It is estimated that over 20 million Americans suffer from osteoarthritis (OA), an often painful condition in which the articular cartilage, which serves as a cushion and gliding surface between the bones, deteriorates and wears away. With the aging of our population, it is anticipated that this number will double over the next two decades.
In 2004 the estimated medical costs associated with the treatment of arthritis exceeded $86 billion. The traditional treatment of osteoarthritis has included activity modification, lifestyle changes, both over-the-counter and prescription medications, injection therapy and surgery. Over the past several decades additional interest has also been shown in the use of complementary and alternative medicine (CAM). Foremost among these has been the widely publicized and marketed use of the dietary supplements glucosamine and chondroitin sulfate. In a large national survey which evaluated American’s use of CAM, arthritis was among the top reasons given. Glucosamine with or without chondroitin were among the most frequent “non-vitamin, non-mineral, natural products” used. This has occurred despite the fact that until recently there has been no well-designed study proving their effectiveness or safety.
Both glucosamine and chondroitin sulfate are naturally occurring substances found within the human body. They are one of the major components of connective tissue substrate and are an important component of articular cartilage. Glucosamine is involved in stimulating the formation and repair of cartilage. Chondroitin sulfate is responsible for preventing other enzymes from degrading the substructure of cartilage. Glucosamine is usually obtained from the shells of shrimp, lobster and crabs while chondroitin sulfate is harvested from the cartilage of sharks and cattle. Both substances are also capable of being laboratory-produced. They are usually sold individually or in combination and recently are appearing with other supplements, combinations touted by their manufacturers to treat and even cure a growing number of joint and soft tissue conditions and injuries. Being dietary supplements, they are not regulated by the United States’ Food and Drug Administration (FDA) in the same manner of prescription drugs. Therefore, their efficacy and safety are more often than not unscientific claims made by their manufacturers and distributors. Nor does the FDA take an active role in insuring the quality control of these manufactured supplements. Numerous studies have in fact shown that the quality and quantity of these within individual products varies considerably and, more often than not, is not accurately reflected on their packaging. They are widely available through pharmacies, grocery stores, bulk food distributors, “health food” outlets and even online.
A fairly large number of early studies used to promote these supplements to the lay population, on closer scrutiny, involved small groups of patients in poorly designed retrospective studies. Standardization of testing protocols was often times not utilized. Also of concern is that many of these studies were supported by the manufacturers and distributors of the products themselves opening the door to a very real possibility of biasing results and under-reporting potential side effects.
In an attempt to clarify the value and safety of the use of glucosamine and chondroitin sulfate in the treatment of osteoarthritis, the National Institute of Health (NIH) through its National Center for Complementary and Alternative Medicine (NCCAM) and the National Institute of Arthritis, Musculoskeletal and Skin Diseases, instituted a study known as the Glucosamine/Chondroitin Arthritis Interventional Trial (GAIT). It was initiated in the year 2000 and its results were subsequently published in the New England Journal of Medicine in February 2006. The study was multicenter, prospective, double-blind, placebo and celecoxib controlled. A prospective study involves enrolling patients utilizing strict criteria and then assigning them randomly to various treatment groups. Having a double-blind set-up, neither the prescribing physicians nor the patients themselves knew what drug they were receiving. This prevents bias in the patients’ perspective of subjective responses to treatment and physicians’ evaluation of outcomes. The mean age of the patients was 59 years and 64% of the patients were women. They were randomly assigned to treatment groups which received either 1500 mg of glucosamine daily, 1200 mg of chondroitin sulfate daily, the glucosamine and chondroitin sulfate in combination, 200 mg of celecoxib (Celebrex) daily or a placebo for 24 weeks. A placebo is a sham drug of inert material utilized in controlled studies. It is essentially a “sugar” pill. The patients were monitored on a regular basis and pre-enrollment and post-study pain and function assessments were accomplished using several well-established and standardized forms. The results were then evaluated using strict statistical analysis.
According to the author of the study, “Overall glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20%.” The supplements taken alone or in combination did not reduce pain effectively particularly in those patients with mild to moderate subjective pain symptoms. The subgroup of patients with moderate to severe pain seemed to have a greater response that was significantly higher with combined supplement therapy than placebo. They felt, however, that this group was perhaps too small to warrant calling these results conclusive and that an additional study was necessary and is currently ongoing.
The incident of adverse reactions in all treatment groups was small. Of additional interest, however, was a very high response rate in the subgroup of patients administered the placebo. They did note this high rate of response to placebo has been seen in other studies evaluating various treatment modalities in patients with osteoarthritis. They felt in part this may be partly due to the patients’ biases and expectations as well as the enrollment of patients with relatively mild symptoms.
It must be remembered that this large study was designed primarily for the purpose of evaluating the effectiveness in glucosamine and chondroitin sulfate in alleviating pain symptoms in patients with osteoarthritis. An additional potential benefit of these dietary supplements as touted by their manufacturers, distributors and the lay media has been that of delaying and potentially reversing the effects of established osteoarthritis. To date, no well-designed study is available or has been performed to substantiate these claims; therefore, one should not assume that these supplements are capable of living up to these claims. Evidently the NIH, as a follow-up study to the GAIT, plans on evaluating these claims. There does not appear to be any justification for individuals taking these dietary supplements for these reasons at the present time. In particular, there is no evidence to show that these substances taken prophylactically by individuals who do not currently have osteoarthritis will prevent or delay its onset in the future.
- In a large, well-designed study undertaken by the National Institute of Health and reported in the New England Journal of Medicine, the use of the dietary supplements glucosamine and chondroitin sulfate have not been shown to be any more effective in significantly reducing pain in patients with osteoarthritis of the knee as compared to a placebo. The use of these dietary supplements considering their lack of FDA monitoring, the expense incurred in their use and still long-term questions regarding their safety, should be viewed with skepticism.
- While the GAIT study did seem to show that there may be some benefit in patients with moderately severe pain symptoms, the authors of the study felt that the study group was too small to draw accurate conclusions and that further evaluation of its use in these particular patients is warranted.
- Glucosamine and chondroitin sulfate have not been scientifically proven to delay the progression or alter the natural history of osteoarthritis. Taking these supplements for this reason or in the belief their prophylactic use may prevent or delay the development of osteoarthritis should probably be discouraged.
- Patients need to be aware of the fact that dietary supplements such as glucosamine and chondroitin sulfate are not regulated by the FDA in the same manner as prescription drugs and product quality, quantity and safety are of concern.
- Traditional treatment regimes utilized in osteoarthritis including over-the-counter analgesics such as acetaminophen as well as prescribed nonsteroidal anti-inflammatory medications, activity modification, supervised exercise programs, weight loss and patient education remain the keystones in the treatment of patients with osteoarthritis. They should certainly not be abandoned in the belief that dietary supplements based on our current understanding are an essential part of these regimes nor should they be used to supplement all or portions of them.
Clegg, D.O., et al, New England Journal of Medicine, 2006, Volume 354 – 8, pages 795-808
New England Journal of Medicine:www.nejm.org
National Center for Complementary and Alternative Medicine:www.nccam.nih.gov
National Institute of Health: www.nih.gov
Tri-Valley Orthopedic Specialists, Inc.: www.trivalleyorthopedics.com