Glucosamine and lower mortality and cancer incidence: Selection bias in the observational studies

Glucosamine is a widely used supplement to treat joint pain and osteoarthritis despite inconclusive randomized trial results on its effectiveness. In contrast, observational studies associate glucosamine with significant reductions in mortality and cancer incidence. We evaluated the extent of bias, particularly selection bias, to explain these surprising beneficial effects.We searched the literature to identify all observational studies reporting on the effect of glucosamine use on major outcomes.We identified 11 observational studies, reporting a mean 16% reduction in all-cause mortality (hazard ratio [HR] 0.84, 95% CI: 0.81-0.87) with glucosamine use, as well as significant reductions in cancer incidence and other major diseases including cardiovascular, respiratory and diabetes. We show that these significant effects can result from selection bias due to collider stratification, as all studies used "prevalent" cohorts, where glucosamine use started before cohort entry, and where subjects agreed to join the cohorts. Our illustration of the bias using the UK Biobank publication involving a half-million subjects shows how a true rate ratio of mortality of 1.0 in the population can result in a biased rate ratio of 0.82 in the prevalent cohort.The observational studies reporting significant reductions in mortality, cancer incidence and other outcomes with glucosamine were affected by selection bias from collider stratification. In the absence of properly conducted observational studies that circumvent this bias by considering "new users", the studies to date cannot support the prescription of this supplement as a preventive measure for mortality, cancer, and other chronic diseases.