Zinc-Induced Hematologic Toxicities: A Systematic Review of Descriptive Studies

Zinc is an essential trace element, but excessive exposure can disrupt copper metabolism and lead to clinically significant hematologic abnormalities. This systematic review aimed to synthesize published evidence on zinc-induced hematologic toxicities. Literature search was performed in PubMed and Scopus to identify descriptive studies reporting zinc-induced hematologic toxicity in humans. Eligible studies described anemia, neutropenia, leukopenia, thrombocytopenia, pancytopenia, or bone marrow suppression attributed to zinc exposure. Data on patient demographics, zinc source and dose, duration of exposure, laboratory and bone marrow findings, treatment strategies, and outcomes were extracted. Study quality was assessed using Joanna Briggs Institute critical appraisal tools. Thirty-four publications describing 37 individual cases were included, spanning from 1972 to 2025. Zinc exposure most commonly resulted from oral supplements, denture adhesive creams, and coin ingestion, with reported daily elemental zinc doses ranging from approximately 50 mg to more than 1500 mg and exposure durations ranging from weeks to years. Anemia was present in nearly all cases, most often accompanied by neutropenia and leukopenia, with pancytopenia occurring in cases of severe or prolonged exposure. Serum copper levels were reduced in all patients. Bone marrow examination frequently revealed vacuolated hematopoietic precursors and ring sideroblasts, leading to frequent initial misdiagnosis as myelodysplastic syndrome. Discontinuation of zinc exposure with copper supplementation resulted in hematologic recovery in the majority of cases, typically within weeks to months, while neurological manifestations improved more slowly and were sometimes incomplete. Zinc-induced hematologic toxicity is an uncommon but underrecognized and largely reversible condition. Excessive zinc exposure should be considered in patients presenting with unexplained anemia and cytopenias. Routine assessment of zinc exposure and copper status can prevent misdiagnosis, support timely treatment, and decrease the risk of persistent neurological complications.