Vitamin D loaded into lipid nanoparticles shows insulinotropic effect in INS-1E cells.

Increasing evidence suggests a beneficial role of vitamin D (VitD) supplementation in addressing the widespread VitD deficiency, but currently used VitD3 formulations present low bioavailability and toxicity constrains. Hence, poly(L-lactide-co-glycolide) (PLGA) nanoparticles (NPs), solid-lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) were investigated to circumvent these issues. PLGA NPs prepared by emulsification or nanoprecipitation presented 74 or 200 nm, and association efficiency (AE) of 68 % and 17 %, respectively, and a rapid burst release of VitD3. Both SLN and NLCs presented higher polydispersity and larger NPs size, around 500 nm, which could be reduced to around 200 nm by use of hot high-pressure homogenization in the case of NLCs. VitD3 was efficiently loaded in both SLNs and NLCs with an AE of 82 and 99 %, respectively. While SLNs showed burst release, NLCs allowed a sustained release of VitD3 for nearly one month. Furthermore, NLCs showed high stability with maintenance of VitD3 loading for up to one month at 4 °C and no cytotoxic effects on INS-1E cells up to 72 h. A trending increase (around 30 %) on glucose-dependent insulin secretion was observed by INS-1E cells pre-treated with VitD3. This effect was consistently observed in the free form and after loading on NLCs. Overall, this work contributed to further elucidation on a suitable delivery system for VitD3 and on the effects of this metabolite on ß cell function.

Vitamin D [Serum 25(OH) cholecalciferol] Insufficiency is Associated With Childhood Asthma: Recent Case-Control Findings From Bangladesh.

Objectives. To evaluate the interaction between childhood asthma and S. 25(OH) cholecalciferol among Bangladeshi children. Methods. This case control study was conducted in child asthma clinic, Bangladesh Shishu Hospital Institute during March-August 2021. Comparison was made between clinically-diagnosed (following GINA guideline) asthmatic children (2-12 years-old) (cases = 87) and age and sex-matched children having no respiratory illness (controls = 90) using SPSS' (Statistical Package for Social Science, V.23.0 Windows) software. Results. Serum 25(OH) cholecalciferol was found to be significantly lower among the cases than the controls (P < .01). The cases had 3.4 times higher likelihood of having low vitamin D (combined deficient + insufficient) than the controls (P < .01). Conclusions. The results of the study demonstrate an association of Serum 25 (OH) cholecalciferol with asthma which underscores the importance of potential future trial to evaluate the efficacy of Vitamin-D supplementation for understanding the outcomes of asthmatic Bangladeshi children.

Effect of cholecalciferol supplementation on hand grip strength, walking speed, and expression of vitamin D receptor, interleukin-6, and insulin-like growth factor-1 in monocyte in pre-frail older adults: A randomized double-blind placebo-controlled trial.

AIM: To investigate the effect of cholecalciferol supplementation on hand grip strength, walking speed, and expression of vitamin D receptor (VDR), interleukine-6 (IL-6) and insulin-like growth factor-1 (IGF-1) in monocyte in pre-frail older adults. METHODS: We conducted a randomized double-blinded placebo-controlled clinical trial for 12 weeks, involving 120 pre-frail older adults who were randomized to the cholecalciferol group (cholecalciferol 4000 IU/day) or the placebo group. All subjects were given calcium lactate 500 mg/day. Hand grip strength and walking speed, as primary outcomes, were analyzed using intention-to-treat analysis. The expression of VDR, IGF-1 and IL-6 in monocytes, as secondary outcomes, were analyzed using per-protocol analysis. RESULTS: After a 12-week intervention, there was a significant increase in serum 25(OH)D levels in both groups, with the increase being higher in the cholecalciferol group than in the placebo group (49.05 vs. 24.01 ng/mL; P < 0.001). No statistically significant differences were observed in hand grip strength (P = 0.228) and walking speed (P = 0.734) between the groups. There were no differences in the expression of VDR (P = 0.513), IL-6 (P = 0.509), and IGF-1 (P = 0.503) monocytes between the groups. CONCLUSIONS: Cholecalciferol supplementation for 12 weeks increased serum 25(OH)D levels among pre-frail older adults. However, it did not improve hand grip strength and walking speed, and nor did it change the expression of VDR, IL-6, and IGF-1 in monocytes. Geriatr Gerontol Int 2024; ••: ••-••.

Unlocking the potential-vitamin D in prostate cancer prevention.

Prostate cancer poses a significant health challenge globally, demanding proactive prevention strategies. This editorial explores the emerging role of vitamin D in prostate cancer prevention. While traditionally associated with bone health, vitamin D is increasingly recognized for its broader impact on immune function, cellular signaling, and cancer prevention. Epidemiological studies suggest an intriguing link between vitamin D deficiency and elevated prostate cancer risk, particularly in regions with limited sunlight exposure. Mechanistically, vitamin D regulates cellular processes, inhibiting unchecked cancer cell growth and bolstering immune surveillance. Personalized prevention strategies, considering individual factors, are deemed essential for harnessing the full potential of vitamin D. To unlock this potential, the future calls for robust research, public awareness campaigns, dietary improvements, and vigilant medical guidance. Collaborative efforts are poised to pave the way toward a future where vitamin D stands as a sentinel in prostate cancer prevention, ushering in hope and improved health for men worldwide.

The antimicrobial effect of different vitamin D compounds on Streptococcus mutans and their impact on glycosyltransferase expression.

Background: Streptococcus mutans is a virulent microorganism associated with dental caries. This in vitro study aimed to investigate the antimicrobial effects of Cholecalciferol (D3) and Doxercalciferol (D2), against S. mutans and on glycosyltransferase gene expression. Methods: Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of D3 and D2 for S. mutans were determined according to the Clinical Laboratory Standards Institute guidelines. The effect of the compounds on environmental pH in 1% w/v and 5% w/v sucrose broth cultures after 24 hours were assessed colorimetrically. Additionally, their impact on glycosyltransferases gene expression (GtfB, GtfC, GtfD) in 5% w/v sucrose culture was evaluated using quantitative real-time PCR. Results: The MBCs of D3 and D2 were 83 µg/ml and 166 µg/ml respectively. Both compounds were effective in preventing the local pH drop <5.5 at ≥166 µg/ml in sucrose supplemented cultures. However, the compounds did not inhibit pH drop at MIC values. Notably, D2 upregulated GtfD expression significantly (p < 0.05) and downregulated GtfB and GtfC. Conclusion: Vitamin D2 and D3 inhibited S. mutans mediated pH drop in sucrose supplemented cultures and altered glycosyltransferase expression, suggesting potential therapeutic roles in dental caries prevention. Further research is needed to assess their full impact on S. mutans survival under environmental stresses.

Intermittent High-Dose Vitamin D3 Administration in Neonates with Multiple Comorbidities and Vitamin D Insufficiency.

BACKGROUND: Neonates have an increased risk of vitamin D insufficiency due to the inadequate supplementation of mothers and infants after birth. Insufficiency of vitamin D is frequently detected in critically ill patients and is associated with disease severity and mortality. There is yet to be a consensus on the appropriate regimen of vitamin D3 supplementation in high-risk infants. AIM: The main objectives of this study were to determine the prevalence of vitamin D insufficiency in neonates with severe comorbidities and to evaluate whether high-dose vitamin D3 oral administration leads to normal plasmatic concentrations without side effects. METHODS: The current study was a randomized, prospective trial of 150 patients admitted to the Neonatal Intensive Care Unit (NICU) at Maria Sklodowska Curie Emergency Children's Hospital in Bucharest. Patients were divided into three subgroups based on the chronological order of their admission date. Each subgroup received a different pharmaceutical product of vitamin D3. We administered a dosage of 10,000 IU/kg of vitamin D3 orally in three steps, as follows: at admission, one week after admission, and one month from the first administration, targeting a serum 25-hydroxyvitamin D concentration of at least 40 ng/mL. RESULTS: Most neonates (68%) achieved an optimum vitamin D level after one month, even though only 15% of patients had an optimum concentration at admission. After the first high dose of vitamin D3, there was a 27% increase in the mean vitamin D plasmatic level compared to admission levels. However, after one month, the concentrations decreased in all subgroups due to the gap of three weeks between the last two administrations. CONCLUSIONS: An intermittent, weekly high-dose vitamin D3 oral administration leads to a steadier increase and normalization of vitamin D concentration in most critically ill neonates. However, high-dose vitamin D3 administered orally after three weeks decreases vitamin D levels in this high-risk population.

Should I Supplement Vitamin D in a Patient With Sepsis?

Sepsis is a potentially fatal organ failure produced by the host's immune response to infection. It is critical to identify risk factors associated with a poor prognosis in septic patients in order to develop new therapy options. Vitamin D deficiency (25-hydroxyvitamin cholecalciferol < 20 ng/mL) is common in critical and septic patients. Serum vitamin D concentrations are associated with an increased incidence of mortality in critically ill adult patients. In critically ill patients, vitamin D supplementation (a very high vitamin D 3 or cholecalciferol loading dosage as a single bolus dose ranging from 400,000 to 540,000 IU) is feasible and safe. Some of the trials and their post-hoc analyses evaluating vitamin D supplementation in severely sick individuals, including septic patients, suggested possible benefits in mortality (reduced 28-day mortality in the range of 8.1%-17.5%), and other outcomes (reduction in hospital length in the range from 9 to 18 days, and decrease in duration of mechanical ventilation in the range from 5 to 10 days). Despite the fact that many studies support the provision of vitamin D to septic patients, there are still many studies that contradict this opinion, and there is still debate about the recommendation to use vitamin D in sepsis. A pragmatic clinical approach in severe sepsis could be supplementation of vitamin D if serum levels are diminished (< 30 ng/mL). It appears that a single ultrahigh dose of vitamin D 3 (cholecalciferol) could be administered to the septic patient via an enteral tube, followed by daily or monthly maintenance doses. Parenteral administration might be reserved for a subgroup of septic patients with gastrointestinal, hepatic, or renal dysfunction. Future clinical trials designed exclusively for septic patients are required to assess the potential advantages of vitamin D. Possible impacts of selective activators of vitamin D receptors, such as paricalcitol, should be elucidated in sepsis. This emphasizes the requirement for more study and confirmation of any potential beneficial effects of vitamin D in sepsis.

Alert for the high prevalence of vitamin D deficiency in adolescents in a large Brazilian sample.

OBJECTIVE: To estimate the prevalence of vitamin D deficiency and severe deficiency in children and adolescents, in a large Brazilian sample. METHODOLOGY: Results of 413,976 25(OH)D measurements in children and adolescents aged 0 to 18 years collected between 01/2014 and 10/2018 were obtained from the database of a Clinical Laboratory. In this population, 25 hydroxyvitamin D concentrations below 20 ng/mL are considered deficient, and below 12 ng/mL as severe deficiency. All measurements were performed by immunoassay and the results were distributed by gender, age group, seasonality, and latitude. RESULTS: The mean of 25(OH)D levels was 29.2 ng/mL with a standard deviation of 9.2 ng/mL. Of the total samples, 0.8% had a concentration < 12 ng/mL, and 12.5% of the samples had a concentration < 20 ng/mL, with a higher prevalence in females. Children under 2 years of age had the lowest prevalence. The effects of latitude and seasonality were quite evident. In samples of female adolescents from the southern region in winter, 36% of vitamin D deficiency and 5% of severe deficiency were found. CONCLUSION: In this large number of measurements of 25(OH)D in children and adolescents, 12.5% had a deficiency and 0.8% had severe deficiency. A greater deficiency was observed among adolescents, especially females, which raises questions about the need for supplementation during this period of life.

Vitamin D Deficiency in Pediatric Oncology Patients: A Single-Center Experience in Saudi Arabia.

Background There is a lack of local studies on vitamin D deficiency in children with cancer. This study aims to estimate the prevalence of vitamin D deficiency in the pediatric oncology population at King Abdul-Aziz Medical City (KAMC) in Jeddah, addressing knowledge gaps for improved clinical practice and future research. Methods This retrospective observational study was conducted from 2016 to 2021 at the pediatric oncology clinic in National Guard Hospital, Jeddah. The study focused on children aged 14 or younger at cancer diagnosis, data encompassed patient demographics, cancer details, and treatment information, including serum measurements of vitamin D (25(OH)D, calcium, phosphate, alkaline phosphatase). Vitamin D levels were categorized as deficient (<25 ng/ml), insufficient (25-49 ng/ml), sufficient (≥50- 125 ng/ml), or hypervitaminosis (>125 ng/ml), based on our center reference range and the validation of the assay. Results In this retrospective study of 155 pediatric oncology patients, the majority aged 0 to 10 years (78%), findings reveal a male preponderance (54.2%) and a more prevalent in patients with hematological malignancies (85%). Chemotherapy was administered to 98%, with 7% underwent radiotherapy, and 89% received steroids. Analysis of serum 25-OH vitamin D levels indicated an overall deficiency and insufficiency at diagnosis (63%) and post-therapy (43%). Age and gender had a significant influence on vitamin D levels at diagnosis, with older children and females exhibiting lower concentrations. However, these differences diminished by the end of therapy. Notably, hematological malignancy patients often presented insufficient vitamin D levels, while solid tumor patients frequently had sufficient levels. Clinical outcomes showed a high survival rate (90.7%), limited bone density assessments (18.1%), and a 14.2% prevalence of hypervitaminosis. Conclusion In summary, our study reveals that over two-thirds of pediatric oncology patients experience vitamin D deficiency and insufficiency at the time of diagnosis, particularly notable in females and older children. Notably, those with solid tumors exhibit higher baseline 25-OH vitamin D concentrations compared to counterparts with hematological malignancies. The findings underscore the importance of educating both patients and caregivers on supplementation and sun exposure to mitigate the prevalence of deficient and insufficient vitamin D levels in pediatric oncology cases.

Alcohol use disorder and muscle weakness: Original study of the effect of vitamin D supplementation in ambulatory participants with alcohol use disorder.

INTRODUCTION: Chronic alcohol-related myopathy presents with proximal muscle weakness. We studied the effect of vitamin D supplementation on muscle weakness in adults with alcohol use disorder. METHOD: Randomized controlled trial. Participants were community-dwelling adults with alcohol use disorder. Participants allocated to VIDIO, vitamin D intensive outreach, received bimonthly oral doses of 50,000‒100,000 IU cholecalciferol for 12 months. Participants allocated to CAU, care as usual, received prescriptions of once-a-day tablets containing 800 IU cholecalciferol and 500 mg calcium carbonate. Data included demographic variables, laboratory tests, alcohol use, and rating scales of help-seeking and support. Main outcomes were the participants' quadriceps maximum voluntary contractions (qMVC) and serum-25(OH)vitamin D concentrations, 25(OH)D. RESULTS: In 66 participants, sex ratio 50/16, mean age 51 year, alcohol use was median 52 [IQR 24‒95] drinks per week. Baseline qMVC values were 77% (SD 29%) of reference values. Laboratory tests were available in 44/66 participants: baseline 25(OH)D concentrations were 39.4 (SD 23.7) nmol/L. Thirty-one participants with 25(OH)D concentrations <50 nmol/L received either VIDIO or CAU and improved in qMVC, respectively with mean 51 (P<0.05) and 62 Newton (no P-value because of loss of follow-up) after one year of treatment. Vitamin D status increased with mean +56.1 and +37.4 nmol/L, respectively in VIDIO and CAU. CONCLUSION: The qMVC values improved during vitamin supplementation in adults with vitamin D deficiency and alcohol use disorder. Despite higher 25(OH)D concentrations in VIDIO, in terms of muscle health no advise could be given in favor of one vitamin strategy over the other. TRIAL REGISTRATION: Netherlands Trial Register (NTR) identifier: NTR4114.

Influence of vitamin D supplementation on bone mineral content, bone turnover markers, and fracture risk in South African schoolchildren: multicenter double-blind randomized placebo-controlled trial (ViDiKids).

Randomized controlled trials (RCTs) to determine the influence of vitamin D on BMC and fracture risk in children of Black African ancestry are lacking. We conducted a sub-study (n = 450) nested within a phase 3 RCT of weekly oral supplementation with 10 000 IU vitamin D3 vs placebo for 3 yr in HIV-uninfected Cape Town schoolchildren aged 6-11 yr. Outcomes were BMC at the whole body less head (WBLH) and LS and serum 25-hydroxyvitamin D3 (25(OH)D3), PTH, alkaline phosphatase, C-terminal telopeptide, and PINP. Incidence of fractures was a secondary outcome of the main trial (n = 1682). At baseline, mean serum 25(OH)D3 concentration was 70.0 nmol/L (SD 13.5), and 5.8% of participants had serum 25(OH)D3 concentrations <50 nmol/L. Among sub-study participants, end-trial serum 25(OH)D3 concentrations were higher for participants allocated to vitamin D vs placebo (adjusted mean difference [aMD] 39.9 nmol/L, 95% CI, 36.1 to 43.6) and serum PTH concentrations were lower (aMD -0.55 pmol/L, 95% CI, -0.94 to -0.17). However, no interarm differences were seen for WBLH BMC (aMD -8.0 g, 95% CI, -30.7 to 14.7) or LS BMC (aMD -0.3 g, 95% CI, -1.3 to 0.8) or serum concentrations of bone turnover markers. Fractures were rare among participants in the main trial randomized to vitamin D vs placebo (7/755 vs 10/758 attending at least 1 follow-up; adjusted odds ratio 0.70, 95% CI, 0.27 to 1.85). In conclusion, a 3-yr course of weekly oral vitamin D supplementation elevated serum 25(OH)D3 concentrations and suppressed serum PTH concentrations in HIV-uninfected South African schoolchildren of Black African ancestry but did not influence BMC or serum concentrations of bone turnover markers. Fracture incidence was low, limiting power to detect an effect of vitamin D on this outcome.

Vitamin D­the "sunshine vitamin"­is essential for helping the body to absorb calcium from the diet, which is laid down in bone to improve its strength. There is a lack of clinical trials testing whether vitamin D supplements can improve bone content of calcium and other minerals, or reduce risk of bone fractures (broken bones) in children of Black African ancestry. We therefore conducted such a study, recruiting 1682 schoolchildren aged 6­11 yr living in Cape Town, South Africa. We found that a weekly dose of 10 000 international units (250 micrograms) of vitamin D3, given by mouth for 3 yr, was effective in boosting vitamin D levels in trial participants who received it. However, this did not have any effect on bone content of calcium and other minerals. Relatively few children experienced a broken bone during the study, so we were unable to say with confidence whether or not vitamin D supplements might affect this outcome.

Serum vitamin D3 (25-OH vit D3) concentrations and hemogram changes in calves with enzootic pneumonia.

BACKGROUND: Enzootic pneumonia is an important disease complex associated with insufficient colostrum intake after birth, adverse environmental conditions, and stress. Vitamin D deficiency may be an important predisposing factor for this disease. OBJECTIVE: This study aimed to investigate in calves with enzootic pneumonia. METHODS: A total of 30 calves, aged 3-5 months, under the same care and feeding conditions were used. Groups were formed according to Clinical Respiratory Scoring as the group with mild/moderate enzootic pneumonia (n = 10), the group with severe enzootic pneumonia (n = 10), and the healthy control group (n = 10) without any disease. Blood samples were collected from the jugular vein of animals in all groups on Day 0; a complete blood count was performed, and serum vitamin D levels were measured using the Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) method. RESULTS: Although no statistical differences were observed in total leukocyte, lymphocyte, eosinophil, basophil, hemoglobin, and hematocrit levels between groups, statistically significant differences in blood neutrophil, monocyte, and erythrocyte counts were found between the groups. Monocyte counts were statistically decreased in the mild/moderate group compared with the control group. Neutrophil counts were significantly higher in the mild/moderate and severe groups than in the control group. Erythrocyte counts were increased in the mild/moderate and severe groups compared with the control group. Vitamin D concentrations were statistically lower in the mild/moderate and severe groups than in the control group. However, no statistical differences in Vitamin D concentrations were observed between the mild/moderate and severe groups. There was a negative and significant correlation between erythrocyte counts and vitamin D concentrations (r = -0.64, P < .0001). While erythrocyte counts increased in the severe group compared with the mild/moderate group, vitamin D concentrations decreased. Also, a negative and significant correlation was observed between platelet counts and vitamin D concentrations (r = -0.74, P < .0001). CONCLUSIONS: The results of this study determined that serum vitamin D concentrations in calves with pneumonia were lower than those in healthy calves. Detailed studies on the etiologic and prognostic importance of low vitamin D levels in calves with enzootic pneumonia may provide valuable data for prevention and treatment.

Rickets Types and Treatment with Vitamin D and Analogues.

The definition of "Vitamin D" encompasses a group of fat-soluble steroid compounds of different origins with similar chemical structures and the same biological effects. Vitamin D deficiency and/or a defect in the process of its synthesis or transport predispose individuals to several types of rickets. In addition to cholecalciferol, ergocalciferol, and vitamins D3 and D2, there are also active metabolites for the treatment of this condition which are commercially available. Calcitriol and aphacalcidiol are active metabolites that do not require the renal activation step, which is required with calcifediol, or hepatic activation. The purpose of this review is to summarize current approaches to the treatment of rickets for generalist physicians, focusing on the best vitamin D form to be used in each type, or, in the case of X-linked hypophosphatemic rickets (XLH), on both conventional and innovative monoclonal antibody treatments.

The Efficacy and Safety of High-Dose Cholecalciferol Therapy in Hemodialysis Patients.

Vitamin D deficiency and insufficiency are highly prevalent in CKD, affecting over 80% of hemodialysis (HD) patients and requiring therapeutic intervention. Nephrological societies suggest the administration of cholecalciferol according to the guidelines for the general population. The aim of the observational study was to evaluate the efficacy and safety of the therapy with a high dose of cholecalciferol in HD patients with 25(OH)D deficiency and insufficiency to reach the target serum 25(OH)D level > 30 ng/mL. A total of 22 patients (16 M), with an average age of 72.5 ± 13.03 years and 25(OH)D concentration of 13.05 (9.00-17.90) ng/mL, were administered cholecalciferol at a therapeutic dose of 70,000 IU/week (20,000 IU + 20,000 IU + 30,000 IU, immediately after each dialysis session). All patients achieved the target value > 30 ng/mL, with a mean time of 2.86 ± 1.87 weeks. In the first week, the target level of 25(OH)D (100%) was reached by 2 patients (9.09%), in the second week by 15 patients (68.18%), in the fourth week by 18 patients (81.18%), and in the ninth week by all 22 patients (100%). A significant increase in 1,25(OH)2D levels was observed during the study. However, only 2 patients (9.09%) achieved a concentration of 1,25(OH)2D above 25 ng/mL-the lower limit of the reference range. The intact PTH concentrations remained unchanged during the observation period. No episodes of hypercalcemia were detected, and one new episode of hyperphosphatemia was observed. In conclusion, our study showed that the administration of a high-therapeutic dose of cholecalciferol allowed for a quick, effective, and safe leveling of 25(OH)D concentration in HD patients.

Fatty acid/monoglyceride type and amount modulate fat-soluble vitamin absorption from mixed assemblies in mice.

We investigated the effects of fatty acid/ monoglyceride type and amount on the absorption of fat-soluble vitamins. Micelles or vesicles made with either caprylic acid (CA) + monocaprylin (MC) or oleic acid (OA) + monoolein (MO) at low or high concentrations were infused in bile duct-ligated mice. Retinol + retinyl ester and γ-tocopherol intestinal mucosa contents were higher in mice infused with CA + MC than with OA + MO (up to + 350 % for vitamin A and up to + 62 %, for vitamin E; p < 0.05). Cholecalciferol intestinal mucosa content was the highest in mice infused with micelles with CA + MC at 5 mg/mL (up to + 105 %, p < 0.05). Retinyl ester plasma response was higher with mixed assemblies formed at low concentration of FA + MG compared to high concentration (up to + 1212 %, p < 0.05), while no difference in cholecalciferol and γ-tocopherol plasma responses were measured. No correlation between size or zeta potential and vitamin absorption was found. The impact of FA and MG on fat-soluble vitamin absorption thus differs from one vitamin to another and should be considered to formulate adequate vitamin oral or enteral supplements.

A Prospective Open-Label Dose-Response Study to Correct Vitamin D Deficiency in Cirrhosis.

BACKGROUND: Patients with advanced liver disease often have vitamin D deficiency, but the daily dosages of vitamin D3 needed to raise their serum 25-hydrodroxyvitamin D [25(OH)D] concentrations are unknown. OBJECTIVE: We aimed to establish the dose-response relationship between vitamin D3 and 25(OH)D in patients with liver cirrhosis. DESIGN: An open-label study of orally-administered vitamin D3 (gelcaps) was conducted in patients with liver cirrhosis using a tiered-dosing regimen: 4,000 IU/d for baseline 25(OH)D ≤ 15 ng/mL and 2,000 IU/d for baseline 25(OH)D > 15 to ≤ 25 ng/mL (NCT01575717). Supplementation continued for 6 months, or until liver transplantation. Changes in 25(OH)D were measured after ≥ 3 months. Dose-response data on 48 patients (21 receiving 4000 IU/d and 27 receiving 2,000 IU/d) reporting ≥ 80% adherence were analyzed using generalized estimating equations (GEE). RESULTS: Among the 48 patients, 39 (81%) had 25(OH)D > 20 ng/mL while on supplements, and none experienced hypercalcemia. The magnitude of the increase in 25(OH)D was approximately twofold greater in patients receiving the higher dose. The mean incremental increase was 5.1 ng/ml ± 3.9 of 25(OH)D per 1000 IU/d of vitamin D3. Multivariable models demonstrated a significant positive relationship between baseline 25(OH)D and serum albumin (p < 0.01) and hemoglobin (p = 0.01), and a negative relationship with the MELD score (p < 0.01) and total bilirubin (p < 0.01). CONCLUSIONS: A two-tiered dosing regimen of daily oral vitamin D3 supplementation safely raised 25(OH)D concentrations in the majority of adults with liver cirrhosis who were adherent to supplement use.

Effects of Vitamin D Supplementation in Elite Athletes: A Systematic Review.

Background: Deficiency in vitamin D has been shown to increase the risk of injury. Purpose: To synthesize current placebo-controlled randomized trials investigating the effect of vitamin D supplementation in elite athletes on (1) aerobic capacity; (2) anaerobic measures, such as strength, speed, and anaerobic power; (3) serum biomarkers of inflammation; and (4) bone health. Study Design: Systematic review; Level of evidence, 1. Methods: A literature search was conducted on November 30, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included were randomized, placebo-controlled studies of longer than 2 weeks on subjects with active participation in organized sport. Excluded were nonrandomized controlled trial study designs, vitamin D administration routes other than oral, studies that did not use vitamin D supplementation as the sole intervention, and studies with nonathletic or military populations. Results: Out of 2331 initial studies, 14 studies (482 athletes) were included. Of the 3 studies that assessed aerobic capacity, 2 demonstrated significantly greater improvements in maximal oxygen uptake and physical working capacity-170 (P < .05) in supplemented versus nonsupplemented athletes. Measurements of anaerobic power and strength were consistently increased in supplemented groups compared with nonsupplemented groups in 5 out of the 7 studies that assessed this. Of the 6 studies that assessed sprint speed, 4 found no significant difference between supplemented and nonsupplemented groups. Aside from 1 study that found significantly lower interleukin-6 levels in supplemented athletes, measures of other inflammatory cytokines were not affected consistently by supplementation. The 4 studies that assessed markers of bone health were conflicting regarding benefits of supplementation. One study found demonstrated improvements in bone mineral density in response to supplementation (P = .02) compared with control whereas another found no significant difference between supplemented and nonsupplemented groups. However, in 3 other studies, serum biomarkers of bone turnover such as bone-specific alkaline phosphatase, parathyroid hormone, and N-terminal telopeptide appeared to be higher in subjects with lower serum vitamin D levels (P < .05). Conclusion: Results of this systematic review indicated that the greatest benefit of vitamin D supplementation in elite athletes may be improving aerobic endurance, anaerobic power, and strength. More research is needed to determine the effect of vitamin D supplementation on bone health and injury risk in this population.

Cholecalciferol Exhibits no Antibacterial Effect on Staphylococcus aureus and Escherichia coli: an in-vitro Study.

BACKGROUND: The pleiotropic effect of cholecalciferol (vitamin D3) has gained significant momentum and has been explored widely. OBJECTIVES: The study aimed to investigate the antimicrobial effect of cholecalciferol against S. aureus and E. coli. METHODS: An in-vitro study was performed for the antimicrobial effect of cholecalciferol against S. aureus and E. coli. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined following the broth microdilution method. RESULTS: The MIC value of cholecalciferol against both S. aureus and E. coli was 0.312 mg/ml, and the MBC for both organisms was 1.25 mg/ml. However, we also observed a significant antimicrobial effect in the dimethyl sulfoxide (DMSO) control at 12.5% (v/v). Therefore, the observed antimicrobial effect may be attributed to DMSO, indicating cholecalciferol does not directly inhibit S. aureus and E. coli. CONCLUSION: This study indicates that cholecalciferol does not directly inhibit S. aureus and E. coli. Hence, we suggest exploring the antibacterial properties of other vitamin D analogs, such as calcitriol or its synergetic effect with other antimicrobial agents.

Vitamin D3 as an add-on treatment for multiple sclerosis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Vitamin D deficiency has been linked to a higher risk of multiple sclerosis (MS) and disease progression. However, the efficacy of vitamin D3 as an adjuvant therapy for MS remains a controversial topic. OBJECTIVE: To perform a systematic review and meta-analysis of randomized controlled trials to assess the impact of adjunct high-dose vitamin D3 on clinical and radiological outcomes. METHODS: PubMed, Embase, and Cochrane Library were searched for trials published until December 18th, 2022. Authors independently selected randomized controlled trials involving patients with MS, with an intervention group receiving high dose (≥ 1000 IU/day) cholecalciferol and reporting clinical or radiological outcomes. Authors independently extracted data and assessed the risk of bias using a standardized, pilot-tested form. The meta-analysis was conducted using RStudio for EDSS at the last follow-up, ARR, and new T2 lesion count. RESULTS: We included 9 studies with 867 participants. No significant reduction of EDSS (MD = 0.02, CI 95 % [-0.37; 0.41], p = 0.91), ARR (MD -0.03, CI 95 % [-0.08; 0.02], p = 0.26), or new T2 lesions (MD -0.59, CI 95 % [-1.24;0.07], p = 0.08) was observed at 6-24 months. We found no evidence of publication bias. CONCLUSION: The findings of this meta-analysis strengthen current evidence that vitamin D3 supplementation has no significant impact on clinical outcomes in patients with MS. However, the non-significant reduction of new T2 lesions could precede long-term clinical benefits and should be validated in additional studies.

Integrated Management of an Adult Patient with Mucopolysaccharidosis type IVA: A Case Report with a Six-Year Follow-up.

Mucopolysaccharidosis type IVA (MPS-IVA) is a rare lysosomal storage disease caused by N-acetylglucosamine-6-sulfate-sulfatase enzyme deficiency. MPS-IVA patients show severe extra-skeletal and skeletal manifestations, featured by bone pain and deformities, frailty fractures and early onset osteoporosis. The enzyme replacement therapy (ERT) with elosulfase-α stabilizes the MPS-IVA extra-skeletal manifestations but does not significantly improve MPS-IVA skeletal manifestations. We administered an integrated therapy to an MPS-IVA 41-year-old male patient, composed of zoledronic acid, cholecalciferol and a normocalcemic (calcium intake ≥1 g/day), hyposodic (sodium intake ≤5 g/day), and normocaloric diet (bone-diet), other than ERT. During the six-year follow-up, the patient did not develop any adverse events, obtaining an improvement of bone mineral density and quality of life. Given our results, we propose this integrated treatment (i.e. ERT, zoledronic acid, cholecalciferol, and bone diet) in the management of MPS-IVA adult patients. LEARNING POINTS: Mucopolysaccharidosis type IVA (MPS-IVA) is a genetic, rare, and degenerative spondylo-epiphyso-metaphyseal dysplasia characterized by extra-skeletal and skeletal manifestations. The latter impacts on MPS-IVA patient daily activities, and enzyme replacement therapy has a poor efficacy in improving skeletal involvement.The proposed integrated management with enzyme replacement therapy, zoledronic acid, cholecalciferol and bone diet improve both bone mineral density and the prognosis quoad valetudinem of our MPS-IVA patient.