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Chondroitin Sulfate- Foremost for Arthritis Formulas

By Yousry Naguib, Ph.D.
Supplement Industry Executive (January/February 2001)

            Chondoritin sulfate alone or in combination with glucosamine are widely touted in the media as a treatment for mild to moderate osteoarthritis (OA). Both supplements are described as a medical miracle that can halt, reverse, and may even cure OA The market for chondroitin and glucosamine supplements has been estimated {1} to be over five hundred million dollars in retail sales between July 1998 and May 1999.
            Chondroitin comes from the cartilage of sharks, cows and pigs. Shark serves as the major source of chondroitin sulfate.
            Chondroitin sulfate (CS) is an important component of the body’s natural building blocks for the cartilage found in joints. CS is a glycosaminoglycan, a polymeric material consisting of repeating glucuronic acid and N-acetylgalactosamine units. The N-acetylgalactosamine is substituted with sulfate at either the 4- or 6-position, with approximately one sulfate being present per disaccharide unit.
            Chondroitin sulfate is found in the proteoglycans of cartilage. Glucosamine on the other hand acts as the building block for the biosynthesis of glycosaminoglycans needed for the formation of proteoglycans that are important constituents of the cartilage.           
            Osteoarthritis (OA) is the most common form of arthritis and accounts for more than half of all arthritis cases in the United States. OA is a degenerative joint disease that affects more than 20 million Americans, mostly women over the age 45. OA results from progressive loss of cartilage proteoglycans (cartilage breakdown). Cartilage is a highly differentiated tissue that cushions and protects joints against the friction caused by the rubbing together of bones. OA most commonly affects the hands and large weight-bearing joints, such as the knees and hips. The typical clinical symptoms are pain, followed by inflammation, swelling, and stiffness as the disorder progresses, leading to restriction of movement such as walking, climbing stairs or using hands, thus altering the patient’s quality of life.
            OA is commonly diagnosed by radiographic technique, which is useful for people who do not exhibit symptoms. OA is only symptomatic in about half of afflicted people.


            Non-steroidal anti-inflammatory drugs (NSAID) such as Ibuprofen, Indomethacin, and Diclofenac are often used to alleviate OA symptoms, but suffer from serious adverse effects such as ulcer and stomach bleeding. The desire to avoid these side effects led to the development of a new NSAID class of drugs known as COX-2 inhibitors (Celebrex and Vioox). They are considered to have lower risk for stomach irritation and bleeding, but are not free of side effects, such as indigestion, diarrhea and abdominal pain. Chondroitin sulfate and glucosamine supplements, on the other hand, are free of these side effects and have become popular remedies for treating OA. Chondroitin sulfate has been used for years in veterinarian medicine to treat symptoms of OA.



            Pharmacokinetics of CS in healthy volunteers showed it to be rapidly absorbed when it is dissolved in water [2]. Lower and delayed absorption is observed when CS is administered in gastro-resistant capsules. Low molecular weight CS showed superior kinetic profile than high molecular weight CS. The molecular weights as well as the 4- and 6-sulfate isomeric composition of chondroitin depend on the source and the extraction procedure.

Clinical Trials

            A French randomized, double blind, placebo controlled trial [3] on 104 patients with OA demonstrated the efficacy of CS, given orally at the dose of 800mg/day for one year, in reducing functional impairment by 50%. Another French trial [4], involving 127 patients with knee OA found that the efficacy of 1200mg CS as a single daily dose does not differ from that of 400mg dose given three times a day, as judged by the clinical parameters spontaneous joint pain and Lequesne index. The Lequesne index for hip and knee is a measure of severity (disability scale).
            A 6-month trial in Hungary [5] involving patients with knee OA who were giving 400mg CS twice a day concluded that CS acts as a symptomatic slow-acting drug in knee OA. A similar conclusion was reached by researchers in Switzerland [6], who conducted a one-year randomized, double blind, controlled trial on 42 patients with symptomatic knee OA. Patients received 800mg of CS per day. The study found CS was well tolerated, and significantly reduced pain and increased overall mobility capacity. The benefit of symptomatic slow-acting drugs for OA is to reduce the need for drugs with a less favorable safety profile, such as non-steroidal anti-inflammatory drugs.

The first US six-months trial [7] on the efficacy of chondroitin sulfate in the treatment of knee osteoarthritis is reported in the journal of Osteoarthritis Cartilage 2000, September issue. In a randomized, placebo-controlled study, 93 patients with OA of the knee were given a combination of low molecular weight sodium chondroitin sulfate (800mg), glucosamine HCl (1000mg), and manganese ascorbate (152mg) twice daily. After 6 months, a significant improvement in the severity of the OA of the knee was observed in patients with mild to moderate OA of the knee.
            A similar study was conducted by the US Navy on 34 males with chronic pain and radiographic degenerative disease of the knee [8]. After 16 weeks of treatment, the double-blind study found that patients who took the therapeutic combination of chondroitin sulfate (1,200mg/day), glucosamine HCl (1,500mg/day), and manganese ascorbate (226mg/day) experienced significant relief of knee pain but no improvement in function.

Meta-analysis of Clinical Trials

Researchers in Austria reported a meta-analysis of controlled clinical trials of the efficacy of chondroitin sulfate in the treatment of osteoarthritis [9]. Only 7 of a total of 16 trials were selected. Patients (372) on chondroitin treatment for 120 or more days showed at least 50% improvement in OA symptoms compared to placebo

McAlindon and colleagues at Boston University School of Medicine evaluated the benefit of chondroitin and glucosamine for OA symptoms using meta-analysis combined with systematic quality assessment of clinical trials of these supplements in knee and/or hip OA [10]. Fifteen of 37 studies were selected on the basis of being double blind, randomized, placebo-controlled trials of 4 or more weeks’ duration. The study concluded that both chondroitin sulfate and glucosamine preparations are likely to be effective therapies for the symptomatic treatment of osteoarthritis.

            Researchers in Japan found that CS prepared from salmon nasal cartilage reduced fat storage in mice fed a high fat diet, an action that was attributed to inhibition of small intestinal absorption of dietary fat [11].

            Chondroitin sulfate is the major glycosaminoglycan of the arterial wall. An in-vitro study found that chondroitin-4-sulfate, and not chondroitin-6-sulfate inhibited copper induced oxidation of the lipoprotein HDL. The antioxidant activity was shown to be due to the ability of chondroitin-4-sulfate to bind copper thus resulting in less copper available for HDL oxidation [12]. The study suggested that CS could play a beneficial role in reducing risk of atherosclerosis, the leading cause of heart attacks.

Possible Drug Interactions
            The Arthritis Foundation advises patients taking the blood thinning medication heparin to have their blood clotting activity monitored while on chondroitin. Patients taking the blood thinner Coumadin (Warfarin) should also consult with their physician. Chondoritin sulfate does not interfere with NSAIDs, such as aspirin. Although chondroitin contains sugar like molecules, it is considered safe for diabetics.  

Chondroitin sulfate is safe and well tolerated in oral doses. It promotes production of cartilage proteoglycans and thus therapeutically beneficial in osteoarthritis. Research and clinical studies support the oral administration of chondroitin for the hip and knee joint diseases, as an agent to reduce both symptoms and the need for non-steroidal anti-inflammatory drugs. 

[1] Hartman Group, Bellevue, Washington
[2] Anti-inflammatory activity of chondroitin sulfate. Ronca et al. Osteoarthritis Cartilage 1998; 6 Suppl A:14
[3] Anti-arthrosis treatments: efficacy and tolerance of chondroitin sulfate. Conrozier T. Presse Med 1998; 27:1862
[4] Efficacy and tolerability of chondroitin sulfate 1200mg/day vs chondroitin sulfate 3x400mg/day. Burgeois et al. Osteoarthritis cartilage 1998; 6 Suppl A:25
[5] Efficacy and tolerability of oral chondroitin sulfate as a symptomatic slow-acting drug for knee osteoarthritis.Bucsi and Poor. Osteoarthritis cartilage 1998; 6 Suppl A:31
[6] Effects of oral chondroitin sulfate on the progression of knee osteoarthritis: a pilot study. Uebelhart et al. Osteoarthritis cartilage 1998; 6 Suppl A:39
[7] Efficacy of a combination of FCHG49 glucosamine hydrochloride, TRH 122 low molecular weight sodium chondroitin sulfate, and manganses ascorbate in the mangement of knee osteoarthritis. Das et al. Osteoarthritis cartilage 2000; 8:343
[8] Glucosamine, chondroitin, and manganese ascorbate for degenerative diseae of the knee or low back: a randomized, double-blind, placebo-controlled pilot study. Leffler et al. Mil Med 1999; 164:85
[9] A meta-analysis of chondroitin sulfate in the treatment of osteoarthritis. Leeb et al. J Rheumatol 2000; 27:205
[10] Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. McAlindon et al. JAMA 2000; 283:1469
[11] Inhibitory effects ofchondroitin sulfate prepared from salmon nasal cartilage on fat storage in mice fed a high fat diet. Han et al. Int J Obes Relat Metab Disord 2000; 24:1131
[12] Chondroitin-4-sulfate protects high-density lipoprotein against copper-dependent oxidation. Arch Biochem Biophys 1999; 365:143