Vitamin D ... is hydroxylated at the 25 position in liver to produce 25-hydroxy-vitamin D3 which is the major metabolite circulating in the plasma. The metabolite is further hydroxylated in the kidney to 1,25-dihydroxy-vitamin D3, the most active metabolite in initiating intestinal transport of calcium & phosphate & mobilization of mineral from bone.
A polar, biologically active metabolite of vitamin D2, 25-hydroxyergocalciferol, which is about 1.5 times more active in curing rickets in rats, has been isolated from pig plasma.
来源:Hazardous Substances Data Bank (HSDB)
代谢
Dihydrotachysterol 是一种维生素 D 类似物，可以被认为是维生素 D2 的还原产物... 在抗佝偻病活性测试中，Dihydrotachysterol 的活性大约是维生素 D 的 1/450，但在高剂量下，它在动员骨矿物质方面比维生素 D 要有效得多。
Dihydrotachysterol is a vitamin D analog that may be regaurded as a reduction product of vitamin D2 ... Dihydrotachysterol is about 1/450 as active as vitamin D in the antirachitic assay, but at high doses it is much more effective than vitamin D in mobilizing bone mineral.
◉ Summary of Use during Lactation:Vitamin D is a normal component of human milk. Daily maternal vitamin D supplementation in the 400 to 2,000 IU (10 to 50 mcg) range produces milk concentrations that are inadequate to deliver the daily requirement to an exclusively breastfed infant, and inadequate to correct pre-existing infant vitamin D deficiency through breastfeeding alone. Breastfeeding mothers who take vitamin D supplements in this range should give their infants a daily vitamin D supplement of at least 400 IU (10 mcg) to meet pediatric nutritional guidelines. Daily maternal vitamin D dosages at or above 4,000 IU (100 mcg) achieve milk levels can potentially meet the daily infant goal intake of at least 400 IU (10 mcg), depending on the mother's underlying vitamin D status and daily infant milk intake. Obese mothers may have higher requirements.
Holder pasteurization decreased median levels of the major forms of vitamin D in breastmilk by 20% in one study.
◉ Effects in Breastfed Infants:Maternal daily doses of 400 to 6,400 IU have not been associated with any short-term biochemical abnormalities in breastfed infants.
An 11-day-old, exclusively breastfed, term, female neonate experienced asymptomatic, mild hypercalcemia (total serum calcium 11.4 mg/dL). The mother was taking maintenance vitamin D2 100,000 IU daily to maintain normal calcium and phosphorus status after a pre-pregnancy thyroid-parathyroidectomy, plus a prenatal vitamin containing 400 IU daily vitamin D (form not specified) during pregnancy and lactation. Vitamin D2 and 25-OH-vitamin D2 levels in cord blood and in milk at 14 days of age were both markedly elevated. Serum vitamin D levels were not measured in the infant. The combination of high daily breastmilk vitamin D2 intake plus a high infant serum level present at birth likely contributed to the abnormal calcium value.
In a study in northern India, short-term maternal use of oral 60,000 IU vitamin D3 once daily for 10 days beginning after birth was not associated with any differences in serum calcium or phosphorus levels, or of urinary calcium/creatinine ratios, in their exclusively breastfed infants at 14 weeks and 6 months of age compared to infants of mothers given placebo. Infants of mothers given vitamin D had a lower frequency of biochemical rickets compared to placebo (0 vs 17%), but no difference in the frequency of radiological rickets (3.6% vs 3.4%).
In a pilot study measuring the epigenomic effects of maternal vitamin D supplementation on the mother and infant, 10 women were given 3,800 IU or 400 IU of oral vitamin D3 once daily beginning at 24 to 28 weeks gestation and continuing through 4 to 6 weeks postpartum. Gestational age at birth was not reported, but presumed to be term. All infants were fully or partially breastfed. Those partially breastfed only received an average of about 10 mL formula daily during the study period. Methylation of cytosine-guanine dinucleotides in infant leukocyte genomic DNA were significantly different between the two groups. Since 2 out of 3 infants in the low-dose group received postpartum vitamin D supplementation and 5 out of 7 in the high-dose group did not, larger controlled studies are needed to determine the effects of vitamin D exposure through breastmilk on the infant epigenome.
One hundred fifty-two mothers in northern India, most of whom were vitamin D deficient, were randomized to receive 120,000 IU (3000 mcg) of vitamin D one time within 7 days postpartum followed by the same dose at 6, 10, and 14 weeks postpartum to coincide with scheduled infant immunization, or placebo. Infants of mothers in the placebo group received 400 IU (10 mcg) of daily vitamin D while those in the treatment group received placebo. At 14 weeks, infant growth parameters and serum biochemical indicators of bone mineral and liver homeostasis were similar between the two groups. At 9 months, dental growth and diarrheal or respiratory illness frequency were also not different.
One hundred fourteen vitamin D deficient mothers in northern India were randomized to receive vitamin D3 60,000 IU (1,500 mcg) or placebo as a single dose starting between 24 and 48 hours after delivery, and then repeated at 6, 10, and 14 weeks postpartum. Over 90% of participants were exclusively breastfeeding. At 6 months of age, 6 infants in the control group and no infants in the treatment group developed biochemical rickets, while 2 infants and 1 infant, respectively, developed radiological rickets. Infants of mothers in the treatment group reportedly had normal serum calcium and phosphorus concentrations at 6 months of age, although specific results were not given, and this outcome was not reported for the control group.
One hundred ninety mothers in Qatar were randomized to receive either 600 IU or 6000 IU vitamin D beginning within 4 weeks postpartum. Infants of the mothers in the low-dose group were given 400 IU daily while those in the high-dose group received daily placebo. At the scheduled 4- and 7-month postpartum study visits, infant growth parameters, serum calcium and parathyroid hormone levels, and parent reported infant health status, were not different between the two groups.
Two hundred twenty healthy, non-obese, breastfeeding mothers in Rajasthan, India were randomized to receive 120,000 IU or 12,000 IU of vitamin D3 once a month for 12 months beginning in the first postpartum month. Infants in both groups had normal serum calcium, phosphate, and alkaline phosphate levels at baseline and at 12 months. There was no significant differences in growth parameters, bone mineral content or density between the two groups at 12 months.
One thousand three hundred pregnant women in Dhaka, Bangladesh were randomized to receive an oral tablet of 4,200 IU, 16,800 IU, 28,000 IU of vitamin D3, or placebo once weekly beginning prenatally between 17- and 24-weeks gestational age. The placebo group and some in the 28,000 IU group continued to receive their assigned treatment for 26 weeks postpartum while the others stopped treatment after delivery. Baseline maternal vitamin D status was similar across all participants with 65% biochemically vitamin D deficient. Breastfeeding duration was similar between each of the groups. The median duration of exclusive breastfeeding was 12 to 14 weeks. Infant vitamin D supplementation was uncommon (<10%). One thousand one hundred sixty-four infants were available for analysis. There were no differences between the groups in infant growth at 1 year postpartum. There were also no differences in infant mortality, hospitalizations, respiratory tract infections, rickets, serum calcium status, or early childhood bone mineral density and grip strength. Infant hypercalcemia and hypercalciuria occurred rarely (0-1%) and did not differ between groups.
One hundred forty-eight exclusively breastfeeding postpartum patients were given either 400 or 6,400 IU daily of vitamin D3 beginning within 4 to 6 weeks of delivery. Average baseline infant serum 25-OH-vitamin D was <50 nmol/L (range undetectable to 113.8 nmol/L). Infants of mothers in the 400 IU daily group were given a 400 IU daily vitamin D supplement, while those in the 6,400 IU daily group were given placebo. There were no differences between the two groups in biochemical markers of calcium status, bone mineral content or density at 1, 4, or 7 months of age.
◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.
The effect of calcitriol (1,25-dihydroxyvitamin D3) on the conversion of ergocalciferol (vitamin D2) to 25-hydroxyvitamin D in 20 normal subjects receiving 2 separate doses of ergocalciferol, one with and one without concomitant administration of calcitriol is described. The concurrent administration of the 2 drugs made no difference to serum calcitriol concentrations.
The effects of glutethimide therapy, 500 mg/day, on the metabolism of vitamin D in a 77 yr old female patient who had taken an overdose of vitamin D2 are reported. Hypercalcemia in this patient was associated with raised serum concentrations of total 25-hydroxyvitamin D and total 1,25-dihydroxyvitamin D. Eight days after administration of glutethimide, plasma gamma-glutamyltransferase activity rose above the upper limit of normal, peaking at 90 IU/L on days 18-22 of therapy. The plasma calcium concentration fell to within the normal range on day 13. The serum concentration of 1,25-dihydroxyvitamin D began to fall within 4 days, and after 8 days it was near the lower limit of the reference range, at 70 pmol/L. The serum concentration of total 25-hydroxyvitamin D did not change appreciably until hepatic enzymes were induced; thereafter it fell gradually. Although the 25-hydroxyvitamin D concentration remained high, the concentration of 1,25-dihydroxyvitamin D did not rise again but remained within the lower part of the normal range.
The effect of a high cholesterol diet and corticosteroids on the toxicity of vitamin D2 in rats was studied. Vitamin D2 was administered orally at the dosage of 5X10+4 to 60X10+4 IU/kg, once daily for 4 days. Animals fed cholesterol showed a decrease in mortality due to vitamin D2 treatment. Dietary cholesterol inhibited toxic responses such as a diminished growth rate following anorexia, elevated serum calcium level and calcium deposition in tissues, which were produced by a sublethal dose of vitamin D2 (20X10+4 IU/kg, once daily for 4 days). Animals pretreated with the high cholesterol diet from 2 wk before the first vitamin D2 administration showed much more symptomatic relief than those given this diet after the first vitamin D2 administration. On the other hand, dexamethasone as well as corticosterone remarkably increased the mortality due to vitamin D2. The degree of vitamin D2 toxicity, enhanced by dexamethasone, was correlated with the degree of hypercalcemia and tissue calcification. Therefore, the inhibitory effect of cholesterol is not likely to be due to activation of the cholesterol corticosterone system in the adrenal gland.
The effect of short term treatment with pharmacological doses of vitamin D2 or vitamin D3 on the serum concentration of 1,25(OH)2D metabolites was examined in epileptic patients on chronic anticonvulsant drug therapy. Nine patients were studied before and after treatment with vitamin D2 4000 IU daily for 24 wk and 10 before and after treatment with vitamin D3 in the same dose. Before treatment the serum concentrations of 1,25(OH)2D and 25(OH)D were significantly lower in epileptics than in normal subjects (p< 0.01). 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. The serum concentration of 25(OH)D2 and 25(OH)D increase significantly, whereas there was a small decrease in 25(OH)D3. Vitamin D3 treatment did not change the serum concentration of 1,25(OH)2D3 whereas serum 25(OH)D3 increased significantly. The correlation between the serum ratio of 1,25(OH)2D2/1,25(OH)2D3 and 25(OH)D2/25(OH)D3 estimated on vitamin D2 treated epileptic patients and normal subjects was highly significant (p< 0.01). The data indicate that the serum concentration of 1,25(OH)2D2 and 1,25(OH)2D3 are directly proportional to the amount of their precursors 25(OH)D2 and 25(OH)D3 and that the concentration of total 1,25(OH)2D is tightly regulated.
Both vitamin D2 & vitamin D3 are absorbed from the small intestine, although vitamin D3 may be absorbed more efficiently. The exact portion of the gut that is most effective in vitamin D absorption reflects the vehicle in which the vitamin is dissolved. Most of the vitamin appears first within chylomicrons in lymph.
The presence of bile is required for absorption of ergocalciferol and the extent of GI absorption may be decreased in patients with hepatic, biliary, or GI disease (e.g., Crohn's disease, Whipple's disease, sprue).
A longitudinal, randomized, double blind, placebo controlled study was conducted for 6 months to monitor ultraviolet B light exposure in human milk-fed infants both with and without supplemental vitamin D2, and to measure longitudinally the bone mineral content, growth, and serum concentrations of calcium, phosphorus, 25-hydroxyvitamin D3, 25-hydroxyvitamin D2, 1,25-dihydroxyvitamin D, and parathyroid hormone. Sequential sampling was performed of 46 human milk-fed white infants; 24 received 400 IU/day of vitamin D2, and 22 received placebo. An additional 12 patients were followed who received standard infant formula. 83% of patients completed a full 6 months of the study. Ultraviolet B light exposure and measurements of growth did not differ between groups. At 6 months, the human milk groups did not differ significantly in bone mineral content or serum concentrations of parathyroid hormone or 1,25-dihydroxyvitamin D, although total 25-hydroxyvitamin D values were significantly less in the unsupplemented human milk group (23.53 + or - 9.94 vs 36.96 + or - 11.86 ng/ml; p< 0.01). However, 25-hydroxyvitamin D3 serum concentrations were significantly higher in the unsupplemented human milk-fed group compared with the supplemented group (21.77 + or - 9.73 vs 11.74 + or - 10.27 ng/ml, p< 0.01) by 6 months of age. It was concluded that unsupplemented, human milk-fed infants had no evidence of vitamin D deficiency during the first 6 months of life.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
对维生素D和25-羟基维生素D在猫体内提升血浆浓度的能力进行了比较。与ergocalciferol相比，通过口服油剂形式的cholecalciferol能够迅速提升血浆中cholecalciferol的浓度，随后迅速下降。相比之下，血浆中的25-羟基维生素D浓度在给药后第3天达到峰值，并在接下来的5天内保持升高。当向10只猫口服油剂形式的337微克cholecalciferol和ergocalciferol时，血浆中cholecalciferol和ergocalciferol的峰值浓度出现在给药后8或12小时。cholecalciferol的峰值浓度是ergocalciferol的两倍以上（570 +/- 80 vs. 264 +/- 42 nmol/l）。cholecalciferol的0-169小时曲线下面积也是ergocalciferol的两倍多。当以亲脂性乳剂形式给予ergocalciferol和cholecalciferol时，血浆中25-羟基维生素D3的浓度高于25-羟基维生素D2。当两种维生素以营养范围内的含量包含在饮食中时，血浆中25-羟基维生素D2的浓度是25-羟基维生素D3的0.68。猫对ergocalciferol的排斥似乎是由于结合蛋白对两种形式维生素D代谢物的亲和力不同造成的。这些结果表明，猫对ergocalciferol的利用效率为cholecalciferol的0.7，以维持血浆中25-羟基维生素D的浓度。
A comparison was made of the ability of ergocalciferol and cholecalciferol to elevate plasma concentrations of vitamin D and 25-hydroxyvitamin D in cats. Cholecalciferol, given as an oral bolus in oil, resulted in a rapid elevation of plasma concentration of chole
