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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.
Sources
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.
Therapeutic Dosages
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. 1 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. 2 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. 3
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. 4 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. 5 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. 6 7 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. 8 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. 9 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. 10 Another trial involving 147 women with osteoarthritis found glucosamine to be no more effective than home exercises over an 18-month period. 11 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. 12 In another, very large (1,583-participant) study, neither glucosamine (as glucosamine hydrochloride) nor glucosamine plus chondroitin was more effective than placebo. 13 And finally, a trial failed to find benefit with glucosamine plus chondroitin. 14 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. 15 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. 16 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). 17 18 19 20 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. 21 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. 22 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. 23
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. 24 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.
References
- 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. 357(9252):251-6.
- Qiu GX, Weng XS, Zhang K, Zhou YX, Lou SQ, Wang YP, Li W, Zhang H, Liu Y. [A multi-central, randomized, controlled clinical trial of glucosamine hydrochloride/sulfate in the treatment of knee osteoarthritis] Zhonghua Yi Xue Za Zhi. 85(43):3067-70.
- Lippiello L, Woodward J, Karpman R, et al. In vivo chondroprotection and metabolic synergy of glucosamine and chondroitin sulfate. Clin Orthop. 2000;:229-240.
- 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. 357(9252):251-6.
- Noack W, Fischer M, Förster KK, Rovati LC, Setnikar I. Glucosamine sulfate in osteoarthritis of the knee. Osteoarthritis Cartilage. 2(1):51-9.
- Qiu GX, Gao SN, Giacovelli G, Rovati L, Setnikar I. Efficacy and safety of glucosamine sulfate versus ibuprofen in patients with knee osteoarthritis. Arzneimittelforschung. 48(5):469-74.
- Müller-Fassbender H, Bach GL, Haase W, Rovati LC, Setnikar I. Glucosamine sulfate compared to ibuprofen in osteoarthritis of the knee. Osteoarthritis Cartilage. 2(1):61-9.
- 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.
- Rindone JP, Hiller D, Collacott E, Nordhaugen N, Arriola G. Randomized, controlled trial of glucosamine for treating osteoarthritis of the knee. West J Med. 172(2):91-4.
- Rozendaal RM, Koes BW, van Osch GJ, Uitterlinden EJ, Garling EH, Willemsen SP, Ginai AZ, Verhaar JA, Weinans H, Bierma-Zeinstra SM. Effect of glucosamine sulfate on hip osteoarthritis: a randomized trial. Ann Intern Med. 148(4):268-77.
- Kawasaki T, Kurosawa H, Ikeda H, Kim SG, Osawa A, Takazawa Y, Kubota M, Ishijima M. 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. 26(3):279-87.
- 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. 51(5):738-45.
- Clegg DO, Reda DJ, Harris CL, Klein MA, O'Dell JR, Hooper MM, Bradley JD, Bingham CO 3rd, Weisman MH, Jackson CG, Lane NE, Cush JJ, Moreland LW, Schumacher HR Jr, Oddis CV, Wolfe F, Molitor JA, Yocum DE, Schnitzer TJ, Furst DE, Sawitzke AD, Shi H, Brandt KD, Moskowitz RW, Williams HJ. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. 354(8):795-808.
- Messier SP, Mihalko S, Loeser RF, Legault C, Jolla J, Pfruender J, Prosser B, Adrian A, Williamson JD. Glucosamine/chondroitin combined with exercise for the treatment of knee osteoarthritis: a preliminary study. Osteoarthritis Cartilage. 15(11):1256-66.
- Vlad SC, LaValley MP, McAlindon TE, Felson DT. Glucosamine for pain in osteoarthritis: why do trial results differ? Arthritis Rheum. 56(7):2267-77.
- Usha PR, Naidu MU. Randomised, Double-Blind, Parallel, Placebo-Controlled Study of Oral Glucosamine, Methylsulfonylmethane and their Combination in Osteoarthritis. Clin Drug Investig. 24(6):353-63.
- Brandt KD. Effects of nonsteroidal anti-inflammatory drugs on chondrocyte metabolism in vitro and in vivo. Am J Med. 83(5A):29-34.
- Brooks PM, Potter SR, Buchanan WW. NSAID and osteoarthritis--help or hindrance? J Rheumatol. 9(1):3-5.
- Shield MJ. Anti-inflammatory drugs and their effects on cartilage synthesis and renal function. Eur J Rheumatol Inflamm. 13(1):7-16.
- Palmoski MJ, Brandt KD. Effects of some nonsteroidal antiinflammatory drugs on proteoglycan metabolism and organization in canine articular cartilage. Arthritis Rheum. 23(9):1010-20.
- 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. 357(9252):251-6.
- Pavelká K, Gatterová J, Olejarová M, Machacek S, Giacovelli G, Rovati LC. 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.
- Bruyere O, Pavelka K, Rovati LC, Gatterová J, Giacovelli G, Olejarová M, Deroisy R, Reginster JY. 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. 16(2):254-60.
- Braham R, Dawson B, Goodman C. The effect of glucosamine supplementation on people experiencing regular knee pain. Br J Sports Med. 37(1):45-9; discussion 49.