Habitual Glucosamine Use and Risk of Sepsis: A 16-Year Follow-Up Study

OBJECTIVES: Despite the well-documented anti-inflammatory and antioxidant properties of glucosamine, a supplement commonly used to relieve osteoarthritis and joint pain, its potential link with sepsis is yet to be elucidated. To evaluate the association between habitual glucosamine use and the risk of sepsis and 28-day mortality following sepsis in a large cohort. DESIGN: A large-scale cohort study. SETTING: This was a retrospective cohort study of prospectively collected data, including 437,133 participants of the U.K. Biobank. PATIENTS: A total of 437,133 participants from the U.K. Biobank. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Information on glucosamine use was collected through touchscreen questionnaires at baseline. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for the associations between habitual glucosamine use and risk of sepsis and 28-day mortality following sepsis. During a median follow-up of 13.6 years, 13,458 incident cases of sepsis and 2,555 deaths within 28 days post-sepsis were identified. In the multivariable-adjusted model, habitual glucosamine use was associated with a lower risk of sepsis (HR, 0.87; 95% CI, 0.83-0.92) and 28-day mortality following sepsis (HR, 0.79; 95% CI, 0.70-0.89). These associations were consistent across stratified and sensitivity analyses. Mediation analysis revealed that 1.2-7.0% of the association for sepsis and 2.8-5.4% of the association for 28-day mortality following sepsis were mediated through inflammatory biomarkers, including C-reactive protein and systemic immune-inflammation index (all p < 0.001). CONCLUSIONS: Our findings elucidated that habitual use of glucosamine was associated with lower risks of sepsis and post-sepsis mortality. The observed associations might be partially mediated through inflammatory pathways.