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Background: Apart from the well-established skeletal effects, vitamin D has been explored as a secretagogue influencing various adipokines, including adiponectin and irisin. Recent evidence suggests that specific forms of 25-Hydroxyvitamin D (25(OHD), such as free and bioavailable 25(OH)D, may provide more accurate measurements of vitamin D status. The relationship between vitamin D status and serum irisin and adiponectin concentrations remains largely unexplored, particularly during pregnancy. Methods: We analyzed data from 67 healthy maternal-neonatal pairs from Northern Greece at birth. Biochemical and hormonal tests were conducted on each maternal-neonatal pair. The vitamin D forms were estimated using validated mathematical models. Subsequently, regression analyses were conducted to determine the association between the vitamin D forms and adipokine levels. Results: Bioavailable maternal 25(OH)D was inversely associated with neonatal irisin concentrations [b=-73.46 (-140.573 to -6.341), p=0.034]. No other associations were observed between maternal vitamin D status and neonatal adipokine concentrations. Conclusion: In conclusion, maternal bioavailable vitamin D concentrations are inversely associated with neonatal serum irisin concentrations, warranting further studies to evaluate the underlying mechanisms for this finding. [ABSTRACT FROM AUTHOR]

• The study investigated maternal and neonatal determinants of neonatal vitamin D deificiency. • A total of 129 mother-neonates pairs from Northern Greece were classified according neonatal vitamin D status at birth. • Risk of neonatal deficiency was 6.89 increased for neonates of vitamin D deficient (<50 nmol/l) mothers. • Use of alcohol during pregnancy was associated with a 5.5-fold higher risk for neonatal hypovitaminosis D. Absence of adequate maternal vitamin D supplementation and decreased maternal ultraviolet exposure during pregnancy are key determinants for the manifestation of neonatal hypovitaminosis D at birth. These parameters may vary, according to country-specific dietary patterns, health policies and sunshine exposure. We aimed to investigate differences in calcium metabolism and anthropometric profiles according to neonatal vitamin D status at birth, in a sunny region of Northern Greece. A secondary aim was to identify maternal parameters as risk factors for developing neonatal vitamin D deficiency at birth. A total of 129 mother-neonate pairs were included in the study and classified into three groups, according to neonatal 25-hydroxy-D [25(OH)D)] concentrations at birth [deficiency (<30 nmol/l), insufficiency (30−50 nmol/l) and sufficiency (>50 nmol/l)]. Neonatal biochemical and anthropometric profiles and maternal demographic, social, dietary and biochemical profiles were comparatively evaluated between the three groups. Univariate and multivariate logistic regression was performed to identify independent associations of maternal factors with neonatal vitamin D status. Vitamin D deficient-neonates manifested higher parathyroid hormone (7.20 ± 2.60 vs 5.50 ± 1.50 pg/ml, p = 0.01) and lower corrected calcium (10.70 ± 0.70 vs 11.30 ± 1.30 mg/dl, p = 0.02) concentrations compared with vitamin d -insufficient neonates. Mothers of vitamin D deficient and insufficient neonates had a lower total of 25(OH)D (31.7 ± 19.2 and 36.5 ± 22.3 vs 53.3 ± 39.0 nmol/l, p < 0.01) and 25(OH)D 3 (27.4 ± 17.5 and 33.3 ± 19.9 vs 47.3 ± 36.7 nmol/l, p < 0.01 and p = 0.04, respectively) concentrations respectively, compared with those of vitamin D-sufficient neonates. Maternal use of alcohol during pregnancy was associated with a 5.57-fold higher risk for neonatal vitamin D deficiency at birth (OR 5.57, 95 % CI1.17–26.56, p = 0.03). Newborns with vitamin D deficiency presented a 6.89-fold higher risk of having been given birth by vitamin D deficient mothers (OR 6.89, 95 % CI 3.09–15.38, p < 0.01). In conclusion, neonatal vitamin D deficiency is associated with maternal 25(OH)D concentrations at birth and maternal alcohol use. Further studies are required to replicate these findings in other regions and populations. [ABSTRACT FROM AUTHOR]

Background/Objectives : The Mediterranean diet has been widely suggested to exert significant beneficial effects on endothelial oxidative status and cardiometabolic health. Greek Orthodox monasteries, due to their specific nutritional and sartorial habits, comprise a population thatstrictly adheres to nutritional patterns with restricted eating and a plant-based subset of the Mediterranean diet, often accompanied by profound hypovitaminosis D. Time-restricted eating (TRE) is also adopted bya large part of the general lay Greek population for health-promoting reasons, without restrictions on animal product consumption, as imposed by Orthodox religious fasting. However, the comparative effects of these nutritional patterns on oxidative stress markers remain scarce. Methods : The present study attempted to evaluate the effects of Christian Orthodox fasting (COF) in a group of vitamin D-deficient and overweight Orthodox nuns from Central and Northern Greece compared to the implementation of TRE, a 16:8 dietary regimen (16 h of food abstinence and 8 h of feeding) in a cohort of adult women from the general population from the same region with regard to markers of endothelial oxidative status. A group of 50 women from two Orthodox monasteries in Northern Greece and one group of 50 healthy lay women were included. During the enrollment, a detailed recording of their dietary habits was performed, along with a scientific registry of their demographic and anthropometric characteristics (via bioimpedance). The Orthodox nuns followed a typical Orthodox fasting regimen [daily feeding window (8 a.m.-4 p.m.)], whereas the lay women followed a TRE 16:8 regimen with the same feeding time-window with a recommendation to follow a low-fat diet, without characteristics of the Mediterranean diet. We included a complete biochemical analysis, as well as calciotropic profiles [calcium-Ca, albumin, parathyroid hormone-PTH, and 25-hydroxyvitamin D-25(OH)D] and markers of TAC (total antioxidant capacity), GSH (glutathione),and thiobarbituric acid reactive substances (TBARSs) concentrations as markers of oxidative status. Results : All the groups were compared at the baseline regarding their calcium, PTH, and 25(OH)D concentrations, with no statistically significant differences between the groups apart from higher PTH levels in the nuns due to lower 25(OH)D levels. The Orthodox nuns manifested a lower median GSH compared to the controls (6.0 vs. 7.2, p 0.04) and a higher median TAC (0.92 vs. 0.77, p < 0.001). The TBARS comparisons showed no significant difference between the two groups. No significant associations of oxidative status with 25(OH)D, PTH, and the markers of glucose homeostasis were evident. Conclusions : The results of this small pilot study indicate that both dietary regimens have advantages over the oxidative markers compared to each other, with increased TAC in the group of Orthodox nuns after a 16-week period of COF compared to a 16:8 TRE and increased GSH concentrations in the lay women group. Future randomized trials are required to investigate the superiority or non-inferiority between these dietary patterns in the daily clinical setting.

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/m 2 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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Irisin has been recently identified as an adipomyokine produced during physical activity and involved in the browning of adipose tissue. Despite the emerging evidence suggesting an inverse relationship between irisin plasma concentrations and adverse metabolic outcomes, the exact impact of diet on irisin levels remains obscure. Thus, we aimed to assess the effects of two dietary patterns, Christian Orthodox fasting (OF) and 16:8 time-restricted eating (TRE), on circulating irisin levels among overweight, metabolically healthy, adults. Plasma irisin, glucose and lipid parameters, calcium homeostasis, and anthropometry were evaluated in 29 Orthodox fasters and 14 age and body mass index (BMI)-matched TRE controls (mean age and BMI, 48.8 years and 28.7 kg/m 2 , respectively) at three, distinct time points-before the implementation of the energy-restricted diets (baseline), at the end of the dietary intervention (7 weeks) and 5 weeks after participants returned to their typical dietary habits (12 weeks from baseline). Repeated measures analysis was applied to assess differences between the two groups and the effect of several indices on irisin levels at all three time points. At 12 weeks, the OF group manifested higher irisin concentrations compared with both its baseline values (64.3 ± 54.4 vs. 43.6 ± 42.2 ng/mL, p = 0.01) and those of the TRE group at the same time point (64.3 ± 54.4 vs. 44.2 ± 26.6 ng/mL, p = 0.04). Glycemic, lipid, and anthropometric parameters were not found to correlate with irisin levels. In contrast, parathyroid hormone (PTH) concentrations at 12 weeks correlated with irisin concentrations ( p = 0.04), indicating that lower values of irisin are expected for higher PTH measurements. The findings of this pilot study suggest favorable long-term effects of OF on irisin levels. The interplay between irisin, PTH, and diet warrants further investigation.

A hypocaloric diet, based on Orthodox fasting (OF) was followed by 29 overweight adults. A low-calorie, 16/8, time restricted eating (TRE) pattern was followed by 16 age- and weight-matched participants. Anthropometric, lipid, glycaemic and inflammation markers were assessed at baseline, at the end of the intervention (7 weeks from baseline) and 6 weeks after the cessation of diets (13 weeks from baseline). There was a trend of weight loss in both groups, which was evident at week 7 (TRE: -2.1 ± 1.0; OF: -2.0 ± 0.5 kg, p  < 0.001 from baseline) and remained significant at week 13 (TRE: -2.9 ± 0.7; OF: -2.6 ± 0.3 kg, p  < 0.001 from baseline). In the OF group, lipid concentrations declined at week 7 compared with baseline, increasing at week 13 compared with week 7. Our findings suggest that OF promotes a decrease in lipid concentrations, which however, is not evident 6 weeks after its end.

Accumulating evidence suggests a potential implication of vitamin D biological network in the pathogenesis of diabetes mellitus. The megalin-cubilin endocytotic system constitutes a key transport structure, with a modulating role in vitamin D metabolism. We aimed to assess the contribution of variants in the CUBN gene to the genetic risk of Type 2 Diabetes Mellitus (T2DM). 95 polymorphisms within CUBN were genotyped in 716 patients with T2DM and 542 controls of Greek origin. Samples were analyzed on Illumina Human PsychArray. Permutation test analysis was implemented to determine statistical significance. Twenty-five-hydroxy-vitamin-D [25(OH)D)] levels were measured in a sub-group of participants (n = 276). Permutation analysis associated rs11254375&#95;G/T (p emp  = 0.00049, OR = 1.482), rs6602175&#95;G/T (p emp  = 0.016, OR = 0.822), rs1801224&#95;G/T (p emp  = 0.025, OR = 0.830), rs4366393&#95;A/G (p emp  = 0.028, OR = 0.829) and rs7071576&#95;A/G (p emp  = 0.04, OR = 1.219) with T2DM. Mean 25(OH)D concentrations were significantly lower in patients with T2DM compared to controls (16.70 ± 6.69 ng/ml vs 18.51 ± 6.71 ng/ml, p < 0.001), although both groups were vitamin D deficient. In a further quantitative analysis, rs41301097 was strongly associated with higher 25(OH)D concentrations (p = 5.233e-6, beta = 15.95). Our results indicate a potential role of CUBN gene in T2DM genetic susceptibility in the Greek population. These findings may also denote an indirect effect of vitamin D metabolism dysregulation on the pathogenesis of T2DM. Further studies are required to replicate our findings and clarify the complex underlying mechanisms., Competing Interests: Declaration of Competing Interest Authors report no conflict of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: Christian Orthodox fasting (COF), a periodical vegetarian subset of the Mediterranean diet, has been proven to exert beneficial effects on human health. Athonian fasting is a pescetarian COF variation, where red meat is strictly restricted throughout the year. Previous studies have examined the COF nutritional synthesis and health effects in general population fasters (GF) and Athonian monks (AM), separately. The aim of this study is to comparatively evaluate the characteristics and effects of this nutritional advocacy between the two populations., Methods: The study included 43 male GFs (20-45 y of age) and 57 age-matched male AMs following COF. Dietary intake data were collected in both groups during a restrictive (RD) and a nonrestrictive (NRD) day. Nutritional, cardiometabolic, and anthropometric parameters were compared between the two cohorts., Results: AM presented lower daily total caloric intake for both RD (1362.42 ± 84.52 versus 1575.47 ± 285.96 kcal, P < 0.001) and NRD (1571.55 ± 81.07 versus 2137.80 ± 470.84 kcal, P < 0.001) than GF.They also demonstrated lower body mass index (23.77 ± 3.91 versus 28.92 ± 4.50 kg/m 2 , P <0.001), body fat mass (14.57 ± 8.98 versus 24.61 ± 11.18 kg, P = 0.001), and homeostatic model assessment for insulin resistance values (0.98 ± 0.72 versus 2.67 ± 2.19 mmol/L, P < .001) than GF. Secondary hyperparathyroidism (parathyroid hormone concentrations: 116.08 ± 49.74 pg/mL), as a result of profound hypovitaminosis D [25(OH)D: 9.27 ± 5.81 ng/mL], was evident in the AM group., Conclusions: The results of the present study highlight the unique characteristics of Athonian fasting and its value as a health-promoting diet. The effects of limitation of specific vitamins and minerals during fasting warrants further investigation., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Vitamin D concentrations during pregnancy are measured to diagnose states of insufficiency or deficiency. The aim of this study is to apply accurate assays of vitamin D forms [single- hydroxylated [25(OH)D₂, 25(OH)D₃], double-hydroxylated [1α,25(OH)₂D₂, 1a25(OH)₂D₃], epimers [3-epi-25(OH)D₂, 3-epi-25(OH)D₃] in mothers (serum) and neonates (umbilical cord) to i) explore maternal and neonatal vitamin D biodynamics and ii) to identify maternal predictors of neonatal vitamin D concentrations., Methods: All vitamin D forms were quantified in 60 mother- neonate paired samples by a novel liquid chromatography -mass spectrometry (LC-MS/MS) assay. Maternal characteristics [age, ultraviolet B exposure, dietary vitamin D intake, calcium, phosphorus and parathyroid hormone] were recorded. Hierarchical linear regression was used to predict neonatal 25(OH)D concentrations., Results: Mothers had similar concentrations of 25(OH)D₂ and 25(OH)D₃ forms compared to neonates (17.9 ± 13.2 vs. 15.9 ± 13.6 ng/mL, p=0.289) with a ratio of 1:3. The epimer concentrations, which contribute approximately 25% to the total vitamin D levels, were similar in mothers and neonates (4.8 ± 7.8 vs. 4.5 ± 4.7 ng/mL, p=0.556). No correlation was observed in mothers between the levels of the circulating form (25OHD₃) and its active form. Neonatal 25(OH)D₂ was best predicted by maternal characteristics, whereas 25(OH)D₃ was strongly associated to maternal vitamin D forms (R²=0.253 vs. 0.076 and R2=0.109 vs. 0.478, respectively). Maternal characteristics explained 12.2% of the neonatal 25(OH)D, maternal 25(OH)D concentrations explained 32.1%, while epimers contributed an additional 11.9%., Conclusions: By applying a novel highly specific vitamin D assay, the present study is the first to quantify 3-epi-25(OH)D concentrations in mother-newborn pairs. This accurate assay highlights a considerable proportion of vitamin D exists as epimers and a lack of correlation between the circulating and active forms. These results highlight the need for accurate measurements to appraise vitamin D status. Maternal characteristics and circulating forms of vitamin D, along with their epimers explain 56% of neonate vitamin D concentrations. The roles of active and epimer forms in the maternal-neonatal vitamin D relationship warrant further investigation.