How is a low copper level managed and investigated?

From the Guidelines

Low copper levels should be managed with copper supplementation, and the investigation of underlying causes should begin with serum copper and ceruloplasmin levels, as well as assessment of zinc levels, as high zinc can deplete copper 1.

Management of Low Copper Levels

The management of low copper levels involves copper supplementation, with initial treatment typically involving oral copper supplements such as copper gluconate or copper sulfate at doses of 2-4 mg elemental copper daily for adults.

• In severe cases or when oral absorption is compromised, intravenous copper may be administered as copper chloride at 0.5-1.5 mg/day.
• When giving additional zinc and copper, a ratio of 8- to 15-mg zinc to 1-mg copper should be maintained, and close monitoring is required if higher zinc or copper doses are indicated because each affects the absorption of the other 1.

Investigation of Underlying Causes

Investigation of underlying causes includes:

• Serum copper and ceruloplasmin levels, with low values confirming deficiency.
• A complete blood count to check for anemia or neutropenia.
• Assessment of zinc levels, as high zinc can deplete copper.
• Evaluation of malabsorption through tests like albumin levels and stool studies.
• Clinicians should investigate potential causes including malnutrition, malabsorption syndromes (celiac disease, inflammatory bowel disease), gastric bypass surgery, excessive zinc supplementation, and certain medications like penicillamine.

Importance of Copper

Copper is essential for many physiological processes, including iron metabolism, connective tissue formation, and antioxidant defense, which explains why deficiency can lead to anemia, neutropenia, osteoporosis, and neurological symptoms.

Treatment Duration

Treatment duration depends on the underlying cause, with supplementation continuing until levels normalize and then addressing the primary condition.

Parenteral Nutrition

In patients on long-term parenteral nutrition, plasma Cu and ceruloplasmin should be monitored, especially if they develop PN-associated liver disease or if they have high gastrointestinal fluid losses 1.

• Copper requirements are estimated to be 40 mg/kg per day Cu for preterm infants and 20 mg/kg per day for term infants and children.
• The high Cu content in gastrointestinal fluid means that losses should be balanced by a higher Cu intake (increased by 10-15 mg/kg) in PN.

From the FDA Drug Label

Take 3-4 times daily. Ages 12 and older: 10 drops. Ages 2-11: 5 drops. Under age 2: Consult a doctor. The management of low copper levels may involve taking copper sulfate orally, with the dosage depending on the patient's age:

• Ages 12 and older: 10 drops, 3-4 times daily
• Ages 2-11: 5 drops, 3-4 times daily
• Under age 2: consultation with a doctor is required 2 Investigation of low copper levels is not directly addressed in the provided drug labels.

From the Research

Low Copper Level Management

• Copper deficiency can be managed through oral or intravenous copper replacement in the form of copper gluconate, copper sulfate, or copper chloride 3
• Hematological manifestations of copper deficiency are fully reversible with copper supplementation over a 4- to 12-week period 3
• However, neurological manifestations are only partially reversible with copper supplementation 3

Investigation of Low Copper Levels

• Diagnosis of copper deficiency is made by measuring serum copper, serum ceruloplasmin, and 24-h urine copper levels 3
• Metabolic balance studies have demonstrated that daily copper losses are approximately 1.3 mg/day, and the average adult male must consume a diet containing at least 2 mg copper/day to remain in copper balance 4
• Dietary factors that may affect the bioavailability of copper include the levels of copper, zinc, and molybdenum in the diet; iron deficiency; ascorbic acid intake; intake of carbohydrates, including fructose, glucose, and starch; and fiber and phytate intakes 5

Dietary Recommendations

• A safe and adequate range of intake for copper was established in 1980, with a range of 2 to 3 mg/day 5
• However, some studies suggest that this range may be too low, and that a higher intake of copper may be necessary to prevent deficiency 6
• Certain foods, such as liver and shellfish, are high in copper and should be avoided by individuals with Wilson's disease 7
• On the other hand, augmenting low copper diets with high copper foods may be beneficial for individuals with low copper levels 6