A Look at Recent Clinical Trials

Osteoarthritis affects more than 20 million individuals in the United States and is one of the leading causes of disability in the aging population.¹ Osteoarthritis is a degenerative disorder leading to the breakdown of cartilage within the joint. The joints most typically affected include the joints of the hands and the larger joints of the hips and knees. Many supplements claim to help relieve the pain of osteoarthritis, including the very popular glucosamine and chondroitin supplements.

Glucosamine and Chondroitin: What are They and What do They Do?

Glucosamine and chondroitin are molecules that contribute to glycosaminoglycan and proteoglycan structure. Glycosaminoglycans and proteoglycans are important constituents of joint cartilage, and they aid in attracting water to the joint. When a patient has osteoarthritis, the loss of these constituents within the cartilage matrix leads to dehydration and fissuring of the cartilage.

Do Glucosamine and Chondroitin Supplements Work?

In recent years, a number of studies have emerged evaluating the benefits of glucosamine and chondroitin supplementation. One study evaluated the effect of 1,500mg of glucosamine sulfate in addition to exercises in 39 women with knee arthritis versus exercise alone for 12 weeks. The study found that glucosamine supplementation had no additional effect beyond that of exercise alone.² One review evaluated the results of 19 previous studies on over 3,000 patients and compared the effects of glucosamine sulfate versus glucosamine Hcl. The analysis concluded that glucosamine sulfate may have some positive effects on function in those with knee arthritis, but that glucosamine Hcl has no positive effects on function or pain after 6 months of therapy.³ One clinical trial followed 605 patients with osteoarthritis of the knee who supplemented with 1,500mg of glucosamine sulfate, 800mg chondroitin sulfate, both 1,500mg glucosamine sulfate and 800mg chondroitin sulfate, or a placebo for two years. After two years, there were significant improvements in certain x-ray parameters of the knee but no change in pain level.⁴According to the Cochrane Review, the conclusions surrounding glucosamine supplementation are mixed. The authors of the Cochrane Review found that a slight improvement in pain and functioning may be seen with glucosamine supplementation, though many of the positive clinical trials are old and of poor quality.⁵The Cochrane Review found that chondroitin supplementation may improve pain more significantly than glucosamine. The Review found that chondroitin users experienced between 10-20% pain reduction after 6 months. The Review also found positive changes in the joint appearance on x-ray after chondroitin supplementation.⁶

Are Glucosamine and Chondroitin Supplements Safe?

Many clinical trials have shown that glucosamine and chondroitin supplements have the same safety as placebo pills. Patients who did have side effects experienced mild reactions that were temporary. These reactions included digestive upset, diarrhea, and nausea. These supplements have also demonstrated safety for long term use up to three years.⁷

Additional Considerations

When evaluating these clinical trials, it is important for readers to remember the underlying cause of osteoarthritis. Glucosamine and chondroitin are intended to repair damaged cartilage and improve hydration of the joint. However, if the cause of the damaged cartilage is not addressed, then glucosamine and chondroitin supplementation may be ineffective. Naturopathic physicians should evaluate the timing of glucosamine and chondroitin supplementation and consider these supplements once underlying factors are under control, including weight reduction, blood sugar control, and underlying inflammation. Once the ongoing joint damage has slowed down or ceased, glucosamine and chondroitin supplements may be appropriate to help rebuild the cartilage matrix.

Conclusions

In the last 3 years, the research on glucosamine and chondroitin supplementation has generated mixed results. Many recent trials have found little to no benefit from supplementation, while some studies have found slight improvements in joint functioning, x-ray findings, and pain. The Cochrane Review, considered by many to be the gold standard for medical recommendations, finds that chondroitin supplementation may confer more benefit for patients with osteoarthritis than glucosamine. Safety studies have found glucosamine and chondroitin supplements to be very safe. As a conclusion, patients with osteoarthritis should consider supplementation with glucosamine sulfate and chondroitin sulfate due to its excellent safety profile. However, patients should discuss the possible benefits with their naturopathic physicians. Some patients with shellfish allergies should avoid glucosamine and chondroitin supplements. Patients should also be aware that it may take 6 months or more to notice any benefits and that benefits may be slight.

Kimberly M. Sanders, ND, is a licensed naturopathic physician in Connecticut. She graduated from the University of Bridgeport and completed her CNME-accredited residency training there, as well. She was named 3-time MVP of the ZRT Cup Competition as a medical student. Dr Sanders currently owns ArthroWell Naturopathic, a specialty practice in rheumatology. She has undergone extensive pediatric and rheumatology training, and has lectured on the topic of autoimmunity and autism at the annual CNPA and NHAND conferences. Her passion in practice is finding the underlying cause of immune dysfunction and restoring balance to the immune system with functional medicine.

References:

Jeffries MA, Donica M, Baker LW, Stevenson ME, Annan AC, Humphrey MB. Genome-wide DNA methylation study identifies significant epigenomic changes in osteoarthritic cartilage. Arthritis Rheumatol. 2014 Oct. 66(10):2804-15.
Durmus D, Alayli G, Bayrak IK, Canturk F. Assessment of the effect of glucosamine sulfate and exercise on knee cartilage using magnetic resonance imaging in patients with knee osteoarthritis: a randomized controlled clinical trial. J Back Musculoskelet Rehabil. 2012;25(4):275-84.
Wu D, Huang Y, Gu Y, Fan W. Efficacies of different preparations of glucosamine for the treatment of osteoarthritis: a meta-analysis of randomised, double-blind, placebo-controlled trials. Int J Clin Pract. 2013;67(6):585-94.
Fransen M, Agaliotis M, Nairn L, et al. Glucosamine and chondroitin for knee osteoarthritis: a double-blind randomised placebo-controlled clinical trial evaluating single and combination regimens. Ann Rheum Dis. 2015 May;74(5):851-8.
Towheed T, Maxwell L, Anastassiades TP, et al. Glucosamine therapy for treating osteoarthritis. Cochrane Database of Systematic Reviews. 2005;2.
Singh JA, Noorbaloochi S, MacDonald R, Maxwell LJ. Chondroitin for osteoarthritis. Cochrane Database of Systematic Reviews. 2015;1.
Erickson JM, Messer TM. Glucosamine and Chondroitin Sulfate Treatment of Hand Osteoarthritis. J Hand Surgery. 2013;38(8):1638-40.