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Actions of vitamin D3, analogs on human prostate cancer cell lines: comparison with 1,25-dihydroxyvitamin D3.

Data from epidemiological studies has suggested that vitamin D deficiency may promote prostate cancer, although the mechanism is not understood. We have previously demonstrated the presence of vitamin D receptors (VDR) in three human prostate carcinoma cell lines (LNCaP, PC-3, and DU-145) as well as in primary cultures of stromal and epithelial cells derived from normal and malignant prostate tissues. We have also shown that 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] can elicit an antiproliferative action in these cells. In the present study we compared the biological actions of 1,25-(OH)2D3 to those of a series of natural vitamin D3 metabolites and several synthetic analogs of vitamin D3 known to exhibit less hypercalcemic activity in vivo. In ligand binding competition experiments, we demonstrated the following order of potency in displacing [3H]1,25-(OH)2D3 from VDR: EB-1089 > 1,25-(OH)2D3 > MC-903 > 1,24,25-(OH)3D3 > 22-oxacalcitriol (OCT) > 1 alpha,25-dihydroxy-16-enecholecalciferol (Ro24-2637) > 25-hydroxyvitamin D3, with EB-1089 being approximately 2-fold more potent than the native hormone. No competitive activity was found for 25-hydroxy-16,23-diene-cholecalciferol. When compared for ability to inhibit proliferation of LNCaP cells, MC-903, EB-1089, OCT, and Ro24-2637 exhibited 4-, 3-, and 2-fold greater inhibitory activity than 1,25-(OH)2D3. Interestingly, although OCT and Ro24-2637 exhibit, respectively, 10 and 14 times lower affinity for VDR than 1,25-(OH)2D3, both compounds inhibited the proliferation of LNCaP cells with a potency greater than that of the native hormone. The relative potency of vitamin D3 metabolites and analogs to inhibit cell proliferation correlated well with the ability of these compounds to stimulate prostate-specific antigen secretion by LNCaP cells as well as with their potency to induce the 25-hydroxyvitamin D3-24-hydroxylase messenger RNA transcript in PC-3 cells. In conclusion, these results demonstrate that synthetic analogs of vitamin D3, known to exhibit reduced calcemic activity, can elicit antiproliferative effects and other biological actions in LNCaP and PC-3 cell lines. It is noteworthy that although binding to VDR is critical for 1,25-(OH)2D3 action, the analog data indicate that additional factors significantly contribute to the magnitude of the biological response. Finally, the strong antiproliferative effects of several synthetic analogs known to exhibit less calcemic activity than 1,25-(OH)2D3 suggest that these compounds potentially may be useful as an additional therapeutic option for the treatment of prostate cancer.

Binding Sites↗

Vitamin D metabolism and the response to 1,25-dihydroxycholecalciferol in Osteoporosis.

The metabolism of isotopically-labelled cholecalciferol and the response to small doses of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) was studied in a group of women with osteoporosis presenting with crush vertebral fracture. No abnormality of vitamin D metabolism was detected. The administration of 1 microgram 1,25-(OH)2D3 for between 8 and 20 days was associated with an increased intestinal absorption and urinary excretion of calcium but caused no improvement in calcium balance. There was a small but significant rise in serum calcium and phosphorus and significant reduction in immunoassayable parathyroid hormone levels during treatment. It is concluded that 1,25-(OH)2D3 is unlikely to be of value in the management of osteoporosis.

Aged↗

Effects of a short-term vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women.

Calcium supplementation is effective in reducing blood pressure in various states of hypertension, including pregnancy-induced hypertension and preeclampsia. In addition, calcitropic hormones are associated with blood pressure. The hypothesis is that short-term therapy with calcium and vitamin D(3) may improve blood pressure as well as secondary hyperparathyroidism more effectively than calcium monotherapy. The effects of 8 weeks of supplementation with vitamin D(3) (cholecalciferol) and calcium on blood pressure and biochemical measures of bone metabolism were studied. The sample consisted of 148 women (mean +/- SD age, 74 +/- 1 yr) with a 25-hydroxycholecalciferol (25OHD(3)) level below 50 nmol/L. They received either 1200 mg calcium plus 800 IU vitamin D(3) or 1200 mg calcium/day. We measured intact PTH, 25OHD(3), 1,25-dihydroxyvitamin D(3), blood pressure, and heart rate before and after treatment. Compared with calcium, supplementation with vitamin D(3) and calcium resulted in an increase in serum 25OHD(3) of 72% (P < 0.01), a decrease in serum PTH of 17% (P = 0.04), a decrease in systolic blood pressure (SBP) of 9.3% (P = 0.02), and a decrease in heart rate of 5.4% (P = 0.02). Sixty subjects (81%) in the vitamin D(3) and calcium group compared with 35 (47%) subjects in the calcium group showed a decrease in SBP of 5 mm Hg or more (P = 0.04). No statistically significant difference was observed in the diastolic blood pressures of the calcium-treated and calcium- plus vitamin D(3)-treated groups (P = 0.10). Pearson coefficients of correlation between the change in PTH and the change in SBP were 0.49 (P < 0.01) for the vitamin D(3) plus calcium group and 0.23 (P < 0.01) for the calcium group. A short-term supplementation with vitamin D(3) and calcium is more effective in reducing SBP than calcium alone. Inadequate vitamin D(3) and calcium intake could play a contributory role in the pathogenesis and progression of hypertension and cardiovascular disease in elderly women.

Aged↗

Altered sensitivities to potential inhibitors of cholesterol biosynthesis in Niemann-Pick type C fibroblasts.

Cultured fibroblasts from patients with Niemann-Pick disease type C (NP-C) are characterized by the lysosomal accumulation of unesterified cholesterol and the inability of low-density lipoprotein (LDL) to stimulate cholesterol esterification, in addition to impaired LDL-mediated down-regulation of LDL receptor activity and cellular cholesterol synthesis. Although a defect in the transport of cholesterol from lysosomes to other intracellular membrane sites has been suggested, it is unclear how cells regulate the levels of cellular sterols and whether their membrane cholesterol requirements are satisfied or not. We studied the esterification of exogenously added cholesterol, total levels of cellular cholesterol and cholesteryl ester, cholesterol synthesis from a two-carbon precursor, and sensitivities to potential inhibitors of cholesterol biosynthesis in proliferating NP-C cells. We observed the following: (a) esterification of [3H]cholesterol was decreased but the total amount of cellular cholesteryl ester was not decreased; (b) synthesis of cholesterol from [3H]acetate was increased; and (c) cells were hypersensitive to cholecalciferol, an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, and were resistant to filipin, which binds to membrane sterols and presumably damages the membrane. The results indicate that NP-C cells depend on the cellular cholesterol synthetic pathway for their proliferation, but the plasma membrane sterols are presumably decreased. The altered sensitivities to potential inhibitors of cholesterol biosynthesis should be a useful marker for diagnosis and genetic studies.

Acetates↗

The biochemical effects of physiologic amounts of dietary boron in animal nutrition models.

This review summarizes evidence that supports working hypotheses for the roles of boron in animal model systems. It is well established that vascular plants, diatoms, and some species of marine algal flagellates have acquired an absolute requirement for boron, although the primary role of boron in plants remains unknown. Recent research findings suggest that physiologic amounts of supplemental dietary boron (PSB) affect a wide range of metabolic parameters in the chick and rat model systems. Much of the current interest in boron animal nutrition began with the initial finding that PSB stimulates growth in cholecalciferol (vitamin D3)-deficient chicks, but does not markedly affect growth in chicks receiving adequate vitamin D3 nutriture. The finding suggests that boron affects some aspect of vitamin D3 metabolism or is synergistic with vitamin D3 in influencing growth. Vitamin D3 regulates energy substrate utilization, and current research findings indicate that dietary boron modifies that regulatory function. The concentration of circulating glucose, the most thoroughly investigated metabolite to date, responds to PSB, especially during concomitant vitamin D3 deficiency. In chicks, PSB substantially alleviated or corrected vitamin D3 deficiency-induced elevations in plasma glucose concentrations. The influence of vitamin D3 on cartilage and bone mineralization is mediated in part through its role as a regulator of energy substrate utilization; calcification is an energy-intensive process. There is considerable evidence that dietary boron alleviates perturbations in mineral metabolism that are characteristic of vitamin D3 deficiency. In rachitic chicks, PSB alleviated distortion of the marrow sprouts of the proximal tibial epiphysial plate, a distortion characteristic of vitamin D3 deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Nutritional Physiological Phenomena↗

Apoptosis induction of POS canine osteosarcoma cells by vitamin D and retinoids.

Vitamin D3: 1-alpha, 25(OH)2D3 (calcitriol), 22-oxa-1,25(OH)2D3 (OCT), cholecalciferol (vitamin D3), and retinoids: all-trans retinoic acid (ATRA) and 9-cis retinoic acid, induced morphological changes in POS canine osteosarcoma cells into elongated, spindle or fibroblast like-shaped cells, and apoptotic like cell death characterized by cell shrinkage, condensation and margination of the nucleus for all drugs at 10(-6)M-10(-9)M after 72 to 120 hr culture. Apoptosis as shown by DNA laddering was induced at 48 hr by all drugs at 10(-6)M, 10(-7)M at 96 hr, 10(-8)M and 10(-9)M at 120 hr respectively. These vitamins are suggested to adjunct antineoplastic agents in canine osteosarcoma therapy by induction of apoptosis.

Animals↗

Levels of active metabolites of vitamin D3 in the callus of fracture repair in chicks.

The levels of the active metabolites of vitamin D were measured in the callus and in the epiphyseal growth plate of chicks given radioactive cholecalciferol during fracture healing. Those levels were correlated with the histological findings. Three groups of chicks were studied: a control group with no fracture, chicks with fractures fixed by Kirschner wire, and chicks with unfixed fractures. A significant increase in the levels of the active metabolites was found in the callus during the first few days after fracture. The levels of 25-hydroxycholecalciferol [25(OH)D3] and of 24,25-dihydroxycholecalciferol [24,25(OH)2D3] were higher when there was no fixation, while those of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] were higher after fixation. The concentrations of these metabolites in the proximal epiphysis of the tibia were similar to those found in the callus. Based on these findings it is suggested that the active metabolites of vitamin D are directly involved in the process of fracture repair.

Animals↗

Supplementation with oral vitamin D3 and calcium during winter prevents seasonal bone loss: a randomized controlled open-label prospective trial.

UNLABELLED: Bone metabolism follows a seasonal pattern with high bone turnover and bone loss during the winter. In a randomized, open-label 2-year sequential follow-up study of 55 healthy adults, we found that supplementation with oral vitamin D3 and calcium during winter abolished seasonal changes in calciotropic hormones and markers of bone turnover and led to an increase in BMD. Supplementation with oral vitamin D3 and calcium during the winter months seems to counteract the effects of seasonal changes in vitamin D and thus may be beneficial as a primary prevention strategy for age-related bone loss. INTRODUCTION: Bone metabolism follows a seasonal pattern characterized by high bone turnover and bone loss during winter. We investigated whether wintertime supplementation with oral vitamin D3 and calcium had beneficial effects on the circannual changes in bone turnover and bone mass. MATERIALS AND METHODS: This prospective study comprised an initial observation period of 12 months ("year 1"), followed by an intervention during parts of year 2. Fifty-five healthy subjects living in southwestern Germany (latitude, 49.5 degrees N) were randomized into two groups: 30 subjects were assigned to the treatment group and received oral cholecalciferol (500 IU/day) and calcium (500 mg/day) during the winter months of year 2 (October-April), while 25 subjects assigned to the control group obtained no supplements. Primary endpoints were changes in calciotropic hormones [serum 25(OH)D, 1,25(OH)2D, and parathyroid hormone], markers of bone formation (serum bone-specific alkaline phosphatase) and of bone resorption (urinary pyridinoline and deoxypyridinoline), and changes in lumbar spine and femoral neck BMD. RESULTS: Forty-three subjects completed the study. During year 1, calciotropic hormones, markers of bone turnover, and BMD varied by season in both groups. During the winter months of year 1, bone turnover was significantly accelerated, and lumbar spine and femoral BMD declined by 0.3-0.9%. In year 2, seasonal changes in calciotropic hormones and markers of bone turnover were either reversed or abolished in the intervention group while unchanged in the control cohort. In the subjects receiving oral vitamin D3 and calcium, lumbar and femoral BMD increased significantly (lumbar spine: +0.8%, p = 0.04 versus year 1; femoral neck: +0.1%, p = 0.05 versus year 1), whereas controls continued to lose bone (intervention group versus control group: lumbar spine, p = 0.03; femoral neck, p = 0.05). CONCLUSIONS: Supplementation with oral vitamin D3 and calcium during winter prevents seasonal changes in bone turnover and bone loss in healthy adults. It seems conceivable that annually recurring cycles of low vitamin D and mild secondary hyperparathyroidism during the winter months contributes, at least in part and over many years, to age-related bone loss. Supplementation with low-dose oral vitamin D3 and calcium during winter may be an efficient and inexpensive strategy for the primary prevention of bone loss in northern latitudes.

Absorptiometry, Photon↗

Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women.

Long-term vitamin D and calcium supplementation is effective in reducing nonvertebral fractures in elderly people. Increased bone fragility caused by secondary hyperparathyroidism (sHPT) and impaired balance are known risk factors for hip fractures. The hypothesis is that short-term therapy with calcium and vitamin D may improve body sway as well as sHPT more effectively than calcium monotherapy. The effects of 8 weeks of supplementation with vitamin D (cholecalciferol) and calcium on body sway and biochemical measures of bone metabolism were measured. The sample consisted of 148 women (mean [+/-SD] age, 74 +/- 1 years) with a 25-hydroxycholecalciferol level below 50 nmol/liter. They received either 1200 mg of calcium plus 800 IU of vitamin D or 1200 mg of calcium per day. We measured intact parathyroid hormone (PTH), markers of bone turnover, and body sway before and after treatment. Falls and fractures among the participants were followed over a 1-year period. Compared with calcium mono, supplementation with vitamin D and calcium resulted in an increase in serum 25-hydroxyvitamin D of 72% (p < 0.0001), a decrease in the serum PTH of 18% ( p = 0.0432), and a decrease in body sway of 9% (p = 0.0435). The mean number of falls per subject during a 1-year follow-up period was 0.45 for the calcium mono group and 0.24 for the calcium and vitamin D group (p = 0.0346). Short-term supplementation with vitamin D and calcium improves sHPT and body sway and therefore may prevent falls and subsequent nonvertebral fractures in elderly women.

Aged↗

Serum levels of intact parathyroid hormone in elderly patients with hip fracture living at home.

The serum levels of intact parathyroid hormone and cholecalciferol metabolites have been measured in patients with hip fracture above 70 years of age admitted to hospital from home-living conditions and compared with serum levels in age- and sex-matched home-living control subjects. It was found that patients with hip fracture had significantly lower levels of calcidiol (29.7 +/- 15.9 vs 46.0 +/- 27.8 nmol/l) and calcitriol (63.6 +/- 25.0 vs 91.1 +/- 39.5 pmol/l) with no difference in serum levels of intact parathyroid hormone (4.7 +/- 2.1 vs 5.3 +/- 3.3 pmol/l). The data suggest that secondary hyperparathyroidism is not an important risk factor in our population of patients with hip fracture.

Aged↗

Long-term vitamin D3 supplementation may have adverse effects on serum lipids during postmenopausal hormone replacement therapy.

OBJECTIVE: The positive short-term effects of postmenopausal hormone replacement therapy (HRT) on serum lipids are well known, but it has been suggested that they vanish with time. Cholecalciferol (vitamin D3) is widely used to prevent postmenopausal osteoporosis but the influence of vitamin D3 on serum lipids is poorly known. The long-term effects of HRT and vitamin D3 on the concentrations of serum lipids were studied in a population-based prospective 3-year study. DESIGN AND METHODS: 464 women were randomized into four treatment groups: (i) HRT (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate), (ii) Vit D3 (vitamin D3 300 IU/day), (iii) HRT+Vit D3 (both as above), (iv) placebo (calcium lactate 500 mg/day). RESULTS: 320 women completed the study. After three years of treatment, serum concentrations of low density lipoprotein (LDL) cholesterol decreased in the HRT group (10.1%, P<0.001) and the HRT+Vit D3 group (5.9%, P=0.005), increased in the Vit D3 group (4.1%, P=0.035) but remained unchanged in the placebo group. The concentrations of total cholesterol decreased by 5.8% in the HRT group (P<0.001) and by 3.3% in the HRT+Vit D3 group (P=0.023), but did not change in the other two groups. Serum concentrations of high density lipoprotein (HDL) cholesterol decreased in the Vit D3 group (5.2%, P=0.001), HRT+Vit D3 group (3.7%, P=0.046), and the placebo group (4.5%, P=0.006) but did not change significantly in the HRT group. The HDL/LDL ratio increased in the HRT group (10.5%, P=0.006) and decreased in the Vit D3 group (10.5%, P<0.001) whereas no changes occurred in the other two groups. In addition, serum triglycerides increased similarly in all groups (14.0-18.8%, P<0.05-0.001). CONCLUSIONS: Our results confirm the positive long-term effect of HRT with sequential estradiol valerate and cyproterone acetate on serum lipid concentrations. In addition, the results suggest that vitamin D3 supplementation may have unfavorable effects on lipids in postmenopausal women. Pure vitamin D3 treatment was associated with increased serum LDL cholesterol. Furthermore, the beneficial effects of HRT on serum LDL cholesterol content were reduced when estradiol valerate was combined with vitamin D3. However, the relevance of these associations to cardiovascular morbidity remains to be established.

Analysis of Variance↗

Utilization of phytate and nonphytate phosphorus in chicks as affected by source and amount of vitamin D3.

Commercial and laboratory-strain crossbred chicks responded (P < .01) markedly to 1alpha-hydroxycholecalciferol (1alpha-OH D3) during the 2nd and 3rd wk of life. Bone-ash responses exceeded 50% when this compound was added at 20 microg/kg to phosphorus (P)-deficient corn-soybean meal diets containing surfeit levels (25 microg/kg) of cholecalciferol (D3). Phosphorus excretion was decreased (P < .01) and, thus, retention was increased (P < .01) when 1alpha-OH D3 was supplemented. A P-deficient (.10% P) casein-amino acid purified diet, devoid of D3, was used to determine whether 15 microg/kg of D3 was sufficient to facilitate optimal absorption of the nonphytate P contained in this diet. Bone ash responded to .075% P addition (KH2PO4), and chicks fed diets with .175% nonphytate P exhibited further bone-ash responses to 15 microg/kg of D3 or 10 microg/kg 1alpha-OH D3. Higher levels of either of these D3 compounds did not produce additional responses. This suggested that 15 to 25 microg/kg of D3 in a P-deficient corn-soybean meal diet (.28% phytate P and .14% nonphytate P) is more than adequate to facilitate optimal absorption of the nonphytate P present in the diet. A P-deficient casein-dextrose diet (.13% nonphytate P and 15 microg/kg D3) was fed in the final chick assay, and chicks fed this diet did not show bone ash responses to 1alpha-OH D3 or to microbial-derived phytase (1,470 units/kg). Thus, with P-deficient corn-soybean meal diets containing at least 15 microg D3/kg, 1alpha-OH D3 supplementation markedly increased weight gain and bone ash because it increased the utilization of phytate P.

Animals↗

Intestinal calcium transfer and alkaline phosphatase activity in relation with vitamin D and glucide diet.

For four weeks after weaning, rats were fed either on a diet without any calcium utilization factors (-D) or on the same diet with cholecalciferol (+D) or sorbitol (S). In the -D group, blood calcium levels decreased whilst alkaline phosphatase activities in blood and bone were increased. For +D and S groups, these parameters were normal. Using everted or in situ ligatured loops, calcium transfer from a CaCl2 + 45Ca solution was measured in the duodenum, the jejunum and in the ileum. Alkaline phosphatase activity from these regions was also measured. For the three diets and for all regions of the intestine, there was a good correlation between calcium transfer and phosphatase activity. These values were higher in the duodenum than in the ileum or jejunum, and also higher in the ileum in the +D group than in the -D and S groups although this was not significant. These low levels in the S group which were, sometimes, even lower than those seen in the -D group contrasted with blood and bone levels of alkaline phosphatase, which were normal for the S and +D groups. There was also a discrepancy between the low values found for both phosphatase activity and calcium transfer in rats S in the experiments where the calcium transfer assay was carried out in calcium solution and those found in experiments were both calcium and carbohydrate were present. In the latter, enhanced levels of intestinal phosphatase activity were observed, as well as a marked, albeit delayed, increase in intestinal calcium transfer. Onset latency and rapid offset are reminiscent of induction of bacterial enzymes by carbohydrates.

Alkaline Phosphatase↗

Fat-soluble and water-soluble vitamin contents of breast milk from Japanese women.

To determine the concentrations of fat-soluble and water-soluble vitamins in the maternal milk of Japanese women, we collected human milk samples from more than 4,000 mothers living throughout Japan between December 1998 and September 1999, and defined as group A the 691 samples among these that met the following conditions: breast milk of mothers who were under 40 y of age, who did not smoke habitually and/or use vitamin supplements, and whose babies showed no symptoms of atopy and had birth weights of 2.5 kg or more. We then analyzed the contents of vitamins individually. Large differences were observed among the contents of individual human milk samples. The mean contents of each component were as follows: vitamin A, 159.0 +/- 95.2 IU/100 mL; vitamin E, 0.325 +/- 0.165 alpha-TE mg/100mL; vitamin D3 (cholecalciferol), 8.0 +/- 10.7 ng/100mL; vitamin B1 (thiamin), 12.3 +/- 3.2 microg/100 mL; vitamin B2, 38.4 +/- 12.7 microg/100 mL; vitamin B6, 5.7 +/- 2.5 microg/100 mL; vitamin B12, 0.04 +/- 0.02 microg/100 mL; vitamin C, 5.1 +/- 1.9 mg/100 mL; biotin, 0.50 +/- 0.23 microg/100 mL; choline, 9.2 +/- 1.8 mg/100 mL; folic acid, 6.2 +/- 2.9 microg/100 mL; inositol, 12.6 +/- 3.6 mg/100 mL; niacin (nicotinamide), 32.9 +/- 20.4 microg/100 mL and pantothenic acid, 0.27 +/- 0.09 mg/100 mL. The concentrations of derivatives and/or related compounds of vitamin A (retinol, beta-carotene), vitamin E (alpha-, beta-, gamma-, and delta-tocopherol), and B2 (riboflavin, FMN, and FAD) were determined separately. The contents of each were found to vary greatly as the duration of lactation increased. The present results indicate that it is necessary to evaluate individual differences in human milk in order to perform valid research regarding infant formula.

Ascorbic Acid↗

Uptake of [3H]vitamin D3 from low and high density lipoproteins by cultured human fibroblasts.

The plasma distribution and cellular uptake of [3H]vitamin D3 was studied in vitro using cultured human fibroblasts. Incubation of [3H]vitamin D3 (cholecalciferol) with plasma followed by sequential ultracentrifugal fractionation of the lipoproteins indicated that 2-4% of the radioactivity associated with the very low density lipoprotein (VLDL), 12% with low density lipoprotein (LDL), and approximately 60% with the high density lipoprotein (HDL). The remaining radioactivity, 25%, was associated with the sedimented plasma fractions. By comparison, an average of 86% of the radioactivity from [3H]1,25-dihydroxycholecalciferol associated with the sedimented plasma fractions. The uptake of [3H]vitamin D3 from plasma, LDL, or HDL was studied in cultured human cells; uptake by normal fibroblasts was greatest from LDL and least from plasma. The cellular association of vitamin D3 was time, concentration, and temperature dependent. At a concentration of 50 micrograms LDL/ml of medium, the uptake of [3H]vitamin D3 from LDL at 37 degrees C was rapid and reached a maximum at approximately 4 hr; it was slower from HDL but continued to increase slowly up to 24 hr. The significance of these in vitro findings is uncertain since much of the vitamin D3 absorbed from the intestine reportedly associates with chylomicrons and is rapidly taken up by the liver.

Cells, Cultured↗

Intestinal lead and calcium absorption: effect of 1,25-dihydroxycholecalciferol and lead status.

This study was designed to investigate, in some detail, the relative effects of the hormonal form of vitamin D (1,25-dihydroxycholecalciferol) on duodenal Pb and Ca absorption as a function of dietary Pb level. When cholecalciferol-deficient chicks were chronically repleted with physiologic levels of 1,25-dihydroxycholecalciferol (1,25(OH)2D3), as the sole source of the vitamin, 203Pb and 47Ca absorption were enhanced over 4- and 8-fold, respectively. Ingestion of Pb during the repletion period had no significant effect on the intestinal Ca absorption response to 1,25-(OH)2D3 even at a very high dietary Pb level. The efficiency of intestinal 203Pb absorption was, however, significantly diminished by dietary Pb, in an apparent dose-dependent fashion. The results indicate that the extent to which systemic Ca homeostatic mechanisms influence intestinal Pb absorption is dependent, in large part, on Pb status.

Alkaline Phosphatase↗

Effects of feeding graded levels of vitamin D3 on egg shell pimpling in aged hens.

Pimpled egg shells are one of the various types of egg shell problems in the industry today. In this study, graded levels of vitamin D3 (D3) (0, 138, 275, 550, 2200, 22,000, 44,000, and 88,000 ICU of D3/kg of feed) were fed in a corn-soy ration to Single Comb White Leghorn hens (78 weeks of age), randomly assigned to one of the eight treatments. Feed consumption, egg production, egg weight, egg specific gravity, and pimple score were determined at weekly or biweekly intervals for a 10-week period. At termination of the experiment, calcium, sodium, potassium, and ash content of the uterus and serum calcium levels were assayed. Results showed that a significant (P less than .05) linear increase in pimple score, uterine ash, and serum calcium occurred as dietary levels of D3 increased. Egg production and egg specific gravity were correlated to D3 level in a quadratic fashion. Uterine sodium levels declined with increased D3 in the diet, while potassium values showed no differences. Calcium levels of uterine tissue tended to increase with increased D3. The lowest (0 ICU/kg) and highest level of D3 (88,000 ICU/kg) significantly decreased feed consumption. It was concluded that egg shell pimpling is directly related to level of cholecalciferol (D3) in the diet.

Aging↗

Effect of dietary aluminum and vitamin D interaction on growth and calcium and phosphorus metabolism of broiler chicks.

The interaction of dietary aluminum (as aluminum sulfate) and vitamin D on growth performance and calcium and phosphorus metabolism was investigated using male broiler chicks. A corn-soybean broiler starter diet, containing .88% Ca and .45% available P and without added cholecalciferol (vitamin D3), was fed with 0 or .2% Al and with 0, 100, or 200 ICU of vitamin D3/kg of diet in a complete factorial arrangement. Four replicate cages of 10 chicks, 1 day of age, were assigned to each dietary treatment. Average body weight gain (328 versus 545 g), feed intake (611 versus 784 g), gain:feed (.54 versus .68), and plasma inorganic P (4.2 versus 6.7 mg/dL) were significantly reduced (P < .05) in chicks fed diets with .2% Al, compared with those fed 0% Al. These four variables were improved by increasing the level of vitamin D3 in the diet from 0 to 100 ICU/kg. However, further improvements were not obtained by elevating the vitamin D3 level to 200 ICU/kg. There were significant interactions of Al and vitamin D3 on gain, feed intake, and gain:feed, but not on plasma P. Gain and feed intake were significantly decreased by Al at each level of vitamin D3. Plasma total Ca was significantly increased by vitamin D3, but was unaffected by Al. Increasing the level of dietary vitamin D3 did not completely alleviate the negative effects of Al.

Aluminum↗