Modeling human vitamin D status in experimental rodents

Abstract

We studied the effect of vitamin D3 (VD3) intake on VD status and markers of calcium (Ca) homeostasis. Experiment 1: 10 week old Sprague Dawley rats raised on a 400 IU/kg VD3 diet were fed one of five diets containing 400, 1,000, 5,000, 10,000, or 20,000 IU VD3/kg for 4 weeks (n=10 per diet). C57/BL6 mice were fed these diets until 10 wks of age (n=6 per diet). Serum 25 hydroxyvitamin D (25OH D) was directly related to VD3 intake in rats and mice (15 or 7.2 ng/ml per 1,000 IU VD3). Body weight (BW), serum Ca, and duodenal gene expression were not altered but high VD3 decreased serum 1, 25-dihydroxyvitamin D (1,25 D) and renal 1alpha-hydroxylase (CYP27B1) mRNA (−75% and −88% at 20,000 IU/kg). Thus, rodents tolerate high VD intake by balancing elevated 25OH D levels and the VD endocrine system. Experiment 2: Rats and mice were fed AIN93G diets containing 25, 50, 100, 200, 400, or 1,000 IU VD3/kg from weaning until 12 weeks of age (n=6 group). Serum 25OH D declined with lower VD3 following a split-line regression (break point at 200 IU/kg, 4-fold steeper slope below this point). BW and serum Ca were normal, however, renal CYP27B1 mRNA increased 2-fold in rats fed < 200 IU VD3/kg suggesting stimulation of the VD endocrine system. For scientists who wish to model the suboptimal vitamin D status common in humans, dietary VD3 levels below the NRC requirement for rodents of 1000 IU/kg are required. Supported by NIH awards DK054111 and CA101113 to JCF