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National Institutes of Health • National Center for Complementary and Integrative Health

NCCIH Clinical Digest. For health professionals.

Dietary Supplements for Osteoarthritis:
What the Science Says

May 2014

Glucosamine, Chondroitin Sulfate, or the Combination

Glucosamine and chondroitin sulfate—taken separately or together—are marketed for supporting joint health. They have also been widely used for treating OA. The preponderance of evidence indicates little or no meaningful effect on pain or function. Independent clinical practice guidelines published in 2012 by the American College of Rheumatology (ACR) [95KB PDF], and in 2010 by the American Academy of Orthopaedic Surgeons (AAOS) recommend not using glucosamine or chondroitin for OA. Recommendations from Osteoarthritis Research Society International (OARSI) published in 2014 conclude that current evidence does not support use of glucosamine or chondroitin in knee OA for disease-modifying effects, but leave unsettled the question of whether either may provide symptomatic relief. 

Strength of the Evidence Base

  • The evidence base on the effects of glucosamine and chondroitin sulfate for osteoarthritis is of sufficient size and quality to permit independent systematic reviews and meta-analyses, and inclusion of specific recommendations in independent clinical practice guidelines.


  • A 2009 Cochrane systematic review of 25 studies found evidence of improvement in pain and function in studies using one manufacturer’s preparation of glucosamine, not in studies using preparations from other companies.
  • Three reports from the NIH-funded Glucosamine/chondroitin Arthritis Intervention Trial (GAIT), compared glucosamine, chondroitin sulfate, the two in combination, celecoxib, and placebo. There were no clinically significant differences in pain or function following 6 months and 2 years of treatment. There was also no evidence that glucosamine, chondroitin, or the combination could prevent the progression of OA, based on joint space width measurements.
  • A 2007 meta-analysis considered 20 controlled clinical trials comparing chondroitin with placebo or n treatment in 3846 patients with OA of the hip or knee. The investigators concluded that “large-scale, methodologically sound trials indicate that the symptomatic benefit of chondroitin is minimal or nonexistent. Use of chondroitin in routine clinical practice should therefore be discouraged.”
  • A 2010 network meta-analysis analyzed 10 glucosamine and chondroitin trials involving 3,803 patients with knee or hip OA published similar results. The investigators concluded that glucosamine, chondroitin, or a combination did not significantly reduce pain or change joint space compared to placebo.
  • A 2014 double-blind randomized placebo-controlled trial compared glucosamine, chondroitin, the combination, or placebo in 605 patients with knee osteoarthritis. While symptomatic improvement was seen in all four groups over the study period, there were no differences in symptomatic improvement. A very small but statistically significant reduction in joint space narrowing was seen in the glucosamine–chondroitin combination group at 2 years.


Glucosamine and chondroitin appear to be relatively safe and well tolerated when used in suggested doses over a 2-year period. In a few specific situations, however, possible side effects or drug interactions should be considered:

  • No serious side effects have been reported in large, well-conducted studies of people taking glucosamine, chondroitin, or both for up to 3 years.
  • However, glucosamine or chondroitin may interact with warfarin.
  • Although recent studies conducted by the U.S. Food and Drug Administration show that high doses of glucosamine hydrochloride taken by mouth in rats may promote cartilage regeneration and repair, this dose was also found to cause severe kidney problems in the rats—a serious side effect of the treatment.

Dimethyl Sulfoxide (DMSO) and Methylsulfonylmethane (MSM)

DMSO and MSM are two chemically related dietary supplements that have been used for arthritic conditions. However, evidence does not suggest that DMSO and MSM are helpful for OA symptoms.

Strength of the Evidence Base

  • The current evidence base on efficacy of DMSO and MSM for osteoarthritis is limited to clinical trials reports and a meta-analysis of a small number of studies.


  • A 2011 meta-analysis of a small number of studies looked at topical (applied to skin) DMSO and oral (taken by mouth) MSM as potential products for OA of the knee. There was no evidence of significant reductions in pain compared to placebo.


  • Although there are limited safety data available, some side effects from topical DMSO have been reported, including upset stomach, skin irritation, and garlic taste, breath, and body odor.
  • Only minor side effects are associated with MSM in humans including allergy, upset stomach, and skin rashes.

S-Adenosyl-L-methionine (SAMe)

SAMe is a molecule that is naturally produced in the body and is often taken as a dietary supplement. There is not enough evidence to support the use of SAMe for OA of the knee or hip.

Strength of the Evidence Base

  • The current evidence base on efficacy of SAMe for osteoarthritis is limited to clinical trials reports and a systematic review.


  • A 2009 systematic review concluded that there was not enough evidence to use SAMe for OA of the knee or hip. The reviewers did indicate that small improvements in pain and function were seen in some but not all studies.


  • SAMe is generally considered safe.
  • Common side effects include gastrointestinal problems, dry mouth, headache, sweating, dizziness, and nervousness.

Herbal Remedies

Although some results suggest that a few herbs may be beneficial for OA symptoms, the overall evidence is weak. In addition, not all herbs have been studied or prepared in a consistent way, and conclusions among reviews of the literature provide conflicting interpretations. There is also a general lack of safety data available for many herbal medicines.

Avocado/Soybean Unsaponifiables

Avocado/soybean unsaponifiables (ASU) are supplements made from avocado oil and soybean oil extracts and have been studied, mostly in Europe, for their effects on osteoarthritis.

Strength of the Evidence Base

  • The current evidence base on efficacy of ASU is limited to clinical trials reports and a systematic review.


  • A 2009 Cochrane review of two combined studies of ASU showed beneficial effects on functional index, pain, intake of NSAIDs, and global evaluation.


  • There are limited safety data available.

Other Herbal Remedies

Strength of the Evidence Base

  • The current evidence base on efficacy of other herbal therapies for osteoarthritis, such as willow bark and tipi tea, is limited to clinical trials reports and a systematic review.


  • Authors of a 2009 Cochrane review concluded that evidence for willow bark, topical capsaicin, and tipi tea is insufficient to support their use.


  • There are limited safety data available.


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NCCIH Clinical Digest is a service of the National Center for Complementary and Integrative Health, NIH, DHHS. NCCIH Clinical Digest, a monthly e-newsletter, offers evidence-based information on complementary health approaches, including scientific literature searches, summaries of NCCIH-funded research, fact sheets for patients, and more.

The National Center for Complementary and Integrative Health is dedicated to exploring complementary health products and practices in the context of rigorous science, training complementary health researchers, and disseminating authoritative information to the public and professionals. For additional information, call NCCIH's Clearinghouse toll-free at 1-888-644-6226, or visit the NCCIH Web site at NCCIH is 1 of 27 institutes and centers at the National Institutes of Health, the Federal focal point for medical research in the United States.



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