Zinc-induced Copper Deficiency Research Articles

Zinc Toxicity: Understanding the Limits.

Zinc, a vital trace element, holds significant importance in numerous physiological processes within the body. It participates in over 300 enzymatic reactions, metabolic functions, regulation of gene expression, apoptosis and immune modulation, thereby demonstrating its essential role in maintaining overall health and well-being. While zinc deficiency is associated with significant health risks, an excess of this trace element can also lead to harmful effects. According to the World Health Organization (WHO), 6.7 to 15 mg per day are referred to be the dietary reference value. An excess of the recommended daily intake may result in symptoms such as anemia, neutropenia and zinc-induced copper deficiency. The European Food Safety Authority (EFSA) defines the tolerable upper intake level (UL) as 25 mg per day, whereas the Food and Drug Administration (FDA) allows 40 mg per day. This review will summarize the current knowledge regarding the calculation of UL and other health risks associated with zinc. For example, zinc intake is not limited to oral consumption; other routes, such as inhalation or topical application, may also pose risks of zinc intoxication.

Iatrogenic Copper Deficiency: Risks and Cautions with Zinc Prescribing.

Copper deficiency resulting from prescribing zinc in high doses is a rare but life-changing diagnosis that is frequently overlooked. The aim of this study is to gauge how often zinc-induced copper deficiency is missed, to raise awareness of the condition and to stress the need for guidelines for prescribing zinc. Suspected cases of zinc-induced copper deficiency were retrospectively obtained by selecting those patients with hyperzincaemia and hypocupraemia from the database of the Scottish Trace Element Laboratory. Case records were reviewed to determine the validity of the suspected diagnosis. After exclusions, 23 instances of high serum zinc and low serum copper concentrations were found. A positive diagnosis of zinc-induced copper deficiency was made in 14 patients of which 7 (50%) were previously undiagnosed. Serum zinc and copper concentrations are rarely measured in patients prescribed zinc and so the vast majority of cases of zinc-induced copper deficiency are likely to be undiagnosed. We recommend the current official advice on the dose and frequency of zinc administration is revised in order to limit, and potentially eradicate, the condition.

Acquired Hyperzincaemia Due to Zinc-Laden Denture Adhesives Leading to Hypocupraemia as a Cause of Neutropenia

IntroductionCopper deficiency or hypocupraemia is a rare cause of anaemia and neutropenia.Case descriptionWe hereby present the case of a 34-year-old female with gastric bypass surgery who presented with neutropenic fever, abdominal pain and diarrhoea, later found to have extended-spectrum beta-lactamase resistant Escherichia coli urinary tract infection and small bowel bacterial overgrowth syndrome, with her anaemia and neutropenia being caused by copper deficiency due to hyperzincaemia induced by using zinc denture adhesive cream.DiscussionVarious causes of copper deficiency have been recognized including, but not limited to, malnutrition, gastrectomy, gastric bypass surgery, protein-losing enteropathies (coeliac disease, tropical sprue), Wilson disease and Menkes syndrome. Copper deficiency caused by zinc overuse is not very prevalent. The haematologic abnormalities associated with copper deficiency are neutropenia, sideroblastic anaemia and/or pancytopenia.ConclusionBecause of its low prevalence and nonspecific haematologic and clinical manifestations, the diagnosis of zinc-induced copper deficiency (ZICD) can be missed.LEARNING POINTSZinc toxicity is a rare cause of hypocupraemia.The bone marrow and haematological manifestations of copper deficiency are not pathognomonic but include sideroblastic anaemia, pancytopenia or neutropenia.Early detection of hypocupraemia as a cause for neutropenia will improve morbidity and mortality by avoiding untoward infections due to neutropenia, neurological decline or unnecessary interventions.

A coin crisis: a case report of pica with minireview

Pica is defined as a feeding and eating disorder where there is consumption of nonnutritive substances not consistent with cultural practices or social norms. Its aetiology is still unknown, as its prevalence and optimal treatment, which seem to vary with patients' characteristics and the specific behaviours involved. The authors present a case report of pica treated with copper supplementation, with further diagnostic and treatment considerations. Clinical records and interviews were used. A review was conducted using PubMed database. A 59-year-old patient, diagnosed with paranoid schizophrenia, presented with sideroblastic anaemia secondary to zinc-induced copper deficiency in the context of pica. These behaviours ceased with copper supplementation. After 2-year remission, the patient was discontinued on oral copper. One week after, pica behaviours reoccurred, with further remission with renewed copper treatment. Based on temporal relationship, we propose that there might be an association between copper supplementation and pica, not related to its plasma levels. As far as we know, this is the first case report in the literature with such a long-term follow-up of pica treatment. Our findings challenge the cause-effect relation between micronutrient deficiency and pica and prompts further research in the non-adaptive theories of this poorly understood clinical entity.

The predictive value of low plasma copper and high plasma zinc in detecting zinc-induced copper deficiency.

Zinc-induced copper deficiency is a condition whose diagnosis is often delayed allowing severe and usually irreversible neurology symptoms to develop. Plasma copper concentrations are usually low and plasma zinc concentrations high. The aim of this study was to measure the predictive value of this combination of results as a means of facilitating its early diagnosis. Low plasma copper (≤6 µmol/L) and high plasma zinc results (>18 µmol/L) were retrieved from the laboratory database from 2000 to 2014. Medical records and laboratory notes of the corresponding 20 patients found were accessed to determine which were likely to have zinc-induced copper deficiency. Fifteen (75%) patients were diagnosed with zinc-induced copper deficiency which was symptomatic in 13. Of the five remaining patients, two were treated with zinc because of Wilson's disease which was the cause of hypocupraemia, two were treated parenterally with zinc, and insufficient information was available in the final patient. The combination of a low plasma copper and high plasma zinc is strongly predictive for the diagnosis of zinc-induced copper deficiency. There is the therefore an opportunity for the reporting biochemist to facilitate in its earlier diagnosis so enabling treatment to be implemented before the condition deteriorates.

An Interactive Session on Nutritional Pathologies for Health Professional Students.

Various studies have emphasized the need to improve the nutrition training of health professionals, which will help them to provide optimal patient care. Nutrition-based interactive sessions may serve as an efficient approach to instigate an interest in nutrition among the students. Here we report the reception and effectiveness of a nutrition-pathology based interactive activity that we designed and implemented in the gastroenterology course given to the second year students at our medical school. The activity involved team work, individual accountability and peer-teaching. Nutrition pathology case stems (Kwashiorkor, vitamin B-12 deficiency, zinc deficiency and zinc-induced copper deficiency) were posted on the course website for the students to read before the session. At the start of the session, all the groups (each made up of four members) took a pre-quiz. Each student was then given an information sheet describing one case. Each group discussed the four cases with students acting as the “teacher” for the case assigned to them. A post-quiz was administered to the groups to assess acquisition of knowledge as well as in-depth thinking about the nutrition aspects discussed. The efficacy of the session measured by pre (39% questions correctly answered in total) and post-quizzes (96% questions correctly answered in total) and the overwhelmingly positive student feedback indicated that the session was highly effective. Ninety-five percent of students thought that the session demonstrated the clinical relevance of nutrition, while 98% students found the peer teaching to be engaging.

Zinc-induced copper deficiency: a diagnostic pitfall of myelodysplastic syndrome

Zinc-induced copper deficiency: a diagnostic pitfall of myelodysplastic syndrome

Neurotoxicology: Five new things.

Neurotoxic disease can mimic many common neurologic disease states, including parkinsonism, myelopathy, neuropathy, and encephalopathy. Accurate diagnosis and appropriate treatment may result in a favorable outcome. This review highlights 5 areas of neurotoxicology for which there is an emerging understanding of disease processes or patterns of exposure, including 3 specific metal toxicities (manganism, zinc-induced copper deficiency, and cobalt-chromium neuropathy). Toxin-induced posterior reversible encephalopathy syndrome is more widely recognized and reported in association with an ever-growing list of drugs. Two new categories of street drugs, synthetic cathinones and cannabinoids, have been identified as public health threats due to their popularity, availability, and severity of toxicity.

Zinc-Induced Copper Deficiency: Masquerade of Myelodysplastic Syndrome

Excess zinc ingestion is a rare cause of copper deficiency that can lead to sideroblastic anemia and neutropenia that often is not recognized clinically. We present a case of a 55-year-old man with a 3-week history of fatigue and generalized weakness. Laboratory testing detected macrocytic anemia (Hb, 5.9 g/dL; MCV, 107.9 fL), severe leukopenia (1.5 × 10 …

Zinc-Induced Copper Deficiency

Copper deficiency is a rare cause of sideroblastic anemia and neutropenia that often is not suspected clinically. The morphologic findings in bone marrow, while not pathognomonic, are sufficiently characteristic to suggest the diagnosis, leading to further testing to establish the correct diagnosis. Excess zinc ingestion is among the causes of copper deficiency. We present 3 cases of zinc-induced copper deficiency in which the diagnosis first was suggested on the basis of bone marrow examination. The first patient was a 47-year-old man with a debilitating peripheral neuropathy that had progressed during the previous 18 months, mild anemia, and severe neutropenia. The second was a 21-year-old man receiving zinc supplementation for acrodermatitis enteropathica in whom moderate normocytic anemia and neutropenia developed. The third patient was a 42-year-old man with anemia, severe neutropenia, and a peripheral neuropathy that had progressed during 8 months. The bone marrow findings in all cases suggested copper deficiency, which was confirmed by further laboratory testing and determined to be due to zinc excess. The morphologic features, clinical manifestations, differential diagnosis, and pathogenetic mechanisms are discussed.

Zinc-Induced Copper Deficiency

Copper deficiency is a rare cause of sideroblastic anemia and neutropenia that often is not suspected clinically. The morphologic findings in bone marrow, while not pathognomonic, are sufficiently characteristic to suggest the diagnosis, leading to further testing to establish the correct diagnosis. Excess zinc ingestion is among the causes of copper deficiency. We present 3 cases of zinc-induced copper deficiency in which the diagnosis first was suggested on the basis of bone marrow examination. The first patient was a 47-year-old man with a debilitating peripheral neuropathy that had progressed during the previous 18 months, mild anemia, and severe neutropenia. The second was a 21-year-old man receiving zinc supplementation for acrodermatitis enteropathica in whom moderate normocytic anemia and neutropenia developed. The third patient was a 42-year-old man with anemia, severe neutropenia, and a peripheral neuropathy that had progressed during 8 months. The bone marrow findings in all cases suggested copper deficiency, which was confirmed by further laboratory testing and determined to be due to zinc excess. The morphologic features, clinical manifestations, differential diagnosis, and pathogenetic mechanisms are discussed.

Suspected zinc-induced copper deficiency in growing kittens exposed to galvanised iron

AIM: To investigate the possible causes of fading coat colour and an acquired hind-limb ataxia affecting sixteen 4- to 5-month-old kittens in a closed feline colony during 1993 and 1994. METHODS: Records of kittens and litters born in the colony between 1991 and 1997 were analysed. The kittens had been kept from birth until approximately 5 months of age in plastic cages with galvanised iron bar doors. Histopathological sections from 4 of the worst affected ataxic kittens necropsied in 1993 were re-examined. In addition, 6 of the original 16 affected kittens that survived were re-examined as 4- to 5-year-old adults, which were moderately ataxic; these cats were then humanely killed for necropsy. RESULTS: In the kittens, clinical signs included lordosis, dysmetria, ataxia of the hind-limbs and fading coat colour; histopathological lesions included Wallerian-type degeneration in the spinal cord, pons and medulla, and neuronal degeneration in the vestibular nuclei and ventral horns of the spinal cord. Analysis of colony data ruled out an inherited disease, and there was no evidence of dietary inadequacy orexcess. Similar, though milder, clinical and histopathological changes were noted in the affected adults. CONCLUSIONS: Circumstantial evidence is consistent with a diagnosis of zinc-induced copper deficiency caused by the ingestion of zinc oxide from the galvanised iron bar doors. CLINICAL RELEVANCE: Because of the possibility of zinc- induced copper deficiency, galvanised iron should be avoided when designing and constructing cages for cats in veterinary clinics, pet shops and boarding facilities.

Zinc-induced copper deficiency in a coin swallower

In humans, acquired copper deficiency anemia is rare. This report describes a 58-yr-old man with metal pica, especially coins, who presented with symptomatic anemia. His workup led to the diagnosis of zinc-induced copper deficiency. We believe that, in this man, leaching of zinc from pennies explained the clinical and laboratory findings. This case demonstrates that health care workers should consider the possibility of zinc-induced copper deficiency when confronted with patients with unexplained anemia who have ingested coins or other zinc-containing metals.

Excessive zinc ingestion. A reversible cause of sideroblastic anemia and bone marrow depression

Two patients with sideroblastic anemia secondary to zinc-induced copper deficiency absorbed excess zinc secondary to oral ingestion. The source of excess zinc was a zinc supplement in one case; in the other, ingested coins. In each case, the sideroblastic anemia was corrected promptly after removal of the source of excess zinc. These two cases emphasize the importance of recognizing this clinical entity, since the myelodysplastic features are completely reversible.

Excessive Zinc Ingestion

Two patients with sideroblastic anemia secondary to zinc-induced copper deficiency absorbed excess zinc secondary to oral ingestion. The source of excess zinc was a zinc supplement in one case; in the other, ingested coins. In each case, the sideroblastic anemia was corrected promptly after removal of the source of excess zinc. These two cases emphasize the importance of recognizing this clinical entity, since the myelodysplastic features are completely reversible. (<i>JAMA</i>. 1990;264:1441-1443)

Zinc-induced copper deficiency

Copper deficiency was found in an adult patient who had received excessive daily oral zinc for 10 mo. The deficiency was characterized by hypochromic-microcytic anemia, leukopenia, and neutropenia. Although initially thought to be caused by iron deficiency, the anemia did not respond to oral or intravenous iron. Cessation of zinc tablets and ingestion of an oral copper preparation daily for 2 mo failed to correct the anemia or leukopenia. It was not until shortly after intravenous administration of a cupric chloride solution during a 5-day period, at a total dose of 10 mg, that serum copper and ceruloplasmin levels increased and the anemia, leukopenia, and neutropenia resolved. These data suggest that the elimination of excess zinc is slow and that, until such elimination occurs, the intestinal absorption of copper is blocked.

Zinc toxicity in the ferret

Ferrets were fed 500, 1500 and 3000 ppm zinc in their diets for up to 6 months. The groups fed the two highest concentrations of zinc showed severe signs of toxicity between 1 to 2 weeks and the ferrets on the 3000 ppm diet died in less than 2 weeks. The lesions in this group were a diffuse nephrosis, haemorrhages in the intestine and a severe macrocytic hypochromic anaemia. There was a more severe diffuse nephrosis and some glomerular damage in the 1500 ppm group. These ferrets also had a macrocytic hypochromic anaemia. In both the 1500 and 3000 ppm groups there was an increase in zinc and a depression of copper in the liver and kidney tissue. All the zinc-treated ferrets showed decreased serum caeruloplasmin oxidase activity. The results indicated that the anaemia was more the result of the haemorrhages than of the zinc-induced copper deficiency. These findings suggest that ferrets are more susceptible to excess of dietary zinc than other species so far studied.

Iron and Copper Effects on Serum Ceruloplasmin Activity of Rats with Zinc-Induced Copper Deficiency

SummaryThe results of the two experiments conducted to determine the effects of high zinc diets on CPA were as follows: The CPA dropped precipitously in approximately 1 week. The i.p. administration of 100 μg of copper induced a significant rise in CPA. The administration of iron and copper brought about a significant rise in CPA over and above that when copper alone was administered in both control and zinc-fed groups. Copper alone had no effect on CPA of the control rats while iron alone had no effect on CPA level of the zinc-fed rats. However, iron alone increased the CPA of the control rats.