The Relationship Between Trace Element Levels and Arginines in Individuals with Metabolic Syndrome: An Exploratory Cross-Sectional Analysis of Endocrine and Nitric Oxide Metabolism

Background: Metabolic syndrome (MetS) is characterized by a cluster of cardiometabolic abnormalities associated with endothelial dysfunction, oxidative stress, and chronic low-grade inflammation. Disturbances in the arginine–nitric oxide (NO) pathway and alterations in trace element homeostasis have independently been implicated in the pathogenesis of MetS. However, the associations between essential and potentially toxic trace elements and biomarkers of arginine metabolism remain poorly understood. This study aimed to investigate the associations between serum trace element concentrations and arginine metabolism biomarkers in individuals with metabolic syndrome. Methods: This cross-sectional study included 72 adults with MetS diagnosed according to International Diabetes Federation criteria. Serum concentrations of manganese (Mn), selenium (Se), copper (Cu), zinc (Zn), antimony (Sb), molybdenum (Mo), and thallium (Tl) were determined by inductively coupled plasma mass spectrometry (ICP-MS). Asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), N-monomethyl-L-arginine (L-NMMA), and citrulline were quantified in all samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and all reported analyses are based on these LC-MS/MS values. The study was not powered for multivariable modeling, and the findings are therefore hypothesis-generating. Results: Citrulline correlated positively with Zn (ρ = 0.514, q < 0.001), Se (ρ = 0.428, q = 0.002), and Cu (ρ = 0.370, q = 0.008) and inversely with Mn (ρ = −0.505, q < 0.001). SDMA correlated inversely with Mn (ρ = −0.379, q = 0.007). The HC3-robust SDMA model was significant overall (R2 = 0.219, p = 0.005), whereas the adjusted Mn coefficient did not reach conventional statistical significance and its 95% CI included zero (B = −0.00475, 95% CI, −0.00955 to 0.00004; p = 0.052). An increase of one interquartile range in Mn corresponded to a predicted SDMA change of −0.0414 µmol/L (95% CI, −0.0832 to 0.0003). The citrulline model was significant overall (R2 = 0.271, p < 0.001). Conclusions: Zn, Se, Cu, and Mn were associated with citrulline and SDMA; however, the adjusted estimates were imprecise. These exploratory cross-sectional findings do not establish causality, specificity to MetS, or clinical benefit and require confirmation in controlled prospective studies.