Glucosamine vs MSM: what to choose and for whom

When your knee hurts after a run or squats, your hand reaches on its own for a jar “for joints”. But what to choose — glucosamine, MSM or their combination? Our editorial team offers a practical approach: who can benefit from each option, how to choose a form and dose, how to assess the result and when supplements are not the answer.

Whom these supplements make sense for at all

Glucosamine and MSM have been studied mainly in people with osteoarthritis — a degenerative joint disease that occurs more often after the age of 45–50, with excess weight and after injuries. It is precisely in this group that a possible benefit should be sought.

For young athletes with acute pain after an injury, these supplements are not a first-line remedy. Pain, swelling, “clicking” or joint instability may indicate damage to the meniscus, ligaments or cartilage, and these should be assessed by a doctor. A supplement here may only delay the correct diagnosis.

It is also important to understand that the basis of osteoarthritis management, according to all guidelines, is exercise, body-weight control and patient education. Supplements are at best an additional tool, not a replacement for these measures.

But if you have chronic moderate pain, a diagnosis of osteoarthritis has already been made and you are doing exercises, a trial course of a supplement may be a reasonable step — provided that you clearly assess the result.

When it is more logical to choose glucosamine

Glucosamine has the largest volume of research among “joint” supplements, and this is its main advantage. If you want to try an agent for which it is already known what to expect and what not, glucosamine is a clear starting point.

Positive results were more often obtained with crystalline glucosamine sulphate at a dose of 1500 mg once a day, as in the study by Reginster and colleagues (2001). It is precisely this form that the European society ESCEO considers a possible agent for the baseline therapy of knee osteoarthritis. Studies with the hydrochloride, such as GAIT, were less convincing.

So if choosing glucosamine, it is logical to look specifically for the sulphate with a clearly stated dose. It is also worth remembering that the American (ACR) and international (OARSI) guidelines do not recommend glucosamine — that is, the scientific community has no consensus on it.

Glucosamine may be appropriate for older people with knee osteoarthritis who are already doing exercises and want to try an additional agent with a long history of safe use.

When you can try MSM

MSM is an option for those in whom glucosamine did not help or is not suitable, for example because of a seafood allergy (although non-crustacean glucosamine also exists). MSM is produced synthetically, so the problem of a shellfish allergy does not arise here.

The evidence base for MSM is smaller: the pilot study by Kim and colleagues (2006) showed a reduction in pain and an improvement in function in knee osteoarthritis with 6 g of MSM per day for 12 weeks. The study is small, so expectations should be kept moderate.

There are also small studies of MSM in the context of physical exercise — on muscle soreness and markers of oxidative stress — but their results are inconsistent, and it is too early to draw practical conclusions for athletes.

The combination of glucosamine and MSM is another option. Usha and Naidu (2004) reported that the combination gave a somewhat better result than each substance separately, but this is a single small study, and it has not yet received broader confirmation.

• choose glucosamine if you want the option with the most research;
• consider MSM if glucosamine did not suit you or you have a seafood allergy;
• a combination is possible, but the advantage is weakly proven.

Forms, doses and a “trial course”

The usual dose of glucosamine in studies is 1500 mg per day, taken at once or in several doses. For MSM, studies used from 1.5 to 6 g per day, more often splitting the dose into two intakes. It is better to take both supplements with meals to reduce stomach discomfort.

A practical approach is a “trial course” with clear criteria. Before starting, rate your pain on a scale from 0 to 10, note how many steps you can climb without pain, and whether you wake up at night. After 12 weeks, repeat the assessment. If there is no change, there is no point in continuing.

Count the dosage in combination products carefully: to get 1500 mg of glucosamine and several grams of MSM, you often need many capsules a day, and manufacturers sometimes state a serving that contains much less.

Who should refrain or consult a doctor

People taking warfarin should use glucosamine only after a consultation: cases of an enhanced anticoagulant effect have been described. Patients with diabetes should monitor their glycaemia at the start of use.

With a crustacean allergy, choose glucosamine from non-crustacean sources or consider other options together with a doctor. People with asthma are also advised to use caution, since isolated reactions have been described.

For pregnant and breastfeeding women these supplements are not recommended because of insufficient safety data. Children and adolescents usually do not need them.

And most importantly: if joint pain is accompanied by swelling, redness, fever, blocked movement or arose after an injury, you need a doctor, not a trial course of supplements.

Editorial conclusions

For people with osteoarthritis who want to try a supplement, a logical starting point is crystalline glucosamine sulphate 1500 mg per day as an addition to exercise and weight control.

MSM is an alternative in cases of glucosamine intolerance or its ineffectiveness; its evidence base is smaller and the effect moderate.

Any of these supplements should be assessed against clear criteria and abandoned if there is no result after 3 months.

We also recommend reading “Glucosamine or MSM: what's the difference”, our review of chondroitin and an article on exercises for the knee joint.

References

1. 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.
2. 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.
3. Kim LS, Axelrod LJ, Howard P, et al. Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial. Osteoarthritis Cartilage. 2006;14(3):286–294.
4. Usha PR, Naidu MUR. Randomised, double-blind, parallel, placebo-controlled study of oral glucosamine, methylsulfonylmethane and their combination in osteoarthritis. Clin Drug Investig. 2004;24(6):353–363.
5. Bruyère O, Honvo G, Veronese N, et al. An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Semin Arthritis Rheum. 2019;49(3):337–350.
6. Bannuru RR, Osani MC, Vaysbrot EE, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019;27(11):1578–1589.
7. Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American College of Rheumatology/Arthritis Foundation guideline for the management of osteoarthritis of the hand, hip, and knee. Arthritis Care Res. 2020;72(2):149–162.