administration of a bone resorption inhibitor, bisphosphonate (Rizzoli et al., 1994; Selby et al., 1995).
As Table 7-1 illustrates, hypercalcemias can result either from clinically prescribed intakes of vitamin D or from the inadvertent consumption of high amounts of the vitamin. The plasma (or serum) calcium levels reported range from 2.82 to 4.00 mmol/liter (normal levels are 2.15 to 2.62 mmol/liter) in those individuals with intakes of 1,250 µg (50,000 IU)/day or higher. There is no apparent trend relating “vitamin D intake-days” with plasma calcium levels.
The hypercalcemia associated with hypervitaminosis D gives rise to multiple debilitating effects (Chesney, 1990; Holmes and Kummerow, 1983; Parfitt et al., 1982). Specifically, hypercalcemia can result in a loss of the urinary concentrating mechanism of the kidney tubule (Galla et al., 1986), resulting in polyuria and polydipsia. A decrease in glomeruler filtration rate also occurs. Hypercalciuria results from the hypercalcemia and the disruption of normal reabsorption processes of the renal tubules. In addition, the prolonged ingestion of excessive amounts of vitamin D and the accompanying hypercalcemia can cause metastatic calcification of soft tissues, including the kidney, blood vessels, heart, and lungs (Allen and Shah, 1992; Moncrief and Chance, 1969; Taylor et al., 1972).
The central nervous system may also be involved: a severe depressive illness has been noted in hypervitaminosis D (Keddie, 1987). Anorexia, nausea, and vomiting have also been observed in hypercalcemic individuals treated with 1,250 to 5,000 µg (50,000 to 200,000 IU)/day of vitamin D (Freyberg, 1942). Schwartzman and Franck (1987) reviewed cases in which vitamin D was used to treat osteoporosis in middle-aged and elderly women. These women had health problems in addition to osteoporosis. Intake of vitamin D between 1,250 µg (50,000 IU)/week and 1,250 µg (50,000 IU)/day for 6 weeks to 5 years was found to be associated with reduced renal function and hypercalcemia.
Some evidence supports calcification of renal and cardiac tissue following excess vitamin D intake that is not associated with hypercalcemia. In a study of 27 patients with hypoparathyroidism, Parfitt (1977) found that a mean intake of 2,100 µg (84,000 IU)/day of vitamin D for 5 years was associated with reduced renal function, nephrolithiasis, and nephrocalcinosis. Parfitt hypothesized that these results were a direct effect of vitamin D, since it was not associated with hypercalcemia in these patients. However, these results