It has been almost a decade since I last reviewed chondroitin sulfate research¹. At that time, I reviewed 5 studies, all of which had impressive results. Last year, a large meta-analysis of chondroitin supplementation for arthritis of the hip and knee was released². For those practitioners who favor the use of chondroitin sulfate, it was not encouraging. Conversely, providers who were skeptical felt validated. After a very thorough read, here are the facts as I see them.

• 1,453 references were identified in a literature search on chondroitin sulfate spanning 36 years.
• 291 of the studies and trials were potentially eligible.
• 22 studies qualified and included 4,056 patients.
• The mean amount of subjects per study was 120.
• The range of subjects was 17 to 631.
• The median age was 61.
• The average age range was 50 to 67.
• Seven trials reported the duration of symptoms, the range of which was 4 to 10 years.
• Doses ranged from 800 mg to 2000 mg with a median of 1000 mg.
• Study times ran from 6 to 103 weeks with a median of 25 weeks.
• Study follow-up times were 13 to 132 weeks with a median of 31 weeks.

• 22/22 allowed pain medication.
• 21/22 were randomized studies.
• 20/22 used oral chondroitin sulfate.
• 19/22 used placebo control.
• 18/20 had results favoring chondroitin sulfate over control.
• 17/20 had placebo controls.
• 12/20 had adequate patient blinding.
• 11/20 had a follow-up of greater than 6 months.
• 9/20 had a follow-up of less than 6 months.
• 9/18 that favored chondroitin sulfate had results that were not statistically significant according to the authors.
• 5/20 measured and reported radiological joint space changes.(See below)
• 2/22 studies used injectable chondroitin sulfate.
• 2/20 no difference between chondroitin sulfate group and control group
• 2/20 had an increase of pain in the control group.
• 2/20 had results showing no differences between chondroitin sulfate and control groups.
• 1/20 had clear nonprofit funding.
• 0/20 had increased pain in the chondroitin group.
• 2/3 of the best studies, (according to the authors³) had no effect.

In the 5 studies that measured joint spaces, the chondroitin groups lost a mean of 0.23 mm less than the control group. The minimum difference was 0.16 mm less than control. The authors commented there may be bias due to the small sample sizes of the 5 studies that measured joint space changes with x-rays. In other words, they insinuated that the chondroitin sulfate advantage over controls in slowing of the joint space would not be seen in larger studies.

• "No robust evidence supports the use of chondroitin in osteoarthritis."
• "Symptomatic benefit is minimal to nonexistent."
• "We deem it unlikely that patients with advanced osteoarthritis will benefit."
• "We cannot exclude a clinically relevant affect of chondroitin in patients with low-grade osteoarthritis."
• "In patients with low-grade osteoarthritis, the use of chondroitin should be restricted to randomized control trials."
• "In patients with advanced osteoarthritis a clinically relevant benefit is unlikely, and the use of chondroitin should be discouraged."

In this meta-analysis, the use of chondroitin to control osteoarthritis of the knee and hip was not impressive. However 18/20 oral studies that met a vigorous inclusion criteria did slightly favor chondroitin and although the authors felt only 9/18 reached statistical significance only 2/20 reached statistical significance for no effect and 0/20 favored placebo. In my own personal experience of over 20 years in practice, it appears that many patients subjectively benefit from the use of chondroitin sulfate (most of the time accompanied by glucosamine sulfate). Whether this is simply placebo or appropriate biochemistry is yet to be determined. After a close look at this study, I respectfully disagree with the authors and make the following conclusion: Chondroitin sulfate may not help everyone, but it is certainly worth a trial and is definitely safe.

References
¹ Andersen, G.D. Chondroitin Sulfate Research Update. Dynamic Chiropractic. 1999;17:9, 37.
² Osteoarthritis of the Knee or Hip. Annals of Internal Medicine. 2007;146:580-590

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