Glucosamine

What is glucosamine?

Glucosamine is a natural substance found in mucopolysaccharides, mucoproteins, and chitin.¹

Glucosamine has attained great popularity as a nutritional supplement, primarily for osteoarthritis. There have been large industry-sponsored clinical trials as well as independent studies. Glucosamine is popular with patients, in part due to the encouragement of the medical profession who, when it was first marketed, advocated it as a low-risk alternative to non-steroidal anti-inflammatory drugs.²

Mechanism of action

Glucosamine occurs naturally (made by combination of glucose and the amino acid glutamine by the enzyme glucosamine synthetase) and is one of the 'building blocks' of cartilage. Glycosaminoglycans and proteoglycans are larger molecules made from glucosamine in combination with proteins such as collagen and elastin. They form the extracellular matrix and the cartilage in joints.

Animal models and in vitro experiments suggest that glucosamine stimulates cartilage production and inhibits degradation by influencing chondrocyte activity. However, limited in vivo studies suggest that very little orally ingested glucosamine reaches the joint. This does not rule out an unknown mechanism of action elsewhere but leaves no clear theory to explain an effect.^{3 4}

Evidence

Evidence is mixed, with most authors now agreeing that the case for any significant effect is unproven.

A Cochrane review in 2005 found mixed results but did not find evidence that glucosamine was superior to placebo for treating pain and functional impairment. suggested that whilst glucosamine appeared superior to placebo for treatment of pain and functional impairment from symptomatic osteoarthritis in around 2,500 patients, the benefit at three months was less than that measured at six weeks.⁵

A 2009 systematic review looked at five systematic reviews and one clinical guideline. It concluded that there was evidence for clinical impact but that more research was needed and that as none of the trial data came from the UK, caution should be exercised in applying it here.⁶

A 2012 review concluded that evidence was at best mixed and that any symptomatic effect observed varied greatly with the preparation used and the quality of the trial.⁴

A further systematic review in 2103 concluded that glucosamine was ineffective for pain reduction in patients with knee OA, but may have function-modifying effects when administered for more than 6 months. However, glucosamine showed no pain-reduction benefits after 6 months of therapy.⁷

A 2018 review of 61 randomised controlled trials found that oral celecoxib is more effective than placebo on relieving pain and improving physical function, followed by the combination of glucosamine and chondroitin. Paracetamol was considered likely to be the least effective intervention option for knee and/or hip osteoarthritis.⁸

Indications

The BNF states that glucosamine can be used for symptomatic relief of mild to moderate osteoarthritis of the knee.¹

However, NICE guidance recommends that glucosamine is not offered as a treatment option for osteoarthritis.⁹

Side effects

The side effects listed in the BNF are:¹

• Common or very common: constipation; diarrhoea; fatigue; gastrointestinal discomfort; headache; nausea.

• Uncommon: flushing; skin reactions.

• Rare or very rare: jaundice.

• Frequency not known: angioedema; asthma; diabetes mellitus; dizziness; hypercholesterolaemia; oedema; vomiting.

Contra-indications¹

The BNF does not provide any contraindications for glucosamine but the cautions list is as follows: asthma; impaired glucose tolerance; predisposition to cardiovascular disease.

The manufacturers advise avoiding during pregnancy and breastfeeding.

Dr Mary Lowth is an author or the original author of this leaflet.