Glucosamine is a popular nutritional supplement and natural component of cartilage that is frequently combined with chondroitin sulfate and used for osteoarthritis and nonspecific joint pain. Glucosamine has been implicated in isolated case reports in causing clinically apparent liver injury, but the role of glucosamine as opposed to other herbal components or contaminants has not been shown, and liver injury due to glucosamine or chondroitin must be very rare if it occurs at all.


Glucosamine (gloo kose' a meen) is a natural component of cartilage that is a widely used as an over-the-counter nutritional supplement purported to decrease the pain and cartilage loss of osteoarthritis. Glucosamine is commonly taken in combination with chondroitin (kon droe' i tin), which is a glycosaminoglycan that is also present in cartilage. Glucosamine is an amino sugar and a prominent molecule in the biochemical pathways of synthesis of glycosylated proteins and lipids. It is also a major component of keratin sulfate and hyaluronic acid which are present in articular cartilage and synovial fluid. Both glucosamine and chondroitin are reduced in osteoarthritis. Glucosamine is commercially available alone and in combination with chondroitin and widely used for osteoarthritis and arthritic pain. Controlled trials of glucosamine with and without chondroitin have yielded conflicting results. In the largest US study of glucosamine for early osteoarthritis, glucosamine alone and the combination of glucosamine and chondroitin were no more beneficial than placebo in alleviating joint pain or preventing progression of cartilage damage. Glucosamine is typically taken in doses of 500 mg three times daily and chondroitin sulfate in doses of 200 to 400 mg three times daily. Side effects are uncommon and mild and may include abdominal discomfort, nausea, fatigue and headache; but in placebo controlled trials, side effects during glucosamine therapy were no more frequent than with receipt of placebo.


In controlled trials, glucosamine and its combination with chondroitin have not been linked to serum enzyme elevations or to instances of clinically apparent liver injury. In addition, cases of clinically apparent liver injury have not been reported from prospective trials. Recently, several cases reports and small series of clinically apprent liver injury attributed to glucosamine (with or without chondroitin) have been published, but the relationship of glucosamine itself as opposed to other herbals in the implicated products or to potential contaminants, remains unclear and several cases were considered only "possibly" related to glucosamine. The time to onset is usually 1 to 4 weeks after starting the preparation and the pattern of injury is typically hepatocellular or mixed. At least one instance of acute liver failure has been reported. Immunoallergic features (rash, fever, eosinophilia) can occur, but are usually not prominent. Most patients were reported to recover within 4 to 8 weeks of stopping. There have not been instances of rechallenge with glucosamine, and the purity and concentration of glucosamine in the products used have not been reported.

Likelihood score: D (possible rare cause of clinically apparent liver injury).

Mechanism of Injury

The mechanism by which glucosamine or chondroitin might cause liver injury is unclear. Glucosamine is a simple amino sugar and chondroitin a glycosaminoglycan. Both are natural products found in cartillage in humans and mammals. The glucosamine in commercially available dietary supplements is usually prepared from the exoskeletons of shellfish or from fermentation of grain. The concentration, purity and freedom from contaminants in commercially available preparations of glucosamine and chondroitin is not always clear.

Outcome and Management

The severity of the liver injury in reports of glucosamine hepatotoxicity has varied from mild, asymptomatic elevations in serum enzymes to clinically apparent hepatitis that can be severe and even fatal. There is no information on management or the role for corticosteroids or other interventions except for prompt discontinuation of the suspected agent.

Drug Class: Herbal and Dietary Supplements


Case 1. Acute liver injury attributed to a glucosamine containing dietary and herbal supplement.

[Modified from: Ossendza RA, Grandval P, Chinoune F, Rocher F, Chapel F, Bernardini D. [Acute cholestatic hepatitis due to glucosamine forte]. Gastroenterol Clin Biol 2007; 31: 449-50. French.]

A 52 year old man developed weakness followed by jaundice and generalized itching arising 3 weeks after starting capsules of Glucosamine forte. He had no previous history of liver disease or drug allergies and denied alcohol abuse and risk factors for viral hepatitis. He had no other major medical illnesses and was taking glucosamine for low back pain. On presentation, physical examination revealed jaundice, but no fever or rash. Laboratory testing showed a total bilirubin of 10.9 mg/dL, ALT 263 U/L, AST 63 U/L, GGT 240 U/L and alkaline phosphatase 714 U/L (Table). He tested negative for markers of hepatitis A, B, C and E as well as EBV, cytomegalovirus and herpes simplex. Tests for autoantibodies were negative. Abdominal ultrasound and CT scans were normal with no evidence of biliary obstruction. A liver biopsy showed canalicular cholestasis, hepatocellular necrosis and lobular inflammation with one microgranuloma, which overall was considered compatible with drug induced liver injury. Glucosamine had been stopped a week before clinical presentation and his symptoms improved rapidly. Serum bilirubin rose to 13.9 and then gradually began to fall. Liver tests fell into the near normal range within 8 weeks of stopping the supplement and were completely normal when he was seen 4 months later.

Key Points

Laboratory Values


Some values estimated from Figure 1.


This was a typical case of cholestatic-mixed hepatitis due to a medication, but in this instance the only drug being taken was a commercial preparation of glucosamine. Typical of cholestatic hepatitis was the presentation with pruritus and the somewhat delayed recovery. While the dietary supplement appears to be fairly convincingly implicated as the cause of the liver injury, what is uncertain is whether glucosamine per se versus a possible contaminant was responsible. Glucosamine is a simple amino sugar and is used by millions of people. Reports of hepatic injury from glucosamine are few (less than a dozen in the published literature) and always limited by the lack of proof of purity of the dietary supplement used.



Glucosamine – Generic

Chondroitin sulfate – Generic


Herbal and Dietary Supplements


(Glucosamine Hydrochloride) Fact Sheet at MedlinePlus, NLM

(Glucosamine Sulfate) Fact Sheet at MedlinePlus, NLM

(Chondroitin Sulfate) Fact Sheet at MedlinePlus, NLM

Fact Sheet at National Center for Complementary and Integrative Health, NIH



References updated: 12 March 2018

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