Chondroitin sulfate
   
Chondroitin sulfate
Background
Chondroitin was first extracted and purified in the 1960s. It is currently manufactured from natural sources (shark/beef cartilage or bovine trachea) or by synthetic means. The consensus of expert and industry opinions support the use of chondroitin and its common partner agent, glucosamine, for improving symptoms and arresting (or possibly reversing) the degenerative process of osteoarthritis.
Synonyms
ACS4-ACS6, CDS, chondroitin sulfate A, chondroitin sulfate C, chondroitin sulphate A sodium, chondroitin-4-sulfate, chondroitin-6-sulfate, chondroitin sulfuric acid, chondroprotective agents, chonsurid, condroitin, Condrosulf®, CS, CSA, CSC, disease modifying osteoarthritis drugs (DMOAD), GAG, galacotosaminoglucuronoglycan sulfate (Matrix®), mesoglycan (heparan sulfate-52%, dermatan sulfate-35%, heparin-8%, chondroitin sulfate-5%), SYSADOA ( " symptomatic slow acting drug in osteoarthritis " )
Evidence
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
Uses based on scientific evidenceGrade* Osteoarthritis
Multiple controlled clinical trials since the 1980s have examined the use of oral chondroitin in patients with osteoarthritis of the knee and other locations (spine, hips, finger joints). Most of these studies have reported significant benefits in terms of symptoms (such as pain), function (such as mobility), and reduced medication requirements (such as anti-inflammatories). However, most studies have been brief (6 months duration) with methodological weaknesses: a wide variety of patient classifications and outcome variables have been used resulting in heterogeneity between trials; most analyses are not on an intention-to-treat basis; relationships between investigators and manufacturers are often not clarified; and blinding and randomization are frequently not well described. Despite these weaknesses and potential for bias in the available results, the weight of scientific evidence points to a beneficial effect when chondroitin is used for 6-24 months. Longer term effects are not clear. Preliminary studies of topical chondroitin have also been conducted. Chondroitin is frequently used with glucosamine. Glucosamine has independently been demonstrated to benefit patients with osteoarthritis (particularly of the knee). It remains unclear if there is added benefit of using these two agents together compared to using either alone.
A
Ophthalmologic uses
Chondroitin is sometimes used as a component of eye drop solutions, including prescription-only preparations such as Viscoat®. These solutions should only be used under the supervision of an ophthalmologist.
B
Coronary artery disease (secondary prevention)
Several studies in the early 1970s assessed the use of oral chondroitin for the prevention of subsequent coronary events in patients with a history of heart disease or myocardial infarction. Although favorable results were reported, due to methodological weaknesses in this research and the widespread current availability of more proven drug therapies for patients in this setting, a recommendation cannot be made in this area.
C
Interstitial cystitis
There is preliminary research administering intravesicular chondroitin in patient diagnosed with interstitial cystitis. Additional evidence is necessary before a firm conclusion can be drawn.
C
* Key to grades
A: Strong scientific evidence for this use;
B: Good scientific evidence for this use;
C: Unclear scientific evidence for this use;
D: Fair scientific evidence against this use (it may not work);
F: Strong scientific evidence against this use (it likely does not work).
Uses based on tradition or theory
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
Angina, anti-inflammatory, chronic venous ulcers, gonarthrosis, hyperlipidemia, iron deficiency anemia, kidney stones, leukemia, malaria, myocardial infarction, osteoporosis, premature labor prevention.
Dosing
The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.
Standardization:
Standardization involves measuring the amount of certain chemicals in products to try to make different preparations similar to each other. It is not always known if the chemicals being measured are the " active " ingredients.
Oral:
Monotherapy: Doses of 200-400mg twice to three times daily, or 800-1200mg once daily have been used in studies. Higher doses (up to 2000mg) appear to have similar efficacy. In the treatment of osteoarthritis, full effects may take several weeks to occur.
Combination with glucosamine: It is not clear what dose is optimal when used in combination with glucosamine or whether the combination is as effective as or more effective than either agent alone.
Intravenous/Intramuscular:
For osteoarthritis, 50-100mg as a single daily injection or divided into two daily injections has been used. Medical supervision is recommended.
Children (younger than 18 years):
Insufficient evidence.
Safety
The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.
Allergies:
Use cautiously if allergic or hypersensitive to chondroitin sulfate products.
Side Effects and Warnings:
There is limited long-term safety data on chondroitin, although it appears to be well tolerated in most trials.
Adverse effects that have been rarely reported or are theoretical include: headache, motor uneasiness, euphoria, hives, rash, photosensitivity, hair loss, breathing difficulties, subjective tightness in the throat or chest, exacerbation of previously well-controlled asthma, chest pain, elevated blood pressure, lower extremity edema, gastrointestinal pain/dyspepsia, nausea, diarrhea, constipation, transaminitis, increased risk of bleeding (theoretical), bone marrow suppression (animal research), eyelid edema.
Use with caution in patients with bleeding disorders or taking anticoagulant medications. Avoid in pregnant or breastfeeding women.
Pregnancy and Breastfeeding:
Avoid in pregnant or breastfeeding women as effects are unknown, and there is structural similarity to heparin, which is contraindicated during pregnancy.
Methodology
This patient information is based on a professional level monograph edited and peer-reviewed by contributors to the Natural Standard Research Collaboration ().
Selected references
1. Blotman F, Loyau G. Clinical trial with chondroitin sulfate in gonarthrosis [abstract]. Osteoarthritis Cart 1993;1:68.
2. Bourgeois P, Chales G, Dehais J, et al. Efficacy and tolerability of chondroitin sulfate 1200 mg/day vs chondroitin sulfate 3 x 400 mg/day vs placebo. Osteoarthritis Cartilage 1998;6 Suppl A:25-30.
3. Bucsi L, Poor G. Efficacy and tolerability of oral chondroitin sulfate as a symptomatic slow-acting drug for osteoarthritis (SYSADOA) in the treatment of knee osteoarthritis. Osteoarthritis Cartilage 1998;6 Suppl A:31-36.
4. Cohen M, Wolfe R, Mai T, et al. A randomized, double blind, placebo controlled trial of a topical cream containing glucosamine sulfate, chondroitin sulfate, and camphor for osteoarthritis of the knee. J Rheumatol 2003;30(3):523-528.
5. Conrozier T. [Anti-arthrosis treatments: efficacy and tolerance of chondroitin sulfates (CS 4 & 6)]. Presse Med 1998;27 (36) :1862-1865.
6. Danao-Camara T. Potential side effects of treatment with glucosamine and chondroitin. Arthritis Rheum 2000;43(12):2853.
7. Das A, Jr., Hammad TA. Efficacy of a combination of FCHG49 glucosamine hydrochloride, TRH122 low molecular weight sodium chondroitin sulfate and manganese ascorbate in the management of knee osteoarthritis. Osteoarthritis Cartilage 2000;8(5):343-350.
8. Du J, White N, Eddington ND. The bioavailability and pharmacokinetics of glucosamine hydrochloride and chondroitin sulfate after oral and intravenous single dose administration in the horse. Biopharm Drug Dispos 2004;25(3):109-116.
9. Fleish AM, Merlin C, Imhoff A, et al. A one-year randomized, double-blind, placebo-controlled study with oral chondroitin sulfate in patients with knee osteoarthritis. Osteoarthritis and Cartilage 1997;5:70.
10. L'Hirondel JL. [Clinical double blind study with oral application of chondroitin sulfate vs. placebo for treatment of tibio femoral gonarthrosis in 125 patients]. Litera Rheumatologica 1992;14:77-84.
11. Leeb BF, Petera P, Neumann K. [Results of a multicenter study of chondroitin sulfate (Condrosulf) use in arthroses of the finger, knee and hip joints]. Wien Med Wochenschr 1996;146(24):609-614.
12. Leeb BF, Schweitzer H, Montag K, et al. A metaanalysis of chondroitin sulfate in the treatment of osteoarthritis. J Rheumatol 2000;27(1):205-211.
13. Leffler CT, Philippi AF, Leffler SG, et al. Glucosamine, chondroitin, and manganese ascorbate for degenerative joint disease of the knee or low back: a randomized, double-blind, placebo-controlled pilot study. Mil Med 1999;164(2):85-91.
14. Limberg MB, McCaa C, Kissling GE, et al. Topical application of hyaluronic acid and chondroitin sulfate in the treatment of dry eyes. Am J Ophthalmol 1987;103(2):194-197.
15. Malaise M, et al. Efficacy and tolerability of 800 mg oral chondroitin sulfate in the treatment of knee osteoarthritis: a randomized double-blind multicentre study versus placebo. Litera Rheumatologica 1999;24:31-42.
16. Mazieres B, Loyau G, Menkes CJ, et al. [Chondroitin sulfate in the treatment of gonarthrosis and coxarthrosis. 5-months result of a multicenter double-blind controlled prospective study using placebo]. Rev Rhum Mal Osteoartic 1992;59(7-8):466-472.
17. McAlindon TE, LaValley MP, Gulin JP, et al. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA 2000;283(11):1469-1475.
18. McGee M, Wagner WD. Chondroitin Sulfate Anticoagulant Activity Is Linked to Water Transfer: Relevance to Proteoglycan Structure in Atherosclerosis. Arterioscler Thromb Vasc Biol 2003;23(10):1921-1927.
19. Morreale P, Manopulo R, Galati M, et al. Comparison of the antiinflammatory efficacy of chondroitin sulfate and diclofenac sodium in patients with knee osteoarthritis. J Rheumatol 1996;23(8):1385-1391.
20. Morrison LM, Branwood AW, Ershoff BH, et al. The prevention of coronary arteriosclerotic heart disease with chondroitin sulfate A: preliminary report. Exp Med Surg 1969;27(3):278-289.
21. Morrison LM. Reduction of ischemic coronary heart disease by chondroitin sulfate A. Angiology 1971;22(3):165-174.
22. Obara M, Hirano H, Ogawa M, et al. Does chondroitin sulfate defend the human uterine cervix against ripening in threatened premature labor? Am J Obstet Gynecol 2000;182(2):334-339.
23. Richy F, Bruyere O, Ethgen O, et al. Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis. Arch Intern Med 2003;163(13):1514-1522.
24. Rozenfeld V, Crain JL, Callahan AK. Possible augmentation of warfarin effect by glucosamine-chondroitin. Am J Health Syst Pharm 2004;61(3):306-307.
25. Shankland WE. The effects of glucosamine and chondroitin sulfate on osteoarthritis of the TMJ: a preliminary report of 50 patients. Cranio 1998;16(4):230-235.
26. Steinhoff G, Ittah B, Rowan S. The efficacy of chondroitin sulfate 0.2% in treating interstitial cystitis. Can J Urol 2002;9(1):1454-1458.
27. Tallia AF, Cardone DA. Asthma exacerbation associated with glucosamine-chondroitin supplement. J Am Board Fam Pract 2002;15(6):481-484.
28. Towheed TE, Anastassiades TP. Glucosamine and chondroitin for treating symptoms of osteoarthritis: evidence is widely touted but incomplete. JAMA 2000;283(11):1483-1484.
29. Uebelhart D, Chantraine A. Efficacite clinique du sulfate de chondroitine dans la gonarthrose: Etude randomisee en double-insu versus placebo [abstract]. Rev Rhumatisme 1994;10:692.
30. Uebelhart D, Knüssel O, Theiler R. Efficacy and tolerability of oral avian chondroitin sulfate in painful knee osteoarthritis [abstract]. Schweiz Med Wochenschr 1999;129(33):1174.
31. Uebelhart D, Thonar EJ, Zhang J, et al. Protective effect of exogenous chondroitin 4,6-sulfate in the acute degradation of articular cartilage in the rabbit. Osteoarthritis Cartilage 1998;6 Suppl A:6-13.
32. Uebelhart D, Malaise M, Marcolongo R, et al. Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate: a one-year, randomized, double-blind, multicenter study versus placebo. Osteoarthritis Cartilage 2004;12(4):269-276.
33. Van Blitterswijk WJ, Van De Nes JC, Wuisman PI. Glucosamine and chondroitin sulfate supplementation to treat symptomatic disc degeneration: Biochemical rationale and case report. BMC Complement Altern Med 2003;3(1):2.
34. Verbruggen G, Goemaere S, Veys EM. Chondroitin sulfate: S/DMOAD (structure/disease modifying anti- osteoarthritis drug) in the treatment of finger joint OA. Osteoarthritis Cartilage 1998;6 Suppl A:37-38.
35. Volpi N. Oral bioavailability of chondroitin sulfate (Condrosulf) and its constituents in healthy male volunteers. Osteoarthritis Cartilage 2002;10(10):768-777.
THIS EVIDENCE-BASED MONOGRAPH WAS PREPARED BY THE NATURAL STANDARD RESEARCH COLLABORATION ().
April 01, 2004 
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