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DRI DIETARY REFERENCE INTAKES FOR Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride
TOLERABLE UPPER INTAKE LEVELS
Hypervitaminosis D is characterized by a considerable increase in plasma 25(OH)D concentration to a level of approximately 400 to 1,250 nmol/liter (160 to 500 ng/ml) (Jacobus et al., 1992; Stamp et al., 1977). Because changes in circulating levels of 1,25(OH)2D are generally small and unreliable, the elevated levels of 25(OH)D are considered the indicator of toxicity. However, increases in circulating levels of 1,25(OH)2D in the range of 206.5 to 252.6 pmol/liter (85.9 to 105.1 pg/ml) have been reported (DeLuca, 1984; Holick, 1995; Reichel et al., 1989), which might contribute to the expression of toxic symptoms. As indicated earlier, serum 25(OH)D is a useful indicator of vitamin D status, both under normal conditions and in the context of hypervitaminosis D (Hollis, 1996; Jacobus et al., 1992).
The data in Table 7-1 suggest a direct relationship between vitamin D intake and 25(OH)D levels. Serum levels of 25(OH)D have diagnostic value, particularly in distinguishing the hypercalcemia due to hypervitaminosis D from that due to other causes, such as hyperparathyroidism, thyrotoxicosis, humoral hypercalcemia of malignancy, and lymphoma (Lafferty, 1991; Martin and Grill, 1995).
The adverse effects of hypervitaminosis D are probably largely mediated via hypercalcemia, but limited evidence suggests that direct effects of high concentrations of vitamin D may be expressed in various organ systems, including kidney, bone, central nervous system, and cardiovascular system (Holmes and Kummerow, 1983). Human case reports of pharmacologic doses of vitamin D over many years describe severe effects at intake levels of 250 to 1,250 µg/day (10,000 to 50,000 IU/day) (Allen and Shah, 1992). The available evidence concerning the adverse effects of hypervitaminosis D mediated by hypercalcemia and direct target tissue toxicity are briefly discussed below.
Hypercalcemia of Hypervitaminosis D
Hypercalcemia results primarily from the vitamin D-dependent increase in intestinal absorption of calcium (Barger-Lux et al., 1996) and the enhanced resorption of bone. Resorption of bone (hyperosteolysis) has been shown to be a major contributor to the hypercalcemia associated with hypervitaminosis D in studies that demonstrated rapid decreases in blood calcium levels following the