Evidence of a probable role for 25-hydroxyvitamin D in the regulation of human calcium metabolism.

1,25-Dihydroxyvitamin D [1,25-(OH)2D] is the principal mediator of the biologic effects of vitamin D. We showed previously that obese white subjects have low serum vitamin D and 25-hydroxyvitamin D (25-OHD) with increased serum-immunoreactive parathyroid hormone (PTH) and 1,25-(OH)2D, low urinary calcium, and increased urinary cyclic adenosine 3',5'-monophosphate (cyclic AMP) compared with nonobese white individuals. To determine whether 25-OHD modulates calcium metabolism, the effects of 25-OHD3, 40-100 micrograms/day for 9 days, were compared in seven obese and seven nonobese white subjects who were between the ages of 20 and 34 years. Each of them was hospitalized on a metabolic ward and given a constant daily diet that contained 400 mg calcium, 900 mg phosphate, and 18 mEq magnesium. Whereas 25-OHD3 increased mean serum 25-OHD from 7 +/- 1 to 37 +/- 5 ng/ml (P less than 0.01) and urinary calcium from 102 +/- 18 to 146 +/- 17 mg/day (P less than 0.001) and decreased mean serum 1,25-(OH)2D from 40 +/- 2 to 28 +/- 2 pg/ml (P less than 0.01) and urinary cyclic AMP from 3.23 +/- 0.57 to 2.00 +/- 0.17 nM/dl GF (P less than 0.05), it did not change mean serum calcium, ionized calcium, phosphate, magnesium, immunoreactive PTH or urinary phosphate, or creatinine clearance in the obese subjects. In contrast, 25-OHD3 increased mean serum 25-OHD from 16 +/- 1 to 46 +/- 4 pg/ml (P less than 0.001) but did not alter mean serum 1,25-(OH)2D or urinary calcium or cyclic AMP in the nonobese subjects.(ABSTRACT TRUNCATED AT 250 WORDS)