Effects of Vitamin D2 and 25-Hydroxyvitamin D2 Supplementation on Plasma Vitamin D Epimeric Metabolites in Adult Cats

Abstract

Feline vitamin D status is based on dietary consumption but metabolism of this essential nutrient and the efficacy of supplementation forms are poorly described in cats. The aim of this study was to further elucidate the metabolites of vitamin D2 in cats and to compare the effectiveness of vitamin D2 and 25(OH)D2 for increasing feline vitamin D status. Eight adult male castrated domestic shorthair cats received vitamin D2 or 25(OH)D2 in a single crossover design. Vitamin D2 was dosed daily in a molar equivalent dosage to vitamin D3 ingested in the diet while 25(OH)D2 was provided at a daily dose of 20% molar equivalent intake of dietary vitamin D3 based on its expected higher potency. Plasma concentrations of 25-hydroxyvitamin D epimers were evaluated at baseline then every 2 weeks for a total of 10 weeks. Analysis of multiple vitamin D metabolite concentrations was completed at the end of each supplementation period, followed by a washout period preceding the second phase of the crossover trial. Results showed that supplementation with 25(OH)D2 more effectively and rapidly raised circulating 25(OH)D2 levels in cat plasma compared to vitamin D2. Formation of C-3 epimers of 25(OH)D3, 25(OH)D2, and 24,25R(OH)2D3, but not 24,25(OH)2D2, were observed in feline plasma. The abundant concentrations of epimeric forms of vitamin D metabolites found in circulation suggest that these metabolites should be considered during vitamin D analyses in cats. Further studies using 25(OH)D and vitamin D2 forms are needed to conclude safety and efficacy of these vitamers for supplementation in this species.

Dietary 25-hydroxyvitamin D3 effects on vitamin D status, plasma metabolites and urine mineral excretion in adult cats

“…Plasma concentrations of 25(OH)D 3 and 24,25-dihydroxyvitamin D 3 (24,25[OH] 2 D 3 ) and their C-3 α-epimers were determined by chromatographic methods. 8 Blood and plasma aliquots were submitted to the University of Missouri Veterinary Medical Diagnostic Laboratory (VMDL) for clinical hematology and chemistry analyses. Serum was submitted for iCa and PTH determinations (Michigan State University Veterinary Diagnostic Laboratory, Lansing).…”

“…Ingested calcidiol is a suggested effective means of raising vitamin D status in cats with enteropathies and hepatopathies. 8 However, vitamin D activity, as may be imparted by ingested calcidiol binding to intestinal epithelial vitamin D receptors, hypothetically may stimulate excessive intestinal phosphorus and calcium absorption and, in turn, stimulate undesired urinary excretion of phosphorus, calcium and magnesium. [9][10][11][12] We hypothesized that dietary supplementation with the vitamin D 3 form of calcidiol, 25(OH)D 3 , may cause clinically significant increases in urinary mineral excretion by cats.…”

Age-dependent changes in plasma concentrations of 25-hydroxyvitamin D may complicate vitamin D status assessment of immature cats

“…Concentrations of 25-hydroxyvitamin D 3 (25 (OH)D 3 ) and 24,25-dihydroxyvitamin D 3 (24,25 (OH) 2 D 3 ) and those of their C-3 epimers in plasma were determined using previously described chromatographic methods with minor modifications for determining metabolite recoveries ( 2 ). In place of radiolabeled internal standards, the α-epimer of 25-hydroxyvitamin D 2 (3-epi-25-hydroxyvitamin D 2 ) and 24 RS ,25-dihydroxyvitamin D 2 (Isosciences, Ambler, PA) were added (25 or 50 ng in 20 μL of methanol) and incubated overnight with assayed plasma aliquots of 0.5 or 1.0 mL at 4°C, before liquid and solid-phase extractions.…”

“…Concentrations of 25 (OH) D determined with these methods may be inaccurate because of unknown cross-reactivities with plasma 3-epi-25 (OH)D 3 and the dihydroxy vitamin D metabolite, 24,25-dihydroxyvitamin D (24,25 (OH) 2 D) ( 8 , 9 ), which is abundant in cats. Concentrations of 24,25 (OH) 2 D in human plasma are typically low, only about 10% of concentrations of 25 (OH)D. Whereas in cat plasma, concentrations of 24,25 (OH) 2 D 3 are 30 to 50% of those of 25 (OH)D 3 ( 2 , 10 , 11 ). Additionally, C-3 epimers of 24,25 (OH) 2 D 3 are reported in cat plasma, with the α-epimeric form of 24,25 (OH) 2 D 3 occurring at low concentrations relative to the β-epimeric form ( 4 ).…”

“…25 (OH) D is readily measurable, has a long circulating half-life, and occurs in concentrations assumed to be proportional to body vitamin D stores. In recent years, quantification of 25 (OH) D in plasma in cats has become complicated by discovery of C-3 epimers of 25-hydroxyvitamin D 3 (25 (OH)D 3 ) and 25-hydroxyvitamin D 2 ( 1 , 2 ). Because of recommendations for supplementing feline diets with vitamin D 3 (cholecalciferol) rather than vitamin D 2 (ergocalciferol) ( 3 ), finding 25-hydroxyvitamin D 2 epimers in cat plasma should be rare.…”