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Improvement in glucose tolerance and beta-cell function in a patient with vitamin D deficiency during treatment with vitamin D.

Glucose metabolism was studied in a patient with vitamin D deficiency during its treatment with small doses of vitamin D. A continuous infusion of glucose test was performed to assess glucose tolerance and insulin sensitivity and beta-cell function were derived by mathematical modelling. Fasting glucose was 5.6 mmol/l and achieved glucose after the infusion was 10.4 mmol/l confirming diabetes. The test was repeated 0.5, 1, 3 and 5 months after starting treatment. Serum calcium increased glucose intolerance from 1.76 to 2.0, 2.08, 1.96 and 2.0 mmol/l, respectively; vitamin D reached supraphysiological levels initially and returned to normal levels, and parathyroid hormone levels were normalized. Her weight did not change during treatment. Glucose tolerance improved during treatment and achieved glucose was 9.4, 8.6, 9.2 and 9.0 mmol/l at 0.5, 1, 3 and 5 months, respectively; insulin sensitivity did not change. Beta-cell function improved from 101% at diagnosis to 126%, 147%, 173% and 198% at 0.5, 1, 3 and 5 months, respectively. Improvement in beta-cell function and consequently in glucose tolerance is likely to have been due to correction of hypocalcaemia, vitamin D deficiency and secondary hyperparathyroidism.

Aged↗

Intestinal phosphate absorption: influence of vitamin D and non-vitamin D factors.

The transport of inorganic phosphate (P) was measured in the absence of electrochemical gradients across rat jejunum in vitro. Active P absorption was demonstrated in young, vitamin D-deficient (-D) rats, whereas active P secretion was found in normal, non-vitamin D-deficient adult rats, suggesting regulation of intestinal P transport by age-dependent but vitamin D-independent mechanisms. 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] stimulated mucosal-to-serosal P flux (Jm----s) without affecting serosal-to-mucosal P flux (Js----m), causing further increases in net P absorption (Jnet) in -D rats and reduction in net P secretion in normal adult rats, confirming a previously described role of this hormone on P absorption. We then examined the effect of increasing extracellular (buffer) P concentration [P] on this 1,25(OH)2D3-stimulated active P absorption in jejunum from -D rats. At [P] of 0.024, 0.24, and 2.4 mM, 1,25(OH)2D3 consistently stimulated Jm----s without affecting Js----m, causing an increment in Jnet. At 7.5 mM [P], however, this Jm----s stimulatory effect of 1,25(OH)2D3 was no longer observed. Moreover, at this [P] the Js----m exceeded Jm----s in both -D and 1,25(OH)2D3-repleted rats, converting the active P absorption into active P secretion in both treatment groups. These observations suggest the participation of local mechanisms, such as the ambient [P] of the transporting enterocytes, in the regulation of intestinal P absorption. Finally, the influence of dietary P deprivation on P absorption was studied in -D rats, with or without either vitamin D3 or 1,25(OH)2D3 repletion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Vitamin-D-fortified liquid milk--a highly effective method of vitamin D administration for house-bound and institutionalised elderly.

The aim of the study was to assess the efficacy and acceptability of vitamin-D-fortified liquid milk in the management of hypovitaminosis D in an elderly institutionalised population. The design was a single-blind randomised controlled study. In phase I, patients were encouraged to drink an increased quantity of either fortified or unsupplemented milk for 3 months. In phase II, patients were continued on either fortified or on unsupplemented milk which was given as part of the everyday diet for a further 6 months with no extra encouragement of any patient to take additional amounts. Ninety-eight patients (mean age 84 years) from extended care wards at the Department of Medicine for the Elderly, St. James's Hospital, Dublin, Ireland, participated in the study. Seventy-eight patients completed phase I, and 62 completed phase II. A general biochemical screen and 25-hydroxy vitamin D measurements were performed at entry and repeated 3 and 9 months later. The average milk intake per patient in phase I was 454 ml/day in the unsupplemented group and 359 ml/day in the fortified milk group. In phase II, the average daily milk intake per patient was 235 ml in the unsupplemented milk group and 140 ml in the fortified milk group. Seventy-four patients (94%) of the total who completed phase I had serum vitamin D baseline levels below the normal range. In the fortified milk group, mean vitamin D levels rose from 2.4 to 14.80 ng/ml (p < 0.001) at the end of phase I and remained significantly elevated at 10.2 ng/ml (p < 0.001) at the end of phase II.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Prediction of bone mass density variation by bone remodeling markers in postmenopausal women with vitamin D insufficiency treated with calcium and vitamin D supplementation.

The aim of this study was to determine whether early changes in bone markers could predict long-term response in bone mineral density (BMD) after calcium (500 mg) and vitamin D (400 IU) supplementation twice daily in ambulatory elderly women with vitamin D insufficiency (25-hydroxyvitamin D, <12 ng/ml). One hundred and ninety-two women (mean age, 75 +/- 7 yr) were randomized to receive either the supplementation (n = 95) or a placebo (n = 97) in a double-blind, controlled clinical trial for 1 yr. In comparison with the placebo group, supplementation significantly increased BMD, normalized 25-hydroxyvitamin D and significantly decreased intact PTH and bone remodeling markers. The initial values of telopeptide cross-links were correlated with improvement in total body BMD [urinary N-telopeptides (NTX), r = 0.38; C-telopeptides (CTX), r = 0.32; serum CTX, r = 0.28], and the 3-month changes in the same markers were correlated with improvement in total body (urinary N-telopeptides, r = -0.29; serum CTX, r = -0.26) and vertebral BMD (CTX, r = -0.26; all P < 0.05). We concluded that short-term changes in bone resorption markers can predict long-term variations in BMD in elderly women with vitamin D insufficiency receiving calcium and vitamin D supplementation.

Aged↗

Fluorinated vitamin D analogs to probe the conformation of vitamin D in its receptor complex: 19F-NMR studies and biological activity.

To investigate vitamin D conformation, specifically the A-ring and seco-B ring parts, in its complex with the vitamin D receptor (VDR), we have previously suggested the use of 19F-NMR spectroscopy and have synthesized three fluorovitamin D derivatives to be used for the study, 4,4-difluoro-1alpha,25-dihydroxyvitamin D3 [4,4-F2-1,25-(OH)2D3, 2a], and (10Z)- and (10E)-19-fluoro-1alpha,25-dihydroxyvitamin D3 [19-F-1,25-(OH)2D3, 3a, 4a]. In this paper, we examined the 19F-NMR spectra of these and related fluorovitamin D compounds in detail. In the low temperature 19F-NMR spectra, we observed two well-separated rigid conformations of 2a (51:49) and 4a (84:16), while only one conformation was detected with 3a. The two observed conformers of 2a and 4a were respectively assigned to the known alpha- and beta-conformers formed by the flipping of the A-ring where the C(19) exocyclic methylene points to the alpha- and beta-faces. The single conformation observed for 3a was assigned to the alpha-conformer. We detected no other conformation in the 19F-NMR of all vitamin D compounds examined. The effect of solvents on the 19F chemical shifts of fluorovitamin D compounds was found to be small (less than 6.3 ppm). This was much smaller than the difference between the two A-ring conformers (13-30 ppm). Using the dynamic 1H-NMR studies of fluorovitamin D compounds, we determined the free energy of activation for the interconversion between the two conformations of 2a (9.9 kcal/mol) and 4a (10.8, 11.5 kcal/mol). Introduction of the 1alpha-hydroxyl group raised the activation energy about 1 kcal/mol. The affinity for VDR was evaluated, and the relative potency of 2a, 3a and 4a was found to be 1%, 8% and 9%, respectively, of that of 1,25-(OH)2D3 (1). Though the affinity for VDR was considerably reduced in these compounds, the ability to activate gene transcription was similar and remained in the range 30-50% of the effect of 1. This biological information in combination with the NMR properties indicates that 2a and 4a are promising probes for studying the VDR-bound A-ring conformation of vitamin D.

Binding Sites↗

[The effects of long-term intake of restricted calcium, vitamin D, and vitamin E and cadmium-added diets on various organs and bones of mice: a histological and the roentgenological study].

The toxic effects of long-term administration of cadmium (Cd) on the kidneys, liver, and hind leg bones were studied histologically and roentgenologically in 29-day-old female ICR-strain mice separated into groups variously fed 1) a commercial (calcium [1.17%], vitamin D [220IU/100g], vitamin E [10mg/100g]) diet, 2) a low Ca (0.18% diet, 3) a low Ca and low D (50IU/100g) diet, and 4) a low Ca, low D and low E (5mg/100g) diet. Though the levels of vitamin D and vitamin E were designed to be low in each diet, their amounts fulfilled the nutritional requirements. Three subgroups in each category were fed Cd at dietary concentrations of 0, 20 or 40 ppm. After 12, 18 or 24 months on these diets the mice were sacrificed. 1) In the groups fed the commercial diet containing Cd, prominent swelling of the glomerulus and thickening of the basement membrane of glomerulus were observed. This did not occur in the groups fed the commercial diet without Cd. 2) In the groups fed the Cd-added low-Ca diet the following findings were more prominent compared with the low-Ca diet group. In the kidneys, swelling of the glomerulus, hyaline casts in tubular lumina and cellular infiltration of the interstitial tissue were present. In the liver, cellular infiltration on the interstitial tissue were present. In the liver, cellular infiltration of the interstitial tissue occurred. In the hind leg bones, thinning of trabeculae and ossification of the Achilles's tendon were seen. 3) In the Cd-added low-Ca, D diet groups, there was atrophy of glomerulus, thickening of basement membrane of glomerulus, and atrophy of tubular epithelial cells in the kidneys, while in the liver, binuclate cells, anisonucleosis and enlargement of Kupffer cells were seen. In the hind leg bones, thinning of the cortex and trabeculae were present. All of these findings were more prominent in this group than in the low-Ca, group. 4) In the Cd-added low-Ca, D, E, diet groups subjects the following findings were more prominent than in the low-Ca, D, E, diet group. In the kidneys, there was swelling of glomerulus and in the liver, there were binuclate cells, anisonucleosis, and cellular infiltration into interstitial tissue. In the hind leg bones, thinning of the cortex and trabeculae, a decrease of cartilage cells and a decrease of osteocytes were seen. These histological and roentgenological changes were seen to increase in a dose-dependent manner with the amount of dietary Cd.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[The effects of long-term intake of restricted calcium, vitamin D, and vitamin E and cadmium-added diets on the bone mass of mouse femoral bone: a microdensitometrical study].

Effects of undernutrition on development of cadmium (Cd) poisoning were investigated in mice over a long experimental period ranging from 29 days to 24 months. The study was designed to examine low in calcium, low in vitamin D and low in vitamin E diets, which were considered neither to induce lesions of Ca, vitamin D and vitamin E deficiency nor in nutrition. Twenty-nine-day-old female ICR strain mice were separated into 7 groups and different diets were given to each group. Group I a commercial diet (Intact), Group II a low in Ca and low in D diet, Group III a low in Ca, low in D and low in E diet, Group IV a low in Ca, low in D and 20ppm Cd diet, Group V a low in Ca, low in D and 40ppm Cd diet, Group VI a low in Ca, low in D, low in E and 20ppm Cd diet and Group VII a low in Ca, low in D, low in E and 40ppm Cd diet. Using X-rays of the hind legs, the bone density was measured at the middle of the femur employing a densitometer; effects of the undernutrition and the cadmium-added diet on bone density were investigated referring to five indices: 1) peaks of the density of the middle of the bone cortex (h1, h2) (the maximum density of the bone cortex (h1 + h2)/2 [hmax]), 2) the lowest density of the middle of the bone marrow (h3) (the minimum density of the bone marrow [hmin]), 3) the bone cortical width (d1 + d2), 4) the bone marrow width (d) and 5) the cortical bone index (the ratio of cortical bone width to bone width. [CBI]). The long-term effects of cadmium. a) Comparisons among groups II, IV and V.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

[The effects of long-term intake of restricted calcium, vitamin D, vitamin E and cadmium-added diets on the skeletal muscles of mice: an enzyme histochemical study].

To clarify the effect of chronic cadmium exposure on muscles, 29-day-old female ICR strain mice were separated into 7 groups and various diets were given to each group. Group I a commercial diet (Intact), Group II a diet low in calcium and low in vitamin D, Group III a diet low in Ca, low in D and low in vitamin E, Group IV a low in Ca, low in D and 20ppm cadmium-added diet, Group V a low in Ca, low in D and 40ppm Cd diet, Group VI a low in Ca, low in D, low in E and 20ppm Cd diet and Group VII a low in Ca, low in D, low in E and 40ppm Cd diet. The levels of vitamin D and vitamin E were designed to be low in each diet but their amounts fulfilled the minimum nutritional requirements. The experimental period was long, ranging from 29 days to 24 months. Using a microscope, two skeletal muscles, the soleus (red muscle) and the gastrocnemius (white muscle) of mice with chronic Cd effects were observed after staining with H. E. and analyzed after enzyme histochemical reaction to ATPase. Using ATPase stain, type I muscle fibers were distinguished from type II muscle fibers. The long-term effects of cadmium. 1) Comparisons among groups II, IV and V. After 18 months it was found in group IV that myopathic muscle damage (increased random variation of fiber size [Size] and widening of interstitial tissue [Widening]) were more prominent that in group II. In group V myopathic muscle damage (Size and Widening) and type II atrophy were more prominent that in group IV. At 24 months it was found in group IV that myopathic muscle damage (Size, internal nuclei [IN] and Widening) and type I and type II atrophy were more prominent than in group II. In group V myopathic muscle damage (Size, IN and Widening) and type I and type II atrophy were more prominent than in group IV. 2) Comparisons among group III, VI and VII.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

Seasonal changes in serum vitamin A, vitamin E and beta-carotene concentrations in Japanese Black breeding cattle in Hyogo prefecture.

The influence of the season on serum vitamin A, E and beta-carotene concentrations was studied in Japanese Black breeding cattle. Blood samples were collected from 13 cows once a month for a year to determine the serum vitamin concentrations. Mean serum concentrations (+/- SE) of retinol, alpha-tocopherol and beta-carotene were 21.3 +/- 0.5 microg/dl (range 9.9 to 44.9), 215.9 +/- 8.0 microg/dl (range 59.7 to 551.6) and 67.3 +/- 5.1 microg/dl (range 10.6 to 425.2), respectively. All these concentrations were lower than the recommended levels. Serum retinol and alpha-tocopherol concentrations in summer were lower than those in winter. These results suggest that the vitamin A, E and beta-carotene status of Japanese Black breeding cows is inadequate, and feeding high quality forages or dietary vitamin supplementation during summer should be recommended.

Animals↗

Prevention of rickets and vitamin D deficiency: new guidelines for vitamin D intake.

Rickets in infants attributable to inadequate vitamin D intake and decreased exposure to sunlight continues to be reported in the United States. It is recommended that all infants, including those who are exclusively breastfed, have a minimum intake of 200 IU of vitamin D per day beginning during the first 2 months of life. In addition, it is recommended that an intake of 200 IU of vitamin D per day be continued throughout childhood and adolescence, because adequate sunlight exposure is not easily determined for a given individual. These new vitamin D intake guidelines for healthy infants and children are based on the recommendations of the National Academy of Sciences.

Adolescent↗

Renal tubular acidosis type 2 with Fanconi's syndrome, osteomalacia, osteoporosis, and secondary hyperaldosteronism in an adult consequent to vitamin D and calcium deficiency: effect of vitamin D and calcium citrate therapy.

OBJECTIVE: To describe a unique example of renal tubular acidosis type 2 (RTA 2) in conjunction with Fanconi's syndrome and osteomalacia consequent to vitamin D and calcium deficiency in an adult without underlying gastrointestinal disease. METHODS: We review the clinical, hormonal, histomorphometric, and micro-computed tomographic findings and the response to therapy with vitamin D and calcium in our patient. RESULTS: On admission, a 33-year-old African American woman had the following laboratory findings: serum ionized calcium 3.8 mg/dL (0.95 mmol/L), venous pH 7.26, bicarbonate 20 mEq/L, chloride 111 mEq/L, alkaline phosphatase 1,192 U/L (20.26 microkat/L) (normal, 40 to 136 U/L), 25-hydroxyvitamin D <5 ng/mL (<12 nmol/L) (normal, 10 to 60 ng/mL), parathyroid hormone 1,620 pg/mL (165.2 pmol/L) (normal, 10 to 60 pg/mL), aldosterone 68.4 ng/dL (1,894.7 pmol/L) (normal, 4.5 to 35.4 ng/dL), supine plasma renin activity 19.8 ng/mL per hour (5.35 ng/L per second) (normal, 0.5 to 1.8 ng/mL per hour), and aminoaciduria. A lumbar spine bone density T-score was -4.6, and a femoral neck T-score was -4.9. An undecalcified tetracycline-labeled bone biopsy specimen showed severe osteomalacia, severe osteoporosis, and peritrabecular fibrosis. A small intestinal biopsy revealed normal findings. Results of an ammonium chloride loading test and a bicarbonate infusion test were consistent with RTA 2. After 24 months of vitamin D and calcium therapy, results of serum and urine chemistry studies and bicarbonate infusion normalized. The lumbar spine T-score improved to -2.0, and the femoral neck T-score improved to -2.7. Bone biopsy specimens demonstrated resolution of the osteomalacia. CONCLUSION: Nutritional vitamin D and calcium deficiency may cause RTA 2, Fanconi's syndrome, and osteomalacia in adults as well as in children.

Acidosis, Renal Tubular↗

The role of interleukin-6 in vitamin A deficiency during Plasmodium falciparum malaria and possible consequences for vitamin A supplementation.

Kinetics of serum levels of interleukin-6 (IL-6) were studied in patients with acute Plasmodium falciparum malaria in relation to vitamin A and its binding proteins, retinol binding protein (RBP) and pre-albumin. It was found that IL-6 levels followed the rise and decrease of parasitaemia by 12 hr and correlated inversely with levels of vitamin A and its binding proteins. These data suggest that vitamin A supplementation alone might still be insufficient to restore a malaria-induced vitamin A deficiency.

Adult↗

Vitamins and minerals 4: overview of folate and the B vitamins.

Many studies have suggested that elevated homocysteine levels are an independent risk factor for cardiovascular disease, stroke and Alzheimer's disease. Lower levels of the three water-soluble vitamins--folate (folic acid), vitamin B6 and vitamin B12--are primary determinants of high blood homocysteine levels. In the fourth of an occasional series on vitamins, minerals and supplements, June Thompson looks at the role folate, in particular, may play in reducing homocysteine in the body and in protecting the body from some other diseases.

Alzheimer Disease↗

Effect of oral methionine and vitamin E on blood lipid peroxidation in vitamin B6 deficient rats.

Lipid peroxidation in blood of vitamin B6 deficient rats was significantly increased when compared to pair-fed controls. The observed increased lipid peroxidation in vitamin B6 deficiency was correlated with high levels of lipids, metal ions and low levels of antioxidants, alpha-tocopherol, ascorbic acid and reduced GSH. Supplementation of methionine or vitamin E along with the vitamin B6 deficient diet restored the levels of antioxidants to near normal and also protected against oxidative stress. However plasma TBARS level as well as total lipids were still elevated in M-B6 diet fed rats and normalized in E-B6-d rats.

Animals↗

Correlation of serum vitamin A and its transport protein (RBP) in malnourished and vitamin A deficient children.

Eighty nine children were studied for retinol (vitamin A) estimation and its transport protein--retinol-Binding Protein (RBP). Serum levels of retinol, RBP and serum protein and albumin were found to be low in children with signs of vit. A deficiency irrespective of their nutritional status. Serum levels of retinol and RBP were risen significantly almost double, after the oral and parenteral administration of vitamin A. PEM interferes with hepatic synthesis of RBP and the release of RBP from the liver depends on vitamin A. Vitamin A is a limiting factor, the presence of which is required for the release of apo-RBP from the liver.

Blood Proteins↗

Vitamin A, vitamin E, retinol binding protein (RBP), and prealbumin in digestive cancers.

The existence of a relation between vitamin A and vitamin E and human cancers is supported by epidemiologic investigations. The aim of this study is to link the level of these vitamins to those of plasmatic protein carriers like retinol binding protein (RBP) and prealbumin (TTR), in three groups of subjects: healthy patients (n = 78), polyp (n = 34) and digestive cancer patients (n = 70). A paired t-test did not reveal any significant variation in any parameter between the polyp group and controls, but did evidence a significant decrease in serum levels of retinol (p less than 2.10(-4], RBP (p less than 2.10(-4), TTR (p less than 10(-5), and alpha-tocopherol (p less than 2.10(-3), in cancer cases as against control subjects. Comparison of RBP renal clearance and retinol tissue clearance in cancer and healthy patients indicates that the decrease in circulating retinol levels cannot be attributed to an increase in peripheral consumption. The simultaneous reduction of RBP and TTR serum levels is to be considered as a sign of protein denutrition. Thus our results suggest that the decrease serum levels of vitamins A and E observed in digestive cancers are a consequence of this nutritional deficiency.

Adult↗

The diagnosis of vitamin B12 deficiency in sheep: comparison of serum vitamin B12 levels measured by a microbiological and a radioisotope dilution technique.

Serum vitamin B12 from 6 sheep fed a diet containing 0.06 mg cobalt per kg dry matter (DM) was analysed by a radioisotope dilution (RID) technique. The results were compared with values obtained by a microbiological method (Lactobacillus leichmannii - ATCC 7830) specific for "true" vitamin B12. Serum vitamin B12 concentrations were four to six times greater during the 16 weeks experimental period with the RID method as compared to the microbiological technique. During the course of the experiment, values obtained by the RID method remained superior to the threshold value (200 pg B 12/ml) of the microbiological method. This investigation indicates that the RID method is not suitable for the rapid diagnosis of vitamin B12 deficiency in subclinically cobalt-deficient sheep.

Animals↗

Comparison of the activity of the cis and trans isomer of vitamin K1 in vitamin K-deficient and coumarin anticoagulant-pretreated rats.

The cis and trans isomers of vitamin K1 have been prepared at a purity of better than 99.5% and tested for effect on plasma level of factor VII in coumarin anticoagulant-pretreated and vitamin K-deficient rats. Both isomers show activity, but in coumarin anticoagulant-pretreated animals the cis isomer has approximately 10% and in vitamin K-deficient approximately 1% of the activity of the trans isomer. The cis isomer also shows slower onset and rate of increase of the response. Reduction of the 2',3'-double bond of the phytyl side chain of either isomer to the same 2',3'-dihydro derivative of vitamin K1 leaves the activity of the trans isomer unchanged but increases the activity of the cis isomer to that of the trans isomer. The results suggest that the phytyl side chain not only serves to increase lipid solubility, but may play a more direct functional role.

Animals↗