Previously undescribed vitamin D C-3 epimer occurs in substantial amounts in the blood of cats

Abstract

Objectives The aim of this report is to describe the identification of a novel vitamin D metabolite, a C-3, alpha-epimer of 25-hydroxycholecalciferol (3-epi-25(OH)D), in serum and plasma extracts of cat blood and compare its abundance in cat, dog and rat serum to 25-hydroxycholecalciferol (25(OH)D), a conventional marker of vitamin D status. Methods Serum 25(OH)D and 3-epi-25(OH)D concentrations were measured in healthy cohorts of cats (n = 8), dogs (n = 8) and rats (n = 17) using validated reverse and normal-phase high-performance liquid chromatography methods. The methods were verified using liquid chromatography tandem mass spectrophotometry. Dietary intake and dietary concentrations of vitamin D were also measured for evaluation of species differences and effect of dietary change on vitamin D metabolite concentrations. Differences between cat serum and plasma metabolite concentrations were determined. Results Detectable concentrations of 3-epi-25(OH)D were observed in all cats and rats. No 3-epi-25(OH)D was detected in dogs, where our limit of detection was 5 ng/ml. There were significant differences ( P <0.05) in serum concentrations of 25(OH)D and 3-epi-25(OH)D among species, with cats having the greatest concentrations of both metabolites. Serum and plasma results were not significantly different. A diet change, which resulted in an increase in vitamin D intake among the cats, affected serum concentration with an increase ( P = 0.004) in 3-epi-25(OH)D but no significant change in 25(OH)D. Conclusions and relevance Serum and plasma of cats contain 3-epi-25(OH)D in varied and extraordinary concentrations, much greater than in rats and certainly than that of dogs, a species for which the metabolite was not detected. Importantly, this finding indicates a C-3 epimerization pathway is quantitatively significant for vitamin D metabolism in domestic cats, making 3-epi-25(OH)D assays essential for the evaluation of vitamin D status in cats and positioning the cat as a novel model for study of this pathway.

Vitamin D metabolism in dogs and cats and its relation to diseases not associated with bone metabolism

“…Recently, a new vitamin D metabolite has been discovered in cats, a 25(OH)D epimer, identified as 3-epi-25(OH)D 3 (Sprinkle, Hooper, & Backus, 2018), which was not identified in the serum and plasma of dogs by the authors. Epimerization is an important chemical process for the regulation of some steroid hormones, but the biological functions of 3-epi-25(OH)D 3 have not yet been fully elucidated.…”

“…In this study, eight cats consumed a diet containing 1.36 IU/g of cholecalciferol for over 3 years. This metabolic pathway seems to be an important protective mechanism and may explain why cats are considered resistant to vitamin D intoxication (Sih, Morris, & Hickman, 2001;Sprinkle et al, 2018). It is noteworthy that the two diets provided contained cholecalciferol levels between the adequate intake (0.224 IU/g of dry matter) and the safe upper limit (30 IU/g of dry matter) according to the NRC (2006).…”

“…In the study by Sprinkle et al (2018), the effect of increased vitamin D intake on serum concentrations of metabolites 25(OH)D and 3-epi-25(OH)D 3 was investigated. In this study, eight cats consumed a diet containing 1.36 IU/g of cholecalciferol for over 3 years.…”

“…After increasing cholecalciferol intake, serum concentrations of 25(OH)D remained relatively constant while concentrations of 3-epi-25(OH)D 3 increased. This metabolic pathway seems to be an important protective mechanism and may explain why cats are considered resistant to vitamin D intoxication (Sih, Morris, & Hickman, 2001;Sprinkle et al, 2018). This was demonstrated by Sih et al (2001) that conducted a study with 57 cats which were fed with a diet with 63-fold higher amount of cholecalciferol than recommended by the NRC, and after 18 months, no signs of intoxication or impairment of renal function were observed by measuring biochemical markers, urinalysis and histological evaluation of renal tissue, although mean 25(OH)D plasma concentrations reached 429.4 ± 46.12 ng/ml, about 3.47 times higher than mean 25(OH)D plasma concentrations of the control group (123.76 ± 6.08 ng/ml).…”

Vitamin D Metabolism and Its Role in Mineral and Bone Disorders in Chronic Kidney Disease in Humans, Dogs and Cats

“…A new metabolite of vitamin D, 3-epi-25(OH)D 3 was detected in great amounts in the blood circulation of cats, but not in dogs. Then, the measurement of 3-epi-25(OH)D 3 should be considered in the reliable assessment of vitamin D status in cats [90].…”