Chondroitin

Chondroitin sulfate (galactosaminoglucuronoglycan sulfate) refers to a group of polysulfated glycosaminoglycans such as chondroitin-4-sulfate, chondroitin-6-sulfate, and others. Structurally, the chondroitin molecule resembles heparanoids; it is actually a minor component of danaparoid sodium (a mixture of heparan sulfate, dermatan sulfate, and chondroitin sulfate in a 21:3:1 ratio).It is commonly prepared from bovine or porcine cartilage sources.

Uses and Benefits:

Chondroitin sulfate is marketed for use alone and in combination with glucosamine for musculoskeletal and joint pain. It has been primarily studied for osteoarthritis. Injectable forms are FDA-approved as viscoelastic agents for ophthalmic surgery.

Pharmacology:

Chondroitin sulfate is a mucopolysaccharide that the body uses in the synthesis of cartilage. Its potential chondroprotective properties stem from its role as one of the "building blocks" for synthesis of new cartilage, as well as its inhibition of leukocyte elastase, an inflammatory enzyme that contributes to cartilage degradation.In vitro models demonstrate stimulation of proteoglycan production and collagen and hyaluronic acid syn­thesis. Animal studies have shown beneficial effects on serum lipids and atherogenesis, as well as antithrombogenic activity. Because it is a large molecule, chondroitin is poorly absorbed; oral bioavailability is 8-18%.

Clinical Trials:

. Chondroitin Sufate Alone For Osteoarthritis (OA) - Numerous clinical trials of chondroitin have been conducted, and two recent meta-analyses of these trials have been published in peerre­viewed journals. The first meta-analysis examined only random­ized, double-blind, controlled studies of oral chondroitin sulfate (CS) that met specific criteria for objective outcome measures. 6 Seven of 16 available trials were included in the analysis for a total of 372 patients with hip and knee OA. Assessment of pain scores using a visual analogue scale (VAS) revealed significant differ­ences between CS and placebo groups. The mean VAS of pain decreased by 43% at 3 months and by 58% at study end (150-365 days) in the CS group, compared to 20% at both time points in the placebo group. In the six trials that used the Lequesne index (an­other validated OA symptom scale), pooled data represented a decrease of 49% for CS patients and < 20% for controls.

Accounting for standard deviations of results, 55-65% of CS patients would have greater benefit than placebo patients. All seven trials reported that the reduction in concomitant analgesic medication was significantly greater in the CS groups, although no patients were able to discontinue analgesics completely. Investigators postulated that CS in combination with analgesics is more effective than CS alone. Doses used in the seven studies ranged from 800 to 2000 mg/day, which did not correlate with dif­ferences in efficacy outcome measures.

The second meta-analysis included nine clinical trials with a total of 799 patients using chondroitin sulfate (two intramuscu­larly, seven oral).? This analysis took into account the varying out­come measures by calculating an overall effect size, which was 0.78 for chondroitin (a moderate effect). However, when influ­ences such as trial size and trial quality were considered, the cal­culated effect sizes ranged from 0.3 (small effect) to 1.7 (very large effect). The investigators concluded that chondroitin does have efficacy in the treatment of OA, but that the efficacy is likely to be overestimated due to methodological flaws they identified in the existing trials. A problem common to both meta-analyses is that some trials included in the analyses were available only in abstract form, thereby limiting analysis of the quality of the trials.

The second was a randomized, double-blind comparison trial at examined the effects of 1 month of treatment with diclofenac : ;odium 150 mg/day versus 3 months of treatment with chon­droitin sulfate 1200 mg/day. These protocols were followed by placebo, so that each group completed 6 months of treatment.9 rhe investigators reported a greater lasting benefit from CS, as measured by decrease in an objective pain scale at 3 and 6 months. Chondroitin may have a long duration of effect, lasting well into the placebo period; however, comparison of treatments given for different time periods prevents firm conclusions.

In Combination-One randomized, double-blind, placebo­controlled crossover study compared the efficacy of 8 weeks of treatment with a combination of glucosamine hydrochloride (1500 mg/day), CS (1200 mg/day), and manganese ascorbate (228 mg/day) versus placebo in active military personnel with degener­ative joint disease of the knee or lower back. 10 Statistically signifi­cant improvements were seen in VAS and patient assessments of efficacy, but not in the Lequesne index, acetaminophen use, or physical examination scores. Because both chondroitin and glu­cosamine may exhibit benefits that last beyond the active treat­ment period, a major study limitation is the crossover design with no washout period.

For patients with temporomandibular joint syndrome, an un­controlled case series of 50 patients treated with 3200 mg/day glucosamine HCI, 2400 mg/day CS, and 2000 mg/day ascorbic acid reported subjective decreases in perception of "joint noise," pain, and swelling.

Other Uses-One small, preliminary, crossover study exam­ined intranasal chondroitin sulfate solution and placebo for the reduction of snoringY Mean sleep time spent snoring was 31.3% with chondroitin vs. 46.5% with placebo, suggesting possible ther­apeutic benefit. Oral CS was reported to be of benefit in 120 pa­tients with coronary heart disease over 6 years. However, this was an uncontrolled and inadequate study, and no similar reports have been made in the last 30 years.

Adverse Effects:

Gastrointestinal effects of mild epigastric pain, diarrhea, and constipation are the most commonly reported adverse events. However, in controlled trials, side effects were generally equal to or less frequent than those in placebo groups.

Side Effects and Interactions:

Although increased anticoagulation effects have been a concern because of the chemical structure resembling heparanoids, no problems have been documented in clinical studies, even at CS doses up to 10 g daily in patients on anticoagulant therapy.

Cautions:

Increased endogenous chondroitin sulfate levels were associated with poor outcomes and increased tumor progression in prostate cancer patients in one study.Until more data is available, patients with prostate cancer or elevated prostate-specific antigen levels should consider this possible disadvantage of chondroitin use. Because chondroitin is prepared from bovine sources, there is a potential for viral transmission. Safety during pregnancy and lactation has not been determined.

Preparations & Doses:

Doses of chondroitin sulfate used in osteoarthritis trials with positive results usually ranged from 800 to 1500 mg daily; the most common dose is 400 mg t.i.d. An optimum dosage has not been determined in dose-response studies.

Summary Evaluation

The evidence, although not definitive, is sufficient to support the use of chondroitin sulfate for symptoms of mild to moderate osteoarthritis. Like glucosamine, symptom reduction appears to be similar to that of analgesic doses of nonsteroidal anti-inflammatory drugs, with a more minimal adverse event profile. There is in­sufficient information at this point to determine if the combination of glucosamine sulfate and chondroitin sulfate provides additional or synergistic benefit over use of either product alone.