Serum 25OHD Concentrations Research Articles

6721 Short-Term Responses of Serum 25-Hydroxyvitamin D to Weekly Calcifediol or Cholecalciferol in Healthy Subjects

Abstract Disclosure: R.B. Caldeira: None. A.S. Nunes: None. F.Z. Cazzetta: None. M.S. Medeiros: None. L.B. Oliveira: None. M.P. Bandeira: None. F.F. Bandeira: None. Introduction: Recent studies have shown that oral calcifediol (CAL) induces faster serum 25-hydroxyvitamin D (25OHD) increases than cholecalciferol (CHO) as demonstrated in some studies on SARS-Cov2 infection. It is hypothesized that this rapid elevation is due to the unique mode of intestinal absorption of CAL to the portal vein system in comparison with CHO which is absorbed mainly by the lymphatic route. Data on weekly administration of calcifediol are still scarce. The aim of the present study was to compare serum 25OHD responses in the short term (30 days) to weekly doses of CAL or CHO in healthy subjects. Methods and Results: We studied 35 subjects (34% men, mean age 24.6 ± 4.6 years, BMI 22.9 ± 2.9 kg/m², waist circumference 74.7 ± 6.5 cm, SBP 111.1 ± 12.7 mmHg, and DBP 73.1 ± 9.1 mmHg) who were randomized to receive weekly oral CAL 70 mcg (18 subjects) or CHO 350 mcg (14,000 IU, 17 subjects). Doses were chosen based on the 2000 IU/day potency equivalence. Patients were matched for age, gender, BMI, and BP. They were contacted weekly to confirm medication adherence. Serum 25OHD concentrations were measured before administration of both agents and 24 hours after the last dose, using an immunochemiluminescent assay (Abbott Diagnostics, Lake Forest, IL, USA) with a detection range from 4.9 to 151.3 ng/ml. At baseline serum 25OHD was 32.1 ±8.8 vs 33.1 ± 6.6 in CAL and CHO groups respectively (p=0.691). In CAL group 8 subjects had serum 25 OHD < 30 ng/mL (1 subject had 14.7 ng/mL) and in the CHO none had serum 25OHD below 20 ng/mL and 5 subjects had levels between 20 and 30 ng/mL. After 1 month, serum 25OHD levels rose significantly 3.3 times more with CAL than with CHO (+29.61 ± 7.39 ng/mL vs. 9.00 ± 3.50 ng/mL; p < 0.001). In CHO group one subject remained with 25OHD below 30 ng/mL after the intervention. Conclusion: We found a rapid and robust elevation of serum 25OHD levels with CAL compared to CHO at similar potency doses. This may have clinical implications for conditions in which there is a need for immediate availability of 25OHD to peripheral tissues. Presentation: 6/2/2024

The Importance of Determining the Level of Bone Metabolism Markers and Vitamin D in the First Year of Life in the Kazakh Population.

The research aimed to determine the importance of vitamin D and markers of bone metabolism in the overall assessment of bone mineralization during a child's first year of life. The 198 children were selected by screening all infants seen at our pediatric clinic over a 2-year period from 2020-2022 and including those who met the eligibility criteria of being aged 0 to 1 year, healthy with no chronic conditions, and not on vitamin D supplementation. Children were divided into 3 groups depending on the content of vitamin D in the blood serum: sufficient, insufficient, and deficient. The markers of bone tissue status included: markers of mineral metabolism (calcium, phosphorus, parathyroid hormone, calcitonin), a marker of bone formation (osteocalcin), resorption marker (deoxypyridinoline). Laboratory values were obtained at the time of study enrollment during the initial study visit. Labs were not repeated during the course of the study. A quarter of the infants exhibited vitamin D deficiency at enrollment with serum 25OHD concentrations below 20 ng/mL, which showed a positive correlation with serum calcium and phosphorus -concentrations and a negative correlation with PTH, while osteocalcin and deoxypyridinoline concentrations remained consistent regardless of vitamin D status. The study's practical significance allows for the recommendation of using vitamin D -concentrations as a marker to detect bone formation and mineral metabolism disorders in children during their first year of life. By identifying and addressing these issues early on, the health care system aims to ensure better musculoskeletal health for children.

Discordant responses of bone formation and absorption markers in Japanese infants with vitamin D deficiency: a comprehensive matched case-control study.

Vitamin D deficiency during infancy has been associated with increased bone turnover rate and bone mineral loss. However, few studies have examined bone turnover markers (BTMs) for both bone formation and resorption in infants with vitamin D deficiency. Here, we analyzed serum concentrations of 25OHD, intact parathormone (iPTH), and BTMs including total alkaline phosphatase (ALP), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), and serum type I collagen N-telopeptide (NTx) as well as basic clinical characteristics of 456 infants (626 samples) aged less than 12mo born at Saitama City Hospital, Japan (latitude 35.9° North) between January 2021 and December 2022. One hundred sixteen infants (147 samples) were classified as having vitamin D deficiency (25OHD < 12.0ng/mL), and 340 infants (479 samples) had sufficient vitamin D levels (25OHD ≥ 12.0ng/mL). In addition to 25OHD and ALP, both TRACP-5b and sNTx were measured in 331 infants (418 samples), while 90 infants (105 samples) had only TRACP-5b measured and 101 infants (103 samples) had only sNTx measured. Statistical comparison of 104 subjects each in the vitamin D deficiency and sufficiency groups after matching for the background characteristics revealed that the vitamin D deficiency group had significantly higher levels of ALP and iPTH compared with the sufficiency group (P = <.0001, .0012, respectively). However, no significant differences were found in TRACP-5b and NTx levels between the 2 groups (P = .19, .08, respectively). Our findings suggest discordant responses between bone formation and resorption markers in subclinical vitamin D deficiency during infancy.

No evidence of a causal relationship between miscarriage and 25-hydroxyvitamin D: a Mendelian randomization study.

Is there a causal relationship between 25-hydroxyvitamin D (25OHD) and miscarriage? In this study, little evidence of a causal relationship was found between low serum 25OHD concentration or vitamin D deficiency and the risk of miscarriages. Associations between low vitamin D levels and increased risk of miscarriage have been reported, but causality is unclear. The latest and largest genome-wide association studies (GWAS) for serum 25OHD concentration (n = 417580), vitamin D deficiency (426 cases and 354812 controls), miscarriage (16906 cases and 149622 controls), and the number of miscarriages (n = 78700) were used to explore the causal association between serum vitamin D levels and miscarriage by two-sample Mendelian randomization analysis. This study was based on summary GWAS results from the FinnGen database and the UK Biobank. The random-effect inverse-variance weighted method was regarded as the primary analysis; MR-Egger, weighted median, weighted mode, simple mode, and MR-pleiotropy residual sum and outlier (MR-PRESSO) were further employed as complementary methods. MR-Egger intercept analysis and MR-PRESSO were employed to test pleiotropy, and Cochran's Q statistic and leave-one-out sensitivity analysis were used to determine the heterogeneity and robustness of the overall estimates, respectively. There was insufficient evidence of causal associations between serum 25OHD concentration and miscarriage (odds ratio (OR) = 0.995, 95% CI: 0.888 to 1.114, P = 0.927), or the number of miscarriages (β = -0.004, 95% CI: -0.040 to 0.032, P = 0.829). Furthermore, little evidence of causality between genetically determined vitamin D deficiency to miscarriage (OR = 0.993, 95% CI: 0.966 to 1.021, P = 0.624), or the number of miscarriages (β = 0.001, 95% CI: -0.009 to 0.011, P = 0.828), was observed. The results of the sensitivity analysis were robust, and no significant heterogeneity or horizontal pleiotropy was found. This study is limited by the absence of female-specific GWAS data and the limited amount of GWAS data available for this study, as well as the need for caution in generalizing the findings to non-European ethnic groups. These findings enhance the current understanding of the intricate association between vitamin D and pregnancy outcomes, challenging prevailing beliefs regarding the strong association with miscarriage. The results provide a special perspective that may prompt further exploration and potentially offer insights for guiding future research and informing clinical guidelines pertaining to the management of miscarriage. This project was supported by the Hubei Provincial Natural Science Foundation Program General Surface Project (2022CFB200), the Key Research & Developmental Program of of Hubei Province (2022BCA042), the Fundamental Research Funds for the Central Universities (2042022gf0007, 2042022kf1210), and the Interdisciplinary Innovative Talents Foundation from Renmin Hospital of Wuhan University (JCRCWL-2022-001, JCRCYG-2022-009). All authors have no conflicts of interest to declare. N/A.

Histomorphometric analysis of patients with femoral neck fracture and 25-hydroxyvitamin D deficiency: a cross-sectional study.

Vitamin D deficiency causes osteoporosis, bone mineralization disorders, and osteomalacia. Osteomalacia is diagnosed using blood biochemical tests, clinical symptoms, and imaging; however, accurate detection of mineralization disorders requires tissue observation. We investigated the prevalence of bone mineralization disorders and their relationship with serum 25-hydroxyvitamin D (25OHD) levels in patients with untreated osteoporosis with femoral neck fractures. A non-demineralized specimen was prepared from the femoral head removed during surgery in 65 patients. Bone histomorphometry of cancerous bone in the femoral head center was conducted. Osteoid volume per bone volume (OV/BV) and osteoid thickness (O.Th) were measured as indicators of mineralization disorder. The mean serum 25OHD level (11.9 ± 5.7ng/mL) was in the deficiency range (< 12ng/mL). There were no clinically diagnosed cases of osteomalacia (OV/BV > 10% and O.Th > 12.5µm); however, one case of mineralization disorder, considered histologically pre-osteomalacia (OV/BV > 5% and O.Th < 12.5µm), was observed (OB/BV, 17.6%; O.Th, 12.3µm). Excluding this case, those with severe (25OHD < 12ng/mL, at risk of osteomalacia; n = 39) and non-severe deficiency (25OHD ≥ 12ng/mL; n = 25) did not significantly differ in OV/BV (%; 0.77 ± 0.54 vs. 0.69 ± 0.38, p = 0.484) or O.Th (µm; 5.32 ± 1.04 vs. 5.13 ± 0.78, p = 0.410). Further, 25OHD and OV/BV were not significantly correlated (R = -0.124, p = 0.327). This is the first study in the twenty-first century to examine serum 25OHD concentrations and bone mineralization disorders in Japanese patients with osteoporosis. The results indicate that vitamin D deficiency does not necessarily cause bone mineralization disorders and rarely leads to osteomalacia.

Tip 1 Diyabette Serum Vitamin D Bağlayan Protein Düzeylerinin Araştırılması: Glisemik Kontrol ve Hastalık Süresinin Etkisi

Aim: Patients with type 1 diabetes mellitus (T1DM) are known to be more prone to vitamin D deficiency. Vitamin D studies in this&#x0D; patient population have traditionally been performed using serum 25OHD levels. However, vitamin D binding protein (VDBP) has&#x0D; been less studied. This study aims to compare serum VDBP levels in T1DM with healthy controls. It also aims to investigate the factors&#x0D; affecting VDBP levels such as disease duration, HbA1c, insulin dose, and age in diabetic subjects.&#x0D; Material and Methods: A research study was conducted at Çanakkale Onsekiz Mart University Health Practice and Research Hospital.&#x0D; The study included 11-17 years old children with T1DM and healthy controls. Serum VDBP and 25OHD concentrations were compared&#x0D; with appropriate statistical methods according to the normal distribution of relevant parameters. For the diabetic subjects, insulin doses&#x0D; and duration of diabetes were recorded. Spearman’s correlation test was utilized to assess associations between continuous variables, and&#x0D; regression analysis was employed to determine predictors of serum VDBP levels.&#x0D; Results: The study enrolled 89 subjects, including 40 with diabetes. Serum 25OHD levels were similar in the T1DM group and control&#x0D; group (17.03 IQR:12.89-22.08) and (17.62 IQR:11.68-24.48), respectively (p=0.701). However, VDBP levels were significantly lower in&#x0D; the T1DM group (335 μg/ml, IQR: 199.8-517.2 μg/ml) compared to the control group (471.2 μg/ml, IQR: 368.3-533.2 μg/ml) (p &lt; 0.015).&#x0D; In the entire group, only the presence of diabetes affected VDBP levels (B=87.236, SE=34.802, p=0.014). On the other hand, HbA1c,&#x0D; duration of diabetes, and insulin dose had no influence on VDBP in the diabetes group.&#x0D; Conclusion: Serum VDBP levels were significantly lower in T1DM patients but in this group, disease duration, insulin dose, and&#x0D; metabolic control did not affect serum VDBP levels. Serum VDBP concentrations in T1DM may be affected by other parameters rather&#x0D; than metabolic parameters. Therefore, future studies should focus on addressing this knowledge gap.

ASSOCIATION VITAMIN D TO GLAUCOMA: A SYSTEMATIC REVIEW

Background: Glaucoma is a chronic progressive optic neuropathy that causes irreversible damage. Therefore, early diagnosis and appropriate treatment to control various risk factors associated with glaucoma are important. Risk factors associated with the development of glaucoma have been reported by many researchers and include both ocular and non-ocular (systemic) factors such as myopia, central corneal thickness, disc hemorrhage, and genetic factors. The aim: This study aims to show association vitamin D to glaucoma. Methods: By comparing itself to the standards set by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, this study was able to show that it met all of the requirements. So, the experts were able to make sure that the study was as up-to-date as it was possible to be. For this search approach, publications that came out between 2013 and 2023 were taken into account. Several different online reference sources, like Pubmed and SagePub, were used to do this. It was decided not to take into account review pieces, works that had already been published, or works that were only half done. Result: In the PubMed database, the results of our search brought up 89 articles, whereas the results of our search on SagePub brought up 98 articles. The results of the search conducted for the last year of 2013 yielded a total 13 articles for PubMed and 26 articles for SagePub. The result from title screening, a total 2 articles for PubMed and 18 articles for SagePub. In the end, we compiled a total of 10 papers. We included five research that met the criteria. Conclusion: Decreased serum 25-OHD concentration was associated with the presence but not the severity of POAG. It was suggested that Vitamin D deficiency should be considered a potential risk factor for the development of open-angle glaucoma.

Vitamin D Status, Vitamin D Receptor Polymorphisms, and the Risk of Incident Rosacea: Insights from Mendelian Randomization and Cohort Study in the UK Biobank.

Previous cross-sectional studies have failed to definitively establish a causal relationship between serum 25-hydroxyvitamin D (25OHD) concentrations and the onset of rosacea. To investigate the potential association between serum 25OHD levels, vitamin D receptor (VDR) polymorphisms, and the risk of developing incident rosacea. This cross-sectional population-based cohort study utilizing 370,209 individuals from the UK Biobank. Cox proportional hazard regression models and two-sample Mendelian randomization (MR) analyses were applied to explore the causative relationship between 25OHD and incident rosacea. Our findings revealed that elevated levels of serum 25OHD were inversely correlated with the risk of incident rosacea. Specifically, compared to participants with 25OHD levels below 25 nmol/L, the multivariate-adjusted HR for incident rosacea was 0.81 (95% CI: 0.70, 0.94) in those with 25OHD levels exceeding 50 nmol/L. Further, in comparison to individuals with serum 25OHD less than 25 nmol/L and the rs731236 (TaqI) AA allele, those with serum 25OHD higher than 75 nmol/L and the TaqI GG allele had a multivariate-adjusted HR of 0.51 (95% CI 0.32 to 0.81) for developing rosacea. Results from the MR study supported a significant association, with each standard deviation increase in serum 25OHD concentrations correlating to a 23% reduced risk of rosacea (HR = 0.77, 95% CI: 0.63, 0.93). The findings of this cohort study indicate an inverse association between increased concentrations of serum 25OHD and the risk of developing incident rosacea. While our results highlight the potential protective role of vitamin D, the definitive efficacy of vitamin D supplementation as a preventive strategy against rosacea requires further investigation.

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

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

SERUM PARATHORMONE, VITAMIN D AND CARDIOVASCULAR RISK FACTORS

Objective: The aim of this study is to evaluate the associations of serum 25-OHD and PTH concentrations with blood pressure and hypertension mediated target organ damage including left ventricular hypertrophy (LVH) and carotid intima-media thickness (IMT). Design and method: This observational retrospective study included 98 patients admitted at Hypertension Research Center of Federico II University Hospital in Naples without CKD. We collected serum 25-OHD, PTH, creatinine, BMI, lipid profile, blood glucose and office blood pressure. All patients underwent carotid doppler ultrasound and echocardiography. Results: Mean age of the participants was 53±17 years and 69% were men. Pearson's correlation analysis indicated that PTH levels correlated directly with age, diabetes, dyslipidemia, hypertension, fasting glucose, on statin therapy, left ventricular mass and inversely with the GFR, total cholesterol, LDL and vit D level. Vit. D levels correlated inversely with PTH, diabetes and carotid plaque. Multivariate regression models indicated that PTH was significantly associated with higher fasting glucose and with vit D while Vit D was associated with lower GFR and PTH level. Conclusions: In a population at high cardiovascular risk, Vit. D and PTH are not directly associated with hypertension but might influence association with other cardiovascular risk factors and markers.

Genetic correlation, causal relationship, and shared loci between vitamin D and COVID-19: A genome-wide cross-trait analysis.

Observational studies have shown that vitamin D supplementation reduces the risk of COVID-19 infection, yet little is known about the shared genomic architectures between them. Leveraging large-scale genome-wide association study (GWAS)summary statistics, we investigated the genetic correlation and causal relationship between genetically determined vitamin D and COVID-19 using linkage disequilibrium scoreregression and Mendelian randomization (MR)analyses, and conducted a cross-trait GWAS meta-analysis to identify the overlapping susceptibility loci of them. We observed a significant genetic correlation between genetically predicted vitamin D and COVID-19(rg = -0.143, p = 0.011), and the risk of COVID-19infection would decrease by 6% for every 0.76 nmol L-1 increase of serum 25 hydroxyvitamin D (25OHD)concentrations in generalized MR (OR = 0.94, 95%CI: 0.89-0.99, p = 0.019). We identified rs4971066 (EFNA1) as a risk locus for the joint phenotype of vitamin D and COVID-19.In conclusion, genetically determined vitamin D is associated with COVID-19. Increased levels of serum 25OHD concentration may benefit the prevention and treatment of COVID-19.

Vitamin D Status in Diabetic Moroccan Children And Adolescents: a Case-control Study

Background: Type 1 diabetes mellitus (T1DM) incidence is currently increasing worldwide, and different environmental players along with genetic predisposition, could be involved as powerful triggers of this disease onset. In this study, we aim to shed the light on the relationship between 25OHD deficiency and T1DM. Patients and methods: A case-control study was laid out to compare serum 25OHD level between T1DM patients and controls. A total of 147 T1DM patients aged under 19 years old were recruited from our Endocrinology-Diabetology and Nutrition department between October 2014 and December 2019. A total of 147 controls were randomly enlisted from clinical biochemistry laboratory of our center, and were carefully matched. The levels of 25OHD in the serum were determined in T1DM patients and nondiabetic controls. Results: Average serum 25OHD concentration was established in both groups; reaching 19,29 ±6,13 ng/ml in the control arm and 15,02 ± 6,48 ng/ml in the selected group with T1DM independently of the disease duration. However, the mean serum 25OHD concentration was not significantly different between the two T1DM subgroups according to diabetes duration below or above 5 years, and 25OHD concentration remained lower either in winter or summer months. A negative correlation was noticed between HbA1c and serum 25 OHD concentration in T1DM patients and was statistically significant (p<0,05). Conclusion: Key messages on the importance of vitamin D status, particularly in diabetic children and adolescents, should be spread widely in order to start a suitable vitamin supplementation, and establish guidelines regarding its timing at adequate recommended doses..

Sun Exposure Score and Vitamin D Levels in Moroccan Women of Childbearing Age.

Sunlight exposure is an essential source of vitamin D for many humans. However, hypovitaminosis D is a global public health problem. This study aimed to develop and validate a sun exposure score (SES) and correlate it with serum 25-hydroxyvitamin D levels in women of childbearing age. One hundred and sixty women aged 18 to 45 years residing in Meknes, Morocco, were included. A questionnaire estimating the sun exposure score and blood analysis of serum 25-OHD concentration were performed. The questionnaire's reliability and construct validity were evaluated using Cronbach's alpha and factor analysis. Spearman's test was used to assess the correlation between SES and 25-OHD levels. The score's reliability and construct validity were good, with Cronbach's alpha values >0.70 and factorial saturation ranging from 0.696 to 0.948. Serum 25-OHD levels were significantly associated with the total sun exposure score, and all SES domains (Rho was 0.615 (p < 0.0001), 0.307 (p < 0.0001), 0.605 (p < 0.0001), and 0.424 (p < 0.0001) for total SES, indoor exposure domain, outdoor exposure domain, and sun protection practice domain, respectively). In addition, median 25-OHD levels increased significantly when sun exposure was changed from insufficient to sufficient (p < 0.0001). The results suggest that the sun exposure score could be used as a clinical tool to assess vitamin D levels in women of childbearing age.

Vitamin D status in chimpanzees in human care: a Europe wide study

While vitamin D deficiency is a public health concern in humans, comparatively little is known about vitamin D levels in non-human primates. Vitamin D plays a crucial role in overall health and its deficiency is associated with a range of disorders, including cardiovascular disease, which is a leading cause of death in great apes. Serum samples (n = 245) from chimpanzees (Pan troglodytes) housed at 32 European zoos were measured for 25-hydroxyvitamin D2, 25-hydroxyvitamin D3 and total 25-hydroxyvitamin D (25-OHD) using liquid chromatography and tandem mass spectrometry. Of these samples, 33.1% indicated inadequate vitamin D status, using the human reference interval (25-OHD < 50 nmol/L). The season of the year, health status of the animal, and the provision of daily outdoor access had a significant effect on vitamin D status. This is the first large-scale study on vitamin D status of non-human great apes in human care. Inadequate 25-OHD serum concentrations are widespread in the chimpanzee population in Europe and could be a risk factor for the development of idiopathic myocardial fibrosis, a major cause of mortality in this species, as well as other diseases. A review of husbandry and nutrition practices is recommended to ensure optimal vitamin D supply for these endangered animals.

Particulate matter may have a limited influence on maternal vitamin D levels

Evidence for an association between the amount of particulate matter (PM) in the atmosphere and vitamin D status of pregnant women is limited. We aimed to examine the independent association between PM and maternal levels of serum 25-hydroxyvitamin D (25OHD) during the second trimester and to explore possible modifications to the association by meteorological factors. 27,768 pregnant women presenting for prenatal examination who were tested for serum 25OHD concentration during the second trimester between January 1, 2016, and December 31, 2020, were included in this retrospective analysis. Exposure to PM was evaluated based on daily average PM with an aerodynamic diameter of ≤ 2.5 μm (PM2.5) and PM with an aerodynamic diameter of ≤ 10 μm (PM10). Corresponding meteorological data for daily average atmospheric temperature, atmospheric pressure, relative humidity, sunshine duration, and wind speed were collected. The maximum cumulative effects of PM2.5 occurred at lag 45 days, and the maximum cumulative effects of PM10 occurred at lag 60 days. In crude models, 45-day moving daily average PM2.5 concentrations were negatively associated with 25OHD levels (β, − 0.20; 95% CI − 0.21 to − 0.19), as were 60-day moving daily average PM10 concentrations (β, − 0.14; 95% CI − 0.15 to − 0.14). After adjusting for temporal and meteorological factors, the effect values were drastically reduced (adjusted β of PM2.5, − 0.032; 95% CI − 0.046 to − 0.018; adjusted β of PM10, − 0.039; 95% CI − 0.049 to − 0.028). Our study showed there was a small, independent, negative association between PM in the atmosphere and maternal serum 25OHD levels during the second trimester of pregnancy after adjusting for temporal and/or meteorological factors, which indicates that PM may have a limited influence on maternal serum 25OHD levels. Besides taking vitamin D supplements, pregnant women should keep participating in outdoor activities while taking PM protection measures to improve their vitamin D levels when PM levels are high in winter and spring.

Genetic factors help explain the variable responses of young children with cystic fibrosis to vitamin D supplements.

Children with cystic fibrosis (CF) are susceptible to fat-soluble vitamin deficiencies unless supplemented, but even large doses of vitamin D may not prevent low 25-hydroxyvitamin D (25OHD) concentrations. The explanation for these vitamin D non-responders has been elusive. We utilized data from whole genome sequencing (WGS) to test the hypothesis that genetic variations predict responsiveness to vitamin D supplementation in a prospective cohort study of children with CF in the first 3 years of life. One hundred and one infants born during 2012-2017 and diagnosed with CF through newborn screening were studied. Serum 25OHD concentrations and vitamin D supplement doses were assessed during early infancy and annually thereafter. WGS was performed, the resultant variant calling files processed, and the summary statistics from a recent genome-wide association study were utilized to construct a polygenic risk score (PRS) for each subject. Overall, the prevalence of vitamin D insufficiency (<30ng/mL) was 21% in the first 3 years of life. Among the 70 subjects who always adhered to vitamin D supplement doses recommended by the US CF Foundation guidelines, 89% were responders (achieved vitamin D sufficiency) by 3 years of age, while 11% were transient or non-responders. Multiple regression analysis revealed that PRS was a significant predictor of 25OHD concentrations (p<0.001) and the likelihood of being an earlier responder in the first 3 years of life (p<0.01). A limited SNP analysis revealed variants in four important genes (GC, LIPC, CYP24A1, and PDE3B) that were shown to be associated with 25OHD concentrations and vitamin D responder status. Other determinants included vitamin D supplement dose, season at 25OHD measurement, and pancreatic functional status. Applying WGS in conjunction with utilizing a PRS approach revealed genetic variations that partially explain the unresponsiveness of some children with CF to vitamin D supplementation. Our findings suggest that a nutrigenomics strategy could help promote personalized treatment in CF.

Associations between Serum 25-Hydroxyvitamin D Levels and Health-Related Quality-of-Life Measures in Patients with Breast Cancer: A Longitudinal Study.

Recent evidence suggests that vitamin D might lower breast cancer mortality. There is also growing interest in vitamin D's potential association with health-related quality-of-life (HRQoL). Associations between circulating 25-hydroxyvitamin D (25OHD) concentrations and HRQoL were examined prospectively among breast cancer survivors at the time of diagnosis and 1 year later. 504 women with incident early-stage breast cancer at Roswell Park Comprehensive Cancer Center were included, and 372 patients provided assessments 1 year later. At each timepoint, participants provided blood samples and completed the SF-36 Health Survey, and surveys on perceived stress, depression, and fatigue. Season-adjusted serum 25OHD concentrations were analyzed in relation to HRQoL measures using multivariable logistic regression models. Approximately 32% of participants had deficient vitamin D levels at diagnosis, which decreased to 25% at 1 year. Concurrently, although SF-36 physical health summary scores were lower at 1 year, mental health summary scores improved, and levels of depression and perceived stress were lower. In comparison with women with sufficient 25OHD levels (>30 ng/mL) at diagnosis, those who were deficient (<20 ng/mL) had significantly worse HRQoL at diagnosis and 1 year later. Vitamin D deficiency 1 year post-diagnosis was also associated with worse HRQoL, particularly among breast cancer survivors who took vitamin D supplements. Breast cancer survivors with vitamin D deficiency were more likely to report lower HRQoL than those with sufficient levels at the time of diagnosis and 1 year post-diagnosis. Our results indicate a potential benefit of vitamin D supplementation for improving breast cancer survivorship.

Relationships of Serum 25-Hydroxyvitamin D Concentrations, Diabetes, Genetic Susceptibility, and New-Onset Chronic Kidney Disease.

The prospective relation of vitamin D status with the risk of chronic kidney diseases (CKD) remains uncertain. We aimed to examine the association of serum 25-hydroxyvitamin D (25OHD) with new-onset CKD in participants with and without diabetes at baseline and examine the potential modifications by genetic susceptibility on the association. Included were 348,243 adults from the UK Biobank without prior CKD at baseline. Serum 25OHD concentrations were measured by chemiluminescent immunoassay method. Genetic risk score of CKD was calculated by 263 single nucleotide polymorphisms, which showed significant associations with estimated glomerular filtration rate. The primary outcome was new-onset CKD. During a median follow-up duration of 12.1 years, 9,344 new-onset CKD were documented. Overall, there was a significant inverse association between baseline serum 25OHD and new-onset CKD in participants with diabetes (per SD increment, adjusted hazard ratio [HR] 0.91; 95% CI 0.86-0.96), but not in those without diabetes (per SD increment, adjusted HR 0.98; 95% CI 0.96-1.01; P-interaction between serum 25OHD and diabetes = 0.004). Accordingly, among participants with diabetes, compared with those baseline serum 25OHD <25 nmol/L, a significantly lower risk of new-onset CKD was found in those with 25OHD ≥50 nmol/L (adjusted HR 0.77; 95% CI 0.67-0.89). Moreover, the genetic risk of CKD did not significantly modify the association between baseline serum 25OHD and new-onset CKD among participants with diabetes (P-interaction = 0.127). There was an inverse association between baseline serum 25OHD and new-onset CKD in participants with diabetes. The inverse association was not found in participants without diabetes.

Genetic variations of vitamin D receptor and vitamin D supplementation interaction in relation to serum vitamin D and metabolic traits: a systematic review and meta-analysis.

Background: It is now becoming increasingly recognized that the effects of vitamin D supplementation may vary by several factors including vitamin D deficiency status, ethnicity, and/or the presence of genetic variants, which affect individual responses to supplementation. This study investigates the interaction between metabolic traits and circulating 25-hydroxyvitamin-D (25OHD) concentration with 4 polymorphisms of vitamin D receptor (VDR) including BsmI, ApaI, TaqI, FokI, and vitamin D supplementation. Methods: A systematic review and meta-analysis of papers until August 2021 on PubMed, The Cochrane Library, Scopus, Web of Science, Google Scholar, ProQuest, Science Direct, and Embase about the association between functionally relevant VDR variants and vitamin D supplementation on circulating 25OHD and metabolic traits. Results: A total of 2994 cases from 16 randomized controlled trial (RCT) studies were included in meta-analyses. There were no significant changes in the serum concentrations of 25OHD and metabolic traits after vitamin D supplementation in different variants of BsmI, ApaI, TaqI, and FokI polymorphism in the VDR gene in the overall analysis (p>0.05). However, the results showed there is significant interaction between these above VDR polymorphisms and vitamin D supplement on serum 25OHD level after subgroup analyses based on the study duration, gender, age, BMI, health status, Hardy-Weinberg Equilibrium, PCR, and race (p<0.05). Conclusions: The present meta-analysis demonstrates that the effect of vitamin D supplementation on serum 25OHD and metabolic traits is independent of genetic variants of the VDR gene (BsmI, ApaI, TaqI, and FokI). However, future trials should consider inter-individual differences and, in particular, should aim to clarify whether certain subgroups of individuals may benefit from vitamin D supplementation in the context of metabolic health.

Efficacy and safety of a novel source of dietary 25-hydroxycholecalciferol in growing pigs.

A randomized complete block design experiment was conducted to determine the safety and efficacy of supplementation of increasing concentrations of a novel, bacterial fermentation-derived vitamin D source on growth performance and tissue deposition of 25-hydroxycholecalciferol (25OHD3) in growing swine. Dietary treatments were as follows: commercial control with vitamin D3 (CON) at NRC recommended concentrations and three diets composed of CON + increasing inclusions (25, 50, and 250 µg/kg equivalent) of 25OHD3 from a novel source (CON + 25; CON + 50; and CON + 250, respectively). Pigs (n = 144) were assigned to 24 pens which were allotted to one of the four dietary treatments and fed for 42 d. Blood samples were collected for 25OHD3 concentration determination and individual body weights (BW) were measured on experimental day 0, 39, and 63. On day 42, tissues from 48 pigs (12 pigs per dietary treatment) were analyzed for 25OHD3 concentration. No differences were observed in growth performance. Day 39 serum 25OHD3 concentrations were greatest in CON + 250-fed pigs and linearly decreased as dietary 25OHD3 inclusion decreased (P < 0.0001). On day 42, tissue 25OHD3 concentrations increased linearly as 25OHD3 increased in the diet (P < 0.0001). On day 63, 21 d after dietary 25OHD3 withdrawal, serum 25OHD3 concentrations of all 25OHD3-fed pigs decreased to that of or within 2.76 ± 0.89 ng/mL of CON-fed pigs which demonstrates that feeding 250 µg/kg 25OHD3 is well tolerated by growing pigs and will clear the body within 21 d.