Yiling Yan, Manrong Xu, Ruixin Wang, Shengdi Lu, Yun Shen, Feng Liu
Current cohort evidence indicates that glucosamine use is associated with a modestly lower risk of developing colorectal cancer and with lower mortality from all causes, cardiovascular disease, and cancer overall. The evidence for colorectal cancer-specific mortality was based on only 2 studies with substantial heterogeneity and remains inconclusive. Because all included studies were observational, these findings represent associations rather than evidence of a causal protective effect. Given the modest effect sizes, healthy-user bias and residual confounding are plausible and possibly major explanations for the observed associations, and even a small degree of unmeasured confounding could account for part or all of them. Well-designed studies with improved exposure characterization, and ideally causal designs such as Mendelian randomization, are needed to determine whether these associations are causal and clinically meaningful.
BACKGROUND AND AIM: This systematic review and meta-analysis aimed to evaluate whether habitual glucosamine use is associated with colorectal cancer risk and survival outcomes in the general population.
METHODS: Following PRISMA 2020 guidance, we systematically searched PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews from inception to January 10, 2026. Prospective cohort studies comparing glucosamine users with non-users and reporting adjusted effect estimates were eligible. Two reviewers independently extracted data and assessed study quality using the Newcastle-Ottawa Scale. Adjusted hazard ratios or relative risks were pooled using fixed- or random-effects models based on heterogeneity quantified with I².
RESULTS: From 347 records, 18 prospective cohort studies met eligibility criteria; five outcomes (colorectal cancer incidence, colorectal cancer-specific mortality, all-cause mortality, cardiovascular mortality, and overall cancer mortality) were quantitatively synthesized. Glucosamine use was associated with a lower incidence of colorectal cancer across 5 studies (pooled HR 0.87, 95% CI 0.82 to 0.92; I² = 36%). For colorectal cancer-specific mortality, the evidence was limited to only 2 studies with substantial heterogeneity (I² = 81%) and effect estimates in opposite directions, and the pooled estimate showed no clear association (pooled RR 0.99, 95% CI 0.57 to 1.71); this outcome should therefore be regarded as inconclusive. Glucosamine use was also associated with lower all-cause mortality in 4 studies (pooled HR 0.84, 95% CI 0.76 to 0.94; I² = 65%), lower cardiovascular mortality in 4 studies (pooled HR 0.82, 95% CI 0.75 to 0.89; I² = 44%), and a modest reduction in overall cancer mortality in 4 studies (pooled HR 0.94, 95% CI 0.91 to 0.98; I² = 7%). Results were stable in leave-one-out sensitivity analyses. All estimates represent associations derived from observational cohort studies and cannot establish causation.
CONCLUSIONS: Current cohort evidence indicates that glucosamine use is associated with a modestly lower risk of developing colorectal cancer and with lower mortality from all causes, cardiovascular disease, and cancer overall. The evidence for colorectal cancer-specific mortality was based on only 2 studies with substantial heterogeneity and remains inconclusive. Because all included studies were observational, these findings represent associations rather than evidence of a causal protective effect. Given the modest effect sizes, healthy-user bias and residual confounding are plausible and possibly major explanations for the observed associations, and even a small degree of unmeasured confounding could account for part or all of them. Well-designed studies with improved exposure characterization, and ideally causal designs such as Mendelian randomization, are needed to determine whether these associations are causal and clinically meaningful.