Abstract
BACKGROUND: Limited evidence exists about the relationship between serum carotenoid and mortality in metabolic syndrome (MetS) patients, and the effects of medication use on this association remains unclear. METHODS: The study encompassed 2,521 MetS patients from the National Health and Nutrition Examination Survey (NHANES) 2001-2006 and 2017-2018. A total of 7 serum carotenoids were evaluated. Death data were sourced from the National Death Index, with causes assessed using ICD-10 codes. Bayesian kernel machine regression (BKMR) and random survival forest (RSF) were utilized to investigate serum carotenoid mixture on mortality and identify key carotenoids. "Qgcompint" R package was used to explore the modifying effects of medication use. RESULTS: The serum carotenoid levels at baseline ranged from 0.04 to 1.37 µmol/L. During a follow-up of 15.1 years, there were 696 deaths (27.61%), with 247 (35.49%) by cardiovascular disease (CVD), 148 (21.26%) by cancer, and 301 (43.25%) by other diseases. Individual and combined serum carotenoids were negatively associated with all-cause mortality (HR range:0.70-0.88, 95%CI range:0.56-0.99, all P < 0.05). α-carotene (VIMP = 0.223 in RSF) and lutein/zeaxanthin (PIP = 1.000 in BKMR) emerged as the greatest contributors to all-cause mortality. Lipid-lowering drugs attenuate the negative effect of serum carotenoids on MetS patients' mortality (P(int) = 0.014). CONCLUSION: The present study identified a protective effect of serum carotenoid on mortality in MetS patients, which was probably weakened by lipid-lowering drugs. Early dietary interventions for MetS patients taking lipid-lowering drugs, particularly those rich in carotenoids like α-carotene and lutein/zeaxanthin, could help reduce mortality.