Glucosamine

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Clinical studies

A meta-analysis that includes all trials in the table except Rozendaal's negative trial of glucosamine sulfate concluded that glucosamine hydrochloride is not effective and that the effect of glucosamine sulfate is uncertain.[1]

Selected randomized controlled trials of glucosamine[2][3][4][5]
Trial Patients Intervention Outcome Results
Glucosamine Placebo
Reginster[2]
2001
Sponsored by manufacturer		 212 patients with knee osteoarthritis
30% dropped out		 1500 mg glucosamine sulphate for 3 years Loss of mean joint-space
Loss at minimum joint space (visual)
WOMAC pain score[6]
Did not use intention to treat analysis.		 0.06 mm†
0.40 mm†
-24.3%†		 0.31 mm
0.11 mm
+9.8%
Pavelka[3]
2002
Sponsored by manufacturer		 202 patients with hip osteoarthritis
40% dropped out		 1500 mg glucosamine sulphate for 3 years Loss at minimum joint space (visual)
WOMAC pain score[6]
Used intention to treat analysis.		 0.40 mm†
-2.0†		 -0.19 mm
-1.3
GAIT[4]
2006		 1583 patients with knee osteoarthritis 1500 mg glucosamine hydrochloride daily for 24 weeks Response of 20% decrease in WOMAC pain score[6] All subjects: 64%
Mild OA: 64%
Moderate/severe OA: 66%‡		 All subjects: 60%
Mild OA: 62%
Moderate/severe OA: 54%
GAIT[7]
2008		 1583 patients with knee osteoarthritis 1500 mg glucosamine hydrochloride daily for 24 weeks Loss of joint space width at two years 0.013 mm 0.166 mm (not significant)
Rozendaal[5]
2008		 222 patients with hip osteoarthritis 1500 mg glucosamine sulfate daily for 2 years Loss at minimum joint space
WOMAC pain score[6]		 -0.094 mm
-1.9		 -0.057 mm
-0.3
† p < 0.05
‡ All comparisons were insignificant and less than occurred with celecoxib; however, the combination of glucosamine and chondroitin gave significant 79% improvement among moderate/severe patients.

Although earlier randomized controlled trials were conflicting, more recent and larger trials show that neither glucosamine sulfate[5] nor glucosamine hydrochloride[4][7] is effective for osteoarthritis. The evidence both for and against glucosamine's efficacy has led to debate among physicians about whether to recommend glucosamine treatment to their patients.[8]

Multiple clinical trials in the 1980s and 1990s, all sponsored by the European patent-holder, Rottapharm, demonstrated a benefit for glucosamine. However, these studies were of poor quality due to shortcomings in their methods, including small size, short duration, poor analysis of drop-outs, and unclear procedures for blinding.[9][10] Rottapharm then sponsored two large (at least 100 patients per group), three-year-long, placebo-controlled clinical trials of the Rottapharm brand of glucosamine sulfate. These studies both demonstrated a benefit for glucosamine treatment.[11][3] There was not only an improvement in symptoms but also an improvement in joint space narrowing on radiographs. This suggested that glucosamine, unlike pain relievers such as NSAIDs, can actually help prevent the destruction of cartilage that is the hallmark of osteoarthritis. On the other hand, several subsequent studies, independent of Rottapharm, but smaller and shorter, did not detect any benefit of glucosamine.[12][13]

This situation led the National Institutes of Health to fund a large, multicenter clinical trial studying reported pain in osteoarthritis of the knee, comparing groups treated with chondroitin sulfate, glucosamine, and the combination, as well as both placebo and celecoxib.[14] The results of this 6-month trial found that patients taking glucosamine HCl, chondroitin sulfate, or a combination of the two had no statistically significant improvement in their symptoms compared to patients taking a placebo.[4] The group of patients who took celecoxib did have a statistically significant improvement in their symptoms. These results suggest that glucosamine and chondroitin did not effectively relieve pain in the overall group of osteoarthritis patients. However, exploratory analysis of a subgroup of patients suggested that the supplements may be effective in patients with pain classified as moderate to severe (see testing hypotheses suggested by the data).

An accompanying editorial noted that "It is disappointing that the GAIT investigators did not use glucosamine sulfate ... since the results would then have provided important information that might have explained in part the heterogeneity in the studies reviewed by Towheed and colleagues[PMID 15846645]"[15] But this concern is not shared by pharmacologists at the PDR who state, "The counter anion of the glucosamine salt (i.e. chloride or sulfate) is unlikely to play any role in the action or pharmacokinetics of glucosamine".[16] Finally, a randomized controlled trial of glucosamine sulfate was also negative.[5]

  1. ↑ Vlad SC, Lavalley MP, McAlindon TE, Felson DT (2007). "Glucosamine for pain in osteoarthritis: Why do trial results differ?". Arthritis Rheum 56 (7): 2267-2277. DOI:10.1002/art.22728. PMID 17599746. Research Blogging.
  2. ↑ 2.0 2.1 Reginster JY, Deroisy R, Rovati LC, et al (January 2001). "Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial". Lancet 357 (9252): 251–6. DOI:10.1016/S0140-6736(00)03610-2. PMID 11214126. Research Blogging.
  3. ↑ 3.0 3.1 3.2 Pavelká K, Gatterová J, Olejarová M, Machacek S, Giacovelli G, Rovati LC (October 2002). "Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study". Arch. Intern. Med. 162 (18): 2113–23. PMID 12374520. [e] Cite error: Invalid <ref> tag; name "pmid12374520" defined multiple times with different content
  4. ↑ 4.0 4.1 4.2 4.3 Clegg DO, Reda DJ, Harris CL, et al (February 2006). "Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis". N. Engl. J. Med. 354 (8): 795–808. DOI:10.1056/NEJMoa052771. PMID 16495392. Research Blogging. Cite error: Invalid <ref> tag; name "pmid16495392" defined multiple times with different content
  5. ↑ 5.0 5.1 5.2 5.3 Rozendaal RM, Koes BW, van Osch GJ, et al (February 2008). "Effect of glucosamine sulfate on hip osteoarthritis: a randomized trial". Ann. Intern. Med. 148 (4): 268–77. PMID 18283204. [e] Cite error: Invalid <ref> tag; name "pmid18283204" defined multiple times with different content Cite error: Invalid <ref> tag; name "pmid18283204" defined multiple times with different content
  6. ↑ 6.0 6.1 6.2 6.3 Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW (December 1988). "Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee". J. Rheumatol. 15 (12): 1833–40. PMID 3068365. [e]
  7. ↑ 7.0 7.1 Sawitzke AD, Shi H, Finco MF, et al (October 2008). "The effect of glucosamine and/or chondroitin sulfate on the progression of knee osteoarthritis: a report from the glucosamine/chondroitin arthritis intervention trial". Arthritis Rheum. 58 (10): 3183–91. DOI:10.1002/art.23973. PMID 18821708. Research Blogging.
  8. ↑ Manson and Rahman, 2004
  9. ↑ Adams ME. "Hype about glucosamine," Lancet, 1999 Jul 31;354(9176):353-4. PMID 10437858.
  10. ↑ McAlindon TE, LaValley MP, Gulin JP, Felson DT. "Glucosamine and Chondroitin for Treatment of Osteoarthritis: A Systematic Quality Assessment and Meta-analysis," JAMA, 2000; 283:1469-1475. PMID 10732937.
  11. ↑ Reginster JY, Deroisy R, Rovati LC, Lee RL, Lejeune E, Bruyere O, Giacovelli G, Henrotin Y, Dacre JE, Gossett C. "Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial," Lancet, 2001 Jan 27; 357(9252):251-6. PMID 11214126.
  12. ↑ Hughes R, Carr A. "A randomized, double-blind, placebo-controlled trial of glucosamine sulphate as an analgesic in osteoarthritis of the knee," Rheumatology (Oxford), 2002 Mar; 41(3):279-84. Full text online.
  13. ↑ Cibere J, Kopec JA, Thorne A, Singer J, Canvin J, Robinson DB, Pope J, Hong P, Grant E, Esdaile JM, "Randomized, double-blind, placebo-controlled glucosamine discontinuation trial in knee osteoarthritis," Arthritis Rheum. 2004 Oct 15; 51(5):738-45. PMID 15478160.
  14. ↑ Clinicaltrials.gov
  15. ↑ Hochberg MC. "Nutritional supplements for knee osteoarthritis--still no resolution," N Engl J Med, 2006 Feb 23; 354(8):858-60. PMID 16495399.
  16. ↑ PDR Health
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