Serum reference intervals for essential and toxic trace elements in a healthy population: A basis for nutritional monitoring and clinical intervention

Abstract

Background & aims Trace elements play a crucial role in human metabolism, and both deficiencies and toxic exposures can have significant clinical implications. This study aimed to establish clinically relevant reference intervals for essential and toxic trace elements in serum from a healthy adult population to support nutritional assessment and public health monitoring. Methods A cross-sectional study was conducted in 501 healthy adults. Serum concentrations of essential [cobalt (Co), copper (Cu), iron (Fe), iodine (I), manganese (Mn), molybdenum (Mo), selenium (Se), zinc (Zn)] and toxic [(arsenic (As), cadmium (Cd), chromium (Cr), lead (Pb), mercury (Hg), nickel (Ni)] trace elements were measured using inductively coupled plasma mass spectrometry (ICP-MS). Reference intervals (2.5th–97.5th percentiles) were calculated following CLSI guidelines, and stratified analyses were performed based on sex and age. Results Reference intervals were established for each element, revealing significant sex-related differences. Women exhibited higher serum concentrations of Co, Cu, Mo, Cd, and Hg, and lower Fe compared to men. Age-related differences were also observed for several elements, with distinct sex-specific trends particularly for Cu and Hg. While serum levels of most essential elements were within expected physiological ranges, Se concentrations were suboptimal in a considerable proportion of the population, suggesting potential nutritional inadequacy. Toxic element levels remained generally low, indicative of minimal environmental exposure. Conclusions Essential trace element concentrations were generally adequate within the Northern Spain population, with the notable exception of Se, where a significant proportion exhibits low levels, suggesting a potential benefit from dietary supplementation or intervention. Toxic element concentrations were low corresponding to a basal level of environmental exposure; however, observed variations by age and sex highlight the importance of ongoing monitoring.