Increased Serum 25OHD Research Articles

A Fracture Liaison Service to Address Vitamin D Deficiency for Patients Hospitalized for Osteoporotic Fracture.

Addressing vitamin D deficiency (VDD) is important for fracture secondary prevention. To explore the function of a fracture liaison service (FLS) to address VDD. An observational study of patients admitted to the Massachusetts General Hospital with fractures between January 1, 2016, and October 31, 2023, cared for by the FLS. Ergocalciferol 50 000 international units (50ku-D2) oral daily for 3 to 7 days. VDD prevalence. Efficacy of inpatient daily 50ku-D2 in raising serum 25-hydroxyvitamin D (25OHD) levels. Of the 2951 consecutive patients, 724 (24.53%) had VDD (defined by 25OHD ≤ 19 ng/mL). Men (252/897, or 28.09%) were more likely than women (472/2054, or 22.98%) to have VDD (P = .003). VDD was seen in 41.79% (117/280), 24.41% (332/1360), and 20.98% (275/1311) of patients of aged ≤59, 60 to 79, and ≥80 years, respectively (P < .00001). Of the 1303 patients with hip fractures, 327 (25.09%) had VDD, which was associated with a longer length of stay (8.37 ± 7.35 vs 7.23 ± 4.78 days, P = .009) and higher trend of 30-day-readmission rate (13.63% vs 18.35%, P = .037). In a cohort of 32 patients with complete data, each dose of 50ku-D2 increased serum 25OHD by 3.62 ± 2.35 ng/mL without affecting serum calcium or creatinine levels. VDD was seen in nearly 25% of Massachusetts General Hospital FLS patients and more prevalent in male and younger patients. VDD was associated with longer length of stay and higher 30-day-readmission risk in patients with hip fracture. Daily 50ku-D2 appeared to be a practical way to quickly replete vitamin D in the inpatient setting.

The Effect of Vitamin D Supplementation in Pregnant Women with Overweight and Obesity: A Randomised Controlled Trial.

The impact of vitamin D supplementation on 25-hydroxyvitamin D (25OHD) levels, metabolic status, and pregnancy outcomes in pregnant women with overweight and obesity (OW/OB) is uncertain. This study aimed to examine whether administrating 800 IU of vitamin D3 orally would improve maternal serum 25OHD levels, lipid profile, and pregnancy outcomes compared to 400 IU. This was a two-arm, parallel, non-blinded randomised controlled trial involving 274 pregnant women recruited from KK Women's and Children's Hospital, with a body mass index of ≥25 kg/m2 within 16 weeks gestation. The participants were randomly assigned to receive 800 IU/day (intervention group) or 400 IU/day (control group) of oral vitamin D3 supplements. The primary outcomes were maternal serum 25OHD and lipid levels at 24-28 weeks gestation. The secondary outcomes included maternal and birth outcomes. Compared with controls (n = 119), the intervention group (n = 112) exhibited higher 25OHD levels at 24-28 weeks gestation (adjusted mean difference 6.52 nmol/L; 95% confidence interval 2.74, 10.31). More women in the intervention group achieved sufficient 25OHD levels (77.7% vs. 55.5%; p < 0.001). No differences were observed in lipid profiles or maternal or birth outcomes between the groups. An additional 400 IU of oral vitamin D3 supplementation increased serum 25OHD levels but did not impact lipid profiles or pregnancy outcomes.

Vitamin D Knowledge, Awareness, and Attitudes of Adolescents and Adults: A Systematic Review

IntroductionThe aims of this systematic review were 2-fold: (1) evaluate the effect of vitamin D educational interventions on serum 25-hydroxyvitamin D (25-OHD) concentration in adolescents (aged 10–19 years) and adults, and (2) assess the association between serum 25-OHD concentration and vitamin D knowledge, awareness of vitamin D deficiency risk, and attitudes toward behaviors associated with acquiring vitamin D. MethodsMedline, CINAHL, Embase, and SPORTDiscus were systematically searched for studies reporting associations between serum 25-OHD concentration and vitamin D knowledge, awareness, and attitudes. Results were summarized narratively. Effect sizes were calculated when data were available. ResultsEight studies reported experimental effects (2 randomized controlled trials, 1 cluster randomized trial, 4 quasi-experiments, 1 clinical audit), and 14 reported cross-sectional associations. Seven of 8 interventions reported no effect of educational interventions on serum 25-OHD concentration. A slight majority (53%; κ = 19) of studies reported statistically significant associations between serum 25-OHD concentration and vitamin D knowledge and attitudes. Implications for Research and PracticeThe few educational interventions employed to increase serum 25-OHD concentration lack effectiveness. Future studies may use randomized controlled trial designs, enroll those at risk for vitamin D insufficiency and underrepresented in the literature, increase the salience of the information to the target population, and include safe sun exposure recommendations.

Determination of Optimal Vitamin D Dosage in Children with Cholestasis

BackgroundVitamin D deficiency in patients with cholestasis is due to impaired intestinal vitamin D absorption, which results from decreased intestinal bile acid concentration. Patients with cholestasis usually do not achieve optimal vitamin D status when a treatment regimen for children without cholestasis is used. However, data on high-dose vitamin D treatment in patients with cholestasis are limited.MethodsThis study is a prospective study that included pediatric patients with cholestasis (serum direct bilirubin > 1 mg/dL) who had vitamin D deficiency (serum 25-hydroxyvitamin D, 25-OHD, < 20 ng/mL). In Phase 1, single-day oral loading of 300,000 IU (or 600,000 IU if weight ≥ 20 kg) of vitamin D2 was administered, followed by an additional loading if serum 25-OHD < 30 ng/mL, and 4-week continuation of treatment using a vitamin D2 dose calculated based on the increment of 25-OHD after first loading. In Phase 2, oral vitamin D2 (200,000 IU/day) was administered for 12 days, followed by 400,000 IU/day of vitamin D2 orally for another 8 weeks if serum 25-OHD < 30 ng/mL.ResultsPhase 1: Seven patients were enrolled. Three out of seven patients had a moderate increase in serum 25-OHD after loading (up to 20.3–27.2 ng/mL). These patients had conditions with partially preserved bile flow. The remaining four patients, who had biliary atresia with failed or no Kasai operation, had low increments of serum 25-OHD. Phase 2: Eleven patients were enrolled. Eight out of 11 patients had a moderate increase in serum 25-OHD after 200,000 IU/day of vitamin D2 for 12 days. Serum 25-OHD continued increasing after administering 400,000 IU/day of vitamin D2 for another 8 weeks, with maximal serum 25-OHD of 15.7–22.8 ng/mL.ConclusionVery high doses of vitamin D2 (200,000 and 400,000 IU/day) partly overcame poor intestinal vitamin D absorption and resulted in moderate increases in serum 25-OHD in pediatric patients with cholestasis, particularly when cholestasis was caused by uncorrectable bile duct obstruction.

Vitamin D Levels and Risk of Male Factor Infertility: A Mendelian Randomization Study.

No consensus exists about the causal relationship between vitamin D (VD) and male factor infertility due to heterogeneity and confounding factors even in randomized controlled trials (RCTs). This study aimed to investigate the causal association between 25 hydroxyvitamin D (25OHD) levels and male factor infertility through Mendelian randomization (MR) and provide complementary information for optimization of future RCTs. Two-sample MR analyses with four steps were performed. Single-nucleotide polymorphisms (SNPs) for VD were extracted from 417,580 Europeans in the UK Biobank, and the summary-level data of male factor infertility (825 cases and 85,722 controls) were extracted from the FinnGen. Totally 99 SNPs robustly associated with the 25OHD were included, and a 1-unit increase in genetically predicted natural-log transformed 25OHD levels was associated with decreased risk of male factor infertility (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.44-0.89; p=0.010), which was consistent in all three sensitivity analyses (MR-Egger, weighted median, and weighted mode methods). The conclusion still stands after removing SNPs which explained more variation in the male factor infertility than the 25OHD (OR, 0.61; 95% CI, 0.42-0.88; p=0.009; n=62), and which were associated with confounders (body mass index, type 2 diabetes, smoking, and coronary artery diseases) of male factor infertility (OR, 0.58; 95% CI, 0.39-0.85; p=0.005; n=55). VD supplement to increase serum 25OHD levels may be clinically beneficial for male factor infertility in the general population. The well-designed RCTs should be performed in priority to address this question.

Increasing vitamin D levels to improve fertilization rates in cattle.

Recently, interest in supplementing vitamin D (Vit D) to improve aspects of health, mainly in human fertility, has emerged. Still, supplementation of Vit D above the minimum required levels has yet to be explored in cattle despite evidence for Vit D receptors in reproductive tissues. The objective of this study was to establish if a dose-response relationship exists between Vit D exposure and success of in vitro production (IVP) of embryos and, if acute supplementation of Vit D improves pregnancy rates during timed artificial insemination (TAI) of dairy cows. Cumulus-oocyte complexes (COCs) were obtained from ovaries acquired from a local abattoir and cultured in five different IVP treatments from three separate collections (Control, 50, 100, 150, and 200 ng/mL of 1,25(OH)2D3; n = 20-30 COCs/group). In Experiment 2, dairy breed cows (n = 100) were synchronized for TAI with the PresynchOvsynch protocol. Cows received 150,000 IU of Vit D (n = 48) or castor oil as control (n = 53) along with gonadotropin-releasing hormone (GnRH) 24 h before TAI. Serum samples were collected before and 24 h after treatment. A small cohort of cows (n = 4) received the same treatments in two separate cycles and follicular fluid (FF) was collected after 24 h for calcidiol (25OHD) analyses. Increased concentrations of Vit D resulted in decreased rates of maturation of COC (150 and 200 ng/mL vs. control and 50 ng/mL; P = 0.01). Supplementation with 50 ng/mL resulted in greater numbers of early blastocyst and blastocyst stage embryos (P < 0.009). Pregnancy at first breeding did not differ (P = 0.13) between groups, but serum 25OHD increased in treated females after 24 h (P = 0.002). The FF 25OHD levels were reflective of serum levels, however, the observed increase in the treatment cycle (P = 0.04) was parallel to an overall increase in serum 25OHD during the entire second cycle, likely due to increased environmental sunlight exposure (March, control vs. May, treatment). A similar increase in the serum 25OHD in the lactating commercial herd maintained in covered housing was not observed, although experiments were conducted during a similar timeframe. This herd had levels of 25OHD near the low end of sufficiency according to National Research Council (NRC) guidelines. We conclude mild Vitamin D supplementation with concentrations at the higher end of NRC guidelines can improve maturation rates of recovered COCs. However, longer term supplementation may be needed to appreciate any benefits on fertility.

The effect of combined magnesium and vitamin D supplementation on vitamin D status, systemic inflammation, and blood pressure: A randomized double-blinded controlled trial

ObjectivePoor vitamin D and magnesium status is observed in individuals who are overweight and obese (Owt/Ob) and is often associated with a heightened risk of cardiovascular disease. Magnesium is a cofactor that assists vitamin D metabolism. We aimed to determine the efficacy of a combined magnesium and vitamin D regimen compared with vitamin D only on increasing serum 25-hydroxyvitamin D (25OHD) concentrations and the effects of these supplements on cardiometabolic outcomes. MethodsThis 12-week double-blinded randomized controlled trial had three treatment arms: magnesium + vitamin D (MagD; 360 mg magnesium glycinate + 1000 IU vitamin D 3 × daily), vitamin D only (VitD; 1000 IU vitamin D 3 × daily), and placebo. A total of 95 Owt/Ob participants were randomized into one of these three study arms. Anthropometry, dietary intake, concentrations of serum 25OHD, serum parathyroid hormone (PTH), serum inflammatory markers, and blood pressure were obtained at baseline and week 12. ResultsThe MagD group experienced the greatest increase in serum 25OHD concentrations (6.3 ± 8.36 ng/mL; P < 0.05). There was a decrease in systolic blood pressure (7.5 ± 8.26 mmHg; P < 0.05) for individuals who had a baseline systolic blood pressure of >132 mmHg in the MagD group. There were no statistically significant treatment effects on serum PTH concentrations and markers of inflammation. ConclusionsA combined MagD treatment may be more effective in increasing serum 25OHD concentrations compared with VitD supplementation alone in Owt/Ob individuals.

Mendelian randomization study updates the effect of 25-hydroxyvitamin D levels on the risk of multiple sclerosis

BackgroundObservational studies and previous Mendelian randomization (MR) studies have shown that genetically low 25-hydroxyvitamin D (25OHD) levels are associated with a high susceptibility to multiple sclerosis (MS). The present MR study aims to update the causal estimates for the effects of 25OHD levels on MS risk.MethodsTo date, the largest genome-wide association study (GWAS) for serum 25OHD (n = 401,460) and MS (14,498 MS cases and 24,091 controls) was used to assess the effect of serum 25OHD levels on MS. All participants were of European ancestry. The MR-egger_intercept test and Cochran’s Q statistic were used to determine the pleiotropy and the heterogeneity, respectively. MR-egger, weighted median, inverse variance weighted (multiplicative random effects), simple mode, and weighted mode methods were used to evaluate the causal association of serum 25OHD levels with MS. Finally, the effect of a single 25OHD SNP (single nucleotide polymorphism) on MS was used to test the SNP bias.ResultsOne hundred and fifteen newly identified serum 25OHD genetic variants were extracted from a large-scale serum 25OHD GWAS dataset. The 20 most effective and independent 25OHD genetic instrumental variables were extracted from the MS GWAS summary statistics. Pleiotropy analysis suggested no significant pleiotropic variant among the 20 selected 25OHD genetic instrument variants in MS GWAS datasets. As serum levels of 25OHD based on genetic changes increased, the risk of MS decreased using MR-egger (Beta = − 0.940, p = 0.001; OR = 0.391), weighted median (Beta = − 0.835, p = 0.000; OR = 0.434), IVW (Beta = − 0.781, p = 0.000; OR = 0.458), simple mode (Beta = − 1.484, p = 0.016; OR = 0.227), and weighted mode (Beta = − 0.913, p = 0.000; OR = 0.401). Our results were robust, with no obvious bias based on investigating the single 25OHD SNP on MS.ConclusionsOur analysis suggested a causal association between genetically increased serum 25OHD levels and reduced MS in the European population.

The supplementary effects of omega-3 fatty acid alone and in a combination with vitamin D3 on serum leptin levels: A randomized clinical trial on men and women with vitamin D deficiency

Purpose: This randomized clinical trial (RCT) was designed to assess the effect of VD3, n-3FA, and their combination on serum leptin levels in people with vitamin D deficiency (VDD). Subjects and methods: One hundred and forty six participants, were randomly assigned into four groups supplemented with the dose of 50,000 IU VD3 taken weekly (D), 300 mg n-3FA taken daily (Om), and their combination (D+Om) or control (C) for eight weeks. Fasting baseline and follow-up (10 weeks; 8 weeks supplementation plus washout period of 2 weeks) of serum 25 hydroxyvitamin D (25OHD), leptin, glucose, triglycerides (TG), parathyroid hormone (PTH), calcium, and phosphorus were assayed. A paired T-test was used to assess the changes in serum leptin levels over of the follow-up period. Results: Significant increase in follow-up serum leptin (10.62 ± 7.18 to 14.42 ± 8.29 ng/mL, P = 0.002) and TG (154 ± 84.4 to 200.1 ± 79, P = 0.015) levels were observed in n-3-FA supplemented group. Combination therapy (VD3 plus n-3 FA) significantly increased serum 25OHD (13.49 ± 4.64 to 37.09 ± 11.13 ng/mL, P &amp;lt; 0.001), TG levels (114.3 ± 57.3 to 139.1 ± 60.7 mg/mL, P = 0.007) and insignificantly serum leptin (6.74 ± 4.87 to 8.01 ± 6.77 ng/mL, P = 0.269). Conclusion: Our study referred that notable elevation in leptin and TG levels might be linked to leptin resistance. However, further RCTs are required to clarify possible consequences resulted from the extensive administration of n-3FA supplements and their combinations with high doses of VD3 supplements on humans’ health.

Role of vitamin D-vitamin D receptor signaling on hyperoxia-induced bronchopulmonary dysplasia in neonatal rats.

Vitamin D exerts therapeutic effects on bronchopulmonary dysplasia (BPD), but its underlying mechanisms remain unclear. The present study was designed to investigate the effects of vitamin D on hyperoxia-induced BPD and elucidate the underlying mechanisms. Neonatal rats were exposed to either room air (control) or 75% O2 (hyperoxia) and intraperitoneally injected with vitamin D3. After 14 days, a histopathological examination was performed in the lungs of rats. Serum 25-hydroxyvitamin D (25OHD) was measured by liquid chromatography-tandom mass spectrometry (LC-MS)/MS. Interleukin 1 beta (IL-1β) and interferon gamma (IFN-γ) were measured by specificenzyme-linked immunosorbent assays. The messenger RNA and protein levels of vitamin D receptor (VDR), vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), and hypoxia-inducible factor 1α (HIF-1α) were determined by real-time quantitative reverse transcription polymerase chain reaction and immunoblot analysis, respectively. Treatment with vitamin D3 increased serum 25OHD and upregulated VDR in lung tissues with or without hyperoxia. In addition, treatment with vitamin D3 attenuated alveolar simplification, increased VEGF and VEGFR2, and protected alveolar simplification induced by hyperoxia. Furthermore, treatment with vitamin D3 resulted in a decrease of IL-1β and IFN-γ and an increase of HIF-1α in lung tissues under hyperoxia conditions. Vitamin D exerts protective effects on hyperoxia-induced BPD in neonatal rats by regulating vitamin D-VDR signaling pathways.

Serum 25OHD3 of Obese Mice Is Affected by Liver Injury and Correlates with Testosterone Levels and Sperm Motility

Introduction: The concentration of 25-hydroxycholecalciferol (25OHD₃) in the serum of obese people is low and often accompanied by symptoms of low fertility. Therefore, vitamin D is recommended as a potential treatment option. However, after clinical trials, it was found that vitamin D cannot effectively increase the concentration of 25OHD₃ in the serum of obese people. How obesity causes low 25OHD₃ concentration and low fertility is unclear. Methods: We analyzed the physiological and pathological changes in obese mice induced by a high-fat diet (HFD) and the changes in mice after supplementing with 25OHD₃. Results: The concentration of 25OHD₃ in the serum of obese mice induced by HFD was significantly reduced, and these mice showed liver hypertrophy accompanied by abnormal liver injury, testicular hypertrophy, low testosterone levels, high leptin levels, and low sperm motility. The mRNA and protein expression of CYP2R1 of hydroxylated vitamin D₃ was significantly reduced; CYP11A1 and CYP11A2, which synthesize testosterone, were significantly reduced. After supplementing with 25OHD₃, there was an increase in serum 25OHD₃ concentration, testosterone level, and sperm motility, but it cannot improve the degree of obesity, CYP2R1 expression, and liver damage. Conclusion: Our research shows that there is a metabolic interference mediated by 25OHD₃ and testosterone between obesity and low sperm motility. The results of this study can provide a scientific basis for studying the mechanism of 25OHD₃ and hormone regulation and treating obese people with low sperm motility.

EFFICACY OF DOUBLE DOSE VERSUS STANDARD DOSE ERGOCALCIFEROL ON VITAMIN D STATUS AMONG PATIENTS WITH CHRONIC KIDNEY DISEASE

Background: Patients with chronic kidney disease (CKD) have an exceptionally high rate of 25-hydroxyvitamin D (25-OHD) deficiency. Modest supplementation with ergocalciferol to raise serum 25-OH-D levels might improve bone and mineral disorders in CKD. Limited evidence is available regarding dosage of ergocalciferol supplement in CKD populations.&#x0D; Objectives: The study aimed to examine the effectiveness of double-dose ergocalciferol on serum 25-OHD, serum intact parathyroid hormone (PTH) levels and mineral and safety profiles compared with standard-dose ergocalciferol among CKD subjects.&#x0D; Methods: The study employed a 12-week open labeled, randomized, controlled design among patients with CKD at stages III-IV and serum 25-OHD &lt;30 ng/mL. Patients were randomized in 2 groups: standard dose treated with ergocalciferol as recommended by K/DOQI guidelines or double dose of ergocalciferol from recommendations. Serum testing including 25-OHD, intact PTH, phosphate and calcium was performed at baseline and week 12.&#x0D; Results: Sixty-three patients were included [standard-dose group (N=30) and double-dose group (N=34)]. At the end of the 12 weeks, 20 (58.8%) patients in the double dose ergocalciferol group achieved sufficiency compared with 6 (20%) patients in the standard dose ergocalciferol group (p&lt;0.05). A significant increase in serum 25-OHD levels (13.6±9.9 vs. 8.5±6.8 ng/mL, p=0.030) and decrease in serum PTH level group (-16.8±26.4 vs. -0.3±26.8 pg/mL, p=0.030) was found in the double-dose group compared with the standard-dose group. No adverse effect was associated with the treatment.&#x0D; Conclusion: The study demonstrated that high dose oral ergocalciferol had higher efficacy to increase serum 25-OHD and decrease serum PTH levels among patients with CKD than standard-dose ergocalciferol after 12 weeks of treatment.

“Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study”

ObjectiveThe vitamin D endocrine system may have a variety of actions on cells and tissues involved in COVID-19 progression especially by decreasing the Acute Respiratory Distress Syndrome. Calcifediol can rapidly increase serum 25OHD concentration. We therefore evaluated the effect of calcifediol treatment, on Intensive Care Unit Admission and Mortality rate among Spanish patients hospitalized for COVID-19. DesignParallel pilot randomized open label, double-masked clinical trial. SettingUniversity hospital setting (Reina Sofia University Hospital, Córdoba Spain.) Participants76 consecutive patients hospitalized with COVID-19 infection, clinical picture of acute respiratory infection, confirmed by a radiographic pattern of viral pneumonia and by a positive SARS-CoV-2 PCR with CURB65 severity scale (recommending hospital admission in case of total score > 1). ProceduresAll hospitalized patients received as best available therapy the same standard care, (per hospital protocol), of a combination of hydroxychloroquine (400 mg every 12 h on the first day, and 200 mg every 12 h for the following 5 days), azithromycin (500 mg orally for 5 days. Eligible patients were allocated at a 2 calcifediol:1 no calcifediol ratio through electronic randomization on the day of admission to take oral calcifediol (0.532 mg), or not. Patients in the calcifediol treatment group continued with oral calcifediol (0.266 mg) on day 3 and 7, and then weekly until discharge or ICU admission. Outcomes of effectiveness included rate of ICU admission and deaths. ResultsOf 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50 %) p value X2 Fischer test p < 0.001. Univariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment versus without Calcifediol treatment: 0.02 (95 %CI 0.002−0.17). Multivariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment vs Without Calcifediol treatment ICU (adjusting by Hypertension and T2DM): 0.03 (95 %CI: 0.003-0.25). Of the patients treated with calcifediol, none died, and all were discharged, without complications. The 13 patients not treated with calcifediol, who were not admitted to the ICU, were discharged. Of the 13 patients admitted to the ICU, two died and the remaining 11 were discharged. ConclusionOur pilot study demonstrated that administration of a high dose of Calcifediol or 25-hydroxyvitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalization due to proven COVID-19. Calcifediol seems to be able to reduce severity of the disease, but larger trials with groups properly matched will be required to show a definitive answer.

Effects of 12‐week multivitamin supplementation on serum 25‐hydroxycholecalciferol levels in pre‐menopausal females

PURPOSEWe sought to examine if multivitamin supplementation (MV) affected serum 25‐hydroxycholecalciferol (25OHD) levels in pre‐menopausal women during a 12‐week intervention.METHODSWomen between the ages of 21–40 years who were apparently healthy and refrained from MV supplementation at least one month prior to the trial were recruited from the local Auburn, AL community. PRE testing occurred between the hours of 0600–0900 5±2 days following the menses phase of each participants’ last menstrual cycle and involved a fasted blood draw, body mass assessment, and blood pressure assessment. Following PRE testing, participants were randomly assigned in a double‐blinded fashion to either the MV group (n=43, 24±4 years old, 23.3±2.9 kg/m2) or placebo group (n=51, 23±3 years old, 23.1±2.7 kg/m2). MV capsules (per 2 beadlets‐in‐capsule serving) contained 50 mcg (2000 IU) of vitamin D3, 6.7 mg alpha tocopherol (10 IU) of vitamin E as mixed tocopherols, 90 μg vitamin K2 MK7, 600 μg (1000 DFEs) 5‐methyltetrahydrofolate, 8 μg B12, 8 mg iron, 50 mg magnesium, 1 mg boron, and 320 mg omega‐3 fatty acids. Placebo capsules contained safflower oil and cellulose beadlets. Participants in both groups were instructed to consume two capsules per day with breakfast for 12 weeks. Following the 12‐week intervention, participants reported to the laboratory between the hours of 0600–0900 5±2 days following the menses phase of the last menstrual cycle for the POST assessment which replicated PRE testing procedures. Serum 25OHD analysis was performed in a blinded fashion at a CLIA‐certified hematology laboratory (East Alabama Medical Center, Opelika, AL, USA). All dependent variables were analyzed using 2×2 (supplement × time) repeated measures ANOVAs. LSD post hoc tests were performed when significant interactions were observed, and statistical significance was established at p&lt;0.05.RESULTSSignificant supplement×time interactions were observed for dietary vitamin D intake (p&lt;0.001) and serum 25OHD levels. Four‐day food recalls indicated MV supplementation significantly increased the PRE to POST intakes of vitamin D levels (1.7±2.1 mcg/d to 51.2±1.4 mcg/d, p&lt;0.001), whereas no change in intake was observed in the placebo group. Notably, vitamin D intakes were similar at PRE and POST in the MV group when removing values added through supplementation suggesting that increases in this group were strictly due to supplementation. MV supplementation also increased serum 25OHD from PRE to POST (32.7±13.2 ng/mL to 47.0±16.2 ng/mL, p&lt;0.001), whereas no change occurred in the placebo group. Interestingly, 78% of MV participants presented low serum 25OHD levels (&lt;40 ng/mL) prior to supplementation, and MV supplementation reduced this prevalence to merely 30%. Conversely, these prevalence rates were above 70% in the placebo group prior to and following the intervention.CONCLUSIONSThese data clearly demonstrate that MV supplementation significantly increases serum 25OHD levels.Support or Funding InformationThis study was funded by a grant awarded to MDR and KCY by Ritual, Inc. Support was also provided by The GHT Companies, and Kappa BioSciences.Legend: Bar graphs are plotted as means ± standard deviation values (which are also indicated numerically at the bottom of each bar), and gray data points indicate individual respondents. The significant group × time (G × T) interaction prompted LSD post hoc tests within each group and between groups at each time point. This metric increased from PRE to POST in MV group (“*”, p&lt;0.05). Additionally, POST values were clearly elevated in the MV group (“#”, p&lt;0.05).Figure 1

Effect of Intravenous 25OHD Supplementation on Bone Turnover and Inflammation in Prolonged Critically Ill Patients.

Critically ill patients have low circulating 25-hydroxyvitamin D (25OHD), vitamin D binding protein (DBP), and 1,25-dihydroxyvitamin D [1,25(OH)2D]. Low 25OHD is associated with poor outcomes, possibly explained by its effect on bone and immunity. In this prospective, randomized double-blind, placebo-controlled study, we investigated the feasibility of normalizing 25OHD in prolonged (>10 days) critically ill patients and the effects thereof on 1,25(OH)2D, bone metabolism, and innate immunity. Twenty-four patients were included and compared with 24 matched healthy subjects. Patients were randomized to either intravenous bolus of 200 μg 25OHD followed by daily infusion of 15 μg 25OHD for 10 days, or to placebo. Parameters of vitamin D, bone and mineral metabolism, and innate immune function were measured. As safety endpoints, ICU length of stay and mortality were registered. Infusion of 25OHD resulted in a sustained increase of serum 25OHD (from median baseline 9.2 -16.1 ng/ml at day 10), which, however, remained below normal levels. There was no increase in serum 1,25(OH)2D but a slight increase in serum 24,25(OH)2D. Mineral homeostasis, innate immunity and clinical safety endpoints were unaffected. Thus, intravenous 25OHD administration during critical illness increased serum 25OHD concentrations, though less than expected from data in healthy subjects, which suggests illness-induced alterations in 25OHD metabolism and/or increased 25OHD distribution volume. The increased serum 25OHD concentrations were not followed by a rise in 1,25(OH)2D nor were bone metabolism or innate immunity affected, which suggests that low 25OHD and 1,25OHD levels are part of the adaptive response to critical illness.

Effect of sun exposure versus oral vitamin D supplementation on serum 25-hydroxyvitamin D concentrations in young adults: A randomized clinical trial

Vitamin D inadequacy is associated with a wide range of diseases. However, optimal strategies to improve vitamin D status, especially in Asian populations, remain unclear. We tested the hypotheses that (1) relevant sun exposure or oral vitamin D supplementation would significantly increase serum 25-hydroxyvitamin D (25OHD) concentrations compared with placebo, (2) sun exposure and supplementary vitamin D would be similar in serum 25OHD increases, and (3) the two interventions may have different effects on cardio-metabolic markers. In this 8-week randomized placebo-controlled clinical trial including vitamin D-deficient adults in Seoul (37°N), Korea, changes in serum 25OHD concentrations were compared between the sun exposure (daily≥20-30min around noon, n=50), oral vitamin D3 (500IU/d, n=50), and control (placebo, n=50) groups. Both sun exposure and oral vitamin D3 effectively increased serum 25OHD concentrations. Compared with placebo, the between-group least-squares mean (LSM) differences in changes were 2.2ng/mL (95% CI: 0.2, 4.2) in the sun exposure group and 8.5ng/mL (6.5, 10.5) in the oral vitamin D3 group. Increases in serum 25OHD were greater with oral vitamin D3 than with sun exposure (LSM difference in changes=6.3ng/mL, 95% CI: 4.3, 8.3). More participants in the oral vitamin D3 group (54.2%) achieved serum 25OHD concentrations≥20ng/mL at week 8 than those in the sun exposure (12.2%) or control (4.3%) groups. Compliance with sun exposure advice was relatively low, and only those with adequate compliance had a significant increase in serum 25OHD. Changes in the cardio-metabolic markers were mostly insignificant in all groups. Enhanced sun exposure and 500IU/d of oral vitamin D3 supplementation significantly increased serum 25OHD concentrations. However, our protocol for sun exposure was not as effective as 500IU/d of oral vitamin D3 supplementation. This trial was registered at clinicaltrials.gov as NCT03310242.

The effects of two vitamin D regimens on ulcerative colitis activity index, quality of life and oxidant/anti-oxidant status

BackgroundThe optimum dosage for vitamin D supplementation has not yet been elucidated in patients with Ulcerative colitis (UC). The aim of this study was to investigate the effects of two vitamin D regimens in UC patients with vitamin D deficiency.MethodsIn this double blind randomized clinical trial, 50 patients with mild to moderate UC, who met inclusion criteria, received either 1000 or 2000 IU/day of vitamin D (as low dose or high dose group, respectively) for 12 weeks. Serum 25-hydroxy vitamin D (25-OHD) level, total antioxidant capacity (TAC), and Total Oxidant Status (TOS), the inflammatory bowel disease questionnaire − 9 (IBDQ-9) score and the Simple Clinical Colitis Activity Index Questionnaire (SCCAI) score were assessed before and after intervention.ResultsAt the end of study, serum 25-OHD levels significantly increased in the high dose group (P < 0.001) and the increase was significantly more than low dose group (6.7 ± 3.8 ng/mL in the high dose group versus 0.2 ± 0.5 ng/mL in the low dose group) (P < 0.001). Serum TOS concentration decreased significantly (− 0.37 ± 0.26) only in the high dose group (P value = 0.023). There was no statistically significant change in serum TAC between two groups during the study. IBDQ-9 mean score significantly increased in high dose group compared to the low dose group (P value = 0.001) and SCCAI score in both groups reduced (− 2.58 ± 2.16 and − 0.9 ± 0.3 in high dose and low dose respectively), while this reduction was significant only in the high dose group (P value ≥0.001).ConclusionOur results indicate that 2000 IU daily dose of vitamin D can increase serum 25-OHD concentration, and quality of life, while it reduces disease activity in UC patients with vitamin D deficiency. We recommend assessment of the vitamin D status in all patients with UC because they may benefit from vitamin D therapy.

Assessing the effect of omega-3 fatty acid combined with vitamin D3 versus vitamin D3 alone on estradiol levels: a randomized, placebo-controlled trial in females with vitamin D deficiency.

PurposeOutcomes investigating the effect of vitamin D3 (VD3) and omega-3 fatty acids (Omega-3FA) on serum estradiol (E2) are scarce and conflicting. No previous study has investigated the effect of VD3 combination with Omega-3FA on E2 levels. This study was designed to investigate the effect of VD3, Omega-3FA and VD3 plus Omega-3FA on serum E2 levels in premenopausal females diagnosed with vitamin D deficiency (VDD).Subjects and methodsThis randomized, placebo-controlled clinical trial was designed to evaluate the effects of 50,000 IU VD3 taken weekly, 300 mg Omega-3FA taken daily and their combination by the study participants for 8 weeks. The mid-follicular serum levels of E2 and 25-hydroxy vitamin D (25OHD) were assessed at 8 weeks. The study was conducted during winter on a convenience sample of healthy premenopausal Jordanian females with diagnosed VDD. Fasting serum levels for 25OHD and E2 were assessed at baseline and the end of the trial (after 8 weeks). Data were entered into SPSS and analyzed.ResultsHealthy premenopausal Jordanian females (N=86) with diagnosed VDD, mean age 32.8±8.9 years, were recruited into the study. Supplementation of VD3 alone resulted in a significant increase in serum 25OHD (13.4±7.9–28.2±7.1 ng/mL, P<0.001) and a significant decrease in E2 levels (85.7±16.5–60.3±20.6 pg/mL, P=0.001). Omega-3FA intake led to a significant decrease in serum 25OHD levels (21.2±12.8–13.6±9.2 ng/mL, P=0.001) and a significant increase in E2 levels (56.3±19.2–78.4±23.7 pg/mL, P=0.006). Combination therapy (VD3 plus Omega-3FA) resulted in a significant increase in both 25OHD (12.0±4.7–35.1±9.5 ng/mL, P<0.001) and E2 (43.0±23.4–57.3±31.5 pg/mL, P=0.028) levels.ConclusionResults of this study provide vital insight into the effects of D3, Omega-3FA and a combination of their supplementation on premenopausal Jordanian females with diagnosed VDD. Eight weeks of therapy led to decreased E2 level by VD3 and increased level by Omega-3FA supplementation. With regard to 25OHD, its level was increased by VD3 and decreased by Omega-3FA supplementation. Combination of VD3 plus Omega-3FA increased the levels of both E2 and 25OHD.Trial registrationThis trial was registered at clinicaltrials.gov as NCT03333564.

Effect of 25-hydroxyvitaminD on Helicobacter pylori eradication in patients with type2 diabetes.

SummaryBackgroundVarious studies have reported a lower Helicobacter pylori eradication rate and a more frequent reinfection rate in type 2 diabetes mellitus (T2DM). Vitamin D has anti-inflammatory and immunoregulatory activity and the role of the vitamin D receptor (VDR) in the antimicrobial activity against H. pylori has been reported. When it comes to the risk factors of H. pylori eradication, the function of vitamin D is not always taken into account. The aim of this study was to assess the role of 25-hydroxyvitamin D in H. pylori eradication in T2DM.MethodsIn this retrospective study data from 160 patients with T2DM who underwent eradication therapy for H. pylori in Anhui Provincial Hospital between July 2015 and September 2017 were analyzed. According to eradication status, patients were divided into two groups, the successful eradication group (n = 124) and the eradication failure group (n = 36). The following information was obtained from participants’ records before eradication treatment: age, sex, body mass index (BMI), duration of T2DM, prescription of medication use, smoking and drinking history. All patients were tested for glycated hemoglobin (HbA1c), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL‑C), triglyceride (TG) and 25-hydroxyvitamin D (25-OHD) at baseline.ResultsThe H. pylori was eradicated in 124 (77.5%) patients, while in 36 (22.5%) patients the treatment was unsuccessful. The eradication failure group had a lower mean vitamin D concentration than the group with successful eradication (15.09 ± 7.72 ng/ml vs. 19.87 ± 6.35 ng/ml, p = 0.004). The estimated odds ratio (OR) for eradication failure in individuals with serum vitamin D deficiency (<20 ng/ml) compared to those with sufficient vitamin D levels (>30 ng/ml) were 1.489 (95% confidence interval, CI: 1.046–2.121, P = 0.027), Individuals with long duration of diabetes (≥10 years) had odds of eradication failure of 1.467 (95% CI: 1.017–2.114, P = 0.040) compared to subjects with short duration of diabetes (<10 years).ConclusionsLower 25-OHD was not only associated with H. pylori eradication failure but was also related to dyslipidemia in T2DM patients. Increasing serum 25-OHD to appropriate levels by activated vitamin D use may improve the eradication rate.

Effectiveness of two vitamin D3 repletion protocols on the vitamin D status of adults with a recent spinal cord injury undergoing inpatient rehabilitation: a prospective case series.

Prospective case series. To assess the effectiveness and safety of two vitamin D3 repletion protocols given to individuals with spinal cord injury (SCI). Publicly-funded intensive inpatient rehabilitation center, Montreal, Canada. Thirty adults with recent SCI complete or incomplete sensorimotor impairments were recruited upon admission from designated regional SCI trauma centers. Participants with serum 25OHD ≤ 30 nmol/L were given 10,000 IU of weekly and 1000 IU of daily vitamin D3 for 36.8 ± 11.9 days (higher dose: HD). Subjects with serum 25OHD > 30 nmol/L received 1000 IU of daily vitamin D3 for 38.2 ± 11.6 days (lower dose: LD). Outcomes were changes in 25OHD levels from baseline to the end of the study period and safety outcomes. Thresholds for vitamin D deficiency, insufficiency and sufficiency were: 25OHD levels ≤30 nmol/L, 30-74 nmol/L, and ≥75 nmol/L. At baseline, 34 and 66% of participants had serum 25OHD < 30 and >30 nmol/L. Both protocols induced a rise in serum 25OHD with a greater increase in the HD vs. LD regimen (31.4 [95% CI: 16.7, 46.0] vs. 11.7 nmol/L [95% CI: 2.2, 21.2]). None of the participants given the HD remained vitamin D deficient, but only one achieved vitamin D sufficiency. Nearly all individuals on the LD regimen remained vitamin D insufficient with only two reaching vitamin D sufficiency. No adverse effects were observed over the course of the supplementation. Although 1000 IU of daily vitamin D3 alone or in combination with weekly 10,000 IU for an average of 37.6 days increased serum 25OHD, they were unsuccessful in improving the impaired vitamin D status during inpatient rehabilitation of individuals with a recent SCI.