Copper Deficiency: Causes, Manifestations, and Treatment

Abstract

Background: The metabolism of the essential trace element copper remains incompletely understood and, until recently, nearly ignored in acute medicine. Menkes disease was for long the only known copper deficiency condition, but several case reports and investigations conducted over the last 2 decades have shown that deficiency is more frequent than previously suspected, with devastating individual consequences and potential public health consequences. The copper needs in healthy individuals are 0.9 mg/d, which translates to 0.3 mg/d intravenously in parenteral nutrition; the present review aims at gathering actual knowledge. Method and results: A review of literature was conducted in PubMed and Cochrane systematic reviews to identify the most recent information about copper deficiency and generate a narrative review. Copper deficiency has hereditary and acquired origins, the latter being the most frequent. Clinical manifestations are nonspecific but affect all organs and systems, particularly the hematologic (anemia) and the neurologic (myeloneuropathy) systems. Deficiency also affects the cardiovascular, cutaneous, and immune systems. Severe copper deficiency due to reduced absorption after bariatric bypass surgery has become frequent. Conclusion: Deficiency is more frequent than previously recognized, probably because of changing nutrition patterns but also because of some treatments that have become very common such as bypass bariatric surgery and, in acute medicine, prolonged continuous renal replacement therapy. The patients may present with severe hematologic and neurologic complications that go untreated because copper deficiency was not considered in the differential diagnosis: These complications often need active intravenous repletion with doses 4-8 times the usual nutrition recommendations. (Nutr Clin Pract. 2019;34:504-513)

Micronutrients in Liver Disease: Roles, Risk Factors for Deficiency, and Recommendations for Supplementation

“…The first clinical sign of copper deficiency is a microcytic anemia that is unresponsive to iron therapy . Other clinical and neurological signs of deficiency include leukopenia, pancytopenia, hypercholesterolemia, delayed wound healing, sensory ataxia, lower extremity spasticity or paresthesia, myeloneuropathy, and optic neuropathy …”

“…Serum copper levels often mirror the ceruloplasmin concentration, as 80%–95% of copper is transported by ceruloplasmin. Whereas blood copper is considered a fair screening test for deficiency, serum ceruloplasmin concentration is recommended to guide repletion strategies . The RDA for copper is 900 µg.…”

“…Supplementation is indicated if ceruloplasmin is <20 mg/dL. Clinical judgment is required in the presence of inflammation, however, as ceruloplasmin is an acute phase reactant and will be elevated (ie, copper may appear normal) in acute illness and chronic inflammatory diseases such as hepatitis or malignancy . Although there is little evidence on optimal dose and duration of copper supplementation, IV supplementation of 2–4 mg/d (not to exceed 10 mg/d) for 6 days has been suggested for the general population, followed by enteral supplementation of 3–8 mg/d until level normalization or symptom resolution .…”

“…Clinical judgment is required in the presence of inflammation, however, as ceruloplasmin is an acute phase reactant and will be elevated (ie, copper may appear normal) in acute illness and chronic inflammatory diseases such as hepatitis or malignancy . Although there is little evidence on optimal dose and duration of copper supplementation, IV supplementation of 2–4 mg/d (not to exceed 10 mg/d) for 6 days has been suggested for the general population, followed by enteral supplementation of 3–8 mg/d until level normalization or symptom resolution . A recently published case series in patients with chronic liver disease found that, in as little as 3 weeks, serum ceruloplasmin levels improved with copper supplementation of 2 mg/d (IV or oral), and this dose was safe to administer for up to 1 year …”

Micronutrient Deficiencies in Medical and Surgical Inpatients

“…Deficiencies have also been shown to affect specific geographic areas—drinking water may or may not be rich in copper depending on the pipe composition. The deficiency is most frequently acquired [39], e.g., due to insufficient intakes in vulnerable populations, increased demands (pregnancy, lactation, wound healing), malabsorption (including high phytic content of vegetarian diets), increased losses (e.g., major burns, continuous renal replacement therapy), and from hereditary diseases [40,41].…”