Supplement Forms/Alternate Names
• Glucosamine Hydrochloride; Glucosamine Sulfate; N-Acetyl Glucosamine
Principal Proposed Uses
• Osteoarthritis (Relieving Symptoms and Possibly Slowing the Course of the Disease)
Other Proposed Uses
• Muscle Injury Prevention; Osteochondritis; Rheumatoid Arthritis; Tendonitis
Glucosamine, most commonly used in the form glucosamine sulfate, is a simple molecule derived from glucose, the principal sugar found in blood. In glucosamine, one oxygen atom in glucose is replaced by a nitrogen atom. The chemical term for this modified form of glucose is amino sugar .
Glucosamine is produced naturally in the body, where it is a key building block for making cartilage.
There is no US Dietary Reference Intake for glucosamine. Your body makes all the glucosamine it needs from building blocks found in foods.
Glucosamine is not usually obtained directly from food. Glucosamine supplements are derived from chitin, a substance found in the shells of shrimp, lobsters, and crabs.
Osteoarthritis is a disease in which cartilage in joints becomes stiffer and may wear away. Glucosamine is used to treat this condition. A typical dosage of glucosamine is 500 mg 3 times daily. A 1,500-mg dose taken once daily is another option. 6
Glucosamine is available in three forms: glucosamine sulfate, glucosamine hydrochloride, and N-acetyl glucosamine. All three forms are sold as tablets or capsules. There is some dispute over which form is best. One study provides some evidence that glucosamine hydrochloride and glucosamine sulfate are equally effective. 53
Glucosamine is often sold in combination with chondroitin . It is not known whether this combination treatment is better than glucosamine alone, although animal studies suggest that this may be the case. 7,8
Glucosamine is widely accepted as a treatment for osteoarthritis . However, the current evidence from double-blind studies is highly inconsistent, with many of the most recent and best-designed studies failing to find significant benefit. 9-15,23,24,32,41-45,54,70,72 According to the positive studies, glucosamine acts more slowly than conventional treatments, such as ibuprofen, but eventually produces approximately equivalent benefits. In addition, unlike conventional treatments, glucosamine might also help prevent progressive joint damage, thereby slowing the course of the disease. 15,42,50 However, both these potential benefits remain controversial in light of the most recent trials.
Glucosamine has also shown some promise for osteochondritis of the knee, a cartilage disease related to osteoarthritis. 46
Some athletes use glucosamine, in the (unproven) belief that it can prevent muscle and tendon injuries . It has also been suggested as a treatment for tendonitis . However, there is no meaningful scientific evidence to support these potential uses. Exercise can also produce short-term muscle soreness. In one study, use of glucosamine not only failed to prove effective for reducing this type of pain, it actually increased it. 63 However, one study found somewhat inconsistent evidence hinting that glucosamine might aid recovery from acute knee injuries experienced by competitive athletes. 66
Glucosamine might also be helpful for rheumatoid arthritis , according to a double-blind, placebo-controlled study of 51 people. 59 In this study, use of glucosamine at a dose of 1,500 mg daily significantly improved symptoms. It did not, however, alter measures of inflammation as determined through blood tests.
What Is the Scientific Evidence for Glucosamine?
Relieving Osteoarthritis Symptoms
Inconsistent evidence suggests that glucosamine supplements might relieve pain and other symptoms of osteoarthritis. Two types of studies have been performed, those that compared glucosamine against placebo and those that compared it against standard medications.
In the placebo-controlled category, one of the best trials was a 3-year, double-blind study of 212 people with osteoarthritis of the knee. 15 Participants receiving glucosamine showed reduced symptoms as compared to those receiving placebo.
Benefits were also seen in other double-blind, placebo-controlled studies, enrolling a total of more than 1,000 people and ranging in length from 4 weeks to 3 years. 16,32, 42,44-45,61
Other double-blind studies, enrolling a total of more than 400 people, compared glucosamine against ibuprofen. These studies found glucosamine equally effective as the drug. 19-21 Furthermore, one of the placebo-controlled trials noted above (unfortunately, only reported in abstract form) also included people given the drug piroxicam, and again found equivalent benefits. 17,18
However, most recent studies have been less promising. In four studies involving a total of about 500 people, use of glucosamine failed to provide any meaningful improvement in symptoms. 23,24,41,55 And the list goes on. In a study involving 222 participants with hip osteoarthritis, 2 years of treatment with glucosamine was no better than placebo for pain, function, or x-ray findings. 70 Another trial involving 147 women with osteoarthritis found glucosamine to be no more effective than home exercises over an 18-month period. 71
In a double-blind trial, researchers evaluated the effects of stopping glucosamine after taking it for 6 months. Involving 137 people with osteoarthritis of the knee, the study found that participants who stopped using glucosamine (and, unbeknownst to them, took placebo instead) did no worse than people who stayed on glucosamine. 56
In another, very large (1,583-participant) study, neither glucosamine (as glucosamine hydrochloride) nor glucosamine plus chondroitin was more effective than placebo. 57 Another trial failed to find benefit with glucosamine plus chondroitin. 65 And finally, in a systematic review including 10 randomized trials involving 3,803 patients with osteoarthritis of hip or knee, researchers found that glucosamine alone or with chondroitin did not improve pain. 72 It appears that most of the positive studies were funded by manufacturers of glucosamine products, and most of the studies performed by neutral researchers failed to find benefit. 67
Many popular glucosamine products combine this supplement with methylsulfonylmethane (MSM). One study published in India reported that both MSM and glucosamine improve arthritis symptoms as compared to placebo, but that the combination of MSM and glucosamine was even more effective than either supplement separately. 64 However, India has not yet achieved a reputation for conducting reliable medical trials.
Slowing the Course of Osteoarthritis
Conventional treatments for osteoarthritis reduce the symptoms, but don't slow the actual progress of the disease. In fact, nonsteroidal anti-inflammatory drugs, such as indomethacin, might actually speed the progression of osteoarthritis by interfering with cartilage repair and promoting cartilage destruction (though the evidence for this is weak). 1-5 In contrast, two studies reported that glucosamine can slow the progression of osteoarthritis.
A 3-year, double-blind, placebo-controlled study of 212 people found indications that glucosamine may protect joints from further damage. 25 Over the course of the study, individuals given glucosamine showed some actual improvement in pain and mobility, while those given placebo worsened steadily. Perhaps even more importantly, x-rays showed that glucosamine treatment prevented progressive damage to the knee joint. Another large, 3-year study enrolling 202 people found similar results. 42 Furthermore, a follow-up analysis, done 5 years after the conclusion of these two studies, found suggestive evidence that use of glucosamine reduced the need for knee replacement surgery. 68
Note: As with the positive studies of glucosamine for reducing symptoms, all of these studies were funded by a major glucosamine manufacturer.
Relieving Knee Pain Due to Osteochondritis
A 12-week, double-blind, placebo-controlled study examined the effectiveness of glucosamine at 2,000 mg daily in 50 people with continuing knee pain, mostly caused by osteochondritis (damage to the articular cartilage of the knee) rather than osteoarthritis. 46 The results were somewhat equivocal, but appeared to indicate that glucosamine could improve symptoms. Some participants may have also had osteoarthritis, so the results of this study are a bit difficult to interpret.
Glucosamine appears to be a generally safe treatment and has not been associated with significant side effects. A few case reports and animal studies raised concerns that glucosamine might raise blood sugar in people with diabetes, but subsequent studies have tended to lay these concerns to rest. 34-39,48,49,52,58,60,69 Glucosamine does not appear to affect cholesterol levels either. 62
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7. Lippiello L, Woodward J, Karpman R, et al. In vivo chondroprotection and metabolic synergy of glucosamine and chondroitin sulfate. Clin Orthop. 2000;:229-240.
8. Lippiello L, Karpman RR, Hammad T. Synergistic effect of glucosamine HCL and chondroitin sulfate on in vitro proteoglycan synthesis by bovine chondrocytes. Presented at: American Academy of Orthopaedic Surgeons 67th Annual Meeting; March 15-19, 2000; Orlando, Fla.
9. Noack W, Fischer M, Forster KK, et al. Glucosamine sulfate in osteoarthritis of the knee. Osteoarthritis Cartilage. 1994;2:51-59.
10. Rovati LC. A large, randomized, placebo-controlled, double-blind study of glucosamine sulfate vs. piroxicam and vs. their association, on the kinetics of the symptomatic effect in knee osteoarthritis. Osteoarthritis Cartilage. 1994;2(suppl 1):56.
11. Rovati LC. The practical development of a selective drug for osteoarthritis: glucosamine sulfate. Presented at: The Ninth EULAR Symposium; October 7-10, 1996; Madrid, Spain.
12. Qiu GX, Gao SN, Giacovelli G, et al. Efficacy and safety of glucosamine sulfate versus ibuprofen in patients with knee osteoarthritis. Arzneimittelforschung. 1998;48:469-474.
13. Muller-Fassbender H, Bach GL, Haase W, et al. Glucosamine sulfate compared to ibuprofen in osteoarthritis of the knee. Osteoarthritis Cartilage. 1994;2:61-69.
14. Thie NM, Prasad NG, Major PW. 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. 2001;28:1347-1355.
15. Reginster JY, Deroisy R, Rovati L, et al. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet. 2001;357:251-256
16. Noack W, Fischer M, Forster KK, et al. Glucosamine sulfate in osteoarthritis of the knee. Osteoarthritis Cartilage. 1994;2:51-59.
17. Rovati LC. A large, randomized, placebo controlled, double-blind study of glucosamine sulfate vs. piroxicam and vs. their association, on the kinetics of the symptomatic effect in knee osteoarthritis. Osteoarthritis Cartilage. 1994;2(suppl 1):56.
18. Rovati LC. The practical development of a selective drug for osteoarthritis: glucosamine sulfate. Presented at: The Ninth EULAR Symposium; October 7-10, 1996; Madrid, Spain.
19. Qiu GX, Gao SN, Giacovelli G, et al. Efficacy and safety of glucosamine sulfate versus ibuprofen in patients with knee osteoarthritis. Arzneimittelforschung. 1998;48:469-474.
20. Muller-Fassbender H, Bach GL, Haase W, et al. Glucosamine sulfate compared to ibuprofen in osteoarthritis of the knee. Osteoarthritis Cartilage. 1994;2:61-69.
21. Thie NM, Prasad NG, Major PW. 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. 2001;28:1347-1355.
22. Das A Jr and Hammad TA. 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 . 2000;8:343-350.
23. Rindone JP, Hiller D, Collacott E, et al. Randomized, controlled trial of glucosamine for treating osteoarthritis of the knee. West J Med. 2000;172:91-94.
24. Houpt JB, McMillan R, Wein C, et al. Effect of glucosamine hydrochloride in the treatment of pain of osteoarthritis of the knee. J Rheumatol. 1999;26:2423-2430.
25. Reginster JY, Deroisy R, Rovati L, et al. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet. 2001;357:251-256.
26. Cohen M, Wolfe R, Mai T, et al. A randomized, double blind, placebo controlled trial of a topical cream containing glucosamine sulfate, chondroitin sulfate, and camphor for osteoarthritis of the knee. J Rheumatol. 2003;30:523-528.
27. Tallia AF, Cardone DA. Asthma exacerbation associated with glucosamine-chondroitin supplement. J Am Board Fam Pract. 2002;15:481-484.
28. Jimenez SA. The effects of glucosamine on human chondrocyte gene expression. Presented at: The Ninth EULAR Symposium; October 7-10, 1996; Madrid, Spain.
29. Hellio MP. The effects of glucosamine on human osteoarthritic chondrocytes. In vitro investigations. Presented at: The Ninth EULAR Symposium; October 7-10, 1996; Madrid, Spain.
30. Setnikar I, Pacini MA, Revel L. Antiarthritic effects of glucosamine sulfate studied in animal models. Arzneimittelforschung. 1991;41:542-545.
31. Setnikar I. Antireactive properties of "chondroprotective" drugs. Int J Tissue React. 1992;14:253-261.
32. Crolle G, D'Este E. Glucosamine sulfate for the management of arthrosis: a controlled clinical investigation. Curr Med Res Opin. 1980;7:104-109.
33. Qiu GX, Gao SN, Giacovelli G, et al. Efficacy and safety of glucosamine sulfate versus ibuprofen in patients with knee osteoarthritis. Arzneimittelforschung. 1998;48:469-474.
34. Shankar RR, Zhu JS, Baron AD. Glucosamine infusion in rats mimics the beta-cell dysfunction of non-insulin-dependent diabetes mellitus. Metabolism. 1998;47:573-577.
35. Head K. Personal communication of case reports. 1999.
36. Patti ME, Virkamaki A, Landaker EJ, et al. Activation of the hexosamine pathway by glucosamine in vivo induces insulin resistance of early postreceptor insulin signaling events in skeletal muscle. Diabetes. 1999;48:1562-1571.
37. Virkamaki A, Yki-Jarvinen H. Allosteric regulation of glycogen synthase and hexokinase by glucosamine-6-phosphate during glucosamine-induced insulin resistance in skeletal muscle and heart. Diabetes. 1999;48:1101-1107.
38. Almada AL, Harvey PW, Platt KJ. Effect of chronic oral glucosamine sulfate upon fasting insulin resistance index (FIRI) in nondiabetic individuals [abstract]. FASEB J. 2000;14:A750.
39. Monauni T, Zenti MG, Cretti A, et al. Effects of glucosamine infusion on insulin secretion and insulin action in humans. Diabetes. 2000;49:926-935.
40. Ajiboye R, Harding JJ. The non-enzymic glycosylation of bovine lens proteins by glucosamine and its inhibition by aspirin, ibuprofen and glutathione. Exp Eye Res. 1989;49:31-41.
41. 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;41:279-284.
42. Pavelka K, Gatterova J, Olejarova M, et al. Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study. Arch Intern Med. 2002;162:2113-2123.
43. McAlindon TE, LaValley MP, Gulin JP, et al. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA. 2000;283:1469-1475.
44. D’Ambrosio E, Casa B, Bompani R, et al. Glucosamine sulphate: a controlled clinical investigation in arthrosis. Pharmatherapeutica. 1981;2:504-508.
45. Drovanti A, Bignamini AA, Rovati AL. Therapeutic activity of oral glucosamine sulfate in osteoarthrosis: a placebo-controlled double-blind investigation. Clin Ther. 1980;3:260-272.
46. Braham R, Dawson B, Goodman C. The effect of glucosamine supplementation on people experiencing regular knee pain. Br J Sports Med. 2003;37:45-49.
47. Nguyen P, Mohamed SE, Gardiner D, et al. A randomized double-blind clinical trial of the effect of chondroitin sulfate and glucosamine hydrochloride on temporomandibular joint disorders: a pilot study. Cranio. 2001;19:130-139.
48. Scroggie DA, Albright A, Harris MD. The effect of glucosamine-chondroitin supplementation on glycosylated hemoglobin levels in patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized clinical trial. Arch Intern Med. 2003;163:1587-1590.
49. Yu JG, Boies SM, Olefsky JM. The effect of oral glucosamine sulfate on insulin sensitivity in human subjects. Diabetes Care. 2003;26:1941-1942.
50. Richy F, Bruyere O, Ethgen O, et al. Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis. Arch Intern Med. 2003;163:1514-1522.
51. Bruyere O, Pavelka K, Rovati LC, et al. Glucosamine sulfate reduces osteoarthritis progression in postmenopausal women with knee osteoarthritis: evidence from two 3-year studies. Menopause. 2004;11:138-143.
52. Tannis AJ, Barban J, Conquer JA. Effect of glucosamine supplementation on fasting and non-fasting plasma glucose and serum insulin concentrations in healthy individuals. Osteoarthritis Cartilag.e 2004;12:506-511.
53. Qiu GX, Weng XS, Zhang K, et al. A multi-central, randomized, controlled clinical trial of glucosamine hydrochloride/sulfate in the treatment of knee osteoarthritis. Zhonghua Yi Xue Za Zhi. 2005;85:3067-3070.
54. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. 2006;354:795-808.
55. McAlindon T, Formica M, LaValley M, et al. Effectiveness of glucosamine for symptoms of knee osteoarthritis: results from an internet-based randomized double-blind controlled trial. Am J Med. 2004;117:643-649.
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Last reviewed August 2013 by EBSCO CAM Review Board
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