Effect of Chronic Zinc Intoxication on Copper Levels, Blood Formation and Polyamines

A twenty year old woman presented herself for routine examination after she had taken between 440 and 5700 mg elemental zinc or an average of 2300 mg every day for four months. The most striking laboratory findings were a serum zinc level of 7760 mcg/dl, a serum copper of 8 mcg/dl and undetectable ceruloplasmin. The patient was severly anemic and showed macrocytosis and neutropenia. Other abnormal parameters were a slightly elevated serum glucose, slightly depressed serum globulin and total protein, a very high alkaline phosphatase and low cholesterol. Polyamines were normal. Oral copper therapy and cessation of excess zinc produced remarkable reversal of all abnormal parameters beginning in the first week and virtual recovery of anemia and neutropenia by the fourth week post-treatment. Polyamine levels increased to between four and ten times normal during the period of accelerated blood formation, then reverted to normal. Macrocytosis rather than microcytosis in zinc toxicity or severe copper deficiency has been seen (Brain Bk) Centre Princeton, New Jersey 08540 only in cases where generous supplements of vitamin C were supplied as in this case. There is a strong likelihood that the vitamin C fortuitously prevented even more severe anemia. The possible benefit of vitamin C and of zinc gluconate vs. zinc sulfate in zinc therapy is discussed. It appears that with proper monitoring, far larger doses of zinc than are now customary may be used if found to be therapeutically valuable. The need for zinc in human nutrition is now well established. In addition to its obvious use in zinc deficiency, zinc in larger than replacement levels is emerging as a potent therapeutic agent in many widely varying conditions (Prasad et al., 1963; Pories et al., 1967; Husain, 1969; Portnoy and Molokhia, 1972; Pfeiffer and Cott, 1974; Neldner and Hambidge, 1975; Brewer et al., 1977; Simkin, 1977). This ever expanding use of larger doses of zinc has created a need for more data on.human toxicity. There have been numerous reports of acute toxicity from a single or short term exposure to high levels (as many as several grams) of zinc (Cowan, 1947; Brown et al., 1964; Murphy, 1970; Gallery et al., 1972; Chunn, 1973), and now patients being treated for sickle cell anemia (Prasad et al., 1978) or to promote wound healing (Pories et al., 1976) have provided data on the effects of extended exposure. However, the