Glucosamine and Chondroitin Found to be Ineffective for Relief of Arthritis Pain

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For over a decade, chondroitin and glucosamine have been recommended in guidelines, prescribed by general practitioners and rheumatologists, and used by patients as over-the-counter medications to modify the clinical and radiological course of arthritis. Nevertheless, a recent meta-analysis in the British Journal of Medicine (BMJ) measuring pain intensity and joint inflammation in over 3,800 patients concludes that chondroitin, glucosamine and their combination do not reduce joint pain or have an impact on narrowing of joint space [1].

Knee cartilage

Cartilage is an elastic, fibrous connective tissue found in many areas of the human body, including the joints between bones, the elbow, the knee and the ankle. Glucosamine and chondroitin are key structural components in cartilage and are frequently prescribed to reduce joint pain and slow the progression of the disease. It has been thought that oral administration of these compounds compensates for the loss of cartilage in damaged joints. Glucosamine and chondroitin are partially absorbed in the intestine and several studies suggest that at least some of what was ingested can reach the joints. Nevertheless, the recent study, not a clinical trial itself, but a study of studies (i.e. a meta-analysis), compared glucosamine hydrochloride, glucosamine sulphate, and/or chondroitin with placebos and found that none reduced pain intensity or changed the width of joint space (i.e. reduction of inflammation) [1].

The ten trials evaluated were each large scale, enrolling at least 200 patients with arthritis of the knee or hip, for a total of 3,803 patients. Each trial was randomized and controlled. Results among the trials were inconsistent, spurring this network meta-analysis to try to reconcile them. The authors note that [1]:

Results from randomised trials about the effectiveness of chondroitin and glucosamine are conflicting. Trials that have reported large effects on joint pain were often hampered by poor study quality and small sample sizes, whereas large methodologically sound trials often found only small or no effects.

Indeed, small trials did not always adequately conceal allocation, so the investigators were not always properly blinded. Patients were not always properly blinded either. Not all small trials included an intention to treat analysis, meaning that not all patients initially randomized were necessarily analyzed at each time point. And the experimental preparations had not always been subjected to appropriate quality control, so their concentrations were unconfirmed. Moreover, the authors mention that industry-independent trials show smaller effects than commercially funded trials, suggesting bias.

In the meta-analysis, statistical analysis showed no clinically relevant effect of chondroitin, glucosamine or their combination on perceived joint pain. The effects on minimal width of joint space were also clinically irrelevant and non-significant.

It has recently been shown in a double-blind, controlled crossover study of 45 patients with osteoarthritis that another popular arthritis treatment, the wearing of copper and magnetic bracelets, does not alleviate pain [2-3]. Yet arthritis sufferers have few options. Arthritis can be treated with analgesics and non-steroidal anti-inflammatory drugs, but these can have serious gastrointestinal and cardiovascular side effects, especially when used for long periods of time. Like other illnesses, arthritis can wax and wane but always regresses to an average severity. Sufferers will often seek treatment when their symptoms flare up and then misinterpret a natural abatement as a response to whatever treatment they chose.

Researchers are still trying to rationally design a therapy for arthritis. A five year clinical trial in England is testing the ability of mesenchymal stem cells, those derived from a patient’s own blood marrow, to repair worn cartilage in 70 people with arthritis of the knee. Hopefully, these people can be spared knee replacement surgery. Vitamin D is also being investigated as a treatment for arthritis, since vitamin D has anti-inflammatory activity on the T cells that are so damaging in the development of rheumatoid arthritis and many people with arthritis have low levels of vitamin D [4].

The authors of this meta-analysis conclude by indicating that they found no harmful effects of glucosamine or chondroitin, so patients perceiving a benefit from them can continue to take them without worry. But since “the range and distribution of pain scores in patients receiving supplements and placebo are near identical,” they suggest that these patients pay for the supplements on their own and the coverage of costs by health authorities and/or health insurers for these preparations to patients who have not received other treatments should be discouraged.

References

  1. Wandel et al. Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. BMJ. 2010 Sep 16;341:c4675. doi: 10.1136/bmj.c4675.
    View abstract
  2. Richmond et al. Therapeutic effects of magnetic and copper bracelets in osteoarthritis: a randomised placebo-controlled crossover trial. Complement Ther Med. 2009 Oct-Dec;17(5-6):249-56. Epub 2009 Aug 28.
    View abstract
  3. Pittler et al. Static magnets for reducing pain: systematic review and meta-analysis of randomized trials. CMAJ. 2007 Sep 25;177(7):736-42.
    View abstract
  4. Jeffery et al. 1,25-Dihydroxyvitamin D3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3. J Immunol. 2009 Nov 1;183(9):5458-67.
    View abstract