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.     

Distribution and Determinants of Vitamin D-Binding Protein,Total, “Non-Bioavailable”, Bioavailable,and Free 25-Hydroxyvitamin D Concentrations among Older Adults

Background: serum 25-hydroxyvitamin D (25(OH)D) (“total 25 OH(D)”) is the most commonly used indicator of vitamin D status. However, 25(OH)D is mostly bound to the vitamin D binding protein (VDBP) or albumin in blood, and it has been suggested that the remaining bioavailable or free 25(OH)D may be more relevant for vitamin D associated health outcomes. We aimed to explore distributions and determinants of VDBP, total, bioavailable, complementary “non-bioavailable”, and free 25(OH)D in a large cohort of older adults in Germany. Methods: total 25(OH)D, VDBP, and albumin concentrations were measured in blood samples of 5899 men and women aged 50–75 years and used to calculate bioavailable (and complementary “non-bioavailable”) and free 25(OH)D concentrations. Linear regression models were used to evaluate associations of potential determinants of the various vitamin D biomarkers. Results: mean concentrations of VDBP, total, non-bioavailable, bioavailable, and free 25(OH)D were 323.6 µg/mL, 49.8 nmol/L, 43.4 nmol/L, 2.5 ng/mL, and 5.7 pg/mL, respectively. Seasonal variations were observed for all markers, with peak values in spring for VDBP and in summer for total, non-bioavailable, bioavailable, and free 25(OH)D. Consistent inverse associations were seen with age and body mass index for all markers, but divergent associations were seen with C-reactive protein. Strong variations by VDBP genotypes were seen for bioavailable and free 25(OH)D, and, in opposite direction for non-bioavailable 25(OH)D. Conclusion: commonalities and differences in determinants of various markers of vitamin D status were observed, which may help to enable a better understanding of their potential role for various vitamin D related health outcomes.     

Factors Associated with Serum Vitamin D Metabolites and Vitamin D Metabolite Ratios in Premenopausal Women

The most representative indicator of vitamin D status in clinical practice is 25(OH)D₃, but new biomarkers could improve the assessment of vitamin D status and metabolism. The objective of this study is to investigate the association of serum vitamin D metabolites and vitamin D metabolite ratios (VMRs) with potentially influential factors in premenopausal women. This is a cross-sectional study based on 1422 women, aged 39–50, recruited from a Madrid Medical Diagnostic Center. Participants answered an epidemiological and a food frequency questionnaire. Serum vitamin D metabolites were determined using an SPE–LC–MS/MS platform. The association between participant’s characteristics, vitamin D metabolites, and VMRs was quantified by multiple linear regression models. Mean 25(OH)D₃ concentration was 49.2 + 18.9 nmol/L, with greater deficits among obese, nulliparous, dark-skinned women, and with less sun exposure. A lower R2 ratio (1,25(OH)₂D₃/25(OH)D₃) and a higher R4 (24,25(OH)₂D₃/1,25(OH)₂D₃) were observed in nulliparous women, with high sun exposure, and those with low caloric intake or high consumption of calcium, vitamin D supplements, or alcohol. Nulliparous women had lower R1 (25(OH)D₃/Vit D₃) and R3 (24,25(OH)₂D₃/25(OH)D₃), and older women showed lower R3 and R4. Vitamin D status modified the association of the VMRs with seasons. VMRs can be complementary indicators of vitamin D status and its endogenous metabolism, and reveal the influence of certain individual characteristics on the expression of hydroxylase enzymes.     

Vitamin D Receptor and Vitamin D Binding Protein Gene Polymorphisms Are Associated with Renal Allograft Outcome

Vitamin D deficiency has adverse effects on renal allograft outcomes, and polymorphisms of genes encoding vitamin D-binding protein (VDBP) and vitamin D receptor (VDR) are defined to play a role in these conditions. The goal of the current investigation was to evaluate the connection between those polymorphisms with acute rejection, viral infection history, and recipients’ vitamin D status. In this study, 115 kidney transplant recipients and 100 healthy individuals were included. VDR polymorphisms including FokI (rs2228570), Apal (rs7975232), BsmI (rs1544410), as well as VDBP (rs7040) polymorphisms were studied using high resolution melting (PCR-HRM) analysis among the studied groups. The frequency of G allele in Apal rs7975232 polymorphism in the kidney transplant recipients was 0.63 times lower than healthy individuals (p = 0.026). Further, the G allele frequency in VDBP rs7040 polymorphism was significantly lower in patients with allograft rejection (p = 0.002). Considering the incidence of viral infection, significant differences were identified between the frequencies of VDR FokI (OR = 2.035; 95% CI 1.06–2.89, p = 0.030) and VDBP rs7040 (OR = 0.40; 95% CI 0.24–0.67, p < 0.001) T alleles in the studied groups. Moreover, the VDBP rs7040 GG genotype distribution was low in the recipients with a history of viral infection (p = 0.004). VDR (FokI) and VDBP (rs7040) alleles and their genotype distribution are significantly associated with allograft outcomes including allograft rejection and viral infection in the studied population.     

Vitamin D Metabolite Ratio in Pregnant Women with Low Blood Vitamin D Concentrations Is Associated with Neonatal Anthropometric Data

Existing evidence on the correlation between maternal vitamin D concentrations and birth outcomes is conflicting. Investigation of these associations requires accurate assessment of vitamin D status, especially in individuals with low 25-hydroxyvitamin D (25(OH)D) concentrations. This study examined the correlations between birth outcomes and the maternal vitamin D metabolite ratio (VMR) 1 (defined as the ratio of 24,25(OH)₂D₃ to 25(OH)D) and VMR2 (defined as the ratio of 3-epi-25(OH)D₃ to 25(OH)D) using data from the Japan Environment and Children’s Study at Chiba Regional Center. A total of 297 mother–neonate pairs were analyzed. Using liquid chromatography–tandem mass spectrometry, we measured 25(OH)D₂, 25(OH)D₃, 24,25(OH)₂D₃, and 3-epi-25(OH)D₃ concentrations in maternal serum samples. These data were analyzed in relation to birth anthropometric data using multivariable linear regression. Of the study participants, 85.2% showed insufficient vitamin D concentrations. VMR1 was strongly correlated with 25(OH)D concentrations, whereas VMR2 showed a weak correlation. Only VMR2 was associated with all anthropometric data. VMR2 in pregnant women with low vitamin D blood concentrations is a useful marker for neonatal anthropometric data and is independent of 25(OH)D. Accurate measurement of vitamin D metabolites could help better understand the effects of vitamin D on birth outcomes.     

A Prospective Cohort Study of Bioavailable 25-Hydroxyvitamin D Levels as a Marker of Vitamin D Status in Nontuberculous Mycobacterial Pulmonary Disease

Research on vitamin D in patients with nontuberculous mycobacterial (NTM) pulmonary disease (PD) is limited. We aimed to compare the vitamin D parameters of patients with NTM-PD to those of a healthy control group, and to assess the possible predictive markers for a clinical response. We prospectively enrolled 53 patients with NTM-PD between January 2014 and December 2016. The clinical data and vitamin D indices, including total, free, bioavailable 25-(OH)D, and vitamin D binding protein (VDBP) genotyping, were measured at baseline and six months after enrollment. An external dataset of 226 healthy controls was compared with the NTM-PD group. The mean age of subjects was 53 years; 54.5% were male. The NTM-PD group was older, predominantly female, and had a lower body mass index (BMI) than the controls. The proportion of patients with vitamin D concentration <50 nmol/L was 52.8% in the NTM-PD group and 54.9% in the control group (p = 0.789). The bioavailable 25-(OH)D concentrations of the NTM-PD group and the controls were similar (6.9 nmol/L vs. 7.6 nmol/L, p = 0.280). In the multivariable analysis, bioavailable 25-(OH)D concentrations were associated with NTM-PD, adjusting for age, sex, BMI, and VDBP levels. Bioavailable 25-(OH)D concentrations were significantly associated with susceptibility to NTM-PD, but not with treatment outcomes. Lower bioavailable 25-(OH)D might be a risk factor for NTM-PD.     

Hormonal Relationships to Bone Mass in Elderly Spanish Men as Influenced by Dietary Calcium and Vitamin D

We aim to evaluate whether calcium and vitamin D intake is associated with 25-hydroxyvitamin D (25-OH-Vitamin D₃) and parathyroid hormone (PTH) serum concentrations or is associated with either the phalangeal dual energy X-ray absorptiometry (pDXA) or the quantitative bone ultrasound (QUS) in independent elderly men. Serum PTH and 25-OH-Vitamin D₃ were measured in 195 healthy elderly men (mean age: 73.31 ± 5.10 year). Food intake was quantified using a dietetic scale. Participants with 25-OH-Vitamin D₃ levels ≥ 30 ng/mL (75 nmol/L) and a calcium intake of 800–1200 mg/day exhibited the lowest PTH levels (41.49 ± 16.72 ng/mL). The highest PTH levels (75.60 ± 14.16 ng/mL) were observed in the <30 ng/mL group 25-OH-Vitamin D₃ with a calcium intake >1200 mg/day. No significant differences in the serum PTH levels based on the serum 25-OH-Vitamin D3 levels were observed among participants with a calcium intake of 800–1200 mg/day. Serum PTH was inversely correlated with serum 25-OH-Vitamin D₃ in the entire patient sample (r = −0.288, p = 0.019). No differences in any of the three densitometry techniques were observed between any of the age groups in the 800–1200 mg/day and >1200 mg/day calcium intake groups. PTH levels correlate negatively with serum 25-OH-Vitamin D₃ levels, and neither calcium nor vitamin D intake exert a strong influence on either of the two parameters.     

Association between Vitamin D Receptor Polymorphism and Serum Vitamin D Levels in Children with Low-Energy Fractures

Objective: Fractures of bones, especially forearm fractures, are very common in children and their number is increasing. This study was designed to determine the impact of vitamin D serum levels and vitamin D receptor (VDR) polymorphisms on the occurrence of low-energy fractures in children.

Methods: The study group consisted of 100 children with clinically relevant bone fractures and a control group consisted of 127 children without fractures. Total vitamin D [25(OH)D3 plus 25(OH)D2] serum concentrations were evaluated in every patient. Genotypes for 4 restriction fragment length polymorphisms of the vitamin D receptor gene (FokI, ApaI, TaqI, and BsmI) were determined by standard polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) techniques.

Results: Differences in concentrations of vitamin D were observed between the group with bone fractures (median = 12 ng/ml) and the control group (median = 16 ng/ml; p = 0.000044).

Higher levels of vitamin D reduced the risk of fracture by 1.06 times (p = 0.0005). No impact of particular VDR polymorphism on the occurrence of low-energy fractures in children was detected. However, there were significant differences in the prevalence of FokI polymorphism genotypes between the fracture and control groups (p = 0.05). Furthermore, the recessive “aa” genotype of ApaI polymorphism and the dominant “TT” genotype of TaqI polymorphism were associated with higher levels of vitamin D (p = 0.005 and p = 0.036, respectively).

Conclusions: Vitamin D deficiency is an independent risk factor for fractures in children. ApaI polymorphism recessive “aa” and TaqI polymorphism dominant “TT” genotypes are associated with higher levels of vitamin D in serum.     

Vitamin D status: effects on parathyroid hormone and 1, 25-dihydroxyvitamin D in postmenopausal women

BACKGROUND: Low serum 25-hydroxyvitamin D ?25(OH)D concentrations are commonly found in the elderly and are associated with hip fracture. Treatment with vitamin D and calcium can reduce the risk of fracture. The relation between the rise in parathyroid hormone (PTH) with age and the decrease in 25(OH)D is not clear. Neither is there any consensus on the serum concentration of 25(OH)D required for bone health. OBJECTIVE: Our objective was to study the relations between serum PTH, serum vitamin D metabolites, and other calcium-related variables in postmenopausal women. DESIGN: This was a cross-sectional study of 496 postmenopausal women without vertebral fractures attending our menopausal osteoporosis clinics. RESULTS: PTH was significantly positively related to age and serum 1, 25-dihydroxyvitamin D ?1,25(OH)(2)D and inversely related to 25(OH)D and plasma ionized calcium. There was a step-like increase in PTH as serum 25(OH)D fell below 40 nmol/L. In women with 25(OH)D concentrations >40 nmol/L, 1,25(OH)(2)D was positively related to 25(OH)D; in women with 25(OH)D concentrations 40 nmol/L, 1,25(OH)(2)D was most closely (inversely) related to plasma creatinine. Therefore, with serum 25(OH)D concentrations increasingly <40 nmol/L, serum 1,25(OH)(2)D becomes critically dependent on rising concentrations of PTH. CONCLUSION: The data suggest that aging women should maintain 25(OH)D concentrations >40 nmol/L (which is the lower limit of our normal range for healthy young subjects) for optimal bone health.     

Vitamin D Status and Gestational Diabetes in Russian Pregnant Women in the Period between 2012 and 2021: A Nested Case–Control Study

Several meta-analyses found an association between low maternal serum 25-hydroxyvitamin D (25(OH)D) level and gestational diabetes mellitus (GDM). However, some of them reported significant heterogeneity. We examined the association of serum 25(OH)D concentration measured in the first and in the second halves of pregnancy with the development of GDM in Russian women surveyed in the periods of 2012–2014 and 2018–2021. We conducted a case–control study (including 318 pregnant women) nested on two previous studies. In 2012–2014, a total of 214 women (83 GDM and 131 controls) were enrolled before 15 weeks of gestation and maternal serum 25(OH)D concentrations were measured twice: at 8th–14th week of gestation and simultaneously with two-hour 75 g oral glucose tolerance test (OGTT) at 24th–32nd week of gestation. In the period of 2018–2021, 104 women (56 GDM and 48 controls) were included after OGTT and 25(OH)D concentrations were measured at 24th–32nd week of gestation. Median 25(OH)D levels were 20.0 [15.1–25.7] vs. 20.5 [14.5–27.5] ng/mL (p = 0.565) in GDM and control group in the first half of pregnancy and 25.3 [19.8–33.0] vs. 26.7 [20.8–36.8] ng/mL (p = 0.471) in the second half of pregnancy, respectively. The prevalence rates for vitamin D deficiency (25(OH)D levels < 20 ng/mL) were 49.4% and 45.8% (p = 0.608) in the first half of pregnancy and 26.2% vs. 22.1% (p = 0.516) in the second half of pregnancy in women who developed GDM and in women without GDM, respectively. The frequency of vitamin D supplements intake during pregnancy increased in 2018–2021 compared to 2012–2014 (p = 0.001). However, the third trimester 25(OH)D levels and prevalence of vitamin D deficiency (25.5 vs. 23.1, p = 0.744) did not differ in women examined in the periods of 2012–2014 and 2018–2021. To conclude, there was no association between gestational diabetes risk and maternal 25(OH)D measured both in the first and in the second halves of pregnancy. The increased prevalence of vitamin D supplements intake during pregnancy by 2018–2021 did not lead to higher levels of 25(OH)D.     

Upregulation of Irisin and Vitamin D-Binding Protein Concentrations by Increasing Maternal 25-Hydrovitamin D Concentrations in Combination with Specific Genotypes of Vitamin D-Binding Protein Polymorphisms

Dyshomeostasis of vitamin D-binding protein (VDBP) has been implicated in the pathogenesis of various pregnancy complications, including preeclampsia, preterm birth, gestational diabetes, and adverse metabolic profiles in the offspring. VDBP polymorphisms have been consistently reported to contribute to this intriguing interplay. Until recently, the effects of VDBP polymorphism heterogeneity on maternal and neonatal adipomyokine profiles have not been investigated, specifically after incorporating the different maternal and neonatal 25-hydroxyvitamin D concentration cut-offs at birth. We aimed to investigate the potential effects of maternal and neonatal VDBP polymorphisms on adiponectin, irisin, and VDBP concentrations at birth, according to different cut-offs of vitamin D status, in maternal–neonatal dyads recruited from the sunny region of Northern Greece. We obtained blood samples from 66 mother–child pairs at birth. Results indicated that (i) Neonatal serum biomarkers were not affected by any included neonatal VDBP polymorphism according to different cut-offs of neonatal vitamin D status at birth, (ii) neonatal VDBP concentration was elevated in neonates with maternal rs7041 GG genotype, (iii) maternal 25(OH)D at ≤75 nmol/L resulted in increased concentrations of maternal VBDP and irisin concentrations in women with CC genotype for rs2298850 and rs4588,whereas this effect was also evident for this cut-off for neonatal VDBP concentrations at birth for GC genotype for rs 7041, and (iv) no significant effect of neonatal VDBP polymorphisms was observed on neonatal VDBP, adiponectin, or irisin levels when stratified according to maternal 25(OH)D cut-offs. In conclusion, these findings confirm that among women with the combination of CC genotype for rs2298850 and rs4588, a specific high cut-off of maternal 25(OH)D results in increasing maternal VBDP concentrations, hence providing a mechanistic rationale for aiming for specific cut-offs of vitamin D after supplementation during pregnancy, in daily clinical practice.     

Vitamin D Deficiency in Pregnant Ukrainian Women: Effects of Alcohol Consumption on Vitamin D Status

Objective: Heavy alcohol consumption can alter vitamin D status; however, the relationships between alcohol consumption and vitamin D concentrations in pregnant women have not been well studied. The aim of this study was to investigate the vitamin D status in a population of alcohol-exposed (N = 180) and low/unexposed control (N = 179) Ukrainian pregnant women.

Methods: Women who attended prenatal care facilities in 2 regions of Ukraine (Rivne and Khmelnytsky) for a routine prenatal visit were screened for the study. At the time of enrollment (20.4 ± 7.0 weeks of gestation), blood samples and alcohol consumption data (during a typical week around conception and the most recent 2 weeks) were collected. Vitamin D status was assessed by 25-hydroxyvitamin D [25(OH)D] concentrations.

Results: A high prevalence of suboptimal vitamin D status in pregnant Ukrainian women was observed. Overall, 50.1% and 33.4% of the women were classified as vitamin D deficient [25(OH)D < 20 ng/mL] or insufficient [25(OH)D ≥ 20 ng/mL and ≤30 ng/mL], respectively, based on 2011 Endocrine Society guidelines. Alcohol-exposed women had significantly lower 25(OH)D concentrations than low/unexposed women in Spring (p = 0.006) and Winter (p = 0.022). When vitamin D concentrations were grouped into sunny season (Summer + Fall) compared to not sunny season (Winter + Spring), there was a significant ethanol by season interaction (p = 0.0028), with alcohol-drinking women having lower circulating vitamin D compared to low/unexposed women in seasons of low sun availability.

Conclusions: These data suggest that when vitamin D concentrations are generally low (e.g., during seasons of low sun availability), alcohol consumption during pregnancy has a negative impact on vitamin D status.     

Vitamin D Receptor Gene Polymorphism and Vitamin D Status in Population of Patients with Cardiovascular Disease—A Preliminary Study

The association between vitamin D receptor (VDR) polymorphism and the risk of cardiovascular diseases (CVD) remains unclear. This study aimed to assess a relationship between the VDR genotypes, plasma concentrations of vitamin D metabolites, and the occurrence of cardiovascular and metabolic disorders. Fifty-eight patients treated for various cardiological afflictions were included. Identification of VDR polymorphisms: ApaI, TaqI, BsmI, and FokI were carried out using the PCR-RFLP method. Plasma concentrations of 25-hydroxyvitamin-D2, 25-hydroxyvitamin-D3, and 3-epi-25-hydroxyvitamin D3 were assessed by the UPLC-MS/MS method. Lower incidence of BsmI AA genotype in the studied patients was observed compared with healthy controls, but the difference was insignificant. Among patients with the TT genotype, frequency of hypertension was higher than among carriers of other ApaI genotypes (p < 0.01). In addition, carriers of the TT ApaI, TC TaqI, and GA BsmI genotypes had an increased risk of obesity, while the presence of the FokI TT genotype was associated with a higher incidence of heart failure and hypertension. In conclusion, the BsmI AA genotype can be protective against CVD, but this observation needs study on a larger group of patients. Particular VDR genotypes were associated with 25-hydroxyvitamin-D levels, and the mechanism of this association should be further investigated.     

Monitored Supplementation of Vitamin D in Preterm Infants: A Randomized Controlled Trial

Appropriate supplementation of vitamin D can affect infections, allergy, and mental and behavioral development. This study aimed to assess the effectiveness of monitored vitamin D supplementation in a population of preterm infants. 109 preterm infants (24 0/7–32 6/7 weeks of gestation) were randomized to receive 500 IU vitamin D standard therapy (n = 55; approximately 800–1000 IU from combined sources) or monitored therapy (n = 54; with an option of dose modification). 25-hydroxyvitamin D [25(OH)D] concentrations were measured at birth, 4 weeks of age, and 35, 40, and 52 ± 2 weeks of post-conceptional age (PCA). Vitamin D supplementation was discontinued in 23% of infants subjected to standard treatment due to increased potentially toxic 25(OH)D concentrations (>90 ng/mL) at 40 weeks of PCA. A significantly higher infants’ percentage in the monitored group had safe vitamin D levels (20–80 ng/mL) at 52 weeks of PCA (p = 0.017). We observed increased vitamin D levels and abnormal ultrasound findings in five infants. Biochemical markers of vitamin D toxicity were observed in two patients at 52 weeks of PCA in the control group. Inadequate and excessive amounts of vitamin D can lead to serious health problems. Supplementation with 800–1000 IU of vitamin D prevents deficiency and should be monitored to avoid overdose.     

Maternal Vitamin D Status and Gestational Weight Gain as Correlates of Neonatal Bone Mass in Healthy Term Breastfed Young Infants from Montreal,Canada

The implications of maternal gestational weight gain (GWG) and vitamin D status to neonatal bone health are unclear. We tested whether maternal 25-hydroxyvitamin D (25(OH)D) and GWG relate to neonatal bone mineral content (BMC) and bone mineral density (BMD). Healthy term appropriate for gestational age breastfed neonates (n = 142) and their mothers were recruited 24–36 h after delivery and followed at 1.0 ± 0.5 month. At birth, obstetric data were collected and newborn serum 25(OH)D was measured. At 1 month, neonatal whole-body (WB) BMC, WB BMC relative to body weight (WB BMC/kg), lumbar spine BMC and BMD, maternal and neonatal 25(OH)D concentrations, and anthropometry were measured. Infant BMC and BMD between maternal 25(OH)D (<50, ≥50 nmol/L) and GWG (insufficient, adequate, and excessive) categories were compared. Maternal 25(OH)D was not related to infant whole-body BMC, BMC/kg, lumbar spine BMC, and BMD. Infants in the excessive maternal GWG category had greater (p = 0.0003) whole-body BMC and BMC/kg and lumbar spine BMC and BMD than inadequate GWG, and greater (p = 0.0063) whole-body BMC/kg and lumbar spine BMC and BMD than adequate GWG. These results suggest that maternal GWG, but not vitamin D status, modestly relates to bone mass in neonates.     

Vitamin D metabolism in magnesium deficient chicks

To determine if alterations in vitamin D metabolism are associated with the development of hypocalcemia in magnesium (Mg) deficiency, we measured plasma Mg, calcium (Ca), phosphorus (P) and vitamin D metabolites in growing chicks pair-fed diets adequate (1000ppm) or low (130ppm) in Mg for up to 15 days. A third group received a low Ca (0.2%) diet adequate in Mg and served as a positive control group in which the classical response to hypocalcemia was demonstrated. A progressive decline in plasma Mg in the Mg deficient chicks was associated with progressive and severe hypocalcemia. There was no rise in plasma 1,25-dihydroxycholecalcifetol (DHCC) in response to hypocalcemia in the Mg deficient chicks. In contrast, chicks fed low dietary Ca with adequate Mg exhibited a 3-fold elevation in circulating 1,25-DHCC and maintained plasma calcium slightly below that of control animals. The failure of the Mg deficient chicks to increase 1,25-DHCC production in response to hypocalcemia was not associated with inadequate circulating 25-hydroxycholecalciferol or increased plasma 24,25-DHCC. 1α-hydroxylase activity, measured in isolated renal tubules, was not elevated in the Mg deficient chicks, compared to controls. A significant correlation between plasma 1,25-DHCC and 1α-hydroxylase activity suggested that metabolic turnover of 1,25-DHCC was not significantly altered by Mg deficiency. The data suggest that the progression of hypocalcemia during Mg deficiency may be related to insufficient production of 1,25-DHCC in response to the prevailing hypocalcemia.     

Total,Bioavailable, and Free 25-Hydroxyvitamin D Equally Associate with Adiposity Markers and Metabolic Traits in Mexican Adults

Epidemiological studies suggest a relationship between total 25-hydroxyvitamin D [25(OH)D], adiposity, and metabolic traits. The bioavailability of 25(OH)D is regulated by the albumin, vitamin D binding protein (VDBP), and variants of the GC gene. Therefore, it is not clear if bioavailable or free 25(OH)D offer additional benefits compared to total 25(OH)D when estimating the magnitude of these associations. Our aim was to evaluate the association between 25(OH)D (total, free and bioavailable) with adiposity and metabolic traits. This was a cross-sectional study of 1904 subjects from the Health Workers Cohort Study from Mexico. Free and bioavailable 25(OH)D were calculated based on VDBP and albumin determinations, using a formula adjusted for the GC gene diplotypes. Adiposity and metabolic traits were measured with standardized procedures. Free and bioavailable 25(OH)D levels correlated with total 25(OH)D, r = 0.71 and 0.70, respectively (p < 0.001). Total, bioavailable and free 25(OH)D levels were negatively associated with the adiposity marker (visceral adiposity index) and metabolic traits (metabolic syndrome, type 2 diabetes, triglycerides, triglycerides/HDL-c ratio, and triglycerides/glucose index) in multivariate regression models (ORs = 0.73 to 0.96). Our findings suggest that free and bioavailable 25(OH)D do not offer additional advantages over total 25(OH)D regarding its association with adiposity and several metabolic traits in Mexican adults.     

Vitamin D Levels Are Associated with Cardiac Autonomic Activity in Healthy Humans

Vitamin D deficiency (≤50nmol/L 25-hydroxy vitamin D) is a cardiovascular (CV) risk factor that affects approximately one billion people worldwide, particularly those affected by chronic kidney disease (CKD). Individuals with CKD demonstrate abnormal cardiac autonomic nervous system activity, which has been linked to the significant rates of CV-related mortality in this population. Whether vitamin D deficiency has a direct association with regulation of cardiac autonomic activity has never been explored in humans. Methods: Thirty-four (34) healthy, normotensive subjects were studied and categorized based on 25-hydroxy vitamin D deficiency (deficient vs. non-deficient, n = 7 vs. 27), as well as 1,25-dihydroxy vitamin D levels (above vs. below 25th percentile, n = 8 vs. 26). Power spectral analysis of electrocardiogram recordings provided measures of cardiac autonomic activity across low frequency (LF) and high frequency (HF, representative of vagal contribution) bands, representative of the sympathetic and vagal limbs of the autonomic nervous system when transformed to normalized units (nu), respectively, as well as overall cardiosympathovagal balance (LF:HF) during graded angiotensin II (AngII) challenge (3 ng/kg/min × 30 min, 6 ng/kg/min × 30 min). Results: At baseline, significant suppression of sympathovagal balance was observed in the 25-hydroxy vitamin D-deficient participants (LF:HF, p = 0.02 vs. non-deficient), although no other differences were observed throughout AngII challenge. Participants in the lowest 1,25-dihydroxy VD quartile experienced significant withdrawal of inhibitory vagal control, as well as altered overall sympathovagal balance throughout AngII challenge (HF, mean difference = −6.98 ± 3 nu, p = 0.05; LF:HF, mean difference = 0.34 ± 0.1, p = 0.043 vs. above 25th percentile). Conclusions: Vitamin D deficiency is associated with suppression of resting cardiac autonomic activity, while low 1,25-dihydroxy vitamin D levels are associated with unfavourable cardiac autonomic activity during an acute AngII stressor, offering a potential pathophysiological mechanism that may be acting to elevate CV risk in in populations with low vitamin D status.     

Comparison of Vitamin D and 25-Hydroxyvitamin D Concentrations in Human Breast Milk between 1989 and 2016–2017

Background: Breast milk is considered the optimal source of nutrition during infancy. Although the vitamin D concentration in human breast milk is generally considered poor for infants, vitamin D in breast milk is an important source for exclusively breastfed infants. Increases in vitamin D insufficiency and deficiency in lactating mothers may reduce vitamin D concentrations in breast milk. This study aimed to compare vitamin D and 25-hydroxyvitamin D (25OHD) concentrations in breast milk collected in 1989 and 2016–2017 and simultaneously analyze them with liquid chromatography-tandem mass spectrometry (LC-MS/MS); the association between the lifestyle of recent lactating mothers (2016–2017) and vitamin D status in human breast milk was also evaluated. Method: Lactating mothers were recruited from three regions of Japan in 1989 (n = 72) and 2016–2017 (n = 90), and milk from 3–4 months was collected in summer and winter. The samples were strictly sealed and stored at −80℃ until measurement. Breast milk vitamin D and 25OHD concentrations were analyzed by LC-MS/MS. Vitamin D intake, sun exposure, and sunscreen use of the lactating mothers in 2016–2017 were assessed. Results: Both vitamin D and 25OHD concentrations in breast milk were higher in the summer regardless of the survey year. Significantly lower vitamin D and 25OHD concentrations were observed in 2016–2017 compared with 1989 in summer, but no survey year difference was observed in winter. The stepwise multiple regression analyses identified season, daily outdoor activity, and suntan in the last 12 months as independent factors associated with vitamin D₃ concentrations. Conclusion: The results suggest that low vitamin D status in recent lactating mothers may have decreased vitamin D and 25OHD concentrations in breast milk compared with the 1980s. These results are helpful for developing public health strategies to improve vitamin D status in lactating mothers and infants.     

Vitamin D and Calcium Status in South African Adolescents with Alcohol Use Disorders

Adequate vitamin D and calcium are essential for optimal adolescent skeletal development. Adolescent vitamin D insufficiency/deficiency and poor calcium intake have been reported worldwide. Heavy alcohol use impacts negatively on skeletal health, which is concerning since heavy adolescent drinking is a rising public health problem. This study aimed to examine biochemical vitamin D status and dietary intakes of calcium and vitamin D in 12–16 year-old adolescents with alcohol use disorders (AUD), but without co-morbid substance use disorders, compared to adolescents without AUD. Substance use, serum 25-hydroxyvitamin D (s-25(OH)D) concentrations, energy, calcium and vitamin D intakes were assessed in heavy drinkers (meeting DSM-IV criteria for AUD) (n = 81) and in light/non-drinkers without AUD (non-AUD) (n = 81), matched for age, gender, language, socio-economic status and education. Lifetime alcohol dose was orders of magnitude higher in AUD adolescents compared to non-AUD adolescents. AUD adolescents had a binge drinking pattern and “weekends-only” style of alcohol consumption. Significantly lower (p = 0.038) s-25(OH)D (adjusted for gender, smoking, vitamin D intake) were evident in AUD adolescents compared to non-AUD adolescents. High levels of vitamin D insufficiency/deficiency (s-25(OH)D < 29.9 ng/mL) were prevalent in both groups, but was significantly higher (p = 0.013) in the AUD group (90%) compared to the non-AUD group (70%). All participants were at risk of inadequate calcium and vitamin D intakes (Estimated Average Requirement cut-point method). Both groups were at risk of inadequate calcium intake and had poor biochemical vitamin D status, with binge drinking potentially increasing the risk of the latter. This may have negative implications for peak bone mass accrual and future osteoporosis risk, particularly with protracted binge drinking.