Neurological function and copper: Too much or not enough?
Copper is a trace element found in all body tissues and is required for many cellular functions. One of copper’s most important roles in the human body is promoting neurological function by playing a role in antioxidant defense and neurotransmitter synthesis. Copper has been implicated in nervous system diseases, including Alzheimer disease, amyotrophic lateral sclerosis (Lou Gehrig disease), and Parkinson disease.1 Copper deficiency will ultimately result in neurological symptoms, but copper excess also may be damaging to the nervous system.
Known causes of copper deficiency are malabsorption, medications, gastric or intestinal surgeries, and hemodialysis. Copper is absorbed in the small intestine, mostly in the duodenum. Malabsorption syndromes, such as celiac disease, and certain medications may alter copper absorption and cause a copper deficiency. Undernutrition associated with chronic diarrhea and patients on a strict milk-based diet also may develop copper deficiency over time. Medications such as H2 antagonists or proton pump inhibitors can decrease copper absorption because gastric acid and pepsin are required to release bound copper from foods. Excessive zinc supplementation can induce a copper deficiency by reducing the amount of copper absorbed in the enterocytes of the small intestine. One example of unexpected zinc intake is long-term use of denture adhesives containing high amounts of zinc.2
Another important cause of copper deficiency is Roux-en-Y gastric bypass surgery for obesity. Although copper deficiency is rarely reported in this population, it likely occurs fairly often.3 Patients typically present years after gastric bypass surgery with gait changes and peripheral neuropathies. The most common symptoms of copper deficiency are paresthesias and altered vibration perception in the legs combined with unaltered touch or strength. Patients also may present with anemia and decreased white blood cell count. In this setting, copper deficiency may be misdiagnosed as vitamin B12 deficiency because it is a more widely known complication of gastric bypass surgery. Evaluation of methylmalonic acid as an indicator of vitamin B12 status and serum copper or ceruloplasmin should prevent such misdiagnosis.
Oral copper supplementation should be used to correct copper deficiency and has even been effective in patients with copper malabsorption. Of note, an anemia resulting from copper deficiency may correct within 1 to 2 months, but some neurological changes may be permanent. These issues underscore the importance of closely monitoring for nutritional deficiencies in patients after gastric bypass surgery.
In contrast to copper deficiency, copper toxicity is rare because the human body regulates copper storage through biliary excretion. Ingestion of copper in amounts up to 0.5 mg/kg/d appears to be safe. Consuming amounts between 10 and 15 mg/kg/d copper can cause a metallic taste, vomiting, and diarrhea. In patients with a genetic predisposition such as Wilson disease, chronic ingestion of excessive copper can result in liver cirrhosis and progressive basal ganglia degeneration in the brain. Copper deposition in the basal ganglia causes Parkinsonian symptoms, such as dystonia and tremor. Excessive copper also may deposit in the eye, causing a Kayser–Fleischer ring, which is present in about 95% of patients with neurological symptoms of copper toxicity.
Both copper deficiency and copper toxicity can cause neurological disturbances. Although copper deficiency and toxicity are rare conditions, at-risk patients should be monitored due to the severity of the neurological symptoms.
Am J Clin Nutr. 2008;88(3):855S–8S.
J Obes. 2012;2012:608534.