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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc
related to marginal copper status (Klevay, 1989). However, the myocardial changes observed in copper-deficient animals are very different from those of ischemic heart disease in humans (Danks, 1988). In severely deficient animals, the myocardium is hypertrophied and may rupture. Coronary artery resistance is decreased in copper-deficient animals, but it is increased in ischemic heart disease.
Several other clinical observations deserve further investigation, but there is insufficient evidence to link them to marginal copper status. Glucose tolerance was lower in two of a group of eight men consuming 80 μg/day of copper than in men consuming higher levels of copper (Klevay et al., 1986), but similar observations have not been reported at lower intakes of copper in other studies. One study reported a negative correlation between ceruloplasmin concentration and blood pressure during a hand grip exercise (Lukaski et al., 1988), but the link between blood pressure and dietary copper has not been investigated further in humans. An index of immune function declined in a depletion study with copper intakes of 380 μg/day that resulted in decreases in indexes of copper status, but other indexes of immune function did not decline and repletion did not result in reversal of the change (Kelley et al., 1995). Changes in blood clotting factors V and VIII were observed in one study with copper intakes of 570 μg/day (Milne and Nielsen, 1996). The role of copper as an antioxidant has led to interest in the possibility that copper deficiency impairs antioxidant status (Johnson et al., 1992). A report of changes in some, but not other, markers of bone metabolism with a dietary copper intake of 700 μg/day deserves further investigation (Baker et al., 1999). Changes in catecholamine metabolism have been investigated, but results are inconsistent (Bhathena et al., 1998).
SELECTION OF INDICATORS FOR ESTIMATING THE REQUIREMENT FOR COPPER
Several indicators are used to diagnose copper deficiency. These indicators—serum or plasma copper concentration, ceruloplasmin concentration, and erythrocyte superoxide dismutase activity—are low with copper deficiency and respond to copper supplementation. However, except when diets are deficient in copper, they do not reflect dietary intake and may not be sensitive to marginal copper status. In addition, serum copper and ceruloplasmin concentrations increase during pregnancy and with a number of diseases, and therefore copper deficiency could be masked under these