Effects of 25-hydroxycholecalciferol supplementation in maternal diets on reproductive performance and the expression of genes that regulate lactation in sows.

One hundred Yorkshire × Landrace sows were randomly assigned to one of two dietary treatments (diet ND: 6,000 IU vitamin D3 /d feed; diet 25-D: 200 µg/day 25OHD3 feed). The experiment began on d 90 of gestation and continued until weaning on day 21 of lactation. In sows that received 25OHD3 , the growth rate of the piglets before weaning was significantly accelerated (0.266 kg/day, p < .05). Sow serum was collected after weaning, and those in the 25OHD3 group were found to have significantly higher serum calcium (CA) and phosphorus (PI) levels (p < .05). Interestingly, the oestrus cycle of sows fed 25OHD3 was significantly shortened (p < .05), the oestrus time was concentrated on the fifth day after weaning, and the piglets were born with a higher degree of uniformity (p < .05). Colostrum was collected on the day of delivery, and the colostrum of sows fed 25OHD3 contained higher milk fat content than the control group (p < .05). 25OHD3 supplementation increased the mRNA and protein expression of INSIG1 and SREBP1, which regulate milk fat synthesis, in the mammary gland of lactating sows (p < .05). In conclusion, 25OHD3 supplementation in maternal diets improved reproductive performance, milk fat content and the mRNA and protein levels of genes regulating milk fat synthesis in lactating sows.

25-hydroxyvitamin D levels in the early healing of osteoporotic hip fracture and their relationship with clinical outcome / Niveles de 25-hidroxivitamina D en la fase precoz de la fractura osteoporótica de cadera y su relación con los resultados clínicos

INTRODUCTION: vitamin D is involved in recovery after an osteoporotic hip fracture (OHF). Previous studies have reported decreased serum vitamin D levels during fracture healing. OBJECTIVES: our aim was to evaluate: a) serum 25-hydroxyvitamin D3 (25OHD3) levels in patients with OHF at hospital admission and 8 days post-admission, and b) the relationship between 25OHD levels and clinical outcomes. METHODS: a prospective study including 66 patients aged over 65 years hospitalized for OHF. We gathered data on baseline demographic characteristics, medical history, Mini Mental State (MMS) assessment, Activities of Daily Living (ADL) results, nutritional assessment, and type of fracture and surgery. Laboratory results were collected on bone biomarkers, albumin, 25OHD3, and IL6. Clinical outcomes included length of stay, complications, and mortality. In the statistical analysis, a t-test was used for continuous variables and a chi-square test for qualitative variables. Linear regression models were used for the multivariate analysis, adjusted for covariates. RESULTS: our study population had low serum vitamin D levels at admission, with a mean [(standard error of the mean (SEM)] of 12.04 (1.03) ng/mL. Both 25OHD3 and interleukin 6 (IL-6) levels significantly declined (p < 0.001) during the early post-fracture phase. A greater decline in 25OHD3 levels was significantly associated with longer hospital stay (p = 0.042, multivariate analysis). Serum 25OHD3 levels were also associated with cognitive status as assessed using the MMS exam. CONCLUSIONS: 25OHD3 levels were reduced in OHF patients at admission, and significantly decreased during the first 8 days post-admission. 25OHD3 levels were associated with MMS-assessed cognitive status. A greater decline in serum 25OHD3 was associated with a longer hospital stay

INTRODUCCIÓN: la vitamina D se ha relacionado con la recuperación tras la fractura osteoporótica de cadera (FOC). Estudios previos muestran un descenso de los niveles de vitamina D en la fase precoz tras la fractura. OBJETIVOS: evaluar: a) los niveles séricos de 25-hidroxivitamina D3 (25OHD3) al ingreso y a los 8 días del ingreso en hospitalizados por FOC; b) la relación de los niveles de 25OHD3 con los resultados clínicos, así como con el nivel cognitivo y funcional. MÉTODOS: estudio prospectivo de 66 pacientes (> 65 años) ingresados por FOC. Se estudiaron las características demográficas, los antecedentes personales, la valoración nutricional, el test Mini Mental State (MMS), el cuestionario Activities of Daily Living (ADL), el tipo de fractura y de cirugía, y parámetros bioquímicos del metabolismo óseo, la 25OHD3, la albúmina y la interleuquina 6. Como resultados clínicos se analizaron: estancia hospitalaria, complicaciones y mortalidad durante el ingreso. El análisis estadístico consistió en: a) prueba de la t para las variables continuas y χ2 para las cualitativas; b) análisis multivariable utilizando modelos de regresión lineal ajustados según el análisis de la covarianza. RESULTADOS: la población estudiada muestra niveles bajos de 25OHD3 al ingreso: media [± error estándar de la media (EEM)] = 12,04 (1,03) ng/mL. Durante el ingreso, 25OHD3 e interleuquina 6 decrecen significativamente (p < 0,001). El descenso de 25OHD3 se asocia con la estancia hospitalaria (p = 0,042 en análisis multivariable). Los valores disminuidos de 25OHD3 se asocian a un bajo nivel cognitivo (p = 0,042). CONCLUSIONES: los pacientes ingresados por fractura osteoporótica de cadera tienen niveles bajos de 25OHD3 que decrecen significativamente tras 8 días de ingreso. El descenso de 25OHD3 se asocia significativamente a la estancia hospitalaria. Los niveles disminuidos de 25OHD3 se asocian a un peor estado cognitivo evaluado mediante el MMS

Association of serum vitamin D levels with chronic disease and mortality / Asociación de los niveles séricos de vitamina D con la enfermedad crónica y la mortalidad

INTRODUCTION: whether hypovitaminosis D is an overarching cause of increased mortality or a prognostic marker of poor health has not been well elucidated. OBJECTIVES: we sought to determine the association of serum 25-hydroxyvitamin D [25-(OH)-D3] levels with the clinical biochemical parameters and mortality risk in chronic diseases. METHODS: we reviewed the clinical charts and collected the clinical biochemical parameters of patients diagnosed with chronic conditions who had at least one 25-(OH)-D3 determination, with or without calcium and vitamin D supplementation, and who were selected using a cluster random sampling design (n = 1,705). The analysis was focused on metabolic disorders (type-2 diabetes mellitus [T2DM] and obesity), autoimmune disorders, and mortality. Multivariate logistic regression analyses were performed. RESULTS: low 25-(OH)-D3 levels were reported in 1,433 (84.0 %) patients, of which 774 (45.4 %) had insufficiency (20-29 ng/mL) and 659 (38.6 %) patients had deficiency (< 20 ng/mL). Lower 25-(OH)-D3 levels in T2DM patients were associated with higher glycosylated hemoglobin levels (p < 0.001). Patients with 25-(OH)-D3 levels < 12.5 ng/mL had a higher mortality risk than those with levels ≥ 12.5 ng/mL (HR: 3.339; 95 % CI: 1.342-8.308). We observed lower 25-(OH)-D3 levels in patients with grade-III obesity (p = 0.01). We found a higher risk of 25-(OH)-D3 deficiency in rheumatoid arthritis, type-1 diabetes, and systemic lupus erythematosus (p = 0.032, p = 0.002, p = 0.049, respectively). CONCLUSIONS: we found a significant relationship between 25-(OH)-D3 levels and glycemic control, body mass index, autoimmune disease, and mortality risk. Nevertheless, whether hypovitaminosis D plays a causal role or is a consequence of chronic disease remains controversial

INTRODUCCIÓN: si la hipovitaminosis D constituye una causa general de mayor mortalidad o un marcador de mal pronóstico para la salud no se ha dilucidado por completo. OBJETIVOS: determinar la asociación de los niveles séricos de 25-hidroxivitamina D [25-(OH)-D3] con los parámetros clínico-bioquímicos y el riesgo de mortalidad en la enfermedad crónica. MÉTODOS: se revisaron los expedientes clínicos y recopilamos los parámetros clínico-bioquímicos de pacientes diagnosticados de enfermedades crónicas que tenían al menos una determinación de 25-(OH)-D3, con o sin suplemento de calcio y vitamina D, y que se seleccionaron mediante muestreo aleatorio por grupos (n = 1705). El análisis se centró en los trastornos metabólicos (diabetes mellitus de tipo 2 [DM2] y obesidad), los trastornos autoinmunes y la mortalidad. Se realizaron análisis multivariados de regresión logística. RESULTADOS: se encontraron niveles bajos de 25-(OH)-D3 en 1433 (84,0 %) pacientes, de los cuales 774 (45,4 %) tenían insuficiencia (20-29 ng/mL) y 659 (38,6 %) tenían deficiencia (< 20 ng/mL) de esta vitamina. Los niveles más bajos de 25-(OH)-D3 en los pacientes con DM2 se asociaron a niveles más altos de hemoglobina glucosilada (p < 0,001). Los pacientes con niveles de 25-(OH)-D3 < 12,5 ng/mL tenían mayor riesgo de mortalidad que aquellos con niveles ≥ 12,5 ng/mL (HR: 3,339; IC del 95 %: 1,342-8,308). Apreciamos niveles más bajos de 25-(OH)-D3 en los pacientes con obesidad de grado III (p = 0,01). Se encontró un mayor riesgo de deficiencia de 25-(OH)-D3 en la artritis reumatoide, la diabetes de tipo 1 y el lupus eritematoso sistémico (p = 0,032, p = 0,002, p = 0,049, respectivamente). CONCLUSIONES: apreciamos una relación significativa entre los niveles de 25-(OH)-D3 y el control glucémico, el índice de masa corporal, la enfermedad autoinmune y el riesgo de mortalidad. Sin embargo, sigue siendo controvertido si la hipovitaminosis D desempeña un papel causal o constituye una consecuencia de las enfermedades crónicas

Italian Association of Clinical Endocrinologists (AME) and Italian Chapter of the American Association of Clinical Endocrinologists (AACE) Position Statement: Clinical Management of Vitamin D Deficiency in Adults

Vitamin D deficiency is very common and prescriptions of both assay and supplementation are increasing more and more. Health expenditure is exponentially increasing, thus it is timely and appropriate to establish rules. The Italian Association of Clinical Endocrinologists appointed a task force to review literature about vitamin D deficiency in adults. Four topics were identified as worthy for the practicing clinicians. For each topic recommendations based on scientific evidence and clinical practice were issued according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) System. (1) What cut-off defines vitamin D deficiency: even though 20 ng/mL (50 nmol/L) can be considered appropriate in the general population, we recommend to maintain levels above 30 ng/mL (75 nmol/L) in categories at risk. (2) Whom, when, and how to perform screening for vitamin D deficiency: categories at risk (patients with bone, liver, kidney diseases, obesity, malabsorption, during pregnancy and lactation, some elderly) but not healthy people should be screened by the 25-hydroxy-vitamin D assay. (3) Whom and how to treat vitamin D deficiency: beyond healthy lifestyle (mostly sun exposure), we recommend oral vitamin D (vitamin D2 or vitamin D3) supplementation in patients treated with bone active drugs and in those with demonstrated deficiency. Dosages, molecules and modalities of administration can be profitably individually tailored. (4) How to monitor the efficacy of treatment with vitamin D: no routine monitoring is suggested during vitamin D treatment due to its large therapeutic index. In particular conditions, 25-hydroxy-vitamin D can be assayed after at least a 6-month treatment. We are confident that this document will help practicing clinicians in their daily clinical practice.

Comparison of two methods for measuring 25-OH vitamin D in the follow-up of patients after bilio-pancreatic diversion bariatric surgery.

OBJECTIVE: Our objective was to compare the ECLIA from Roche versus the LC-MS/MS method for quantitation of serum 25-hydroxy-vitamin D in patients who have undergone bariatric surgery. DESIGN AND METHODS: Cross-sectional and correlational studies were performed on three different groups for the 25-OH-D levels quantitated by both methods. The control group of apparently healthy subjects was randomly selected in a clinical chemistry laboratory. Test groups were patients who had undergone bilio-pancreatic diversion (BPD) and were supplemented either with vitamin D2 or with vitamin D3. The number of samples per group was established according to the CLSI recommendation protocol (EPO9-A2-IR). RESULTS: The agreement of LC-MS/MS with the Roche method was acceptable in the apparently healthy subjects group and in the post-BPD D3-supplemented group with an average bias of -1.7% and -9.2%, respectively. However, this agreement was unacceptable in the post-BPD D2-supplemented group with an average bias of -45.3%. The LC-MS/MS enabled us to detect four patients who had excess vitamin D or poisoning with vitamin D for which it was necessary to stop the supplementation with vitamin D in the D2 -supplemented group. CONCLUSION: Despite the apparent good agreement between the Roche method and LC-MS/MS in the healthy subjects group and in the post-DBP D3-supplemented patient group, a considerable bias seems to exist, particularly in the presence of D2. The LC-MS/MS method is therefore the most accurate method to follow the vitamin D2 -supplemented bariatric population.

Treatment of vitamin D deficiency: divergence between clinical practice and expert advice.

BACKGROUND: Current recommendations for the treatment of vitamin D deficiency vary from calciferol 800 IU per day to loading doses of vitamin D followed by maintenance therapy of up to 2000 IU per day. OBJECTIVE: To assess the preparations and doses of vitamin D used to load and maintain patients with serum 25-hydroxyvitamin D (25OHD) <25 nmol/l. METHODS: We examined all requests for serum 25OHD over a 12-month period, from September 2009 to 2010 in southwest Scotland. We wrote to all 33 general practices asking whether they usually started replacement therapy with a loading dose and/or recommended over-the-counter maintenance preparations. We accessed the Emergency Care Summary for all patients with serum 25OHD <25 nmol/l to determine whether they had been prescribed maintenance therapy. RESULTS: Serum 25OHD was requested in 1162 patients. Levels were <25 nmol/l in 282 (24%) patients, only 173 (61%) of whom were receiving vitamin D replacement therapy 3-15 months after diagnosis. Only four (1.4%) were prescribed a loading dose. One hundred and fifty-three (54%) were treated with cholecalciferol or ergocalciferol and 19 (7%) with alfacalcidol or calcitriol. The median dose of chole/ergocalciferol was 800 IU per day, usually in combination with 1200 mg calcium per day. CONCLUSIONS: We have shown a divergence between clinical practice and even the most conservative expert advice for vitamin D replacement therapy. Possible explanations are conflicting advice on treatment and difficulty obtaining suitable vitamin D preparations, particularly high dose vitamin D and vitamin D without calcium, in the UK.

Plasma appearance and disappearance of an oral dose of 25-hydroxyvitamin D2 in healthy adults.

25-Hydroxyvitamin D (25(OH)D) half-life is a potential biomarker for investigating vitamin D metabolism and requirements. We performed a pilot study to assess the approach and practical feasibility of measuring 25(OH)D half-life after an oral dose. A total of twelve healthy Gambian men aged 18-23 years were divided into two groups to investigate the rate and timing of (1) absorption and (2) plasma disappearance after an 80 nmol oral dose of 25(OH)D2. Fasting blood samples were collected at baseline and, in the first group, every 2 h post-dose for 12 h, at 24 h, 48 h and on day 15. In the second group, fasting blood samples were collected on days 3, 4, 5, 6, 9, 12, 15, 18 and 21. Urine was collected for 2 h after the first morning void at baseline and on day 15. 25(OH)D2 plasma concentration was measured by ultra-performance liquid chromatography-tandem MS/MS and corrected for baseline. Biomarkers of vitamin D, Ca and P metabolism were measured at baseline and on day 15. The peak plasma concentration of 25(OH)D2 was 9·6 (sd 0·9) nmol/l at 4·4 (sd 1·8) h. The terminal slope of 25(OH)D2 disappearance was identified to commence from day 6. The terminal half-life of plasma 25(OH)D2 was 13·4 (sd 2·7) d. There were no significant differences in plasma 25(OH)D3, total 1,25(OH)2D, parathyroid hormone, P, Ca and ionised Ca and urinary Ca and P between baseline and day 15 and between the two groups. The present study provides data on the plasma response to oral 25(OH)D2 that will underpin and contribute to the further development of studies to investigate 25(OH)D half-life.

Selective monitoring of vitamin D2 and D3 supplementation with a highly specific 25-hydroxyvitamin D3 immunoassay with negligible cross-reactivity to 25-hydroxyvitamin D2.

BACKGROUND: The effects of vitamin D2 and D3 supplementation on circulating concentrations of 25(OH)D3 require reliable analytical tools for specific determination of 25(OH)D3 and 25(OH)D2. We have developed a highly specific 25-OH Vitamin D3 ELISA with negligible cross-reactivity towards 25(OH)D2. METHODS: 25(OH)D3 concentrations were measured in several study participants; 1) 641 healthy men and women; 2) 39 postmenopausal women receiving 400-800 IU vitamin D3 daily for 4 months; 3) 45 men and women with hip fracture receiving 1000 IU vitamin D2 daily for 3 months. RESULTS: This 25-OH Vitamin D3 ELISA had minimal cross-reactivity to 25(OH)D2, (0.7%), and demonstrated a high correlation (r2 = 0.93) with 25(OH)D3 determined by HPLC. 25(OH)D3 increased by 14% in subjects receiving vitamin D3 for 4 months (p < 0.01), whereas there was no significant change in 25(OH)D3 levels in those receiving vitamin D2. CONCLUSIONS: We report that 25(OH)D3 ELISA was used for evaluation of 25(OH)D3 concentrations in subjects receiving vitamin D2 and D3 supplementation. The increase of 25(OH)D3 in circulation with vitamin D3 supplementation and lack of increase with vitamin D2 supplementation suggest that this assay has sufficient sensitivity and specificity to be used as a reliable measurement of nutritional vitamin D3 status in humans.

Secondary hyperparathyroidism in primary osteoporosis and osteopenia: optimizing calcium and vitamin D intakes to levels recommended by expert panels may not be sufficient for correction.

OBJECTIVE: To compare biochemical variables, renal function and calcium and vitamin D intakes in euparathyroid and hyperparathyroid patients with primary osteoporosis and osteopenia and describe the measures necessary to normalize serum PTH in the patients with secondary hyperparathyroidism. DESIGN AND PATIENTS: We reviewed the charts of normocalcemic patients with primary osteoporosis and osteopenia first seen during the years 1991-2003 and identified 75 with elevated serum PTH levels at baseline. These patients were compared to all the 143 euparathyroid patients first seen in 1998 and 1999. Patients were restudied after 1 year and we attempted to follow patients with secondary hyperparathyroidism until PTH levels became normal. MEASUREMENTS: At baseline serum PTH, ionized calcium, inorganic phosphate, alkaline phosphatase, creatinine, a complete blood count and serum 25 hydroxy vitamin D were measured in the early morning fasting state. These tests were repeated at follow up. RESULTS: In one-third of the hyperparathyroid patients, the standard baseline treatment failed to correct the secondary hyperparathyroidism necessitating extraordinary measures including unusually large doses of vitamin D (i.e. 50 000 IU vitamin D(2) twice weekly) or the substitution of calcium citrate for calcium carbonate as a calcium supplement. CONCLUSION: Large doses of vitamin D are frequently necessary to suppress secondary hyperparathyroidism in patients with primary osteoporosis and osteopenia. This suggests that vitamin D metabolism may be altered in some of these patients.

Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low vitamin D levels.

AIMS: To test whether a single large dose of vitamin D2 can improve endothelial function in patients with Type 2 diabetes mellitus and low serum 25-hydroxyvitamin D levels. METHODS: Double-blind, parallel group, placebo-controlled randomized trial. A single dose of 100,000 IU vitamin D2 or placebo was administered to patients with Type 2 diabetes over the winter, when levels of circulating 25-hydroxyvitamin D were likely to be lowest. Patients were enrolled if their baseline 25-hydroxyvitamin D level was < 50 nmol/l. Endothelial function and blood pressure were measured and fasting blood samples were taken at baseline and 8 weeks after administration of vitamin D. RESULTS: Forty-nine per cent of subjects screened had 25-hydroxyvitamin D levels < 50 nmol/l. Thirty-four subjects completed the study, with a mean age of 64 years and a baseline 25-hydroxyvitamin D level of 38.3 nmol/l. Vitamin D supplementation increased 25-hydroxyvitamin D levels by 15.3 nmol/l relative to placebo and significantly improved flow mediated vasodilatation (FMD) of the brachial artery by 2.3%. The improvement in FMD remained significant after adjusting for changes in blood pressure. Vitamin D supplementation significantly decreased systolic blood pressure by 14 mmHg compared with placebo; this did not correlate with change in FMD. CONCLUSIONS: Vitamin D insufficiency is common in patients with Type 2 diabetes during winter in Scotland. A single large dose of oral vitamin D2 improves endothelial function in patients with Type 2 diabetes and vitamin D insufficiency.

Effects of vitamin D metabolites on intestinal calcium absorption and bone turnover in elderly women.

BACKGROUND: The relative importance of vitamin D metabolites in the regulation of gut calcium absorption has not been well studied in elderly women living in an environment with abundant sunlight. OBJECTIVE: The objective was to examine the determinants of active gut calcium absorption ( +/- SD: 42 +/- 11%) after an overnight fast with the use of a low (10 mg) calcium load. DESIGN: One hundred twenty elderly women aged 74.7 +/- 2.6 y underwent an active calcium absorption test with a radioactive calcium tracer, dietary analysis, and measurement of markers of bone turnover and calcium metabolism. RESULTS: The mean serum 25-hydroxyvitamin D [25(OH)D] concentration at the time of the calcium absorption test was 68 +/- 29 nmol/L. Gut calcium absorption was correlated with 25(OH)D but not 1,25-dihydroxyvitamin D (calcitriol), the free calcitriol index, or dietary calcium intake. After adjustment for age, calcitriol concentration, and dietary calcium intake, the significant determinant of fractional calcium absorption was the 25(OH)D concentration (r = 0.34, P = 0.001). When body weight was included in the regression, both 25(OH)D (beta = 1.20 x 10(-3)) and calcitriol (beta = 1.00 x 10(-3)) were significantly correlated with calcium absorption. Despite the strong relation between 25(OH)D and gut calcium absorption, there was no relation with other aspects of bone turnover or calcium metabolism. CONCLUSION: These data suggest that at low calcium loads, 25(OH)D is a more important determinant of gut calcium absorption than is calcitriol in elderly women exposed to abundant sunlight, but that this relation has little effect on overall calcium metabolism.