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At least 19 recordsLinked to original sources
PubMed2006

Associations between vitamin D, vitamin D receptor gene and the androgen receptor gene with colon and rectal cancer.

The transcriptional activity of the vitamin D receptor (VDR) gene is regulated, at least in part, by the androgen receptor (AR) gene. We evaluate how the number of polyglutamine (CAG) repeats of the AR gene influence colorectal cancer in conjunction with vitamin D, sunshine exposure and VDR. Studies of colon (1,580 cases and 1,968 controls) and rectal (797 cases and 1,016 controls) cancer were used. Vitamin D intake and average hours of sunshine exposure interacted with AR genotype in men. Men with low vitamin D intake or low levels of sunshine exposure who had 23+ CAG repeats of the AR gene had the greatest risk of colon cancer. ORs for men with 23 or more CAG repeats of the AR gene and in the lowest tertile of vitamin D intake or sunshine exposure were 1.71 (95% CI 1.14, 2.56) and 1.51 (95% CI 1.09, 2.09). Men with high levels of sunshine exposure were at reduced risk of developing rectal cancer if they had 23 or more CAG repeats (OR 0.62 95% CI 0.39, 0.97) than if they had fewer than 23 CAG repeats. The FF genotype of the Fok1 VDR gene was associated with reduced risk of colon cancer among women with any allele of 23+ CAG repeats (OR 0.62 95% CI 0.44, 0.88), whereas men with the LL/bb VDR genotypes were at reduced risk of rectal cancer if they also had 23+ CAG repeats (OR 0.71 95% CI 0.48, 1.05) relative to men with fewer than 23 CAG repeats of the AR gene. These data provide support for the role of vitamin D and sunshine exposure in the etiology of colorectal cancer and suggest that AR gene may modulate the association.

Adult↗
PubMed1981

[New findings on the metabolism and importance of the D vitamins, with special reference to the use of vitamin D].

Animal-experimental examinations show that the peroral or intramuscular application of a high dose of vitamin D2 or of D3 leads to a toxic effect of these compounds on the osteocytes and that the hypercalcaemia evoked by this is mainly to be traced back to an increased deliberation of calcium from the bones. After application of a larger dose of vitamin D the activation mechanism in the liver and in the kidneys is much inhibited for several weeks so that no formation of 1,25-hydroxy-vitamin-D takes place; consequently, no furthering effect on the mineralisation of the bones is performed. Therefore, it is recommended to use physiological doses in the prevention of rachitis (500-1,000 IU a day). During the pregnancy the activity of the enzymes which participate in the activation of the D-vitamins increases in the liver and the kidneys. The kidneys of the fetuses are able to form 1,25-hydroxy-vitamin-D. Vitamin D and 25-hydroxy-vitamin-D transgress through the placenta into the fetuses. Due to the adaptation mentioned and the increased formation of 1,25-hydroxy-vitamin-D the absorption of calcium and phosphate increases during pregnancy. Recent pathobiochemical knowledge concerning the metabolism of the D-vitamins in several diseases are described.

Bone and Bones↗
PubMed1995

Seasonal variation in vitamin D, vitamin D-binding protein, and dehydroepiandrosterone: risk of prostate cancer in black and white men.

Our previous study provided evidence that higher serum levels of the active form of vitamin D, 1,25-dihydroxyvitamin D (1, 25-D), might possibly slow the progression of subclinical to clinically significant prostate cancer in both black and white men, especially after age 57. This paper extends the prior study by contrasting seasonal variation in 1,25-D and its precursor, 25-hydroxyvitamin D (25-D), in case and control subjects. In addition, the risk of prostate cancer is related to serum levels of vitamin D-binding protein (VDBP) and total dehydroepiandrosterone and to polymorphic variation in VDBP. The expected elevated summer levels of 25-D were seen in case and control subjects and, as expected, 1,25-D did not vary throughout the year in the control subjects. Unexpectedly, lower case levels of 1,25-D were limited largely to the summer months (P = 0.01) in both black and white cases and to cases greater than or equal to the median age of 57 years. Levels of VDBP and dehydroepiandrosterone and the frequencies of VDBP polymorphisms were similar in case and control subjects, although striking differences were seen in allelic frequencies in black and white men. These observations provide additional evidence that vitamin D metabolism may impact the risk of prostate cancer.

Adult↗
PubMed1998

[D-vitamin and vitamin D deficiency among Asian immigrants].

Vitamin D deficiency, often complicated by osteomalacia, among Asian immigrants (especially females) is now also recognized in the Nordic countries. The article reviews the history of vitamin D featuring its discovery as well as a contemporary perspective, and describes the complex etiology of the disease. The symptoms, diagnostic approach and recommended treatment are also summarized.

Asia↗
PubMed1995

[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↗
PubMed2004

Micronutrients and the risk of type 1 diabetes: vitamin D, vitamin E, and nicotinamide.

Evidence from animal experiments and human observational studies suggests that some dietary micronutrients may protect against the development of type 1 diabetes. The most promising data so far have been obtained for a beneficial role of vitamin D. Beneficial effects of vitamin E (or other antioxidants) in diabetes development remain hypothetical. Despite plausible theoretical background evidence from animal experiments and supportive data from pilot studies, randomized, controlled trials using nicotinamide have not provided any evidence for a beneficial effect.

Animals↗
PubMed1982

Inhibition of the in vitro growth of Plasmodium falciparum by D vitamins and vitamin D-3 derivatives.

D vitamins are effective inhibitors of the in vitro intraerythrocytic growth of Plasmodium falciparum. Disappearance of the parasitemia was observed after 48 h contact between infected cells and 5 x 10(-6) M 1 alpha-hydroxycholecalciferol, 5 x 10(-5) M 25-hydroxycholecalciferol (25-OH-D-3), 1 alpha, 25-dihydroxycholecalciferol or 2.5 x 10(-4) vitamin D-2 and D-3. A 48 h pretreatment of healthy erythrocytes with 5 x 10(-5) M 25-OH-D-3 did not change their susceptibility to invasion by the parasite and their ability to support the growth of P. falciparum. Ionomycin, a calcium ionophore, and EGTA prevented parasite development at concentrations greater than 2 x 10(-7) M and 4 x 10(-4) M, respectively, but did not antagonize the inhibitory activity of 25-OH-D-3. Addition of 25-OH-D-3 for 12 or 24 h duration to synchronized cultures, showed that the drug had a schizonticidal action, but was without effect when parasites were in the ring form.

Animals↗
PubMed1995

[New fluorogenic dienophile: synthesis, reaction with vitamin D, vitamin A and microcystins, and application to fluorometric assays].

We designed and synthesized a new sensitive and highly reactive fluorogenic reagent (1a, DMEQ-TAD) targeting a conjugated diene. DMEQ-TAD reacted quantitatively with major vitamin D metabolites and synthetic analogs under a variety of conditions to yield the corresponding 6,19-cycloadducts as a mixture of the C(6) epimers. The stereochemistry of the adducts was determined by their CD spectra on the basis of the exciton chirality method. The fluorescent products can be quantified linearly down to 10 fmol by HPLC. The new fluorometric method was successfully used in the assays of 25-OHD3, 24,25-(OH)2D3 and 25,26-(OH)2D3 in the human plasma. The method was proved to be reliable and precise compared with the HPLC-UV assay method. Reactions of DMEQ-TAD with retinoic acid (21a) and its geometrical isomers (21b-d) having a conjugated pentaene system afforded 7,10-adducts (24a-d) as major products together with 5,8-adducts (26a-d) in about 9:1 ratio (70-95% yield) except for the 9Z-isomer (21e) which gave only a 5,8,11,14-bis-adduct (27). DMEQ-TAD reacted with microcystins LR, YR and RR, at the conjugated diene part to yield 4,7-cycloadducts as a pair of epimers in good yield.

Fluorescent Dyes↗
PubMed2000

Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis.

BACKGROUND: Due to their known effects on bone metabolism, Vitamin D and related compounds have been proposed for the prevention of osteoporosis and fractures. OBJECTIVES: To determine the effects of supplementation with Vitamin D or a Vitamin D analogue in the prevention of fractures of the axial and appendicular skeleton in elderly men or women with involutional or post-menopausal osteoporosis. SEARCH STRATEGY: We searched MEDLINE, EMBASE, BIOSIS, CINAHL, HealthPLAN, Dissertation Abstracts, Index to UK Theses, Current Contents, and bibliographies of identified trials and reviews. Trials were also obtained from the Cochrane Musculoskeletal Injuries Group trials register. Date of the most recent search: December 1995. SELECTION CRITERIA: Any randomised or quasi-randomised trial which compared Vitamin D or a Vitamin D analogue, either alone or in combination with calcium supplementation, with a placebo, no intervention, or the administration of calcium supplements, with fracture as an outcome, in elderly men or women with involutional or post-menopausal osteoporosis. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality, by use of a seven item scale, and extracted data. Additional information was sought from trialists. Where possible the data were pooled. MAIN RESULTS: Fourteen trials recording 13 different comparisons were included. In the only trial of Vitamin D alone, protection against hip fracture was not confirmed. Two regimens, each represented by one large trial, which showed limited evidence of efficacy in reducing the incidence of hip or other appendicular skeleton fractures were: 1) Oral Vitamin D when accompanied by calcium supplementation. 2) 1,25 dihydroxy Vitamin D (calcitriol). This appeared more effective than calcium in a direct comparison. Regimens showing limited evidence of efficacy in reducing the incidence of vertebral deformity were: 1) 1,25 dihydroxy Vitamin D (calcitriol), which appeared more effective than calcium in one large trial, and more effective than placebo from pooled results of two small trials. 2) Oral 1-alpha hydroxy Vitamin D (alfacalcidol), when administered with calcium supplements (two small trials, which lacked power to confirm a possible effect). Hypercalcaemia and gastro-intestinal symptoms, reported in less than 5% of participants, were slightly more common when Vitamin D analogues were taken. However, the risk of death was marginally less. REVIEWER'S CONCLUSIONS: Uncertainty remains about the efficacy of regimens which include Vitamin D or its analogues in fracture prevention. Particularly if co-supplementation of calcium is required, significant cost differences are likely to exist between regimens. Further randomised trials with economic evaluation are desirable before community fracture prevention programmes employing Vitamin D supplementation can be confidently introduced.

Aged↗
PubMed2004

Osteoblast differentiation and control by vitamin D and vitamin D metabolites.

Vitamin D plays a major role in the regulation of mineral homeostasis and affects bone metabolism. Most effects of vitamin D have been attributed to the 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) metabolite. 1,25-(OH)2D3 regulates its own metabolism by mediating the 24-hydroxylase activity, which leads to the degradation of the molecule but intermediate products (24-hydroxylated forms of 25-(OH)D3 and 1,25-(OH)2D3) may be biologically active too. In this review we describe the direct effects of 1,25-(OH)2D3 on osteoblast function (proliferation, apoptosis, expression of specific bone proteins and growth factors) and mineralization. The role of the vitamin D receptor, vitamin D metabolism and the effects on osteoblast gene expression are documented. Vitamin D acts often in interaction with factors. The effects of 1,25-(OH)2D3 on the expression of growth factors and its interaction with growth factors and hormones in the control of osteoblast differentiation are discussed. Finally, the current status of the development of synthetic vitamin D analogs with bone anabolic characteristics for therapeutic application is described.

Animals↗
PubMedDate not supplied

Three-dimensional structure-function relationship of vitamin D and vitamin D receptor model.

On the basis of conformational analysis of the vitamin D side chain and studies using conformationally restricted synthetic vitamin D analogs, we have suggested the active space region concept of vitamin D: The vitamin D side-chain region was grouped into four regions (A, G, EA and EG) and the A and EA regions were suggested to be important for vitamin D actions. We extended our theory to known highly potent vitamin D analogs and found a new region F. The analogs which occupy the F region have such modifications as 22-oxa, 22-ene, 16-ene and 18-nor. Altogether, the following relationship between the space region and activity was found: Affinity for vitamin D receptor (VDR), EA > A> F > G > EG; Affinity for vitamin D binding protein (DBP), A >> G,EA,EG; Target gene transactivation, EA > F > A > EG > or = G; Cell differentiation, EA > F > A > EG > or = G; Bone calcium mobilization, EA > GA > F > or = EG; Intestinal calcium absorption, EA = A > or = G >> EG. We modeled the 3D structure of VDR-LBD (ligand binding domain) using hRARgamma as a template, to develop our structure-function theory into a theory involving VDR. 1alpha,25(OH)(2)D(3) was docked into the ligand binding pocket of the VDR with the side chain heading the wide cavity at the H-11 site, the A-ring toward the narrow beta-turn site, and the beta-face of the CD ring facing H3. Amino acid residues forming hydrogen bonds with the 1alpha- and 25-OH groups were specified: S237 and R274 forming a pincer type hydrogen-bond for the 1alpha-OH and H397 for the 25-OH. Mutants of several amino acid residues that are hydrogen-bond candidates were prepared and their biologic properties were evaluated. All of our mutation results together with known mutation data support our VDR model docked with the natural ligand.

Animals↗
PubMed2005

Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis.

BACKGROUND: Vitamin D and related compounds have been used to prevent fractures. OBJECTIVES: To determine the effects of vitamin D or analogues, with or without calcium, in the prevention of fractures in older people. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group trials register, the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005), MEDLINE, EMBASE, CINAHL, and reference lists of articles. Most recent search: March 2005. SELECTION CRITERIA: Randomised or quasi-randomised trials comparing vitamin D or an analogue, alone or with calcium, against placebo, no intervention, or calcium, reporting fracture outcomes, in older people. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality, and extracted data. Data were pooled, where admissible, using the fixed-effect model, or random-effects model if the relative risks were heterogeneous. MAIN RESULTS: Vitamin D alone showed no statistically significant effect on hip fracture (seven trials, 18,668 participants, RR 1.17, 95% CI 0.98 to 1.41), vertebral fracture (four trials, 5698 participants, RR (random effects) 1.13, 95% CI 0.50 to 2.55) or any new fracture (eight trials, 18,903 participants, RR 0.99, 95% CI 0.91 to 1.09). Vitamin D with calcium marginally reduced hip fractures (seven trials, 10,376 participants, RR 0.81, 95% CI 0.68 to 0.96), non-vertebral fractures (seven trials, 10,376 participants, RR 0.87, 95% CI 0.78 to 0.97), but there was no evidence of effect of vitamin D with calcium on vertebral fractures. The effect appeared to be restricted to those living in institutional care. Hypercalcaemia was more common when vitamin D or its analogues was given compared with placebo or calcium (14 trials, 8035 participants, RR 2.38, 95% CI 1.52 to 3.71). The risk was particularly high with calcitriol (three trials, 742 participants, RR 14.94, 95% CI 2.95 to 75.61). There was no evidence that vitamin D increased gastro-intestinal symptoms (seven trials, 10,188 participants, RR (random effects) 1.03, 95% CI 0.79 to 1.36) or renal disease (nine trials, 10,107 participants, RR 0.80, 95% CI 0.34 to 1.87). AUTHORS' CONCLUSIONS: Frail older people confined to institutions may sustain fewer hip and other non-vertebral fractures if given vitamin D with calcium supplements. Effectiveness of vitamin D alone in fracture prevention is unclear. There is no evidence of advantage of analogues of vitamin D compared with vitamin D. Calcitriol may be associated with an increased incidence of adverse effects. Dose, frequency, and route of administration of vitamin D in older people require further investigation.

Aged↗
PubMed1993

Exogenous calciferol (vitamin D) and vitamin D endocrine status among elderly nursing home residents in the New York City area.

OBJECTIVE: To determine the role and relative importance of sources of exogenous calciferol (vitamin D) in maintaining vitamin D endocrine status in the mid-winter and early spring in a representative sample of institutionalized elderly persons in the New York City area. DESIGN: Cross-sectional survey. SETTING: A privately-run urban nursing home and the long-term care unit of a suburban public hospital. PARTICIPANTS: Residents aged 60 years and older scheduled for a routine annual physical examination and an additional group of individuals ascertained by random sampling. Those with a history of anti-convulsant or glucocorticoid use, liver disease, chronic renal disease (or serum creatinine > 1.5 mg/dL), parathyroid disease, Paget's disease, gastric surgery, or pharmacological vitamin D use were excluded. Of 301 sampled individuals, 221 were found eligible to participate, and 109 were successfully enrolled. RESULTS: The average vitamin D intake was 379 IU/day (range 55-1006 IU/day) and total vitamin D intake was below the Recommended Dietary Allowance in 16% of subjects. Fifty percent of total vitamin D intake came from fortified milk, and 26% came from vitamin supplements. Vitamin supplement use was not associated with low dietary intake. Among subjects taking a supplement containing 400 IU/day, none had serum calcidiol levels below 15 ng/mL, while among subjects with vitamin D intake between 200 and 400 IU/day, 46% had serum calcidiol levels below 15 ng/mL and 14% had calcidiol levels below 10 ng/mL. Vitamin D intake from non-supplement sources (but not from supplements) appeared to have a negative association with serum calcitriol levels. CONCLUSIONS: Many nursing home residents may require vitamin supplements in order to achieve optimal levels of calciferol replacement. The choice of a vehicle for calciferol replacement may affect calcitriol levels.

Aged↗
PubMed2003

Hypovitaminosis D and vitamin D deficiency in exclusively breast-feeding infants and their mothers in summer: a justification for vitamin D supplementation of breast-feeding infants.

OBJECTIVE: To determine the prevalence of hypovitaminosis D in exclusively breast-feeding infants and their mothers in a community where maternal sunshine exposure is low. STUDY DESIGN: Serum levels of calcium, phosphate, alkaline phosphatase, 25-hydroxy vitamin D (25-OHD), and intact parathyroid hormone were measured in 90 unsupplemented healthy term breast-feeding Arab/South Asian infants and their mothers in summer. Maternal dietary vitamin D intake was also estimated. RESULTS: The median age of infants was 6 weeks. The median serum 25-OHD concentrations in mothers (8.6 ng/mL) and infants (4.6 ng/mL) were low, and 61% of the mothers and 82% of the 78 infants tested had hypovitaminosis D (serum 25-OHD <10 ng/mL). The infants with hypovitaminosis D had elevated serum alkaline phosphatase and a tendency to higher serum intact parathyroid hormone levels. The average daily maternal vitamin D intake from commercial milk was 88 IU. CONCLUSIONS: Hypovitaminosis D is common in summer in exclusively breast-feeding infants and their mothers. The results provide justification for vitamin D supplementation of breast-feeding infants and mothers in the United Arab Emirates. Low vitamin D intake probably contributed to low maternal vitamin D status.

25-Hydroxyvitamin D 2↗
PubMed2002

Use and indication of vitamin D and vitamin D analogues in patients with renal bone disease.

Vitamin D plays a pivotal role in the pathogenesis and treatment of renal bone disease. Vitamin D levels decline in the early phase of renal failure, however, through a compensatory mechanism parathyroid hormone (PTH) stimulates the production of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3), calcitriol) to return it to normal circulating concentrations. Nevertheless, resistance to calcitriol is observed and may be related to the decreased presence of the heterodimeric, DNA-binding partner for the vitamin D receptor protein. In end-stage kidney disease (ESKD) the circulating levels of calcitriol are invariably low. The indications of vitamin D therapy are the replacement of the missing hormone vs suppression of hyperparathyroidism (HPT) requiring daily low-dose oral vs intermittent 'pulse' or oral administration. However, this therapy must be accompanied by careful patient monitoring to avoid hypercalcaemia and low bone turnover. Low bone turnover is not merely a histologic entity, but a clinical condition associated with a high risk of extraosseous calcifications, in particular in the cardiovascular system, leading to increased morbidity. Thus, determination of bone turnover in patients with ESKD is essential. Bone biopsy is the gold standard to assess bone turnover, however, it is not always available and nephrologists rely on PTH levels. The intact PTH assay measures PTH(1-84) and large C-PTH fragments, which may antagonize the PTH(1-84) effects on bone. An assay that measures exclusively PTH(1-84) has recently become available and a calculated PTH(1-84)/C-PTH fragment ratio has been shown to be the best predictor of bone turnover in patients with ESKD not treated with vitamin D or with other medications known to affect bone metabolism. 1,25-dihydroxy-22-oxavitamin D(3) (22-oxacalcitriol, OCT) is a vitamin D analogue that could control serum PTH concentrations without deleterious effects on bone.

Chronic Kidney Disease-Mineral and Bone Disorder↗