Higher arsenic exposure linked to increased risk of metabolic liver disease

Background and objectives

While metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with obesity, the cause of its rapidly rising prevalence is not well understood. In this study, we aimed to examine the association between arsenic exposure and MASLD in humans.

Methods

Urinary inorganic arsenic data from the National Health and Nutrition Examination Survey, 2011–2020, were used. These were combined with death certificate data from the National Death Index of the National Center for Health Statistics to ascertain mortality rates. Weighted linear regression and chi-squared analysis were performed.

Results

The analysis included 6,386 participants after exclusions. The mean urinary arsenic level was 5.92 µg/L in participants with MASLD versus 5.59 µg/L in those without. Alanine aminotransferase levels exhibited a statistically significant increasing trend across both continuous arsenic levels and arsenic quintiles. A statistically significant upward trend was observed for the income-to-poverty ratio and body mass index but not for education status. MASLD prevalence was highest among the white population, while an increasing trend was observed in the Hispanic population over the years (p < 0.001). The proportion of Mexican Americans increased to 12.6% in the MASLD group versus 8.09% in the non-MASLD cohort (p < 0.001). There was a statistically significant increase in the odds of MASLD across arsenic exposure levels, with individuals in the highest quintile having a 32% greater likelihood compared to those in the lowest quintile (p-trend = 0.002). The odds further increased to 55% in the highest quintile (odds ratio 1.55, 95% confidence interval: 1.19–2.03; p-trend < 0.001). MASLD was more prevalent in females than males (57.9% vs. 47.6%; p < 0.001), and the mean age increased from 46.9 years to 49.9 years (p = 0.016).

Conclusions

In this nationally representative study, higher urinary arsenic levels were significantly associated with a 55% increased odds of MASLD (95% CI: 1.2–2.0) in the highest quintile, independent of traditional metabolic risk factors. These findings persist across key subgroups, suggesting arsenic may contribute to hepatic steatosis even at moderate exposure levels typical in the U.S. population. Screening for arsenic exposure (e.g., urinary biomarkers, well-water testing) in high-risk regions (e.g., Southwest U.S.) could identify populations for targeted liver disease prevention. Regulatory efforts to reduce arsenic in food and water supplies (e.g., U.S. Food and Drug Administration limits for rice products) may concurrently mitigate the MASLD burden.