Medically reviewed on Aug 15, 2018
Common Name(s): Chitosamine
Glucosamine is being investigated extensively for its action in osteoarthritis. However, there is a lack of consensus in clinical trials regarding its efficacy.
In clinical studies of arthritis, glucosamine dosage has typically been 1.5 g/day, as a single dose or in divided doses.
No absolute contraindications have been identified.
Information regarding safety and efficacy in pregnancy and lactation is lacking.
None well documented.
Glucosamine is generally considered safe. Use caution when administering to persons with poorly controlled diabetes.
Mutagenicity studies are limited and conflicting.
Glucosamine is a component of mucopolysaccharides, mucoproteins, and chitin. Chitin is found in yeasts, fungi, arthropods, and various marine invertebrates as a major structural component of the exoskeleton. It also occurs in other animals and members of the plant kingdom. 1
Chemically, chitin is a biopolymer that is like cellulose but differs in having predominantly unbranched chains of beta (1-4)-2-acetamido-2-deoxy-D-glucose or N-acetyl-D-glucosamine residues. Basically, it can be perceived as a cellulose derivative in which the C-2 hydroxyl groups of the polymer have been replaced by acetamide moieties. Chitin is a normal component of shellfish such as crab, shrimp, and lobster. 2 , 3 Glucosamine is isolated from chitin and is chemically 2-amino-2-deoxyglucose. 3 It can also be prepared synthetically. Glucosamine sulfate is the preferred form. N-acetyl-D-glucosamine (NAG) is also sold but has no advantages over glucosamine, nor has the potential of NAG in a sustained-release or topical formulation shown any greater benefit. 2 , 4 , 5
Uses and Pharmacology
Glucosamine is commercially available alone or in combination with chondroitin sulfate (with or without mineral elements). Only studies evaluating the effect of glucosamine alone are discussed in this monograph.Osteoarthritis
In osteoarthritis, the most common form of arthritis, there is a progressive degeneration of cartilage glycosaminoglycans (GAG). Formation of glucosamine is the rate-limiting step in GAG biosynthesis. It is biochemically formed from the glycolytic intermediate fructose-6-phosphate by way of amination of glutamine as the donor, ultimately yielding glucosamine-6-phosphate. This is subsequently acetylated to galactosamine before being incorporated into growing GAG. Thus, glucosamine taken orally is proposed to provide an essential building block for cartilage regeneration; however, this may be an oversimplification. 3 , 6 , 7 , 8Animal data
Animal studies have been conducted but are less important than the large number of clinical trials.Clinical data
An update of an older Cochrane meta-analysis is available that includes high quality clinical trials. An earlier review found that glucosamine sulfate 1,500 mg/day for 6 weeks resulted in an improvement in function and less pain, 9 but the inclusion of newer, higher quality trial data show less consistent and less favorable results. 6 , 10 For the 20 included studies (N = 2,570), glucosamine demonstrated a 28% improvement in pain outcome and a 21% improvement in function using the Lequesne Index. Outcomes using the Western Ontario and McMaster osteoarthritis (WOMAC) pain, stiffness, and function indices did not reach statistical significance compared with placebo. 6 A limitation of the analysis is the quality of the preparations used in the individual trials. Analysis of the studies using the Rotta brand of glucosamine (available in the United States) provides differing results from the non- Rotta studies. Studies using the Rotta preparation reported glucosamine to be significantly better in reduction of pain compared with placebo. Studies using non- Rotta preparation showed no statistical difference compared with placebo. Variations in the content of glucosamine compared with label amounts can be up to 100%. 6 , 10
The findings of 2 large trials have been published subsequent to the Cochrane meta-analysis. The Glucosamine Unum In Die Efficacy (GUIDE) trial (N = 318) was industry-sponsored and conducted in a European population, while the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) (N = 1,583) was sponsored by the National Institutes of Health and conducted in the United States. 11 , 12 Both trials considered a total daily dosage of glucosamine 1,500 mg for osteoarthritis of the knee. The GUIDE trial favored glucosamine over placebo using the Lequesne Index and WOMAC function index, but results were not significant for the WOMAC pain index. Acetaminophen achieved similar results to glucosamine for the WOMAC indices. 11 Overall results of GAIT indicated no differences for glucosamine over placebo using the WOMAC and outcome measures in rheumatology clinical trials—Osteoarthritis Research Society International indices. However, a subgroup analysis, which was not part of the original study design, suggested glucosamine was effective in treating moderate to severe osteoarthritis (n = 354). 12
Three studies using radiographic methodology have been conducted regarding the ability of glucosamine to protect cartilage from further loss. A subgroup analysis of the results of 2 of these studies favored glucosamine over placebo. After 3 years, no further joint space narrowing was shown in postmenopausal women (319 of a total of 414 participants) taking glucosamine 1,500 mg/day. Total WOMAC indices were also favorable for glucosamine. 6 , 13 , 14 , 15Other uses
Glucosamine dosage in clinical studies of arthritis has typically been 1.5 g/day, as a single dose or in divided doses up to 3 times per day. 3 , 6 Doses of up to 3,200 mg/day have been used in trials, but evidence for improved efficacy at this dosage has not been established. 3 Healthy young adults had no adverse reactions from infusions of 9.7 g, while 1 in 5 subjects experienced headache when 30.5 g was infused. 3
Information regarding safety and efficacy in pregnancy and lactation is lacking. Avoid use.
None well documented. Glucosamine metabolism does not depend on the CYP-450 pathway. 3
The majority of adverse reactions reported have been mild, including itching and gastric discomfort (eg, diarrhea, heartburn, nausea, vomiting). These reactions are similar to those experienced with placebo, but are fewer than those reported with nonsteroidal anti-inflammatory drugs. 6
Concern regarding the effect of glucosamine on glucose homeostasis has been raised based largely on theoretical considerations, animal studies, and case reports. 19 , 20 , 21 , 22 , 23 , 24 However, specifically designed studies have failed to show any detrimental effects associated with usual dosages, and no concerns have been raised regarding adverse reactions in the many randomized clinical trials conducted. 3 , 6 , 25 , 26 , 27 Long-term effects of glucosamine on insulin secretion and insulin resistance have not been established. Advise patients with poorly controlled diabetes to use caution. 25
A theoretical link between glucosamine and the development of atherosclerosis is suspected, but there is no supporting clinical evidence. Glucosamine has been found to have a stimulatory effect on the growth rate and toughness of nails. A case of possible exacerbation of asthma with the use of a glucosamine/chondroitin preparation has been reported, as well as an immediate hypersensitivity reaction to glucosamine. 6
Mutagenicity studies have shown variable results. Glucosamine failed to show mutagenicity in Escherichia coli reverse mutation and Salmonella typhimurium studies, but it induced breaks in bacteriophage DNA. Glucosamine produced a significant increase in chromosome aberration frequency in mice bone marrow cells versus control, whereas no significant increases in micronucleated polychromatic erythrocyte and bone marrow cells were demonstrated in another experiment. 3
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