Association of vitamin D deficiency with post-exercise hypotension and arterial stiffness following prolonged endurance exercise in healthy young men.

BACKGROUND: Vitamin D is associated with vascular function; however, the impact of different vitamin D levels on vascular elasticity following prolonged exercise remains uncertain. The primary objective of this study was to investigate the association of vitamin D levels with changes in peripheral pulse wave velocity (pPWV) and the magnitude of acute post-exercise hypotension (PEH) following prolonged endurance exercise in healthy young men. METHODS: All the participants were divided into two groups: the 25-hydroxyvitamin D (25(OH)D) sufficiency group (25(OH)D ≧50 nmol/L) and the deficiency group (25(OH)D < 50 nmol/L). A cardiopulmonary exercise test for maximal oxygen uptake (V.O2max) was performed on the graded cycling. The prolonged exercise was set at 60% V.O2max for 120 min of continuous riding on a stationary bicycle. The pPWV and blood pressure were measured at baseline and 0, 15, 30, 45, 60 min after prolonged endurance exercise. RESULTS: Post hoc analysis revealed that the vitamin D sufficient group had a greater magnitude of PEH than the deficiency group at post-45 min. Multiple linear regression analyses showed a significant correlation between 25(OH)D and both pPWV (p = 0.036) and PEH (p = 0.007), after adjusting for V.O2max, weight, height, and physical activity. In addition, the 25(OH)D deficiency group also had higher pPWV at post-15 min (5.41 ± 0.93 vs 4.84 ± 0.75 m/s), post-30 min (5.30 ± 0.77 vs 4.87 ± 0.50 m/s), post-45 min (5.56 ± 0.93 vs 5.05 ± 0.68 m/s) than the sufficiency group. CONCLUSIONS: There was a positive correlation between 25(OH)D levels and systolic PEH following prolonged endurance exercise. Individuals with sufficient 25(OH)D status may have better vascular elasticity and more efficient blood pressure regulation during exercise.

Cord Blood 25-Hydroxyvitamin D Level is Correlated with a Risk for Atopic Dermatitis: Systematic Review and Meta-Analysis.

Although Indonesia is located in an equatorial region with adequate year-round sun exposure, the prevalence of 25-hydroxyvitamin D (25[OH]D) deficiency is as high as 90%. Mothers are especially vulnerable to deficiencies due to changes in their gastrointestinal system. Previous studies have reported a correlation between the 25[OH]D status of mothers with atopic dermatitis (AD) and their offspring. However, studies investigating maternal cord blood 25[OH]D levels and the incidence of AD have yielded controversial results due to its variability. As such, this systematic review and meta-analysis aimed to evaluate the correlation between maternal cord blood 25[OH]D levels and the risk for AD. In accordance with Preferred Reporting System for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the PubMed, Cochrane Library and ScienceDirect databases were searched for relevant observational studies and a meta-analysis was performed to obtain odds ratios (OR) and corresponding 95% confidence intervals (CI). Nine studies were included in the qualitative synthesis, five of which were included in the quantitative synthesis. Meta-analysis revealed that cord blood 25[OH]D levels < 50 nmol/L were associated with a 60% higher risk for the development of AD (OR = 1.60; 95% CI: 1.15, 2.22; I2 = 0%; P < 0.05). However, qualitative synthesis revealed a variety of cord blood 25[OH]D measurements and different methods of diagnosing AD in each study. Based on the current analysis, maternal cord blood 25[OH]D levels were significantly correlated with the risk for AD. Therefore, studies investigating 25[OH]D supplementation in pregnant women and its efficacy in decreasing the risk for AD are needed, especially in tropical and equatorial countries. This study also serves as a proof of concept that cord blood 25[OH]D levels can be used as a more affordable predictive parameter for AD.

In vivo contribution of Cyp24a1 promoter vitamin D response elements.

CYP24A1 is a multifunctional, P450 mitochondrial 24-hydroxylase enzyme that is responsible for catabolism of the most active vitamin D hormone (calcitriol, 1,25(OH)2D3), its precursor (calcifediol, 25(OH)D3), and numerous other vitamin D metabolites at the 23- and 24-carbon positions. In the kidney, Cyp24a1 is induced by 1,25(OH)2D3, induced by FGF23, and potently suppressed by PTH to tightly control the circulating blood levels of 1,25(OH)2D3. This gene is believed to be under the control of a pair of classic promoter proximal (PRO) vitamin D response elements (VDREs) that are aided by distal, downstream (DS) containing enhancers that we identified more recently. The DS1 enhancer cluster was found to respond to PTH and FGF23 actions in a kidney-specific manner. The DS2 enhancer cluster was found to assist in the response of 1,25(OH)2D3 in kidney, as well as other target tissues. Despite this knowledge, the in vivo contribution of the PRO VDREs to gene expression, what drives Cyp24a1 basal expression in the kidney, how FGF23 activates Cyp24a1, and importantly, how PTH suppresses Cyp24a1, all remain unknown. Here in this study, we utilize homology directed CRISPR to mutate one or both VDREs in the PRO region of the Cyp24a1 gene in vivo in the mouse to address these questions. We found that the VDRE (VDRE1) more proximal to the to the transcriptional start site (TSS) is the dominant VDRE of the pair and mutation of both VDREs leads to a dramatic loss of VDR, a reduction of Cyp24a1 gene expression in the kidney, and a near elimination of 1,25(OH)2D3 induction in the intestine. FGF23 induction of Cyp24a1 was reduced with mutation of the PRO VDREs, however, co-treatment of 1,25(OH)2D3 and FGF23 synergistically increased Cyp24a1 expression even with the loss of the PRO VDREs. PTH suppression of Cyp24a1 gene expression was unchanged with PRO VDRE mutations, despite a minor reduction in total pCREB occupancy. Finally, VDR occupancy was dramatically reduced across the DS enhancers in the Cyp24a1 locus after the PRO VDREs mutation. Taken together, our data suggest a cooperative relationship between the DS and PRO enhancers in the regulation of Cyp24a1 by 1,25(OH)2D3 and FGF23, and despite the overall reduction of CREB on the genome it appeared that suppression either does not rely on CREB or that the PRO VDREs are unconnected to PTH suppression altogether. These studies point to the DS1 region as a basal switch for Cyp24a1 expression and help further define the interconnected genomic control of these hormones on vitamin D catabolism.

The Prevalence of Low Vitamin D in Elite Para-Athletes: A Systematic Review.

BACKGROUND: Vitamin D insufficiency (25OHD, 50-75 nmolˑl- 1) is a common issue within healthy adults and elite athletes and is associated with decreased musculoskeletal health and performance. However, few studies have identified the prevalence and risk factors associated with vitamin D insufficiency within elite Para-Athletes. METHODS: An electronic search was completed on the 5th January 2023 and updated on the 21st June 2024, searching Web of Science, PubMed, Scopus, Cochrane Library and EASY (originally OpenGrey). To meet the eligibility criteria, retrieved studies were required to include at least one baseline measure of a vitamin D biomarker from elite Para-Athletes performing at national or international levels and therefore all quantitative study designs could be included. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist (8-item) for analytical cross-sectional studies. Data from the eligible studies was extracted and charted, with a supporting narrative synthesis. RESULTS: The search strategy retrieved 3083 articles, of which ten studies met the inclusion criteria. In total there were n = 355 Para-Athletes, 69.6% of which comprised of males in the included studies. Across the ten included studies, n = 546 samples were taken from n = 355 Para-Athletes across different seasons and based upon the 25(OH)D insufficiency and deficiency thresholds set by each individual study 43.2% of the samples were considered insufficient and 28.1% deficient. During the winter months vitamin D insufficiency was at its most prevalent at 74.1%, compared to 57.1% in summer of the 25(OH)D samples measured in Para-Athletes. Wheelchair athletes who competed in indoor sports were also more susceptible to low vitamin D. CONCLUSION: This review has highlighted that vitamin D insufficiency and deficiency is highly prevalent in elite level Para-Athletes, all year, across both summer and winter months. Therefore, this review highlights the need for education, treatment, and preventative measures in elite Para-Athletes throughout the year. REGISTRATION: The following systematic review was prospectively registered through PROSPERO International prospective register of systematic reviews (PROSPERO registration ID number: CRD42022362149).

Evaluation of serum vitamin D metabolites, phagocytosis, and biomarkers of inflammation in dogs with naturally occurring diabetes mellitus.

Naturally occurring diabetes mellitus (NODM) is one of the most common endocrine disorders in dogs and its etiology closely resembles type 1 diabetes mellitus (T1DM) in people. Human patients with T1DM commonly have cellular derangements consistent with inflammation, impaired immune function, and hypovitaminosis D. There is little information available regarding inflammatory biomarkers, immune function, and vitamin D status in diabetic dogs. Therefore, our objectives were to assess inflammatory biomarkers, vitamin D metabolites, and phagocytic capacity in diabetic dogs and determine whether associations exist with these variables and the level of clinical control or vitamin D metabolites. This was a prospective case-control study that included 20 otherwise healthy diabetic dogs (clinically controlled, n = 10; uncontrolled, n = 10) and 20 non-diabetic, healthy, age (± 2 years), breed, and sex matched controls. Complete blood count, biochemical panel, urinalysis, and fructosamine were performed at a single commercial reference laboratory. Basal plasma tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, and IL-10 were measured using a canine-specific multiplex bead-based assay. Serum C-reactive protein (CRP) was measured using a commercially available ELISA kit. Serum 25-hydroxyvitamin (OH)D3 and 24,25-dihydroxyvitamin (OH)2D3 were measured with HPLC. Phagocytosis of opsonized-Escherichia coli (E. coli) was evaluated with flow cytometry. Diabetic dogs had higher serum CRP concentrations than controls (p = 0.02). Plasma IL-8 concentrations were higher in diabetic dogs with uncontrolled clinical disease compared to controls (p = 0.02). Diabetic dogs had a lower percentage of leukocytes that phagocytized opsonized-E. coli (p = 0.02), but an increased number of bacteria phagocytized per cell (p < 0.001) compared to controls. No between-group differences were identified in vitamin D metabolites, nor were associations found between vitamin D and any variables. Fructosamine had a positive association with serum CRP concentration (rho = 0.35, p = 0.03) and number of bacteria phagocytized per cell (rho = 0.45, p = 0.004) in our cohort (n = 40). Like people with T1DM, diabetic dogs have a proinflammatory phenotype and phagocytic dysregulation that may be correlated with glycemic control.

The effect of vitamin D supplementation on markers of insulin resistance in women with polycystic ovarian syndrome: a systematic review.

BACKGROUND: Insulin resistance (IR) is a common pathology in women with polycystic ovarian syndrome (PCOS) involved in increased rates of cardiometabolic disease such as diabetes and cardiovascular disease. Low serum vitamin D is often associated with insulin resistance but there is no consensus on whether vitamin D supplementation can ameliorate markers of IR in PCOS. OBJECTIVES: We assessed evidence on the effects of vitamin D supplementation (≥ 1000 IU/day), without the use of additional supplements or other pharmacological treatments known to affect IR, on markers of IR and glycemic control in women with PCOS. DESIGN: A systematic search was conducted using PubMed, Medline and Web of Science databases from January 2000 up to November 2023. Randomized controlled trials that assessed the effects of vitamin D supplementation in women with PCOS, on fasting glucose, fasting insulin, glycated haemoglobin (HbA1c) or homeostatic model assessment for insulin resistance (HOMA-IR) were included. RESULTS: 9 studies were identified. Study populations ranged from 28 to 180 participants, with mean ages ranging from 22 to 30 years. Daily vitamin D doses ranged from 1714-12,000 IU. Of the included studies, 3 reported statistically significant reductions in fasting glucose, 2 reported reductions in fasting insulin, 2 reported reductions in HOMA-IR, none reported reductions in HbA1c and 5 reported no differences in any of the relevant outcomes. CONCLUSIONS: In conclusion, in RCTs of vitamin D supplementation in women with PCOS, the majority of studies do not report statistically significant improvements in fasting glucose, fasting insulin, HbA1c or HOMA-IR. However, as a minority of studies report some statistically significant results, further investigation may be warranted. REGISTRY: PROSPERO ID: CRD42023486144.

Establishment of Reference Intervals for Bone Turnover Biomarkers in Healthy Populations in Northern China.

Aim: This study was intended to establish the reference intervals of bone turnover markers (BTMs) for healthy populations. Methods: According to the Clinical Laboratory Standards Institute (CLSI) EP28-A3c, we recruited 774 healthy Chinese and investigated their clinical characteristics and relationships among gender, age, season and BTMs. The reference intervals of BTMs for healthy populations in Hebei of China were established through defining the central 95% range of all observations. Results: We found that gender were associated with 25(OH)D, OC, ß-CTX, and P1NP (P < 0.05), but not PTH1-84 (P=0.138). All serum BTMs showed differences among different age groups (P < 0.01). The level of 25 (OH) D in winter showed statistical differences with spring, summer, and autumn (P<0.05). The OC level showed statistical difference between summer and winter (P=0.000). The P1NP levels showed statistical difference between spring and winter (P=0.019), summer and winter (P=0.000), and summer and autumn (P=0.012), respectively. The PTH1-84 levels in winter showed statistical differences with spring, and summer (all P=0.000), while there was no statistically significant difference in ß- CTX levels between seasons. Conclusion: We have established the reference intervals of several BTMs for healthy individuals in Hebei of China, which have statistical significance across different age groups and genders, and there are also significant differences between different seasons. Therefore, the Chinese medical laboratories in different locations should group individuals according to gender and age groups in different seasons, and establish corresponding biological reference intervals.

Association between 25 hydroxyvitamin D and serum uric acid level in the Chinese general population: a cross-sectional study.

BACKGROUD: The relationship between serum uric acid (SUA) and 25-hydroxyvitamin D (25(OH)D) has been variably characterized in existing literature, with inconsistent results regarding its nature and implications in the Chinese population. This study aims to clarify this association, considering the potential impact of vitamin D levels on SUA. METHODS: This cross-sectional study involved 7,086 individuals from the Second Affiliated Hospital of Zhejiang University School of Medicine, screened throughout 2020. We collected data on 25(OH)D, SUA, and other metabolic markers. Logistic regression models adjusted for confounding factors were utilized to analyze the relationships. RESULTS: Our findings illustrate a statistically significant inverted U-shaped relationship between 25(OH)D and SUA. The identified threshold effect at 28.82 ng/ml is pivotal; with 25(OH)D levels below this point associated with an increased risk of hyperuricemia (odds ratio: 1.0146, p = 0.0148), and levels above it offering protective benefits (odds ratio: 0.9616, p = 0.0164). CONCLUSIONS: Our findings confirm a nonlinear, inverted U-shaped correlation between 25(OH)D and SUA, emphasizing the importance of maintaining vitamin D levels within a specific range to effectively manage hyperuricemia. These results support the implementation of personalized vitamin D supplementation strategies to optimize metabolic health outcomes, highlighting the complex interplay between vitamin D status and uric acid levels.

Accelerated bone loss in late reproductive-aged and perimenopausal women with vitamin D insufficiency.

INTRODUCTION: The association between serum vitamin D levels and bone mineral density (BMD) varies by race and gender. This study aimed to evaluate this relationship between serum vitamin D levels and BMD, and changes of BMD over time in Korean women. MATERIALS AND METHODS: We analyzed data from 586 generally healthy Korean women aged 29-79 who underwent health check-ups at Seoul National University Gangnam Center between 2010 and 2011 (baseline measurement) and 2015-2016 (follow-up). Dual energy X-ray absorptiometry (DEXA) and serum 25-hydroxyvitamin D (25OH-D) level measurements were conducted. We assessed the association between serum 25OH-D levels and BMD, as well as changes in BMD over time. RESULTS: The mean age of participants was 51.3 ± 7.9 years, with a mean follow-up interval of 4.6 ± 0.7 years, and mean serum 25OH-D level of 20.6 ± 8.5 ng/ml. Baseline serum 25OH-D levels did not correlate with BMD values at the lumbar spine, femoral neck, or total femur, nor with changes in BMD over time. A significant negative association was found between perimenopausal status and BMD changes at all sites, and between premenopausal status and lumbar bone mass, compared to postmenopausal status in the 25OH-D < 20 ng/ml group. This association was not observed in women with higher serum 25OH-D levels. CONCLUSIONS: Serum 25OH-D levels did not correlate with BMD levels or changes in BMD overall. However, in late reproductive-aged and perimenopausal women with serum 25OH-D insufficiency, there was a significant association with accelerated bone loss.

Vitamin D Deficiency-A Public Health Issue in Children.

BACKGROUND: 25-hydroxyvitamin D [25(OH)D] deficiency is a global health concern, particularly in pediatric populations, with implications for musculoskeletal health and overall well-being. This study aimed to evaluate serum 25(OH)D levels in a pediatric population and assess the prevalence of deficiency and insufficiency. METHODS: A retrospective analysis was conducted on data from 741 pediatric patients (2-17 years old) who visited an urban hospital for children for acute respiratory and gastrointestinal conditions in the span of 2 years. Serum 25(OH)D levels were measured using chemiluminescent microparticle immunoassay. Statistical analyses were performed to assess the prevalence of deficiency and insufficiency, seasonal variations, and correlations with age and daylight exposure. RESULTS: Of the 739 pediatric patients analyzed, a substantial proportion exhibited insufficient (31.80%) or deficient (36.54%) serum 25(OH)D levels. While younger age groups generally had higher mean 25(OH)D levels, a negative correlation was observed between 25(OH)D levels and age. Sunlight exposure variations did not significantly impact serum 25(OH)D levels. Despite diverse daylight exposure patterns, there were no significant differences between longer and shorter daylight periods. CONCLUSIONS: This study highlights the high prevalence of 25(OH)D deficiency and insufficiency in the pediatric population, emphasizing the need for public health monitoring and targeted supplementation strategies. Findings underscore the importance of regular consultations with healthcare providers to ensure optimal 25(OH)D levels in children, with potential implications for revising current sufficiency thresholds. Addressing 25(OH)D deficiency is crucial for promoting musculoskeletal health and overall well-being in children.

Exploring the unique association between high-density lipoprotein cholesterol and vitamin D deficiency in adults aged 20-59: findings based on the NHANES database.

BACKGROUND: Serum lipids are highly heritable and play an important role in cardiovascular and metabolic health. However, the relationship between high-density lipoprotein cholesterol (HDL-C) and serum 25-hydroxyvitamin D [25(OH)D] levels is unclear. This study aims to explore the association between serum 25(OH)D levels and HDL-C in adults aged 20-59. METHODS: This cross-sectional study was based on data from the National Health and Nutrition Examination Survey (NHANES). Multivariable logistic regression was used to assess the relationship between HDL-C and serum 25(OH)D, with further analysis using smooth spline fitting and generalized additive models. RESULTS: A total of 28,084 adults were included in the study. After adjusting for multiple variables, we found a significant positive correlation between HDL-C and serum 25(OH)D levels (ß = 8.3, 95% CI: 7.24-9.35, p < 0.001). Stratified subgroup analysis by gender showed that females consistently exhibited a positive correlation (ß = 10.12, 95% CI: 9.07-11.18, p < 0.001), while males demonstrated an inverted U-shaped relationship between HDL-C and serum 25(OH)D. CONCLUSION: In the population aged 20-59, HDL-C levels are significantly associated with serum 25(OH)D levels. Clinically, simultaneous monitoring of HDL-C and vitamin D is recommended to better assess and manage cardiovascular health. Increasing vitamin D intake should be considered, especially for males with low HDL-C levels, to prevent related health issues.

Seasonal variation of total and bioavailable 25-hydroxyvitamin D [25(OH)D] in the healthy adult Slovenian population.

Objective: The aim of our study was to compare the total 25(OH)D fraction, the bioavailable vitamin fraction, and the free vitamin D fraction in spring and fall in a group of healthy individuals. Methods: In our study, we collected blood samples from healthy participants at the end of both summer and winter, and measured serum levels of albumin, DBP, and 25(OH)D. Utilizing these data, we calculated the percentage of free and bioavailable vitamin D. Our cohort comprised 87 participants, with a male-to-female ratio of 14:73, aged 35.95 ± 12.55 years, ranging from 19 to 70 years. We employed the chemiluminescence method to determine the vitamin 25(OH)D levels, the ELISA method was utilized to determine DBP levels, the albumin BCP Assay was performed using the ADVIA biochemical analyzer (Siemens) and an online calculator was used to determine the free and bioavailable 25(OH)D levels. Results: Our findings indicate significantly lower 25(OH)D levels in winter (44.13 ± 17.82 nmol/L) compared to summer (74.97 ± 22.75 nmol/L; p < 0.001). For vitamin D binding protein there was no significant difference from summer (236.2 ± 164.39 mg/L) to winter (239.86 ± 141.9 mg/L; p = 0.77), albumin levels were significantly higher in summer (49.37 ± 4.15 g/L vs. 47.97 ± 3.91 g/L, p = 0.01), but the magnitude of the change may not be large enough to be solely responsible for the stability of vitamin D levels throughout the year. In the winter season a significantly lower calculated bioavailable 25(OH)D vitamin (7.45 ± 5.66 nmol/L against 13.11 ± 8.27 nmol/L; p < 0.001) was observed, and the free fraction also showed a significant decrease (17.3 ± 12.9 pmol/L versus 29.7 ± 19.1 pmol/L; p < 0.0001). We observed a moderately positive correlation between 25(OH)D and bioavailable percentage in winter (r = 0.680; p < 0.001), in contrast with a lower positive association in summer (r = 0.343; p < 0.001). Conclusion: Our data suggest a positive correlation between total and bioavailable 25(OH)D levels. In addition to the statistically significant variation in 25(OH)D between the two observation periods, there was an additional variation in the free vitamin D percentage. The summertime synthesis of vitamin D in the skin could contribute directly to the free fraction of vitamin D. Standardizing the measurement of free 25(OH)D and clinical studies is necessary to establish reference values before these methods can be implemented in clinical practice.

Differential performance regarding the relationship of C3-epi-25(OH)D3 levels and %C3-epi-25(OH)D3 with common pediatric diseases: a case control study.

BACKGROUND: Recently, the C3-epimer of 25-hydroxyvitamin D [C3-epi-25(OH)D] has become a topic of interest among 25-hydroxyvitamin D [25(OH)D] metabolites. Although it can lead to an overestimation of vitamin D storage, its relationship with disease occurrence remains controversial, possibly related to the great extent of tracking of 25(OH)D by C3-epi-25(OH)D over time. This study aimed to investigate the differential performance of C3-epi-25(OH)D3 and its percentage [%C3-epi-25(OH)D3] with respect to 20 common paediatric diseases. METHODS: This study involved 805 healthy children and adolescents and 2962 patients with common paediatric diseases. We investigated sex, age, and seasonal differences in C3-epi-25(OH)D3 and %C3-epi-25(OH)D3 levels; their variations on 20 common paediatric diseases; and their degree of correlation with 25(OH)D3 levels and various diseases. RESULTS: Among the healthy underage participants, C3-epi-25(OH)D3 and %C3-epi-25(OH)D3 changed similarly, with no sex differences. Moreover, their levels were higher in the infant period than in the other periods (t = 5.329-5.833, t = 4.640-5.711, all Padj < 0.001), and in spring and summer than in autumn and winter (t = 3.495-6.061, t = 3.495-5.658, all Padj < 0.01). Under healthy and disease conditions, C3-epi-25(OH)D3 was positively correlated with 25(OH)D3 (ρ = 0.318 ~ 0.678, all P < 0.017), whereas %C3-epi-25(OH)D3 was not, except in patients with nephrotic syndrome (ρ=-0.393, P = 0.001). Before and after adjusting for 25(OH)D3, the relationship of C3-epi-25(OH)D3 with the diseases was notably different. However, it was almost consistent for %C3-epi-25(OH)D3. Our results indicated that %C3-epi-25(OH)D3 was associated with short stature, nephrotic syndrome, lymphocytic leukaemia, rickets, paediatric malnutrition, and hypovitaminosis D (OR = 0.80 ~ 1.21, all P < 0.05). CONCLUSIONS: The %C3-epi-25(OH)D3 can correct the properties of C3-epi-25(OH)D3 to better track 25(OH)D3 and may be more suitable for exploring its pathological relevance. Further detailed studies of each disease should be conducted.

Umbrella Review on the Relationship between Vitamin D Levels and Cancer.

BACKGROUND: Cancer is a growing public health problem and cancer is linked to vitamin D via several mechanisms. Recent umbrella reviews on the extra-skeletal effects of vitamin D did not turn their attention to cancer. Accordingly, an overview of the current state of research is needed. MATERIALS AND METHODS: An umbrella review was conducted to provide an overview of systematic reviews on the association between vitamin D and incidence or mortality of breast cancer, colorectal cancer, lung cancer, pancreatic cancer, and prostate cancer. RESULTS: Inverse correlations were found between the vitamin D level (measured by circulating 25(OH)D) and mortality for all five types of cancer. For breast cancer, colorectal cancer, lung cancer, and pancreatic cancer, there are also hints of a lower incidence due to higher 25(OH)D levels. CONCLUSION: As most reviews include observational studies, conclusions on causality cannot be made. Methodological differences between the included reviews and different study designs in the individual studies lead to methodological problems. Despite these problems, the review shows inverse correlations between 25(OH)D levels and mortality, and mostly inverse correlations between 25(OH)D levels and incidence.

The effect of an acute bout of exercise on circulating vitamin D metabolite concentrations: a randomised crossover study in healthy adults.

The effect of acute exercise on circulating concentrations of vitamin D metabolites is unclear. To address this knowledge gap, we examined the effect of a bout of treadmill-based exercise versus rest on circulating concentrations of 25(OH)D3, 25(OH)D2, 3-epi-25(OH)D3, 24,25(OH)2D3, 1,25(OH)2D3, and vitamin D2 and D3 in healthy men and women. Thirty-three healthy adults (14 females, 41 (15) years, body mass index 26.2 (3.7) kg/m2, V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{max}}}}$ 36.2 (9.2) ml/kg/min; mean (SD)) completed two laboratory visits involving 60 min of moderate-intensity treadmill exercise (60% V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{max}}}}$ ) versus 60 min of seated rest, both in an overnight fasted-state, as part of a randomised crossover design. Venous blood samples were drawn at baseline, immediately (0 h), 1 h and 24 h after the exercise or rest-period. There was a significant time × trial interaction effect for total circulating 25(OH)D (P = 0.0148), 25(OH)D3 (P = 0.0127) and 1,25(OH)2D3 (P = 0.0226). Immediately post-exercise, 25(OH)D, 25(OH)D3 and 1,25(OH)2D3 concentrations were significantly elevated compared to the control resting condition, and 1,25(OH) 2D3 remained significantly elevated 1 h later. Circulating albumin, vitamin D binding protein, calcium and parathyroid hormone were elevated immediately post-exercise. Thus, an acute bout of moderate intensity exercise transiently increases concentrations of circulating 25(OH)D and 1,25(OH)2D3 compared to resting conditions. KEY POINTS: Observational studies suggest that acute exercise might change circulating concentrations of vitamin D metabolites, but this has not been investigated using randomised crossover studies and using robust analytical procedures. In this study, we used a randomised crossover design to examine the effect of a bout of treadmill-based exercise (vs. rest) on circulating concentrations of a wide range of vitamin D metabolites in healthy humans. We show that an acute bout of moderate intensity exercise transiently increases concentrations of circulating 25(OH)D and 1,25(OH)2D3 compared to resting conditions. These findings indicate that regular exercise could lead to transient but regular windows of enhanced vitamin D biological action.

Changes in RANKL, OPG, and 25(OH)D Levels in Children with Leukemia from Diagnosis to Remission.

BACKGROUND: The receptor activator of the nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) pathway is a determining pathway in the balance between bone formation and resorption, and disruptions in this complex can affect bone metabolism. METHODS: This study analyzes the changes in RANKL, OPG, and 25(OH)D levels; the RANKL/OPG ratio; and other bone turnover markers (BTMs) from diagnosis to complete remission in children with acute lymphoblastic leukemia (ALL). This is a prospective observational cohort study, carried out at the Instituto Mexicano del Seguro Social, Mexico City, including 33 patients (4-17 years) with newly diagnosed B-cell ALL. The patients were treated with the HP09 chemotherapy protocol. Children who had previously been treated with corticosteroids were excluded. A peripheral blood sample at diagnosis and remission was collected to determine the 25(OH)D and BTM concentrations. RESULTS: Increased RANKL (p = 0.001) and osteocalcin (p < 0.001) levels and RANKL/OPG ratio (<0.001) and a decreased OPG level (p = 0.005) were observed at remission, predominantly in the high-risk (HR) relapse and vitamin D deficiency groups. A negative association between RANKL and OPG (r = -0.454, p = 0.008) was observed. CONCLUSIONS: we suggest that the RANKL/OPG ratio could serve as a bone remodeling marker in ALL patients.

Association of serum 25-hydroxyvitamin D3 levels with carotid artery intima-media thickness and carotid atherosclerotic plaques in smokers.

OBJECTIVE: This study explores the association of serum 25-hydroxyvitamin D3 (25(OH)D3) levels with carotid artery intima-media thickness (CIMT), and the presence of carotid atherosclerotic plaques in individuals with a history of smoking. METHODS: A total of 469 patients suspected of having carotid atherosclerosis, aged 52 to 73 years with an average age of 65.26 ± 4.37 years, were recruited from the author's hospital from January 2023 to October 2023. All patients had a smoking history of nearly 5 years. Based on their serum 25(OH)D3 levels, they were divided into two groups: the normal group (serum level 30-50 ng/mL, n = 300) and the deficiency group (<30 ng/mL, n = 169). General details of the two patient groups were collected. Carotid artery ultrasound was employed to assess pulse wave velocity (PWV), carotid artery compliance coefficient (CC), and CIMT. Blood chemistry analysis measured serum lipid metabolism indicators including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HD-LC). The relationship between CIMT and each variable was analyzed through Pearson correlation, and logistic regression was used to identify risk factors influencing carotid artery plaque development. RESULTS: General patient information between the two groups showed no significant differences (P > 0.05). Patients in the 25(OH)D3 deficiency group exhibited elevated left and right PWV and CC compared to the 25(OH)D3 normal group (P < 0.05). The deficiency group exhibited larger CIMT and plaque area compared to the normal group (P < 0.05). Additionally, the deficiency group demonstrated higher levels of TC, LDL-C, and HD-LC compared to the normal group (P < 0.05). A moderate positive correlation was found between TC, LDL-C, and CIMT (P < 0.05), while a strong positive correlation existed between 25(OH)D3 and CIMT (P < 0.05). In smokers, the formation of carotid artery plaque was associated with factors such as patient age, CIMT, serum LDL-C, and 25(OH)D3 levels (P < 0.05). As age, CIMT, LDL-C levels increased, and 25(OH)D3 levels decreased, the risk of carotid plaques in smokers increased (P < 0.05). CONCLUSIONS: Smokers with lower 25(OH)D3 levels exhibit higher CIMT and more prominent carotid atherosclerotic plaques, indicating increased arterial stiffness and elevated cardiovascular risk. These findings demonstrate crucial implications that insufficient levels of vitamin D may potentially contribute to a higher risk of atherosclerosis among smokers.

25-Hydroxyvitamin D, Vitamin D Binding Protein and Gestational Diabetes Mellitus: A Two-Sample Mendelian Randomization Study.

BACKGROUND: Numerous studies have examined whether vitamin D is associated with gestational diabetes mellitus (GDM). Nevertheless, it is still challenging to determine the causality, due to a number of shortcomings in observational research and randomized controlled trials. OBJECTIVE: Mendelian randomization (MR) with two samples was conducted to investigate the potential causative association between 25-hydroxyvitamin D (25(OH)D), vitamin D binding protein (VDBP) and GDM risk. METHODS: Publicly accessible summary data from independent cohorts were used for two-sample MR. For 25(OH)D, we obtained data from UK Biobank, IEU and EBI, then performed a meta-analysis to enhance the statistical power (via METAL); for VDBP, data were obtained from the INTERVAL study; for GDM, data were obtained from FinnGen. The inverse variance weighted (IVW) approach was performed as the main analysis, together with several sensitivity analyses, such as MR-Egger, maximum likelihood, weighted median, and weighted mode. RESULTS: The IVW results revealed a weak negative causal connection between 25(OH)D and GDM risk [OR (95% CI) = 0.71 (0.50, 0.99), p = 0.046]. However, the causal association was unstable according to sensitivity analyses, and Cochran's Q test revealed significant heterogeneity. After removing BMI-related IVs, the causal association between 25(OH)D and GDM disappeared [OR (95% CI) = 0.76 (0.55, 1.06), p = 0.101]. In addition, our study found no proof to support the assumption that VDBP level was related to GDM risk causally [OR (95% CI) = 0.98 (0.93, 1.03), p = 0.408]. CONCLUSIONS: According to this study, a weak negative causal association between 25(OH)D and GDM risk was found, while we had little proof to support the link between VDBP and GDM. To further explore whether total or free 25(OH)D levels and GDM are causally related, GWAS data with an emphasis on women of reproductive age and other ethnic groups are required.

Effects of added 25(OH)D3 with varying standardized total tract digestible phosphorus concentrations on nursery pig performance, bone characteristics, and serum vitamin D status.

A total of 360 pigs (DNA 600 × 241; initially 5.8 kg) were used in a 45-d growth study to evaluate the effects of adding 25(OH)D3 with 3 levels of standardized total tract digestible (STTD) P on nursery pig growth performance, bone and urine characteristics, and serum vitamin D. Pigs were weaned at 19 d of age and randomly allotted to 1 of 6 dietary treatments with 5 pigs per pen and 12 replications per treatment. Dietary treatments were arranged in a 2 × 3 factorial with main effects of 25(OH)D3 (0 or 50 µg/kg equivalent to 2,000 IU/kg of vitamin D3; Hy-D, dsm-firmenich, Plainsboro, NJ) and STTD P (70%, 100%, or 130% of the NRC [NRC 2012. Nutrient requirements of swine. 11th rev. ed. Natl. Acad. Press, Washington, DC) requirement estimate on a dietary percentage basis]. All diets contained 1,653 IU/kg of vitamin D3. On day 45, 1 pig per pen was euthanized to collect the right fibula, metacarpal, and 2nd and 10th ribs. Overall, increasing STTD P increased (quadratic, P ≤ 0.003) ADG, ADFI, and G:F with minimal improvement above 100% of the NRC STTD P requirement estimate. Added 25(OH)D3 had no effect on growth performance. Increasing STTD P decreased urinary Ca concentration (linear, P < 0.001) and increased urinary P concentration (quadratic, P < 0.001). When pigs were fed added 25(OH)D3, serum 25(OH)D3 increased (quadratic, P = 0.005) as STTD P increased but no differences were observed when 25(OH)D3 was not added and STTD P increased (25(OH)D3 × STTD P interaction, P = 0.032). When pigs were fed 25(OH)D3, serum 1,25(OH)2D3 increased (quadratic, P < 0.001) as STTD P decreased but the increase was not significant when no 25(OH)D3 was fed (STTD P × 25(OH)D3 interaction, P = 0.002). Bone ash percentage and weight increased (quadratic, P ≤ 0.065) in all bones as STTD P increased. Added 25(OH)D3 had no effect on bone density or bone ash weight; however, the reduction in bone ash percentage observed with reducing STTD P level tended to be less when 25(OH)D3 was provided (linear interaction, P = 0.098). Increasing STTD P decreased the likelihood of abnormal histologic bone lesions in the 10th rib. In summary, added 25(OH)D3 had limited effect on growth performance; however, an increase in serum concentrations of 25(OH)D3 and 24,25(OH)2D3 was observed. The addition of 25(OH)D3 to P-deficient diets increased percentage bone ash. Increasing STTD P to 100% of NRC [NRC 2012. Nutrient requirements of swine. 11th rev. ed. Natl. Acad. Press, Washington, DC] requirement estimate increased growth and 130% of NRC maximized bone ash.

Vitamin D3 must be activated through a 2-step hydroxylation process to be metabolically active. Dietary addition of 25-hydroxyvitamin D3 [25(OH)D3] bypasses the hydroxylation step in the conversion of vitamin D3 to 25(OH)D3 in the liver and provides a greater concentration of 25(OH)D3 in circulation. The hypothesis of our experiment was that supplementing 25(OH)D3 to existing dietary levels of vitamin D3 would increase pig growth performance and bone development when added to diets deficient or marginally deficient in P. Overall, added 25(OH)D3 had limited effect on growth performance or urine parameters; however, added 25(OH)D3 increased serum concentrations of 25(OH)D3 and 24,25-dihydroxycholecalciferol [24,25(OH)2D3] and increased bone ash when added to diets deficient in P for bone mineralization (70 or 100% of the NRC (2012) standardized total tract digestible [STTD] P requirement estimate). Increasing STTD P to 100% of the NRC (2012) requirement estimate increased growth while 130% of NRC maximized bone ash.

Unlocking insights: Navigating COVID-19 challenges and Emulating future pandemic Resilience strategies with strengthening natural immunity.

The original COVID-19 vaccines, developed against SARS-CoV-2, initially mitigated hospitalizations. Bivalent vaccine boosters were used widely during 2022-23, but the outbreaks persisted. Despite this, hospitalizations, mortality, and outbreaks involving dominant mutants like Alpha and Delta increased during winters when the population's vitamin D levels were at their lowest. Notably, 75 % of human immune cell/system functions, including post-vaccination adaptive immunity, rely on adequate circulatory vitamin D levels. Consequently, hypovitaminosis compromises innate and adaptive immune responses, heightening susceptibility to infections and complications. COVID-19 vaccines primarily target SARS-CoV-2 Spike proteins, thus offering only a limited protection through antibodies. mRNA vaccines, such as those for COVID-19, fail to generate secretory/mucosal immunity-like IgG responses, rendering them ineffective in halting viral spread. Additionally, mutations in the SARS-CoV-2 binding domain reduce immune recognition by vaccine-derived antibodies, leading to immune evasion by mutant viruses like Omicron variants. Meanwhile, the repeated administration of bivalent boosters intended to enhance efficacy resulted in the immunoparesis of recipients. As a result, relying solely on vaccines for outbreak prevention, it became less effective. Dominant variants exhibit increased affinity to angiotensin-converting enzyme receptor-2, enhancing infectivity but reducing virulence. Meanwhile, spike protein-related viral mutations do not impact the potency of widely available, repurposed early therapies, like vitamin D and ivermectin. With the re-emergence of COVID-19 and impending coronaviral pandemics, regulators and health organizations should proactively consider approval and strategic use of cost-effective adjunct therapies mentioned above to counter the loss of vaccine efficacy against emerging variants and novel coronaviruses and eliminate vaccine- and anti-viral agents-related serious adverse effects. Timely implementation of these strategies could reduce morbidity, mortality, and healthcare costs and provide a rational approach to address future epidemics and pandemics. This perspective critically reviews relevant literature, providing insights, justifications, and viewpoints into how the scientific community and health authorities can leverage this knowledge cost-effectively.