Abstract
BACKGROUND: Liver cancer incidence and mortality are escalating globally. Magnesium intake has been studied extensively in nonmalignant liver pathology, but the association between dietary intake of magnesium and primary liver malignancy has not been previously evaluated. OBJECTIVES: We aimed to determine the association between total magnesium intake and primary liver cancer risk. METHODS: Using the NIH-American Association of Retired Persons (NIH-AARP) Diet and Health Study prospective cohort, we estimated the association between magnesium intake and the risk of incident primary liver cancer using Cox proportional hazard modeling adjusted for relevant confounders. Comprehensive stratified and sensitivity analyses were performed. RESULTS: During 6.4 million person-years of follow-up time, 1067 primary liver cancers occurred in 536,359 participants. Higher magnesium intake was independently associated with a lower risk of liver cancer (P-trend = 0.005), with intakes in the highest compared with lowest quartile associated with 35% lower risk (HR: 0.65; 95% CI: 0.48, 0.87). The dose-related inverse association was more pronounced in moderate and heavy alcohol users (HR: 0.54; 95% CI: 0.35, 0.82; P-trend = 0.006), and this interaction was statistically significant (P-interaction = 0.04). CONCLUSIONS: Based on a prospective cohort analysis, we demonstrated that magnesium intake is associated with a lower risk of primary liver cancer, which was more pronounced among moderate and heavy alcohol users. Robust experimental and mechanistic data provide a biological basis to support these findings.