cholecalciferol and 1-25-dihydroxyergocalciferol

Patients with chronic kidney disease (CKD) demonstrate complex mineral metabolism derangements and a high prevalence of vitamin D deficiency. However, the optimal method of 25-hydroxyvitamin D (25(OH)D) repletion is unknown, and trials analysing the comparative efficacy of cholecalciferol and ergocalciferol in this population are lacking. We conducted a randomised clinical trial of cholecalciferol 1250μg (50 000 IU) weekly v. ergocalciferol 1250μg (50 000 IU) weekly for 12 weeks in forty-four non-dialysis-dependent patients with stage 3-5 CKD. The primary outcome was change in total 25(OH)D from baseline to week 12 (immediately after therapy). Secondary analyses included the change in 1,25-dihydroxyvitamin D (1,25(OH)2D), parathyroid hormone (PTH), D2 and D3 sub-fractions of 25(OH)D and 1,25(OH)2D and total 25(OH)D from baseline to week 18 (6 weeks after therapy). Cholecalciferol therapy yielded a greater change in total 25(OH)D (45·0 (sd 16·5) ng/ml) v. ergocalciferol (30·7 (sd 15·3) ng/ml) from baseline to week 12 (P<0·01); this observation partially resulted from a substantial reduction in the 25(OH)D3 sub-fraction with ergocalciferol. However, following cessation of therapy, no statistical difference was observed for total 25(OH)D change from baseline to week 18 between cholecalciferol and ergocalciferol groups (22·4 (sd 12·7) v. 17·6 (sd 8·9) ng/ml, respectively; P=0·17). We observed no significant difference between these therapies with regard to changes in serum PTH or 1,25(OH)2D. Therapy with cholecalciferol, compared with ergocalciferol, is more effective at raising serum 25(OH)D in non-dialysis-dependent CKD patients while active therapy is ongoing. However, levels of 25(OH)D declined substantially in both arms following cessation of therapy, suggesting the need for maintenance therapy to sustain levels.

Topics: 25-Hydroxyvitamin D 2; Academic Medical Centers; Adult; Aged; Calcifediol; Calcitriol; Cholecalciferol; Cohort Studies; Dietary Supplements; Double-Blind Method; Ergocalciferols; Female; Follow-Up Studies; Humans; Kansas; Male; Middle Aged; Outpatient Clinics, Hospital; Parathyroid Hormone; Renal Insufficiency, Chronic; Reproducibility of Results; Vitamin D Deficiency

Interactions between calcium and vitamin D may have implications for the regulation of serum 25-hydroxyvitamin D [25(OH)D] and its catabolism and, consequently, the vitamin D dietary requirement.. We investigated whether different calcium intakes influenced serum 25(OH)D and indexes of vitamin D activation and catabolism during winter and in the context of both adequate and inadequate vitamin D intakes.. A 15-wk winter-based, randomized, placebo-controlled, double-blind vitamin D₃ intervention (20 μg/d) study was carried out in free-living men and women aged ≥50 y (n = 125) who were stratified according to calcium intakes [moderate-low (<700 mg/d) or high (>1000 mg/d) intake]. The serum 25(OH)D concentration was the primary outcome, and serum calcium, parathyroid hormone (PTH), 1,25-dihydroxyvitamin D [1,25(OH)₂D], 24,25-dihydroxyvitamin D [24,25(OH)₂D], the ratio of 24,25(OH)₂D to 25(OH)D, vitamin D-binding protein, and free 25(OH)D were exploratory outcomes.. A repeated-measures ANOVA showed there was no significant (P = 0.2) time × vitamin D treatment × calcium intake grouping interaction effect on the mean serum 25(OH)D concentration over the 15-wk intervention period. Serum 25(OH)D concentrations increased (P ≤ 0.005) and decreased (P ≤ 0.002) in vitamin D₃ and placebo groups, respectively, and were of similar magnitudes in subjects with calcium intakes <700 mg/d (and even <550 mg/d) compared with >1000 mg/d. The response of serum PTH, 1,25(OH)₂D, 24,25(OH)₂D, the ratio of 24,25(OH)₂D to 25(OH)D, and free 25(OH)D significantly differed in vitamin D₃ and placebo groups but not by calcium intake grouping.. We found no evidence of a vitamin D sparing effect of high calcium intake, which has been referred to by some authors as "vitamin D economy." Thus, recent dietary vitamin D requirement estimates will cover the vitamin D needs of even those individuals who have inadequate calcium intakes.

Topics: 24,25-Dihydroxyvitamin D 3; 25-Hydroxyvitamin D 2; Aged; Aged, 80 and over; Aging; Calcifediol; Calcitriol; Calcium; Calcium, Dietary; Cholecalciferol; Dietary Supplements; Double-Blind Method; Ergocalciferols; Female; Humans; Ireland; Male; Middle Aged; Nutritional Requirements; Seasons; Vitamin D Deficiency

The purpose of this study was to determine 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and 1,25-dihydroxyvitamin D2 [1,25(OH)2D2] levels in healthy adults consuming 1000 IU vitamin D2 or vitamin D3 per day for 11 weeks.. Blood from 34 healthy male and female adults, aged 18 to 79 years, from a placebo-controlled, double-blind study who received a placebo, 1000 IU vitamin D3, or 1000 IU vitamin D2 daily for 11 weeks at end of winter was analyzed. Serum levels of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, 1,25(OH)2D2, and 1,25(OH)2D3 were determined by liquid chromatography-tandem mass spectroscopy.. Of the adults, 82% were vitamin D insufficient (serum 25-hydroxyvitamin D [25(OH)D <30 ng/mL]) at the start of the study. Administration of vitamin D2 and vitamin D3 induced similar increases in total 25(OH)D as well as in 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3, respectively. Compared with placebo and adjusting for baseline levels, 1000 IU daily of vitamin D2 was associated with a mean increase of 7.4 pg/mL (95% confidence interval, 4.4-10.3) in 1,25(OH)2D2, which was accompanied by a mean decrease of 9.9 pg/mL (-15.8 to -4.0) in 1,25(OH)2D3. No such differences accompanied administration of 1000 IU daily of vitamin D3.. Vitamin D2 and vitamin D3 were effective in raising and maintaining total serum concentrations of 25(OH)D. Ingestion of vitamin D2 also resulted in an increase in serum concentrations of 1,25(OH)2D2. This increase was accompanied by a comparable decrease in serum concentrations of 1,25(OH)2D3; therefore, the total 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations did not significantly change after 11 weeks compared with baseline levels. Ingestion of vitamin D3 did not alter serum concentrations of 1,25(OH)2D3 or total 1,25(OH)2D. Therefore, ingestion of 1000 IU vitamin D2 or vitamin D3 for 11 weeks was effective in raising total serum concentrations of 25(OH)D as well as sustaining serum concentrations of total 1,25(OH)2D.

Topics: Adolescent; Adult; Aged; Calcitriol; Cholecalciferol; Chromatography, Liquid; Dose-Response Relationship, Drug; Double-Blind Method; Ergocalciferols; Female; Humans; Longitudinal Studies; Male; Middle Aged; Placebos; Reference Values; Regression Analysis; Tandem Mass Spectrometry; Vitamins; Young Adult

As a nongenomic action, 1,25-dihydroxyvitamin D3 (1,25D3) induces L-type Ca(2+) channel-mediated extracellular Ca(2+) influx in human aortic smooth muscle cells (HASMCs), which activates a disintegrin and metalloprotease 10 (ADAM10) to cleave and shed the ectodomain of tumor necrosis factor receptor 1 (TNFR1). In this study, we examined the potencies of other vitamin D3 and D2 analogs to stimulate the ectodomain shedding of TNFR1 in HASMCs. 25-Hydroxyvitamin D3 (25D3), a precursor of 1,25D3, and elocalcitol, an analog of 1,25D3, caused ectodomain shedding of TNFR1 within 30 min, whereas 1,25-dihydroxyvitamin D2 (1,25D2) and paricalcitol, a derivative of 1,25D2, did not. Both 25D3 and elocalcitol rapidly induced extracellular Ca(2+) influx and markedly increased intracellular Ca(2+), while 1,25D2 and paricalcitol caused only small increases in intracellular Ca(2+). 25D3- and elocalcitol-induced TNFR1 ectodomain sheddings were abolished by verapamil and in Ca(2+)-free media. Both 25D3 and elocalcitol caused the translocation of ADAM10 to the cell surface, which was inhibited by verapamil, while 1,25D2 and paricalcitol did not cause ADAM10 translocation. When ADAM10 was depleted by ADAM10-siRNA, 25D3 and elocalcitol could not induce ectodomain shedding of TNFR1. The plasma membrane receptor, endoplasmic reticulum stress protein 57 (ERp57), but not the classic vitamin D receptor, mediated the nongenomic action of vitamin D to induce ectodomain shedding of TNFR1. In summary, like 1,25D3, 25D3 and elocalcitol caused ADAM10-mediated ectodomain shedding of TNFR1, whereas 1,25D2 and paricalcitol did not. The difference may depend on their affinities to ERp57 through which extracellular Ca(2+) influx is induced.

Topics: ADAM Proteins; ADAM10 Protein; Amyloid Precursor Protein Secretases; Calcitriol; Calcium; Calcium Channels, L-Type; Cells, Cultured; Cholecalciferol; Ergocalciferols; Humans; Membrane Proteins; Muscle, Smooth, Vascular; Protein Disulfide-Isomerases; Protein Structure, Tertiary; Receptors, Calcitriol; Receptors, Tumor Necrosis Factor, Type I; Vitamin D

C24-Hydroxylation was evaluated as a possible activation pathway for vitamin D2 and vitamin D3. Routine assays showed that 24-hydroxyvitamin D2 and 1,24-dihydroxyvitamin D2 could be detected in rats receiving physiological doses (100 IU/day) of vitamin D2; however, 24-hydroxyvitamin D3 could not be detected in rats receiving similar doses of vitamin D3. In rats, 24-hydroxyvitamin D2 was very similar to 25-hydroxyvitamin D2 at stimulating intestinal calcium transport and bone calcium resorption. The biological activity of 24-hydroxyvitamin D2 was eliminated by nephrectomy, suggesting that 24-hydroxyvitamin D2 must undergo 1 alpha-hydroxylation to be active at physiological doses. In vivo experiments suggested that when given individually to vitamin D deficient rats, 24-hydroxyvitamin D2, 25-hydroxyvitamin D2, and 25-hydroxyvitamin D3 were 1 alpha-hydroxylated with the same efficiency. However, when presented simultaneously, 24-hydroxyvitamin D2 was less efficiently 1 alpha-hydroxylated than either 25-hydroxyvitamin D3 or 25-hydroxyvitamin D2. 1,24-Dihydroxyvitamin D2 was also approximately 2-fold less competitive than either 1,25-dihydroxyvitamin D2 or 1,25-dihydroxyvitamin D3 for binding sites on the bovine thymus 1,25-dihydroxyvitamin D receptor. These results demonstrate that 24-hydroxylation followed by 1 alpha-hydroxylation of vitamin D2 represents a minor activation pathway for vitamin D2 but not vitamin D3.

Topics: Animals; Binding, Competitive; Biological Transport; Calcifediol; Calcitriol; Calcium; Cholecalciferol; Ergocalciferols; Hydroxylation; Male; Nephrectomy; Protein Binding; Rats

A radio-immunoassay (RIA) for determination of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) and 1,25-dihydroxyergocalciferol (1,25(OH)2D2) in serum was compared with a competitive protein binding assay using calf thymus receptor to clarify the comparability of measurements in subjects treated with either vitamin D2 or vitamin D3 (4000 IU per day for 8 weeks). Before and during treatment with vitamin D3 the two assay techniques were concordant, but during vitamin D2 treatment the serum concentrations of 1,25(OH)2D2 and 1,25(OH)2D3 were higher when measured by RIA. The study demonstrates that during vitamin D2 treatment unknown compounds, recognized only by the antiserum, co-elute with 1,25(OH)2D2 and 1,25(OH)2D3 in high pressure liquid chromatography. It can be concluded that the radio-immunoassay used here cannot replace the calf thymus receptor assay.

Topics: Adult; Calcitriol; Calcium; Cholecalciferol; Ergocalciferols; Female; Humans; Menopause; Middle Aged; Radioimmunoassay; Radioligand Assay; Thymus Gland

Studies on the discrimination between ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) by chickens have led to conflicting conclusions. To investigate this problem in more detail, radiolabeled vitamin D and vitamin D metabolites were administered intravenously, which allowed determination of their relative plasma clearance rates. The study involved three groups of adult male chickens (five per group). Birds in group 1 were co-dosed with [3H]vitamin D2 and [3H]vitamin D3. Birds in group 2 were co-dosed with [3H]25-dihydroxyvitamin D2 and [3H]25-dihydroxyvitamin D3 and birds in group 3 were co-dosed with [3H]1,25-dihydroxyvitamin D3 and [3H]1,25-dihydroxyvitamin D2. The results indicated that the plasma turnover rate of [3H]vitamin D2 is 1.5 times faster than that of [3H]vitamin D3. Plasma turnover of the 25-hydroxylated metabolites differed, with [3H]25-dihydroxyvitamin D2 clearing faster (11 times) than [3H]25-dihydroxyvitamin D3. The largest difference appeared in the 1,25-dihydroxyvitamin D2 turnover rates with 1,25-dihydroxyvitamin D2 clearing approximately 33 times faster then [3H]1,25-dihydroxyvitamin D3. These data, therefore, indicate that discrimination against vitamin D2 sterols in the chick occurs primarily between steps in the metabolism of vitamin D and not at the point of metabolism or excretion of the parent vitamin.

Topics: 25-Hydroxyvitamin D 2; Animals; Calcifediol; Calcitriol; Chickens; Cholecalciferol; Ergocalciferols; Male; Metabolic Clearance Rate

Serum concentrations of vitamin D2 and vitamin D3 metabolites were measured in 19 normal subjects before and during treatment with either vitamin D2 or vitamin D3, 4000 IU per day for 8 weeks. Vitamin D2 treatment increased the serum concentration of 1,25(OH)2D2, but a corresponding decrease in 1,25(OH)2D3 resulted in an unchanged serum concentration of total 1,25(OH)2D. During treatment with vitamin D3, the serum concentration of 1,25(OH)2D metabolites was unchanged. We conclude that the production of 1,25(OH)2D is tightly regulated and that 1 alpha-hydroxylase does not discriminate between D2 and D3 metabolites in normal subjects.

Topics: Adult; Animals; Biological Assay; Calcitriol; Chickens; Cholecalciferol; Chromatography, High Pressure Liquid; Dihydroxycholecalciferols; Ergocalciferols; Female; Humans; Intestinal Mucosa; Middle Aged; Thymus Gland