A comprehensive narrative review synthesizing global epidemiology of essential trace mineral deficiencies and toxic element exposure, biomarker characteristics for each element, and the role of serum multi-element analysis (ICP-MS) as a public health tool. Covers both essential minerals (iron, zinc, selenium, copper, iodine, manganese, molybdenum, chromium) and toxic metals (arsenic, cadmium, lead, mercury, nickel) in the same framework.
Key numbers
- Global disease burden: essential mineral deficiencies contribute to approximately 7% of the global disease burden annually; 372 million preschool-aged children and 1.2 billion women of childbearing age are deficient in at least one key micronutrient (p. 7).
- Iron deficiency: anemia affects over 30% of women of reproductive age; WHO data (p. 5).
- Global coverage: more than 68% of the global population (over 5 billion people) do not consume adequate iodine; deficiencies in iron, zinc, and folate affect more than 50% of the global population (p. 5).
- Subclinical deficiencies: estimated to be twice as prevalent as clinically manifest conditions (p. 6).
- Serum copper reference ranges (Table 7): median 729 µg/L (Serbia) to 1,226 µg/L (Denmark) across 9 countries (p. 29).
- Serum zinc reference ranges (Table 7): median 660 µg/L (Denmark) to 1,150 µg/L (Australia) across 9 countries (p. 29).
- Serum selenium reference ranges (Table 7): median 65.7 µg/L (Serbia) to 130 µg/L (Australia) across 9 countries (p. 29).
- Copper deficiency manifestations: anemia not responsive to iron supplementation, neutropenia, myelopathy, peripheral neuropathy, bone abnormalities (p. 7).
- Mercury-selenium antagonism: inorganic mercury binds selenium, reducing bioavailability for selenoprotein synthesis (p. 9).
- Toxic metal co-exposure in low-income settings: lead, cadmium, and arsenic compete with or displace essential divalent metals, exacerbating functional deficiency at the same dietary intake level (p. 9-10).
- Biomarkers for essential trace minerals: Table 5 covers chromium, copper, iron, iodine, manganese, molybdenum, selenium, and zinc (p. 23-24).
- Biomarkers for toxic elements: Table 6 covers arsenic, cadmium, lead, mercury (p. 26).
- LOD/LOQ: not reported for biomarker reference intervals cited (review of published population studies; original analytical specifications are in cited primary literature).
Methods (brief)
Narrative review commissioned within a research group at the University of Santiago de Compostela. Funded by FECYT (PR295) and USC projects. The serum reference ranges in Table 7 are drawn from published population studies in Australia, Belgium, Denmark, France, Germany, Serbia, Slovenia, Switzerland, and USA; the original studies used ICP-MS or ICP-OES. Because this is a review paper, LOD/LOQ and CRM data are not independently determined.
Evidence fitness
This source is the principal reference for global deficiency prevalence figures, multi-country serum reference range data (Table 7), biomarker characteristics tables (Tables 5 and 6), and characterization of toxic metal co-exposure effects on essential mineral status. The global deficiency figures (7% of disease burden, 372 million preschool children, 1.2 billion women, 68% of global population with inadequate iodine) are sourced here. The between-country variation in serum zinc, copper, and selenium is documented in Table 7. These data support the cross-metal considerations section of the target page and illustrate the absence of harmonized international reference intervals.
Limitations
Narrative review without systematic search protocol. Country coverage in Table 7 is limited to high- and upper-middle-income countries; representative data for low-income countries are sparse. Reference intervals vary by analytical method, pre-analytical handling, and population demographics; direct comparison across the nine countries in Table 7 should be made cautiously. Global deficiency prevalence figures are from WHO and FAO reports, not independently calculated by the authors.
Related evidence
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