et al., 1988). Their serum copper concentrations ranged from 0.9 to 7.2 μmol/L and ceruloplasmin concentrations ranged from 30 to 125 mg/L. Two patients had neutropenia, one had macrocytic, normochromic anemia, and some had bone abnormalities including reduced bone density. Neutrophil counts normalized and bone abnormalities improved after copper supplementation. If the copper intake of these patients is extrapolated to adults on the basis of caloric intake, copper deficiency might be expected to develop in adults at an intake of 440 μg/2,900 kcal for men and 290 μg/1,900 kcal for women. This deduction is consistent with a study in which healthy young men who were fed a diet containing 380 μg/day of copper for 42 days had a decline in serum copper and ceruloplasmin concentrations and then an increase with copper repletion (Turnlund et al., 1997). Although serum copper and ceruloplasmin concentrations of these men did not fall to the deficient range in 42 days and clinical symptoms did not appear, these effects might be expected had the low copper diet been continued. In a number of other studies at higher levels of copper intake (i.e., at 600 μg/day and above), serum copper and ceruloplasmin concentrations did not decline significantly (Milne, 1998; Turnlund et al., 1990).
Results of depletion studies in laboratory animals have led to interest in a number of conditions in humans that may be associated with marginal copper intake over a long period. Insufficient data are available at this time to establish whether these conditions are related to dietary copper.
A report of increased blood cholesterol concentrations in one young man consuming 830 μg/day of copper (Klevay et al., 1984) suggested that elevated blood cholesterol concentration may be associated with marginal amounts of dietary copper. This effect was not observed in other subjects or in a number of other studies with this or lower levels of dietary copper. In one study, blood cholesterol concentration decreased with lower dietary copper (Milne and Nielsen, 1996), and in a copper supplementation study investigators found increased blood cholesterol concentrations with supplementation (Medeiros et al., 1991).
Heart beat irregularities were reported in some studies, and investigators linked them to dietary copper intake (Milne, 1998). However, heart beat irregularities are common in normal, healthy people, and other studies with lower copper intake demonstrated that such irregularities, monitored during copper depletion and repletion, were common at all intake levels of dietary copper (Turnlund et al., 1997). Myocardial disease occurs in severely deficient weanling rats, and one investigator has hypothesized that ischemic heart disease is