Signaling through the vitamin D receptor has been shown to be biologically active and important in a number of preclinical studies in prostate and other cancers. Epidemiologic data also indicate that vitamin D signaling may be important in the cause and prognosis of prostate and other cancers. These data indicate that perturbation of vitamin D signaling may be a target for the prevention and treatment of prostate cancer. Large studies of vitamin D supplementation will be required to determine whether these observations can be translated into prevention strategies. This paper reviews the available data in the use of vitamin D compounds in the treatment of prostate cancer. Clinical data are limited which support the use of vitamin D compounds in the management of men with prostate cancer. However, clinical trials guided by existing preclinical data are limited.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Calcifediol/blood* ; Calcitriol/therapeutic use* ; Clinical Trials as Topic ; Ergocalciferols/therapeutic use* ; Humans ; Male ; Prostatic Neoplasms/prevention & control* ; Signal Transduction ; Vitamin D/metabolism* ; Vitamin D Deficiency/epidemiology*

Vitamin D is present in two forms, ergocalciferol (vitamin D2) produced by plants and cholecalciferol (vitamin D3) produced by animal tissues or by the action of ultraviolet light on 7-dehydrocholesterol in human skin. Both forms of vitamin D are biologically inactive pro-hormones that must undergo sequential hydroxylations in the liver and the kidney before they can bind to and activate the vitamin D receptor. The hormonally active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D], plays an essential role in calcium and phosphate metabolism, bone growth, and cellular differentiation. Renal synthesis of 1,25(OH)2D from its endogenous precursor, 25-hydroxyvitamin D (25OHD), is the rate-limiting and is catalyzed by the 1alpha-hydroxylase. Vitamin D dependent rickets type I (VDDR-I), also referred to as vitamin D 1alpha-hydroxylase deficiency or pseudovitamin D deficiency rickets, is an autosomal recessive disorder characterized clinically by hypotonia, muscle weakness, growth failure, hypocalcemic seizures in early infancy, and radiographic findings of rickets. Characteristic laboratory features are hypocalcemia, increased serum concentrations of parathyroid hormone (PTH), and low or undetectable serum concentrations of 1,25(OH)2D despite normal or increased concentrations of 25OHD. Recent advances have showed in the cloning of the human 1alpha-hydroxylase and revealed mutations in its gene that cause VDDR-I. This review presents the biology of vitamin D, and 1alpha-hydroxylase mutations with clinical findings.
Animals ; Biology ; Bone Development ; Calcitriol ; Calcium ; Cholecalciferol ; Clone Cells ; Cloning, Organism ; Dehydrocholesterols ; Ergocalciferols ; Humans ; Hydroxylation ; Hypocalcemia ; Kidney ; Liver ; Muscle Hypotonia ; Parathyroid Hormone ; Receptors, Calcitriol ; Rickets ; Seizures ; Skin ; Ultraviolet Rays ; Vitamin D ; Vitamins

BACKGROUND: Determining the concentration profiles of serum 25-hydroxyvitamin D (25OHD) may aid in the clinical diagnosis and treatment of vitamin D deficiency. To date, the standardized liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay has been used for accurate and precise determination of 25-hydroxyvitamin D levels. Here, we evaluated the performance of the recently developed and introduced PerkinElmer Vitamin D kit and compared the measurements obtained by RIA and LC-MS/MS methods. METHODS: We evaluated the accuracy, precision, linearity, lower limit of quantification (LLOQ), recovery, and carry-over of the MSMS Vitamin D kit. Clinical specimens from 80 patients were used for the comparison between the MSMS Vitamin D kit (PerkinElmer, USA) and the RIA kit (DiaSorin, USA). RESULTS: The MSMS Vitamin D kit was found to produce intra-assay and inter-assay coefficients of variation (CVs) of less than 6% for precision and showed a bias of less than 5%. The MSMS Vitamin D kit displayed linearity within the range for total vitamin D levels of 4.5-150 ng/mL, and the lower limit of quantification for 25OHD was 0.38 ng/mL. The RIA measurements of 25OHD showed a correlation of y=0.9931x+0.2216 (r2=0.74) with the LC-MS/MS values. CONCLUSIONS: The LC-MS/MS assay of 25OHD3 and 25OHD2 showed excellent performance when using the MSMS Vitamin D kit and in terms of 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) derivatization. Further, the results obtained were well correlated with those obtained using the RIA method. Thus, assays using the MSMS Vitamin D kit are considered as more standardized, and they enable quicker and more accurate analysis and help reduce inter-laboratory variation than that by other existing methods.
25-Hydroxyvitamin D 2 ; Bias (Epidemiology) ; Calcifediol ; Humans ; Mass Spectrometry ; Tandem Mass Spectrometry ; Triazoles ; Vitamin D ; Vitamin D Deficiency ; Vitamins

Cardiorenal syndrome (CRS) refers to a constellation of conditions whereby heart and kidney diseases are pathophysiologically connected. For clinical purposes, it would be more appropriate to emphasize the pathophysiological pathways to classify CRS into: (1) hemodynamic, (2) atherosclerotic, (3) uremic, (4) neurohumoral, (5) anemic??hematologic, (6) inflammatory-oxidative, (7) vitamin D receptor (VDR) and/or FGF23-, and (8) multifactorial CRS. In recent years, there have been a preponderance data indicating that vitamin D and VDR play an important role in the combination of renal and cardiac diseases. This review focuses on some important findings about VDR activation and its role in CRS, which exists frequently in chronic kidney disease patients and is a main cause of morbidity and mortality. Pathophysiological pathways related to suboptimal or defective VDR activation may play a role in causing or aggravating CRS. VDR activation using newer agents including vitamin D mimetics (such as paricalcitol and maxacalcitol) are promising agents, which may be related to their selectivity in activating VDR by means of attracting different post-D-complex cofactors. Some, but not all, studies have confirmed the survival advantages of D-mimetics as compared to non-selective VDR activators. Higher doses of D-mimetic per unit of parathyroid hormone (paricalcitol to parathyroid hormone ratio) is associated with greater survival, and the survival advantages of African American dialysis patients could be explained by higher doses of paricalcitol (>10 microg/week). More studies are needed to verify these data and to explore additional avenues for CRS management via modulating VDR pathway.
Cardio-Renal Syndrome ; Dialysis ; Ergocalciferols ; Heart ; Heart Diseases ; Hemodynamics ; Humans ; Kidney Diseases ; Parathyroid Hormone ; Receptors, Calcitriol ; Renal Insufficiency, Chronic ; Vitamin D ; Vitamins

PURPOSE: To evaluate the clinical characteristics of vitamin D deficiency and its association with iron deficiency anemia (IDA). METHODS: A total of 171 children aged less than two years underwent 25-hydroxyvitamin D3 tests between January 2007 and July 2009. The study was classified into two groups: normal and vitamin D insufficiency, by their vitamin 25-hydroxyvitamin D3 levels. RESULTS: In total, 120 children were in the normal group (mean age, body weight and heights 12.5+/-7.0, 9.3+/-0.9 kg and 76.8+/-1.1 cm), and 51 children in the vitamin D insufficiency group (9.9+/-5.4 months, 9.0+/-0.9 kg and 75.1+/-0.9 cm). Vitamin D insufficiency was most commonly diagnosed in the spring (44%). The proportion of complete breast-feeding was higher in the insufficiency (92%), and 25.5% of the children in the deficient group also experienced IDA compared that 12% of normal group. Ten children in the insufficiency group experienced bony changes. Six children received calcitriol medication in the normal group, in whom the mean vitamin 25-hydroxyvitamin D3 level increased from 39.6+/-14.6 ng/mL (pre-medication) to 41.8+/-17.2 ng/mL (post-medication), and 13 in the insufficiency group, in whom the mean vitamin 25-hydroxyvitamin D3 increased from 20.7+/-7.0 ng/mL to a mean post-treatment level of 43.7+/-23.8 ng/mL. CONCLUSION: This study demonstrated that approximately 30% of children aged < or =2 years experienced vitamin D insufficiency associated with subclinical rickets. Many children also experienced concurrent IDA. Guidelines for vitamin D supplement in such children must therefore be established.
Aged ; Anemia ; Anemia, Iron-Deficiency ; Body Weight ; Calcifediol ; Calcitriol ; Child ; Humans ; Iron ; Prevalence ; Rickets ; Vitamin D ; Vitamin D Deficiency ; Vitamins

PURPOSE: It is well known that obesity is related to vitamin D deficiency (VDD). We investigated the response to vitamin D replacement in normal-weight and overweight children. METHODS: This was a prospective study including 62 Korean children with VDD. VDD was defined as a serum 25-hydroxycholecalciferol (25(OH)D) concentration <20 ng/mL. Overweight was defined as a body mass index (BMI)≥the 85th percentile (n=21), and normal weight as a BMI between the 5th and 84th percentiles (n=41). All participants received vitamin D3 supplementation (2,000 IU/day) for 8 weeks. The serum levels of 25(OH)D, PTH and biochemical parameters were measured before and after treatment. RESULTS: The mean age was 10.0±1.4 years in normal-weight children and 10.0±2.1 years in overweight children (P=0.93). After 8 weeks of treatment, 61.9% of normal-weight children and 47.6% of overweight children achieved vitamin D sufficiency (P =0.30). The mean serum 25(OH)D levels after vitamin D replacement were 33.8±7.6 ng/mL and 30.3±6.6 ng/mL in normal-weight and overweight children, respectively (P =0.10). The mean calcium/creatinine ratios after treatment were 0.09±0.07 and 0.08±0.06 in the normal-weight and overweight groups, respectively, and no hypercalciuria was found. In multiple regression analysis, the response to vitamin D replacement was influenced by the BMI (β=-1.0, P=0.03) and sex (β=-4.0, P=0.04). CONCLUSIONS: Eight weeks of vitamin D replacement (2,000 IU/day) is sufficient to overcome vitamin D deficiency in normal-weight and overweight children without any complications.
Body Mass Index ; Calcifediol ; Child ; Cholecalciferol ; Humans ; Hypercalciuria ; Obesity ; Overweight ; Prospective Studies ; Vitamin D Deficiency ; Vitamin D ; Vitamins

BACKGROUND/AIMS: The exact relationship between vitamin D deficiency and inflammatory bowel disease (IBD) remains unclear. We evaluated the effect of vitamin D3 administration on inflammatory responses and disease severity in patients with IBD. METHODS: We investigated the serum 25-hydroxyvitamin D3 [25-(OH)D], C-reactive protein (CRP) levels and the partial Mayo score (PMS) in patients with IBD. Vitamin D3 was administered in patients with either vitamin D deficiency or insufficiency and CRP, serum vitamin D levels and PMS were re-examined at 6 months of administration. RESULTS: In 88 patients with Crohn's disease (CD), a negative correlation was found between serum vitamin D and CRP. In 178 patients with ulcerative colitis (UC), serum vitamin D showed no association with CRP or PMS. Serum vitamin D increased from 11.08±3.63 to 22.69±6.11 ng/mL in 29 patients with CD and from 11.45±4.10 to 24.20±6.61 ng/mL in 41 patients with UC who received vitamin D3 treatment (P<0.001 and P<0.001, respectively). In patients with CD, median ΔCRP was –0.24 in the normalized vitamin D group and –0.11 in the non-normalized group (P=0.308). In patients with UC, median ΔCRP was −0.01 in the normalized vitamin D group and 0.06 in the non-normalized group (P=0.359). CONCLUSIONS: Although a negative correlation was found between serum vitamin D and CRP levels in patients with CD, administration of vitamin D did not improve the CRP level in patients with CD. In patients with UC, serum vitamin D level was unrelated to CRP or PMS.
C-Reactive Protein ; Calcifediol ; Cholecalciferol ; Colitis, Ulcerative ; Crohn Disease ; Humans ; Inflammatory Bowel Diseases ; Vitamin D Deficiency ; Vitamin D ; Vitamins

BACKGROUND: Vitamin D has been recently shown to play important roles in the functioning of various systems. Most of the current analytical methods for measuring vitamin D levels are based on immunoassays. We simultaneously measured the levels of 25-hydroxyvitamin D3 [ 25(OH)D3 ] and 25-hydroxyvitamin D2 [ 25(OH)D2 ] in human serum by performing ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) after Diels-Alder derivatization with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) and evaluated the performance of our method. METHODS: After liquid-liquid extraction, samples were dried under N2 at 50degrees C for 1 hr followed by Diels-Alder derivatization with ethyl acetate containing 0.1 mg/mL PTAD. The samples were resuspended in 60 microL of methanol:10 mM ammonium formate solution (1:1, V/V). C18 UPLC column and positive ion multiple reaction monitoring transitions such as m/z 558.35-->298.1, 25(OH)D3; m/z 570.35-->298.1, 25(OH)D2; and m/z 564.35-->298.1, hexadeuterated-25(OH)D3 were used for UPLC-MS/MS. RESULTS: The within-run imprecision (CVs) for 25(OH)D3 and 25(OH)D2 were 3.5-4.0% and 3.8-4.2%, respectively, and the corresponding between-run CVs were 3.3-5.5% and 4.7-5.8%. The lower limit of quantification for 25(OH)D3 and 25(OH)D2 were 0.5 and 1.0 ng/mL, respectively. The curve for interassay calibration variability data obtained over concentrations of 0-120 ng/mL for 25(OH)D3 and 0-90 ng/mL for 25(OH)D2 was linear and reproducible [ 25(OH)D3, R2=0.993; 25(OH)D2, R2=0.998]. The total 25(OH)D levels in Koreans (average, 18.7 ng/mL) were lower than those in American Caucasians, and the percentage of people with total 25(OH)D levels under 10 ng/mL was 8.1%. CONCLUSIONS: Our method to measure 25(OH)D3 and 25(OH)D2 levels by performing UPLC-MS/MS after PTAD derivatization showed good performance as a sensitive and reproducible method for routine analysis of vitamin D status.
25-Hydroxyvitamin D 2 ; Acetates ; Calcifediol ; Calibration ; Formates ; Humans ; Immunoassay ; Liquid-Liquid Extraction ; Mass Spectrometry ; Quaternary Ammonium Compounds ; Tandem Mass Spectrometry ; Triazoles ; Vitamin D

Microglia are activated by inflammatory and pathophysiological stimuli in neurodegenerative diseases, and activated microglia induce neuronal damage by releasing cytotoxic factors like nitric oxide (NO). Activated microglia synthesize a significant amount of vitamin D3 in the rat brain, and vitamin D3 has an inhibitory effect on activated microglia. To investigate the possible role of vitamin D3 as a negative regulator of activated microglia, we examined the effect of 25-hydroxyvitamin D3 on NO production of lipopolysaccharide (LPS)-stimulated microglia. Treatment with LPS increased the production of NO in primary cultured and BV2 microglial cells. Treatment with 25-hydroxyvitamin D3 inhibited the generation of NO in LPS-activated primary microglia and BV2 cells. In addition to NO production, expression of 1-alpha-hydroxylase and the vitamin D receptor (VDR) was also upregulated in LPS-stimulated primary and BV2 microglia. When BV2 cells were transfected with 1-alpha-hydroxylase siRNA or VDR siRNA, the inhibitory effect of 25-hydroxyvitamin D3 on activated BV2 cells was suppressed. 25-Hydroxyvitamin D3 also inhibited the increased phosphorylation of p38 seen in LPS-activated BV2 cells, and this inhibition was blocked by VDR siRNA. The present study shows that 25-hydroxyvitamin D3 inhibits NO production in LPS-activated microglia through the mediation of LPS-induced 1-alpha-hydroxylase. This study also shows that the inhibitory effect of 25-hydroxyvitamin D3 on NO production might be exerted by inhibiting LPS-induced phosphorylation of p38 through the mediation of VDR signaling. These results suggest that vitamin D3 might have an important role in the negative regulation of microglial activation.
Animals ; Brain ; Calcifediol* ; Cholecalciferol ; Microglia* ; Negotiating ; Neurodegenerative Diseases ; Neurons ; Nitric Oxide* ; Phosphorylation ; Rats ; Receptors, Calcitriol ; RNA, Small Interfering

BACKGROUND: It is still unclear the ideal vitamin D dosage once the deficiency and insufficiency is treated. Once deficiency was corrected we prospectively treated patients with 2,000 IU of vitamin D3 to check whether this dosage is enough to keep them above the 30 ng/mL of 25-hydroxy-vitamin D (25[OH]D). METHODS: One hundred and thirty-five Saudi Arabian men and women treatment naïve for the vitamin D deficiency and insufficiency were part of this study. History and clinical examination were done to rule out any metabolic bone disease. Weight and height was taken to calculate the body mass index (BMI). Patients who were vitamin D deficient (≥30 ng/mL), a standard treatment of 50,000 IU of vitamin D3 weekly for 3 months, a blood test for the vitamin D levels at the end of 3 months, maintenance dose of 2,000 IU of vitamin D3 for 3 months and a third blood sample after 3 months. RESULTS: The data for 128 patients was available for analysis. The average age was 44.95±12.97 years with the mean BMI of 29.60±2.59 kg/m2. The baseline 25(OH)D level was 13.16±3.30 ng/mL. The increase in the level of 25(OH)D on 50,000 IU weekly was significant from 13.16±3.3 ng/mL to 36.97±4.67 ng/mL (P < 0.001) and then 2,000 IU daily for next 3 months, the level of 25(OH)D dropped top 20.38±5.42 ng/mL (P < 0.001). CONCLUSIONS: Our study indicates that the maintenance dose of 2,000 IU of vitamin D is not enough for patients to keep the 25(OH)D levels above 30 ng/mL.
Body Mass Index ; Bone Diseases, Metabolic ; Calcifediol ; Cholecalciferol ; Dietary Supplements ; Female ; Hematologic Tests ; Humans ; Male ; Prospective Studies ; Vitamin D Deficiency ; Vitamin D* ; Vitamins*