Vitamin K Nutritional Status and Disease Risk - A Mendelian Randomization Analysis

Vitamin K is an essential nutrient obtained from dietary sources and commonly included in mainstream dietary supplements, playing a key role in regulating physiological functions and maintaining overall health. However, the causal nature of such associations between vitamin K nutritional status and diseases remains obscure. The existence of causality helps to prove the possibility of vitamin K becoming a biomarker for predicting susceptibility to certain diseases. To investigate this hypothesis, we conducted a literature review to identify diseases previously reported to be associated with vitamin K nutritional status, including cardiovascular, musculoskeletal, liver diseases and cancer, as candidate outcome factors. We also selected specific vitamin K subtypes with distinct physiological functions as exposure factors. Subsequently, we utilized a two-sample Mendelian randomization (MR) analysis using publicly available genome-wide association studies (GWAS) statistics to clarify causal relationships and distinguish vitamin K’s role as a risk factor or protective factor for these diseases. Our results showed that genetically predicted circulating vitamin K1 levels were positively associated with ischemic heart disease, myocardial infarction, heart failure, and alcoholic liver disease (ALD) risk, and negatively associated with lung carcinoma risk. Additionally, matrix Gla protein (MGP), as a biomarker of vitamin K2 nutritional status, was found to be positively associated with the risk of breast carcinoma and ALD. Osteocalcin (OC), another vitamin K2 biomarker, was potentially protective against nonalcoholic fatty liver disease (NAFLD). This novel causality discovery highlighted the necessity for further exploration of vitamin K nutritional status as a crucial factor in the pathogenesis and potential as a predictive, diagnostic, and prognostic biomarker for disease, including carcinoma, liver disease, myocardial infarction, heart failure, and related disorders.