Protective effects of spermidine levels against cardiovascular risk factors: An exploration of causality based on a bi-directional Mendelian randomization analysis

The study investigated the causal relationships between spermidine levels and CVD risk factors using a bi-directional MR approach. Employing genetic variants from extensive GWAS datasets as IVs, the study aimed to determine whether spermidine levels can influence CVD risk factors such as blood pressure, blood glucose, and lipid profiles, and vice versa. The findings suggest a protective role of elevated spermidine levels against hypertension, elevated blood glucose, and lipid profiles (LDL-C and HDL-C). Specifically, increased spermidine levels were significantly associated with lower risk of hypertension (IVW beta = -0.0013453913, p = 0.01597648) and suppression risk of elevated blood glucose (IVW beta = -0.08061330, p = 0.02450205). Additionally, there was a notable association with lipid modulation, showing a decrease in LDL-C (IVW beta = -0.01849161, p = 0.01086728) and an increase in HDL-C (IVW beta = 0.0044608332, P = 0.01760051). Conversely, the influence of CVD risk factors on spermidine levels was minimal, with the exception that elevated blood glucose levels resulted in reduced spermidine levels. (IVW beta = -0.06714391, P = 0.01096123). These results underline the potential of spermidine as a modifiable dietary target for the prevention and management of cardiovascular diseases. Further investigations are warranted to explore the underlying biological mechanisms and the applicability of these findings in broader and diverse populations.