Abstract
BACKGROUND: Although salt intake has been linked to multiple cardiometabolic diseases, whether the frequency of adding salt to foods, a reasonable proxy for long-term salt intake, is related to metabolic dysfunction-associated steatotic liver disease (MASLD) incidence remains unknown. METHODS: This prospective study included 494,110 UK Biobank participants (mean age 56.5 years) who were free of MASLD at baseline. Participants were followed for a median of 13.6 years. Cox proportional hazards models were used to examine the relationship between the frequency of adding salt to foods and incident MASLD. Mediation analyses explored the role of blood biomarkers, and interaction analyses assessed whether genetic factors modify this association. RESULTS: Here, we show that among the cohort, 7171 participants develop MASLD during follow-up. Compared to people who never or rarely adding salt, those who sometimes, usually, and always add salt to foods have 7%, 20%, and 35% higher risk, respectively. This association is stronger in people with normal body mass index and those who frequently drink alcohol. Blood markers of inflammation and metabolism, such as C-reactive protein, insulin-like growth factor-1, triglycerides, and urate, partially mediate this relationship. A significant interaction is observed, with PNPLA3 genetic susceptibility amplifying the MASLD risk associated with frequently adding salt to foods. CONCLUSIONS: A higher frequency of adding salt to foods is associated with increased MASLD risk. Reducing table salt use represents a simple, actionable strategy for disease prevention, particularly for genetically susceptible individuals.