Vitamin D3 Concentrations Research Articles

Evaluating the Effects of Maternal Vitamin D Supplementation on the Subsequent Growth Performance and Carcass Characteristics of a Subsample Population of Growing Pigs

A subsample of 448 growing pigs (PIC 327 × 1050), or approximately 50% of pigs weaned from sows fed varying dietary vitamin D regimens, were used in a split-plot design to determine the influence of maternal and nursery vitamin D regimens on growth performance. Sows were previously administered diets containing vitamin D as either: 1) low vitamin D3 (363 IU/lb); 2) medium vitamin D3 (907 IU/lb); 3) high vitamin D3 (4,354 IU/lb); or 4) 23 μg 25(OH)D3/lb (Hy-D, DSM Nutritional Products Inc, Parsippany, NJ) as described by Flohr et al. (20153) throughout gestation and lactation. A total of 52 total litters from 2 consecutive weaning groups were represented in the subsample population for growth performance. Once weaned, pigs were allotted to pens in the nursery based on previously administered maternal vitamin D regimens, then pens were randomly assigned to 1 of 2 nursery vitamin D regimens (907 IU of vitamin D3/lb, or 23 μg 25(OH)D3/lb). Pigs remained on nursery vitamin D regimens for 35 d, then they were provided common growing and finishing diets until market. One pig per pen was bled at weaning and on d 17, 35, and 70 post-weaning to determine growing pig serum vitamin metabolites. At weaning, pig BW was increased (quadratic, P = 0.001) with increased maternal vitamin D3 supplementation. This was because pigs from sows fed the medium concentration of vitamin D3 were heavier at weaning compared to pigs from sows fed the low or high concentration of vitamin D3. Overall from d 0 to 35 in the nursery, pigs from sows fed increasing vitamin D3 had increased (quadratic, P < 0.003) ADG and ADFI, but F/G was similar regardless of maternal Vitamin D regimen. Pigs from sows fed the low concentration of vitamin D3 had poorer (P < 0.002) ADG and final nursery BW compared to those from sows fed 25(OH)D3. Throughout finishing (d 35 post-weaning until market), ADG was increased (quadratic, P = 0.005) and ADFI tended to increase (quadratic, P = 0.055) with increasing maternal vitamin D3 supplementation because pigs from sows fed the medium concentration of vitamin D3 had greater ADG and numerically greater ADFI compared to pigs from sows fed the low or high concentration of vitamin D3. Average daily gain of pigs from sows fed the low concentration of vitamin D3 was lower (P < 0.004) compared to those from sows fed 25(OH)D3. Carcass data were also collected from 734 pigs (approximately 65% of pigs weaned from sows administered vitamin D regimens) from 3 out of the 4 weaning groups used for the experiment. At marketing, live BW and HCW were heavier (P < 0.030) for pigs from sows fed 25(OH)D3 compared to pigs from sows fed the high concentration of vitamin D3. Also, percentage carcass yield increased (quadratic, P = 0.003) with increasing maternal vitamin D3 supplementation. Loin depth (linear P = 0.047) and BF (quadratic, P = 0.031) were both decreased with increasing vitamin D3 supplementation. Overall, it appears that vitamin D3 and 25(OH)D3, whether through maternal supplementation or through the diet, are useful sources of vitamin D to increase serum 25(OH)D3 concentrations in growing pigs. Additionally, 25(OH)D3 (in the nursery diet) can increase serum 25(OH)D3 of nursery pigs more than feeding the same international unit equivalency of vitamin D3. Pigs from sows fed the medium concentration of vitamin D3 performed better after weaning compared to pigs from sows fed the low or high concentrations of vitamin D3; however, this difference may have been confounded with the variance in weaning weight associated with the subsample population used for the growth portion of the study. Also, it is perceived that pigs from sows fed 25(OH)D3 had increased live weight and HCW compared to pigs from sows fed the high concentration of vitamin D3. This research report is available in Kansas Agricultural Experiment Station Research Reports: http://newprairiepress.org/kaesrr/ vol1/iss7/24

Evaluating the Impact of Maternal Vitamin D Supplementation on Sow Performance, Serum Vitamin Metabolites, Neonatal Muscle and Bone Characteristics, and Subsequent Pre-weaning Pig Performance

A total of 56 gestating sows (PIC 1050; 35-d post-insemination) were used in a 30-d trial to determine the serum 25(OH)D3 response to increasing concentrations of vitamins D3. At initiation, sows were randomly allotted to 1 of 7 dietary vitamin D3 treatments (91, 363, 726, 1,451, 2,903, 5,806, or 11,612 IU of vitamin D3/lb of complete diet) with 8 sows per treatment. All sows were fed 5.5 lb daily at 0800. Increasing vitamin D3 increased (quadratic; P < 0.001) serum 25(OH)D3 with the response depicted by the following prediction equation: Serum 25(OH)D3, ng/mL = 35.1746 + (0.002353 × dietary vitamin D3, IU/d) (0.0000000156 × dietary vitamin D3, IU/d2) In Exp. 2, 112 sows and their litters were used to determine the effects of supplemented vitamin D on sow performance, subsequent pre-weaning pig performance, neonatal pig bone and muscle characteristics, and serum vitamin metabolites. Sows were allotted to 1 of 4 dietary regimens: 1) low vitamin D3 (363 IU/lb); 2) medium vitamin D3 (907 IU/lb); 3) high vitamin D3 (4,354 IU/lb); or 4) 23 μg 25(OH)D3/lb (Hy-D, DSM Nutritional Products Inc, Parsippany, NJ), which were fed throughout gestation and lactation. There were 25 to 27 sows per treatment. Overall, increasing maternal vitamin D3 increased (linear, P = 0.001) serum 25 (OH)D3 of sows on d 100 of gestation, at farrowing, and at weaning. Also increasing vitamin D3 in diets fed to sows increased piglet serum 25(OH)D3 at birth (linear, P = 0.001) and weaning (quadratic, P = 0.033). Sows fed 25(OH)D3 had greater (P < 0.001) serum 25(OH)D3 concentrations on d 100 of gestation, at farrowing, and at weaning compared to sows fed the low or medium concentration of vitamin D3; however, they were reduced (P < 0.004) compared to the serum 25(OH)D3 concentrations of sows fed the high concentration of vitamin D3 on the same collection days. Piglets from sows fed 25(OH)D3 had greater serum 25(OH)D3 compared to piglets from sows fed the low and medium concentration of vitamin D3; however, at weaning, serum 25(OH)D3 concentrations were only greater compared to the low concentration of vitamin D3. Also, piglets from sows fed the high concentration of vitamin D had greater (P = 0.011) serum 25(OH)D3 concentration at birth and at weaning, compared to piglets from sows fed 25(OH)D3. Maternal performance, litter characteristics, neonatal bone ash content, and neonatal muscle fiber characteristics were largely unaffected by the maternal vitamin D regimen. Overall, vitamin D3 and 25(OH)D3 both appear to be useful at increasing serum 25(OH) D3 concentrations, but more vitamin D3 (on an IU basis) is needed to achieve similar serum 25(OH)D3 responses compared to feeding 25(OH)D3. Interestingly, sows fed 25(OH)D3 in lactation had less vitamin D transport to the pig than sows fed medium and high concentrations of vitamin D3 suggesting that vitamin D3 is still a more useful metabolite for milk transfer of the vitamin. Due to the lack of impact of maternal vitamin D regimen on sow or pre-weaned pig performance, and neonatal muscle characteristics, more research examining the impact of vitamin D on immune function and novel biological processes is needed to assess the value of vitamin D supplementation strategies in pigs.

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Objectives Vitamin D insufficiency is associated with a 5-fold increased risk for development of preeclampsia. We hypothesize that vitamin D plays an important role in the health of endothelial progenitor cells that participate in maternal and placental vasculogenesis and vascular endothelial repair. We asked if vitamin D antagonizes the negative effects of preeclampsia, or a preeclampsia-like environment, on fetal endothelial progenitor cell function. Methods Umbilical cord blood was obtained from preeclamptic and uncomplicated pregnancies. The mononuclear cells were isolated and seeded onto culture plates for outgrowth of endothelial colony forming progenitor cells (ECFCs). Placental explants from uncomplicated term pregnancies were incubated for 48 h under 2%, 8% or 21% O2. Explant conditioned media (CM) was collected and pooled according to oxygen level. Migration, proliferation, and tubule formation of ECFCs was determined in the presence/absence of CM or maternal serum, and 1,25(OH)2 vitamin D3. We inhibited the VEGF signaling pathway with Su5416 and blocked the VDR with VDR antagonist pyridoxal-5-phosphate or antiVDR siRNA. Results The number of cord blood-derived ECFC colonies was decreased in PE compared with controls (P = 0.04). Preeclampsia ECFCs showed reduced proliferation (P Conclusions Physiological concentrations of vitamin D3 promote the migration and capillary-like tubule formation of ECFCs in culture, minimizing negative effects of preeclampsia or preeclampsia-related factors. Such positive effects of vitamin D on progenitor cell function might improve placental and endothelial function and pregnancy outcome. Disclosures L. Brodowski: None. J. Burlakov: None. C.A. Hubel: None. F. von Versen-Hoynck: None.

Vitamin D and Diabetes: A New Horizon

Diabetes mellitus is a metabolic disease which is caused by absolute or relative insulin deficiency, and the prevalence rate of Type2 diabetes mellitus (T2DM) is growing among Indians as well as through worldwide. Various risk factors play a role in the aetiopathogenesis and in the glycemic control among the type 2 diabetic patients. Therefore, identification of environmental and easily modified risk factors is urgently needed to prevent development of T2DM. One of various such risk factors, vitamin D3 level & therefore serum calcium levels are reported to alter the glycemic control. The major and most well-known function of vitamin D is to maintain calcium and phosphorus homeostasis and promote bone mineralization. However, recent evidence suggests that vitamin D and calcium homeostasis may also be important for a variety of non-skeletal diseases including T2DM. Based on basic and animal studies, vitamin D and calcium have also been suspected as modifiers of diabetes risk. The systemic review was carried out to evaluate the evidences as well as limitation in respect of vitamin D3 and serum calcium level regarding the glycemic control in T2DM. This paper seeks to examine the consistently reported relationship between glycemic control in T2DM and altered vitamin D3 & serum calcium concentrations, with reference to the possible underlying mechanisms. So the status of above two parameters is considered as an important factor in T2DM patients. Its role in present scenario should be understood both as an etiological concept & also as a therapeutic option.

Abstract PL01-03: Vitamin D deficiency and prostate cancer in men with African ancestry

Abstract African-American men are disproportionally affected by prostate cancer in that African-American men are not only at increased risk of prostate cancer compared to American men of European descent, but also are at the highest risk of aggressive prostate cancer and death from prostate cancer. As well vitamin D3 deficiency is rampant in the African-American population. There is a biological component to this deficiency because sun-induced vitamin D3 synthesis in the skin is significantly reduced in melanin-rich pigmented skin. Consequently, about two thirds of African-American men are vitamin D3 deficient compared to about 20% of men of European descent. It is important to maintain a healthy vitamin D3 status because vitamin D3 deficiency increases the risk of prostate cancer mortality. Our group has examined vitamin D3 concentrations, metabolism and mediators in prostate tissue and cells of a racially diverse group of patients to discern differences in African-American men. Citation Format: Larisa Nonn. Vitamin D deficiency and prostate cancer in men with African ancestry. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr PL01-03. doi:10.1158/1538-7755.DISP13-PL01-03

Chronic stress causes neuroendocrine-immune disturbances without affecting renal vitamin D metabolism in rats.

Vitamin D (VD) insufficiency has been repeatedly observed in the medical conditions associated with inflammation, such as cardiovascular disease, diabetes and depression. However, contrasting to the observational evidence, randomized trials of VD supplementation failed to demonstrate such link. Given the recent evidence that the inflammatory process can in turn alter VD metabolism, it has been hypothesized that the insufficient VD status could be the result rather than the cause of chronic inflammation involved in the onset of depression and other disease conditions. Chronic mild stress (CMS) is a valid animal model of depression that accompanied with neuroendocrine-immune disturbances. In the present research, we assessed serum VD concentrations and renal expression of the cytochromes P450 enzymes involved in VD activation (CYP27B1) and catabolism (CYP24A1) of rats following 8-week exposure to CMS. While CMS induced the rats to a depression-like state and increased serum levels of the proinflammatory cytokines and corticosterone, and the antidepressant, sertraline, mitigated depression-like behaviors and neuroendocrine-immune disturbances, neither the stress regimen nor sertraline significantly affected endocrine metabolism of VD. Our data suggest that the stress-induced neuroendocrine-immune disturbances may account for the development of depression, but are not responsible for the insufficient VD status that frequently observed in depressed patients.

Relationship between serum 25-hydroxy vitamin D3 concentration and obesity childhood

Objective To examine the relationship between the concentration of 25-hydroxy vitamin D3[25-(OH)D3] in the serum and the body mass, the severity of obesity, body mass index(BMI), blood lipid, and their predicting role in obesity children. Methods The study recruited 244 subjects, who see the doctor in Wuxi Maternal and Child Health Hospital, Childhood Nutrition Outpatient from Jul.2011 to Feb.2013.The intake dose of vitamin D each day was investigated, and weight, height, BMI, concentration of 25-(OH)D3 in serum, and microelement were also mea-sured.In addition, lipid metabolism of 38 cases with obesity over 3 years old was determined. Results 1.The serum 25-(OH)D3 concentration of obese children was (68.31±23.06) nmol/L.The concentration of 25-(OH)D3 was lowest in the group of obese children over 36 months of age[(55.03±15.18) nmol/L].2.The concentration of 25-(OH)D3 in the group of obese and overweight children was far lower than that of the children in the normal group(F=4.739, P<0.05).3.The concentrations of 25-(OH)D3 in the severely obese children was significantly lower than that of the mild and moderate obesity children(F=9.711, P<0.05).4.There were significantly inverse associations of serum 25-(OH)D3 with weight, weight and height percentage, BMI(r=-0.365, -0.237, -0.175, all P<0.001).5.There were significantly inverse associations between the concentration of 25-(OH)D3 in serum with weight, triglyceride in obese children more than 3 years old(r=0.476, -0.324, all P<0.05). Conclusions The decreasing level of 25-hydroxy vitamin D3 in the serum was associated with obesity.The cause of it might be the increase of the obese adipose tissue, vitamin D getting trapped in fat cells, and all these factors can lead to a less serum vitamin D levels.The vitamin D consumption of obese children is higher than that of normal children, and should supply more vitamin D to reach normal 25-(OH) D3 level. Key words: Serum 25-hydroxy vitamin D3 concentration; Child; Obesity

Role of vitamin D3 in modulation of ΔNp63α expression during UVB induced tumor formation in SKH-1 mice.

ΔNp63α, a proto-oncogene, is up-regulated in non-melanoma skin cancers and directly regulates the expression of both Vitamin D receptor (VDR) and phosphatase and tensin homologue deleted on chromosome ten (PTEN). Since ΔNp63α has been shown to inhibit cell invasion via regulation of VDR, we wanted to determine whether dietary Vitamin D3 protected against UVB induced tumor formation in SKH-1 mice, a model for squamous cell carcinoma development. We examined whether there was a correlation between dietary Vitamin D3 and ΔNp63α, VDR or PTEN expression in vivo in SKH-1 mice chronically exposed to UVB radiation and fed chow containing increasing concentrations of dietary Vitamin D3. Although we observed differential effects of the Vitamin D3 diet on ΔNp63α and VDR expression in chronically irradiated normal mouse skin as well as UVB induced tumors, Vitamin D3 had little effect on PTEN expression in vivo. While low-grade papillomas in mice exposed to UV and fed normal chow displayed increased levels of ΔNp63α, expression of both ΔNp63α and VDR was reduced in invasive tumors. Interestingly, in mice fed high Vitamin D3 chow, elevated levels of ΔNp63α were observed in both local and invasive tumors but not in normal skin suggesting that oral supplementation with Vitamin D3 may increase the proliferative potential of skin tumors by increasing ΔNp63α levels.

Protein restriction: a revisited old strategy with new opportunities?

effect of erythropoietin-stimulating agents in stage 5 chronic kidney disease patients: a randomized crossover study. Nephrol Dial Transplant 2014; 29: 1719–1727 31. Adelibieke Y, Shimizu H, Saito S et al. Indoxyl Sulfate counteracts endothelial effects of erythropoietin through suppression of Akt phosphorylation. Circ J 2013; 77: 1326–1336 32. Cooper A, Mikhail A, Lethbridge MW et al. Pentoxifylline improves hemoglobin levels in patients with erythropoietin-resistant anemia in renal failure. J Am Soc Nephrol 2004; 15: 1877–1882 33. Ferrari P, Mallon D, Trinder D et al. Pentoxifylline improves haemoglobin and interleukin-6 levels in chronic kidney disease. Nephrology (Carlton) 2010; 15: 344–349 34. Kendrick J, Targher G, Smits G et al. 25-Hydroxyvitamin D deficiency and inflammation and their association with haemoglobin levels in chronic kidney disease. Am J Nephrol 2009; 30: 64–72 35. Patel NM, Gutierrez OM, Andress DL et al. Vitamin D deficiency and anemia in early chronic kidney disease. Kidney Int 2010; 77: 715–720 36. Kiss Z, Ambrus C, Almasi C et al. Serum 25(OH)-cholecalciferol concentration is associated with hemoglobin level and erythropoietin resistance in patients on maintenance hemodialysis. Nephron Clin Pract 2011; 117: c373–c378 37. Matias PJ, Jorge C, Ferreira C et al. Cholecalciferol supplementation in hemodialysis patients: effects on mineral metabolism, inflammation, and cardiac dimension parameters. Clin J Am Soc Nephrol 2010; 5: 905–911 38. Chen Y, Abbate M, Tang L et al. L-Carnitine supplementation for adults with end-stage kidney disease requiring maintenance hemodialysis: a systematic review and meta-analysis. Am J Clin Nutr 2014; 99: 408–422 39. Deved V, Poyah P, James MT et al. Ascorbic acid for anemia management in hemodialysis patients: a systematic review and meta-analysis. Am J Kidney Dis 2009; 54: 1089–1097 40. Cossey LN, Rahim F, Larsen CP. Oxalate nephropathy and intravenous vitamin C. Am J Kidney Dis 2013; 61: 1032–1035

Low serum 25(0H) vitamin D3 concentration is associated with increased accumulation of advanced glycation endproducts (AGEs) in the skin of patients with type 1 diabetes

Low serum 25(0H) vitamin D3 concentration is associated with increased accumulation of advanced glycation endproducts (AGEs) in the skin of patients with type 1 diabetes

Correlation between 25-OH vitamin D3 and TSH concentration in population over 65: preliminary report

Correlation between 25-OH vitamin D3 and TSH concentration in population over 65: preliminary report

Correlation among arm circumference index, 25-OH vitamin d3 concentration and lipid profile in patients over 65 years: preliminary study

Correlation among arm circumference index, 25-OH vitamin d3 concentration and lipid profile in patients over 65 years: preliminary study

A black box illuminated: specific detection and quantification of vitamin D3 in small volume human milk samples using nanoLC‐ESI/MS/MS (623.8)

Breastfeeding infants are at particular risk for vitamin D deficiency with human milk as their primary source of vitamin D. Serum 25‐OH‐D is typically used to characterize maternal and infant vitamin D deficiency. However, direct measurement of vitamin D in human milk is critical to illuminate the black box representing maternal vitamin D contribution to the infant during feeding. Here we have developed a sensitive and specific method to quantitate low femtomolar levels of vitamin D3, a common form in human milk, from an individual donor using 1 mL of human milk. The method combines initial saponification of human milk with liquid‐liquid extraction, followed by UPLC clean‐up, derivatization, and nanoLC‐MS/MS analysis. Deuterated D3 was used as internal standard. Full product ion spectra with accurate masses (±20 ppm) were obtained where MRM transitions of m/z 560.385 ‐&gt; 298.119 and 563.404 ‐&gt; 301.137 were used for quantification. Six milk samples from 3 mothers at two lactational stages, 2 weeks and 2 months, were analysed to assess method performance and give initial insight into vitamin D3 over lactation. Vitamin D3 concentrations increased from 0.09 ‐ 2.1 pmole/mL in 2‐week milk to 1.3 ‐ 2.7 pmole/mL in 2‐month milk. Milk from two of the mothers showed an approximate 10‐fold increase over the 6 weeks between sampling, while the third mother had higher initial values of D3 with a modest 30% increase between 2 weeks and 2 months.

Association of Vitamin D3 levels with glycemic control in Type 2 diabetes subjects from Gujarati population-India

Materials and Methods This prospective study comprises of 508 individuals (including 210 T2D & 298 controls). All subjects were categorized into 3 groups according to Vitamin D3 levels. Group-I: included 171 individuals (61 T2D out of 171) with normal Vitamin D3 concentration (≥25 nmol/l), group-II: included 264 subjects (118 T2D out of 264)with mild to moderately Vitamin D3 deficiency (15-24.9 nmol/l) and group-III included 73 subjects (31 T2D out of 73) having severe Vitamin D3 deficiency (≤14.9 nmol/l). Vitamin D3 and glycosylated hemoglobin [HbA1C] level was analyzed for all the subjects.

Comparison of the Pharmacokinetics, Safety, and Tolerability of Vitamin D3 in DP-R206 (150-mg Ibandronate/24,000-IU Vitamin D3 Tablet) and as Monotherapy (24,000 IU) in Healthy Male Korean Adults

BackgroundCombined treatment with a bisphosphonate and vitamin D has been proposed for postmenopausal osteoporosis. A new, fixed-dose combination tablet of ibandronate plus vitamin D3 has been developed for monthly administration to treat postmenopausal osteoporosis. ObjectivesThe main objective of the present study was to compare the pharmacokinetics of vitamin D3 administered in 2 forms: a newly developed ibandronate 150-mg/vitamin D3 24,000-IU tablet (DP-R206, test drug) and a stand-alone vitamin D3 24,000-IU tablet (reference drug). A secondary objective was to evaluate the safety and tolerability of DP-R206 in healthy adult male Korean volunteers. MethodsThis study was a single-dose, open-label, randomized-sequence, 2-treatment, 2-way crossover trial. Blood samples were collected from 24 hours’ predose to 120 hours’ postdose. The plasma concentrations of vitamin D3 were analyzed by using a validated HPLC-MS/MS method. Pharmacokinetic parameters were calculated, and the 90% CIs of the ratios of the geometric means of the parameters were determined from the logarithmically transformed data by using ANOVA. ResultsThirty-sex healthy adult male Korean volunteers with a mean (SD) age of 25.8 (2.7) years, a mean height of 174.0 (5.9) cm, and a mean weight of 69.1 (6.2) kg were enrolled; 29 participants completed the study. The 90% CIs of the ratios of the geometric means (test drug/reference drug) of the baseline-corrected Cmax, AUC0–last, and AUC0–∞ values were 0.93 to 1.24, 0.89 to 1.19, and 0.87 to 1.18, respectively. The 90% CIs of the ratios of the geometric means (test drug/reference drug) of the baseline-uncorrected Cmax, AUC0–last, and AUC0–∞ values were 0.93 to 1.24, 0.88 to 1.19, and 0.87 to 1.18, respectively. Eighty-four adverse events (AEs) were reported in 24 of 32 subjects receiving DP-R206, and 14 AEs were reported in 8 of 29 subjects receiving the vitamin D3 24,000-IU tablet. All of the subjects who experienced AEs recovered without sequelae, and no serious AEs were observed. ConclusionsThe vitamin D3 pharmacokinetics were similar for DP-R206 and the 24,000-IU vitamin D3 tablet. DP-R206 was well tolerated. ClinicalTrials.gov identifier: NCT01577849.

An evaluation of the effects of added vitamin D3 in maternal diets on sow and pig performance1,2

A total of 84 sows (PIC 1050) and their litters were used to determine the effects of supplementing maternal diet with vitamin D3 on sow and pig performance, serum 25-hydroxyvitamin D3 (25(OH)D3), milk vitamin D3, neonatal bone mineralization, and neonatal tissue vitamin D3. After breeding, sows were randomly assigned to 1 of 3 dietary vitamin D3 treatments (1,500, 3,000, or 6,000 IU/kg of complete diets). Sows were bled on d 0 and 100 of gestation and at farrowing and weaning (d 21). Pig BW was recorded at birth and weaning, and serum was collected from 2 pigs/litter at birth, on d 10 and at weaning. A total of 54 pigs (18/treatment) were euthanized at birth and necropsied to sample bones and tissues. Sow and suckling pig performance and neonatal bone ash and bone density did not differ among maternal vitamin D3 treatments; however, sow 25(OH)D3 and milk vitamin D3 increased (linear, P < 0.01) with increasing maternal vitamin D3 supplementation. Piglet serum 25(OH)D3 increased (quadratic, P < 0.03) with increased maternal vitamin D3. Neonatal kidney vitamin D3 tended (quadratic, P = 0.08) to decrease with increasing maternal vitamin D3, but liver vitamin D3 tended (linear, P = 0.09) to increase with increasing maternal vitamin D3. At weaning, a subsample of 180 pigs (PIC 327 × 1050) were used in a 3 × 2 split plot design for 35 d to determine the effects of maternal vitamin D3 and 2 levels of dietary vitamin D3 (1,800 or 18,000 IU/kg) from d 0 to 10 postweaning on nursery growth and serum 25(OH)D3. Overall (d 0 to 35), nursery ADG and G:F were not affected by either concentration of vitamin D3, but ADFI tended (quadratic, P < 0.06) to decrease with increasing maternal vitamin D3 as pigs from sows fed 3,000 IU had lower ADFI compared with pigs from sows fed 1,500 or 6,000 IU/kg. Nursery pig serum 25(OH)D3 increased with increasing maternal vitamin D3 (weaning) on d 0 (linear, P < 0.01), and maternal × diet interactions (P < 0.01) were observed on d 10 and 21 because pigs from sows fed 1,500 IU had greater increases in serum 25(OH)D3 when fed 18,000 IU compared with pigs from sows fed 3,000 IU. In conclusion, sow and pig serum 25(OH)D3, milk vitamin D3, and neonatal tissue vitamin D3 can be increased by increasing maternal vitamin D3, and nursery pig 25(OH)D3 can be increased by increasing dietary vitamin D3; however, sow and pig performance and neonatal bone mineralization was not influenced by increasing vitamin D3 dietary levels.

Maternal Vitamin D Supplementation to Improve the Vitamin D Status of Breast-fed Infants: A Randomized Controlled Trial

To determine whether a single monthly supplement is as effective as a daily maternal supplement in increasing breast milk vitamin D to achieve vitamin D sufficiency in their infants. Forty mothers with exclusively breast-fed infants were randomized to receive oral cholecalciferol (vitamin D3) 5000 IU/d for 28 days or 150,000 IU once. Maternal serum, breast milk, and urine were collected on days 0, 1, 3, 7, 14, and 28; infant serum was obtained on days 0 and 28. Enrollment occurred between January 7, 2011, and July 29, 2011. In mothers given daily cholecalciferol, concentrations of serum and breast milk cholecalciferol attained steady levels of 18 and 8 ng/mL, respectively, from day 3 through 28. In mothers given the single dose, serum and breast milk cholecalciferol peaked at 160 and 40 ng/mL, respectively, at day 1 before rapidly declining. Maternal milk and serum cholecalciferol concentrations were related (r=0.87). Infant mean serum 25-hydroxyvitamin D concentration increased from 17±13 to 39±6 ng/mL in the single-dose group and from 16±12 to 39±12 ng/mL in the daily-dose group (P=.88). All infants achieved serum 25-hydroxyvitamin D concentrations of more than 20 ng/mL. Either single-dose or daily-dose cholecalciferol supplementation of mothers provided breast milk concentrations that result in vitamin D sufficiency in breast-fed infants. clinicaltrials.gov NCT01240265.

Effects of supplemental vitamin D3 on serum 25-hydroxycholecalciferol and growth of preweaning and nursery pigs1,2

Four experiments were conducted to investigate the effects of varying concentrations of supplemental vitamin D3 on pig growth, feed preference, serum 25-hydroxycholecalciferol [25(OH)D3] , and bone mineralization of nursing and weanling pigs. In Exp. 1, 270 pigs (1.71 ± 0.01 kg BW) were administered 1 of 3 oral vitamin D3 dosages (none, 40,000, or 80,000 IU vitamin D3) on d 1 or 2 of age. Increasing oral vitamin D3 increased serum 25(OH)D3 on d 10 and 20 (quadratic, P < 0.01) and d 30 (linear, P < 0.01). No differences were observed in ADG before weaning or for nursery ADG, ADFI, or G:F. Vitamin D3 concentration had no effect on bone ash concentration or bone histological traits evaluated on d 19 or 35. In Exp. 2, 398 barrows (initially 7 d of age) were used in a 2 × 2 split plot design to determine the influence of vitamin D3 before (none or 40,000 IU vitamin D3 in an oral dose) or after weaning (1,378 or 13,780 IU vitamin D3/kg in nursery diets from d 21 to 31 of age) in a 45-d trial. Before weaning (7 to 21 d of age), oral vitamin D3 dose did not influence growth but increased (P < 0.01) serum 25(OH)D3 at weaning (d 21) and tended (P = 0.08) to increase 25(OH)D3 on d 31. Increasing dietary vitamin D3 concentration from d 21 to 31 increased (P < 0.01) serum 25(OH)D3 on d 31. Neither the oral vitamin D3 dose nor nursery vitamin D3 supplements influenced nursery ADG, ADFI, or G:F. In Exp. 3, 864 pigs (initially 21 d of age) were allotted to 1 of 2 water solubilized vitamin D3 treatments (none or 16,516 IU/L vitamin D3 provided in the drinking water from d 0 to 10) in a 30-d study. Providing vitamin D3 increased serum 25(OH)D3 concentrations on d 10, 20, and 30; however, vitamin D3 supplementation did not affect overall (d 0 to 30) ADG, ADFI, or G:F. In Exp. 4, 72 pigs were used in a feed preference study consisting of 2 feed preference comparisons. Pigs did not differentiate diets containing either 1,378 or 13,780 IU vitamin D3/kg but consumed less (P < 0.01) of a diet containing 44,100 IU vitamin D3/kg compared with the diet containing 1,378 IU vitamin D3/kg. Overall, these studies demonstrate that supplementing vitamin D3 above basal concentrations used in these studies is effective at increasing circulating 25(OH)D3, but the supplement did not influence growth or bone mineralization. Also, concentrations of vitamin D3 of 44,100 IU/kg of the diet may negatively affect feed preference of nursery pigs.

αSMA+ Macrophages Skewed From Hematopoietic Stem Cells By Vitamin D3 Initiate Myelofibrosis and Subsequent Osteosclerosis

Myelofibrosis (MF) is characterized as the proliferation of fibroblasts resulting in the replacement of marrow space by collagenous connective tissue fibers and is also known to be frequently complicated with osteosclerosis. However, the pathogenesis of this phenomenon is largely unknown. Allogeneic stem cell transplantation is the therapeutic choice in clinic with complete resolution of the disorder despite the recognition as microenvironment problem by the hematologists. Here, we establish a novel inducible murine MF model and propose a new paradigm in the pathophysiology of MF. Vitamin D receptor-deficient (VDR-/-) mice display rickets type II, which can be restored by high calcium diet, resulting in their usefulness as transplant recipients. We transplanted wild-type (WT) bone marrow (BM) cells into lethally irradiated VDR-/- mice and found that the vast majority died due to BM failure (n=25, median survival 66 days), though for the time being hematopoiesis was reconstituted during the first month after transplantation. The homing of long-term repopulating hematopoietic stem cells (HSCs) into marrow space was normal at 3 hrs, but the HSCs selectively disappeared at 3 weeks after transplantation as assessed by competitive reconstitution. Since VDR-/- mice showed normal hematopoiesis in steady-state, we transplanted VDR-/- BM into lethally irradiated VDR-/- recipients, which resulted in survival with no BM failure. Thus, engraftment failure of the WT HSCs in VDR-/- recipients did not originate from radiation-induced irreversible niche destruction, but it was likely intrinsic to donor HSC behavior. Histological analysis of femurs at 1-2 months after transplantation of WT BM into VDR-/- recipients revealed that the BM cavity was occupied by spindle-shaped cells and silver fibers. There was also prominently increased trabecular bones only in the metaphysis; whereas, normal hematopoietic appearance was observed in the diaphysis. This was initiated by hematopoietic cells since CD45+lin-c-kit+ cells isolated from WT CAG-EGFP transgenic mice as donor source induced the same MF and osteosclerosis in VDR-/- recipients. Metaphysial BM was replaced by monotonous fibroblastic cells in this particular setting; however, these cells were composed of two distinct populations with mutual distribution, 1) GFP+F4/80+ donor-derived macrophages and 2) GFP-osterix+ (or runx2+) host-derived preosteoblasts. These two distinct cells were tangled around each other equally in the fibrotic tissue area, and preosteoblasts were dominant in the osteoscrelotic area. Both populations were positive for αSMA. Since VDR-/- donor cells did not induce MF and it was reported that the level of 1,25(OH)2D3 (vitamin D3) is extremely high in VDR-/- mice, we hypothesized that WT HSCs exposed to high vitamin D3 might differentiate into αSMA+ macrophages and proliferate in vivo. Furthermore, since it is widely known that macrophages are strong supporter of osteoblasts, these cells might drive osteoblast-lineage cells. In the culture of hematopoietic stem/progenitor cell line FDCP-mix, vitamin D3 induced strong F4/80 upregulation together with partial αSMA induction, and MCP1 secretion in the culture supernatant was highly induced depending on vitamin D3 concentration. Strikingly, a diet low in vitamin D3 prevented the development of MF with osteosclerosis in VDR-/- recipients transplanted with WT BM. Thus, in our novel MF model, the true pathogenesis is likely that αSMA+ macrophages as MF-initiating cells perhaps directly differentiated from HSCs through vitamin D3 stimulation, drive the activity of preosteoblasts as a major producer of collagen fibers, and initiate osteosclerosis. We next examined whether this new paradigm could be applied for JAK2 V617F transgenic mice, which display MF with osteosclerosis, and human MF patients (n=3 including two cases with JAK2 V617F mutation). As we expected, marrow fibroblastic cells of both mouse genetic model and human patients were similarly composed of αSMA+CD169+ (or CD163+) macrophages and αSMA+ osteoblastic lineage cells with osterix or runx2 expression. Our study may explain why BMT is useful in clinic because MF is likely initiated by hematopoietic cells. We propose the modulation of vitamin D3 signaling or macrophage-targeted strategies as novel therapeutic choices for MF. Disclosures:No relevant conflicts of interest to declare.

Effects of long-term supplementation of laying hens with high concentrations of cholecalciferol on performance and egg quality

There is current interest in increasing human vitamin D dietary intake without having to modify human eating habits. One method to increase human dietary vitamin D intake is to generate eggs with increased concentrations of vitamin D through high-concentration vitamin D feeding in the diets of laying hens. Although eggs can be produced with high concentrations of vitamin D, the consequences of these diets on hen performance and egg quality have not been validated. The objective of this research is to quantify the effects of high concentrations of cholecalciferol (D3) on laying hen performance and egg quality. Hy-Line W36 laying hens were placed on 1 of 5 experimental diets for 40 wk: 1) control (contained 2,200 IU of D3/kg of diet), 2) control + 7,500 IU of D3/kg of diet (9,700 IU of D3/kg of diet total), 3) control + 15,000 IU of D3/kg of diet (17,200 IU of D3/kg of diet total), 4) control + 22,500 IU of D3/kg of diet (24,700 IU of D3/kg of diet total), and 5) control + 100,000 IU of D3/kg of diet (102,200 IU of D3/kg of diet total). Egg production and hen mortality were monitored daily. Feed intake was determined weekly. Eggs were collected at predetermined points throughout the 40-wk period (19 to 58 wk of bird age) for assessment of egg weight, egg component weights, Haugh unit, yolk color score, specific gravity, egg mass, and feed efficiency. There were no consistent differences among the dietary treatments over the experimental period. Hens supplemented with up to 102,200 IU of D3/kg of diet resulted in no significant reductions in egg production, feed intake, feed efficiency, egg component weights, yolk color, Haugh units, and specific gravity in comparison with the control-fed hens (P > 0.05). These data suggest the addition of cholecalciferol to the diet of the laying hen at concentrations up to 102,200 IU of D3/kg of diet had no consistent negative effects on laying hen performance or egg quality.