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Nutrient Metabolism

Moderate Cholecalciferol Supplementation Depresses Intestinal Calcium Absorption in Growing Dogs

M. A. Tryfonidou¹, J. J. Stevenhagen^*, G.J.C.M. van den Bemd, M. A. Oosterlaken-Dijksterhuis, H. F. DeLuca^**, J. A. Mol, W. E. van den Brom, J.P.T.M. van Leeuwen and H.A.W. Hazewinkel

Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3508 TD Utrecht, The Netherlands; ^* TNO Nutrition and Food Research, 3700 AJ Zeist, The Netherlands; Department of Internal Medicine, Erasmus MC Rotterdam, 3000 DR Rotterdam, The Netherlands; and ^** Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706

¹To whom correspondence should be addressed. E-mail: M.A.Tryfonidou{at}vet.uu.nl.

Hormonal regulation of calcium (Ca) absorption was investigated in a cholecalciferol (vitamin D₃)–supplemented group (hVitD) vs. a control group (cVitD) of growing Great Danes (100 vs. 12.5 µg vitamin D₃/kg diet). Although Ca intakes did not differ, fractional Ca absorption was significantly lower in the hVitD group than in the cVitD group. There were no differences in plasma concentrations of Ca, inorganic phosphate, parathyroid hormone, growth hormone or insulin-like growth factor I between groups. Plasma 25-hydroxycholecalciferol [25(OH)D₃] concentrations were maintained in the hVitD dogs at the same levels as in the cVitD dogs due to increased turnover of 25(OH)D₃ into 24,25-dihydroxycholecalciferol [24,25(OH)₂D₃] and 1,25-dihydroxycholecalciferol [1,25(OH)₂D₃]. In hVitD dogs, the greater plasma 24,25(OH)₂D₃ concentration and the enhanced metabolic clearance rate (MCR) of 1,25(OH)₂D₃ indicated upregulated 24-hydroxylase activity. The increased MCR of 1,25(OH)₂D₃ decreased plasma 1,25(OH)₂D₃ concentrations. In hVitD dogs, the greater production rate of 1,25(OH)₂D₃ was consistent with the 12.9-fold greater renal 1-hydroxylase gene expression compared with cVitD dogs and compensated to a certain extent for the accelerated MCR of 1,25(OH)₂D₃. The moderately decreased plasma 1,25(OH)₂D₃ concentration can only partially explain the decreased Ca absorption in the hVitD dogs. Intestinal vitamin D receptor concentrations did not differ between groups and did not account for the decreased Ca absorption. We suggest that 24,25(OH)₂D₃ may downregulate Ca absorption.

KEY WORDS: • 1,25-dihydroxycholecalciferol • 24,25-dihydroxycholecalciferol • ⁴⁵Ca balance • vitamin D receptor • dogs

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