Evidence that calcium modulates circulating 25-hydroxyvitamin D in man

Abstract

We previously demonstrated in normal subjects that 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D) can prevent the increase in serum 25-hydroxyvitamin D (25-OHD) which occurs in response to vitamin D. An investigation was carried out in eight normal subjects, therefore, to determine whether increases in calcium intake would alter the response of serum 25-OHD to challenge with vitamin D. In control studies, vitamin D, 100,000 U/d for 4 d, significantly increased mean serum 25-OHD from 18 ± 3 to 42 ± 5 ng/ml (p < 0.001), an increment of 24 ng/ml (133%). Mean serum calcium, ionized calcium, phosphorus, creatinine, and 1,25(OH)₂D did not change. In contrast, the same dose of vitamin D and calcium, 2,000 mg/d for 4 d, administered to the same eight subjects produced an increase in mean serum 25-OHD from 19 ± 3 to 31 ± 4 ng/ml (p < 0.001), an increment of only 12 ng/ml (63%) and significantly less than the control (p < 0.02). Mean serum calcium (8.8 ± 0.1 vs. 9.2 ± 0.1 mg/dl, p < 0.01) and ionized calcium (4.79 ± 0.07 vs. 4.85 ± 0.08 mg/dl, p < 0.05) increased significantly in response to vitamin D and calcium, mean serum phosphorus and creatinine did not change, and mean serum 1,25(OH)₂D decreased significantly (37 ± 2 vs. 31 ±4 pg/ml, p < 0.02). In a postcontrol study in six of the normal subjects, vitamin D again significantly increased mean serum 25-OHD from 17 ± 3 to 39 ± 9 ng/ml (p < 0.02), an increment of 22 ng/ml (129%). Urinary calcium increased significantly on each of the four days of the administration of calcium as compared to the control study. The results provide evidence that changes in calcium intake can modulate the metabolism of 25-OHD in man.