Glucosamine is a precursor of multiple cartilage constituents. It is extracted from chitin (in shells of crabs, oysters, and shrimp) and is taken in tablet or capsule form, usually as glucosamine sulfate, but sometimes as glucosamine hydrochloride. Efforts are being made to find alternative biorenewable sources, including metabolically engineered fungi and E. coli(1). Glucosamine is often taken with chondroitin sulfate.
(See also Overview of Dietary Supplements.)
Glucosamine is claimed to relieve pain due to osteoarthritis, possibly with both analgesic and disease-modifying effects. Mechanism is unknown. Mechanism for glucosamine sulfate may be related to improved glycosaminoglycan synthesis as a result of the sulfate moiety. Dosage of glucosamine in all its forms is 500 mg orally 3 times a day.
Evidence supports use of glucosamine sulfate from Rotta Research Laboratorium for treatment of mild-to-moderate osteoarthritis of the knee when given for at least 6 months (2-3). Other formulations still need to be rigorously evaluated. The role of glucosamine sulfate in the treatment of more severe knee osteoarthritis and osteoarthritis in other locations is less well-defined.
The Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), a randomized, double-blinded, placebo-controlled, multicenter clinical trial of 1583 patients with symptomatic osteoarthritis of the knee reported that, alone and in combination with chondroitin sulfate (400 mg 3 times a day), glucosamine hydrochloride (500 mg 3 times a day) did not reduce pain effectively in the all-patient group. However, an exploratory analysis found pain relief with combination therapy in a subgroup of patients with moderate-to-severe knee pain (4). Overall, although studies have reported that the combination of glucosamine and chondroitin provide the most optimal benefit (5), the 2019 American College of Rheumatology/Arthritis Foundation recommends against glucosamine for treatment of any form of osteoarthritis, primarily because of concerns regarding industry sponsorship and publication bias (6).
Allergy (in patients who have shellfish allergy and take forms extracted from shellfish), dyspepsia, fatigue, insomnia, headache, photosensitivity, and nail changes may occur. Patients with chronic liver disease should also avoid glucosamine if possible, because of potential hepatotoxicity when taking glucosamine with or without chondroitin (7).
Liu L, Liu Y, Shin HD, et al: Microbial production of glucosamine and N-acetylglucosamine: advances and perspectives. Appl Microbiol Biotechnol 97(14):6149-6158, 2013. doi: 10.1007/s00253-013-4995-6.
Wu D, Huang Y, Gu Y, et al: Efficacies of different preparations of glucosamine for the treatment of osteoarthritis: a meta-analysis of randomised, double-blind, placebo-controlled trials. Int J Clin Pract 67(6):585-594, 2013. doi: 10.1111/ijcp.12115.
Eriksen P, Bartels EM, Altman RD, et al: Risk of bias and brand explain the observed inconsistency in trials on glucosamine for symptomatic relief of osteoarthritis: a meta-analysis of placebo-controlled trials. Arthritis Care Res (Hoboken) 66(12):1844-1855, 2014. doi: 10.1002/acr.22376.
Clegg DO, Reda DJ, Harris CL, et al: Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med 354(8):795-808, 2006. doi: 10.1056/NEJMoa052771.
Hochberg MC, Martel-Pelletier J, Monfort J, et al: Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib. Ann Rheum Dis 75:37-44, 2016. doi:10.1136/annrheumdis-2014-206792.
Kolasinski SL, Neogi T, Hochberg MC, et al: 2019 American College of Rheumatology/Arthritis Foundation guideline for the management of osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken) 72(2):149‐162. doi:10.1002/acr.24131.
Cerda C, Bruguera M, Parés A: Hepatotoxicity associated with glucosamine and chondroitin sulfate in patients with chronic liver disease. World J Gastroenterol 19(32):5381-5384, 2013. doi: 10.3748/wjg.v19.i32.5381.
The following is an English-language resource that may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
National Institutes of Health (NIH), National Center for Complementary and Integrative Health: Information on the use of glucosamine and chondroitin for osteoarthritis