Toxic Effects Associated with Consumption of Zinc

This research analysis was based on the following publishing:

Igic, Petar G. et al. "Toxic Effects Associated With Consumption Of Zinc". Mayo Clinic Proceedings 77.7 (2002): 713-716.

Abstract

A 27-year-old man with a history of acne presented to his primary care physician because of fatigue and dyspnea on exertion of 4 weeks' duration. He was remarkably pale, orthostatic pulse changes were noted, and a systolic ejection murmur was heard. The patient had profound anemia (hemoglobin concentration, 5.0 g/dL) and neutropenia (neutrophil count, 0.06 x 10(9)/L); he was admitted for further evaluation. A detailed inquiry into his medication history revealed that he was taking several vitamins and Zinc gluconate, 850 to 1000 mg/d for 1 year (US recommended daily allowance, 15 mg), as therapy for acne. A Zinc toxic and copper-deficient state was confirmed by laboratory studies. The patient was treated with intravenous copper sulfate, followed by 3 months of oral therapy. The complete blood cell count, serum copper level, and serum Zinc level returned to normal.

Background:

Zinc supplements are commonly used to treat inflammatory acne. Zinc and copper are competitors for absorption within enterocytes, mediated by metallothionein. Bound complexes are shed and excreted; whereas, unbound zinc and copper are absorbed into the portal circulation.

Metallothionein expression is controlled by Zinc intake; however, Copper binds to Metallothionein with a greater affinity than Zinc; therefore, more copper excretion occurs.

Copper in the form of ceruloplasmin, is cofactor in the reaction that mobilizes iron stores needed for hemoglobin synthesis; therefore, copper deficiency can lead to anemia and neutropenia.

Patient Information:

27-yo male with no remarkable medical history, presented with fatigue and dyspnea on exertion of 4 weeks’ duration; night sweats and unable to work for 7 days due to weakness.

Patient takes daily multivitamin, vitamin E and A, topical benzoyl peroxide, and occasionally ginseng. Patient later admitted to taking Zinc gluconate, 850 to 1000 mg/d for the past year (DRI=11 mg/d) in order to treat his inflammatory acne.

Patient is commodity stock trader, nonsmoker, binge drinker (10 beers per weekend) with a 4.5 kg weight loss within the past month.

Initial values: pulse (88 beats/min), BP (100/50 mm Hg), respirations normal, with remarkably pale skin, hemoglobin (5 g/dL), hematocrit (14.7%), total leukocyte (1.2 x 10^9 L), MCV (85.7 fl), serum Zinc (3.18 µg/mL), and Copper (0.10 µg/mL).

Subject and Protocol:

Day 1, neutropenic precautions, discontinuing Zinc supplements, Copper Sulfate IV at 2 mg/d.

Day 2, neutropenic fever treated with IV antibiotics. Punctured lumbar and right frontal sinusitis, treated with nasal decongestants. Despite IV, patient’s Zinc, Iron & Copper level unchanged.

Day 5-9, subcutaneous human granulocyte colony stimulating factor administered dramatically raised WBC count and ceased neutropenic fever.

Day 9, transfusion of 2 U of packed RBC, oral antibiotics & Copper Sulfate (10 mg/d for first 10 days, 2mg/d for 10 weeks). During next 3 months, CBC, serum Copper and Zinc levels normal.

Major Findings: In order to successfully resolve patient’s anemia and neutropenia, secondary to long term high Zinc ingestion, patient was administered intravenous and oral copper and antibiotic, along with subcutaneous human granulocyte colony stimulating factor.

Implications for Basic Knowledge or Clinical Practice:

An exhaustive list of dietary supplements should be part of medical history

Practitioner awareness and patient communication of supplemental zinc benefits and harms