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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.

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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].

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Last Update: January 10, 2015.



Zinc is an essential mineral and heavy metal that is included in most over-the-counter multivitamin and mineral supplements, and is used therapeutically in higher doses because of its ability to block copper absorption as maintenance therapy of Wilson disease. Zinc has not been associated with worsening of serum enzyme elevations during therapy or with clinically apparent liver injury.


Zinc is an essential trace element that is found in many human enzymes and transcription factors. The recommended dietary allowance is 8 mg per day for women and 11 mg for men. Zinc is widely present in foods, and the typical Western diet has adequate concentrations, the highest levels being found in shellfish and red meats. Zinc deficiency is usually due to malnutrition and reduced dietary intake, but can also occur with strict vegetarian diets. Zinc deficiency is not uncommon in developing countries, but severe deficiencies are rare. Zinc deficiency can be accompanied by growth retardation, infertility, dysgeusia, diarrhea, dermatitis, glossitis, behavioral changes, depression and mental clouding. The recommended daily allowance of zinc is 15 mg per day in men and 12 mg in women, with higher levvels recommended for pregnant or lactating women.

High doses of oral zinc interfere with the absorption of copper and iron, and supplementation above the RDA can cause copper deficiency. Because of its effects on copper balance, zinc has been used to treat Wilson disease, particularly as maintenance therapy once copper levels have been reduced with chelating agents. Wilson disease is a caused by inherited mutation in the ATPase7B gene, which encodes a hepatic enzyme responsible for the transmembrane transport and excretion of copper. The metabolic defect leads to accumulation of free copper in liver and blood and secondarily in other organs, particularly brain and kidney. The disease usually presents in childhood or adolescence with neurologic syndromes, signs of advanced liver disease and hemolytic anemia. Zinc is a unique approach to the treatment of Wilson disease in that it interferes with dietary absorption (probably by increasing intestinal metallothionein), rather than decreasing tissue levels by chelation. Zinc acetate is approved for use in the United States as maintenance therapy of Wilson disease and is available in capsules of 25 and 50 mg under the brand name Galzin. Other zinc formulations have been used to treat Wilson disease, including zinc sulfate and zinc gluconate (Gluzin), but these have not been formally approved for this indication. The recommended dose is 25 to 50 mg two to three times daily. Zinc when given only one daily has little or no effect on copper balance, and is not recommended. Zinc is generally well tolerated, but when given in high doses up to 10% of patients initially have abdominal pains or gastrointestinal intolerance which can require dose adjustment or discontinuation. Long term therapy can potentially lead to copper deficiency.

Zinc overdose has been described and is usually due to ingestion of coins, metallic objects or zinc soldering solutions and rarely to suicidal overdose. Symptoms include rapid onset of epigastric pain, nausea and vomiting and diarrhea, followed by lethargy, dizziness, ataxia, confusion and coma. With high doses, patients develop hypotension, metabolic acidosis and hemolytic anemia that can be severe and life-threatening. Liver injury is generally mild and arises after a day or two. Nevertheless, cases with jaundice, cholestasis and hepatic failure have been described. Therapy of acute zinc overdose generally rests upon hydration, gastric lavage or whole bowel irrigation, correction of metabolic acidosis and anemia and zinc chelation with dimercaprol or EDTA infusions.


In case series and small trials of zinc therapy in patients with Wilson disease, adverse events have included gastrointestinal upset, but serum enzyme elevations and clinically apparent liver injury were not reported. Patients with Wilson disease frequently have liver injury and, in most case series, zinc therapy has been associated with slow improvement in the hepatic manifestations.

Zinc overdose can be associated with liver injury, jaundice and even hepatic failure, usually arising after several days and resembling injury from copper or iron overdose. The injury is clearly direct toxicity.

Drug Class: Chelating Agents, Trace Elements and Metals, Wilson Disease Agents

Other Drugs in the Subclass, Wilson Disease: Dimercaprol, Penicillamine, Trientine



Zinc – Generic, Galzin®


Minerals; Chelating Agents


Product labeling at DailyMed, National Library of Medicine, NIH




References updated: 10 January 2015

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