By Martin S. Lipsky, MD
Adjunct Professor, Institute on Aging, School of Community Health, Portland State University; Dean Emeritus, University of Illinois College of Medicine, Rockford
Dr. Lipsky is a retained consultant for Health Solutions & Strategies.
SYNOPSIS: Doctors often misdiagnose zinc deficiency, and patients prescribed high doses of zinc are at risk for iatrogenic copper deficiency.
SOURCE: Duncan A, et al. The risk of copper deficiency in patients prescribed zinc supplements. J Clin Pathol 2015.doi: 10.1136/jclinpath-2014-202837 Published online June 17, 2015.
Zinc is essential for health in trace amounts, but the amount of zinc in supplement formulations often exceeds the recommended daily amount.1 While there is little evidence to suggest that short-term replacement, even with larger doses, is harmful, longer-term usage of high-dose zinc interferes with copper absorption and might cause a copper deficiency associated with anemia, neutropenia, and neurological symptoms.2
The study investigators reviewed the charts of 70 patients at Glasgow hospitals taking zinc prescribed by their general practitioner.1 Surprisingly, only a little more than half of those prescribed zinc were tested and documented as having low serum levels. Among those with low plasma concentrations, some were attributable to hypoalbuminemia or systemic inflammation and did not represent true deficiencies. In only one instance was a clinician aware of a concomitant copper deficiency, and in only two cases did clinicians check copper levels.
Among the 70 patients, chart review revealed that 9% developed anemia and 7% developed neurological symptoms suggestive of a copper deficiency. Based on their chart review, the authors concluded zinc deficiency is frequently misdiagnosed based on a low level without considering albumin concentration and/or an inflammatory state. The risk of inducing a copper deficiency is rarely considered, and it appears that a significant minority of patients taking high doses of zinc develop an iatrogenic copper deficiency.
Physicians often prescribe zinc supplementation in cases of dementia, poor nutrition, alcohol withdrawal, non-healing pressure ulcers, alopecia, recurrent infections, and anosmia. Patients also self-medicate with zinc to strengthen their immune systems, to hasten resolution of a viral syndrome, to prevent recurrent infections, or, unwittingly, in the form of zinc-containing dental fixatives. In the United States, the dose of solvazinc, a commonly used zinc sulphate supplement, contains 45 mg of elemental zinc or an amount in excess of the U.S.-recommended limit of 40 mg/day.3 True zinc deficiency is rare in the United States, and over a period of months, excessive zinc interferes with copper absorption, which can induce a copper deficiency. Even when clinicians test serum zinc concentrations, they often fail to consider the albumin level or the presence of an inflammatory state.
When I read this article, the number of patients with neurological symptoms, such as tingling and pain induced by zinc supplementation, surprised me. Many clinicians likely view zinc as a safe supplement, and without an appreciation of the zinc-copper relationship might easily overlook relating these symptoms to zinc supplementation. To avoid an iatrogenic copper deficiency, the study authors give three recommendations: check both C-reactive protein and albumin levels when interpreting plasma zinc concentrations, use daily doses that fall below the upper limit of 45 mg/day, and if prescribing zinc for more than 3 months, monitor plasma copper concentrations.
- Duncan A, et al. The risk of copper deficiency in patients prescribed zinc supplements. J Clin Pathol 2015. doi: 10.1136/jclinpath-2014-202837. Published online June 17, 2015.
- Gabreyes AA, et al. Hypocupremia associated cytopenia and myelopathy: A national retrospective review. Eur J Haematol 2013;90:1-9.
- Institute of Medicine. Food and nutrition board dietary reference intakes: Vitamin A, vitamin K, arsenic, boron, and zinc. Washington, DC: National Academy Press; 2001.