Side Effects of Glucosamine and Chondroitin

Glucosamine and chondroitin are among the best-selling joint supplements in Britain, used by runners, lifters and older adults alike. They are generally regarded as safe, but "generally" is not the same as "always". The editorial team reviews the known side effects, the interactions that really matter and what the evidence says about whether they are worth taking.

What glucosamine and chondroitin are

Glucosamine is an amino sugar that the body uses to make glycosaminoglycans, key components of cartilage, tendons and ligaments. Supplements are usually made from the shells of crustaceans such as shrimp and crab, although shellfish-free versions produced by fermentation of corn or other sources are also available.

Chondroitin sulfate is a larger molecule, a glycosaminoglycan found naturally in cartilage. Commercial chondroitin is extracted mainly from bovine, porcine, chicken or shark cartilage. Its quality varies considerably between manufacturers, and analyses have found products containing much less chondroitin than declared.

The two are often combined in a single product, sometimes with MSM, collagen or turmeric. The most common daily amounts used in research are 1,500 mg of glucosamine and 800–1,200 mg of chondroitin, which is also roughly what many UK products provide.

Glucosamine is sold in two main salt forms: glucosamine sulfate and glucosamine hydrochloride. Many of the more positive trials used a crystalline glucosamine sulfate preparation, which has led to debates about whether all forms are equally effective.

Common side effects

In clinical trials, the overall rate of side effects with glucosamine and chondroitin has been similar to placebo. The large GAIT trial in the United States, which compared glucosamine, chondroitin, both together, celecoxib and placebo in people with knee osteoarthritis, found adverse events to be generally mild and evenly distributed.

The most frequently reported complaints are digestive. They usually appear in the first few weeks and often settle on their own or when the supplement is taken with food.

• Nausea and indigestion
• Heartburn and abdominal discomfort
• Bloating and wind
• Diarrhoea or, less commonly, constipation
• Headache and drowsiness (occasional)
• Skin reactions such as rash or itching (rare)

Splitting the daily amount into two or three doses with meals is a simple way to reduce stomach upset. If symptoms persist, switching brands or forms sometimes helps, as excipients and capsule ingredients differ between products.

Chondroitin is typically even better tolerated than glucosamine. Its most common side effects are mild stomach upset and, rarely, swelling of the eyelids or legs, hair loss or irregular heartbeat, although causality for these rare reports is uncertain.

The warfarin interaction

The most clinically important safety issue is the interaction with warfarin. Case reports and pharmacovigilance data have described increases in INR, sometimes with bruising or bleeding, in people on warfarin who started glucosamine, with or without chondroitin.

The mechanism is not fully understood, but the signal was strong enough for UK regulatory advice to recommend that people taking warfarin should not take glucosamine. The British National Formulary lists this interaction as one to avoid or monitor closely.

Direct oral anticoagulants, such as apixaban, have been studied less, and antiplatelet drugs such as aspirin and clopidogrel may also add to bleeding tendencies in theory. Anyone on blood-thinning medicines should mention joint supplements to their pharmacist.

Allergy, blood sugar, asthma and other concerns

Because most glucosamine comes from crustacean shells, people with shellfish allergy are often told to avoid it. Shellfish allergy is usually triggered by proteins in the flesh, not the shell polysaccharide, and studies have not shown a clear allergic risk. Nevertheless, product labels in the UK carry warnings, and caution is reasonable.

Glucosamine is an amino sugar, and early animal studies raised concerns about insulin resistance. A comprehensive review of human data concluded that oral glucosamine at standard doses does not appear to adversely affect glucose metabolism in healthy people or in those with well-controlled diabetes, although monitoring is wise when starting.

There are isolated reports of asthma exacerbations linked to glucosamine. The evidence is limited, but people with asthma should stop the supplement if they notice wheezing or tightness in the chest after starting it.

Pregnant and breastfeeding women should avoid glucosamine and chondroitin because of a lack of safety data. People with kidney disease should check with their doctor, partly because some products contain sodium or potassium salts and partly because of limited data in this group.

Is it worth the risk? What the evidence shows

The benefit side of the equation is uncertain. A network meta-analysis in the BMJ in 2010 concluded that glucosamine, chondroitin and their combination did not reduce joint pain or affect joint space narrowing in a clinically meaningful way compared with placebo. Some individual trials, particularly with crystalline glucosamine sulfate, reported more favourable results.

The NICE guideline on osteoarthritis (NG226, 2022) recommends that glucosamine should not be offered for managing osteoarthritis. It emphasises exercise, weight management and, where needed, topical or oral analgesics instead.

For athletes without osteoarthritis, evidence is even thinner. Joint discomfort in active people more often reflects training load, technique or tendon problems, which respond better to load management and physiotherapy than to supplements.

Some people still report subjective relief. If someone decides to try glucosamine and chondroitin, a reasonable approach is a time-limited trial of around three months, then stopping if there is no clear improvement.

Conclusions of the editorial team

Glucosamine and chondroitin are well tolerated by most people, with mild digestive upset being the main side effect.

The key safety issue is the interaction with warfarin, which can raise INR and bleeding risk. Caution is also appropriate for shellfish allergy, diabetes and asthma, and in pregnancy.

The evidence for benefit is weak, and NICE does not recommend glucosamine for osteoarthritis. If you try it, set a time limit and judge honestly whether it helps.

The editorial team also recommends our articles on MSM for joints, on collagen peptides and tendon health, and on managing knee pain in runners.

References

1. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. 2006;354(8):795–808.
2. Wandel S, Jüni P, Tendal B, et al. Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. BMJ. 2010;341:c4675.
3. Knudsen JF, Sokol GH. Potential glucosamine-warfarin interaction resulting in increased international normalized ratio: case report and review of the literature and MedWatch database. Pharmacotherapy. 2008;28(4):540–548.
4. Simon RR, Marks V, Leeds AR, Anderson JW. A comprehensive review of oral glucosamine use and effects on glucose metabolism in normal and diabetic individuals. Diabetes Metab Res Rev. 2011;27(1):14–27.
5. Reginster JY, Deroisy R, Rovati LC, et al. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet. 2001;357(9252):251–256.
6. National Institute for Health and Care Excellence. Osteoarthritis in over 16s: diagnosis and management (NG226). London: NICE; 2022.