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.

25-Hydroxy vitamin D deficiency is an inferior predictor of peripheral T-cell lymphomas.

The aim of the study was to explore the significance and prognostic value of 25-hydroxy vitamin D (25-(OH) D) deficiency in peripheral T-cell lymphomas (PTCLs). One hundred fifty-six patients of newly diagnosed PTCLs were enrolled in the study. Univariate and multivariate regression analyses were performed to determine independent risk factors for progression-free survival (PFS) and overall survival (OS). Receiver operating characteristic (ROC) curves were plotted, and corresponding areas under the curve (AUC) were calculated to estimate the accuracy of International Prognostic Index (IPI) plus 25-(OH) D deficiency and Prognostic Index for T-cell lymphoma (PIT) plus 25-(OH) D deficiency respectively in PTCL risk stratification. Our results showed that the 25-(OH) D deficiency was an independent inferior prognostic factor for both PFS (P = 0.0019) and OS (P = 0.005) for PTCLs, especially for AITL and PTCL-not otherwise specified (PTCL-NOS). Additionally, adding 25-(OH) D deficiency to PIT indeed has a superior prognostic significance than PIT alone for PFS (P = 0.043) and OS (P = 0.036). Multivariate COX regression analysis revealed that PIT 2‒4, albumin (ALB) ≤ 35 g/L, and 25-(OH) D deficiency were regarded as independent risk factors of PFS and OS. Our results showed that 25-(OH) D deficiency was associated with inferior survival outcome of PTCLs, especially for AITL and PTCL-NOS. PIT plus 25-(OH) D deficiency could better indicate the prognosis for PFS and OS of PTCLs than PIT.

Prevalence and predictors of vitamin D insufficiency in Brazilian children under 5 years of age: Brazilian National Survey on Child Nutrition (ENANI-2019).

To analyse the association of socio-demographic and health factors with vitamin D insufficiency and 25-hydroxyvitamin D (25(OH)D) concentration in Brazilian children aged 6-59 months. Data from 8145 children from the Brazilian National Survey on Child Nutrition (ENANI-2019) were analysed. The serum concentration of 25(OHD)D was measured using a chemiluminescent immunoassay. The prevalence of vitamin D insufficiency (25(OH)D < 50 nmol/l) and 95 % CI was calculated. Logistic and linear regression models were used to identify the variables associated with vitamin D insufficiency and serum 25(OH)D concentrations, respectively. The mean 25(OH)D concentration was 98·6 ± 36·0 nmol/l, and 4·3 % of the children presented vitamin D insufficiency. Children aged 6-23 months (OR = 2·23; 95 % CI 1·52, 3·26); belonging to Southeast (OR = 5·55; 95 % CI 2·34, 13·17) and South (OR = 4·57; 95 % CI 1·77, 11·84) regions; the second tertile of the National Wealth Score (OR = 2·14; 95 % CI 1·16, 3·91) and winter (OR = 5·82; 95 % CI 2·67, 12·71) and spring (OR = 4·84; 95 % CI 2·17, 10·80) seasons of blood collection were associated with a higher chance of vitamin D insufficiency. Female sex (ß = -5·66, 95 % CI - 7·81, -3·51), urban location (ß = -14·19, 95 % CI -21·0, -7·22) and no vitamin D supplement use (ß = -6·01, 95 % CI -9·64, -2·39) were inversely associated with serum 25(OH)D concentration. The age of children and the Brazilian geographical region of household location were the main predictors of vitamin D insufficiency. In Brazil, vitamin D insufficiency among children aged 6-59 months is low and is not a relevant public health problem.

Contribution of body mass index, waist circumference, and 25-OH-D3 on the risk of pre-diabetes mellitus in the Chinese population.

This study aimed to investigate the associations between body mass index (BMI), waist circumference (WC), 25-hydroxy-vitamin D3 (25-OH-D3), and the risk of pre-diabetes mellitus (PDM), as well as their predictive values in identifying PDM. A total of 1688 participants were included in this cross-sectional investigation. Spearman's correlation analysis was used to assess the relationships between candidate indicators and PDM. The impact of indicators on PDM risk was determined by multivariate logistic regression. The receiver operating characteristic (ROC) analysis was performed to evaluate the prognostic value of indicators. Our study indicated a positive correlation between WC, BMI, and 25-OH-D3 and PDM. WC (OR = 1.05, 95% CI = 1.04-1.06, p < 0.001), BMI (OR = 1.11, 95% CI = 1.08-1.15, p < 0.001), and 25-OH-D3 (OR = 1.01, 95% CI = 1.00-1.02, p = 0.037) and an increased risk of PDM. Additionally, the ROC analysis demonstrated that WC (AUC = 0.651, Specificity = 55.00%, Sensitivity = 67.900%) had a higher diagnostic value for predicting PDM compared to the other variables (BMI, 25-OH-D3, TG, TC, LDL-C, HDL-C, and UA). A cut-off value of WC > 80.5 cm predicted PDM with both good sensitivity and specificity. Additionally, the cut-off value of waist circumference (WC) for men with prediabetes was 86.500, while for women with prediabetes, it was 76.500.

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.

Correlation analysis of 25(OH)D with cognitive function in epilepsy patients: A cross-sectional study.

OBJECTIVE: To analyze the correlation between the level of 25(OH)D in peripheral blood and cognitive function in patients with epilepsy, and to find the biomarkers of epilepsy complicated with cognitive dysfunction. METHODS: 68 patients with epilepsy and 30 healthy subjects were included in this study. The 25(OH)D level in peripheral blood of all subjects was detected and the score of the Montreal Cognitive Assessment Scale was performed. The patients with epilepsy were divided into a cognitively normal group (36 cases) and a cognitively impaired group (32 cases) according to the scale score. The inter-group scale score and 25(OH)D level were compared, and the correlation was analyzed. RESULTS: The levels of 25(OH)D and MOCA in epileptic group were significantly lower than those in healthy control group. The 25(OH)D and MOCA of the cognitively impaired group were significantly lower than those of the cognitively normal group. Logistic regression analysis indicated that serum 25(OH)D level was an independent risk factor for epilepsy combined with cognitive impairment (OR = 0.704, P = 0.014). The area under ROC curve of serum 25(OH)D for diagnosis of epilepsy combined with cognitive impairment was 0.924 (95 %CI 0.866,0.981), the critical value was 34.50 nmol/L, the sensitivity was 0.778, and the specificity was 0.906. CONCLUSION: Decreased levels of vitamin D are associated with cognitive impairment associated with epilepsy, and it may be a biomarker for early screening of cognitive impairment.

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.

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.

No causal association between serum vitamin D levels and diabetes retinopathy: A Mendelian randomization analysis.

BACKGROUND AND AIM: Diabetes retinopathy (DR) is a common microvascular complication of diabetes, and it is the main cause of global vision loss. The current observational research results show that the causal relationship between Vitamin D and DR is still controversial. Therefore, we conducted a Mendelian randomization study to determine the potential causal relationship between serum 25-hydroxyvitamin D 25(OH)D and DR. METHODS AND RESULTS: In this study, we selected aggregated data on serum 25(OH)D levels (GWAS ID: ebi-a-GCST90000615) and DR (GWAS ID: finn-b-DM_RETINOPATHY) from a large-scale GWAS database. Then use MR analysis to evaluate the possible causal relationship between them. We mainly use inverse variance weighted (IVW), supplemented by MR Egger and weighted median methods. Sensitivity analysis is also used to ensure the stability of the results, such as Cochran's Q-test, MR-PRESSO, MR-Egger interception test, and retention method. The MR analysis results showed that there was no significant causal relationship between 25(OH)D and DR (OR = 1.0128, 95%CI=(0.9593,1.0693), P = 0.6447); Similarly, there was no significant causal relationship between DR and serum 25 (OH) D levels (OR = 0.9900, 95% CI=(0.9758,1.0045), P = 0.1771). CONCLUSION: Our study found no significant causal relationship between serum 25(OH)D levels and DR, and vice versa. A larger sample size randomized controlled trial is needed to further reveal its potential causal relationship.

Causal effect of serum 25 hydroxyvitamin D concentration on cardioembolic stroke: Evidence from two-sample Mendelian randomization.

BACKGROUND AND AIMS: The putative association between serum 25-hydroxyvitamin D concentration [25(OH)D] and the risk of cardioembolic stroke (CES) has been examined in observational studies, which indicate controversial findings. We performed Mendelian randomization (MR) analysis to determine the causal relationship of serum 25(OH)D with the risk of CES. METHODS AND RESULTS: The summary statistics dataset on the genetic variants related to 25(OH)D was used from the published GWAS of European descent participants in the UK Biobank, including 417,580 subjects, yielding 143 independent loci in 112 1-Mb regions. GWAS summary data of CES was obtained from GIGASTROKE Consortium, which included European individuals (10,804 cases, 1,234,808 controls). Our results unveiled a causal relationship between 25(OH)D and CES using IVW [OR = 0.82, 95% CI: 0.67-0.98, p = 0.037]. Horizontal pleiotropy was not seen [MR-Egger intercept = 0.001; p = 0.792], suggesting an absence of horizontal pleiotropy. Cochrane's Q [Q = 78.71, p-value = 0.924], Rucker's Q [Q = 78.64, p-value = 0.913], and I2 = 0.0% (95% CI: 0.0%, 24.6%) statistic suggested no heterogeneity. This result remained consistent using different MR methods and sensitivity analyses, including Maximum likelihood [OR = 0.82, 95%CI: 0.67-0.98, p-value = 0.036], Constrained maximum likelihood [OR = 0.76, 95%CI: 0.64-0.90, p-value = 0.002], Debiased inverse-variance weighted [OR = 0.82, 95%CI: 0.68-0.99, p-value = 0.002], MR-PRESSO [OR = 0.82, 95%CI 0.77-0.87, p-value = 0.022], RAPS [OR = 0.82, 95%CI 0.67-0.98, p-value = 0.038], MR-Lasso [OR = 0.82, 95%CI 0.68-0.99, p-value = 0.037]. CONCLUSION: Our MR analysis provides suggestive evidence that increased 25(OH)D levels may play a protective role in the development of cardioembolic stroke. Determining the role of 25(OH)D in stroke subtypes has important clinical and public health implications.

Prevalence and risk factors of low vitamin D levels in children and adolescents with familial hypokalemic periodic paralysis.

Patients with familial hypokalemic periodic paralysis (HOKPP) experience episodes of reversible immobility and are at an increased risk of limited sunlight exposure, potentially leading to vitamin D deficiency. However, there is a lack of data on vitamin D levels in this population. We investigated serum vitamin D levels and their associated factors in children with HOKPP. This study included 170 genetically-confirmed children with HOKPP, aged 3-18 years, and 170 age-, sex-, and body mass index (BMI)-matched healthy controls from the Korean Channelopathy Study, a prospective controlled investigation. Anthropometric and clinical characteristics were recorded, and serum levels of calcium, ionized calcium, phosphorus, alkaline phosphatase, 25-hydroxyvitamin D, and intact parathyroid hormone (PTH) were analyzed. Vitamin D deficiency (< 20 ng/mL) was observed in 87.0% of the patients compared to 45.5% of the controls (P < 0.05) during the summer-fall season. During the winter-spring season, 91.7% of the patients and 73.4% of the controls were deficient (P < 0.05). A strong positive correlation was found between onset age of the first paralytic attack and vitamin D levels (r = 0.78, P < 0.01). Conversely, the frequency and duration of paralytic attacks were negatively correlated with vitamin D levels (r = -0.82 and r = -0.65, P < 0.01, respectively). Age, BMI, age at onset, frequency and duration of attacks, and PTH levels were independently associated with vitamin D levels (ß = -0.10, -0.12, 0.19, -0.27, -0.21, and -0.13, P < 0.05, respectively). CONCLUSIONS: Vitamin D deficiency was highly prevalent in children with HOKPP, and vitamin D levels correlated with various disease characteristics. We recommend routine screening for vitamin D levels in these patients to address this prevalent deficiency. Considering the high prevalence of vitamin D deficiency observed, further research on other diseases characterized by reversible immobility is warranted. WHAT IS KNOWN: • A correlation between immobility and low serum vitamin D levels has been established. However, the vitamin D status of patients with familial hypokalemic periodic paralysis (HOKPP) who experience periods of reversible immobility remains unknown. WHAT IS NEW: • Vitamin D deficiency was highly prevalent in children with HOKPP, and vitamin D levels correlated with various disease characteristics.

Association between serum 25-hydroxyvitamin D and vitamin D dietary supplementation and risk of all-cause and cardiovascular mortality among adults with hypertension.

BACKGROUND: The relationship between vitamin D status and mortality among adults with hypertension remains unclear. METHODS: This prospective cohort study involved a sample of 19,500 adults with hypertension who participated in the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2018. We utilized a weighted COX proportional hazard model to assess the association between vitamin D status and mortality. This statistical model calculates hazard ratios (HR) and their corresponding 95% confidence intervals (95% CI). RESULTS: The study indicated that lower serum 25(OH)D concentration was associated with an increased risk of all-cause mortality among individuals with hypertension. Specially. Those with concentrations between 25.0 and 49.9 nmol/L (HR = 1.71, 95%CI = 1.22-2.40) and less than 25.0 nmol/L (HR = 1.97, 95%CI = 1.15-3.39) had higher hazard ratios for all-cause mortality. Individuals with hypertension who took vitamin D supplements had a lower risk of all-cause mortality, but not the risk of CVD mortality (HR 0.75, 95%CI 0.54-1.03), compared to those who did not supplement (HR = 0.76, 95%CI = 0.61-0.94). Subgroup analysis further revealed that vitamin D supplementation was associated with a reduced risk of all-cause mortality among individuals without diabetes (HR = 0.65, 95%CI = 0.52-0.81) and individuals without CVD (HR = 0.75, 95%CI = 0.58-0.97), and a decreased risk of CVD mortality among individuals without diabetes (HR = 0.63, 95%CI = 0.45-0.88) and without CVD (HR = 0.61, 95%CI = 0.40-0.92). Furthermore, higher-dose vitamin D supplementation was also associated with a greater reduction in all-cause mortality among hypertensive individuals, and there was the potential synergistic effect of combining normal-dose calcium and vitamin D supplementation, showing a superior effect on mortality compared to low-dose supplementation in adults with hypertension. CONCLUSIONS: This prospective cohort study demonstrated a significant association between lower serum 25 (OH)D concentration and increased all-cause mortality among adults with hypertension. Furthermore, the study found that vitamin D supplementation had a strong and significantly positive correlation with reduced all-cause and CVD mortality among hypertensive individuals without diabetes or CVD. This positive correlation suggests that vitamin D supplementation could potentially be an effective strategy to reduce the risk of mortality in this specific group of people.

When to suspect infantile hypercalcemia-1?

PURPOSE: The screening test to suspect infantile hypercalcemia-1 (HCINF1) is the measure of 25(OH)D3/24,25(OH)2D3 ratio at mass spectroscopy (MS). When the ratio is > 80, the gold standard for the diagnosis is genetic analysis. Given its limited availability, MS may not represent a screening test and most cases of HCINF1 remain undiagnosed. Aim of the study is to identify cut-offs of serum calcium and PTH useful to suspect patients with HCINF1. METHODS: We compared the levels of total serum calcium and PTH of 6 patients with HCINF1 harboring biallelic CYP24A1 pathogenic variants with 3 different control groups: (1) 12 subjects wild type for CYP24A1; (2) 12 subjects matched for age and sex; (3) 12 subjects matched for vitamin D levels. We validated the cut-offs, testing the number of adult patients affected by HCINF1 reported in the literature that could be identified using these cut-offs. RESULTS: A serum calcium level > 9.6 mg/dL showed the highest sensitivity (100%) and specificity (91%) in the comparison between homozygous and wild-type subjects. A serum PTH index < 0.315 showed the highest sensitivity (100%) and specificity (83.3%). A serum calcium level > 9.6 mg/dL was able to identify all adult HCINF1 patients whereas a PTH ratio < 0.315 identified 89.8% of the cases. Superimposable results were obtained using the other control groups. CONCLUSION: Patients with serum calcium levels higher than 9.6 mg/dL and a PTH index lower than 0.315 are likely to be affected by HCINF1. Their diagnosis may be confirmed using MS and genetic analysis.

The correlation analysis between alterations of serum vitamin D, IL-33 levels, and clinical improvement after narrow-band UVB treatment in vitiligo patients: A case-control study.

BACKGROUND: The etiology of vitiligo has not been completely elucidated. Recently, 25-hydroxyvitamin D (25(OH)D) and IL-33 levels were found to be associated with the development of the vitiligo. The aim was to assess relationship between 25(OH)D, IL-33 levels, and clinical improvement after narrow-band UVB treatment in vitiligo. METHOD: Patients with vitiligo who underwent at least 48 sessions of narrow-band UVB treatment were included in this study. Age, gender, smoking status, family history of vitiligo, type of vitiligo, body surface area affected by vitiligo, and vitiligo activity were recorded. 25(OH)D and IL-33 were measured and compared at baseline, second month, and fourth month. RESULTS: Twenty patients with vitiligo and 20 healthy controls were included in this study. The mean baseline 25(OH)D level of vitiligo group was statistically significantly lower than the control group's (p < .05). The mean baseline IL-33 level was higher in vitiligo group with no statistically significantly difference (p > .05). The increase in 25(OH)D level and the decrease in vitiligo-affected body surface area were found to be statistically significant during treatment (p < .05). The mean IL-33 levels were found to be lower at the second and fourth month compared to baseline. However, there were no statistical significance (p > .05). CONCLUSION: Low levels of 25(OH)D are thought to play a role in the etiopathogenesis of vitiligo. 25(OH)D increase due to phototherapy may have a role in repigmentation independently from the direct effect of narrow-band UVB.

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.

Plasma 25-hydroxyvitamin D deficiency in the peri-operative period is associated with survival outcome in colorectal cancer patients: a meta-analysis.

AIM: Surgery had a significant impact on 25-hydroxyvitamin D (25-(OH)D) levels. Uncertainty still existed regarding the effects of peri-operative 25(OH)D deficiency on colorectal cancer (CRC) patients' prognosis. The purpose of the present study was to explore the potential association between the peri-operative 25(OH)D deficiency and the survival outcome of CRC. METHODS: Seven electronic databases [including PubMed, EMBASE, Web of Science, The Cochrane Library, OvidMEDLINE(R), China National Knowledge Infrastructure (CNKI) and Wangfang data] were searched without language limitations. The primary outcomes were overall survival and all-cause mortality. Secondary outcomes were the incidence of 25(OH)D deficiency and risk variables for low 25(OH)D level in the peri-operative period. RESULTS: 14 eligible studies were obtained with 9324 patients for meta-analysis. In the peri-operative period, the pooled incidence of blood 25(OH)D deficiency was 59.61% (95% CI: 45.74-73.48). The incidence of blood 25(OH)D deficiency post-operatively (66.60%) was higher than that pre-operatively (52.65%, 95% CI: 32.94-72.36). Male (RR = 1.09, 95% CI: 1.03-1.16), rectum tumor (RR = 1.23, 95% CI: 1.03-1.47), spring and winter sampling (RR = 1.24, 95% CI: 1.02-1.49) were the risk factors for the 25(OH)D deficiency. The association between the low 25(OH)D post-operatively and short-term overall survival (HR = 0.43, 95% CI: 0.24-0.77) was most prominent, while a low 25(OH)D pre-operatively (HR = 0.47, 95% CI: 0.31-0.70) was more significantly associated with long-term all-cause mortality than that after surgery. CONCLUSION: Peri-operative 25(OH)D impacted the CRC patients' prognosis. Due to possible confounding effects of systemic inflammatory response (SIR), simultaneous measurement of vitamin D and SIR is essential for colorectal survival.

Genetic Diversity in Bronchial Asthma Susceptibility: Exploring the Role of Vitamin D Receptor Gene Polymorphisms in Varied Geographic Contexts.

Bronchial asthma (BA) exhibits varying prevalence across global populations, prompting a comprehensive investigation into genetic and environmental determinants. Vitamin D is a potent immunomodulator capable of suppressing inflammatory signals in several cell types involved in the asthmatic response; it exerts effects on the immune system by binding to the nuclear vitamin D receptor (VDR). VDR gene genetic variations are affecting serum vitamin D levels with a possible role in the BA risk. The current study aimed to examine the complex interaction of various factors (genetic background, serum vitamin D levels, and geographic location) to identify differences in the influence of these factors on the susceptibility to asthma between populations at different latitudes. Focusing on Eastern European cohorts from Latvia and Lithuania and comparing them with published data on East Asian populations, we explore the impact of VDR gene polymorphisms on BA susceptibility. Genotyping four key VDR SNPs and assessing their association with 25-hydroxyvitamin D levels, our study unveils significant associations of the studied loci with the risk of asthma-both risk-reducing and increasing effects, differently distributed between Baltic and East Asian populations. The functional effects of in silico VDR gene genetic variations are also identified and discussed.

Discordant Health Implications and Molecular Mechanisms of Vitamin D in Clinical and Preclinical Studies of Prostate Cancer: A Critical Appraisal of the Literature Data.

Clinical and preclinical studies have provided conflicting data on the postulated beneficial effects of vitamin D in patients with prostate cancer. In this opinion piece, we discuss reasons for discrepancies between preclinical and clinical vitamin D studies. Different criteria have been used as evidence for the key roles of vitamin D. Clinical studies report integrative cancer outcome criteria such as incidence and mortality in relation to vitamin D status over time. In contrast, preclinical vitamin D studies report molecular and cellular changes resulting from treatment with the biologically active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (calcitriol) in tissues. However, these reported changes in preclinical in vitro studies are often the result of treatment with biologically irrelevant high calcitriol concentrations. In typical experiments, the used calcitriol concentrations exceed the calcitriol concentrations in normal and malignant prostate tissue by 100 to 1000 times. This raises reasonable concerns regarding the postulated biological effects and mechanisms of these preclinical vitamin D approaches in relation to clinical relevance. This is not restricted to prostate cancer, as detailed data regarding the tissue-specific concentrations of vitamin D metabolites are currently lacking. The application of unnaturally high concentrations of calcitriol in preclinical studies appears to be a major reason why the results of preclinical in vitro studies hardly match up with outcomes of vitamin D-related clinical studies. Regarding future studies addressing these concerns, we suggest establishing reference ranges of tissue-specific vitamin D metabolites within various cancer entities, carrying out model studies on human cancer cells and patient-derived organoids with biologically relevant calcitriol concentrations, and lastly improving the design of vitamin D clinical trials where results from preclinical studies guide the protocols and endpoints within these trials.

Impact of phthalate metabolites on vitamin D levels and subclinical inflammation: national health and nutrition examination survey, 2013-2018.

This study explores the association between phthalates and total vitamin D levels and the link between phthalates exposure and subclinical inflammation using monocyte percentage to high-density lipoprotein cholesterol ratio (MHR), utilizing three National Health and Nutrition Examination Survey (NHANES) survey cycles 2013-2018. This study is cross-sectional, utilizing one-time urine samples from randomly selected NHANES participants to assess phthalate metabolites. An inverse association between vitamin D and all Di(2-ethylhexyl) phthalate (DEHP) metabolites was found. The molar sum of DEHP metabolites was inversely associated with vitamin D (ß -2.329; 95% CI -3.937,-0.720). An inverse association was observed between monocarboxynonyl phthalate and vitamin D (ß -0.0278; 95% CI -0.0527,-0.00298). A similar relationship was found between monocarboxyoctyl phthalate and vitamin D (ß -0.0160; 95% CI -0.0242,-0.00775). There was no association between phthalate metabolites and MHR. Stratified analysis showed that the association between phthalate metabolites and MHR may vary according to vitamin D status.

Circulating total 25(OH)D and calculated free 25(OH)D in professional academy footballers at a northerly latitude in the UK.

There is limited data on the vitamin D status of UK-based professional academy footballers. Therefore, the objective of this study was to report total 25(OH)D, free 25(OH)D and free 1, 25(OH)2D at the end of the winter (March) and summer periods (October) in a cohort (n = 27) of professional academy footballers in northern England. Blood samples were collected to measure total 25(OH)D, parathyroid hormone, vitamin D binding protein, albumin and calcium. Free 25(OH)D and 1, 25(OH)2D were calculated. Dietary vitamin D intake and retrospective summer sunlight exposure were also collected. At the end of winter, 2/27 (7.4%) players were vitamin D deficient (25(OH)D < 30 nmol/l) and 11/27 (40.7%) were insufficient (25(OH)D > 30 nmol/l < 50 nmol/l). By the end of summer, none were deficient but 3/14 (21.4%) were still insufficient. Median total 25(OH)D (82.2 nmol/l [IQR: 50.3-90.2] vs. 54.2 nmol/l [IQR: 36.8-71.9]; P = .02), free 25(OH)D (25.8 pmol/l [IQR: 15.1-33.1] vs. 13.2 pmol/l [IQR: 9.0-14.9]; P = .005) and free 1, 25(OH)2D (389 fmol/l [IQR: 209-594] vs. 212 fmol/l [IQR: 108-278]; P = .034) were significantly higher at the end of summer than the end of winter. At the end of winter, free 25(OH)D was lower (P = .003) in those vitamin D insufficient (8.8 pmol/l [IQR: 5.5-11.8]) vs. sufficient (13.7 pmol/l [IQR: 12.0-17.0]). There was a high prevalence of vitamin D insufficiency at the end of the winter. Free 25(OH)D was also lower at the winter timepoint and in players that were insufficient vs. sufficient.