Glucosamine

Glucosamine is an endogenous amino sugar and structural precursor of glycosaminoglycans — polysaccharides that maintain cartilage hydration, elasticity, and compressive resistance. Sold as glucosamine sulfate or hydrochloride at 1500 mg/day, it is one of the most widely used joint supplements globally. Glucosamine partially inhibits glycolysis, mimicking carbohydrate restriction: in C. elegans and ageing C57BL/6 mice this shift activated AMPK, increased mitochondrial biogenesis, and extended lifespan (roughly 8% in nematodes; statistically significant in mice) (Weimer et al., Nature Communications 2014). A UK Biobank cohort of 495,077 adults (Li et al., Annals of the Rheumatic Diseases 2020) found glucosamine use associated with 15% lower all-cause mortality (HR 0.85, 95% CI 0.82–0.89) and 18% lower CVD mortality (HR 0.82, 95% CI 0.74–0.90) over 8.9 years. Suissa et al. (Pharmacoepidemiology and Drug Safety 2022) showed these estimates likely reflect collider stratification bias in prevalent-cohort designs, which can produce spurious 15–20% mortality reductions when the true effect is null. No randomised trial has tested a mortality endpoint; guidelines endorse glucosamine only for symptomatic knee osteoarthritis, where structural benefit evidence remains mixed.