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Fibroblast growth factor‐23 (FGF23) controls the homeostasis of both phosphate and vitamin D. Bone-derived FGF23 can suppress the transcription of 1α‐hydroxylase (1α(OH)ase) to reduce renal activation of vitamin D (1,25(OH)2D3). FGF23 can also activate the transcription of 24‐hydroxylase to enhance the renal degradation process of vitamin D. There is a counter-regulation for FGF23 and vitamin D; 1,25(OH)2D3 induces the skeletal synthesis and the release of FGF23, while FGF23 can suppress the production of 1,25(OH)2D3 by inhibiting 1α(OH)ase synthesis. Genetically ablating FGF23 activities in mice resulted in higher levels of renal 1α(OH)ase, which is also reflected in an increased level of serum 1,25(OH)2D3, while genetically ablating 1α(OH)ase activities in mice reduced the serum levels of FGF23. Similar feedback control of FGF23 and vitamin D is also detected in various human diseases. Further studies are required to understand the subcellular molecular regulation of FGF23 and vitamin D in health and disease.
Molecular Neurology Research Program, University of Helsinki, Helsinki, Finland
Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
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Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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Competence Centre on Health Technologies, Tartu, Estonia
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Molecular Neurology Research Program, University of Helsinki, Helsinki, Finland
Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
School of Basic and Medical Biosciences, King’s College London, Guy’s Hospital, London, United Kingdom
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Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden
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Department of Food and Environmental Sciences, University of Helsinki, Helsinki, Finland
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Objective
The effect of vitamin D at the transcriptome level is poorly understood, and furthermore, it is unclear if it differs between obese and normal-weight subjects. The objective of the study was to explore the transcriptome effects of vitamin D supplementation.
Design and methods
We analysed peripheral blood gene expression using GlobinLock oligonucleotides followed by RNA sequencing in individuals participating in a 12-week randomised double-blinded placebo-controlled vitamin D intervention study. The study involved 18 obese and 18 normal-weight subjects (of which 20 males) with mean (±s.d.) age 20.4 (±2.5) years and BMIs 36 (±10) and 23 (±4) kg/m2, respectively. The supplemental daily vitamin D dose was 50 µg (2000 IU). Data were available at baseline, 6- and 12-week time points and comparisons were performed between the vitamin D and placebo groups separately in obese and normal-weight subjects.
Results
Significant transcriptomic changes were observed at 6 weeks, and only in the obese subjects: 1724 genes were significantly upregulated and 186 genes were downregulated in the vitamin D group compared with placebo. Further analyses showed several enriched gene categories connected to mitochondrial function and metabolism, and the most significantly enriched pathway was related to oxidative phosphorylation (adjusted P value 3.08 × 10−14). Taken together, our data suggest an effect of vitamin D supplementation on mitochondrial function in obese subjects.
Conclusions
Vitamin D supplementation affects gene expression in obese, but not in normal-weight subjects. The altered genes are enriched in pathways related to mitochondrial function. The present study increases the understanding of the effects of vitamin D at the transcriptome level.
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Introduction
Tertiary hyperparathyroidism (THPT) and vitamin D deficiency are commonly seen in kidney transplant recipients, which may result in persistently elevated fibroblast growth factor 23 (FGF23) level after transplantation and decreased graft survival. The aim of this study is to evaluate the effect of vitamin D supplementation on THPT, FGF23-alpha Klotho (KLA) axis and cardiovascular complications after transplantation.
Materials and methods
Two hundred nine kidney transplant recipients were included and further divided into treated and untreated groups depending on whether they received vitamin D supplementation. We tracked the state of THPT, bone metabolism and FGF23–KLA axis within 12 months posttransplant and explored the predictors and risk factors for intact FGF23 levels, KLA levels, THPT and cardiovascular complications in recipients.
Results
Vitamin D supplementation significantly improved FGF23 resistance, THPT and high bone turnover status, preserved better graft function and prevented coronary calcification in the treated group compared to the untreated group at month 12. The absence of vitamin D supplementation was an independent risk factor for THPT and a predictor for intact FGF23 and KLA levels at month 12. Age and vitamin D deficiency were independent risk factors for coronary calcification in recipients at month 12.
Conclusion
Vitamin D supplementation effectively improved THPT, FGF23 resistance and bone metabolism, preserved graft function and prevented coronary calcification after transplantation.
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Background
Internationally, concern has been repeatedly raised about the little notable progress in the collection, analysis and use of population micronutrient status and deficiency data globally. The need for representative status and intake data for vitamin D has been highlighted as a research priority for well over a decade.
Aim and methods
A narrative review which aims to provide a summary and assessment of vitamin D nutritional status data globally. This review divides the world into the Food and Agriculture Organisation’s (FAO) major regions: the Americas, Europe, Oceania, Africa and Asia. Emphasis was placed on published data on the prevalence of serum 25-hydroxyvitamin D (25(OH)D) < 25/30 and <50 nmol/L (reflecting vitamin D deficiency and inadequacy, respectively) as well as vitamin D intake, where possible from nationally representative surveys.
Results
Collating data from the limited number of available representative surveys from individual countries might suggest a relatively low overall prevalence of vitamin D deficiency in South America, Oceania and North America, whereas there is more moderate prevalence in Europe and Asia, and possibly Africa. Overall, the prevalence of serum 25(OH)D < 25/30 and <50 nmol/L ranges from ~5 to 18% and 24 to 49%, respectively, depending on FAO world region. Usual intakes of vitamin D can also vary by FAO world region, but in general, with a few exceptions, there are very high levels of inadequacy of vitamin D intake.
Conclusions
While the burden of vitamin D deficiency and inadequacy varies by world regions and not just by UVB availability, the global burden overall translates into enormous numbers of individuals at risk.
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Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
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Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
Centre for Innovation in Personalized Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
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Background
Measurement of free 25-hydroyvitamin D (25(OH)D) status has been suggested as a more representative marker of vitamin D status than that of total 25(OH)D. Previously, free 25(OH)D could only be calculated indirectly; however, a newly developed direct assay for the measurement of free 25(OH)D is now available. The aim of this study therefore was to investigate directly measured total and free vitamin D levels association with metabolic health in postmenopausal healthy women living in Saudi Arabia.
Methods
A sample of 302 postmenopausal women aged ≥50 years (n = 302) living in Saudi Arabia were recruited in a cross-sectional study design. Blood samples were collected from subjects for measurement of serum levels of total 25(OH)D, directly measured free 25(OH)D, metabolic bone parameters, lipid profile, and other biochemical tests.
Results
A positive correlation was found between directly measured free and total 25(OH)D (r = 0.64, P< 0.0001). Total but not free 25(OH)D showed significant association with serum intact parathyroid hormone (P = 0.004), whilst free 25(OH)D but not total 25(OH)D showed a significant association with total cholesterol and LDL-C (P = 0.032 and P = 0.045, respectively).
Conclusions
Free 25(OH)D and total 25(OH)D were found to be consistently correlated but with different associations to metabolic health parameters. Further research is needed to determine which marker of vitamin D status would be the most appropriate in population studies.
Unit of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden
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Unit of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden
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Unit of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden
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Unit of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden
Unit of Cardiology, Karolinska University Hospital, Stockholm, Sweden
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Unit of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden
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Unit of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden
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Unit of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden
Unit of Cardiology, Karolinska University Hospital, Stockholm, Sweden
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Unit of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden
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The CC genotype of the vitamin D receptor (VDR) polymorphism TaqI rs731236 has previously been associated with a higher risk of developing myopathy compared to TT carriers. However, the mechanistic role of this polymorphism in skeletal muscle is not well defined. The effects of vitamin D on patients genotyped for the VDR polymorphism TaqI rs731236, comparing CC and TT carriers were evaluated. Primary human myoblasts isolated from 4 CC carriers were compared with myoblasts isolated from four TT carriers and treated with vitamin D in vitro. A dose-dependent inhibitory effect on myoblast proliferation and differentiation was observed concurrent with modifications of key myogenic regulatory factors. RNA sequencing revealed a vitamin D dose–response gene signature enriched with a higher number of VDR-responsive elements (VDREs) per gene. Interestingly, the greater the expression of muscle differentiation markers in myoblasts, the more pronounced was the vitamin D-mediated response to suppress genes associated with myogenic fusion and myotube formation. This novel finding provides a mechanistic explanation to the inconsistency regarding previous reports of the role of vitamin D in myoblast differentiation. No effects in myoblast proliferation, differentiation or gene expression were related to CC vs TT carriers. Our findings suggest that the VDR polymorphism TaqI rs731236 comparing CC vs TT carriers did not influence the effects of vitamin D on primary human myoblasts and that vitamin D inhibits myoblast proliferation and differentiation through key regulators of cell cycle progression. Future studies need to employ strategies to identify the primary responses of vitamin D that drive the cellular response towards quiescence.
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Objective
Vitamin D receptors are present in the female reproductive tract. Studies on the association between serum vitamin D level and pregnancy rate of in vitro fertilization (IVF) showed inconsistent results and focused on a single fresh or frozen embryo transfer cycle. The objective of our study was to evaluate if serum vitamin D level before ovarian stimulation was associated with the cumulative live birth rate (CLBR) of the first IVF cycle.
Design
Retrospective cohort study.
Methods
Women who underwent the first IVF cycle from 2012 to 2016 at a university-affiliated reproductive medicine center were included. Archived serum samples taken before ovarian stimulation were analyzed for 25(OH)D levels using liquid chromatography-mass spectrometry.
Results
In total, 1113 had pregnancy outcome from the completed IVF cycle. The median age (25th–75th percentile) of the women was 36 (34–38) years and serum 25(OH)D level was 53.4 (41.9–66.6) nmol/L. The prevalence of vitamin D deficiency (less than 50 nmol/L) was 42.2%. The CLBR in the vitamin D-deficient group was significantly lower compared to the non-deficient group (43.9%, 208/474 vs 50.9%, 325/639, P = 0.021, unadjusted), and after controlling for women’s age, BMI, antral follicle count, type and duration of infertility. There were no differences in the clinical/ongoing pregnancy rate, live birth rate and miscarriage rate in the fresh cycle between the vitamin D deficient and non-deficient groups.
Conclusions
Vitamin D deficiency was prevalent in infertile women in subtropical Hong Kong. The CLBR of the first IVF cycle in the vitamin D-deficient group was significantly lower compared to the non-deficient group.
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Objective
Increased levels of depressive symptoms, fatigue or pain (all dimensions of reduced health-related quality of life (HRQOL)) are common in people with type 2 diabetes mellitus (DM). Earlier studies have reported associations between low vitamin D status and fatigue and depressive symptoms. The aim of the present study was to examine the effects of vitamin D supplementation on dimensions of HRQOL in people with type 2 DM.
Design
Randomised, double-blind, placebo-controlled trial.
Methods
The effect of monthly cholecalciferol 50,000 IU vs placebo on HRQOL was assessed in 275 adults with type 2 DM derived from general practices. HRQOL at baseline and after six months using the Short Form 36 Health Survey (SF-36) was collected. Linear regression analyses were used to compare the change in HRQOL over time between the vitamin D and placebo group.
Results
187/275 (68%) completed baseline and follow-up SF-36 and were included in the analysis. Median serum 25-hydroxyvitamin D almost doubled in the intervention group compared to that in the placebo group (58.5–106.0 nmol/L vs 60.0–61.5 nmol/L, respectively). A small significant difference (adjusted B: −8.90; 95% CI: −17.16 to −0.65) between both groups was seen concerning the SF-36 domain role limitations due to physical problems in disadvantage of the vitamin D group.
Conclusions
Six months of vitamin D supplementation did not improve HRQOL in non-vitamin D-deficient people with type 2 DM managed on oral antidiabetic therapy.
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Purpose
Serum 25-hydroxy vitamin D [25(OH)D] varies greatly with season at northern latitudes. The purpose of this study was to determine if the seasonal variations in serum total 25(OH)D are followed by a concomitant variation in free 25(OH)D or if the variation is damped by alterations in the binding capacity of DBP.
Methods
Serum was collected from 540 healthy blood donors (60% men; mean age 41 ± 13 years) during 12 months and analyzed for total 25(OH)D, directly measured free 25(OH)D, vitamin D-binding protein (DBP) and albumin. Calculated free 25(OH)D was estimated.
Results
The UV-B radiation during the sampling month was positively correlated with the serum levels of total 25(OH)D (r = 0.355, P < 0.001), directly measured free (r = 0.336, P < 0.001) and calculated free 25(OH)D (r = 0.275, P < 0.001), but not with DBP and albumin. The percentage of free 25(OH)D was higher during the winter months than that during the summer months (0.020 ± 0.005% vs 0.019 ± 0.004%; P = 0.007) and higher in participants with a serum 25(OH)D below 25 nmol/L than that in participants with a serum 25(OH)D above 75 nmol/L (0.031 ± 0.007% vs 0.017 ± 0.003%; P < 0.001). iPTH was correlated with directly measured free 25(OH)D (r = −0.226; P < 0.001), but only weakly with calculated free 25(OH)D (r = −0.095; P = 0.027).
Conclusions
Directly measured free serum 25(OH)D was highly correlated with total serum 25(OH)D and followed the same seasonal variation, whereas the serum concentrations of DBP and albumin were stable. The fluctuation in free 25(OH)D was only marginally damped with an increase in the percentage of free 25(OH)D during the winter months and in participants with vitamin D deficiency.
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Objective
Vitamin D plays an important role during pregnancy. The aim was to compare vitamin D status in a group of singleton (SP) and twin pregnancies (TP) using two diagnostic methods: chemiluminescence immunoassay (CLIA) and liquid chromatography with tandem mass spectrometry (LC-MS/MS).
Design
This is a cross-sectional study.
Methods
The study was conducted in the population of SP and TP at the gestational age above 20 + 0 at the Bielanski Hospital in Warsaw, Poland, between October 2020 and January 2023. All patients had their venous blood samples collected and were given an original survey containing questions on demography and vitamin D supplementation.
Results
The study group included 53 Caucasian women with SP and 78 with TP aged from 21 to 47. Considering LC-MS/MS, patients with TP had lower concentrations of 25-hydroxyvitamin D (25(OH)D) than patients with SP. However, no significant difference was observed in the frequency of the occurrence of vitamin D deficiency (25(OH)D < 30 ng/mL). In both groups, the levels obtained with CLIA were significantly lower than in case of LC-MS/MS, however, strongly correlated. The intermethod agreement accounted for 52.4% and the Cohen’s kappa coefficient was 0.142.
Conclusions
The concentration of 25(OH)D in pregnant women depends on the type of gestation (SP/TP) and on the diagnostic methods used (CLIA/LC-MS/MS). Based on LC-MS/MS, the incidence of vitamin D deficiency was low in our group and no differences occurred in its frequency between SP and TP. The intermethod agreement between CLIA and LC-MS/MS on the detection of vitamin D deficiency was low.
Significance statement
This is the first study to compare the concentration of 25(OH)D levels between SP and TP using two methods: CLIA and the gold standard – LC-MS/MS. Based on LC-MS/MS, a low incidence of vitamin D deficiency was observed in our group, in which the vast majority of patients took cholecalciferol supplements. Moreover, there were no differences in its frequency between SP and TP. However, the 25(OH)D level was significantly lower in TP. The intermethod agreement between CLIA and LC-MS/MS on the detection of vitamin D deficiency was low, which is associated with substantial clinical implications.
