They Go Together Like Zinc and CopperA Case Report
Abstract & Commentary
By Russell H. Greenfield, MD
Synopsis: This report describes the unfortunate case of a woman who unwittingly exposed herself to moderately high-dose zinc supplementation for a period of years without attendant copper supplementation, ultimately suffering irreversible neurologic consequences due to copper deficiency. The zinc exposure reported would not be atypical for many widely available multivitamins, some of which may not contain copper.
Source: Spain RI, et al. When metals compete: A case of copper-deficiency myeloneuropathy and anemia. Nat Clin Pract Neurol 2009;5:106-111.
The authors relate the story of a 47-year-old woman with a > 2 year history of progressive knee and back pain, paresthesias, ataxia, and falls. During prior workups the woman had also been found to suffer from anemia requiring whole blood transfusions and leukopenia (results of bone marrow biopsies were unremarkable). She had been evaluated by a neurologist and then referred to a multiple sclerosis clinic where the report's authors work.
The clinic neurologists reviewed her chart to find that results of diagnostic blood work for infection, vitamin deficiency, malignancy, and collagen vascular disease were all essentially unremarkable. An MRI of the spine showed an abnormality within the dorsal cervical and thoracic spine that did not enhance with gadolinium. Results of a brain MRI and evoked potentials were noted to be unremarkable.
On physical examination, the woman was found to have reduced muscle bulk and tone, generalized weakness (worse distally) of the arms, legs, and neck flexors. Gait was markedly ataxic, and lower extremity abnormalities on reflex and sensory testing were present. Results of nerve conduction and electromyographic studies suggested the presence of a severe sensory neuropathy without radiculopathy or myopathy.
On further blood testing low levels of copper and ceruloplasmin and high zinc levels were identified. It was soon determined that the patient had long been using a denture cream that contained 34 mg of zinc. The final diagnosis was myeloneuropathy and anemia due to copper deficiency secondary to zinc overload associated with long-term use of denture cream with a high zinc content.
The woman was switched to a low-zinc denture cream and started on oral copper gluconate 8 mg daily, which was tapered to 2 mg daily over a period of one month. Two months later the woman's copper, ceruloplasmin, and zinc levels, as well as her blood counts, had all normalized. The abnormal spinal cord signal on MRI improved at 6 months and completely resolved at 18 months. Her neurologic features stabilized, but unfortunately did not improve even after 18 months of copper supplementation.
Commentary
Readers may well ask, "Why review a case report in AMA?" This editor's answer is because the point being made by the authors is an extremely important one, especially when considering our numerous patients who make use of vitamins and supplements.
The authors of this case report note that copper is an essential trace element, yet nutritional deficiencies of copper are rare in adults unless a condition is present that affects copper uptake or metabolism, or if dietary intake is markedly deficient in copper as with some parenteral feedings. Zinc interferes with the absorption of copper from foods, and high intakes can result in increased expression of endogenous chelating proteins that have greater affinity for copper than for zinc.
A total of 34 mg of zinc taken daily may not raise a red flag initially, especially when many note the tolerable upper limit of zinc intake to be 40 mg/d. The challenge comes in at least two ways: 1) individual metabolic variation and 2) duration of exposure. It is possible that certain individuals may be more susceptible to copper deficiency even when using a moderate dose of zinc on a regular basis, and that an extended duration of use may cause a gradual loss in copper levels undetectable except by only the most thoughtful of practitioners (as these neurologist authors clearly are). Unfortunately, the presentation of severe copper deficiency is insidious, such that the diagnosis may not be considered for years, during which time irreversible neurologic damage may occur.
Copper is a necessary cofactor for the proper functioning of many proteins and enzymes. Copper deficiency can affect hematologic parameters (sideroblastic anemia, leukopenia, neutropenia), bone health, cardiovascular function, and the neurologic system in a way that closely mimics vitamin B12 deficiency (myeloneuropathy with spastic gait, distal paresthesias, and sensory ataxia). Hematologic abnormalities related to copper deficiency fortunately resolve with copper supplementation; however, neurological signs may stabilize but generally do not improve in a clinically significant manner.
Those at highest risk for copper deficiency include people who have undergone gastric bypass surgery and those using supplemental zinc without supplemental copper. Foods high in copper include legumes, shellfish, and chocolate, but it is unclear whether food sources alone can mitigate the potential for copper deficiency in those at risk.
The bottom line, and the reason for including this paper in this month's issue is simplewe need to teach our patients how to read labels, not just of the foods they buy, but also the multivitamins they purchase and take. While the majority of multivitamins that contain zinc also provide copper there are products that do not. It is important to emphasize the need to take a balanced multivitamin if one is taking such an agent at all, a balance that includes an appropriate intake of copper (0.5-2.0 mg/d) together with a safe dosage of zinc, else the risk of developing a stealth disorder like copper deficiency over time becomes all too real.
This report describes the unfortunate case of a woman who unwittingly exposed herself to moderately high-dose zinc supplementation for a period of years without attendant copper supplementation, ultimately suffering irreversible neurologic consequences due to copper deficiency.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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