Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. 
Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. What was studied?
The article “Anemia Due to Unexpected Zinc-Induced Copper Deficiency” by Chun et al. (2025) investigates a rare case of acquired copper deficiency anemia resulting from prolonged high-dose zinc supplementation. This case study contributes to the expanding body of knowledge on the interplay between trace elements, specifically, how excessive zinc intake disrupts copper absorption by inducing metallothionein production in enterocytes, thereby sequestering copper and causing secondary deficiency. The study meticulously explores hematologic manifestations, including anemia, leukopenia, and neutropenia, arising from this imbalance. Bone marrow findings revealed hallmark features such as cytoplasmic vacuolization in erythroid and myeloid precursors and ring sideroblasts, mimicking myelodysplastic syndromes. These diagnostic features provide critical insight into how micronutrient toxicity may be mistaken for more severe hematological disorders. The work underscores the need for awareness of micronutrient interactions in both clinical and regulatory settings, information that has direct implications for heavy metal certification and safety programs, including those governed by HTMC standards.
Who was studied?
The study reports an 18-year-old female with multiple comorbidities, including cerebral palsy, Lennox–Gastaut Syndrome, and chronic respiratory dependence, who developed anemia and neutropenia during hospitalization for respiratory failure. Laboratory data revealed normocytic, normochromic anemia and severe leukopenia with absolute neutropenia. Further investigation confirmed markedly reduced serum copper (<0.10 mcg/mL) and elevated serum zinc (1.37 mcg/mL). The patient’s medical history disclosed chronic zinc supplementation as part of a ketogenic dietary regimen prescribed externally for seizure management. Following intravenous copper chloride administration and cessation of zinc supplementation, hematologic parameters normalized within one month, confirming the reversible nature of zinc-induced copper deficiency. This single-patient case thus offers an important clinical lens through which micronutrient-related hematological pathologies can be identified and managed.
Most important findings
| Critical Points | Details |
|---|---|
| Mechanistic interaction | Excessive zinc induces metallothionein in intestinal cells, preferentially binding copper and impeding its systemic absorption. This imbalance leads to copper deficiency, impairing enzymes essential for heme synthesis and iron mobilization. |
| Hematologic features | Bone marrow biopsy revealed hypocellularity and vacuolated erythroid/myeloid precursors with occasional ring sideroblasts (<10%), mimicking myelodysplastic morphology. Peripheral smear confirmed normocytic, normochromic anemia without dysplasia. |
| Laboratory findings | Initial tests showed low hemoglobin (6.2 g/dL) and WBC (1.69 ×10⁹/L), markedly decreased serum copper (<0.10 mcg/mL), and elevated zinc (1.37 mcg/mL). After IV copper therapy and zinc cessation, parameters normalized (Hgb 11.4 g/dL; WBC 5.08 ×10⁹/L). |
| Differential diagnoses | Conditions such as myelodysplastic syndrome, Pearson syndrome, and Menkes disease were ruled out based on normal chromosomal findings and lack of dysplasia. |
| Therapeutic response | Intravenous copper chloride led to rapid hematologic recovery, with sustained remission after discontinuation of zinc. Oral copper gluconate may be effective in less severe cases. |
| Clinical significance | The case emphasizes the reversibility of zinc-induced cytopenias and the diagnostic value of marrow vacuolization as a morphological clue to copper deficiency, preventing misdiagnosis and unnecessary interventions. |
| Relevance to HTMC and regulatory oversight | The study reinforces the necessity for stringent regulation and testing of trace element concentrations in supplements and dietary products, especially zinc, to prevent secondary metal deficiencies that may mimic hematologic malignancies. |
Key implications
This study highlights the essential regulatory insight that excessive exposure to one trace metal can disrupt the absorption of another, directly informing HTMC certification standards. Primary regulatory impacts involve establishing permissible zinc concentration thresholds in supplements and clinical nutrition formulations. Certification requirements must emphasize multi-element balance testing to ensure that heavy metal exposure, whether deficiency or excess, does not produce toxicological or hematological sequelae. Industrially, the findings encourage routine trace element screening in health products and fortificants. Research gaps remain regarding the long-term neurohematologic outcomes of reversible copper deficiency, particularly in poly-supplemented patients. Practically, clinicians and regulators should advocate for integrated mineral testing in anemia diagnostics and certify supplement safety within HTMC frameworks.
Citation
Chun N, Aman S, Xu D, Wang J, Zuppan C, Kheradpour A. Anemia Due to Unexpected Zinc-Induced Copper Deficiency. Hematology Reports. 2025;17(4):35. doi:10.3390/hematolrep17040035
