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

Abstract

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 μg/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 < 0.01) and urinary calcium from 102 ± 18 to 146 ± 17 mg/day (P < 0.001) and decreased mean serum 1,25-(OH)₂D from 40 ± 2 to 28 ± 2 pg/ml (P < 0.01) and urinary cyclic AMP from 3.23 ± 0.57 to 2.00 ± 0.17 nM/dl GF (P < 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 < 0.001) but did not alter mean serum 1,25-(OH)₂D or urinary calcium or cyclic AMP in the nonobese subjects. Metabolic balance studies carried out in two of the obese subjects showed that 25-OHD₃ increased serum 25-OHD and urinary calcium and lowered serum 1,25-(OH)₂D. The findings are interpreted to mean that elevated serum 1,25-(OH)₂D and urinary cyclic AMP and low urinary calcium in obese subjects result from a deficiency of vitamin D and 25-OHD, that these changes are reversed by 25-OHD₃, and that in humans 25-OHD has a modest role in the regulation of calcium metabolism that is independent of the regulation by 1,25-(OH)₂D.