Copper deficiency anemia: review article

Ann Hematol. 2018 Sep;97(9):1527-1534. doi: 10.1007/s00277-018-3407-5. Epub 2018 Jun 29.


Copper is a crucial micronutrient needed by animals and humans for proper organ function and metabolic processes such as hemoglobin synthesis, as a neurotransmitter, for iron oxidation, cellular respiration, and antioxidant defense peptide amidation, and in the formation of pigments and connective tissue. Multiple factors, either hereditary or acquired, contribute to the increase in copper deficiency seen clinically over the past decades. The uptake of dietary copper into intestinal cells is via the Ctr1 transporter, located at the apical membrane aspect of intestinal cells and in most tissues. Copper is excreted from enterocytes into the blood via the Cu-ATPase, ATP7A, by trafficking the transporter towards the basolateral membrane. Zinc is another important micronutrient in animals and humans. Although zinc absorption may occur by direct interaction with the Ctr1 transporter, its absorption is slightly different. Copper deficiency affects physiologic systems such as bone marrow hematopoiesis, optic nerve function, and the nervous system in general. Detailed pathophysiology and its related diseases are explained in this manuscript. Diagnosis is made by measuring serum copper, serum ceruloplasmin, and 24-h urine copper levels. Copper deficiency anemia is treated with oral or intravenous copper replacement in the form of copper gluconate, copper sulfate, or copper chloride. Hematological manifestations are fully reversible with copper supplementation over a 4- to 12-week period. However, neurological manifestations are only partially reversible with copper supplementation.

Keywords: Anemia; Copper; Gastric-by-pass; Myelodysplastic anemia; Neuropathy; Optic disease; Zinc.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Anemia / diagnosis
  • Anemia / etiology*
  • Animals
  • Biological Transport
  • Celiac Disease / complications
  • Celiac Disease / diagnosis
  • Celiac Disease / metabolism
  • Copper / deficiency*
  • Copper / metabolism
  • Copper / urine
  • Gastric Bypass / adverse effects
  • Humans
  • Nutrition Disorders / complications*
  • Nutrition Disorders / diagnosis
  • Nutrition Therapy / adverse effects
  • Nutrition Therapy / methods
  • Zinc / blood


  • Copper
  • Adenosine Triphosphatases
  • Zinc