understanding that N-acetyl-D-glucosamine is an important constituent of proteoglycans and glycoproteins. (see tutorial on this site) These agents are ubiquitous in the human body. For added interest see also An Intriguing study That Should Get Your Attention on this site.

Reginater 2001

One of the most exciting studies supporting the use of glucosamine in osteoarthritis was published in the Lancet1. What makes this study so important is that it demonstrates that glucosamine has structure modifying effects on the osteoarthritic knee joint. Previous studies had shown that glucosamine is able to reduce symptoms such as pain. This randomized double blind placebo controlled trial in 106 patients on placebo and 106 on 1,500 milligrams of glucosamine sulphate per day was carried out in patients over the age of 50 with primary knee osteoarthritis. The patients on placebo experienced significant joint space narrowing and the patients on glucosamine did not. The result were statistically significant at p<0.05.

The incidence and type of adverse events reported over the three-year period was not different between the two groups. Routine laboratory tests did not show any abnormalities in system organs or metabolic functions. This is the first study to show that glucosamine can have disease-modifying activity. This trial differed from all other glucosamine clinical trials in two respects a) the patients were treated for 3 years whereas most other trials had a treatment period of only 4 to 8 weeks and b) 1,500 mg was given once daily rather than in two or three divided doses used in other trials.

Pavelka 2002

Pavelka and colleagues carried out a study2 using a protocol similar to the Reginater trial. In this three year study, 101 patients were enrolled into each arm of the study. Sixty-six glucosamine patients and 55 placebo patients completed the trial. Pain and function limitations decreased in all patients who completed the study. However the improvements were significantly larger in the patients receiving glucosamine sulphate. In patients completing each year of treatment with placebo, there was a progressive joint space narrowing. Conversely there was no average joint space narrowing in patients receiving glucosamine sulphate. In each year of the three-year trial, the glucosamine sulphate patients maintained a significantly wider joint space than the placebo patients (P<0.01). Glucosamine patients had significantly lower osteophyte scores than the placebo patients (P<0.03) Adverse effects where identical for the two groups. The authors concluded that glucosamine sulphate is the first agent that meets the requirements for classification as a symptom and structure-modifying drug in osteoarthritis.

Qiu 1998

An earlier study compared glucosamine with ibuprofen3. In this double-blind trial, 178 patients were randomized to one of 2 groups. One group received 1,500 mg of glucosamine sulphate and the other group received 1,200 mg of ibuprofen daily. The daily quantity for each drug was administered in three divided doses. End points included knee pain at rest, with movement and knee tenderness and swelling. Both treatments reduced symptoms of osteoarthritis over the 4-week course of therapy. Glucosamine was better tolerated. None of the glucosamine treated patients dropped out of the study because of adverse events but 10% of ibuprofen patients dropped out because of side effects.

Many other glucosamine trials in osteoarthritis have been reported. Some showed glucosamine to be effective4 5. Others reported no benefit from glucosamine therapy6 7. The positive trials generally had more patients enrolled and thus may have been able to pick up statistical differences that the smaller trials could not.

Thie 2001

In this clinical trial, glucosamine sulphate was compared to ibuprofen in a group of patients with osteoarthritis of the temporomandibular joint (TMJ)8. Forty women and 5 men received either glucosamine sulphate (500 mg three times per day) or ibuprofen (400 mg three time per day) for 90 days in a randomized double blind study. End points included TMJ pain with function, pain-free, and voluntary maximum mouth opening and masticatory muscle tenderness. Acetaminophen (500 mg) use for breakthrough pain was also recorded.

Forty-five patients entered the study and thirty-nine patients completed the study (21 glucosamine sulphate, 18 ibuprofen). Four discontinued due to stomach upset (3 ibuprofen, one glucosamine sulphate), one due to dizziness (glucosamine sulphate) and one due to inadequate pain control (ibuprofen). Fifteen glucosamine sulphate (71%) and 11 ibuprofen (61%) improved, with positive clinical response taken as a 20% decrease in TMJ pain with function. The number of patients with a positive clinical response was not statistically different between groups (p = 0.73). Between-group comparisons revealed that patients taking glucosamine sulphate had a significantly greater decrease in TMJ pain with function between Day 90 and 120 compared with patients taking ibuprofen. The investigators also observed a carry-over effect in the glucosamine treated group.

Salvatore 2000

The University Department of Paediatric Gastroenterology at the Royal Free Hospital in London used N-acetyl-D-glucosamine in the treatment of inflammatory bowel disease9. N-acetyl-D-glucosamine (total daily dose 3-6 g) was administered orally as adjunct therapy to 12 children with severe treatment-resistant inflammatory bowel disease (10 Crohn's disease, 2 ulcerative colitis). Seven of these children suffered from symptomatic strictures. In addition, similar doses were administered rectally as sole therapy in nine children with distal ulcerative colitis or proctitis resistant to steroids and antibiotics. Eight of the children given oral N-acetyl-D-glucosamine showed clear improvement, while four required resection. Of the children with symptomatic Crohn's stricture, only 3 of 7 have required surgery over a mean follow-up of > 2.5 years. Endoscopic or radiological improvement was detected in the other 4 patients. Rectal administration induced remission in two cases, clear improvement in three and no effect in two. In all cases biopsied there was evidence of histological improvement. N-acetyl-D-glucosamine in this small trial was an effective treatment in this population with severe chronic inflammatory bowel disease.

1 Reginster, J. Y., R. Deroisy, et al. (2001). "Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial." Lancet 357(9252): 251-6.

2 Pavelka, K. Gatterova, J. et al (2002) "glucosamine sulfate use and delay of progression of knee osteoarthritis." Arch Intern Med 162:2113 - 2123.

3 Qiu, G. X., S. N. Gao, et al. (1998). "Efficacy and safety of glucosamine sulfate versus ibuprofen in patients with knee osteoarthritis." Arzneimittelforschung 48(5): 469-74

4 Das, A., Jr. and T. A. Hammad (2000). "Efficacy of a combination of FCHG49 glucosamine hydrochloride, TRH122 low molecular weight sodium chondroitin sulfate and manganese ascorbate in the management of knee osteoarthritis." Osteoarthritis Cartilage 8(5): 343-50

5 Noack, W., M. Fischer, et al. (1994). "Glucosamine sulfate in osteoarthritis of the knee." Osteoarthritis Cartilage 2(1): 51-9.

6 Rindone, J. P., D. Hiller, et al. (2000). "Randomized, controlled trial of glucosamine for treating osteoarthritis of the knee." West J Med 172(2): 91-4.

7 Houpt, J. B., R. McMillan, et al. (1999). "Effect of glucosamine hydrochloride in the treatment of pain of osteoarthritis of the knee." J Rheumatol 26(11): 2423-30.

8 Thie, N. M., N. G. Prasad, et al. (2001). "Evaluation of glucosamine sulfate compared to ibuprofen for the treatment of temporomandibular joint osteoarthritis: a randomized double blind controlled 3 month clinical trial." J Rheumatol 28(6): 1347-55.

9 Salvatore, S., R. Heuschkel, et al. (2000). "A pilot study of N-acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease." Aliment Pharmacol Ther 14(12): 1567-79.