Water hardness and all-cause and cause-specific mortality: evidence from a prospective cohort study

The health implications of domestic water hardness remain controversial, with limited prospective evidence on cause-specific mortality. We investigated associations of calcium carbonate (CaCO 3 ), calcium (Ca), and magnesium (Mg) concentrations with all-cause and cause-specific mortality in a prospective cohort. This prospective cohort study included 497,280 UK Biobank participants. Water hardness was categorized using WHO (≥ 200 mg/L) and USGS (≥ 180 mg/L) thresholds, as well as by quartiles (Q1-Q4). Data were analyzed using Cox proportional hazards models, with adjustments for demographic, socioeconomic, genetic (polygenic risk scores), clinical and environmental factors. Penalized splines were fitted to illustrate concentration-response patterns. Pre-specified exploratory interaction analyses of demographic factors and genetic susceptibility were also assessed. Over a median follow-up of 13.7 years, 39,541 all-cause deaths (8.0%) were documented. Cause-specific mortality distributions were cancer 4.0%, cardiovascular disease 1.8%, respiratory diseases 0.6%, and neurological disorders 0.5%. After false-discovery-rate (FDR) adjustment, high water hardness (180–200 mg/L or higher) was associated with increased cancer mortality (HR 1.11–1.12). Each IQR increase in CaCO 3 was associated with an HR of 1.09 (95% CI 1.03–1.15). A nearly linear exposure-mortality relationship was found between water hardness indicators and cancer mortality. Other associations were nominal and did not survive FDR adjustment. WHO-defined hardness > 200 mg/L showed a small increase in all-cause mortality (HR 1.05, 95% CI 1.01–1.09). We observed elevated respiratory-disease mortality in participants in the highest quartile (Q4 vs. Q1 HR 1.27, 95% CI 1.05–1.53), and an inverse nominal association between an IQR increase in Mg and CVD mortality (HR 0.97, 95% CI 0.94–0.99). No significant associations were found in predefined subgroup analyses. These findings suggest that the relationship between water hardness and cancer mortality warrants further investigation and may merit consideration in future reviews of drinking water quality guidelines.