Glucosamine (C₆H₁₃NO₅) is an

amino sugar In organic chemistry, an amino sugar (or more technically a 2-amino-2-deoxysugar) is a sugar molecule in which a hydroxyl group has been replaced with an amine group. More than 60 amino sugars are known, with one of the most abundant being ''N''- ...

and a prominent precursor in the

biochemical Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology an ...

synthesis of

glycosylated Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not ...

proteins and lipids. Glucosamine is part of the structure of two

polysaccharide Polysaccharides (), or polycarbohydrates, are the most abundant carbohydrates found in food. They are long chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages. This carbohydrate can react with w ...

s, chitosan and

chitin Chitin ( C8 H13 O5 N)n ( ) is a long-chain polymer of ''N''-acetylglucosamine, an amide derivative of glucose. Chitin is probably the second most abundant polysaccharide in nature (behind only cellulose); an estimated 1 billion tons of chit ...

. Glucosamine is one of the most abundant

monosaccharide Monosaccharides (from Greek '' monos'': single, '' sacchar'': sugar), also called simple sugars, are the simplest forms of sugar and the most basic units (monomers) from which all carbohydrates are built. They are usually colorless, water- so ...

s. Produced commercially by the

hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysi ...

shellfish Shellfish is a colloquial and fisheries term for exoskeleton-bearing aquatic invertebrates used as food, including various species of molluscs, crustaceans, and echinoderms. Although most kinds of shellfish are harvested from saltwater environ ...

exoskeleton An exoskeleton (from Greek ''éxō'' "outer" and ''skeletós'' "skeleton") is an external skeleton that supports and protects an animal's body, in contrast to an internal skeleton ( endoskeleton) in for example, a human. In usage, some of the ...

s or, less commonly, by fermentation of a grain such as corn or wheat, glucosamine has many names depending on country. Although a common

dietary supplement A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...

, there is little evidence that it is effective for relief of

arthritis Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In som ...

pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...

, and is not an approved

prescription drug A prescription drug (also prescription medication or prescription medicine) is a pharmaceutical drug that legally requires a medical prescription to be dispensed. In contrast, over-the-counter drugs can be obtained without a prescription. The r ...

Dietary supplement

Oral glucosamine is a

and is not a

. Glucosamine is marketed as a supplement to support the structure and function of joints, and the marketing is targeted to people with

osteoarthritis Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the ...

. Commonly sold forms of glucosamine are glucosamine sulfate, glucosamine chondroitin, glucosamine hydrochloride, and ''N''-acetylglucosamine. Of the three commonly available forms of glucosamine, only glucosamine sulfate is given a "likely effective" rating for treating osteoarthritis. Glucosamine is often sold in combination with other supplements such as

chondroitin sulfate Chondroitin sulfate is a sulfated glycosaminoglycan (GAG) composed of a chain of alternating sugars ( N-acetylgalactosamine and glucuronic acid). It is usually found attached to proteins as part of a proteoglycan. A chondroitin chain can have ove ...

and

methylsulfonylmethane Methylsulfonylmethane (MSM) is an organosulfur compound with the formula (CH3)2SO2. It is also known by several other names including methyl sulfone and dimethyl sulfone (DMSO2). This colorless solid features the sulfonyl functional group and is ...

. Glucosamine, along with commonly used chondroitin, is not routinely prescribed to treat people who have symptomatic osteoarthritis of the knee, as there is insufficient evidence that this treatment is helpful. As is common with heavily promoted dietary supplements, the claimed benefits of glucosamine are based principally on clinical and laboratory studies. Clinical studies on glucosamine efficacy are divided, with some reporting relief from arthritic pain and stiffness, while others report no benefit above placebo. , there is no evidence that consumption of glucosamine by sport participants prevents or limits joint damage after injury.

Adverse effects and drug interactions

Glucosamine with or without chondroitin elevates the international normalized ratio (INR) in individuals who are taking the blood thinner,

warfarin Warfarin, sold under the brand name Coumadin among others, is a medication that is used as an anticoagulant (blood thinner). It is commonly used to prevent blood clots such as deep vein thrombosis and pulmonary embolism, and to prevent st ...

. It may also interfere with the efficacy of

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemother ...

for treating

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

symptoms. Adverse effects are mild and infrequent and may include stomach upset, constipation, diarrhea, headache, and rash. Since glucosamine is usually derived from the shells of

, it may be unsafe for those with

shellfish allergy Shellfish allergy is among the most common food allergies. "Shellfish" is a colloquial and fisheries term for aquatic invertebrates used as food, including various species of molluscs such as clams, mussels, oysters and scallops, crustace ...

. Many manufacturers of glucosamine derived from shellfish include a warning that those with a seafood allergy should consult a healthcare professional before taking the product. Alternatively, non-shellfish-derived forms of glucosamine are available. Another concern has been that the extra glucosamine could contribute to diabetes by interfering with the normal regulation of the hexosamine biosynthesis pathway, but several investigations found no evidence that this occurs. Other studies conducted in lean or obese subjects concluded that oral glucosamine at standard doses does not affect

insulin resistance Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to the hormone insulin. Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood glucose (blood sugar ...

Biochemistry

Glucosamine is naturally present in the shells of shellfish, animal bones, bone marrow, and fungi. D-Glucosamine is made naturally in the form of glucosamine-6-phosphate, and is the biochemical precursor of all nitrogen-containing sugars. Specifically in humans, glucosamine-6-phosphate is synthesized from fructose 6-phosphate and

glutamine Glutamine (symbol Gln or Q) is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral ...

by glutamine—fructose-6-phosphate transaminase as the first step of the hexosamine biosynthesis pathway. The end-product of this pathway is uridine diphosphate ''N''-acetylglucosamine (UDP-GlcNAc), which is then used for making

glycosaminoglycan Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case ...

s, proteoglycans, and glycolipids. As the formation of glucosamine-6-phosphate is the first step for the synthesis of these products, glucosamine may be important in regulating their production; however, the way that the hexosamine biosynthesis pathway is actually regulated, and whether this could be involved in contributing to human disease remains unclear.

Manufacturing

Most glucosamine is manufactured by processing

from the shells of

including shrimp, lobsters, and crabs. To meet the demands of vegetarians and others with objections to shellfish, manufacturers have brought glucosamine products to market made using fungus '' Aspergillus niger'' and from fermenting corn.

History

Glucosamine was first prepared in 1876 by Georg Ledderhose by the

with concentrated

hydrochloric acid Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution with a distinctive pungent smell. It is classified as a strong acid. It is a component of the gastric acid in the dige ...

. The

stereochemistry Stereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms that form the structure of molecules and their manipulation. The study of stereochemistry focuses on the relationships between stereoi ...

was not fully determined until the 1939 work of Walter Haworth.

Legal status

United States

In the United States, glucosamine is not approved by the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) for medical use in humans. Since glucosamine is classified as a

in the United States, evidence of safety is required by FDA regulations, but evidence of efficacy is not required so long as it is not advertised as a treatment for a medical condition. In 2004, the FDA declared there was insufficient evidence for supplement manufacturers to state that glucosamine was effective for treating arthritis, joint degeneration, or

cartilage Cartilage is a resilient and smooth type of connective tissue. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck ...

deterioration, a position remaining in effect as of 2018.

Europe

In most of Europe, glucosamine is approved as a medical drug and is sold in the form of glucosamine sulfate. In this case, evidence of safety and efficacy is required for the medical use of glucosamine and several guidelines have recommended its use as an effective and safe therapy for

. The Task Force of the European League Against Rheumatism (EULAR) committee has granted glucosamine sulfate a level of toxicity of 5 in a 0-100 scale, and recent OARSI (Osteoarthritis Research Society International) guidelines for hip and knee osteoarthritis indicate an acceptable safety profile. By 2014, the OARSI did not recommend glucosamine for disease modification, and considered it "uncertain" for symptom relief, in knee osteoarthritis.

Class-action lawsuits

In 2013, without admitting fault, manufacturer Rexall Sundown and NBTY agreed to pay up to to settle consumer claims related to the wording of certain claims on the packaging of glucosamine bottles sold at

Costco Costco Wholesale Corporation ( doing business as Costco Wholesale and also known simply as Costco) is an American multinational corporation which operates a chain of membership-only big-box retail stores (warehouse club). As of 2022, Costc ...

under the Kirkland label. In August 2012, a class-action lawsuit was filed in New York claiming that 21st Century Healthcare, Inc. had falsely advertised that its "Glucosamine 750 Chondroitin 600 Triple Strength" dietary supplements would restore lost cartilage. In April 2013, a San Diego man launched a proposed class-action lawsuit in California Federal Court accusing Nutramax Laboratories,

Walmart Walmart Inc. (; formerly Wal-Mart Stores, Inc.) is an American multinational retail corporation that operates a chain of hypermarkets (also called supercenters), discount department stores, and grocery stores from the United States, headquarter ...

and Rite Aid of falsely advertising the effectiveness of glucosamine.

Research

Humans

Because glucosamine is a precursor for

s, and glycosaminoglycans are a major component of

, research has focused on the potential for supplemental glucosamine to improve cartilage structure and alleviate

, but there is little evidence from

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...

s that it is effective for alleviating arthritis pain.

Bioavailability

Two studies measured the concentrations of glucosamine in the

synovial fluid Synovial fluid, also called synovia, elp 1/sup> is a viscous, non-Newtonian fluid found in the cavities of synovial joints. With its egg white–like consistency, the principal role of synovial fluid is to reduce friction between the articul ...

and plasma after oral administration of glucosamine sulfate to both healthy volunteers and people with osteoarthritis. In the first study, glucosamine sulfate was given to healthy volunteers in doses of 750, 1,500, or 3,000 mg once daily. In the second study, oral glucosamine sulfate capsules (1,500 mg) were given daily for two weeks to 12 people with

. Glucosamine concentrations in plasma and

increased significantly from baseline levels, and the levels in the two fluids were highly correlated. The authors interpreted that these levels could be biologically advantageous to articular cartilage, but the levels are still ten- to one hundredfold lower than required to positively influence the

(

chondrocytes Chondrocytes (, from Greek χόνδρος, ''chondros'' = cartilage + κύτος, ''kytos'' = cell) are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteog ...

) to build new tissue. Glucosamine sulfate uptake in

may be as much as 20%, or it could be negligible, indicating no biological significance.

Veterinary medicine

Dogs

Some studies have shown efficacy of glucosamine supplementation for dogs with osteoarthritis pain, particularly in combination with other nutraceuticals like chondroitin, while others have not. A trial of oral combination capsules (glucosamine, chondroitin, and manganese ascorbate) in dogs with osteoarthritis found no benefit on either gait analysis or subjective assessments by the veterinarian or owner.

Horses

The use of glucosamine in equine medicine exists, but one meta-analysis judged extant research too flawed to be of value in guiding treatment of horses. A number of studies have measured the bioavailability of glucosamine after oral administration to horses. When given as a single oral dose (9 g) with or without

(3 g) to ten horses, glucosamine (hydrochloride) was detected in the blood with a maximum level of at two hours after dosing. Another study examined both the serum and the joint

after nasogastric (oral) or intravenous administration of 20 mg/kg glucosamine hydrochloride to eight adult horses. Although joint fluid concentrations of glucosamine reached 9–15 μmol/L following intravenous dosing, it was only 0.3–0.7 μmol/L with nasogastric dosing. The authors calculated that these glucosamine synovial fluid levels achieved by the oral route were 500 times lower than that required to have a positive effect on the metabolism of

cells. A follow up study by the same research group compared glucosamine sulfate with glucosamine hydrochloride at the same dose (20 mg/kg) in eight horses and found a higher fluid concentration with the sulfate preparation (158 ng/mL compared to 89 ng/mL one hour post oral dose). They concluded that these higher

levels obtained with the sulfate derivative were still too low to have a relevant biological effect on articular cartilage. A three-month trial of an oral dosage regime of a commercial preparation of glucosamine sulfate, chondroitin sulfate and

was performed in veteran horses with no effect on gait stiffness, with exercise alone in the control group being effective. The intravenous use of a combination of ''N''-acetylglucosamine, pentosan polysulfate and sodium hyaluronate in horses with surgically-induced osteoarthritis saw improvements in X-ray changes to the cartilage but not histologically or in biochemical outcomes, suggesting more evidence is needed for this combination and route of administration.

References

External links

*
Glucosamine and Chondroitin for Osteoarthritis Pain, Arthritis Foundation

Glucosamine
DailyMed, U.S. National Library of Medicine * {{portal bar, Medicine Dietary supplements Hexosamines