The Mediterranean diet, but not time-restricted eating, mediates the effects of nesfatin on beta cell function among overweight, metabolically healthy individuals.

Nesfatin concentrations are positively correlated with beta cell function. However, it is unclear whether diet composition mediates this relationship. We recruited 27 overweight individuals who practiced Orthodox fasting (OF), a subset of the Mediterranean diet (MedDiet), for 7 weeks. Fourteen overweight people who practiced 16:8 time-restricted eating served as control group. Anthropometric parameters, biochemical data and adipokine levels were evaluated at baseline and after the end of the diet period (7 weeks from baseline). Subsequently, participants were asked to return to their usual eating plans, and an additional evaluation was performed 5 weeks after the end of the research diets (12 weeks from baseline). We observed a significant and negative correlation between HOMA-B and nesfatin values at 12 weeks, only in the OF group (r = -0.455, p = 0.01). In conclusion, returning to normal eating habits after 7 weeks of strict adherence to MedDiet affects the homeostatic balance between insulin secretion and nesfatin.

Vitamin D and behavioral disorders in older adults: results from the CLIP study.

OBJECTIVES: Vitamin D is involved in brain health and function. Our objective was to determine whether vitamin D deficiency was associated with behavioral disorders in geriatric patients. DESIGN: The observational cross-sectional CLIP (Cognition and LIPophilic vitamins) study. The report followed the STROBE statement. SETTING: Geriatric acute care unit in a tertiary university hospital in France for 3 months at the end of winter and beginning of spring. PARTICIPANTS: 272 patients ≥65 years consecutively hospitalized or seen in consultation. MEASUREMENTS: Participants were separated into two groups according to vitamin D deficiency (i.e., serum 25-hydroxyvitamin D ≤25 nmol/L). Behavior was assessed using the reduced version of the Neuropsychiatric Inventory Scale (NPI-R) score and subscores. Age, sex, BMI, education level, comorbidities, MMSE and GDS scores, use psychoactive drugs and vitamin D supplements, and serum concentrations of calcium, parathyroid hormone, TSH and estimated glomerular filtration rate (eGFR) were used as potential confounders. RESULTS: Participants with vitamin D deficiency (n = 78) had similar NPI-R score (17.4 ± 20.3 versus 17.2 ± 16.1, p = 0.92) but higher (i.e., worse) subscore of agitation and aggressiveness (2.0 ± 3.3 versus 1.2 ± 2.4, p = 0.02) and higher (i.e., worse) subscore of disinhibition (0.99 ± 2.98 versus 0.38 ± 1.42, p = 0.02) than those without vitamin D deficiency (n = 194). In multiple linear regressions, vitamin D deficiency was inversely associated with the subscore of agitation and aggressiveness (ß = 1.37, p = 0.005) and with the subscore of disinhibition (ß = 0.96, p = 0.008). CONCLUSION: Vitamin D deficiency was associated with more severe subscores of agitation and aggressiveness and of disinhibition among older adults. This provides a scientific basis to test the efficacy of vitamin D supplementation on behavioral disorders in older patients with vitamin D deficiency.

Efficiency of the Vitamin D Status Diagnosticator amongst Geriatric Patients with COVID-19.

The vitamin D status diagnosticator (VDSD), a 16-item tool, effectively identifies hypovitaminosis D in healthy older adults and can assist in determining the need for blood tests in this population. Assessing vitamin D levels is particularly crucial in the context of COVID-19. This study aimed to evaluate the VDSD's effectiveness in pinpointing hypovitaminosis D in older adults affected by COVID-19. The research involved 102 unsupplemented geriatric inpatients consecutively admitted to the acute geriatric division of Angers University Hospital, France, with an average age of 85.0 ± 5.9 years (47.1% women). The physician-administered VDSD was conducted simultaneously with the measurement of serum 25-hydroxyvitamin D (25(OH)D). Hypovitaminosis D was defined as a serum 25(OH)D concentration of ≤75 nmol/L for vitamin D insufficiency and ≤50 nmol/L for vitamin D deficiency. Results revealed that 87 participants (85.3%) had vitamin D insufficiency and 63 (61.8%) had vitamin D deficiency. The VDSD accurately identified vitamin D deficiency with an area under the curve (AUC) of 0.81 and an odds ratio (OR) of 40. However, its accuracy in identifying vitamin D insufficiency was lower (AUC = 0.57). In conclusion, the 16-item VDSD, a concise questionnaire, effectively identifies vitamin D deficiency in geriatric patients with COVID-19. This tool can be valuable in guiding the decision to administer vitamin D supplementation during the early stages of COVID-19.

Vitamin D Supplementation: A Review of the Evidence Arguing for a Daily Dose of 2000 International Units (50 µg) of Vitamin D for Adults in the General Population.

Vitamin D deficiency is considered a public health problem due to its worldwide high prevalence and adverse clinical consequences regarding musculoskeletal health. In addition, vitamin D may also be crucial for the prevention of certain extraskeletal diseases. Despite decades of intensive scientific research, several knowledge gaps remain regarding the precise definition of vitamin D deficiency and sufficiency, the health benefits of improving vitamin D status, and the required vitamin D intakes. Consequently, various societies and expert groups have released heterogeneous recommendations on the dosages for vitamin D supplementation. In this brief narrative review, we outline and discuss recent advances regarding the scientific evidence arguing for a daily vitamin D supplementation with 2000 international units (IU) (50 µg) of vitamin D3 to prevent and treat vitamin D deficiency. According to data from randomized controlled trials (RCTs), such a dose may improve some health outcomes and is sufficient to raise and maintain serum 25(OH)D concentrations above 50 nmol/L (20 ng/mL) and above 75 nmol/L (30 ng/mL) in >99% and >90% of the general adult population, respectively. According to large vitamin D RCTs, there are no significant safety concerns in supplementing such a dose for several years, even in individuals with an already sufficient vitamin D status at baseline. A daily vitamin D supplementation with 2000 IU (50 µg) may be considered a simple, effective, and safe dosage to prevent and treat vitamin D deficiency in the adult general population.

Associations of free, bioavailable and total 25-hydroxyvitamin D with neonatal birth anthropometry and calcium homoeostasis in mother-child pairs in a sunny Mediterranean region.

Sufficient vitamin D status is crucial for successful pregnancy and fetal development. The assessment of 25-hydroxyvitamin D (25(OH)D) concentrations is commonly used to evaluate vitamin D status. Our objective was to examine the interrelated biodynamics of maternal and neonatal total, free and bioavailable 25(OH)D in maternal-neonatal dyads at birth and their associations with homeostasis and neonatal birth anthropometry. We analysed a cohort of seventy full-term mother-child pairs. We found positive associations between all neonatal measures of vitamin D status. Maternal forms exhibited a similar pattern of association, except for the bioavailable maternal form. In multivariate analysis, both total and free maternal 25(OH)D concentrations were correlated with all neonatal forms (neonatal total 25(OH)D: 1·29 (95 % CI, 1·12, 1·46) for maternal total 25(OH)D, 10·89 (8·16, 13·63) for maternal free 25(OH)D), (neonatal free 25(OH)D: 0·15 for maternal total 25(OH)D, 1·28 (95 % CI, 0·89, 1·68) for maternal free 25(OH)D) and (0·13 (95 % CI, 0·10, 0·16), 1·06 (95 % CI, 0·68, 1·43) for maternal free 25(OH)D), respectively, with the exclusion of the bioavailable maternal form. We observed no significant interactions within or between groups regarding maternal and neonatal vitamin D parameters and maternal calcium and parathyroid hormone concentrations, and neonatal birth anthropometry. Our study indicates that bioavailable maternal and neonatal 25(OH)D have no significant effects on vitamin D equilibrium, Ca homeostasis and neonatal anthropometry at birth. However, we observed an interaction between maternal and neonatal total and free 25(OH)D concentrations at the maternal-neonatal interface, with no associations observed with other calciotropic or anthropometric outcomes.

A Mediterranean Eating Pattern Combining Energy and Time-Restricted Eating Improves Vaspin and Omentin Concentrations Compared to Intermittent Fasting in Overweight Individuals.

Athonian Orthodox fasting (AOF) is characterized by energy- and time-restricted eating (TRE) and is based on the Mediterranean diet. We aimed to investigate the impact of AOF compared to another TRE model on vaspin, omentin, nesfatin, and visfatin levels. We included 25 individuals (mean age 50.3 ± 8.6 years, 24% men) who practiced AOF and abstained from animal products, with the exception of seafood and fish. This group adopted a 12 h eating interval (08.00 to 20.00). In total, 12 participants (mean age 47.7 ± 8.7 years, 33.3% men) who practiced 16:8 TRE (eating from 09:00 to 17:00) and were allowed to consume meat served as the controls. Anthropometric and dietary data and adipokine levels were prospectively collected at three time points: at baseline, after the end of the diets (7 weeks), and 5 weeks after the participants returned to their typical eating habits (12 weeks from baseline). Vaspin levels decreased [795.8 (422.1-1299.4) (baseline) vs. 402.7 (203.8-818.9) (7 weeks) pg/mL, p = 0.002] and omentin levels increased [568.5 (437.7-1196.5) (baseline) vs. 659.0 (555.7-1810.8) (12 weeks) pg/mL, p = 0.001] in the AOF group, while none of the analyzed adipokines changed significantly in the TRE group. The variations observed in vaspin and omentin concentrations in the AOF group were independent of age, sex, changes in anthropometry and fat intake. In conclusion, AOF can significantly reduce vaspin and increase omentin, whose levels are known to increase and decrease, respectively, in obesity and type 2 diabetes. The implications of these findings for cardiometabolic health warrant further investigation.

The clinical significance of low dose biotin supplements (<300µg/day) in the treatment of patients with hypothyroidism: crucial or overestimated?

BACKGROUND: In the last decade, the combination of the widespread use of streptavidin-biotin technology and biotin-containing supplements (BCS) in the daily clinical practice, have led to numerous reports of erroneous hormone immunoassay results. However, there are no studies assessing the clinical and biochemical significance of that phenomenon, when treating patients with hypothyroidism. Therefore, a prospective study was designed to investigate the potential alterations in the measurement of thyroid hormone concentrations and clinical consequences in patients with hypothyroidism using low -dose BCS containing less than 300 µg/day. METHODS: Fifty-seven patients on thyroxine supplementation, as a result of hypothyroidism and concurrent use of BCS at a dose <300µg/day for 10 to 60 days were prospectively evaluated. Namely, TSH and free T4 (FT4) concentration measurements were performed, during BC supplementation and 10 days post BCS discontinuation and compared to 31 age-matched patients with supplemented hypothyroidism and without BCS. RESULTS: A statistically significant increase in TSH and decline in FT4 concentrations was observed after BCS discontinuation. However, on clinical grounds, these modifications were minor and led to medication dose adjustment in only 2/57 patients (3.51%) in whom TSH was notably decreased after supplement discontinuation. CONCLUSION: Our study suggests that changes in thyroid hormones profiling, due to supplements containing low dose biotin, are of minimal clinical relevance and in most cases don't occult the need to adjust the thyroxine replacement dose in patients with hypothyroidism. Larger, well-designed trials are required to further evaluate this phenomenon.

Intermittent Fasting in Breast Cancer: A Systematic Review and Critical Update of Available Studies.

Breast cancer (BC) is the most-frequent malignancy amongst women, whereas obesity and excess caloric consumption increase the risk for developing the disease. The objective of this systematic review was to examine the impact of intermittent fasting (IF) on previously diagnosed BC patients, regarding quality of life (QoL) scores during chemotherapy, chemotherapy-induced toxicity, radiological response and BC recurrence, endocrine-related outcomes, as well as IF-induced adverse effects in these populations. A comprehensive search was conducted between 31 December 2010 and 31 October 2022, using the PubMed, CINAHL, Cochrane, Web of Science, and Scopus databases. Two investigators independently performed abstract screenings, full-text screenings, and data extraction, and the Mixed Method Appraisal Tool (MMAT) was used to evaluate the quality of the selected studies. We screened 468 papers, 10 of which were selected for data synthesis. All patients were female adults whose age ranged between 27 and 78 years. Participants in all studies were women diagnosed with BC of one of the following stages: I, II (HER2-/+), III (HER2-/+), IV, LUMINAL-A, LUMINAL-B (HER2-/+). Notably, IF during chemotherapy was found to be feasible, safe and able to relieve chemotherapy-induced adverse effects and cytotoxicity. IF seemed to improve QoL during chemotherapy, through the reduction of fatigue, nausea and headaches, however data were characterized as low quality. IF was found to reduce chemotherapy-induced DNA damage and augmented optimal glycemic regulation, improving serum glucose, insulin, and IGF-1 concentrations. A remarkable heterogeneity of duration of dietary patterns was observed among available studies. In conclusion, we failed to identify any IF-related beneficial effects on the QoL, response after chemotherapy or related symptoms, as well as measures of tumor recurrence in BC patients. We identified a potential beneficial effect of IF on chemotherapy-induced toxicity, based on markers of DNA and leukocyte damage; however, these results were derived from three studies and require further validation. Further studies with appropriate design and larger sample sizes are warranted to elucidate its potential standard incorporation in daily clinical practice.

Different patterns of changes in free 25-hydroxyvitamin D concentrations during intermittent fasting among meat eaters and non-meat eaters and correlations with amino acid intake.

We prospectively assessed changes in free 25-hydroxyvitamin D [25(OH)D] and vitamin D binding protein (VDBP) among overweight adults who followed a pescatarian Orthodox intermittent fasting regimen (n = 59) and controls who followed a low-fat 12:12 diet (n = 46). Total and free 25(OH)D, parathyroid hormone, VDBP, anthropometric data, and amino acid intake were evaluated in both groups at three time points: at baseline, 7 weeks after diet implementation, and 5 weeks after participants returned to their usual eating habits (12 weeks from baseline). An increase in amino acid intake between baseline and 12 weeks was independently correlated with higher free 25(OH)D values at 12 weeks for both groups. Our findings suggest that diet can affect free 25(OH)D concentrations, through variations in amino acid intake, independently of exposure to sunlight, providing novel mechanistic insights into the future planning of vitamin D supplementation strategies. However, this hypothesis needs to be tested in larger studies.

Maternal and Neonatal Vitamin D Binding Protein Polymorphisms and 25-Hydroxyvitamin D Cutoffs as Determinants of Neonatal Birth Anthropometry.

BACKGROUND: Vitamin D-binding protein (VDBP) is a vital regulator of optimal vitamin D homeostasis and bioavailability. Apart from its well-documented role as a key component in vitamin D dynamic transfer and circulation, it has a myriad of immunoregulatory functions related to innate immunity, which becomes particularly critical in states of increased immunological tolerance including pregnancy. In this regard, VDBP dyshomeostasis is considered to contribute to the development of several fetal, maternal, and neonatal adverse outcomes. However, precise physiological pathways, including the contribution of specific VDBP polymorphisms behind such phenomena, are yet to be fully deciphered. Our aim was to assess the combined effect of maternal and neonatal VDBP polymorphism heterogeneity in conjunction with different maternal and neonatal 25(OH)D cutoffs on the neonatal anthropometric profile at birth. METHODS: The study included data and samples from a cohort of 66 mother-child pairs at birth. The inclusion criterion was full-term pregnancy (gestational weeks 37-42). Neonatal and maternal 25(OH)D cutoffs were included according to vitamin D status at birth and delivery. Concentrations of 25(OH)D2 and 25(OH)D3 were measured using liquid chromatography-tandem mass spectrometry. RESULTS: The upper arm length of neonates with 25(OH)D ≤ 25 nmol/L was higher in neonate CC carriers for rs2298850. The upper thigh neonatal circumference was also higher in the ones with either 25(OH)D ≤ 50 or ≤75 nmol/L in rs2298850 CG + GG or rs4588 GT + TT carriers. We did not observe any significant effect for maternal VDBP polymorphisms nor for birth maternal 25(OH)D concentrations, on birth neonatal anthropometry. CONCLUSIONS: Our findings emphasize a potential role for neonatal VDBP genotypes rs2298850 and rs4588, in conjunction with specific neonatal 25(OH)D cutoffs, in the range of sufficiency on neonatal growth and development.

Hypercalcemia in Pregnancy Due to CYP24A1 Mutations: Case Report and Review of the Literature.

Pathogenic mutations of CYP24A1 lead to an impaired catabolism of vitamin D metabolites and should be considered in the differential diagnosis of hypercalcemia with low parathyroid hormone concentrations. Diagnosis is based on a reduced 24,25-dihydroxyvitamin D to 25-hydroxyvitamin D ratio and confirmed by genetic analyses. Pregnancy is associated with an upregulation of the active vitamin D hormone calcitriol and may thus particularly trigger hypercalcemia in affected patients. We present a case report and a narrative review of pregnant women with CYP24A1 mutations (13 women with 29 pregnancies) outlining the laboratory and clinical characteristics during pregnancy and postpartum and the applied treatment approaches. In general, pregnancy triggered hypercalcemia in the affected women and obstetric complications were frequently reported. Conclusions on drugs to treat hypercalcemia during pregnancy are extremely limited and do not show clear evidence of efficacy. Strictly avoiding vitamin D supplementation seems to be effective in preventing or reducing the degree of hypercalcemia. Our case of a 24-year-old woman who presented with hypercalcemia in the 24th gestational week delivered a healthy baby and hypercalcemia resolved while breastfeeding. Pathogenic mutations of CYP24A1 mutations are rare but should be considered in the context of vitamin D supplementation during pregnancy.

Effects of Vitamin D Supplementation on 24-Hour Blood Pressure in Patients with Low 25-Hydroxyvitamin D Levels: A Randomized Controlled Trial.

Accumulating evidence suggests that potential cardiovascular benefits of vitamin D supplementation may be restricted to individuals with very low 25-hydroxyvitamin D (25(OH)D) concentrations; the effect of vitamin D on blood pressure (BP) remains unclear. We addressed this issue in a post hoc analysis of the double-blind, randomized, placebo-controlled Styrian Vitamin D Hypertension Trial (2011−2014) with 200 hypertensive patients with 25(OH)D levels <30 ng/mL. We evaluated whether 2800 IU of vitamin D3/day or placebo (1:1) for 8 weeks affects 24-hour systolic ambulatory BP in patients with 25(OH)D concentrations <20 ng/mL, <16 ng/mL, and <12 ng/mL and whether achieved 25(OH)D concentrations were associated with BP measures. Taking into account correction for multiple testing, p values < 0.0026 were considered significant. No significant treatment effects on 24-hour BP were observed when different baseline 25(OH)D thresholds were used (all p-values > 0.30). However, there was a marginally significant trend towards an inverse association between the achieved 25(OH)D level with 24-hour systolic BP (−0.196 per ng/mL 25(OH)D, 95% CI (−0.325 to −0.067); p = 0.003). In conclusion, we could not document the antihypertensive effects of vitamin D in vitamin D-deficient individuals, but the association between achieved 25(OH)D concentrations and BP warrants further investigations on cardiovascular benefits of vitamin D in severe vitamin D deficiency.

Critical Appraisal of Large Vitamin D Randomized Controlled Trials.

As a consequence of epidemiological studies showing significant associations of vitamin D deficiency with a variety of adverse extra-skeletal clinical outcomes including cardiovascular diseases, cancer, and mortality, large vitamin D randomized controlled trials (RCTs) have been designed and conducted over the last few years. The vast majority of these trials did not restrict their study populations to individuals with vitamin D deficiency, and some even allowed moderate vitamin D supplementation in the placebo groups. In these RCTs, there were no significant effects on the primary outcomes, including cancer, cardiovascular events, and mortality, but explorative outcome analyses and meta-analyses revealed indications for potential benefits such as reductions in cancer mortality or acute respiratory infections. Importantly, data from RCTs with relatively high doses of vitamin D supplementation did, by the vast majority, not show significant safety issues, except for trials in critically or severely ill patients or in those using very high intermittent vitamin D doses. The recent large vitamin D RCTs did not challenge the beneficial effects of vitamin D regarding rickets and osteomalacia, that therefore continue to provide the scientific basis for nutritional vitamin D guidelines and recommendations. There remains a great need to evaluate the effects of vitamin D treatment in populations with vitamin D deficiency or certain characteristics suggesting a high sensitivity to treatment. Outcomes and limitations of recently published large vitamin D RCTs must inform the design of future vitamin D or nutrition trials that should use more personalized approaches.

Implementation of Christian Orthodox fasting improves plasma adiponectin concentrations compared with time-restricted eating in overweight premenopausal women.

The exact mechanisms mediating the metabolic effects of Orthodox fasting remain unclear. Plasma adiponectin, biochemical and anthropometrical data were evaluated in 55 Orthodox fasters (OF) and 42 time-restricted eating controls (all women, mean age 47.8 years) at three time points: baseline, end of the dietary intervention (7 weeks) and 5 weeks after participants returned to their typical dietary habits (12 weeks from baseline). In the OF group, there was an increase in adiponectin values at 12 weeks compared with baseline (9815.99 vs 8983.52 mg/ml, p = 0.02) and a reduction in body fat mass between baseline and 12 weeks (35.44 vs 32.17%, p = 0.004) and between 7 and 12 weeks (35.33 vs 32.17%, p = 0.003). In the same group, an inverse correlation between adiponectin and waist circumference values was observed over the entire study period. Our results provide novel evidence that Orthodox fasting has favourable metabolic effects related to improved adiponectin concentrations.

Associations between Genetic Variants in the Vitamin D Metabolism Pathway and Severity of COVID-19 among UAE Residents.

Vitamin D has many effects on cells in the immune system. Many studies have linked low vitamin D status with severity of COVID-19. Genetic variants involved in vitamin D metabolism have been implicated as potential risk factors for severe COVID-19 outcomes. This study investigated how genetic variations in humans affected the clinical presentation of COVID-19. In total, 646 patients with SARS-CoV-2 infection were divided into two groups: noncritical COVID-19 (n = 453; 70.12%) and a critical group (n = 193; 29.87%). Genotype data on the GC, NADSYN1, VDR, and CYP2R1 genes along with data on serum 25-hydroxyvitamin D levels were compiled in patients admitted to a major hospital in the United Arab Emirates between April 2020 and January 2021. We identified 12 single-nucleotide polymorphisms associated with the critical COVID-19 condition: rs59241277, rs113574864, rs182901986, rs60349934, and rs113876500; rs4944076, rs4944997, rs4944998, rs4944979, and rs10898210; and rs11574018 and rs11574024. We report significant associations between genetic determinants of vitamin D metabolism and COVID-19 severity in the UAE population. Further research needed to clarify the mechanism of action against viral infection in vitamin D deficiency. These variants could be used with vaccination to manage the spread of SARS-CoV-2 and could be particularly valuable in populations in which vitamin D deficiency is common.

Rapid and Effective Vitamin D Supplementation May Present Better Clinical Outcomes in COVID-19 (SARS-CoV-2) Patients by Altering Serum INOS1, IL1B, IFNg, Cathelicidin-LL37, and ICAM1.

BACKGROUND: We aimed to establish an acute treatment protocol to increase serum vitamin D, evaluate the effectiveness of vitamin D3 supplementation, and reveal the potential mechanisms in COVID-19. METHODS: We retrospectively analyzed the data of 867 COVID-19 cases. Then, a prospective study was conducted, including 23 healthy individuals and 210 cases. A total of 163 cases had vitamin D supplementation, and 95 were followed for 14 days. Clinical outcomes, routine blood biomarkers, serum levels of vitamin D metabolism, and action mechanism-related parameters were evaluated. RESULTS: Our treatment protocol increased the serum 25OHD levels significantly to above 30 ng/mL within two weeks. COVID-19 cases (no comorbidities, no vitamin D treatment, 25OHD <30 ng/mL) had 1.9-fold increased risk of having hospitalization longer than 8 days compared with the cases with comorbidities and vitamin D treatment. Having vitamin D treatment decreased the mortality rate by 2.14 times. The correlation analysis of specific serum biomarkers with 25OHD indicated that the vitamin D action in COVID-19 might involve regulation of INOS1, IL1B, IFNg, cathelicidin-LL37, and ICAM1. CONCLUSIONS: Vitamin D treatment shortened hospital stay and decreased mortality in COVID-19 cases, even in the existence of comorbidities. Vitamin D supplementation is effective on various target parameters; therefore, it is essential for COVID-19 treatment.

Investigating the Role of Functional Polymorphism of Maternal and Neonatal Vitamin D Binding Protein in the Context of 25-Hydroxyvitamin D Cutoffs as Determinants of Maternal-Neonatal Vitamin D Status Profiles in a Sunny Mediterranean Region.

Recent results indicate that dysregulation of vitamin D-binding protein (VDBP) could be involved in the development of hypovitaminosis D, and it comprises a risk factor for adverse fetal, maternal and neonatal outcomes. Until recently, there was a paucity of results regarding the effect of maternal and neonatal VDBP polymorphisms on vitamin D status during pregnancy in the Mediterranean region, with a high prevalence of hypovitaminosis D. We aimed to evaluate the combined effect of maternal and neonatal VDBP polymorphisms and different maternal and neonatal 25-hydroxyvitamin D (25(OH)D) cut-offs on maternal and neonatal vitamin D profile. Blood samples were obtained from a cohort of 66 mother-child pairs at birth. Our results revealed that: (i) Maternal VDBP polymorphisms do not affect neonatal vitamin D status at birth, in any given internationally adopted maternal or neonatal cut-off for 25(OH)D concentrations; (ii) neonatal VDBP polymorphisms are not implicated in the regulation of neonatal vitamin D status at birth; (iii) comparing the distributions of maternal VDBP polymorphisms and maternal 25(OH)D concentrations, with cut-offs at birth, revealed that mothers with a CC genotype for rs2298850 and a CC genotype for rs4588 tended to demonstrate higher 25(OH)D (≥75 nmol/L) during delivery (p = 0.05 and p = 0.04, respectively), after adjustments for biofactors that affect vitamin D equilibrium, including UVB, BMI and weeks of gestation. In conclusion, this study from Southern Europe indicates that maternal and neonatal VDBP polymorphisms do not affect neonatal vitamin D status at birth, whereas mothers with CC genotype for rs2298850 and CC genotype for rs4588 demonstrate higher 25(OH)D concentrations. Future larger studies are required to establish a causative effect of these specific polymorphisms in the attainment of an adequate (≥75 nmol/L) maternal vitamin D status during pregnancy.

Protein disulfide isomerase A3 might be involved in the regulation of 24-dehydrocholesterol reductase via vitamin D equilibrium in primary cortical neurons.

Vitamin D is a secosteroid hormone mediating its functions via vitamin D receptor (VDR) and an endoplasmic reticulum chaperone, protein disulfide isomerase A3 (PDIA3). From a physiological perspective, there is also a well-established association of cholesterol and vitamin D synthesis, since both share a common metabolic substrate, 7 dehydrocholesterol (7-DHC). Yet, the potential basic pathways, of the biological interplay of DHCR24 and vitamin D equilibrium, on neuronal level, are yet to be determined. In this study, we aimed to investigate the relation between vitamin D pathways and DHCR24 in primary cortical neuron cultures. The neocortex of Sprague-Dawley rat embryos (E16) was used for the preparation of primary cortical neuron cultures. DHCR24 mRNA and protein expression levels were determined by qRT-PCR, Western blotting, and immunofluorescent labeling in 1,25-dihydroxyvitamin D3-treated or VDR/PDIA3-silenced primary cortical neurons. The mRNA expression of DHCR24 was significantly decreased in the cortical neurons treated with 10-8M 1,25-dihydroxyvitamin D3 (p<0.001). In parallel with the mRNA results, DHCR24 protein expression in cortical neurons treated with 10-8M 1,25-dihydroxyvitamin D3 was also significantly lower than untreated neurons (p<0.05). These data were also confirmed with immunofluorescent labeling and fluorescence intensity measurements of DHCR24 (p<0.001). Finally, DHCR24 mRNA expression level was significantly increased in PDIA3 siRNA-treated neurons (p<0.05). Similar to the mRNA results, the DHCR24 protein expression of PDIA3 siRNA-treated neurons was also statistically higher than the other groups (p<0.05). Results of this mechanistic experimental basic study demonstrate that DHCR24 mRNA expression and protein concentrations attenuated in response to vitamin D treatment. Furthermore, we observed that PDIA3 might be involved in this modulatory effect. Our findings indicate a complex interaction of DHCR24 and vitamin D equilibrium, through the involvement of PDIA3 and vitamin D in the modulation of cholesterol metabolism in neuronal cells, requiring future studies on the field.

Vitamin D equilibrium affects sex-specific changes in lipid concentrations during Christian Orthodox fasting.

We aimed to evaluate sex differences in changes of lipid profiles in a cohort of metabolically healthy adults following Orthodox fasting (OF), as well as to assess a potential role of vitamin D status in mediating these variations. 45 individuals (24 premenopausal females, 53.3 %) with mean age 48.3 ± 9.1 years and mean Body Mass Index 28.7 ± 5.8 kg/m2 were prospectively followed for 12 weeks. Anthropometry, dietary and biochemical data regarding serum lipids, and vitamin D status were collected at baseline, 7 weeks after the implementation of OF, and 5 weeks after fasters returned to their standard dietary habits (12 weeks from baseline). According to 25-hydroxy-vitamin D [25(OH)D] measurements, participants were divided into two groups: those with concentrations above and below the median of values. Females with 25(OH)D concentrations below the median manifested a non-significant reduction by approximately 15 % in total and low-density lipoprotein cholesterol during the fasting period, followed by a significant increase 5 weeks after OF cessation (170.7 vs. 197.5 and 99.6 vs. 121.0 mg/dl respectively, p < 0.001). In contrast, males with 25(OH)D levels below the median demonstrated an inverse, non-significant trend of increase in lipid concentrations during the whole study period. Our findings suggest strikingly different inter-gender lipid responses to a dietary model of low-fat, mediated by vitamin D status. Further studies are necessary to reveal the underlying mechanisms and assess the importance of these differences with respect to cardiovascular health and the benefit of vitamin D supplementation strategies.