Many people with knee osteoarthritis turn to glucosamine and MSM (methylsulphonylmethane) supplements seeking relief from pain and stiffness. These over-the-counter products are widely available in UK pharmacies and health shops, often marketed as natural joint support remedies. Glucosamine is a compound found in cartilage, whilst MSM provides sulphur for connective tissue formation. Despite their popularity, clinical evidence for their effectiveness remains mixed and controversial. NICE guidance explicitly recommends against offering glucosamine for osteoarthritis treatment, noting that perceived benefits may reflect placebo effects. This article examines the evidence, typical dosages, safety considerations, and when to seek medical advice for knee pain.

What Are Glucosamine and MSM?

Glucosamine is a naturally occurring compound found in cartilage, the tough tissue that cushions joints. In supplement form, it is typically derived from shellfish shells or produced synthetically. The two main forms available are glucosamine sulphate and glucosamine hydrochloride, with glucosamine sulphate being the most extensively studied. Glucosamine is thought to play a role in building and maintaining healthy cartilage, and many people take it as a dietary supplement to support joint health, particularly in osteoarthritis of the knee.

Methylsulphonylmethane (MSM) is an organosulphur compound that occurs naturally in plants, animals, and humans. It provides a source of sulphur, which is essential for the formation of connective tissue, including cartilage. MSM is marketed as a supplement with purported anti-inflammatory and analgesic properties. It is often combined with glucosamine in over-the-counter joint health products, with manufacturers suggesting that the two compounds may work synergistically to reduce joint pain and improve function.

In the UK, most high-street glucosamine and MSM products are sold as food supplements regulated by the Food Standards Agency. However, it's important to note that if glucosamine products make specific therapeutic claims about treating osteoarthritis, the Medicines and Healthcare products Regulatory Agency (MHRA) may classify them as medicines requiring a marketing authorisation. These products come in various formulations including tablets, capsules, powders, and liquids. As food supplements, they are subject to less rigorous testing for efficacy than prescription medications. Many people with knee osteoarthritis turn to these products seeking relief from pain and stiffness, particularly when looking for alternatives to conventional analgesics.

Clinical Evidence for Effectiveness in Knee Osteoarthritis

The clinical evidence for glucosamine and MSM in treating knee osteoarthritis remains mixed and somewhat controversial. Large-scale trials have produced conflicting results, leading to ongoing debate within the medical community about their true effectiveness.

For glucosamine, the landmark GAIT (Glucosamine/chondroitin Arthritis Intervention Trial) study found that glucosamine hydrochloride alone did not significantly reduce pain compared to placebo in the overall study population. However, a subgroup analysis suggested possible benefits in patients with moderate-to-severe pain. European studies using glucosamine sulphate have shown more promising results, with some trials demonstrating modest improvements in pain and function. Systematic reviews, including Cochrane reviews, have concluded that certain glucosamine preparations may provide some pain relief, but the effect size is small and may not be clinically meaningful for most patients.

NICE guidance on osteoarthritis (NG226) explicitly recommends not to offer glucosamine for the treatment of osteoarthritis. The guidance notes that whilst some patients report subjective benefit, this may reflect a placebo effect. Despite this, some clinicians adopt a pragmatic approach, suggesting that patients who wish to try glucosamine at their own expense may do so for a trial period of 2–3 months to assess individual response, though this is outside NICE recommendations.

Evidence for MSM is even more limited. Small studies have suggested potential benefits for pain and physical function, but these trials often have methodological limitations including small sample sizes and short duration. There is currently insufficient high-quality evidence to draw firm conclusions about MSM's effectiveness. The combination of glucosamine and MSM has been studied in a few trials, with some suggesting additive benefits, but again, the evidence base remains weak and further research is needed to establish whether this combination offers genuine therapeutic advantage over placebo.

Typical Dosage and How to Take Them

If you decide to try glucosamine and MSM supplements, it's important to understand the typical doses used in studies, though you should always follow the specific directions on your product label.

For glucosamine, the doses typically used in studies are:

• 1,500 mg daily of glucosamine sulphate, often taken as a single dose or divided into two or three doses throughout the day

• Glucosamine hydrochloride has been studied at similar doses, though evidence for this form is less robust

• Tablets or capsules are usually taken with food to reduce the risk of gastrointestinal upset

• It may take 4–8 weeks of consistent use before any potential effects become apparent

For MSM, doses used in studies include:

• 1,000–3,000 mg daily, often divided into two or three doses

• Starting with a lower dose (1,000 mg) and gradually increasing may improve tolerability

• MSM can be taken with or without food, though taking it with meals may reduce potential stomach discomfort

When taking combination products containing both glucosamine and MSM, check the label carefully to ensure you understand the amounts of each ingredient and follow the manufacturer's instructions.

Important considerations:

• If you have a shellfish allergy, choose vegetarian or synthetic glucosamine products, as most glucosamine is derived from shellfish

• Glucosamine may affect blood glucose levels, so people with diabetes should monitor their blood sugar more frequently when starting supplementation

• Glucosamine sulphate products are often stabilised with potassium chloride or sodium chloride, which may be relevant if you have kidney disease, heart failure, or take medications like ACE inhibitors or potassium-sparing diuretics

• The MHRA has issued advice that glucosamine may interact with warfarin, potentially affecting INR levels—if you take anticoagulants, discuss supplementation with your GP or anticoagulation clinic and ensure more frequent INR monitoring initially

• These supplements are not generally recommended for people under 18 years of age

• If you notice no improvement after 2–3 months of consistent use, these supplements are unlikely to benefit you, and continued use may not be worthwhile

Potential Side Effects and Safety Considerations

Glucosamine and MSM are generally considered safe and well-tolerated by most people when taken at recommended doses. However, as with any supplement, side effects can occur, and certain individuals should exercise caution.

Common side effects of glucosamine include:

• Mild gastrointestinal symptoms such as nausea, heartburn, diarrhoea, or constipation

• Drowsiness or headache (less common)

• Skin reactions in sensitive individuals

These effects are typically mild and often resolve with continued use or by taking the supplement with food. Serious adverse effects are rare.

MSM side effects are generally minimal but may include:

• Gastrointestinal discomfort, bloating, or diarrhoea

• Headaches

• Some users report difficulty sleeping if taken late in the day or increased energy, though these effects are anecdotal

• Skin reactions or itching

Safety considerations and contraindications:

Pregnancy and breastfeeding: There is insufficient evidence regarding the safety of glucosamine and MSM during pregnancy and lactation. As a precautionary measure, these supplements should be avoided unless specifically recommended by a healthcare professional.

Diabetes: Glucosamine may theoretically affect insulin sensitivity and blood glucose control, though clinical evidence is inconsistent. People with diabetes should monitor blood glucose levels more closely when starting glucosamine and inform their diabetes care team.

Asthma: Some case reports have suggested a possible link between glucosamine and worsening asthma symptoms, though this remains unconfirmed. Individuals with asthma should be vigilant for any respiratory changes.

Anticoagulant therapy: The MHRA has highlighted that glucosamine may enhance the effects of warfarin, leading to increased bleeding risk. If you take warfarin or other anticoagulants, consult your GP or anticoagulation clinic before starting glucosamine, and ensure more frequent INR monitoring initially.

Shellfish allergy: Most glucosamine is derived from shellfish shells. Whilst the allergenic proteins are thought to be removed during processing, individuals with severe shellfish allergies should choose vegetarian alternatives or avoid glucosamine altogether.

If you experience any suspected side effects from these supplements, you can report them through the MHRA Yellow Card Scheme (yellowcard.mhra.gov.uk or the Yellow Card app). Stop taking the supplement and seek urgent medical attention if you develop signs of a severe allergic reaction such as swelling of the face or tongue, or difficulty breathing.

Always inform your GP and pharmacist about all supplements you are taking, as they can interact with prescribed medications or affect the interpretation of certain medical tests.

Alternatives and When to See Your GP

If glucosamine and MSM prove ineffective or unsuitable, several evidence-based alternatives are available for managing knee osteoarthritis pain.

NICE-recommended approaches include:

• Exercise and physical activity: Strengthening and aerobic exercises are among the most effective interventions for knee osteoarthritis, improving pain, function, and quality of life. Physiotherapy can provide tailored exercise programmes.

• Weight management: For those who are overweight, even modest weight loss (5–10% of body weight) can significantly reduce knee pain and improve function.

• Topical NSAIDs: Creams or gels containing non-steroidal anti-inflammatory drugs (such as ibuprofen or diclofenac) applied directly to the knee can provide pain relief with fewer systemic side effects than oral medications and are recommended as first-line treatment.

• Oral analgesics: Paracetamol is not recommended for routine use in osteoarthritis due to limited effectiveness. Oral NSAIDs (such as ibuprofen or naproxen) may be considered for short-term use when topical NSAIDs are insufficient, but should be prescribed with a proton pump inhibitor (PPI) to reduce gastrointestinal risks. They should be used at the lowest effective dose for the shortest duration, with careful consideration of cardiovascular, gastrointestinal, and renal risks.

• Intra-articular corticosteroid injections: For moderate-to-severe pain or during flares, corticosteroid injections into the knee joint can provide temporary relief, typically lasting several weeks to months.

NICE guidance (NG226) specifically recommends against offering intra-articular hyaluronic acid injections for osteoarthritis.

You should contact your GP if:

• Knee pain is severe, persistent, or significantly affecting your daily activities and quality of life

• You experience sudden worsening of pain, swelling, redness, or warmth in the knee (which may indicate infection or other acute problems)

• The knee gives way, locks, or you cannot bear weight on it

• You develop systemic symptoms such as fever alongside joint pain (seek same-day medical attention as this could indicate septic arthritis)

• Conservative measures including supplements, exercise, and over-the-counter pain relief have not provided adequate benefit after 2–3 months

• You are considering starting glucosamine or MSM but have diabetes, take anticoagulants, or have other significant medical conditions

Your GP can assess your knee pain comprehensively, arrange investigations such as X-rays if needed, optimise your treatment plan, and refer you to specialist services including physiotherapy, orthopaedics, or rheumatology when appropriate. Early intervention with evidence-based treatments offers the best chance of maintaining mobility and quality of life with knee osteoarthritis.

Frequently Asked Questions