Joints Journal Club July 2015: Effectiveness of Chondroitin and Glucosamine

This month the Annals of Rheumatologic Disease published a study comparing the effectiveness of Chondroitin + Glucosamine supplements  (C+GS) with anti-inflammatory medication for the treatment of painful knee arthritis (specifically osteoarthritis).  

The study was multi-center (conducted in 4 European countries), prospective randomized-controlled study, in 600 patients.  This is considered the highest level study. 

The study showed a >50% decrease in pain and swelling (based on the WOMAC score) over a course of 6 months for both the NSAIDS (celecoxib) and C+GS groups.  Neither group demonstrated significant side effects.  Interestingly, over 80% of patients demonstrated significant improvement from their baseline function at the beginning of the study.  

These findings support a similar study, the GAIT Trial published in the New England Journal of Medicine in 2006 (see study), which found that C+GS was effective in mild-to-moderate osteoarthritis, although it was not effective in more advanced forms of arthritis (unlike NSAIDS which improved function in all levels of arthritis).  By demonstrating that all patients, even those receiving placebo, improve significantly over time, the GAIT trial suggests that flair-ups of arthritis may inherently get better with time and rest... or that patients expect to see improvements with medication and thus are susceptible to the placebo effect.  Given that C+GS did not majorly outperform placebo, its unlikely that its effects are dramatic (even if they offer some improvement).  

In this study, by 6 months both groups were doing well, however the NSAIDS group achieved better pain relief and function more quickly.  From 1-4 months, NSAIDS group outperformed, however both groups balanced out by 6 months.  

Prior studies have suggested that C+GS have a more gradual onset.  Chondroitin stimulates collagen synthesis (one of the major building blocks of cartilage, which is the major deficiency in osteoarthritis).  Glucosamine inhibits prostaglandins, metalloproteinases and nitric oxide, which are all contribute to inflammation and pain.  Both C+GS prevent the breakdown of glycosaminoglycans which are central to the shock-absorbing effect of our cartilage.  

NSAIDS (anti-inflammatories) like celecoxib directly inhibit prostaglandin production (specifically by blocking cyclooxygenase 2 enzyme "COX-2"). 

This study has some interesting findings, which have been supported in part by prior trials.  The biggest problem with this study was the lack of a "placebo group" which helps to highlight how much improvement in pain is due to the natural course of arthritis.  The study benefits however from comparing this alternative medicine with rigorous methodology, thus minimizing the risk of uncontrolled variables.  Other questions for discussion: why follow for only 6 months, do these two approaches of treatment have effects over a longer time - 1 year, 5 years, 10 years? Arthritis is a chronic disease.  Also, is the WOMAC score the best representation of knee arthritis pain?  How many people were taking the allowed supplemental tylenol, how big of a role did that play?

Good study overall and worth reading!  The GAIT Trial is also an important read if you are interested in this topic.

See full article.