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

Due to the presence of receptors in the cells of numerous body tissues, vitamin D is associated with several physiological functions that go beyond calcium and phosphorus homoeostasis and control of bone metabolism in the body. In humans, several studies have associated lower vitamin D concentrations with numerous diseases, such as cancer, heart disease, autoimmune diseases and infectious diseases, and also with an increase in the total mortality rate of the population. Recently, this nutrient started to gain importance in veterinary medicine, and several articles have shown a correlation between low vitamin D status and diseases unrelated to bone metabolism. The present review aims to highlight the recent publications that investigated this relationship, bringing the evidence that exists so far in dogs and cats.     

Diet is a main source of vitamin D in Finnish pet rabbits (Oryctolagus cuniculus)

During the winter time in Finland, sunlight is inadequate for vitamin D synthesis. Many pet rabbits live as house rabbits with limited outdoor access even during summer and may therefore be dependent on dietary sources of vitamin D. The aims of this study were to report the serum 25‐hydroxyvitamin D concentrations in Finnish pet rabbits and to identify factors that influence vitamin D status. Serum 25‐hydroxyvitamin D concentrations from 140 pet rabbits were determined using a vitamin D enzyme immunoassay (EIA) kit. Eleven rabbits were excluded from the statistical analysis because of unclear dietary data. The remaining 129 rabbits were divided into groups depending on outdoor access during summer (no access n = 26, periodic n = 57, regular n = 46) as well as daily diet: little or no hay and commercial rabbit food ≤1/2 dl (n = 12); a lot of hay and no commercial food daily (n = 23); a lot of hay and commercial food <1 dl (n = 59); a lot of hay and commercial food ≥1 dl (n = 35). The range of serum 25‐hydroxyvitamin D concentration was from 4.5 to 67.5 ng/ml with a mean of 26.1 ng/ml. Statistical general linear model adjusted for weight, age and season indicated that diet was associated with vitamin D concentrations (p = 0.001), but outdoor access during summer was not (p = 0.41). Mean 25‐hydroxyvitamin D concentration was significantly higher in the rabbits receiving a lot of hay and commercial food ≥1 dl (33.9 ± 13.2 ng/ml) than in rabbits in other diet groups (24.0 ± 8.5 ng/ml, 21.7 ± 8.1 ng/ml, and 22.2 ± 18.0 ng/ml, respectively). This investigation showed wide variation in 25‐hydroxyvitamin D concentrations among Finnish pet rabbits. Diet remains a main source since outdoor access seems to be too limited to provide adequate vitamin D synthesis for most of them, and the use of vitamin D supplements is rare.     

Effects of Ultraviolet Radiation on Serum 25-Hydroxyvitamin D Concentrations in Captive Chinchillas (Chinchilla laniger)

Vitamin D is an important hormone in vertebrates, and most animals acquire this hormone through their diet and/or exposure to ultraviolet B (UVB) radiation. To date, no study has determined how chinchillas (Chinchilla laniger) acquire vitamin D. The objective of this study was to determine whether exposure to UVB radiation had an effect on serum 25-hydroxyvitamin D levels in captive chinchillas. Overall, 10 juvenile chinchillas were used for this scientific investigation. Baseline blood samples were collected from the animals while under isoflurane anesthesia to determine their serum 25-hydroxyvitamin D concentrations. The chinchillas were then randomly assigned to 2 treatment groups: Group A, 12 hours of UVB exposure per day and Group B, no UVB exposure. At the end of the study (Day 16), a second blood sample was collected from each animal while again under isoflurane anesthesia to measure serum 25-hydroxyvitamin D concentrations. Mean ± standard deviation serum 25-hydroxyvitamin D concentrations differed significantly (P = 0.048) between juvenile chinchillas provided supplemental UVB radiation (189.0 ± 102.7 nmol/L) and those not provided supplemental UVB radiation (87.8 ± 34.4 nmol/L). This study found that exposing juvenile chinchillas to UVB radiation significantly increased their circulating serum 25-hydroxyvitamin D levels. Because vitamin D is an essential hormone in vertebrates, these findings suggest that the provision of UVB radiation to captive chinchillas may be important. Further research to elucidate the importance of 25-hydroxyvitamin D and UVB radiation in captive chinchillas is required.     

Association of Vitamin D Status and Clinical Outcome in Dogs with a Chronic Enteropathy

Background

Dogs with a chronic enteropathy (CE) have a lower vitamin D status, than do healthy dogs. Vitamin D status has been associated with a negative clinical outcome in humans with inflammatory bowel disease.

Objectives

To examine the relationship between serum 25 hydroxyvitamin D (25(OH)D) concentrations at diagnosis and clinical outcome in dogs with a CE.

Animals

Forty‐one dogs diagnosed with CE admitted to the Royal Dick School of Veterinary Studies, Hospital for Small Animals between 2007 and 2013.

Methods

Retrospective review. Serum 25(OH)D concentrations were compared between dogs which were alive at follow up or had died because of non‐CE‐related reasons (survivors) and dogs which died or were euthanized due to their CE (non‐survivors). A binary logistic regression analysis was performed to determine significant predictors of death in dogs with CE.

Results

Serum concentrations of 25(OH)D at the time a CE was diagnosed were significantly lower in nonsurvivors (n = 15) (median nonsurvivors 4.36 ng/mL, interquartile range 1.6–17.0 ng/mL), median survivors (n = 26) (24.9 ng/mL interquartile range 15.63–39.45 ng/mL, P < .001). Serum 25(OH)D concentration was a significant predictor of death in dogs with CE (odds ratio 1.08 [95% CI 1.02–1.18)]).

Conclusions

Serum 25(OH)D concentrations at diagnosis are predictive of outcome in dogs with CE. The role of vitamin D in the initiation and outcome of chronic enteropathies in dogs is deserving of further study.     

Serum Levels of 25-Hydroxycholecalciferol and 1,25-Dihydroxycholecalciferol in Dogs with Hypercalcaemia

1,25-Dihydroxycholecalciferol (1,25-(OH)2-D3) and 25-hydroxycholecalciferol (25-OH-D3) were measured among dogs with hypercalcaemia (total serum calcium > 3.01 mmol/L) due to various causes. All values were compared to those of healthy control dogs. Serum 1,25-(OH)]2-D3 was measured by a radioimmunoassay test and serum 25-OH-D3 was measured by a protein binding assay. 1,25-(OH)2-D3 ranged from 26 to 332 pmol/L (median 110.0) in dogs with lymphoma (n = 12); from 61 to 398 pmol/L (median 248.0) in dogs with primary hyperparathyreoidism (n = 5); from 28 to 310 pmol/L (median 88.5) in dogs with chronic renal failure (n = 10); and from 60 to 239 pmol/L (median 157.5) in control dogs (n = 24). There was no significant difference in 1,25-(OH)2-D3 among dogs with different causes of hypercalcaemia. 25-OH-D3 ranged from 64 to 291 nmol/L (median 101.5) in dogs with lymphoma; from 66 to 298 nmol/L (median 91.0) in dogs with primary hyperparathyreoidism; from 35 to 184 nmol/L (median 67.0) in dogs with chronic renal failure; and from 48 to 350 nmol/L (median 306.5) in control dogs. 25-OH-D3 was significantly lower in dogs with lymphoma, primary hyperparathyroidism and chronic renal failure than in control dogs. 1,25-(OH)2-D3 and 25-OH-D3 are not predictable in dogs with hypercalcaemia.     

Serum 25‐hydroxyvitamin D concentrations in dogs – correlation with health and cancer risk

25‐hydroxyvitamin D (25(OH)D) is important in bone health as well as many diseases including cancer. Supplementation may increase responsiveness of cancer cells to chemotherapy. Serum 25(OH)D, intact parathyroid hormone (iPTH) and canine C‐reactive protein (c‐CRP) were measured in healthy dogs and dogs with haemoabdomen. Regression analysis determined optimal 25(OH)D concentrations. In healthy dogs (n = 282), mean iPTH concentrations correlated inversely (r² = 0.88, P < 0.001) to 25(OH)D concentrations. Variation in both iPTH and c‐CRP plateaued at 25(OH)D concentrations of 100–120 ng mL^?1. Haemoabdomen dogs (n = 63, 43 malignant and 20 benign) had 25(OH)D concentrations ranging from 19.4 to >150 ng mL^?1. Relative risk of cancer increased with decreasing 25(OH)D concentrations [RR = 3.9 for 25(OH)D below 40 ng mL^?1 (P = 0.0001)]. Serum 25(OH)D concentrations in dogs vary widely, and are influenced by dietary VitD content. Serum vitD measurement can identify dogs for which supplementation may improve health and response to cancer therapy.     

A comparison of UVb compact lamps in enabling cutaneous vitamin D synthesis in growing bearded dragons

The effect of exposure to different UVb compact lamps on the vitamin D status of growing bearded dragons (Pogona vitticeps) was studied. Forty‐two newly hatched bearded dragons (<24 h old) were allocated to six treatment groups (n = 7 per group). Five groups were exposed to different UVb compact lamps for two hours per day, with a control group not exposed to UVb radiation. At 120 days of age, blood samples were obtained and concentrations of 25(OH)D₃, Ca, P and uric acid were determined. In addition, plasma 25(OH)D₃ concentration was determined in free‐living adult bearded dragons to provide a reference level. Only one treatment resulted in elevated levels of 25(OH)D₃ compared to the control group (41.0 ± 12.85 vs. 2.0 ± 0.0 nmol/L). All UVb‐exposed groups had low 25(OH)D₃ plasma levels compared to earlier studies on captive bearded dragons as well as in comparison with the free‐living adult bearded dragons (409 ± 56 nmol/L). Spectral analysis indicated that all treatment lamps emitted UVb wavelengths effective for some cutaneous vitamin D synthesis. None of these lamps, under this regime, appeared to have provided a sufficient UVb dose to enable synthesis of plasma 25(OH)D₃ levels similar to those of free‐living bearded dragons in their native habitat.     

Serum concentrations of 1,25-dihydroxycholecalciferol and 25-hydroxycholecalciferol in clinically normal dogs and dogs with acute and chronic renal failure

OBJECTIVE: To compare serum concentrations of 1,25-dihydroxycholecalciferol (1,25-[OH]2D3) and 25-hydroxycholecalciferol (25-[OH]D3) in healthy control dogs and dogs with naturally occurring acute renal failure (ARF) and chronic renal failure (CRF). ANIMALS: 24 control dogs, 10 dogs with ARF, and 40 dogs with CRF. PROCEDURE: Serum concentrations of 1,25-(OH)2D3 were measured by use of a quantitative radioimmunoassay, and serum concentrations of 25-(OH)D3 were measured by use of a protein-binding assay. RESULTS: Mean +/- SD serum concentration of 1,25-(OH)2D3 was 153 +/- 50 pmol/L in control dogs, 75 +/- 25 pmol/L in dogs with ARF, and 93 +/- 67 pmol/L in dogs with CRF. The concentration of 1,25-(OH)2D3 did not differ significantly between dogs with ARF and those with CRF and was in the reference range in most dogs; however, the concentration was significantly lower in dogs with ARF or CRF, compared with the concentration in control dogs. Mean +/- SD concentration of 25-(OH)D3 was 267 +/- 97 nmol/L in control dogs, 130 +/- 82 nmol/L in dogs with ARF, and 84 +/- 60 nmol/L in dogs with CRF. The concentration of 25-(OH)D3 was significantly lower in dogs with ARF or CRF, compared with the concentration in control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: The concentration of 1,25-(OH)2D3 was within the reference range in most dogs with renal failure. Increased serum concentrations of parathyroid hormone indicated a relative deficiency of 1,25-(OH)2D3. A decrease in the serum concentration of 25-(OH)D3 in dogs with CRF appeared to be attributable to reduced intake and increased urinary loss.     

Effects of 25(OH)D3 supplementation during late gestation on the serum biochemistry and reproductive performance of aged sows and newborn piglets

The purpose of this study was to investigate the effects of diet type (normal or low Ca and P diets) and 25(OH)D₃ supplementation (with or with not 2000 IU/kg 25(OH)D₃) during late gestation on the serum biochemistry and reproductive performance of aged sows and newborn piglets. A total of 40 sows, which are at their 7th parity, were divided into four groups: control group (standard diet), low Ca group, 25(OH)D₃ group and low Ca plus 25(OH)D₃ group respectively (10 in each group). The blood of sows on day 100 and 114 of gestation and newborn piglets was collected for serum biochemical analyses. Results showed that the reproductive performance of sows was not influenced by diet type or 25(OH)D₃ supplementation (p > 0.05). And the addition of 25(OH)D₃ to diet low Ca group caused that the content of serum TG in sows on day 100 of gestation was not different from that of the control group (p > 0.05). The addition of 25(OH)D₃ significantly decreases the content of serum TG in sows on day 114 of gestation (p < 0.05). The addition of 25(OH)D₃ significantly increased the content of serum UREA and CREA in newborn piglets (p < 0.05). Overall, feeding 2000 IU/kg 25(OH)D₃ to aged sows at late gestation had no effects on reproductive performance, but partly contributed to keeping serum TG balance in sows and may indicate increased pressure on kidneys in newborn piglets.     

Tolerance evaluation of overdosed dietary levels of 25‐hydroxyvitamin D3 in growing piglets

Forty‐eight, cross‐bred (GL × LW × P) piglets were used in a 42‐day tolerance trial to assess the effects of feeding diets supplemented with vitamin D or increasing levels of 25‐hydroxyvitamin D₃ (25‐OH‐D₃). Six‐week‐old piglets (24 castrate males, 24 females) were used. Two replicate groups of 6 piglets were randomized by weight and allocated to four dietary treatments. The control group (T1) was supplemented with 50 μg vitamin D₃/kg feed. The experimental groups received 25‐OH‐D₃ at the recommended dose (T2: 50 μg/kg = 1x), at 250 μg/kg (T3: 5x) or at 500 μg/kg (T4: 10x) respectively. Feed intake and daily weight gain were measured weekly, and the animals were examined by a veterinarian daily. After 42 days, body mass, blood, urine, bone and tissue samples were analysed and a pathology examination conducted. Dietary treatments had no significant effect on final body mass or daily weight gain. The 25‐OH‐D₃ plasma concentration in T1 was 17 ± 3 ng/ml (mean ± SD) while the respective values of the experimental groups were significantly increased in T2, T3 and T4. Tissue concentrations of 25‐OH‐D₃ were higher in liver and muscle for T3 and T4 and in skin for T4 than in T1. However, neither gross pathology nor histology, nor blood and urine characteristics, nor bone parameters were affected by dietary treatments. Weight of organs as well as dry matter, ash and calcium content of kidneys remained unaffected by dietary 25‐OH‐D₃ intake. Furthermore, no changes were observed for general indicators of health. The results of this study demonstrated that feeding piglets with 25‐OH‐D₃ at 5 or 10 times the recommended level had no adverse effects on any of the biological parameters measured. It was concluded that 25‐OH‐D₃ can be regarded as a supplement with a very high safety margin when used at the recommended level.     

Effect of diet on serum 25-hydroxyvitamin D concentration in the short-beaked echidna (Tachyglossus aculeatus)

Background Elevated concentrations of 25‐hydroxyvitamin D (25(OH)‐D) were diagnosed in captive short‐beaked echidnas (Tachyglossus aculeatus) from three different zoological facilities within Australia. Results The mean serum 25(OH)‐D concentration in the wild echidnas was 24.7 nmol/L and was significantly higher in captive echidnas from all three facilities: Facility 1, mean 335.5 nmol/L (P < 0.001); Facility 2, mean 187.2 nmol/L (P = 0.003); Facility 3, mean 194 nmol/L (P = 0.005). Animals did not appear to have clinical manifestations of vitamin D toxicosis. The increased serum 25(OH)‐D concentration was attributed to excessive dietary intake and a reduction in the amount of vitamin D₃ in the diet of echidnas from Facility 1 resulted in a marked decrease in the serum 25(OH)‐D concentrations (mean 33 nmol/L). The reduction in serum 25(OH)‐D concentration was statistically significant (P = 0.002) and the resulting concentrations were similar to those of wild echidnas (P = 0.212). Conclusion It is not known what effect an elevated serum 25(OH)‐D concentration has on echidnas.