Oral Administration Of Vitamin D3 Research Articles

Effects of intermittent overload doses of oral vitamin D3 on serum 25(OH)D concentrations and the incidence rates of fractures, falls, and mortality in elderly individuals: A systematic review and meta-analysis.

Vitamin D is commonly used to prevent and treat osteoporosis, with studies indicating its potential to reduce fractures, falls, and mortality. However, meta-analyses present inconsistent findings regarding its efficacy, particularly reflecting significant variability in data and outcomes related to various dosing regimens. In this meta-analysis, we assessed the impact of high-dose intermittent oral administration of vitamin D3 on serum 25(OH)D levels, fractures, falls, and mortality among elderly individuals. We included 14 randomized controlled trials (RCTs) and employed Review Manager 5.4 for statistical analysis. Our findings indicate that intermittent monthly administration of vitamin D3 (over 800 IU per day) significantly raised serum 25(OH)D levels at all timepoints after six months, maintaining levels above 75 nmol/L throughout the year. This regimen showed no increase in all-cause mortality, with a risk ratio (95% CI) of 0.95 (0.87-1.04). Likewise, it did not significantly reduce the risks of falls and fractures, with risk ratios of 1.02 (0.98-1.05) and 0.95 (0.87-1.04) respectively. Although one-year intermittent administration significantly increased the concentration of 25(OH)D in serum, further research is needed to determine if this method would increase the incidence of falls. Therefore, it is not recommended at this stage due to the lack of demonstrated safety in additional relevant RCTs. This study had been registered on PROSPERO (CRD42022363229).

Evaluation of the Effect of Oral Vitamin D3 Supplement on Orthodontic Tooth Movement: A Randomized Clinical Trial Study

Aim: One of the problems that orthodontists commonly face is the prolonged duration of the treatment. Therefore, it is important to find an effective method to increase the rate of orthodontic tooth movement (OTM). This study aimed to evaluate the effectiveness of oral administration of vitamin D3 on OTM rates in humans. Materials and Methods: In this randomized clinical trial study, we selected 29 healthy women aged 18–25 years who sought orthodontic treatment and required bilateral maxillary first premolar extraction. Participants were tested to measure the blood levels of vitamin D3 and, based on the outcomes, were divided into three groups: control (without vitamin D3 deficiency; N = 10), placebo ( N = 9), and experiment ( N = 10), both with vitamin D3 deficiency. Subjects of the last two groups, who were randomly assigned, received 50,000 IU (International Unit) vitamin D3 pearls (Dana Pharmaceutical Company, Tabriz, Iran) or a placebo every 2 weeks for 2 months. Inclusion criteria were patients requiring bilateral extraction of the first premolar in the maxilla. The canines were retracted by nickel-titanium (NiTi) coil springs into the extraction sites. At the beginning, after 1 and 2 months, the distance between canine and lateral teeth on both sides was measured to calculate OTM. Results: In the first month ( t (1–2)), the mean values of OTM in the placebo group were higher than the other groups. However, during the second month ( t (2–3)) and overall ( t (1–3)), the experiment group showed a higher OTM. The experiment and control groups were statistically different in all three time periods ( P-value < .05). The difference between the experiment and placebo groups was only significant in t (2–3) ( P-value < .05). Whereas the placebo and control groups showed a significant difference in t (1–2) ( P-value < .05). Conclusion: Vitamin D3 deficiency seems to increase OTM. Receiving oral supplements of vitamin D3 may not have much effect on increasing the level of vitamin D3. The lowest OTM rate was observed in the control group.

Oral Administration of Vitamin D3 Prevents Corneal Damage in a Knock-Out Mouse Model of Sjögren's Syndrome.

Vitamin D deficiency has been associated with dry eye development during Sjögren's syndrome (SS). Here, we investigated whether repeated oral vitamin D3 supplementation could prevent the corneal epithelium damage in an SS mouse model. 30 female mouse knock-out for the thrombospondin 1 gene were randomized (six per group) in untreated mice euthanized at 6 weeks as negative control (C-) or at 12 weeks as the positive control for dry eye (C+). Other mice were sacrificed after 6 weeks of oral vitamin D3 supplementation in the drinking water (1000, 8000, and 20,000 IU/kg/week, respectively). The C+ mice showed alterations in their corneal epithelial morphologies and thicknesses (p < 0.01 vs. C-), while the mice receiving 8000 (M) and 20,000 (H) IU/kg/week of vitamin D3 showed preservation of the corneal epithelium morphology and thickness (p < 0.01 vs. C+). Moreover, while the C+ mice exhibited high levels and activity of corneal tumor necrosis factor alpha converting enzyme (TACE), neovascularization and fibrosis markers; these were all reduced in the M and H mice. Oral vitamin D3 supplementation appeared to counteract the negative effect of TACE on corneal epithelium in a mouse model of SS-associated dry eye.

The role of vitamin D in the prevention of pathology associated with psoriasis and metabolic syndrome

The paper highlights modern views on the metabolism of vitamin D in the human body. The analysis of the literature data on the mechanisms of the effect of vitamin D deficiency on the pathological processes occurring in the skin with psoriasis is carried out. It is known that psoriasis is associated with a high prevalence of metabolic syndrome, diabetes mellitus, and cardiovascular diseases. There is a direct correlation between a decrease in vitamin D levels and an increased risk of developing metabolic syndrome and cardiovascular mortality, including in patients with psoriasis. Data on the possibility of using vitamin D in dermatology are presented. Based on international and Russian clinical recommendations, the place of oral colecalciferol preparations in the prevention and correction of vitamin D deficiency and deficiency has been determined. The use of oral vitamin D for the simultaneous treatment of psoriasis and metabolic syndrome reduces the risk of cardiovascular diseases and type 2 diabetes mellitus. We analysed the international and domestic recommendations for the treatment of vitamin D deficiency and insufficiency, the use of which makes the oral administration of vitamin D3 (cholecalciferol) optimal for the treatment and prevention of vitamin D deficiency, as the results of several studies showed a higher efficacy of vitamin D3 vs vitamin D2. Vitamin D3 is found in vitamin D-fortified foods and is available as dietary supplements and drugs. The bioavailability of vitamin D in dietary supplements may differ depending on the used vehicle substance.

Vitamin D3 Protects Mice from Diquat-Induced Oxidative Stress through the NF-κB/Nrf2/HO-1 Signaling Pathway.

Vitamin D3, as an indispensable and fat-soluble micronutrient, plays an important role in the health of humans and animals. At present, studies are focusing on the calcium absorption and immunoregulation function of vitamin D3; this study was aimed at exploring the antioxidative stress ability of vitamin D3 on diquat-induced intestinal dysfunction of ICR mice and the underlying mechanism. The results showed that oral gavage of vitamin D3 daily significantly improved the body weight gain and immune organ index and significantly reverted the abnormal changes of ALT, AST, SOD, GSH-Px, T-AOC, and MDA in the serum and jejunum induced by diquat. The addition of vitamin D3 also significantly reduced the concentration of DAO, D-LA, and certain proinflammatory cytokines in serum. Moreover, vitamin D3 improved the pathological morphology of the duodenum, jejunum, colon, liver, and kidney tissues, and it also largely attenuated the degree of inflammatory infiltration of macrophages and cell apoptotic index of jejunal epithelial tissue induced by diquat. The results demonstrated that vitamin D3 significantly recovered the intestinal barrier injury by enhancing the expression of mucins and tight junction proteins in the jejunum. In addition, the results indicated that vitamin D3 could significantly reduce the phosphorylation level of NF-κB (p65) and enhance the expression of Nrf2 and HO-1 in the jejunum compared with the diquat-induced group. This study suggested that oral administration of vitamin D3 can protect mice against oxidative damage by inhibiting the phosphorylation level of NF-κB (p65) and activating Nrf2-related signaling pathways.

Personalise vitamin D3 using physiologically based pharmacokinetic modelling.

Plasma concentration of vitamin D3 metabolite 25‐hydroxyvitamin D3 (25(OH)D3) is variable among individuals. The objective of this study is to establish an accurate model for 25(OH)D3 pharmacokinetics (PKs) to support selection of a suitable dose regimen for an individual. We collated vitamin D3 and 25(OH)D3 plasma PK data from reported clinical trials and developed a physiologically‐based pharmacokinetic (PBPK) model to appropriately recapitulate training data. Model predictions were then qualified with 25(OH)D3 plasma PKs under vitamin D3 and 25(OH)D3 dose regimens distinct from training data. From data exploration, we observed the increase in plasma 25(OH)D3 after repeated dosing was negatively correlated with 25(OH)D3 baseline levels. Our final model included a first‐order vitamin D3 absorption, a first‐order vitamin D3 metabolism, and a nonlinear 25(OH)D3 elimination function. This structure explained the apparent paradox. Remarkably, the model accurately predicted plasma 25(OH)D3 following repeated dosing up to 1250 μg/d in the test set. It also made sensible predictions for large single vitamin D3 doses up to 50,000 μg in the test set. Model predicts 10 μg/d regimen may be ineffective for achieving sufficiency (plasma 25(OH)D3 ≥ 75 nmol/L) for a severely deficient individual (baseline 25(OH)D3 = 10 nmol/L), and it might take the same person over 200 days to reach sufficiency at 20 μg/d dose. We propose to personalize vitamin D3 supplementation protocol with this PBPK model. It would require measuring 25(OH)D3 baseline levels, which is not routinely performed under the current UK public health advice.Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Vitamin D PK exhibits substantial inter‐individual variability. Different officially recommended daily doses are confusing.​ WHAT QUESTION DID THIS STUDY ADDRESS? Is the UK’s recommended 10 µg daily dose sufficient? Should everyone be given same dose?​ WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Our model accurately predicts plasma 25(OH)D under daily oral administration of vitamin D3. The 10 µg daily vitamin D3 dose is insufficient for prophylaxis (plasma 25(OH)D at 75 nmol/L).​ HOW MIGHT THIS CHANGE DRUG DISCOVERY, DEVELOPMENT, AND/OR THERAPEUTICS? Combining blood test to measure 25(OH)D baseline with this PBPK model will help inform dosage selection and select follow‐up date to improve effectiveness of Hypovitaminosis D treatment.

Role of Vitamin D in Prevention of Metabolic Syndrome and Cardiovascular Diseases

Objective: About 90% of cardiovascular diseases can be prevented. In recent years, the role of vitamin D in the prevention of cardiovascular disease and components of metabolic syndrome has been actively discussed. The study aimed to investigate the possible influence of vitamin D3 on the emergence risk of metabolic syndrome and adverse cardiovascular events.&#x0D; Materials and methods: The study enrolled a total of 336 people (170 males and 166 females) aged 50-60 years. For comparative analysis, two groups were formed: Group 1 group involved 150 people treated with placebo, and Group 2 group included 186 people who received vitamin D3 orally in a dose of 2000 IU/day. The duration of treatment and observation was four years. Participants in the study completed a questionnaire developed by the authors of this paper, in which they answered questions about the presence of factors contributing to the development of cardiovascular pathology.&#x0D; Results and Discussion: Daily oral intake of vitamin D3 in a dose of 2000 IU/day for four years did not improve laboratory indicators, which are components of MS, namely, the content in the blood of TC, TG, LDL, HDL, AI, fasting and postprandial glycemia, insulin, and insulin resistance index HOMA2-IR (p&gt;0.05). Prolonged use of vitamin D3 did not reduce the risk of cardiovascular diseases (myocardial infarcts (RR=0.93, 95% CI [0.21-4.09], p=0.92), strokes (RR=1.24, 95% CI [0.18-8.70], p=0.83), stenting (RR=1,23, 95% CI [0.32-4.88], p=0.76), arterial hypertension (RR=1.12, 95% CI [0.47-2.68], p=0.81), as well as cardiovascular death rates (RR=0.83, 95% CI [0.14-4.88], p=0.83) and death from any other causes (RR=0.93, 95% CI [0.21- 4.09], p=0.92).&#x0D; Conclusion: Thus, daily prolonged oral administration of vitamin D3 in a dose of 2000 IU/day does not contribute to the improvement of blood lipid spectrum, glycemia, and insulin resistance in metabolic syndrome and does not reduce the risk of adverse (fatal and non-fatal) cardiovascular events.&#x0D; Bangladesh Journal of Medical Science Vol.20(2) 2021 p.431-438

Vitamin D status and determinants of deficiency among Palestinian females of childbearing age: A case control study

<h2>Summary</h2><h3>Objective</h3> Vitamin D deficiency is a global public health problem and affecting more people in Middle Eastern countries. We set up the present work to investigate vitamin D status and its deficiency determinants among Palestinian females of childbearing age. <h3>Materials and methods</h3> In this study follow up interventional study we recruited 50 vitamin D deficient adult females (17–40 years) and were assigned to receive, under physician supervision, a daily oral dosages of vitamin D₃ (4000 IU) plus 600 mg of calcium for 3 successive months. Also, we included equal number of apparently healthy individuals as a control for baseline comparisons. Relevant hematological and biochemical parameters were measured, statistically analyzed and compared with control as well as with baseline values. <h3>Results</h3> Baseline comparison reveals significant lower hemoglobin level, red blood cell count and significantly higher white blood cell and platelets counts among vitamin D deficient females (<i>P</i>-value <0.001). Serum vitamin D, total calcium and phosphate showed significant lower values, while parathyroid hormone exhibited significantly higher values among cases compared to controls. Marked elevation in serum ferritin level while, iron and TIBC levels showed significant decreased among cases compared to control (P ≤ 0.001). The daily oral administration of vitamin D3 and calcium for 3 months corrected the deficient status of vitamin D. Some statistically significant correlations were reported and discussed between different parameters. <h3>Conclusions</h3> Vitamin D deficiency is prevailing health threating condition among Palestinian females of childbearing age, justifying the necessity for national vitamin D supplementation strategy to ameliorate such prevalent health condition. The current intervention has successfully restorer the deficient status and replenish the body of subjects with sufficient vitamin D.

Influence of the Biofield Energy Treatment on the Pharmacokinetics of 25-Hydroxyvitamin D3 in Male Sprague-Dawley Rats after a Single Oral Dose of Vitamin D3

Vitamin D3 reported having many important roles in bone metabolism, osteoporosis, immunity, and useful in numerous diseases, i.e., cardiovascular, cancers, and neurodegenerative diseases. Unexpectedly, there is little information available about the concentration of 25-hydroxyvitamin D3 in the blood, which is the best indicator of vitamin D3 status after its oral absorption. However, the biological activity of vitamin D3 is mediated via the formation of the active metabolite, 1-α, 25-dihydroxyvitamin D3 . There are several factors that affect its absorption and first-pass metabolism that lead to having very low plasma concentrations of both the metabolites (25-hydroxyvitamin D3 and 1-α, 25-dihydroxyvitamin D3 ) following an oral administration. Thus, the current study was executed to determine the influence of the Trivedi Effect®-Consciousness Energy Treatment on vitamin D3 and rats through the measurement of plasma 25-hydroxyvitamin D3 concentrations after the oral administration of vitamin D3 in male Sprague-Dawley rats. The test item, vitamin D3 was divided into two parts. One part was denoted as the control (without Biofield Energy Treatment/Blessing), while the other part was defined as the Biofield Energy Treated sample, which received the Biofield Energy Treatment by renowned Biofield Energy Healer, Dahryn Trivedi. Additionally, one group of animals also received Consciousness Energy Treatment per se by the Healer under similar conditions. The Biofield Energy Healer who was located in the USA, while the test samples and animals were located in the research laboratory in India. Vitamin D3 oral formulations were administrated by oral gavage at a dose of 500 µg per kg in groups viz. G1 (untreated vitamin D3 ), G2 (Biofield Treated vitamin D3 ), and G3 (Biofield Treated animals received untreated vitamin D3 ) group. The Biofield Energy Treatment increased the maximum plasma concentration (Cmax) of 25-hydroxyvitamin D3 by 3.45% and 72.77% in the G2 and G3 groups, respectively as compared with the G1 group. The area under the plasma concentration– time curve (AUC0–t) of 25-hydroxyvitamin D3 was altered by -11.19% in the G2 group and 59.45% in the G3 group as compared to the G1 group. After oral administration, the Tmax of 25-hydroxyvitamin D3 was altered by -62.97% in G2 and 55.56% in G3 groups compared to G1. The mean residence time (MRT) of 25-hydroxyvitamin D3 was also altered in the G2 group by -12.34% and G3 group by 0.18%, as compared to the G1. The relative oral bioavailability (Fr) of 25-hydroxyvitamin D3 was significantly altered by -11.19% in the G2 group and 59.45% in the G3 group compared to the G1. Biofield Energy Treatment could be an innovative strategy that opens new avenues to overcome poorly absorbed pharmaceuticals/ nutraceuticals/herbal extracts and can also improve the therapeutic performance of orally active molecules.

Effects of vitamin D administration on nociception and spinal cord pro-oxidant and antioxidant markers in a rat model of neuropathic pain.

Reactive oxygen species (ROS) are involved in neuropathic pain, a complicated condition after nerve tissue lesion. Vitamin D appears to improve symptoms of pain and exhibits antioxidant properties. We investigated the effects of oral administration of vitamin D3, the active form of vitamin D, on nociception, the sciatic functional index (SFI), and spinal cord pro-oxidant and antioxidant markers in rats with chronic constriction injury (CCI) of the sciatic nerve, a model of neuropathic pain. Vitamin D3 (500 IU/kg per day) attenuated the CCI-induced decrease in mechanical withdrawal threshold and thermal withdrawal latency (indicators of antinociception) and SFI. The vitamin prevented increased lipid hydroperoxide levels in injured sciatic nerve without change to total antioxidant capacity (TAC). Vitamin D3 prevented increased lipid hydroperoxide, superoxide anion generation (SAG), and hydrogen peroxide (H2O2) levels in the spinal cord, which were found in rats without treatment at 7 and 28 days post-CCI. A significant negative correlation was found between mechanical threshold and SAG and between mechanical threshold and H2O2 at day 7. Vitamin D3 also prevented decreased spinal cord total thiols content. There was an increase in TAC in the spinal cord of vitamin-treated CCI rats, compared to CCI rats without treatment only at 28 days. No significant changes were found in body weight and blood parameters of hepatic and renal function. These findings demonstrated, for first time, that vitamin D modulated pro-oxidant and antioxidant markers in the spinal cord. Since antinociception occurred in parallel with oxidative changes in the spinal cord, the oxidative changes may have contributed to vitamin D-induced antinociception.

The Preventive Effects of Xanthohumol on Vascular Calcification Induced by Vitamin D3 Plus Nicotine

Vascular calcification (VC) is highly prevalent in patients with atherosclerosis, chronic kidney disease, diabetes mellitus, and hypertension. In blood vessels, VC is associated with major adverse cardiovascular events. Xanthohumol (XN), a main prenylated chalcone found in hops, has antioxidant effects to inhibit VC. This study aimed to investigate whether XN attenuates VC through in vivo study. A rat VC model was established by four weeks oral administration of vitamin D3 plus nicotine in Sprague Dawley (SD) rats. In brief, 30 male SD rats were randomly divided into three groups: control, 25 mg/kg nicotine in 5 mL corn oil and 3 × 105 IU/kg vitamin D3 administration (VDN), and combination of VDN with 20 mg/L in 0.1% ethanol of XN (treatment group). Physiological variables such as body and heart weight and drinking consumption were weekly observed, and treatment with XN caused no differences among the groups. In comparison with the control group, calcium content and alkaline phosphatase (ALP) activity were increased in calcified arteries, and XN treatment reduced these levels. Dihydroethidium (DHE) and 2′,7′-dichloroflurescin diacetate (DCFH-DA) staining to identify Superoxide and reactive oxygen species generation from aorta tissue showed increased production in VDN group compared with the control and treatment groups. Hematoxylin eosin (HE) and Alizarin Red S staining were determined to show medial vascular thickness and calcification of vessel wall. Administration of VDN resulted in VC, and XN treatment showed improvement in vascular structure. Moreover, overexpression of osteogenic transcription factors bone morphogenetic protein 2 (BMP-2) and runt-related transcription factor 2 (Runx2) were significantly suppressed by XN treatment in VC. Moreover, downregulation of vascular phenotypic markers alpha-smooth muscle actin (α-SMA) and smooth muscle 22 alpha (SM22α) were increased by XN treatment in VC. Furthermore, XN treatment in VC upregulated nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expressions. Otherwise, Kelch-like ECH-associated protein 1 (Keap1) was alleviated by XN treatment in VC. In conclusion, our findings suggested that XN enhances antioxidant capacity to improve VC by regulating the Nrf2/Keap1/HO-1 pathway. Therefore, XN may have potential effects to decrease cardiovascular risk by reducing VC.

Effects of Vitamin D Deficiency on Proliferation and Autophagy of Ovarian and Liver Tissues in a Rat Model of Polycystic Ovary Syndrome

Aim: We aimed to examine the alterations of the insulin signaling pathway, autophagy, nitrative stress and the effect of vitamin D supplementation in the liver and ovaries of vitamin D deficient hyperandrogenic rats. Methods: Female Wistar rats received eight weeks of transdermal testosterone treatment and lived on a low vitamin D diet (D–T+). Vitamin D supplementation was achieved by oral administration of vitamin D3 (D+T+). Sham-treated (D+T–) and vitamin D deficient animals (D–T–) served as controls. (N = 10–12 per group). Results: D–T+ animals showed decreased LC3 II levels in the liver and increased p-Akt/Akt and p-eNOS/eNOS ratios with decreased insulin receptor staining in the ovaries. Vitamin D supplementation prevented the increase of Akt phosphorylation in the ovaries. Vitamin D deficiency itself also led to decreased LC3 II levels in the liver and decreased insulin receptor staining in the ovaries. D–T+ group showed no increase in nitrotyrosine staining; however, the ovaries of D–T– rats and the liver of D+T+ animals showed increased staining intensity. Conclusion: Vitamin D deficiency itself might lead to disrupted ovarian maturation and autophagy malfunction in the liver. Preventing Akt phosphorylation may contribute to the beneficial effect of vitamin D treatment on ovarian function in hyperandrogenism.

Vitamin D3 intake as regulator of insulin degrading enzyme and insulin receptor phosphorylation in diabetic rats.

Insulin-degrading enzyme (IDE, insulysin) is a rate-limiting enzyme in the insulin degradation process. It is an intracellular 110-kDa thiol zinc-metalloendopeptidase located in the cytosol, peroxisomes, endosomes and cell surface. IDE catalyzes degradation of several small proteins including insulin, amylin and β-amyloid protein. In addition, insulin clearance was expressed as a target in the treatment of type 2 diabetes given the role of hyperinsulinemia in the pathogenesis of insulin resistance. In this study, fourtyadult male Wistar albino rats were used, thirty rats received 20% fructose in drinking water (HFW) for six weeks to induce diabetes. Subsequently, these rats developed significantly higher body weights, dyslipidemia, hyperglycemia and insulin resistance compared to their controls. Significant increase in the levels of serum glucagon, IDE in liver tissue along with an inhibition of insulin receptor phosphorylation were also observed. Concurrent oral administration of vitamin D3 along with HFW resulted in significant decrease of serum glucose, total cholesterol, triacylglycerol and LDL-C levels. Vitamin D alleviated also insulin resistance, where both IDE, glucagon levels showed significant decrease along with activation of insulin receptor phosphorylation. Normal rats, received vitamin D3 only demonstrated non significant changes of the studied biomarkers. We concluded that vitamin D3 ameliorated insulin resistance and hyperinsulinemia in diabetic rat model received HFW through reduction of IDE and activation of insulin receptor phosphorylation.

Arterial stiffness parameters associated with vitamin D deficiency and supplementation in patients with normal cardiac functions.

Arterial stiffness parameters including pulse wave velocity (PWV) and augmentation index (AIx) are associated with increased risk of cardiovascular disease. A close relationship has been demonstrated between vitamin D deficiency and cardiovascular disease. The aim of the present study was to investigate effects of vitamin D deficiency and supplementation on arterial stiffness parameters in patients with normal cardiac functions. Study population consisted of 45 patients with vitamin D deficiency and normal cardiac functions. Median age (interquartile range) was 45.0 (12.00) years, and 33 patients were female. Patients were treated with oral administration of vitamin D3. Arterial stiffness parameters were evaluated using Mobil-O-Graph arteriograph system, which detected signals from the brachial artery before and after treatment. Vitamin D levels significantly increased after treatment (9.0 [6.00] nmol/L vs 29.0 [11.50] nmol/L, p<0.001). No significant difference was observed among conventional echocardiographic parameters before or after treatment. Post-treatment PVW and AIx were significantly lower than baseline measurements (6.8 [1.55] m/s vs 6.4 [1.30] m/s, p<0.001 and 23.0 [22.00]% vs 31.0 [14.50]%, p<0.001, respectively). Baseline vitamin D levels significantly correlated with PWV (r=-0.352, p=0.018). Post-treatment vitamin D levels also significantly correlated with post-treatment PWV (r=-0.442, p=0.002) and AIx (r=-0.419, p=0.004). Multivariate linear regression analysis revealed no independent predictor of baseline log-transformed PWV. Vitamin D supplementation has beneficial effects on arterial stiffness. Arterial stiffness parameters may aid in the assessment of cardiovascular risk in patients with vitamin D deficiency.

25-Hydroxylation of vitamin D3: relation to circulating vitamin D3 under various input conditions

BackgroundNeither the efficiency of the 25-hydroxylation of vitamin D nor the steady state relation between vitamin D3 and 25-hydroxyvitamin D [25(OH)D] has been studied in humans. ObjectiveWe aimed to examine the relation between serum vitamin D3 and 25(OH)D in normal subjects after either oral administration of vitamin D3 or ultraviolet-B radiation across a broad range of inputs. DesignValues for serum vitamin D3 and (OH)D3 were aggregated from 6 studies—1 acute and 5 near-steady state—at various vitamin D3 inputs. In 3 of the steady state studies, vitamin D3 had been administered for 18–26 wk in doses of 0 to 11000 IU/d; in 2 studies, subjects had received solar or ultraviolet-B irradiation. ResultsIn the acute study, subjects receiving a single 100000-IU dose of vitamin D3 had a rise in serum cholecalciferol to a mean of 521 nmol/L at 1 d and then a fall to near-baseline values by 7–14 d. Serum 25(OH)D peaked at 103 nmol/L on day 7 and fell slowly to baseline by day 112. In the 5 steady state studies, the relation of serum 25(OH)D to serum vitamin D3 was biphasic and was well described by a combined exponential and linear function: Y = 0.433X + 87.81[1−exp (−0.468X)], with R2 = 0.448. ConclusionsAt physiologic inputs, there is rapid conversion of precursor to product at low vitamin D3 concentrations and a much slower rate of conversion at higher concentrations. These data suggest that, at typical vitamin D3 inputs and serum concentrations, there is very little native cholecalciferol in the body, and 25(OH)D constitutes the bulk of vitamin D reserves. However, at supraphysiologic inputs, large quantities of vitamin D3 are stored as the native compound, presumably in body fat, and are slowly released to be converted to 25(OH)D.

Vitamin D3 Treatment for Locally Advanced Thyroid Cancer: A Case Report

There are many intricacies in the surgical treatment of locally advanced thyroid cancer, including the medical management of the remaining functional organ and any cosmetic impairments, which are sometimes very difficult to manage and eventually carry a relatively high morbidity and mortality. Here, we report on a case of a 65-year-old female with an extremely locally-advanced thyroid cancer involving both lobes of the thyroid, blood vessels, trachea and esophagus. Despite the severity of her condition, oral administration of vitamin D3 (alphacalcido) has stalled both the tumor growth and further increases of serum thyroglobulin (Tg) level, and has led to a good preservation of quality of life for the last two years. Several reports have previously demonstrated the efficacy of vitamin D3 to inhibit the proliferation of thyroid cancer cell lines in vitro, but clinical evidence has been limited so far. Therefore, this case report provides important evidence for the effectiveness of vitamin D3 therapy against advanced thyroid cancers.

Alteration in bone metabolism with increasing age: Effects of zinc and vitamin D3 in aged rats.

The alteration in bone metabolism with increasing age was investigated in the femoral diaphysis of male rats. Calcium content was highest in the bone from 3-week-old rats (491 +/- 13 mg/g bone ash), falling gradually with aged to 357 +/- 7 and 306 +/- 9 mg/g bone ash in 28- and 52-week-old rats, respectively. Bone zinc content increased until rats were 3 weeks of age, and thereafter remained constant. Deoxyribonucleic acid (DNA) content was highest in the bone from 1-week-old rats, and it decreased markedly with increasing age. Alkaline phosphatase and acid phosphatase activities increased up to 3 weeks, then subsequently declined with age. Thus, the retardation of bone metabolism was induced by ageing. When zinc sulfate (5.0, 10.0 and 20.0 mg Zn/kg body weight) was administered orally for 3 d to 28-week-old rats, alkaline phosphatase activity and calcium content in the femoral diaphysis was elevated markedly by all doses. The oral administration of vitamin D3 (2.0 and 20 micrograms/kg) for 3 d in 28-week-old rats did not produce an appreciable increase in bone alkaline phosphatase activity or calcium content, while 1,25-dihydroxyvitamin D3 (1.5 micrograms/kg) caused a significant increase in those biochemical indices. These results indicate that zinc and 1,25-dihydroxyvitamin D3 play a role as activators in bone metabolism of ageing rats.

カルシウム化合物のカルシウム源としての利用効果の比較

The bioavailability as calcium sources of dibasic calcium phosphate, calcium lactate and calcium carbonate was compared by means of in vivo and in situ experiments. For the in vivo experiment, vitamin D-deficient rats were fed ad libitum on food containing either dibasic calcium phosphate, calcium lactate or calcium carbonate with oral administration of vitamin D3 (200IU/rat/day). There were no significant differences in body weight, food consumption or plasma concentrations of calcium, phosphorus and 25-hydroxyvitamin D3 among the three groups after one week. In the in situ experiment, intestinal calcium absorption of the three calcium compounds was studied using an intestinal loop circulation method using vitamin D-replete and vitamin D-deficient rats. Again, little difference was observed among the respective data for the three calcium compounds. From these results, we concluded that there was practically no significant difference among the three compounds with regard to their bioavailability as calcium sources.

Enhancement of vitamin D3 effect on bone metabolism in weanling rats orally administered zinc sulphate.

The interaction of vitamin D3 and zinc on bone metabolism was investigated in the femur of weanling rats. Oral administration of vitamin D3 (1.0 micrograms/100 g body weight) did not cause any increase in the zinc accumulation in the femoral tissue following treatment with zinc sulphate (1.0 mg Zn/100 g). Administration of vitamin D3 or zinc produced significant increases the alkaline phosphatase activity and DNA content of the femoral diaphysis but not of the epiphysis. The increase in alkaline phosphatase activity was enhanced additionally by simultaneous administration of vitamin D3 and zinc. Moreover, the increase in DNA content was enhanced markedly (about 4 times) by these treatments. At a dose of 0.5 micrograms of vitamin D3 per 100 g, DNA content was at the control level. This level was increased about 2 times by simultaneous administration of zinc (1.0 mg/100 g). The increase in alkaline phosphatase activity following simultaneous administration of vitamin D3 and zinc was significantly inhibited by treatment with cycloheximide, actinomycin D, or mitomycin C. Also, the increase in DNA content was completely inhibited by mitomycin C treatment. The present data suggest that the combination of vitamin D3 and zinc has a multiple effect on the stimulation of bone growth and mineralization in weanling rats, and that this effect is based on a stimulation of the DNA synthesis in bone cells.

Pseudohypoparathyroidism type II and anticonvulsant rickets

A patient treated with anticonvulsants showed hypocalcemia and hyperphosphatemia in association with increased serum parathyroid hormone, reduced serum 25-hydroxy D3, diminished response in phosphorus excretion to exogenous parathyroid hormone and normal response in cyclic AMP excretion. Oral administration of Vitamin D3 resulted in normalization of serum 25-hydroxy D3, calcium, and phosphorus. At this stage, phosphorus excretion after parathyroid hormone returned to normal. These findings suggest that the patient had pseudohypoparathyroidism type II with anti-convulsant medication as a complicating factor.