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.

Persistence of vitamin D deficiency among Italian patients with acute myocardial infarction.

BACKGROUND AND AIMS: Vitamin D deficiency is a common cardiovascular risk factor associated with the development of atherosclerosis. We evaluated changes in 25(OH)D concentrations in 1510 patients with acute myocardial infarction (AMI) over a long observation period, including the COVID-19 pandemic. METHODS AND RESULTS: Patients were separated into four groups according to the year of enrolment, group 1 (2009-2010), group 2 (2014-2016), group 3 (2017-2019), and group 4 (2020-2022). The median 25(OH)D concentration in the overall cohort was 17.15 (10.3-24.7) ng/mL. The median plasma concentrations of 25(OH)D for groups 1, 2, 3, and 4 were 14.45 (7.73-22.58) ng/mL, 17.3 ng/mL (10.33-24.2), 18.95 (11.6-26.73) ng/mL and 19.05 (12.5-27.3) ng/mL, respectively. Although 25(OH)D levels increased over the years, the prevalence of vitamin D deficiency remained high in each group (68.4%, 61.4%, 53.8%, and 52% respectively). Hypovitaminosis D was predicted by the season influence (OR:2.03, p < 0.0001), higher body mass index (OR:1.25; p = 0.001), diabetes mellitus (OR:1.54; p = 0.001), smoking (OR:1.47; p = 0.001), older age (OR:1.07; p = 0.008), higher triglycerides levels (OR:1.02; p = 0.01), and female gender (OR:1.3; p = 0.038). After multivariable adjustment, vitamin D ≤ 20 ng/mL was an independent predictor of mortality. CONCLUSION: Vitamin D deficiency is highly prevalent and persistent in patients with AMI despite a trend towards increasing 25(OH)D concentrations over the years. The frequent lockdowns did not reduce the levels of 25(OH)D in the fourth group. Low levels of 25(OH)D are an independent predictor of mortality.

Association of vitamin D with disease severity in infants with bronchiolitis.

Vitamin D's role in immune system regulation and its contribution to host defenses against respiratory infections may have implications for bronchiolitis pathophysiology. This cross-sectional study aimed to determine the association between the clinical severity of bronchiolitis and serum vitamin D levels in infants. Infants aged 1 month to 12 months, diagnosed with bronchiolitis, and healthy controls attending routine immunization were enrolled. Baseline characteristics were recorded, including clinical details, bronchiolitis severity, and course during hospital stay. Bronchiolitis severity score (BSS) was used to score the severity. A 1-2 ml serum sample was obtained for vitamin D levels estimation. The median age of cases (n = 64; 65.6% male) was 5 [3, 8] months, and that of the control group (n = 30) was 3 [2, 9] months. No statistically significant differences were observed between the two groups in age, gender, weight, mode of delivery, family history of atopy/asthma, feeding pattern, smoke exposure, and daily vitamin D supplementation. The median vitamin D levels were not significantly different between the groups (p = 0.68). Among infants with bronchiolitis, 62.5% had vitamin D insufficiency (≤ 20 ng/ml). A significantly higher median BSS indicates that infants with vitamin D insufficiency exhibited more severe disease (p = 0.019). Although a negative correlation between BSS and vitamin D levels was noted, it did not reach statistical significance [rs = (-)0.17; p = 0.16]. CONCLUSION:  Infants with Vitamin D insufficiency experienced more severe bronchiolitis with elevated BSS scores. It highlights the potential role of vitamin D deficiency in severe bronchiolitis. WHAT IS KNOWN: • Vitamin D level is low in infants with bronchiolitis. WHAT IS NEW: • Infant with low vitamin D level experienced more severe bronchiolitis.

Relationship between Vitamin D Concentration and Lipid Concentration in Patients with NAFLD in the Hulunbuir Region of China.

BACKGROUND: We aimed to characterize the relationship between the serum 25-hydroxyvitamin D concentration and the circulating lipid concentrations of patients with NAFLD in the Hulunbuir region of China. METHODS: One hundred fifty-six patients, who were diagnosed with NAFLD in the Physical Examination Department of the Second Clinical College of Inner Mongolia University for the Nationalities between January 2021 and March 2023, were recruited as NAFLD group, and 160 healthy people were recruited as a control group during the same period. The serum 25(OH)VitD, TBIL, TG, TC, LDL-C, HDL-C, AST, ALT, GGT, and FPG activities of the participants were measured, and hepatic ultrasonography was performed. RESULTS: The BMI of the NAFLD group was higher than of the control group (p < 0.05). The serum 25(OH)VitD3 (p < 0.05) and the HDL-C concentrations of the NAFLD group were lower than those of the normal control group. However, the AST (p < 0.05), ALT (p < 0.05), and GGT (p < 0.05) activities, and the serum TG (p < 0.05), TC (p < 0.05), LDL-C (p < 0.05), and the fasting glucose (p < 0.05) concentrations of the NAFLD group were higher than those of the normal control group. The serum 25(OH)VitD3 concentrations of the NAFLD group significantly cor-related negatively with BMI (r = -0.302, p < 0.01), TG (r = -0.221, p < 0.05), and fasting glucose (r = -0.236, p < 0.05). The BMI, TG, and fasting glucose of vitamin D-deficient participants were higher than of the participants with adequate or insufficient levels of vitamin D (p < 0.05). Finally, the BMI of vitamin D-deficient participants was higher than of those with an adequate vitamin D status (p < 0.05). CONCLUSIONS: A deficiency of 25(OH)VitD is more common in people from the Hulunbuir region of China than elsewhere. In addition, the vitamin D status is significantly associated with NAFLD; as the serum vitamin D concentration decreases, patients with NAFLD show greater dyslipidemia and hyperglycemia and a higher BMI.

Analysis of pupillary responses in pediatric patients with vitamin D deficiency.

PURPOSE: To evaluate the effects of vitamin D deficiency on pupillary responses in the pediatric population. METHODS: The study was conducted using data from the right eyes of 52 children with vitamin D deficiency and 52 healthy children. Measurements were taken under static and dynamic conditions with automatic pupillometry. Static measurements were performed at scotopic, mesopic, and photopic light intensities. The mean pupil dilation speed was calculated by observing the changes in pupil dilation over time according to dynamic measurements. Differences between patient and control groups were analyzed for the static and dynamic measurements and the mean pupil dilation speed. RESULTS: While the two groups were similar in terms of scotopic, mesopic, the first dynamic measurements, and the pupil dilation speed data (p > 0.05), a significant difference was found in the photopic conditions (p = 0.001). The mean pupil diameter of the patient group was 4.46 ± 0.928 mm and 3.95 ± 0.556 mm in the control group under photopic conditions. CONCLUSIONS: Pediatric patients with vitamin D deficiency have significantly larger pupil diameters in photopic conditions than healthy children. These results suggest that there is an autonomic dysfunction in vitamin D deficiency in the pediatric population, especially pointing to the parasympathetic system.

C-reactive protein as a novel biomarker for vitamin D deficiency in alopecia areata.

BACKGROUND: Alopecia areata (AA) is an autoimmune condition characterized by sudden and unpredictable hair loss, with a lifetime incidence of 2%. AA can be divided into three categories: patchy alopecia, alopecia totalis, and alopecia universalis. It can affect a person's psychological health and overall quality of life. Elevated C-reactive protein (CRP) levels in the liver may indicate an inflammatory response in autoimmune diseases. Vitamin D, essential for immune system control and skin health, may be related to AA. Hair follicles contain vitamin D receptors, which control immunological responses in the skin. However, no study has found a relationship between CRP and vitamin D in AA patients in our region. SUBJECTS AND METHODS: An analytical cross-sectional study with a case-control design research investigation of 82 AA patients and 81 healthy controls was carried out. Both groups' medical histories were taken. Biochemical analysis was done for both groups as well as the serum vitamin D levels, and CRP. Genetic analysis for CDX2 rs11568820 variant detected by PCR (T-ARMS-PCR) method and vitamin D receptor (VDR) gene expression measured by real-time PCR analysis for both patients and healthy subjects. RESULTS: CRP levels are higher in AA patients, AA patients with G/G genotypes exhibited higher concentrations of CRP when compared to those with A/A and A/G genotypes while patients with A/A genotypes have higher levels of Serum vitamin D as compared to the A/G and G/G genotypes. G allele was more abundant in AA patients. VDR gene expression was lower in AA compared to control and lower in ophiasis compared to localized and multiple patchy AA. An important inverse linear correlation was observed between vitamin D and CRP levels in ophiasis AA. CONCLUSION: CRP concentrations were found to be elevated in AA patients. The considerable accuracy of CRP in the diagnosis of AA is substantiated by a statistically significant al. A noteworthy inverse linear association was observed between serum vitamin D and CRP concentrations in ophiasis AA.

Combined effects of vitamin D deficiency and systemic inflammation on all-cause mortality and cause-specific mortality in older adults.

BACKGROUND: Vitamin D deficiency and systemic inflammation share common pathological mechanisms in muscle loss, cardio-pulmonary function decline, and abnormal metabolism, which are linked to chronic conditions, senescence, and early mortality. However, their combined effect on mortality in older adults has not been well established. This study longitudinal aimed to explore the independent and combined associations of serum 25-hydroxyvitamin D [25(OH)D] and high sensitivity C-reactive protein (hs-CRP) with mortality risk in Chinese community-based older people. METHODS: 3072 older adults (86.07 ± 11.87 years, 54.52% female) from the Chinese Longitudinal Healthy Longevity Survey (2012-2018) were enrolled. Baseline 25(OH)D and hs-CRP levels were collected, and survival information was recorded in the 2014 and 2018 follow-up waves. Cox proportional hazard regressions were conducted to explore the associations between 25(OH)D, hs-CRP, and mortality. Demographic characteristics, health behaviors, and chronic disease biomarkers were adjusted. RESULTS: During 10,622.3 person-years of follow-up (median: 3.51 years), 1321 older adults died, including 448 deaths due to cardiovascular disease (CVD). Increased mortality risk was associated with lower 25(OH)D and higher hs-CRP quantiles, even after adjusting for each other and multiple covariates (all P-trend < 0.05). In combined analyses, the highest all-cause mortality (HR: 2.18, 95% CI: 1.73 ~ 2.56), CVD mortality (HR: 2.30, 95% CI: 1.64 ~ 3.21), and non-CVD mortality (HR: 2.19, 95% CI: 1.79 ~ 2.49) were obtained in participants with both 25(OH)D deficiency (< 50 nmol/L) and high hs-CRP (≥ 3.0 mg/L), respectively. We observed significant additive interactions of 25(OH)D and hs-CRP on all-cause mortality and non-CVD mortality (RERIS>0). CONCLUSIONS: Low 25(OH)D and high hs-CRP, both independently and jointly, increase mortality risk in Chinese community-dwelling older adults. Thus, priority should be given to early detection and appropriate intervention in older individuals with combined vitamin D deficiency and systemic inflammation. Molecular mechanisms of related adverse health effect are worthy of further investigation.

Left and right ventricular function by echocardiography, tissue doppler imaging, carotid intima media thickness, and asymmetric dimethylarginine levels in female adolescents with vitamin D deficiency.

BACKGROUND: The aim of our study was to assess left and right ventricle systolic and diastolic functions in female adolescents with vitamin D deficiency using conventional echocardiography and pulsed-wave tissue Doppler imaging and to investigate carotid intima media thickness and asymmetric dimethylarginine levels. METHODS: Sixty-six female adolescents were enrolled in this study. The female adolescents were divided into a vitamin D deficiency group (n: 34) and a control group (n: 32). All subjects underwent laboratory blood tests, including asymmetric dimethyl arginine, complete two-dimensional, pulse, and tissue Doppler echocardiography, and measurement of the carotid intima-media thickness. RESULTS: The vitamin D-deficient female adolescent group had normal left and right ventricle systolic and diastolic functions and normal global systolic and diastolic myocardial performance. In the patients with vitamin D deficiency, the carotid intima-media thickness was higher than that in the controls. In the patients within the vitamin D deficiency group, vitamin D was found to be positively correlated with magnesium and negatively correlated with phosphorus and left atrial dimension. CONCLUSIONS: The results of this study demonstrate that vitamin D deficiency in female adolescence is associated with normal myocardial geometry and function. Although it has been associated with normal levels of asymmetric dimethyl arginine concentration, high measured carotid intima-media thickness may reflect endothelial dysfunction.

Comparative Study of Vitamin D Levels in Newly Diagnosed Tuberculosis and a Normal Population.

Background and Objectives: Tuberculosis (TB) is an ancient disease caused by Mycobacterium tuberculosis, a member of the Mycobacterium tuberculosis complex. It contributes to significant morbidity and mortality. Treatment of TB poses a considerable challenge because of emerging drug resistance and the longer duration of therapy. Various past studies, both in vitro and in vivo, have established the role of vitamin D in the pathogenesis and treatment of TB. Results of in vivo studies are inconsistent, and this study aims to determine vitamin D levels and their association with newly diagnosed TB (pulmonary and extrapulmonary) cases and normal populations. Material and Methods: A Prospective Case-Control study with 116 subjects (58 cases and 58 controls) was conducted over two years. 29 cases of pulmonary TB and 29 cases of extrapulmonary TB constituted 58 cases of TB. Vitamin D levels were measured and compared in both the cases and controls. Data analysis was carried out using SPSS software 22.0. Results: The prevalence of vitamin D deficiency was 68.96% in the cases, while it was 51.72% in the controls. The reported median and quartile of serum vitamin D levels were 14.35 ng/mL (8.65, 25.48) in the TB group and 19.08 ng/mL (13.92, 26.17) in the control group. There was a significant statistical difference between the TB and non-TB populations with a p-value of 0.029 on the Mann-Whitney test. Conclusion: Vitamin D deficiency was more prevalent in individuals with TB than those without TB.

Relationship between histopathological findings of patients with dermatochalasis and vitamin D deficiency.

PURPOSE: To compare the histopathological findings of patients who had been diagnosed with dermatochalasis (DC) and had undergone upper eyelid blepharoplasty (ULB) as well as those of controls (C-Group) according to their serum vitamin D (SVD) levels. METHODS: The prospective study included 136 upper eyelid skin from 68 patients who underwent surgery for DC and 53 upper eyelid skin from 53 patients who underwent levator surgery with ULB. The DC Group was then divided into 3 subgroups according to the marginal reflex distance (MRD4). The lymphatic vessel (LV) count and diameter of the largest LV (DLLV) were recorded, the stromal collagen bed (SCB) was observed, and its depth was measured, the interfibrillar edema was examined, and the elastic fiber and macrophage counts and recorded, respectively, and then all of these were evaluated. The SVD levels were compared between the DC patients and the C-Group. RESULTS: In comparison to the C-Group, significant changes were seen in the dilated LV, DLLV, SCB depth, interfibrillar edema, elastic fiber density, and macrophage count in the DC sub-Groups (P < 0.001 for all). While no difference was found between DC sub-Group 1 (MRD4 > 4 mm) and the C-Group (P > 0.05), a significant difference was found between DC sub-Group 2 (MRD4 2-4 mm) and DC sub-Group 3 (MRD4 < 2 mm) for all of the parameters (P < 0.05). A statistically significant difference was also found in the SVD levels between the DC sub-Group 1 and DC sub-Groups 2-3 (P < 0.017, P < 0.001 respectively). CONCLUSION: According to the results of this study, SVD level was significantly lower in DC group. Moreover, an increased LV count and diameter, decreased elastic fiber count, collagen fiber and stromal edema irregularity, and increased macrophage count were found to be associated with the SVD level.

Evaluation of the Relationship Between Vitamin D Deficiency and Subclinical Cardiac Dysfunction Using 2D/3D Strain Echocardiography in Healthy People.

AIM: Vitamin D deficiency has a high prevalence in the population and is highly associated with cardiovascular diseases. The aim of this study was to evaluate subclinical left ventricular (LV) function using strain analysis in healthy individuals with vitamin D deficiency. MATERIAL AND METHODS: 113 healthy volunteers were enrolled in the study (age, 44.1±7 yrs, 34 male). All volunteers underwent two-dimensional (2D) and three-dimensional (3D) speckle tracking echocardiography after conventional echocardiographic evaluation. The subjects were divided into two groups according to their vitamin D concentrations. 61 subjects with vitamin D less than 20 ng / ml were included in the vitamin D deficiency group. The baseline clinical characteristics, laboratory measurements, echocardiographic data, including 2D and 3D global longitudinal strain (GLS) values, were compared between the groups. RESULTS: The 2D GLS values of the subjects with vitamin D deficiency were lower (mathematically less negative) than subjects with normal vitamin D (-16.1±3.4 vs -19.3±4.2, p<0.001). Similarly, the 3D GLS results were lower in subjects with vitamin D deficiency (-18.3±5.2 vs -24.1±6.9, p<0.001). A significant correlation was detected between the vitamin D concentrations and the 2D and 3D GLS measurements. (r=0.765 and r=0.628, respectively, p<0.001). Vitamin D was found to be an independent predictor of impaired 2D and 3D LV GLS (p=0.031, p=0.023, respectively). CONCLUSION: Subclinical LV dysfunction in healthy individuals with vitamin D deficiency was demonstrated by 3D and 2D strain analysis. Due to potential negative effects of vitamin D deficiency on cardiac function, more attention should be paid to healthy individuals with vitamin D deficiency.

Vitamin D deficiency enhances vascular oxidative stress, inflammation, and angiotensin II levels in the microcirculation of diabetic patients.

Low vitamin D (vitD) levels have been reported to be a risk factor for diabetes-related cardiovascular complications. This study examined the effects of vitD deficiency on oxidative stress (OS), inflammation, and levels of the vasoconstrictor angiotensin II (Ang II) in the microvascular tissue of type 2 diabetic patients. Patients were categorized into (i) vitD non-deficient diabetics (DNP, n = 10) and (ii) vitD-deficient diabetics (DDP, n = 10), based on their serum 25(OH)D levels. Subcutaneous fat tissues with intact blood vessels were collected during lower limb surgical procedures. The blood vessel were isolated; measurements of the antioxidant enzyme superoxide dismutase (SOD) activity, OS marker malondialdehyde (MDA), Ang II, and the inflammatory marker, TNF-α of the microvascular tissues were determined. Elevated MDA levels and reduced SOD activity, with higher levels of TNF-α and Ang II were observed in the microvascular tissues of DDP compared to DNP. VitD deficiency did not associate with glycemic parameters (fasting blood glucose and glycated hemoglobin) levels. In conclusion, vitD deficiency was correlated with higher microvascular tissue OS, inflammation, and Ang II levels in type 2 diabetic patients. This may contribute to early vasculopathy that occurs in diabetic patients, thus, may contribute to the planning of therapeutic strategies to delay or prevent cardiovascular complications.

Determination of a Serum 25-Hydroxyvitamin D Reference Ranges in Japanese Adults Using Fully Automated Liquid Chromatography-Tandem Mass Spectrometry.

BACKGROUND: Despite an increasing interest in vitamin D status, a reference range of the nutrient has not been fully established. This is partly due to a paucity of standardized measuring systems with high throughput. In addition, the range may vary by populations and may change with modernization of lifestyles. OBJECTIVES: This study aims to calculate the current reference concentration of 25-hydroxyvitamin D (25(OH)D) among healthy people living in an urban area in Japan. METHODS: A newly developed fully automated liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) system was used to measure serum 25(OH)D concentrations. Reproducibility was assessed by measuring standardized samples. Accuracy was validated by comparing with commercially available immunoassays. Then, mass screening was conducted targeting participants who received medical checkups in Tokyo from April 2019 to March 2020, and the reference ranges were calculated. RESULTS: The coefficients of variations of interoperator and interday reproducibility were 4.1%-8.5% and 3.7%-8.0% for 25-hydroxyvitamin D2 (25(OH)D2) and 4.7%-7.0% and 4.0%-6.9% for 25-hydroxyvitamine D3, respectively. The measured total 25(OH)D concentrations correlated well with those measured by immunoassays. In total, 5518 participants were measured for 25(OH)D concentrations, among whom 98% showed inadequate concentrations (<30 ng/mL). The reference ranges of total 25(OH)D for female, male, and total participants were 7-30 ng/mL, 5-27 ng/mL, and 6-29 ng/mL, respectively. After excluding those with abnormal renal and liver function, the range was 6-30 ng/mL. CONCLUSIONS: The high prevalence of vitamin D insufficiency among seemingly healthy population may be attributed to lifestyle characteristics of people living in urban areas of Japan, including spending less time outdoors and lower intake of traditional foods. Longitudinal follow-up and mass screenings targeting different population will help elucidate reasons for discrepancies between official guidelines and the observed concentrations, to which the well-validated measurement system is essential.

Combined Effect of Omega-3 Fatty Acid and Vitamin D 3 on Oxidized LDL-C and Non-HDL-C Levels in People With Vitamin D Deficiency: A Randomized Controlled Trial.

ABSTRACT: The present randomized clinical trial (RCT) was conducted on Jordanian participants with vitamin D deficiency (VDD) with no other medical conditions, to evaluate the combined effect of 1,25-dihydroxy vitamin D 3 (Vit.D 3 ) and omega-3 fatty acid (n-3FA) supplements (D+) on oxidized low-density lipoprotein (Ox-LDL) and non-high-density lipoprotein cholesterol (non-HDL-C) levels as common predictors of cardiovascular diseases (CVDs). Participants were randomized into 4 groups as follows: a control group (C) that received no supplementations, a Vit.D 3 group that received 50,000 IU of Vit.D 3 every week, an n-3FA group that received 300 mg of omega-3 fatty acid every day, and a D+ group that received a combination of both supplements, with the same dosage administered by the previous groups but with a 4-6-hour time interval between Vit.D 3 and n-3FA administration to avoid any possible interaction. All supplementations were administered orally for 8 weeks. Forty-seven participants were allocated to each group. Twenty-six in the control group, 37 participants in the Vit.D 3 group, 37 participants in the n-3FA group, and 46 participants in the D+ group completed the study to the end. The D+ supplementations significantly increased non-HDL-C (118.99 ± 60.98 to 155.26 ± 43.36 mg/dL, P << 0.05) but decreased Ox-LDL-C levels (69.29 ± 37.69 to 52.81 ± 17.30 pg/mL, P = 0.03). The stepwise regression showed that the serum LDL-C level was the main independent variable involved in the elevation of non-HDL levels (R 2 = 0.837) observed at the end of the trial in the D+ group. The groups that were supplemented with either Vit.D 3 alone or n-3FA alone had an insignificant decrease in the level of Ox-LDL-C. In conclusion, despite the observed hyperlipidemic effect, the combination treatment is recommended by the research team because the decrease in Ox-LDL may offset the hyperlipidemic effect.

Forecasting levels of serum 25-hydroxyvitamin D based on dietary intake, lifestyle and personal determinants in a sample of Southern Europeans.

Vitamin D is an essential nutrient to be consumed in the habitual dietary intake, whose deficiency is associated with various disturbances. This study represents a validation of vitamin D status estimation using a semi-quantitative FFQ, together with data from additional physical activity and lifestyle questionnaires. This information was combined to forecast the serum vitamin D status. Different statistical methods were applied to estimate the vitamin D status using predictors based on diet and lifestyle. Serum vitamin D was predicted using linear regression (with leave-one-out cross-validation) and random forest models. Intraclass correlation coefficients, Lin's agreement coefficients, Bland-Altman plots and other methods were used to assess the accuracy of the predicted v. observed serum values. Data were collected in Spain. A total of 220 healthy volunteers aged between 18 and 78 years were included in this study. They completed validated questionnaires and agreed to provide blood samples to measure serum 25-hydroxyvitamin D (25(OH)D) levels. The common final predictors in both models were age, sex, sunlight exposure, vitamin D dietary intake (as assessed by the FFQ), BMI, time spent walking, physical activity and skin reaction after sun exposure. The intraclass correlation coefficient for the prediction was 0·60 (95 % CI: 0·52, 0·67; P < 0·001) using the random forest model. The magnitude of the correlation was moderate, which means that our estimation could be useful in future epidemiological studies to establish a link between the predicted 25(OH)D values and the occurrence of several clinical outcomes in larger cohorts.

Analytical performance specifications for the measurement uncertainty of 24,25-dihydroxyvitamin D examinations.

OBJECTIVES: The exploration of the metabolites in the degradation pathways of vitamin D (VTD) has gained importance in recent years and simultaneous quantitation of twenty-five-hydroxy vitamin D (25(OH)D) mass concentration together with 24,25-dihydroxyvitamin D (24,25(OH)2D) has been proposed as a newer approach to define VTD deficiency. Yet, no data are available on 24,25(OH)2D biological variation (BV). In this study, we evaluated 24,25(OH)2D's BV on the European Biological Variation Study (EuBIVAS) cohort samples to determine if analytical performance specifications (APS) for 24,25(OH)2D could be generated. METHODS: Six European laboratories recruited 91 healthy participants. 25(OH)D and 24,25(OH)2D concentrations in K3-EDTA plasma were examined weekly for up to 10 weeks in duplicate with a validated LC-MS/MS method. The Vitamin D Metabolite Ratio (24,25(OH)2D divided by 25(OH)D × 100) was also calculated at each time point. RESULTS: Linear regression of the mean 24,25(OH)2D concentrations at each blood collection showed participants were not in steady state. Variations of 24,25(OH)2D over time were significantly positively associated with the slopes of 25(OH)D concentrations over time and the concentration of 25(OH)D of the participant at inclusion, and negatively associated with body mass index (BMI), but not with age, gender, or location of the participant. The variation of the 24,25(OH)2D concentration in participants over a 10 weeks period was 34.6%. Methods that would detect a significant change linked to the natural production of 24,25(OH)2D over this period at p<0.05 would need a relative measurement uncertainty (u%)<14.9% while at p<0.01, relative measurement uncertainty should be <10.5%. CONCLUSIONS: We have defined for the first time APS for 24,25(OH)2D examinations. According to the growing interest in this metabolite, several laboratories and manufacturers might aim to develop specific methods for its determination. The results presented in this paper are thus necessary prerequisites for the validation of such methods.

Assessing vitamin D metabolism - four decades of experience.

One hundred years ago, the role of vitamin D for bone mineralization and the prevention of rickets was discovered. Vitamin D comprises a group of over 50 metabolites with multiple functions that go far beyond calcium homeostasis and bone mineralization. Approximately 50 years ago, first methods for the measurement of 25-hydroxyvitamin D (25(OH)D) in human blood were developed. Over the years, different analytical principals were employed including competitive protein binding assays, high-performance liquid chromatography, various immunoassay and mass spectrometric formats. Until the recent standardization of serum 25(OH)D measurement, agreement between methods was unsatisfactory. Since then, comparability has improved, but substantial variability between methods remains. With the advent of liquid chromatography tandem mass spectrometry (LC-MS/MS), the accurate determination of 25(OH)D and other metabolites, such as 24,25(OH)2D, becomes increasingly accessible for clinical laboratories. Easy access to 25(OH)D testing has triggered extensive clinical research showing that large parts of the population are vitamin D deficient. The variable response of vitamin D deficient individuals to supplementation indicates that assessing patients' vitamin D stores by measuring 25(OH)D provides limited insight into the metabolic situation. Meanwhile, first evidence has emerged suggesting that the simultaneous measurement of 25(OH)D, 24,25(OH)2D and other metabolites allows a dynamic evaluation of patients' vitamin D status on metabolic principals. This may help to identify patients with functional vitamin D deficiency from those without. It can be expected that research into the assessment vitamin D status will continue for another 50 years and that this will help rationalizing our approach in clinical practice.

Association between serum 25(OH)D and risk of all-cause mortality in adults with prior cardiovascular disease: a cohort study from NHANES 2007-2018.

BACKGROUND: Serum vitamin D deficiency is common in the patients with cardiovascular disease (CVD), but the association between serum vitamin D levels and risk of all-cause mortality in patients with CVD is controversial. OBJECTIVE: This study aimed to understand better the association between serum 25(OH)D status and risk of all-cause mortality in patients with prior CVD. METHOD: We conducted a cohort study using data from the National Health and Nutrition Examination Survey from 2007 to 2018 to investigate the association between serum 25(OH)D and the risk of all-cause mortality using multivariate Cox regression models, with further subgroup analyses and interactions smooth curve fitting to address possible nonlinearities. RESULT: A total of 3220 participants with prior CVD were included in this study, with a total of 930 deaths over a median follow-up of 5.52 years, with multivariable-adjusted serum vitamin D levels after natural log transformation (4.31-4.5 ) as a reference in COX regression, and corrected HRs and 95% CIs of 1.81 (1.31, 2.50), 1.34 (1.07, 1.66), 1.28 (1.05, 1.56),1.00 (reference), 1.10 (0.89, 1.37) for all-cause mortality, respectively. Results remained robust in the stratified analysis of interactions, but a L-shaped relationship was detected. We identified an inflection point of 4.5 after multivariate adjustment through a two-stage linear regression model and recursive algorithm. CONCLUSION: Our findings demonstrate that increasing serum 25(OH)D levels may have a L-shaped relationship with risk of all-cause mortality and that increases in serum 25(OH)D levels do not continue to reduce the risk of all-cause mortality.

Evaluation of vitamin D levels and affecting factors of vitamin D deficiency in healthy children 0-18 years old.

The frequency of vitamin D deficiency in healthy children is relatively high. Moreover, vitamin D supplementation in children is under the requested levels. The aim of this study is to determine the frequency of vitamin D deficiency and the factors that influence vitamin D levels in healthy children. During the study period, 3368 vitamin D levels of healthy children, aged 0-18 years, were evaluated retrospectively. Vitamin D levels were categorized as deficiency (< 12 ng/ml), insufficiency (12-20 ng/ml), and sufficiency (> 20 ng/ml). The prevalence of vitamin D deficiency and insufficiency was found to be 18-24.9% in healthy children, respectively. It was found that the frequency of vitamin D deficiency increased with age. In addition, the most severe and highest risk group for vitamin D deficiency were adolescent girls. Moreover, being in the winter or spring season and living in the north of the 40th parallel are the other risk factors for vitamin D deficiency. CONCLUSION:  This study showed that vitamin D deficiency still remains a major problem for healthy children and daily supplementation of vitamin D is mandatory. Prophylactic vitamin D supplementation and adequate sunlight exposure should be provided for all children, in particular healthy adolescents. In addition, future studies may focus on screening for vitamin D status in children who did not receive vitamin D supplementation. WHAT IS KNOWN: • Vitamin D is an essential component in bone metabolism. Seasonality, age, sex, dark skin pigmentation, and limited exposure to sunlight are causes of vitamin D deficiency. • The World Health Organization has drawn attention to this increased frequency, recommending lifelong, regular vitamin D prophylaxis. WHAT IS NEW: • The frequency of vitamin D deficiency and insufficiency was found to be 42.9% in healthy children and the frequency significantly increased with age. • There were almost no cases of prophylactic vitamin D usage in adolescent group which are at the highest risk.

The Impact of Vitamin D deficiency on Depression in Obese Adults.

BACKGROUND: There are studies showing associations between hypovitaminosis D and obesity, obesity and depression, and hypovitaminosis D and depression. This study aims to investigate the relationship between vitamin D levels and depression status of patients followed in an obesity center. METHODS: This retrospective study included 107 obesity patients followed up and treated at an obesity center. Patients were divided into two groups as serum 25(OH)D level < 20 ng/mL (deficient) and ≥ 20 ng/mL (not deficient) and compared in terms of Beck Depression Inventory scores. Patients were also divided into two groups according to BDI scores < 17 and ≥ 17, and serum 25(OH)D levels were evaluated. RESULTS: Patients at higher risk for depression (BDI score ≥ 17) had statistically significantly higher weight (p = 0.003) and BMI (p < 0.001), but had significantly lower serum 25(OH)D levels (p < 0.001). The BDI scores were found to be moderately positively related with the BMI (r = 0.404, p < 0.001), weakly negatively related with vitamin D levels (r = -0.383, p < 0.001), weakly positively related with weight (r = 0.293, p = 0.002). The BDI score me-dians (12 and 8, respectively) were found to be statistically significantly higher in patients with serum 25(OH)D levels of < 20 ng/mL compared to those with ≥ 20 ng/mL (p < 0.001). The increased BMI and decreased serum 25(OH)D levels have been found to independently increase the risk of depression in multivariate logistic regression analysis. The ROC analysis performed to evaluate the discriminative performance of serum 25(OH)D levels in predicting the risk of depression. The analysis showed that the serum 25(OH)D parameter was likely to reveal patients who were at higher risk for depression. For the cutoff point of 25(OH)D ≤ 19.21 level determined by Youden index, the sensitivity was found as 92.86% and the selectivity as 68.82%. CONCLUSIONS: In our study, the BMIs were higher and serum 25(OH)D levels were lower in obese individuals at risk for depression. Understanding or explaining the relationship between vitamin D deficiency and depression will contribute to revealing the preventive or therapeutic role of vitamin D supplementation for depression.