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BACKGROUND Observational studies suggest inverse associations between serum vitamin levels and the risk of heart failure (HF). However, the causal effects of vitamins on HF have not been fully elucidated. Here, we conducted a Mendelian randomization (MR) study to investigate the causal associations between genetically determined vitamin levels and HF. METHODS Genetic instrumental variables for circulating vitamin levels, including vitamins A, B, C, D, and E, which were as- sessed as either absolute or metabolite levels were obtained from public genome-wide association studies. Summary statistics for single-nucleotide-polymorphisms and HF associations were retrieved from the HERMES Consortium (47,309 cases and 930,014 controls) and FinnGen Study (30,098 cases and 229,612 controls). Two-sample MR analyses were implemented to assess the causality between vitamin levels and HF per outcome database, and the results were subsequently combined by meta-analysis. RESULTS Our MR study did not find significant associations between genetically determined circulating vitamin levels and HF risk. For absolute vitamin levels, the odds ratio for HF ranged from 0.97 (95% confidence interval [CI]: 0.85-1.09, P = 0.41) for vitamin C to 1.05 (95% CI: 0.61-1.82, P = 0.85) for vitamin A. For vitamin metabolites, the odds ratio ranged between 0.94 (95% CI: 0.75-1.19, P = 0.62) for α-tocopherol and 1.11 (95% CI: 0.98-1.26, P = 0.09) for γ-tocopherol. CONCLUSION Evidence from our study does not support the causal effects of circulating vitamin levels on HF. Therefore, there may be no direct beneficial effects of vitamin intake on the prevention of primary HF. [ABSTRACT FROM AUTHOR]