Evidence Level
Glucosamine is one of the most extensively studied joint supplements. The large GAIT trial (Clegg et al., 2006, n=1,583) found glucosamine HCl alone did not outperform placebo for overall OA pain, but a subgroup with moderate-to-severe pain showed significant improvement with the glucosamine-chondroitin combination. In contrast, European trials using pharmaceutical-grade glucosamine sulfate (Rotta preparation) have consistently shown significant benefits. Reginster et al. (2001) and Pavelka et al. (2002) demonstrated 3-year structural benefits with glucosamine sulfate, showing reduced joint space narrowing. The discrepancy between US and European trials is largely attributed to differences in formulation (HCl vs. sulfate) and product quality. Current ESCEO guidelines recommend crystalline glucosamine sulfate as a first-step pharmacological treatment for knee OA.