We cannot recommend using glucosamine and chondroitin for patients with symptomatic osteoarthritis of the knee.

Rationale
Twenty-one studies were included as evidence for this recommendation; all were prospective. Twelve focused on glucosamine alone, eight on chondroitin sulfate alone, and one (Clegg et. al86) assessed both. Sixteen were of moderate-strength and five were of high-strength.
  
Among the studies, eleven of 52 outcomes were statistically significant in favor of glucosamine when compared to placebo. WOMAC pain and function subscales scores and VAS pain were the critical outcomes and were not associated with statistical significance at any treatment duration period. When meta-analyses were run for WOMAC pain, function, stiffness and total subscale scores, all meta-analyses showed that the overall effect of glucosamine compared to placebo was not statistically significant.
 
Two studies compared glucosamine to active treatments. Glucosamine was compared to reparagen87 (a poly-herbal supplement), and enzymatic hydrolyzed collagen.88  Glucosamine was found to have no significant effect on pain compared to these treatments.
 
Figure 31 presents the meta-analysis results comparing chondroitin sulfate to placebo in pain scores on the VAS. The weighted mean difference revealed that scores were 11.89 points lower in the chondroitin group than in the placebo group. However, the difference was not clinically important.
 
At this time, both glucosamine and chondroitin sulfate have been extensively studied. Despite the availability of the literature, there is essentially no evidence that minimum clinically important outcomes have been achieved compared to placebo, whether evaluated alone or in combination. The strength of the recommendation is based on lack of efficacy, not on potential harm.
 
One of our search terms was neutraceuticals and we initially maintained a broad focus. However, the original guidance was to evaluate methylsulfonylmethane, omega-3, gelatin, vitamin D, dimethylsulfoxide, antioxidants, and coenzyme Q10. The general term was intended to guide the search of the specific terms. Additionally, the evidence for neutraceuticals was variable and could not be easily summarized. Two moderate-strength studies89;90comparing ginger extract to placebo arose in the included evidence.  The only improvement in pain associated with both statistical significance and clinical importance was measured using WOMAC stiffness. Clinical importance could not be determined for four other pain measures, or they did not meet the minimum clinically important improvement threshold. The findings on outcomes of function were contradictory and low in count, which rendered them inconclusive. Glycosaminoglycan polysulfuric acid (GAGPS)91 produced a true negative finding statistically and clinically, and gubitong was associated with higher WOMAC total scores than glucosamine in a non-control matched study where clinical importance could not be determined.
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