To combat vitamin D insufficiency in a population, reliable diet sources of vitamin D are required. The recommendations to consume more oily fish and the use of UVB-treated yeast are already applied strategies to address vitamin D insufficiency. This study aimed to elucidate the suitability of plant oils as an alternative vitamin D source. Therefore, plant oils that are commonly used in human nutrition were first analyzed for their content of vitamin D precursors and metabolites. Second, selected oils were exposed to a short-term UVB irradiation to stimulate the synthesis of vitamin D. Finally, to elucidate the efficacy of plant-derived vitamin D to improve the vitamin D status, we fed UVB-exposed wheat germ oil (WGO) for 4 weeks to mice and compared them with mice that received non-exposed or vitamin D3 supplemented WGO. Sterol analysis revealed that the selected plant oils contained high amounts of not only ergosterol but also 7-dehydrocholesterol (7-DHC), with the highest concentrations found in WGO. Exposure to UVB irradiation resulted in a partial conversion of ergosterol and 7-DHC to vitamin D2 and D3 in these oils. Mice fed the UVB-exposed WGO were able to improve their vitamin D status as shown by the rise in the plasma concentration of 25-hydroxyvitamin D [25(OH)D] and the liver content of vitamin D compared with mice fed the non-exposed oil. However, the plasma concentration of 25(OH)D of mice fed the UVB-treated oil did not reach the values observed in the group fed the D3 supplemented oil. It was striking that the intake of the UVB-exposed oil resulted in distinct accumulation of vitamin D2 in the livers of these mice. In conclusion, plant oils, in particular WGO, contain considerable amounts of vitamin D precursors which can be converted to vitamin D via UVB exposure. However, the UVB-exposed WGO was less effective to improve the 25(OH)D plasma concentration than a supplementation with vitamin D3.

Background: Acute kidney injury (AKI) constitutes a multi-factorially caused condition, which significantly affects kidney function and can lead to elevated risk of morbidity and mortality. Given the rising scientific evidence regarding vitamin D's (VitD's) multisystemic role, the connection between AKI and VitD is currently being studied, and the complex relation between them has started to be unraveled. Methods: A systematic review had been conducted to identify the pathogenetic relation of VitD and AKI and the potential role of VitD as a biomarker and therapeutic-renoprotective factor. Results: From 792 articles, 74 articles were identified that fulfilled the inclusion criteria. Based on these articles, it has been found that not only can VitD disorders (VitD deficiency or toxicity) cause AKI but, also, AKI can lead to great disruption in the metabolism of VitD. Moreover, it has been found that VitD serves as a novel biomarker for prediction of the risk of developing AKI and for the prognosis of AKI's severity. Finally, animal models showed that VitD can both ameliorate AKI and prevent its onset, suggesting its renoprotective effect. Conclusion: There is a complex two-way pathogenetic relation between VitD disorders and AKI, while, concomitantly, VitD serves as a potential novel predictive-prognostic biomarker and a treatment agent in AKI therapy.

Vitamin D deficiency during pregnancy is common, but whether maternal vitamin D status affects glycolipid metabolism of offspring remains unclear.

Vitamin D is an essential vitamin for the normal formation of bones and calcium absorption. It is synthesized into our body through sunlight exposure and obtained by consuming foods rich in vitamin D (e.g., fatty fish, eggs yolk, dairy products). Its benefits on the health and performance of athletes are well documented. This article outlines some analytical challenges concerning the analytical quantification of vitamin D for its optimal intake, namely, a comprehensive study of the variability of the assay before categorizing any method as the golden standard, assurance of sample comparability to draw meaningful correlations, revision of the intake guidance based on appropriate statistical power analysis, and the implementation of rational strategies for preventing the underlying mechanism of preanalytical factors. Addressing these challenges will enable the effective management of vitamin D in the sports sector.

Background: Serum uric acid can act as a risk factor for cardiovascular disease (CVD) and as antioxidant defense. Vitamin D deficiency can activate the parathyroid to induce the release of parathyroid hormone, which was thought to increase serum uric acid level, and low vitamin D status may also be associated with risk of CVD. No known studies have explored the association between serum 25(OH) D, vitamin D intake, and HU for the American population. Methods: We extracted 15,723 US adults aged 20-85 years from the National Health and Nutrition Examination Survey (NHANES) in 2007-2014. All dietary intakes were evaluated through 24-h dietary recalls. Multivariable logistic regression analysis was performed to examine the associations after adjustment for confounders. Results: Compared to the lowest quintile (Q1), for males, adjusted odds ratios (ORs) of HU in Q2 to Q4 of serum 25(OH) D levels were 0.78 (95% CI, 0.65-0.93), 0.97 (0.81-1.16), and 0.72 (0.60-0.88); ORs in Q2-Q5 of total vitamin D intake were 0.83 (0.69-0.98), 0.69 (0.58-0.83), 0.66 (0.55-0.79), and 0.59 (0.48-0.71), respectively. In females, OR was 0.80 (0.66-0.97) of serum 25(OH) D for Q3, and ORs in Q5 of total vitamin D intake were 0.80 (0.65-0.98). Conclusions: Our findings indicated that the serum 25(OH) D intakes of dietary vitamin D, supplemental vitamin D, and total vitamin D were inversely associated with HU in males. In females, a lower risk of HU with higher serum 25(OH) D, dietary vitamin D, and total vitamin D intake was found, but with no association between supplemental vitamin D intake and the risk of HU.

The fetus depends on the transplacental transfer of vitamin D. Calcifediol (25-OH-D3) is the vitamin D metabolite that crosses the placenta. Previously, oral 25-OH-D3 improved serum 25-OH-D3 compared to vitamin D3 in non-pregnant subjects, although no studies are available in pregnant women. We evaluated the availability of oral 25-OH-D3 compared to vitamin D3 during pregnancy, as well as, their levels in the fetus and effect on metabolism-related proteins. Twenty female rats per group were fed with 25 μg/kg of diet of vitamin D3 (1,000 UI vitamin D/kg diet) or with 25 μg/kg diet of 25-OH-D3. We analyzed 25-OH-D3 levels in maternal and fetal plasma; protein levels of vitamin D receptor (VDR), fatty acid translocase (FAT), and scavenger-receptor class B type-1 (SR-B1) in both maternal liver and placenta; and protein levels of VDR and Glutamate decarboxylase (GAD67) in fetal brain. 25-OH-D3 doubled the concentration of 25-OH-D3 in both maternal and fetal plasma compared to vitamin D3. In addition, maternal liver VDR, FAT, and SR-BI increased significantly in the 25-OH-D3 group, but no changes were found in the placenta. Interestingly, 25-OH-D3 decreased GAD67 expression in the fetal brain and it also tended to decrease VDR (P = 0.086). In conclusion, 25-OH-D3 provided better vitamin D availability for both mother and fetus when administered during pregnancy compared to vitamin D3. No adverse effects on pregnancy outcomes were observed. The effects of 25-OH-D3 on the expression of VDR and GAD67 in fetal brain require further investigation.

Background: A high prevalence of vitamin D deficiency exists in pregnant Indian women (~90%). Increasing evidence suggests that vitamin D could play a pivotal role in maintaining normal glucose homeostasis. We aimed to determine the association between maternal vitamin D concentrations in early pregnancy and the risk of gestational diabetes mellitus (GDM). Methods: A prospective observational study was conducted on healthy pregnant women (n = 392) attending routine antenatal care at St. John's Medical College Hospital, Bangalore recruited at ~12 weeks of gestation. At baseline, details on socio-economic status, obstetric history, dietary intakes, and anthropometry were collected. Venous plasma total vitamin D concentration was assessed using tandem liquid chromatography mass spectrophotometry (LC-MS/MS). Oral glucose tolerance test (OGTT) at recruitment, followed by glucose tolerance test (GTT) at mid-pregnancy was conducted. GDM was diagnosed and confirmed using the International Association of Diabetes and Pregnancy Study Groups (IADPSG) classification. Univariate and adjusted logistic regression models were used to evaluate the associations between total vitamin D concentrations at enrollment with GDM. Results: Of the cohort, 10.2% were diagnosed as GDM. Women with GDM were older (26 vs. 24 years) and heavier (51.6 vs. 51.2 kg) compared to the rest. A higher prevalence of GDM was observed among women with 1st trimester plasma total vitamin D in the lowest quartile (≤23.6 nmol/L) compared to the subjects in the other three quartiles (16.1 vs. 8.6%, p = 0.033). Adjusted multivariable regression analysis showed that women in the lowest quartile of plasma total vitamin D had twice the odds of GDM compared to women belonging to the remaining quartiles [OR = 2.32 (95%CI: 1.10, 4.91), p = 0.028]. Conclusions: Low plasma total vitamin D concentrations in early pregnancy may be associated with a higher risk of GDM.

Vitamin D (Vit D) deficiency (VDD), associated with diverse health conditions, is commonly treated with Vit D3 supplements. However, the gastrointestinal (GI) absorption of Vit D3 in different formulations has not been well studied.

To explore the hepatoprotective role of quercetin and its novel molecular mechanism of action on breast cancer associated hepatic inflammation and fibrosis via Vitamin D receptor (VDR).

Background: COVID-19 pandemic has proved to be an unrelenting health threat for more than a year now. The emerging amount of data indicates that vitamin D, zinc and selenium could be important for clinical presentation of COVID-19. Here, we investigated association of genetic variants related to the altered level and bioavailability of vitamin D, zinc and selenium with clinical severity of COVID-19. Methods: We analyzed variants in genes significant for the status of vitamin D (DHCR7/NADSYN1 rs12785878, GC rs2282679, CYP2R1 rs10741657, and VDR rs2228570), zinc (PPCDC rs2120019) and selenium (DMGDH rs17823744) in 120 Serbian adult and pediatric COVID-19 patients using allelic discrimination. Furthermore, we carried out comparative population genetic analysis among European and other worldwide populations to investigate variation in allelic frequencies of selected variants. Results: Study showed that DHCR7/NADSYN rs12785878 and CYP2R1 rs10741657 variants were associated with severe COVID-19 in adults (p = 0.03, p = 0.017, respectively); carriers of DHCR7/NADSYN TG+GG and CYP2R1 GG genotypes had 0.21 and 5.9 the odds for developing severe disease, OR 0.21 (0.05-0.9) and OR 5.9 (1.4-25.2), respectively. There were no associations between selected genetic variants and disease severity in pediatric patients. Comparative population genetic analysis revealed that Serbian population had the lowest frequency of CYP2R1 rs10741657 G allele compared to other non-Finish Europeans (0.58 compared to 0.69 and 0.66 in Spanish and Italian population, respectively), suggesting that other populations should also investigate the relationship of CYP2R1 variant and the COVID-19 disease course. Conclusion: The results of the study indicated that vitamin D related genetic variants were implicated in severe COVID-19 in adults. This could direct prevention strategies based on population specific nutrigenetic profiles.

Vitamin D deficiency is a widespread issue globally, resulting in increased use of vitamin D supplements. However, it is unclear whether intermittent (weekly or monthly) vitamin D supplementation is as effective as daily supplementation in improving circulating 25-hydroxyvitamin D [25(OH)D] levels.

Background: This systematic review and meta-analysis aimed to assess whether low serum 25-hydroxyvitamin D (25-OHD) level is associated with susceptibility to COVID-19, severity, and mortality related to COVID-19. Methods: Systematic literature searches of PubMed, Scopus, and Embase database up until 9 December 2020. We include published observational prospective and retrospective studies with information on 25-OHD that reported main/secondary outcome. Low serum 25-OHD refers to participants with serum 25-OHD level below a cut-off point ranging from 20 to 30 ng/mL. Other cut-off values were excluded to reduce heterogeneity. The main outcome was mortality defined as non-survivor/death. The secondary outcome was susceptibility and severe COVID-19. Results: There were 14 studies comprising of 999,179 participants. Low serum 25-OHD was associated with higher rate of COVID-19 infection compared to the control group (OR = 2.71 [1.72, 4.29], p < 0.001; I 2: 92.6%). Higher rate of severe COVID-19 was observed in patients with low serum 25-OHD (OR = 1.90 [1.24, 2.93], p = 0.003; I 2: 55.3%), with a sensitivity of 83%, specificity of 39%, PLR of 1.4, NLR of 0.43, and DOR of 3. Low serum 25-OHD was associated with higher mortality (OR = 3.08 [1.35, 7.00], p = 0.011; I 2: 80.3%), with a sensitivity of 85%, specificity of 35%, PLR of 1.3, NLR of 0.44, and DOR of 3. Meta-regression analysis showed that the association between low serum 25-OHD and mortality was affected by male gender (OR = 1.22 [1.08, 1.39], p = 0.002), diabetes (OR = 0.88 [0.79, 0.98], p = 0.019). Conclusion: Low serum 25-OHD level was associated with COVID-19 infection, severe presentation, and mortality.

The aging process is often accompanied by increase in body weight. Older adults with overweight or obesity might have an overconsumption in energy that is accompanied by inadequate intake of protein, vitamin D, and calcium. It is unclear if intake of protein and vitamin D and calcium is sufficient in older adults with overweight/obesity, and whether it differs from older adults with normal weight, since a recent overview of the literature review is lacking. Therefore, we systematically analyzed the current evidence on differences in nutrient intake/status of protein, vitamin D and calcium between older adults with different body mass index (BMI) categories. Randomized controlled trials and prospective cohort studies were identified from PubMed and EMBASE. Studies reporting nutrient intake/status in older adults aged ≥50 years with overweight/obesity and studies comparing between overweight/obesity and normal weight were included. Nutrient intake/status baseline values were reviewed and when possible calculated for one BMI category (single-group meta-analysis), or compared between BMI categories (meta-analysis). Nutrient intake/status was compared with international recommendations. Mean protein (N = 8) and calcium intake (N = 5) was 0.98 gram/kilogram body weight/day (g/kg/d) [95% Confidence Interval (CI) 0.89-1.08] and 965 mg [95% CI: 704-1225] in overweight/obese. Vitamin D intake was insufficient in all BMI categories (N = 5). The pooled mean for vitamin D intake was 6 ug [95% CI 4-9]. For 25(OH)D, the pooled mean was 54 nmol/L [95% CI 45-62], 52 nmol/L [95% CI 46-58], and 48 nmol/l [95% CI 33-62] in normal (N = 7), combined overweight and obese (N = 12), and obese older adults (N = 4), respectively. In conclusion, older adults with overweight and obesity have a borderline sufficient protein and sufficient calcium intake, but insufficient vitamin D intake. The 25(OH)D concentration is deficient for the obese older adults.

Background: Human immunodeficiency virus (HIV) infection is a heavy burden worldwide. Observational studies have reported a high prevalence of vitamin D deficiency (VDD) among people living with HIV (PLWH). However, its deficiency is also a global health problem. Therefore, we conducted a meta-analysis and systemic review to compare differences between HIV-infected subjects and non-HIV-infected subjects. Methods: We searched PubMed, Web of Science, Embase, and Cochrane library. We extracted data, including demographic information, study type, vitamin D-related values, and HIV-related values, ultimately including 15 studies after removing duplicates and screening titles, abstracts, and full texts and finally performing a meta-analysis in terms of vitamin D level and vitamin D deficiency prevalence. Results: Regarding VDD prevalence, the HIV vs. the non-HIV group had an odds ratio of 1.502 (95% CI, 1.023-2.205; P = 0.038). In the subgroup analysis, the odds ratios were 1.647 (95% CI, 1.020-2.659; P = 0.041; I 2 = 94.568) from 7 studies (age over 40), 2.120 (95% CI, 1.122-4.008; P = 0.021; I 2 = 0.000) from 2 studies (BMI less than or equal to 25), 1.805 (95% CI, 1.373-2.372; P = 0.042; I 2 = 74.576) from 7 studies (latitude <40), 2.120 (95% CI, 1.122-4.088; P = 0.021; I 2 = 0.000) from 2 studies (only included male participants), and 2.296 (95% CI, 1.287-4.097; P = 0.005; I 2 = 19.927) from 3 studies (only included ART-experienced participants). Thirteen studies were deemed to have moderate quality, while two had high quality. Conclusions: HIV infected subjects are prone to have VDD compared with general population. ART, older age, lower BMI, lower latitude and male sex may present risk factors for VDD in PLWH. Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=228096.

This study aims to investigate the influence of vitamin D supplementation on immune function of healthy older adults.

Background: The association between circulating vitamin D levels and risk of vitiligo was inconsistent among observational studies, and whether these observed associations were causal remained unclear. Therefore, we aimed to evaluate the effect of vitamin D on the risk of vitiigo using meta-analysis and Mendelian randomization (MR). Methods: At the meta-analysis stage, literature search was performed in PubMed and Web of Science to identify eligible observational studies examining the association of circulating 25-hydroxyvitamin D [25(OH)D] or 25-hydroxyvitamin D3 [25(OH)D3] levels with risk of vitiligo up to April 30, 2021. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) of 25(OH)D and 25(OH)D3 in patients with vitiligo relative to controls were pooled. Then at the MR stage, genetic instruments for circulating 25(OH)D (N = 120,618) and 25(OH)D3 (N = 40,562) levels were selected from a meta-analysis of genome-wide association studies (GWAS) of European descent, and summary statistics of vitiligo were obtained from a meta-analysis of three GWASs including 4,680 cases and 39,586 controls. We used inverse-variance weighted (IVW) as main method, followed by weighted-median and likelihood-based methods. Pleiotropic and outlier variants were assessed by MR-Egger regression and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test. Results: In the meta-analysis, patients with vitiligo had a lower level of circulating 25(OH)D compared with controls [SMD = -1.40; 95% confidence interval (CI): -1.91, -0.89; P < 0.001], while no statistically significant difference of 25(OH)D3 between vitiligo cases and controls was found (SMD = -0.63; 95% CI: -1.29, 0.04; P = 0.064). However, in the MR analyses, genetically predicted 25(OH)D [odds ratio (OR) = 0.93, 95% CI = 0.66-1.31, P = 0.66] and 25(OH)D3 levels (OR = 0.95, 95% CI = 0.80-1.14, P = 0.60) had null associations with risk of vitiligo using the IVW method. Sensitivity analyses using alternative MR methods and instrumental variables (IV) sets obtained consistent results, and no evidence of pleiotropy or outliers was observed. Conclusion: Our study provided no convincing evidence for a causal effect of 25(OH)D or 25(OH)D3 levels on the risk of vitiligo. Further longitudinal and experimental studies, as well as functional studies are warranted to elucidate the role of vitamin D in the development of vitiligo.

Introduction: Circulating vitamin D concentrations have been associated with the risk of type 2 diabetes (T2D). Magnesium has also been reported to be associated with lower T2D risk. Besides, magnesium is an essential cofactor for vitamin D activation. However, the effect of dietary magnesium intake on the association between vitamin D and the risk of T2D has not been studied comprehensively. Therefore, we designed this cross-sectional study to assess the effect modification of magnesium intake on the association between vitamin D and risk of T2D. Research Design and Methods: The present study analyzed data from the National Health and Nutrition Examination Survey (NHANES) continuously from 2007 to 2014, involving 10,249 participants. By having stratified participants based on magnesium intake category (low magnesium intake <267 mg/day; high magnesium intake: ≥267 mg/day), we further evaluated the difference (interaction test) between the relationship of vitamin D with the risk of T2D among low magnesium intake participants and high magnesium intake participants using weighted multivariable logistic regression. Results: In this cross-sectional study, the association of serum vitamin D with the incidence of T2D appeared to differ between the low magnesium intake group and the high magnesium intake group (OR: 0.968, 95%Cl: 0.919-1.02 vs. OR: 0.925, 95%Cl: 0.883-0.97). Furthermore, there was evidence of interaction between vitamin D levels and magnesium intake on decreasing the incidence of T2D (p-value for interaction = 0.001). Conclusions: The results of our study indicated that magnesium intake might affect the association of serum vitamin D with the risk of T2D. Such a finding requires further randomized controlled trials to provide more evidence.

Acute kidney injury (AKI) alters renal hemodynamics, leading to tubular injury, activating pathways of inflammation, proliferation, and cell death. The initial damage caused to renal tissue after an ischemia/reperfusion (I/R) injury exerts an important role in the pathogenesis of the course of AKI, as well as in the predisposition to chronic kidney disease. Vitamin D deficiency has been considered a risk factor for kidney disease and it is associated with tubulointerstitial damage, contributing to the progression of kidney disease. Obesity is directly related to diabetes mellitus and hypertension, the main metabolic disorders responsible for the progression of kidney disease. Furthermore, the expansion of adipose tissue is described as an important factor for increased secretion of pro-inflammatory cytokines and their respective influence on the progression of kidney disease. We aimed to investigate the influence of vitamin D deficiency and obesity on the progression of renal disease in a murine model of renal I/R. Male Wistar rats underwent renal I/R surgery on day 45 and followed until day 90 of the protocol. We allocated the animals to four groups according to each diet received: standard (SD), vitamin D-depleted (VDD), high fat (HFD), or high fat vitamin D-depleted (HFDV). At the end of 90 days, we observed almost undetectable levels of vitamin D in the VDD and HFDV groups. In addition, HFD and HFDV groups presented alterations in the anthropometric and metabolic profile. The combination of vitamin D deficiency and obesity contributed to alterations of functional and hemodynamic parameters observed in the HFDV group. Moreover, this combination favored the exacerbation of the inflammatory process and the renal expression of extracellular matrix proteins and phenotypic alteration markers, resulting in an enlargement of the tubulointerstitial compartment. All these changes were associated with an increased renal expression of transforming growth factor β and reduced expression of the vitamin D receptor. Our results show that the synergistic effect of obesity and vitamin D deficiency exacerbated the hemodynamic and morphological changes present in the evolution of renal disease induced by I/R.

Post-stroke depression (PSD) affects up to one-third of patients who survive stroke. This matched cohort study aimed to investigate the relationship between vitamin D deficiency (VDD) and PSD using a global health research network.

Objective: Laboratory findings indicated that vitamin D might have a potent protective effect on breast cancer, but epidemiology studies reported conflicting results. The aim of the study was to conduct a systematic review and meta-analysis to clarify the efficacy of vitamin D supplementation on risk of breast cancer. Methods: MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and abstracts of three major conferences were searched (up to December 8, 2020). Parallel randomized controlled trials (RCTs) examining the efficacy of vitamin D supplementation on risk of breast cancer or change of mammography compared with placebo in females were included. Data were meta-analyzed using a random-effects model. Bayesian meta-analysis was conducted to synthesize the results using data from observational studies as priors. Results: Seven RCTs were identified for effect of vitamin D on risk of breast cancer, with 19,137 females included for meta-analysis. No statistically significant effect of vitamin D on risk of breast cancer was found in classical random-effects meta-analysis (risk ratio = 1.04, 95% confidence interval: 0.84-1.28, p = 0.71). When Bayesian meta-analyses were conducted, results remained non-significant. There was no statistically significant effect of vitamin D on mammography density observed: mean difference = 0.46, 95% confidence interval: -2.06 to 2.98, p = 0.72. Conclusion: There is insufficient evidence to support the efficacy of vitamin D supplementation in breast cancer risk and change of mammography density. The protective effect of vitamin D on risk of breast cancer from previous observational studies may be overestimated. Systematic Review Registration: PROSPERO, identifier CRD42019138718.