Chondroitin Sulfate

Chondroitin sulfate is used to treat osteoarthritis. Scientific evidence shows no benefit when chondroitin sulfate is taken by itself. However, evidence suggests that in combination with glucosamineglucosamine, it may reduce joint pain, improve joint mobility, and allow reduction of the doses of conventional anti-inflammatory drugs when it is taken for 6 to 24 months. Effects over longer periods are unclear. Mechanism is unknown. Dose is 600 mg orally once/day to 400 mg orally 3 times a day.

Evidence on efficacy of chondroitin sulfate is conflicting. The Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), a large, randomized, double-blinded, placebo-controlled, multicenter clinical trial studied use of glucosamine (500 mg orally 3 times a day), chondroitin sulfate (400 mg orally 3 times a day), and both drugs to treat osteoarthritis of the knee; in the group as a whole, pain was not reduced. However, exploratory subanalyses suggested efficacy in a subgroup of patients with moderate-to-severe knee pain (/Chondroitin Arthritis Intervention Trial (GAIT), a large, randomized, double-blinded, placebo-controlled, multicenter clinical trial studied use of glucosamine (500 mg orally 3 times a day), chondroitin sulfate (400 mg orally 3 times a day), and both drugs to treat osteoarthritis of the knee; in the group as a whole, pain was not reduced. However, exploratory subanalyses suggested efficacy in a subgroup of patients with moderate-to-severe knee pain (1). Prior to that trial, only small trials had studied chondroitin sulfate alone or in combination with glucosamine to treat osteoarthritis. ). Prior to that trial, only small trials had studied chondroitin sulfate alone or in combination with glucosamine to treat osteoarthritis.

A review of 43 randomized, controlled trials has also suggested that the benefit of chondroitin is limited to slight pain improvement in short-term studies, although quality of life may improve (2). A different meta-analysis of 18 randomized placebo-controlled trials found that chondroitin treatment ranging from 13 to 104 weeks reduced pain and improved function (3). It has been suggested the reason for conflicting symptomatic benefit is due to the poor quality of several food-grade chondroitin sulfate supplements and that pharmaceutical-grade chondroitin sulfate with defined percent purity and sequences of oligosaccharides is efficacious and be used for treatment (4). In the randomized placebo-controlled CONCEPT study, efficacy of pharmaceutical-grade chondroitin sulfate 800 mg was superior to placebo and similar to celecoxib in knee osteoarthritis (). In the randomized placebo-controlled CONCEPT study, efficacy of pharmaceutical-grade chondroitin sulfate 800 mg was superior to placebo and similar to celecoxib in knee osteoarthritis (5). Heterogeneity of osteoarthritic symptoms and causes also contribute to the difficulty of use in clinical practice.

The American College of Rheumatology recommends against use of chondroitin for osteoarthritis (6), whereas the European Society of Clinical and Economic Aspects of Osteoarthritis (ESCEO) recommends pharmaceutical-grade chondroitin (7).

No serious adverse effects have been reported. Among the most common adverse effects are stomach pain, nausea, and other gastrointestinal symptoms.

Animal, nonpharmaceutical grade sources of chondroitin sulfate may potentially contain viruses, prions, or bacteria that may cause disease (8).

Chondroitin sulfate may increase the anticoagulant action of warfarin (Chondroitin sulfate may increase the anticoagulant action of warfarin (9).

1. 1. Clegg DO, Reda DJ, Harris CL, et al: Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. : Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis.N Engl J Med 354(8):795-808, 2006. doi:10.1056/NEJMoa052771

2. 2. Singh JA, Noorbaloochi S, MacDonald R, et al: Chondroitin for osteoarthritis. Cochrane Database Syst Rev 1:CD005614, 2015. doi: 10.1002/14651858.CD005614.pub2

3. 3. Honvo G, Bruyère O, Geerinck A, et al: Efficacy of chondroitin sulfate in patients with knee osteoarthritis: a comprehensive meta-analysis exploring inconsistencies in randomized, placebo-controlled trials. Adv Ther 36(5):1085-1099, 2019. doi:10.1007/s12325-019-00921-w

4. 4. Hochberg M, Chevalier X, Henrotin Y, et al: Symptom and structure modification in osteoarthritis with pharmaceutical-grade chondroitin sulfate: what's the evidence? Curr Med Res Opin 29(3): 259-267, 2013. doi: 10.1185/03007995.2012.753430

5. 5. Reginster JY, Dudler J, Blicharski T, et al: Pharmaceutical-grade chondroitin sulfate is as effective as celecoxib and superior to placebo in symptomatic knee osteoarthritis: the ChONdroitin versus CElecoxib versus Placebo Trial (CONCEPT). Ann Rheum Dis 76(9):1537-1543, 2017. doi: 10.1136/annrheumdis-2016-210860

6. 6. 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 [published correction appears in Arthritis Rheumatol. 2021 May;73(5):799]. Arthritis Rheumatol 72(2):220-233, 2020. doi:10.1002/art.41142

7. 7. 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 49(3):337-350, 2019. doi:10.1016/j.semarthrit.2019.04.008

8. 8. Volpi N: Chondroitin sulfate safety and quality. Molecules 12;24(8), 2019. pii: E1447. doi: 10.3390/molecules24081447

9. 9. Knudsen JF, Sokol GH: Potential glucosamine-: Potential glucosamine-warfarin interaction resulting in increased international normalized ratio: case report and review of the literature and MedWatch database. Pharmacotherapy 28(4):540-548, 2008. doi: 10.1592/phco.28.4.540

The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

1. National Institutes of Health (NIH), National Center for Complementary and Integrative Health: General information on the use of glucosamine and chondroitin for osteoarthritisGeneral information on the use of glucosamine and chondroitin for osteoarthritis