Vitamin D3 Concentrations Research Articles

The influence of vitamin D on handgrip strength in elderly trauma patients

Background and objectivesThe treatment of elderly patients is an increasing challenge and the long-term sequelae often affect activities of daily living and quality of life in those patients. Handgrip strength (HGS) appears as a promising value to predict the outcome after trauma in elderly patients and to assess the overall muscle strength. Besides the possible role of psychological and hormonal factors, vitamin D may have a positive influence. Furthermore, some data suggest that Vitamin D is beneficial regarding muscle strength and possibly prevents further falls and injuries in orthogeriatric patients. The purpose of this study was to identify if Vitamin D is an influencing factor for HGSin elderly trauma patients.Materials and methods94 elderly patients in a Level I Trauma Center aged 60 years or older were prospectively enrolled and HGS as well as serum 25-OH Vitamin D concentration (VDC) were measured. In addition, the standardized questionnaires Barthel Index (BI), Parker Mobility Score (PMS), Short Physical Performance Battery (SPPB), Strength, Assistance with walking, Rise from a chair, Climb stairs and Falls (SARC-F) and European Quality of Life 5 Dimensions 5 Levels Questionnaire (EQ-5D-5L), were used to record mental health status and demographic data.ResultsHGS is mainly related to age and sex in elderly trauma patients. HGS was higher in men (meanmale = 27.31 kg (± 8.11), meanfemale = 15.62 kg (± 5.63), p < 0.001 and decreased with age (βage = − 0.58, p < 0.001). A significant negative correlation between HGS and VDC exists in the overall sample (βVDC = − 0.27, pVDC < 0.008), which still remains after adjusting for age (pVDC < 0.004), but is not significant after adjustment for both main confounders, age and sex (pVDC < 0.08). Furthermore, the HGS was lower in pateints who reported frequent falls, stumbling, dizziness or a late onset of menopause, and decreased if patients felt anxious or depressed during measurements (βanxiety+depression = − 0.26, panxiety+depression < 0.01).ConclusionsThese results do not support the hypothesis that Vitamin D has a positive influence on muscle strength measured by HGS. Nevertheless, this study could confirm the usefulness of HGS as a tool to detect the risk for frequent falls or stumbling. Furthermore, HGS seems to be associated with dizziness and age at onset of menopause. A significant decrease of HGS could also be shown in patients with anxiety and depression. This underlines the importance of interdisciplinary treatment of elderly trauma patients and needs to be taken into account for further studies, as especially the psychological motivation seems to have a significant influence and is sometimes not considered enough in elderly musculo-skeletal patients.

Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization.

Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs; p < 1 × 10-9) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci, CD46, IKBKE, PARK2, ULK4, ATG5, and CDKN2A associated with MM risk (p = 4.47 × 10-4-5.79 × 10-14). Mechanistically, we found that the ULK4rs6599175 SNP correlated with circulating concentrations of vitamin D3 (p = 4.0 × 10-4), whereas the IKBKErs17433804 SNP correlated with the number of transitional CD24+CD38+ B cells (p = 4.8 × 10-4) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 (p = 3.6 × 10-4). We also found that the CD46rs1142469 SNP correlated with numbers of CD19+ B cells, CD19+CD3- B cells, CD5+IgD- cells, IgM- cells, IgD-IgM- cells, and CD4-CD8- PBMCs (p = 4.9 × 10-4-8.6 × 10-4) and circulating concentrations of interleukin (IL)-20 (p = 0.00082). Finally, we observed that the CDKN2Ars2811710 SNP correlated with levels of CD4+EMCD45RO+CD27- cells (p = 9.3 × 10-4). These results suggest that genetic variants within these six loci influence MM risk through the modulation of specific subsets of immune cells, as well as vitamin D3-, MCP-2-, and IL20-dependent pathways.

Increased dietary vitamin D3 and calcium partially alleviate heat stress symptoms and inflammation in lactating Holstein cows independent of dietary concentrations of vitamin E and selenium

Twelve multiparous Holstein cows (42.2 ± 5.6 kg of milk/d; 83 ± 27 d in milk) were used in a split-plot design testing the effects of mineral and vitamin supplementation on the time course of animal performance, metabolism, and inflammation markers during heat stress. The main plot was the average concentrations of dietary vitamin E and Se (adequate: 11.1 IU/kg of vitamin E and 0.55 mg/kg of Se, and high: 223 IU/kg of vitamin E and 1.8 mg/kg of Se, respectively). Within each plot, cows were randomly assigned to (1) heat stress (HS) with adequate concentrations of vitamin D3 and Ca (1,012 IU/kg and 0.73%, respectively), (2) HS with high concentrations of vitamin D3 and Ca (HS+D3/Ca; 3,764 IU/kg and 0.97%, respectively), or (3) pair-feeding (PF) in thermoneutrality with adequate concentrations of vitamin D3 and Ca (1,012 IU/kg and 0.73% Ca) in a Latin square design with 14-d periods and 7-d washouts. The highest rectal temperature was recorded at 1700 h for HS (39.4°C; mean of d 1 to 14), being 1.2 and 0.8°C greater than for PF and HS+D3/Ca, respectively. Respiratory rate and water intake were higher in HS (73 breaths/min and 115 L/d, respectively) relative to PF (28 breaths/min and 76 L/d). Heat stress decreased dry matter intake progressively, reaching a nadir on d 5 to 7 (33% reduction) and was not different between treatments. Milk yield decreased progressively in all treatments, but remained greater in PF relative to HS from d 3 to 14 (10%), whereas HS and HS+D3/Ca were not different. Milk fat, protein, and lactose concentrations and yields were lower in HS relative to PF from d 3 to 14, but not different between HS and HS+D3/Ca. Relative to PF, preprandial insulin concentrations were increased in HS, whereas plasma nonesterified fatty acids were decreased on d 7 and 14. Plasma lipopolysaccharide-binding protein concentrations increased in HS cows on d 7 and 14, respectively, relative to PF, whereas they were reduced in HS + D3/Ca on d 14. Plasma C-reactive protein, tumor necrosis factor-α, and fecal calprotectin were increased in HS relative to both PF and HS+D3/Ca on d 7 and 14. Rectal temperature was positively associated with plasma lipopolysaccharide-binding protein (r = 0.72), tumor necrosis factor-α (r = 0.74), C-reactive protein (r = 0.87), and with milk somatic cells (r = 0.75). Plasma 8-hydroxy-2-deoxyguanosine concentrations presented a 3-way interaction, where 8-hydroxy-2-deoxyguanosine was lower in HS than in PF on d 7 and 14, and lower in HS+D3/Ca relative to HS on d 14 in the adequate vitamin E and Se treatment, but no effects were observed in the high vitamin E and Se group. Plasma superoxide dismutase concentrations increased over time, and were higher in HS relative to PF on d 14, whereas HS+D3/Ca was similar to HS. Heat stress markedly reduced milk production and milk components while increasing markers of leaky gut and inflammation. In contrast, vitamin D3 and Ca supplementation reduced hyperthermia (d 7-14), markers of leaky gut, and inflammation independent of dietary concentrations of vitamin E and Se.

Impact of Vitamin D Status Correction on Serum Lipid Profile, Carboxypeptidase N and Nitric Oxide Levels in Saudi Adults.

This study aimed to determine the impact on the lipid profile, carboxypeptidase N (CPN) and nitric oxide (NOx) associated with vitamin D (VD) status correction among Saudi adults with VD deficiency. A total 111 VD deficient (25(OH)D < 50 nmol/L)) adult Saudis aged 18-50 years old (57 females and 54 males) were enrolled in this 6-month interventional study. They were given 50,000 IU VD weekly for the first 2 months and then twice a month for the next 2 months, followed by 1000 IU daily for the last 2 months. The fasting lipid profile and the blood glucose, VD, NOx and CPN concentrations were measured at baseline and after intervention. Post-supplementation, the median VD was significantly higher (p < 0.001) in females [58.3 (50.6-71.2)] and males [57.8 (51.0-71.8)]. HDL cholesterol significantly increased (p = 0.05) and NOx significantly decreased (p = 0.02) in males post-supplementation. Triglycerides were positively associated with NOx in all subjects before (r = 0.44, p = 0.01) and after (r = 0.37, p = 0.01) VD status correction. There was a significant increase in serum levels of CPN2 (p = 0.02) in all subjects. Furthermore, CPN was inversely correlated with NOx (r = -0.35, p = 0.05) in males post-supplementation. In conclusion, VD status correction reduced serum NOx, particularly in males. The inhibition of NOx synthesis may be responsible for the anti-inflammatory effects of VD supplementation. An inverse association was found between NOx and CPN2.

Effect of Vitamin D3 on some Antioxidant Parameters in Chilled Semen in Awassi Ram.

To sustain the viability of the sperm of farm animals, the sperm is chilled. However, reactive oxygen species (ROS) may damage it, resulting in oxidative stress and decreased sperm viability. This study aimed to assess the various concentrations of vitamin D3 as antioxidants in the chilled sperm of Awassi. This study was performed on 23 ejaculates from three Awassi rams. The samples were combined, diluted with Tris-egg yolk extender (1:10), and then divided into aliquots. Aliquots were treated with three vitamin D3 concentrations (T1=0.02, T2=0.004, and T3=0.002 g/ml) and one control without the addition of vitamin D3. The experimental and control groups were chilled to reach 5 ºC. Following treatment, the samples were centrifuged at 2,000 RPM for 20 min at 0 and 72 h after the treatment. Until evaluation, the seminal plasm was stored in a freezer at 20 ºC. In this study, the antioxidant activity of vitamin D3 was evaluated using malondialdehyde (MDA), ROS, total antioxidant capacity (TAC), superoxide dismutase (SOD), and catalase (CAT). The SAS software was used to analyze variance on repeated measures with a single factor. The results indicated that the TAC and SOD were considerably higher in T1, compared to that in T0, T1, and T2. In addition, CAT was considerably higher in T2 than in T0, T1, and T3. However, ROS and MDA did not differ significantly among the experimental groups. Despite the absence of a statistically significant difference among experimental groups, MDA decreased quantitatively on T1, relative to other experimental groups. In conclusion, a deficiency in vitamin D3 has a potential antioxidant capability, introducing a novel method for extending sperm storage.

Pharmacokinetic Interactions Between Bazedoxifene and Cholecalciferol: An Open-Label, Randomized, Crossover Study in Healthy Male Volunteers.

The combined administration of bazedoxifene, a tissue-selective estrogen receptor modulator, and cholecalciferol can be a promising therapeutic option for postmenopausal osteoporosis patients. This study aimed to examine the pharmacokinetic interactions between these two drugs and the tolerability of their combined administration in healthy male subjects. Thirty male volunteers were randomly assigned to one of the six sequences comprised of three treatments: bazedoxifene 20 mg monotherapy, cholecalciferol 1600 IU monotherapy, and combined bazedoxifene and cholecalciferol therapy. For each treatment, a single dose of the investigational drug(s) was administered orally, and serial blood samples were collected to measure the plasma concentrations of bazedoxifene and cholecalciferol. Pharmacokinetic parameters were calculated using the non-compartmental method. The point estimate and 90% confidence interval (CI) of the geometric mean ratio (GMR) were obtained to compare the exposures of combined therapy and monotherapy. The pharmacokinetic parameters compared were the maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUClast). The safety and tolerability of the combined therapy were assessed in terms of the frequency and severity of adverse events (AEs). For bazedoxifene, the GMR (90% CI) of the combined therapy to monotherapy was 1.044 (0.9263-1.1765) for Cmax and 1.1329 (1.0232-1.2544) for AUClast. For baseline-adjusted cholecalciferol, the GMR (90% CI) of the combined therapy to monotherapy was 0.8543 (0.8005-0.9117) for Cmax and 0.8056 (0.7445-0.8717) for AUClast. The frequency of AEs observed was not significantly different between the combined therapy and monotherapy, and their severity was mild in all cases. A mild degree of pharmacokinetic interaction was observed when bazedoxifene and cholecalciferol were administered concomitantly to healthy male volunteers. This combined therapy was well tolerated at the dose levels used in the present study.

The Impact of Cholecaciferol Supplementation on Bone Mineral Density in Long-Term Kidney Transplant Recipients

Although reduced bone mineral density (BMD) is associated with a higher risk of fractures, morbidity, and mortality in kidney transplant patients (KTRs), there is no consensus on optimal treatment for the alterations of BMD in this population. This study aims at assessing the effect of cholecalciferol supplementation on BMD over a follow-up period of 2 years in a cohort of long-term KTRs. Patients with age ≥ 18 years were included and divided into two subgroups based on treatment with bisphosphonate and/or calcimimetics and/or active vitamin D sterols (KTRs-treated) or never treated with the above medications (KTRs-free). BMD was evaluated at lumbar vertebral bodies (LV) and right femoral neck (FN) with standard DEXA at the beginning and end of the study. According to World Health Organization (WHO) criteria, results were expressed as T-score and Z-score. Osteoporosis and osteopenia were defined as T score ≤ -2.5 SD and T score < -1 and >-2.5 SD, respectively. Cholecalciferol was supplemented at a dose of 25,000 IU/week over 12 weeks followed by 1500 IU/day. KTRs-free (n. 69) and KTRs-treated (n. 49) consecutive outpatients entered the study. KTRs-free were younger (p < 0.05), with a lower prevalence of diabetes (p < 0.05) and of osteopenia at FN (46.3 % vs. 61.2 %) compared to KTRs-treated. At the entry none of the study subjects had a sufficient level of cholecalciferol; Z-score and T-score at LV and FN were not different between groups. At the end of the study period, serum cholecalciferol concentration was significantly increased in both groups (p < 0.001); the KTRs-free group presented an improvement in both T-score and Z-score at LV (p < 0.05) as well as a lower prevalence of osteoporotic cases (21.7% vs. 15.9%); in contrast, no changes were recorded in KTR-treated individuals. In conclusion, supplementation with cholecalciferol ameliorated Z-score and T-score at LV in long-term KTRs who had been never treated with active or inactive vitamin D sterols, bisphosphonates, and calcimimetics. Future endeavours are needed to confirm these preliminary findings.

METASTATIC MINERALIZATION IN A ZOOLOGIC COLLECTION OF SPOT-TAILED EARLESS LIZARDS (HOLBROOKIASPP.).

Vitamin and mineral supplements are commonly used in diets for zoologic and companion animals. Because specific nutrient requirements are often unknown, informed decisions are based on literature for related species. Over 18 mon beginning in November 2017, an entire population of spot-tailed earless lizards (Holbrookia lacerata and Holbrookia subcaudalis) died (N = 33). All but two lizards were submitted for histopathology (94%). All examined cases had mineralization in at least one tissue; 71% (22 of 31) had multisystemic mineral deposits consistent with metastatic mineralization. No underlying causes were detected histologically. The supplement used for dusting the food items fed five to six times per week was inadvertently switched for 2 to 4 mon, and the incorrect supplement was found to contain fourfold the intended vitamin D3 concentration. Thus, hypervitaminosis D was considered the most likely cause. Interestingly, eastern collared lizards (Crotaphytus collaris), also fed prey supplemented five to six times a week, and over 50 other insectivorous reptile and amphibian species possibly receiving the supplement one to seven times a week did not appear affected. During this time, only two other cases of metastatic mineralization were diagnosed in other herpetofauna at this institution. Prior to receiving the incorrect supplement, there were no cases of metastatic mineralization detected in the earless lizard population. These cases highlight species-specific sensitivities, and the deleterious effects of excessive or inappropriate supplementation. It is important to confirm product identification on arrival, regularly conduct chemical analysis of supplements, and educate keepers and owners about adverse effects of inappropriate supplementation.

SARS-CoV-2-Omicron-variant Induced COVID-19-Infection in Unvaccinated and Vaccinated Patients: Impact on Immune Response, Symptomatology, and Risk of POST-COVID Syndrome

Worldwide, the SARS-CoV-2-omicron-variant (B.1.1.529) is highly infectious, even in vaccinated patients. Little is known about the duration of acute SARS-CoV-2-omicron-infection, severity of symptoms, immunologic response and development of POST-COVID-syndrome in unvaccinated compared to vaccinated patients after acute SARS-CoV-2 omicron infection. Methods: In 24 patients suffered from acute SARS-CoV-2-omicron infection (10 unvaccinated participants, 5 participants twice vaccinated and 9 participants getting three mRNA vaccinations), symptoms and duration of disease, SARS-CoV-2-omicron immune response, 25(OH)-vitamineD3 and vitamine C were determined in blood 4 weeks after acute infection. In addition, POST-COVID-symptoms and autoantibodies against G protein-coupled receptors in blood were determined 16 weeks after acute infection. Pearson correlations and one-way ANOVA were used. p≤0.05 was assumed to be significant, and p≤0.01 was assumed to be highly significant, respectively. Results: All 24 patients (age: 54 ± 12 years; 16 females - 8 males) complained of mild symptoms during acute omicron-COVID-19 infection. In vaccinated versus (vs) unvaccinated patients the disease duration was significantly prolonged (3.4-times vs 3.8-times). POST-COVID symptoms were reported by 50% of unvaccinated patients, 60%, and 78% of vaccinated patients, respectively. Vaccinated vs unvaccinated patients showed significantly larger number of POST-COVID-symptoms. Vitamin C deficiency was detectable in all patients 4 weeks after acute COVID-19 infection. The 25(OH) Vitamin D3 concentration was within the normal range in all patients. In the SARS-CoV2-immunoblot, the unvaccinated patients showed the same antibody level against the virus core protein (NP) virus compared with the vaccinated patients, but no antibody level against the linking protein (RBD) or the spike protein (S1). Also, unvaccinated vs vaccinated patients showed no immunological response in building neutralizing antibody level IgG-S1 [neutralizing antibody IgG-S1 (norm &lt; 34 BAU/ml) at 0-vaccination vs 2-vaccination vs 3-vaccination = &lt;34 vs 14584 ± 12012.4 vs 15116.7 ± 10997.9 BAU/ml]. 4 weeks after omicron-COVID-19-infection, patients getting 2-vaccination vs 3-vaccination before infection showed a significant 5.4fold vs 14.9fold activation of neutralizing antibody level IgG-S1 (neutralizing antibody IgG-S1 (norm &lt; 34 BAU/ml) in 2-vaccination vs 3-vaccination patients - before / after infection = 2678.5 ± 3454.1 / 14584 ± 12012.4 vs 1012.9 ± 918.5 vs 15116.7 ± 10997.9 BAU/ml). The level of neutralizing antibody IgG-S1 after acute Omicron-COVID-19 infection correlates significantly with the duration of disease. All patients showed a cellular immune response against the SARS-CoV-2-omicron variant in the immune tolerance test (ITT) being significantly more robust in vaccinated vs. unvaccinated patients (ITT-Omicron IL2 / IFN at 0-vaccination vs. 2-vaccination vs. 3- vaccination = 14.8 ± 23.4 / 4.0 ± 4.8 vs. 34.4 ± 28.8 / 21.2 ± 13.0 vs 59.9 ± 103.8 / 29.3 ± 40.0 pg/ml). Autoantibodies level against G-protein coupled receptors are twice as strong in 3-dose vaccinated vs unvaccinated patients. Autoantibody level of ß1-adrenergic receptor or M3-muscarinergic-choline-receptor and the level of cellular immune response ITT-omicron-IL2 significantly correlate with the risk of developing POST-COVID syndrome. Conclusion: Acute SARS-CoV-2-omicron infection causes mild disease in both unvaccinated and vaccinated patients. However, vaccinated patients experienced prolonged disease with each vaccination. Unvaccinated patients showed no level of neutralizing antibodies to IgG-S1 spike compared with vaccinated patients after acute Omicron-COVID-19 infection, which is led back to multiple mutations in the region of the spike genome in the Omicron variant. Acute Omicron-COVID-19 infection after mRNA vaccination increases the risk of a strong immune response (neutralizing antibodies IgG-S1 spike, antibodies IgG-RBD, T-cellular response in IL2 and IFN, Autoantibodies to G-protein coupled receptor ß1-ß2-M2-M3) which correlates with the risk of POST-COVID syndrome. A deficiency of immune modulating micronutrients (vitamin C, vitamin D3, selenium, zinc) might be responsible. Further studies treating POST-COVID patients with high-dose micronutrient infusion are necessary proving to reduce or eliminate the symptoms in POST-COVID patients

Exome-wide screening identifies novel rare risk variants for bone mineral density.

BMD is highly heritable and a major predictor of osteoporotic fractures, but its genetic basis remains unclear. We aimed to identify rare risk variants contributing to BMD. Utilizing the newly released UK Biobank 200,643 exome dataset, we conducted a gene-based exome-wide association study in males and females, respectively. First, 100,639 males and 117,338 females with BMD values were included in the polygenic risk scores (PRS) analysis. Among individuals with lower 30% PRS, cases were individuals with top 10% BMD, and individuals with bottom 10% BMD were the controls. Considering the effects of vitamin D (VD), individuals with the highest 30% VD concentration were selected for VD-BMD analysis. After quality control, 741 males and 697 females were included in the BMD analysis, and 717 males and 708 females were included in the VD-BMD analysis. The variants were annotated by ANNOVAR software, then BMD and VD-BMD qualified variants were imported into the SKAT R-package to perform gene-based burden tests, respectively. The gene-based burden test of the exonic variants identified genome-wide candidate associations in ANKRD18A (P = 1.60 × 10-5, PBonferroni adjust = 2.11 × 10-3), C22orf31 (P = 3.49 × 10-4, PBonferroni adjust = 3.17 × 10-2), and SPATC1L (P = 1.09 × 10-5, PBonferroni adjust = 8.80 × 10-3). For VD-BMD analysis, three genes were associated with BMD, such as NIPAL1 (P = 1.06 × 10-3, PBonferroni adjust = 3.91 × 10-2). Our study suggested that rare variants contribute to BMD, providing new sights for broadening the genetic structure of BMD.

Cholecalciferol 25-Hydroxylation is Similar in Liver Microsomes from Male and Female Rats when Cholecalciferol Concentration is Low

We compared cholecalciferol 25-hydroxylation in liver microsomes of male and female rats. The rate of production of 25-hydroxycholecalciferol was similar in liver microsomes from female rats and those from male rats when cholecalciferol concentration ranged from 50 to 200 nmol/L. The liver cytosolic fraction stimulated the 25-hydroxylase activity of the microsomes up to 100% in both male and female rats at 44 nmol/L cholecalciferol. Cytosol metabolized cholecalciferol to a currently unidentified metabolite. At 300 nmol/L cholecalciferol, synthesis of the cytosolic metabolite was 100% greater than at 100 nmol/L and coincided with 32% lower synthesis of 25-hydroxy-cholecalciferol. These results suggest similar 25-hydroxy-lase activity in liver microsomes from male and female rats and similar ability of liver cytosol from these rats to stimulate 25-hydroxylation at low nanomolar concentrations of cholecalciferol, whereas inhibitory effects of cytosol at higher concentrations of cholecalciferol were shown.

Assessing Adequacy of Cholecalciferol Supplementation in Chicks Using Plasma Cholecalciferol Metabolite Concentrations as an Indicator

Cholecalciferol (vitamin D) deficiency rickets remains an occasional problem in poultry. Diagnosis currently relies on analysis of feed and histopathological examination of bone. These experiments were designed to provide data that might allow diagnosis of cholecalciferol deficiency on the basis of plasma concentrations of 25-hydroxycholecalciferol, a circulating metabolite of cholecalciferol. Day-old broiler chicks were fed corn-soybean meal or purified ingredient cholecalciferol-deficient diets supplemented with 0, 5, 10, 15, 20, 25, 37.5 or 75 µg cholecalciferol/kg diet. Plasma and bone samples were collected 21 d later. Chicks fed the unsupplemented purified ingredient diet became truly deficient, having no detectable plasma concentrations of the cholecalciferol metabolites 25-hydroxycholecalciferol, 1,25-dihydroxycholecalciferol, or 24,25-dihydroxycholecalciferol. Chicks fed the corn-soybean meal diet without supplementation had low but detectable concentrations of both 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol in plasma. Body weight, bone calcium and bone phosphorus concentrations of chicks fed the corn-soybean meal diet suggest that the cholecalciferol requirement of broiler chicks is at least 10 µg/kg diet. At this dietary level of cholecalciferol, plasma 25-dihydroxycholecalciferol concentration was 12.5 nmol/L. One hundred percent of the theoretical maximal response in body weight and bone calcium content was seen at 20 µg cholecalciferol/kg diet, which increased plasma 25-hydroxycholecalciferol concentration to 25 nmol/L in the chicks fed the corn-soybean meal diet. These data provide a nomogram of plasma 25-dihydroxycholecaiciferol concentration that can be expected from including different concentrations of cholecalciferol in the diet, and also offer a means of diagnosing cholecalciferol deficiency in field cases of rickets.

An In-Vitro Evaluation of Toxic Metals Concentration in the Third Molars from Residents of the Legnica-Głogów Copper Area and Risk Factors Determining the Accumulation of Those Metals: A Pilot Study

The purpose of this study was to determine tissue concentration of toxic metals, namely Mn, Cr, Ni, Cu, Fe, Cd, Pb, and Zn, in the removed third molars in patients from the Legnica-Głogów copper district. A group of 69 patients with an average age of 27.3 ± 6.9 years was enrolled into the study. There were 16 (23.2%) men and 53 (76.8%) women. Patients were divided into two groups according to the place of residence—residents of the Legnica-Głogów Copper Area (n = 49) and the control group, residents of Wrocław (n = 20). Determination of the Pb, Cd, Cr, Ni, Fe, Mn, Cu, Zn content was performed by atomic absorption spectrometry in an air–acetylene flame using the SpectraAA atomic absorption spectrometer with a V2 AA240FS flame attachment. The content of Fe and Pb in the third molars was higher among residents of the Legnica-Głogów Copper Area (p = 0.016 and p = 0.002, respectively). The significant risk factors that may contribute to the accumulation of toxic metals in teeth were identified. We showed a significant correlation between the level of Cr, Cu, and Zn and age, and between chromium and vitamin D3 concentration in the blood (p &lt; 0.05 for all).

The stop-feed effect of cholecalciferol (vitamin D3) and the efficacy of brodifacoum combined with cholecalciferol in Y139C-resistant Norway rats (Rattus norvegicus)

Second-generation anticoagulant rodenticides potentially build persistent residues in animals and accordingly pose a risk of secondary poisoning. We examined the effect of a low concentration of cholecalciferol in brodifacoum bait on bait consumption by Norway rats (Rattus norvegicus Berkenhout 1769) and on the control success in a laboratory study and in field trials. Additionally, the efficacy of both baits was determined against resistant Y139C rats. Cholecalciferol caused a strong stop-feed effect after two days in the laboratory study. On two field study sites each, bait containing either 25 mg kg−1 brodifacoum or 25 mg kg−1 brodifacoum and 100 mg kg−1 cholecalciferol was applied to treat infestations of Norway rats. Infestations were assessed pre- and post-treatment. Rats were radio-tagged, and carcasses were searched for during the treatment period. DNA of each rat was genotyped to determine the resistance status conferred by the VKORC1 gene. On all farms, control success exceeded 90%. On farms treated with brodifacoum only, the ratio of total bait consumption to pre-treatment census was significantly higher (6.6 and 4.8 times) than on farms treated with the combination (2.7 and 2.9 times). 78.8% of 183 rats were confirmed Y139C resistant. Bait ingestion was reduced by almost fifty per-cent when cholecalciferol was added to the bait with no impact on control success. All treatments resulted in control levels exceeding 90%, despite a high proportion of anticoagulant-resistant rats. When the use of highly toxic compounds is required in resistance management, addition of cholecalciferol to these baits may reduce the transfer of residues to the environment.

The Dietary Requirement of Juvenile Grass Shrimp (Penaeus monodon) for Vitamin D ,

Two 8-wk experiments were conducted to determine the adequate level of dietary vitamin D for juvenile grass shrimp (Penaeus monodon). In Experiment 1, purified diets with six levels (0, 0.1, 0.5, 2.5, 12.5 and 62.5 mg/kg diet) of supplemental ergocalciferol and cholecalciferol were fed to P. monodon (mean weight 0.19 +/- 0.02 g). In Experiment 2, we used 0, 0.05, 0.1, 0.2, 0.3, 0.6 and 1.0 mg/kg of supplemental cholecalciferol in basal diet fed to the shrimp (mean weight 0.25 +/- 0.03 g). In both experiments, shrimp fed vitamin D-deficient diets grew poorly. In Experiment 1, poorer growth performance was observed in shrimp fed diets containing ergocalciferol compared with those fed the diets containing cholecalciferol. In Experiment 2, weight gain was highest in shrimp fed the diet supplemented with 0.2 mg cholecalciferol/kg diet, followed by the groups fed 0.1 mg/kg, then 0.3 mg/kg, 0.05 and 0.6 mg/kg, 1.0 mg/kg, and finally the unsupplemented control group. The differences among these groups were significant (P < 0.05). The feed efficiency ratio and alkaline phosphatase activity generally followed the same pattern as the weight gain. Analysis by brokenline regression of weight gain and alkaline phosphatase activity of the shrimp in Experiment 2 indicated that the adequate dietary cholecalciferol concentration for growing P. monodon is approximately 0.1 mg/kg.

Effect of Cadmium on Oxidative Stress Indices and Vitamin D Concentrations in Children

Heavy metal poisoning can have serious health consequences, including damage to the brain, kidneys, and other organs. Cadmium is a toxic heavy metal that can accumulate in the body over time and the exposure to this element has been linked to a variety of adverse health effects. Cadmium toxicity can lead to an imbalance in the cellular redox state and be a source of oxidative stress. On the molecular level, cadmium ions negatively affect cellular metabolism, including the disruption of energy production, protein synthesis, and DNA damage. The study has been carried out on a group of 140 school-age children (8 to 14 years old) inhabiting the industrialized areas of Upper Silesia. The study population was divided into two sub-groups based on the median concentration of cadmium in blood (0.27 µg/L): Low-CdB and High-CdB. Measured traits comprised blood cadmium levels (CdB) as well as a blood count and selected oxidative stress markers. This research study aimed to demonstrate a correlation between the impact of exposure to elevated cadmium concentrations in a population of children and certain markers of oxidative stress, and 25-OH vitamin D3 concentration. A negative correlation has been found between cadmium concentration and 25-OH vitamin D3 level, protein sulfhydryl groups content in blood serum, glutathione reductase activity, and lipofuscin and malondialdehyde levels in erythrocytes. The concentration of 25-OH vitamin D3 in the High-CdB group was decreased by 23%. The oxidative stress indices can be considered a valuable indicator of early Cd-toxicity effects to be included in the routinely-applied cadmium exposure monitoring parameters, allowing the evaluation of stress intensity to the cell metabolism.

Serum vitamin D3 levels and overall survival (OS) in patients (pts) with advanced biliary tract cancer (BTC): Analysis of the NIFTY trial cohort.

613 Background: Although growing number of studies have explored the role of vitamin D3 on various cancer types, no study has been conducted in the prospective cohort of advanced BTC. This analysis aimed to evaluate the predictive or prognostic implication of serum vitamin D3 in pts with advanced BTC treated with second-line chemotherapy. Methods: The analysis is the preplanned subgroup analysis of the NIFTY trial, a multicenter, open-label, randomized, phase 2b study which compared the second-line liposomal irinotecan plus 5-FU/leucovorin and 5-FU/leucovorin in pts with advanced BTC. Serum vitamin D3 (25-hydroxyvitamin D [25(OH)D]) levels were measured at baseline (i.e., C1D1) in a total of 176 pts out of 178 pts in the ITT population and were included in the current analysis. Correlation between OS and serum vitamin D3 as a continuous variable was analyzed for linear and non-linear associations. Results: The median age was 64 years (range, 37–84) and 75 patients (42.6%) were women. The baseline serum vitamin D3 levels ranged from 1.39 ng/ml to 140.02 ng/ml in the overall pts. There was no significant difference in the mean vitamin D3 concentration according to the sex (male vs. female: 24.1 vs. 26.7; p=0.43), body mass index (BMI) (&lt;25 vs. 25-29.99 vs. ≥30: 24.0 vs. 30.0 vs 15.9; p=0.18), previous surgery (no vs. yes: 24.1 vs. 27.4; p=0.40), ECOG performance status (0 vs. 1: 24.1 vs. 25.5; p=0.66), and primary tumor site (intrahepatic vs. extrahepatic vs. gallbladder: 25.7 vs. 23.2 vs. 26.2; p=0.74). After adjustment for key prognostic factors including chemotherapy regimens, metastatic sites, or baseline CA 19-9 levels, there was no significant association between baseline serum vitamin D3 and OS (HR=1.06 per 10 increase; 95% CI, 0.97–1.15; p=0.22). In addition, there was no non-linear association between vitamin D3 and OS (p=0.52 for the linear model and p=0.62 for the model with restricted cubic splines). In the subgroup analysis, higher vitamin D3 levels were associated with poorer OS (HR=1.16 per 10 increase; 95% CI, 1.04–1.30; p=0.0072) in female pts. Conclusions: Serum vitamin D3 levels did not show significant relationship with survival in pts with advanced BTC treated with second-line chemotherapy. High vitamin D3 levels might be associated with poorer survival in female pts. Further larger studies are needed.

A Combination of Single-Nucleotide Polymorphisms Is Associated with Interindividual Variability in Cholecalciferol Bioavailability in Healthy Men

Background: Most people require dietary vitamin D to achieve the recommended concentration of 25-hydroxyvitamin D [25(OH)D] in the blood. However, the response to vitamin D supplementation is highly variable among individuals.Objective: We assessed whether the variability in cholecalciferol bioavailability was associated with single-nucleotide polymorphisms (SNPs) in candidate genes.Methods: In a single-group design, 39 healthy adult men with a mean ± SD age of 33 ± 2 y and mean ± SD body mass index (in kg/m2) of 22.9 ± 0.3 were genotyped with the use of whole-genome microarrays. After an overnight fast, plasma 25(OH)D status was measured, and the subjects then consumed a meal that provided 5 mg cholecalciferol as a supplement. Plasma chylomicron cholecalciferol concentration was measured over 8 h, and cholecalciferol response was assessed by calculating the postprandial area under the curve. Partial least squares regression was used to test the association of SNPs in or near candidate genes (61 genes representing 3791 SNPs) with the postprandial cholecalciferol response.Results: The postprandial chylomicron cholecalciferol concentration peaked at 5.4 h. The cholecalciferol response was extremely variable among individuals (CV: 47%). It correlated with the chylomicron triglyceride (TG) response (r = 0.60; P < 0.001) but not with the fasting plasma 25(OH)D concentration (r = 0.04; P = 0.83). A significant (P = 1.32 × 10−4) partial least squares regression model that included 17 SNPs in 13 genes (including 5 that have been associated with chylomicron TG response) was associated with the variance in the cholecalciferol response.Conclusion: In healthy men, there is a high interindividual variability in cholecalciferol bioavailability that is associated with a combination of SNPs located in or near genes involved in both vitamin D and lipid metabolism. This trial was registered at clinicaltrials.gov as NCT02100774.

The genetic correlation and causal association between key factors that influence vascular calcification and cardiovascular disease incidence.

Serum calcium (Ca), vitamin D (VD), and vitamin K (VK) levels are key determinants of vascular calcification, which itself impacts cardiovascular disease (CVD) risk. The specific relationships between the levels of these different compounds and particular forms of CVD, however, remain to be fully defined. This study was designed to explore the associations between these serum levels and CVDs with the goal of identifying natural interventions capable of controlling vascular calcification and thereby protecting against CVD pathogenesis, extending the healthy lifespan of at-risk individuals. Linkage disequilibrium score (LDSC) regression and a two-sample Mendelian randomization (MR) framework were leveraged to systematically examine the causal interplay between these serum levels and nine forms of CVD, as well as longevity through the use of large publically accessible Genome-Wide Association Studies (GWAS) datasets. The optimal concentrations of serum Ca and VD to lower CVD risk were examined through a restrictive cubic spline (RCS) approach. After Bonferroni correction, the positive genetic correlations were observed between serum Ca levels and myocardial infarction (MI) (p = 1.356E-04), as well as coronary artery disease (CAD) (p = 3.601E-04). Negative genetic correlations were detected between levels of VD and CAD (p = 0.035), while elevated VK1 concentrations were causally associated with heart failure (HF) [odds ratios (OR) per 1-standard deviation (SD) increase: 1.044], large artery stroke (LAS) (OR per 1-SD increase: 1.172), and all stroke (AS) (OR per 1-SD increase: 1.041). Higher serum Ca concentrations (OR per 1-SD increase: 0.865) and VD levels (OR per 1-SD increase: 0.777) were causally associated with reduced odds of longevity. These findings remained consistent in sensitivity analyses, and serum Ca and VD concentrations of 2.376 mmol/L and 46.8 nmol/L, respectively, were associated with a lower CVD risk (p < 0.001). Our findings support a genetic correlation between serum Ca and VD and CVD risk, and a causal relationship between VK1 levels and CVD risk. The optimal serum Ca (2.376 mmol/L) and VD levels (46.8 nmol/L) can reduce cardiovascular risk.

Is Vitamin D3 a Worthy Supplement Protecting against Secondary Infections in Dogs with Atopic Dermatitis?

Canine atopic dermatitis (CAD) is a common, chronic, inflammatory skin disease in dogs worldwide. This disease often predisposes for secondary organisms overgrowth and skin infections with pathogens, such as Staphylococcus pseudintermedius and Malassezia pachydermatis. Unfortunately, the causes of this disease in both humans and animals are not fully understood; therefore, the only possible option is a lifelong, symptomatic treatment. The management of CAD is mainly based on limiting contact with allergens and antipruritic therapy, most often with glucocorticoids and antihistamines. A serious problem in this situation is the fact, that long-term administration of glucocorticoids leads to side effects like polyuria, alopecia, increased susceptibility to infection, muscle atrophy, and many others. For this reason, great emphasis is placed on the development of replacement and supportive therapies. It is a well-documented fact that reduced concentrations of serum vitamin D3 contribute to the severity of atopic dermatitis symptoms in humans. Moreover, unlike the most commonly used therapeutic methods, of which the main goal is to ameliorate inflammation and pruritus, namely the symptoms of AD, vitamin D3 supplementation affects some underlying factors of this disease. Therefore, in this review, we summarize the current state of knowledge regarding the role of vitamin D3 in CAD, its protective effect against secondary bacterial and fungal infections, and the potential of its supplementation in dogs.