Estimated lithium exposure in drinking groundwater and stroke risks in the United States

Lithium, a naturally occurring element in drinking water, has demonstrated beneficial effects for stroke in prior research, yet its relationship with stroke risk in the general population remains uncertain.

To evaluate the association between environmental lithium exposure and stroke risk.

We assessed environmental lithium exposure across the United States using monitoring data of 4700 wells for drinking groundwater from the US Geological Survey. Ecological and individual-level analyses were conducted. Ecological associations between county-level lithium concentration and stroke mortality (2015-2019) were evaluated in 3108 counties using multivariable linear regression adjusted for county-level socioeconomic factors. Individual-level associations were examined in 303,153 adults (⩾35 years old) from the All of Us Research Program with electronic health records followed up through 1 October 2023 using stratified Cox models adjusted for individual-level sociodemographic, behavioral, and clinical factors. Lithium was analyzed per interquartile range (IQR) increase and by quartiles.

In ecological analysis, each IQR increase in lithium exposure corresponded to 8.2 fewer stroke deaths per 100,000 population (95% confidence interval (CI) = -9.8, -6.5). Compared with the lowest quartile (⩽ 6.6 µg/L), the highest quartile (> 23.3 µg/L) showed 22.6 fewer deaths per 100,000 (95% CI = -27.4, -17.8); middle quartiles were not associated. In All of Us, each IQR increase was associated with a 23% lower incident stroke risk (hazard ratio (HR) = 0.77, 95% CI = 0.66, 0.90). The highest exposure quartile (> 17.7 µg/L) had a 52% lower risk (HR = 0.48, 95% CI = 0.34, 0.67) versus the lowest; the second (HR = 1.23, 95% CI = 0.73, 2.09) and third (HR = 0.92, 95% CI = 0.50, 1.69) quartiles showed non-significant associations. Results were robust to alternate exposure windows and residential stability restrictions.

Higher naturally occurring lithium concentrations in US groundwater are associated with reduced stroke mortality and incidence, whereas low-to-moderate levels confer no benefit.