Review of Copper Provision in the Parenteral Nutrition of Adults

Abstract

ReviewCopper (Cu) is an essential trace element (TE) required for metabolism in all living cells. It has been known to be an essential component of parenteral nutrition (PN) since 1972.1 Provision of the correct amount of Cu is necessary, not only to avoid deficiency and toxicity, but also to promote optimal recovery.2 This article covers the relevant physiology of Cu. It then discusses Cu deficiency and toxicity and examines the evidence behind the recommendations on Cu provision in PN. It provides practical guidance on assessment of Cu status and Cu requirements. The article focuses on adults because provision of Cu in pediatric PN has recently been covered elsewhere, 3 but pediatric studies have been cited where considered appropriate. PhysiologyCu is among the 3 most abundant transition metals in biological systems, the other 2 being iron (Fe) and zinc (Zn). The human body contains around 100 mg of Cu, more than half of which is in bone and muscle. The highest concentrations are in liver, kidney, and brain, reflecting the high metabolic activity of these organs.2 Only 5% is in blood, about 95% of this being bound to ceruloplasmin (Cp) and the remainder to albumin and amino acids. 4 The serum Cu concentration therefore largely reflects the Cp concentration and is affected by factors influencing Cp. Intracellular Cu is usually bound to chaperones and other proteins because free Cu is potentially harmful to cells.Cu, which functions as a component of cuproproteins, has a variety of physiologic roles. For example, it is required for humoral immunity and production of inflammatory cytokines. 5,6 It was recently suggested that the immune system uses Cu intoxication as a means of intracellular bacterial killing. 7,8 Cu is required for the physiologic response to low Fe stores. It is needed for absorption of dietary Fe, release of Fe from hepatocytes and production of hemoglobin.9 Cp oxidizes Fe from the ferrous to ferric state, enabling its transport by transferrin and subsequent use in erythropoiesis. Superoxide dismutase is an antioxidant cuproenzyme that catalyzes the conversion of superoxide radicals to hydrogen peroxide, which is then reduced to water.10 Cu is also necessary for wound healing because it is required for the synthesis of collagen.The average daily oral intake of Cu is 1.0-1.6 mg, which exceeds the RDA of 0.9 mg.11 Dietary Cu is absorbed mainly in the stomach and upper small intestine.2,12 About 55%-75% of dietary Cu is absorbed, which is a high proportion as compared AbstractThe essential trace element copper (Cu) is required for a range of physiologic processes, including wound healing and functioning of the immune system. The correct amount of Cu must be provided in parenteral nutrition (PN) if deficiency and toxicity are to be avoided. While provision in line with the standard recommendations should suffice for most patients, Cu requirements may be higher in patients with increased gastrointestinal losses and severe burns and lower in those with cholestasis. The tests of Cu status that are c...

Exogenous copper exposure causing clinical wilson disease in a patient with copper deficiency

“…Diagnostic evaluation includes measurement of serum copper, ceruloplasmin, vitamin B12, iron studies, vitamin D, vitamin E, zinc, homocysteine and methylmalonic acid levels [ 15 ]. As an acute phase reactant, ceruloplasmin may be falsely elevated in underlying inflammatory conditions like liver disease, malignancy, pregnancy, infections and diabetes [ 16 ].…”

Copper Deficiency: Causes, Manifestations, and Treatment

“…Patients suffering from any form of malabsorption—whether due to surgical procedures, disease, or inadequate feeding—may present with severe hematological and neurological complications that go unrecognized as copper‐related deficiency and are often not included in the differential diagnosis. Indeed, the presenting symptoms are hardly specific, but anemia and neurologic alterations should alert the clinicians: The hematologic alterations are largely reversible, whereas the neurologic manifestations are only partly so, making it even more important to increase awareness about early manifestation. Ongoing research indicates that the issue of copper deficiency may become a public health issue in terms of prevention of cardiovascular diseases.…”

“…Enteral artificial nutrition typically contains copper, and its utilization is rarely associated with deficit, although cases have been reported . Indeed, copper deficit might be observed when the nutrition is provided distal to the copper absorption site—for instance, through a jejunostomy tube—or if copper content is low.…”

“…Finally, if copper deficiency is suspected, a full blood picture should be ordered, along with checking Fe status and vitamins B12, D, and E: In addition, Zn should be determined during long‐term PN to exclude Zn excess …”

Copper Deficiency Anemia in Older Patients with Swallowing Disorders: A Case Report

“…[9][10][11] Therefore, improvements in knowledge as well as awareness about prophylaxis, diagnosis, and treatment are essential. There has been a considerable number of reports of copper deficiency due to intravenous nutrition with highcalorie infusions, and tube feeding with low copper content [19][20][21] ; however, it is essential to recognize that, depending on the diet contents, there is also a risk of this condition in people who mainly take dysphagia diet.…”