Zinc-Induced Hematologic Toxicities: A Systematic Review of Descriptive Studies.
Level 4 - case-series / case-control
Systematic review of descriptive studies (case reports and case series)
PubMed 42087025 · doi:10.1007/s12011-026-05136-z
What was done
A systematic review searching PubMed and Scopus for descriptive studies published between 1972 and 2025 reporting zinc-induced hematologic toxicities in humans (such as anemia, leukopenia, neutropenia, thrombocytopenia, pancytopenia, or bone marrow suppression). Study quality was appraised using Joanna Briggs Institute critical appraisal tools, and data were synthesized regarding exposure source, dose, duration, bone marrow findings, management, and recovery.
What was found
The review included 34 publications detailing 37 individual cases. Zinc sources included oral supplements, denture adhesive creams, and coin ingestion, with daily elemental zinc doses ranging from ~50 mg to >1500 mg across durations of weeks to years. Serum copper was decreased in all reported patients. Anemia occurred in nearly all patients, typically alongside leukopenia and neutropenia, with pancytopenia occurring in severe or chronic exposure. Bone marrow biopsies frequently showed vacuolated hematopoietic precursors and ring sideroblasts, leading to initial misdiagnosis as myelodysplastic syndrome. Cessation of zinc and initiation of copper supplementation resolved hematologic cytopenias in the majority of patients within weeks to months, whereas neurological deficits resolved more slowly or incompletely.
Why it matters
Excessive zinc intake is an underrecognized, reversible cause of secondary copper deficiency and bone marrow suppression. Clinicians evaluating unexplained cytopenias can prevent invasive misdiagnoses and permanent neurological sequelae by screening zinc and copper levels.
Limits
The evidence base is restricted to a small total sample size (37 cases) derived from case reports and small descriptive series, introducing substantial reporting and publication bias. Doses and durations were primarily retrospective and self-reported, and the true clinical incidence in broader populations cannot be determined from these data.
Cited by
- supports Taking zinc supplements over a long period depletes the body of copper.