• Glucosamine Hydrochloride, Glucosamine Sulfate, N-Acetyl Glucosamine
• Osteoarthritis (Relieving Symptoms and Possibly Slowing the Course of the Disease)
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.
Some but not all studies suggest that glucosamine supplements can relieve pain and improve mobility in osteoarthritis , a disease in which cartilage in joints becomes stiffer and may wear away. Besides possibly relieving symptoms, there is some evidence that glucosamine might actually slow the progression of the disease.
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.
For osteoarthritis, a typical dosage of glucosamine is 500 mg 3 times daily. A 1,500-mg dose taken once daily may also be effective. 6 Be patient; results take weeks to develop.
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 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 And finally, a trial failed to find benefit with glucosamine plus chondroitin.65
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
58. Anderson JW, Nicolosi RJ, Borzelleca JF, et al. Glucosamine effects in humans: a review of effects on glucose metabolism, side effects, safety considerations and efficacy. Food Chem Toxicol. 2004;43:187-201.
60. Muniyappa R, Karne RJ, Hall G, et al. Oral glucosamine for 6 weeks at standard doses does not cause or worsen insulin resistance or endothelial dysfunction in lean or obese subjects. Diabetes. 2006;55:3142-3150.
61. Herrero-Beaumont G, Ivorra JA, Del Carmen Trabado M, et al. Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator. Arthritis Rheum. 2007 Jan 30. [Epub ahead of print]
63. Arendt-Nielsen L, Weidner M, Bartholin D, Rosetzsky A. A double-blind randomized placebo controlled parallel group study evaluating the effects of ibuprofen and glucosamine sulfate on exercise induced muscle soreness. J Musculoskelet Pain. 2007;15:21-28.
64. Usha PR, Naidu MU. Randomised, double-blind, parallel, placebo-controlled study of oral glucosamine, methylsulfonylmethane and their combination in osteoarthritis. Clin Drug Investig. 2004;24:353-363.
65. Messier SP, Mihalko S, Loeser RF, et al. Glucosamine/chondroitin combined with exercise for the treatment of knee osteoarthritis: a preliminary study. Osteoarthritis Cartilage. 2007 Jun 8. [Epub ahead of print]
68. Bruyere O, Pavelka K, Rovati LC, et al. Total joint replacement after glucosamine sulphate treatment in knee osteoarthritis: results of a mean 8-year observation of patients from two previous 3-year, randomised, placebo-controlled trials. Osteoarthritis Cartilage. 2007 Jul 26. [Epub ahead of print]
69. Albert SG, Fishman Oiknine R, Parseghian S, et al. The effect of glucosamine on serum high density lipoprotein cholesterol and apolipoprotein AI levels in people with diabetes mellitus. Diabetes Care. 2007 Aug 6. [Epub ahead of print]
71. Kawasaki T, Kurosawa H, Ikeda H, et al. Additive effects of glucosamine or risedronate for the treatment of osteoarthritis of the knee combined with home exercise: a prospective randomized 18-month trial. J Bone Miner Metab. 2008;26:279-287.
Last reviewed May 2008 by EBSCO CAM Review Board
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