Remote ischemic preconditioning (RIPC) has demonstrated protective effects in patients with lower extremity arterial disease (LEAD) undergoing digital subtraction angiography (DSA) and/or percutaneous transluminal angioplasty (PTA). This study aimed to investigate the impact of RIPC on the metabolomical profile of LEAD patients undergoing these procedures and to elucidate its potential underlying mechanisms. A total of 100 LEAD patients were enrolled and randomly assigned to either the RIPC group (n = 46) or the sham group (n = 54). Blood samples were drawn before and 24 h after intervention. Targeted metabolomics analysis was performed using the AbsoluteIDQ p180 Kit, and changes in metabolite concentrations were compared between the groups. The RIPC group demonstrated significantly different dynamics in nine metabolites compared to the sham group, which generally showed a decrease in metabolite concentrations. The impacted metabolites included glutamate, taurine, the arginine-dimethyl-amide-to-arginine ratio, lysoPC a C24:0, lysoPC a C28:0, lysoPC a C26:1, PC aa C38:1, PC ae C30:2, and PC ae C44:3. RIPC exhibited a ‘stabilization’ effect, maintaining metabolite levels amidst ischemia-reperfusion injuries, suggesting its role in enhancing metabolic control. This may improve outcomes for LEAD patients. However, additional studies are needed to definitively establish causal relationships among these metabolic changes.

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