Special Issue "Vitamin D: Current Issues and New Perspectives"

A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (15 November 2016).

Special Issue Editor

Prof. Dr. Igor Sergeev
E-Mail Website
Guest Editor
Health and Nutritional Sciences, South Dakota State University, Brookings, SD 57007, USA
Interests: vitamin D; calcium; bioactive food components; nutrient regulation of apoptosis; vitamin D, calcium, and bioactives in the prevention of obesity and cancer; vitamin D and cell calcium
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Special Issue Information

Dear Colleagues,

This Special Issue will focus on the potential role and mechanisms of vitamin D for maintaining optimal health and preventing disease. The title, “Vitamin D: Current Issues and New Perspectives”, is intentionally broad, to be of interest to scientists working in the most promising areas of vitamin D research.

Vitamin D3, a hormone precursor and a micronutrient, is increasingly often considered important for disease prevention and maintaining good health throughout the life; however, the causality of these claims has not been mechanistically or probabilistically substantiated. The hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) functions via genomic and nongenomic mechanisms in a number of cell types, and vitamin D hormonal and nutritional status has been linked to multiple diseases and disorders. For example, vitamin D deficiency and insufficiency have been associated with the increased risk of cancer, diabetes, obesity, osteoporosis, infectious and immune-mediated diseases, cardiovascular disease, etc.  A promising approach for the prevention of these diseases may include maintaining the optimal vitamin D status, while specifically designed vitamin D analogs can be used to trigger vitamin D-dependent cellular responses (e.g., intracellular Ca2+ signals, apoptosis, immune response) that are mechanistically linked to the disease treatment. Understanding the role of 1,25(OH)2D3 in regulation of cellular signaling may lead to discovery of novel therapeutic and preventive modalities for various diseases. Understanding the role of vitamin D endocrine system and vitamin D nutritional and hormonal status in regulation of physiological functions may help to develop new approaches for the disease prevention and maintaining good health.   

The purpose of this Special Issue is to provide an update on vitamin D mechanism and function, including novel insights on mechanisms of action of 1,25(OH)2D3 , as well as to discuss the role of and new perspectives for vitamin D in maintaining optimal health and disease prevention. The Editors of Nutrients extend an invitation to scientists to submit original research or reviews on any of the above topics for this Special Issue on vitamin D.

Prof. Dr. Igor N. Sergeev
Guest Editor

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Keywords

  • Vitamin D
  • 1,25-Dihydroxyvitamin D
  • 25-Hydroxyvitamin D
  • Cholecalciferol
  • Calcitriol
  • Calcidiol
  • Vitamin D endocrine system
  • Vitamin D hydroxylases
  • Vitamin D receptor
  • Vitamin D binding protein
  • Calbindin
  • Vitamin D metabolism
  • Vitamin D and Ca2+ signaling
  • Vitamin D status
  • Vitamin D nutrition
  • Vitamin D deficiency
  • Vitamin D analysis methods
  • Vitamin D and health
  • Vitamin D and calcium
  • Vitamin D and bone
  • Vitamin D and muscle
  • Vitamin D and intestine
  • Vitamin D and reproduction
  • Vitamin D and brain
  • Vitamin D and physical performance
  • Vitamin D and disease
  • Vitamin D analogs
  • Cancer
  • Diabetes
  • Obesity
  • Cardiovascular disease
  • Infectious diseases
  • Renal diseases
  • Bone diseases
  • Immune system diseases

Published Papers (26 papers)

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Open AccessArticle
Prevalence and Determinants of Suboptimal Vitamin D Levels in a Multiethnic Asian Population
Nutrients 2017, 9(3), 313; https://doi.org/10.3390/nu9030313 - 22 Mar 2017
Cited by 12
Abstract
This population-based cross-sectional study examined the prevalence and risk factors of suboptimal vitamin D levels (assessed using circulating 25-hydroxycholecalciferol (25(OH)D)) in a multi-ethnic sample of Asian adults. Plasma 25(OH)D concentration of 1139 Chinese, Malay and Indians (40–80 years) were stratified into normal (≥30 [...] Read more.
This population-based cross-sectional study examined the prevalence and risk factors of suboptimal vitamin D levels (assessed using circulating 25-hydroxycholecalciferol (25(OH)D)) in a multi-ethnic sample of Asian adults. Plasma 25(OH)D concentration of 1139 Chinese, Malay and Indians (40–80 years) were stratified into normal (≥30 ng/mL), and suboptimal (including insufficiency and deficiency, <30 ng/mL) based on the 2011 Endocrine Society Clinical Practice Guidelines. Logistic regression models were used to assess the associations of demographic, lifestyle and clinical risk factors with the outcome. Of the 1139 participants, 25(OH)D concentration was suboptimal in 76.1%. In multivariable models, age ≤65 years (compared to age >65 years), Malay and Indian ethnicities (compared to Chinese ethnicity), and higher body mass index, HbA1c, education and income levels were associated with suboptimal 25(OH)D concentration (p < 0.05). In a population-based sample of Asian adults, approximately 75% had suboptimal 25(OH)D concentration. Targeted interventions and stricter reinforcements of existing guidelines for vitamin D supplementation are needed for groups at risk of vitamin D insufficiency/deficiency. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)
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Open AccessArticle
Maternal Vitamin D Status in the Late Second Trimester and the Risk of Severe Preeclampsia in Southeastern China
Nutrients 2017, 9(2), 138; https://doi.org/10.3390/nu9020138 - 14 Feb 2017
Cited by 18
Abstract
The association between maternal vitamin D deficiency and the risk of severe preeclampsia is still debated. In the present study, we aimed to evaluate vitamin D status in Chinese pregnant women and investigate its correlation with the odds of developing severe preeclampsia. A [...] Read more.
The association between maternal vitamin D deficiency and the risk of severe preeclampsia is still debated. In the present study, we aimed to evaluate vitamin D status in Chinese pregnant women and investigate its correlation with the odds of developing severe preeclampsia. A cohort study was performed on 13,806 pregnant women who routinely visited the antenatal care clinics and subsequently delivered at the Wuxi Maternity and Child Health Hospital. All the subjects in the cohort had their serum 25-hydroxyvitamin D (25(OH)D) concentrations measured during pregnancy. A high prevalence of maternal vitamin D deficiency (25(OH)D < 50 nmol/L) was found. Pregnant women who had different BMIs before pregnancy had significantly different serum concentrations of 25(OH)D. There was also a significant difference in the serum 25(OH)D concentration among pregnant women of different ages. The serum 25(OH)D concentration was significantly lower in pregnant women who subsequently developed severe preeclampsia compared with those who did not. Maternal vitamin D deficiency at 23–28 weeks of gestation was strongly associated with increased odds for severe preeclampsia after adjusting for relevant confounders (adjusted OR, 3.16; 95% CI, 1.77–5.65). Further studies are required to investigate whether vitamin D supplementation would reduce the risk of severe preeclampsia and improve pregnancy outcomes. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)
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Open AccessArticle
Association between Obesity and Serum 25(OH)D Concentrations in Older Mexican Adults
Nutrients 2017, 9(2), 97; https://doi.org/10.3390/nu9020097 - 31 Jan 2017
Cited by 7
Abstract
Background: Vitamin D is essential for maintaining bone mineralization and calcium homeostasis, and prevents falls and fractures in older adults. Mexico is undergoing an epidemiologic and demographic transition with increasing obesity rates. The study’s aim was to determine the association of obesity with [...] Read more.
Background: Vitamin D is essential for maintaining bone mineralization and calcium homeostasis, and prevents falls and fractures in older adults. Mexico is undergoing an epidemiologic and demographic transition with increasing obesity rates. The study’s aim was to determine the association of obesity with serum 25-hydroxyvitamin D [25(OH)D] concentrations in older Mexican adults. Methods: Data from 1772 Mexicans, aged ≥50 years, enrolled in a sub-sample of the 3rd wave of the Mexican Health and Aging Study, were included. Serum 25(OH)D concentrations were used to define vitamin D status, and were categorized into tertiles. Body mass index measures were used to categorize older adults into under/normal weight, overweight, and obese groups. Multinomial logistic regression models were used to assess the relationship, adjusting for potential confounders. Results: Approximately 40% and 37% of older Mexican adults were either overweight or obese, respectively. Compared to under/normal weight older Mexicans, obese adults were 1.78 times (95% Confidence Interval (CI) 1.27–2.48) and 1.94 times (95% CI 1.40–2.68) more associated with the first and second tertile concentrations of serum 25(OH)D, respectively. Overweight adults were 1.52 times (95% CI 1.12–2.06) more associated with the second tertile of serum 25(OH)D concentration than under/normal weight adults. Conclusion: Overweight/Obesity was found to be significantly associated with low concentrations of serum 25(OH) in older Mexican adults. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)
Open AccessArticle
25-Hydroxy-Vitamin D Concentration Is Not Affected by Severe or Non-Severe Pneumonia, or Inflammation, in Young Children
Nutrients 2017, 9(1), 52; https://doi.org/10.3390/nu9010052 - 17 Jan 2017
Cited by 5
Abstract
Poor vitamin D status has been associated with increased risk and severity of respiratory tract infections. Whether or not inflammation and infection affects 25-hydroxy vitamin D (25(OH)D) concentration is controversial and is important in the interpretation of observational studies using plasma-25(OH)D as a [...] Read more.
Poor vitamin D status has been associated with increased risk and severity of respiratory tract infections. Whether or not inflammation and infection affects 25-hydroxy vitamin D (25(OH)D) concentration is controversial and is important in the interpretation of observational studies using plasma-25(OH)D as a biomarker for status. Our objectives were to measure whether 25(OH)D concentration was altered by an episode of acute lower respiratory tract infection and whether markers of inflammation predicted the 25(OH)D concentration. Children aged 2–35 months with severe (n = 43) and non-severe (n = 387) community-acquired, WHO-defined pneumonia were included. 25(OH)D concentration and inflammatory markers (cytokines, chemokines, and growth factors) were measured in plasma during the acute phase and 14, 45, and 90 days later. Predictors for 25(OH)D concentrations were identified in multiple linear regression models. Mean 25(OH)D concentration during the acute phase and after recovery (14, 45, and 90 days) was 84.4 nmol/L ± 33.6, and 80.6 ± 35.4, respectively. None of the inflammatory markers predicted 25(OH)D concentration in the multiple regression models. Age was the most important predictor for 25(OH)D concentration, and there were no differences in 25(OH)D concentrations during illness and after 14, 45, and 90 days when adjusting for age. Infection and inflammation did not alter the 25(OH)D concentration in young children with acute lower respiratory tract infections. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)
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Open AccessArticle
Effect of Two Different Multimicronutrient Supplements on Vitamin D Status in Women of Childbearing Age: A Randomized Trial
Nutrients 2017, 9(1), 30; https://doi.org/10.3390/nu9010030 - 04 Jan 2017
Cited by 16
Abstract
The German Nutrition Society raised in 2012 the recommended daily vitamin D intake from 200 to 800 international units (IU) to achieve 25-hydroxyvitamin D (25(OH)D) levels of at least 50 nmol/L, even when endogenous vitamin D synthesis is minimal such as in winter. [...] Read more.
The German Nutrition Society raised in 2012 the recommended daily vitamin D intake from 200 to 800 international units (IU) to achieve 25-hydroxyvitamin D (25(OH)D) levels of at least 50 nmol/L, even when endogenous vitamin D synthesis is minimal such as in winter. We aimed to evaluate this recommendation in women of childbearing age. This is a single-center, randomized, open trial conducted from 8 January to 9 May 2016 in Esslingen, Germany. We randomized 201 apparently healthy women to receive for 8 weeks a daily multimicronutrient supplement containing either 200 IU (n = 100) or 800 IU vitamin D3 (n = 101). Primary outcome measure was serum 25(OH)D. 196 participants completed the trial. Increases in 25(OH)D (median with interquartile range) from baseline to study end were 13.2 (5.9 to 20.7) nmol/L in the 200 IU group, and 35.8 (18.2 to 52.8) nmol/L in the 800 IU group (p < 0.001 for the between group difference). At study end, levels of ≥50 nmol/L were present in 70.4% of the 200 IU group and in 99% of the 800 IU group. Participants on hormonal contraceptives had higher baseline levels and a stronger increase in 25(OH)D. In conclusion, daily supplementation of 800 IU vitamin D3 during wintertime in Germany is sufficient to achieve a 25(OH)D level of at least 50 nmol/L in almost all women of childbearing age, whereas 200 IU are insufficient. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)
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Open AccessArticle
Low Prevalence of Vitamin D Insufficiency among Nepalese Infants Despite High Prevalence of Vitamin D Insufficiency among Their Mothers
Nutrients 2016, 8(12), 825; https://doi.org/10.3390/nu8120825 - 21 Dec 2016
Cited by 7
Abstract
Background: Describing vitamin D status and its predictors in various populations is important in order to target public health measures. Objectives: To describe the status and predictors of vitamin D status in healthy Nepalese mothers and infants. Methods: 500 randomly selected Nepalese mother [...] Read more.
Background: Describing vitamin D status and its predictors in various populations is important in order to target public health measures. Objectives: To describe the status and predictors of vitamin D status in healthy Nepalese mothers and infants. Methods: 500 randomly selected Nepalese mother and infant pairs were included in a cross-sectional study. Plasma 25(OH)D concentrations were measured by LC-MS/MS and multiple linear regression analyses were used to identify predictors of vitamin D status. Results: Among the infants, the prevalence of vitamin D insufficiency (25(OH)D <50 nmol/L) and deficiency (<30 nmol/L) were 3.6% and 0.6%, respectively, in contrast to 59.8% and 14.0% among their mothers. Infant 25(OH)D concentrations were negatively associated with infant age and positively associated with maternal vitamin D status and body mass index (BMI), explaining 22% of the variability in 25(OH)D concentration. Global solar radiation, maternal age and BMI predicted maternal 25(OH)D concentration, explaining 9.7% of its variability. Conclusion: Age and maternal vitamin D status are the main predictors of vitamin D status in infants in Bhaktapur, Nepal, who have adequate vitamin D status despite poor vitamin D status in their mothers. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)
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Open AccessArticle
Anti-Inflammatory Effects of Vitamin D on Human Immune Cells in the Context of Bacterial Infection
Nutrients 2016, 8(12), 806; https://doi.org/10.3390/nu8120806 - 12 Dec 2016
Cited by 26
Abstract
Vitamin D induces a diverse range of biological effects, including important functions in bone health, calcium homeostasis and, more recently, on immune function. The role of vitamin D during infection is of particular interest given data from epidemiological studies suggesting that vitamin D [...] Read more.
Vitamin D induces a diverse range of biological effects, including important functions in bone health, calcium homeostasis and, more recently, on immune function. The role of vitamin D during infection is of particular interest given data from epidemiological studies suggesting that vitamin D deficiency is associated with an increased risk of infection. Vitamin D has diverse immunomodulatory functions, although its role during bacterial infection remains unclear. In this study, we examined the effects of 1,25(OH)2D3, the active metabolite of vitamin D, on peripheral blood mononuclear cells (PBMCs) and purified immune cell subsets isolated from healthy adults following stimulation with the bacterial ligands heat-killed pneumococcal serotype 19F (HK19F) and lipopolysaccharide (LPS). We found that 1,25(OH)2D3 significantly reduced pro-inflammatory cytokines TNF-α, IFN-γ, and IL-1β as well as the chemokine IL-8 for both ligands (three- to 53-fold), while anti-inflammatory IL-10 was increased (two-fold, p = 0.016) in HK19F-stimulated monocytes. Levels of HK19F-specific IFN-γ were significantly higher (11.7-fold, p = 0.038) in vitamin D-insufficient adults (<50 nmol/L) compared to sufficient adults (>50 nmol/L). Vitamin D also shifted the pro-inflammatory/anti-inflammatory balance towards an anti-inflammatory phenotype and increased the CD14 expression on monocytes (p = 0.008) in response to LPS but not HK19F stimulation. These results suggest that 1,25(OH)2D3 may be an important regulator of the inflammatory response and supports further in vivo and clinical studies to confirm the potential benefits of vitamin D in this context. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)
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Open AccessArticle
Maternal Vitamin D Status and Adverse Birth Outcomes in Children from Rural Western Kenya
Nutrients 2016, 8(12), 794; https://doi.org/10.3390/nu8120794 - 07 Dec 2016
Cited by 11
Abstract
Maternal plasma 25-hydroxyvitamin D (25(OH)D) status and its association with pregnancy outcomes in malaria holoendemic regions of sub-Saharan Africa is poorly defined. We examined this association and any potential interaction with malaria and helminth infections in an ongoing pregnancy cohort study in Kenya. [...] Read more.
Maternal plasma 25-hydroxyvitamin D (25(OH)D) status and its association with pregnancy outcomes in malaria holoendemic regions of sub-Saharan Africa is poorly defined. We examined this association and any potential interaction with malaria and helminth infections in an ongoing pregnancy cohort study in Kenya. The association of maternal plasma 25(OH)D status with pregnancy outcomes and infant anthropometric measurements at birth was determined in a subset of women (n = 63). Binomial and linear regression analyses were used to examine associations between maternal plasma 25(OH)D and adverse pregnancy outcomes. Fifty-one percent of the women had insufficient (<75 nmol/L) and 21% had deficient (<50 nmol/L) plasma 25(OH)D concentration at enrollment. At birth, 74.4% of the infants had insufficient and 30% had deficient plasma 25(OH)D concentrations, measured in cord blood. Multivariate analysis controlling for maternal age and body mass index (BMI) at enrollment and gestational age at delivery found that deficient plasma 25(OH)D levels were associated with a four-fold higher risk of stunting in neonates (p = 0.04). These findings add to the existing literature about vitamin D and its association with linear growth in resource-limited settings, though randomized clinical trials are needed to establish causation. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)
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Open AccessArticle
Vitamin D Status and Efficacy of Vitamin D Supplementation in Atopic Dermatitis: A Systematic Review and Meta-Analysis
Nutrients 2016, 8(12), 789; https://doi.org/10.3390/nu8120789 - 03 Dec 2016
Cited by 26
Abstract
Recent literature has highlighted the possible role of vitamin D in atopic dermatitis (AD), and that vitamin D supplementation might help to treat AD. This study determined the relationship between vitamin D level and AD, and assessed the efficacy of vitamin D supplementation. [...] Read more.
Recent literature has highlighted the possible role of vitamin D in atopic dermatitis (AD), and that vitamin D supplementation might help to treat AD. This study determined the relationship between vitamin D level and AD, and assessed the efficacy of vitamin D supplementation. We searched the MEDLINE, EMBASE, and Cochrane databases up to May 2015. Observational studies and randomized controlled trials were included based on the available data on the serum 25-hydroxyvitamin D (25(OH)D) level and quantified data available for severity assessed using the Scoring Atopic Dermatitis (SCORAD) index or Eczema Area and Severity Index (EASI) score. Compared with healthy controls, the serum 25(OH)D level was lower in the AD patients of all ages (standardized mean difference = −2.03 ng/mL; 95% confidence interval (CI) = −2.52 to −0.78), and predominantly in the pediatric AD patients (standardized mean difference = −3.03 ng/mL; 95% CI = −4.76 to −1.29). In addition, the SCORAD index and EASI score decreased after vitamin D supplementation (standardized mean difference = −5.85; 95% CI = −7.66 to −4.05). This meta-analysis showed that serum vitamin D level was lower in the AD patients and vitamin D supplementation could be a new therapeutic option for AD. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)
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Open AccessArticle
Associations of Vitamin D with Inter- and Intra-Muscular Adipose Tissue and Insulin Resistance in Women with and without Polycystic Ovary Syndrome
Nutrients 2016, 8(12), 774; https://doi.org/10.3390/nu8120774 - 30 Nov 2016
Cited by 4
Abstract
Low vitamin D and insulin resistance are common in polycystic ovary syndrome (PCOS) and associated with higher inter- and intra-muscular adipose tissue (IMAT). We investigated associations between vitamin D, IMAT and insulin resistance in a cross-sectional study of 40 women with PCOS and [...] Read more.
Low vitamin D and insulin resistance are common in polycystic ovary syndrome (PCOS) and associated with higher inter- and intra-muscular adipose tissue (IMAT). We investigated associations between vitamin D, IMAT and insulin resistance in a cross-sectional study of 40 women with PCOS and 30 women without PCOS, and pre- and post-exercise in a 12-week intervention in 16 overweight participants (10 with PCOS and six without PCOS). A non-classical body mass index (BMI) threshold was used to differentiate lean and overweight women (BMI ≥ 27 kg/m2). Measurements included plasma 25-hydroxyvitamin D (25OHD), insulin resistance (glucose infusion rate (GIR; mg/m2/min), fasting glucose and insulin, and glycated haemoglobin), visceral fat, mid-thigh IMAT (computed tomography) and total body fat (dual-energy X-ray absorptiometry). Women with both PCOS and low 25OHD levels had the lowest GIR (all p < 0.05). Higher IMAT was associated with lower 25OHD (B = −3.95; 95% CI −6.86, −1.05) and GIR (B = −21.3; 95% CI −37.16, −5.44) in women with PCOS. Overweight women with pre-exercise 25OHD ≥30 nmol/L had significant increases in GIR, and decreases in total and visceral fat (all p < 0.044), but no associations were observed when stratified by PCOS status. Women with PCOS and low 25OHD levels have increased insulin resistance which may be partly explained by higher IMAT. Higher pre-training 25OHD levels may enhance exercise-induced changes in body composition and insulin resistance in overweight women. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)
Open AccessArticle
Older Swedish Adults with High Self-Perceived Health Show Optimal 25-Hydroxyvitamin D Levels Whereas Vitamin D Status Is Low in Patients with High Disease Burden
Nutrients 2016, 8(11), 717; https://doi.org/10.3390/nu8110717 - 11 Nov 2016
Cited by 3
Abstract
Controversy pervades the definition of adequate and optimal vitamin D status. The Institutes of Medicine have recommended serum 25(OH)D levels above 50 nmol/L based upon evidence related to bone health, but some experts, including the Endocrine Society and International Osteoporosis Foundation, suggest a [...] Read more.
Controversy pervades the definition of adequate and optimal vitamin D status. The Institutes of Medicine have recommended serum 25(OH)D levels above 50 nmol/L based upon evidence related to bone health, but some experts, including the Endocrine Society and International Osteoporosis Foundation, suggest a minimum serum 25(OH)D level of 75 nmol/L to reduce the risk of falls and fractures in older adults. In a cross-sectional study, we compared vitamin D status in people ≥75 years selected from four groups with a frailty phenotype, combined with a control group free from serious illness, and who considered themselves completely healthy. Only 13% of the 169 controls were vitamin D deficient (S-25(OH)D) < 50 nmol/L), in contrast with 49% of orthopedic patients with hip fractures (n = 133), 31% of stroke patients (n = 122), 39% of patients visiting the hospital’s emergency department ≥4 times a year (n = 81), and 75% of homebound adult residents in long-term care nursing homes (n = 51). The mean vitamin D concentration of the healthy control group (74 nmol/L) was similar to a suggested optimal level based on physiological data and mortality studies, and much higher than that of many officially recommended cut-off levels for vitamin D deficiency (<50 nmol/L). The present study provides a basis for planning and implementing public guidelines for the screening of vitamin D deficiency and vitamin D treatment for frail elderly patients. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)
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Open AccessArticle
The Effect of Serum 25-Hydroxyvitamin D Concentrations on Elevated Serum C-Reactive Protein Concentrations in Normal Weight, Overweight and Obese Participants of a Preventive Health Program
Nutrients 2016, 8(11), 696; https://doi.org/10.3390/nu8110696 - 04 Nov 2016
Cited by 2
Abstract
The hypothesized effect of vitamin D on C-reactive protein (CRP) has received substantial attention as a potential means to alleviate the risk for cardiovascular disease. However, observational studies have been inconsistent in their reporting of associations between serum 25-hydroxyvitamin D (25(OH)D) and CRP [...] Read more.
The hypothesized effect of vitamin D on C-reactive protein (CRP) has received substantial attention as a potential means to alleviate the risk for cardiovascular disease. However, observational studies have been inconsistent in their reporting of associations between serum 25-hydroxyvitamin D (25(OH)D) and CRP concentrations, and trials and meta analyses have been inconsistent in their conclusions regarding the effect of vitamin D supplementation on CRP concentrations. These supplementation trials were mostly conducted among patients with more or less inflammatory complications and did not consider potential distinctive effects by weight status. To further our understanding of the potential influences of vitamin D on CRP, we analyzed longitudinal observations of 6755 participants of a preventative health program. On average, serum 25(OH)D concentrations increased from 88.3 to 121.0 nmol/L and those of CRP decreased from 1.7 to 1.6 mg/L between baseline and follow up. Relative to obese participants without temporal increases in 25(OH)D, those who showed improvements of <25, 25–50, 50–75, and more than 75 nmol/L at follow up were 0.57 (95% confidence interval: 0.37–0.88), 0.54 (0.34–0.85), 0.49 (0.30–0.80), and 0.48 (0.29–0.78) times as likely to have elevated CRP concentrations (≥1 mg/L), respectively. These associations were less pronounced and not statistically significant for normal weight and overweight participants. Herewith, the findings suggest that promotion of adequate serum 25(OH)D concentrations among obese individuals along with healthy lifestyles may alleviate the public health burden associated with cardiovascular disease. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)
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Open AccessArticle
Maternal Dietary Vitamin D Does Not Program Systemic Inflammation and Bone Health in Adult Female Mice Fed an Obesogenic Diet
Nutrients 2016, 8(11), 675; https://doi.org/10.3390/nu8110675 - 26 Oct 2016
Cited by 6
Abstract
Obesity is associated with systemic inflammation and impaired bone health. Vitamin D regulates bone metabolism, and has anti-inflammatory properties and epigenetic effects. We showed that exposure to high dietary vitamin D during pregnancy and lactation beneficially programs serum concentration of lipopolysaccharide (LPS) and [...] Read more.
Obesity is associated with systemic inflammation and impaired bone health. Vitamin D regulates bone metabolism, and has anti-inflammatory properties and epigenetic effects. We showed that exposure to high dietary vitamin D during pregnancy and lactation beneficially programs serum concentration of lipopolysaccharide (LPS) and bone structure in male offspring fed an obesogenic diet. Here we assessed if this effect is also apparent in females. C57BL/6J dams were fed AIN93G diet with high (5000 IU/kg diet) or low (25 IU/kg diet) vitamin D during pregnancy and lactation. Post-weaning, female offspring remained on their respective vitamin D level or were switched and fed a high fat and sucrose diet (44.2% fat, 19.8% sucrose) until age seven months when glucose response, adiposity, serum LPS, and bone mineral, trabecular and cortical structure, and biomechanical strength properties of femur and vertebra were assessed. There was no evidence for a programming effect of vitamin D for any outcomes. However, females exposed to a high vitamin D diet post-weaning had higher bone mineral content (p = 0.037) and density (p = 0.015) of lumbar vertebra. This post-weaning benefit suggests that in females, bone mineral accrual but not bone structure is compromised with low vitamin D status in utero until weaning in an obesogenic context. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)
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Open AccessArticle
Vitamin D Intake and Serum 25-Hydroxyvitamin D Levels in Korean Adults: Analysis of the 2009 Korea National Health and Nutrition Examination Survey (KNHANES IV-3) Using a Newly Established Vitamin D Database
Nutrients 2016, 8(10), 610; https://doi.org/10.3390/nu8100610 - 29 Sep 2016
Cited by 11
Abstract
Vitamin D is important for maintaining bone health and may prevent various diseases (i.e., cardiovascular disease and cancer). The aim of this study was to estimate vitamin D intakes of Korean adults using the Korea National Health and Nutrition Examination Survey (KNHANES, 2009) [...] Read more.
Vitamin D is important for maintaining bone health and may prevent various diseases (i.e., cardiovascular disease and cancer). The aim of this study was to estimate vitamin D intakes of Korean adults using the Korea National Health and Nutrition Examination Survey (KNHANES, 2009) data and a newly established vitamin D database. KNHANES (2009) participants (n = 4541; 2021 men; 2520 women) aged ≥20 years were included. Dietary vitamin D intake, serum 25-hydroxyvitamin D (25(OH)D), and the relationship between vitamin D intake and serum 25(OH)D were evaluated. In men and women, vitamin D intakes were 4.00 ± 0.17 µg/day and 2.6 ± 0.1 µg/day respectively, and serum 25(OH)D concentrations were 19.78 ± 0.33 ng/mL and 17.10 ± 0.26 ng/mL respectively. Serum 25(OH)D concentrations of men aged <50 years and women aged >20 years were under 20 ng/mL. After adjusting for confounding factors, the positive relationship between vitamin D intake and serum 25(OH)D was observed in total subjects (p < 0.05), excluding participants ≥50 years old. The main food sources for vitamin D among Korean adults were fish/shellfish (71.34%) and egg (14.89%). Korean adults should increase their serum 25(OH)D concentrations by increasing vitamin D intake. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)
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Open AccessArticle
The VITAH Trial—Vitamin D Supplementation and Cardiac Autonomic Tone in Patients with End-Stage Kidney Disease on Hemodialysis: A Blinded, Randomized Controlled Trial
Nutrients 2016, 8(10), 608; https://doi.org/10.3390/nu8100608 - 28 Sep 2016
Cited by 4
Abstract
End-stage kidney disease (ESKD) patients are at increased cardiovascular risk. Vitamin D deficiency is associated with depressed heart rate variability (HRV), a risk factor depicting poor cardiac autonomic tone and risk of cardiovascular death. Vitamin D deficiency and depressed HRV are highly prevalent [...] Read more.
End-stage kidney disease (ESKD) patients are at increased cardiovascular risk. Vitamin D deficiency is associated with depressed heart rate variability (HRV), a risk factor depicting poor cardiac autonomic tone and risk of cardiovascular death. Vitamin D deficiency and depressed HRV are highly prevalent in the ESKD population. We aimed to determine the effects of oral vitamin D supplementation on HRV ((low frequency (LF) to high frequency (HF) spectral ratio (LF:HF)) in ESKD patients on hemodialysis. Fifty-six subjects with ESKD requiring hemodialysis were recruited from January 2013–March 2015 and randomized 1:1 to either conventional (0.25 mcg alfacalcidol plus placebo 3×/week) or intensive (0.25 mcg alfacalcidol 3×/week plus 50,000 international units (IU) ergocalciferol 1×/week) vitamin D for six weeks. The primary outcome was the change in LF:HF. There was no difference in LF:HF from baseline to six weeks for either vitamin D treatment (conventional: p = 0.9 vs. baseline; intensive: p = 0.07 vs. baseline). However, participants who remained vitamin D-deficient (25-hydroxyvitamin D < 20 ng/mL) after treatment demonstrated an increase in LF:HF (conventional: n = 13, ∆LF:HF: 0.20 ± 0.06, p < 0.001 vs. insufficient and sufficient vitamin D groups; intensive: n = 8: ∆LF:HF: 0.15 ± 0.06, p < 0.001 vs. sufficient vitamin D group). Overall, six weeks of conventional or intensive vitamin D only augmented LF:HF in ESKD subjects who remained vitamin D-deficient after treatment. Our findings potentially suggest that while activated vitamin D, with or without additional nutritional vitamin D, does not appear to improve cardiac autonomic tone in hemodialysis patients with insufficient or sufficient baseline vitamin D levels, supplementation in patients with severe vitamin D deficiency may improve cardiac autonomic tone in this higher risk sub-population of ESKD. Trial Registration: ClinicalTrials.gov, NCT01774812. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)
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Open AccessArticle
Parental Encouragement of Healthy Lifestyles for Their Children and Personally Caring about Healthy Lifestyles Is Positively Associated with Children Using Vitamin D Supplements
Nutrients 2016, 8(10), 596; https://doi.org/10.3390/nu8100596 - 24 Sep 2016
Cited by 1
Abstract
Supplement users have better vitamin D status, and parenting is key to promoting a child’s healthy behaviours. We examined the association of parental encouragement of and caring about healthy lifestyles with children’s use of vitamin D supplements and multivitamins. A provincially representative sample [...] Read more.
Supplement users have better vitamin D status, and parenting is key to promoting a child’s healthy behaviours. We examined the association of parental encouragement of and caring about healthy lifestyles with children’s use of vitamin D supplements and multivitamins. A provincially representative sample of grade 5 students (n = 2686; 10–11 years) and their parents across the province of Alberta, Canada, was surveyed in 2014. Students were asked about use of multivitamins and/or vitamin D supplements. Parents were asked whether they cared about and encouraged healthy lifestyles. Mixed effect multiple logistic regression identified the association of parental responses with children’s use of supplements; 29% and 54% of children took vitamin D supplements and multivitamins, respectively. They were more likely to take vitamin D supplements if their parents cared ‘very much’ vs. ‘not at all/a little bit’ about eating healthy foods (OR = 1.43; 95% CI = 1.08, 1.89), cared ‘quite a lot’ (OR = 1.55; 95% CI = 1.17, 2.04) and ‘very much’ (OR = 1.67; 95% CI = 1.26, 2.21) vs. ‘not at all/a little bit’ about physical activity, and encouraged ‘very much’ vs. ‘not at all/a little bit’ their children to eat healthy foods (OR = 1.51; 95% CI = 1.05, 2.17). Children whose parents personally cared for eating healthy foods were more likely to take multivitamins (‘quite a lot’ and ‘very much’ compared to ‘not at all/a little bit’ (OR = 1.60; 95% CI = 1.13, 2.28 and OR = 1.46; 95% CI = 1.04, 2.06, respectively). Education and parental encouragement of healthy lifestyles should be part of the public health initiatives to promote supplementation of vitamin D among children. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)
Open AccessArticle
Seasonal Epidemiology of Serum 25-Hydroxyvitamin D Concentrations among Healthy Adults Living in Rural and Urban Areas in Mongolia
Nutrients 2016, 8(10), 592; https://doi.org/10.3390/nu8100592 - 23 Sep 2016
Cited by 9
Abstract
Many factors put Mongolians at risk of vitamin D deficiency. Despite low levels observed in Mongolian children and pregnant women, there are few data published on the vitamin D status of non-pregnant adults. Between summer 2011 and winter 2013, paired summer and winter [...] Read more.
Many factors put Mongolians at risk of vitamin D deficiency. Despite low levels observed in Mongolian children and pregnant women, there are few data published on the vitamin D status of non-pregnant adults. Between summer 2011 and winter 2013, paired summer and winter blood samples were collected from 320 healthy men and women (20–58 years) living in eight Mongolian provinces. Mean serum 25(OH)D concentrations were 22.5 ng/mL (95% CI: 14.5, 32.5) in summer and 7.7 ng/mL (95% CI: 4.6, 10.8) in winter, with a distribution (<10/10–20/20–30/≥30 ng/mL) of 3.1%/39.3%/39.6%/17.9% in summer and 80.1%/19.5%/0.3%/0.0% in winter. Residents of the capital, Ulaanbaatar, had lower levels in both seasons than any other region, whereas residents of the Gobi desert had the highest. In summer, indoor workers had significantly lower levels than outdoor workers (−2.3 ng/mL; 95% CI: −4.1, −5.7) while levels in males exceeded those in females (4.0 ng/mL; 95% CI: 2.3, 5.7). Effects of region, occupation, and sex were also significant in multivariable regression. In conclusion, Mongolian adults had extremely low serum 25(OH)D, particularly in winter, when 80.1% had concentrations below 10 ng/mL. These results indicate a need for effective vitamin D interventions for the Mongolian adult population, particularly among women and residents of Ulaanbaatar. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)
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Open AccessArticle
Relationship between Vitamin D Status and Autonomic Nervous System Activity
Nutrients 2016, 8(9), 565; https://doi.org/10.3390/nu8090565 - 13 Sep 2016
Cited by 5
Abstract
Vitamin D deficiency is associated with increased arterial stiffness. However, the mechanisms underlying this association have not been clarified. The aim was to investigate whether changes in autonomic nervous system activity could underlie an association between 25 hydroxy vitamin D and arterial stiffness. [...] Read more.
Vitamin D deficiency is associated with increased arterial stiffness. However, the mechanisms underlying this association have not been clarified. The aim was to investigate whether changes in autonomic nervous system activity could underlie an association between 25 hydroxy vitamin D and arterial stiffness. A total of 49 subjects (age = 60 ± 8 years, body mass index = 26.7 ± 4.6 kg/m2, 25 hydroxy vitamin D = 69 ± 22 nmol/L) underwent measurements of pulse wave velocity (PWV) and augmentation index (AIx), spontaneous baroreflex sensitivity, plasma metanephrines and 25 hydroxy vitamin D. Subjects with 25 hydroxy vitamin D ≤ 50 nmol/L were restudied after 200,000 International Units 25 hydroxy vitamin D. Plasma metanephrine was positively associated with AIx (p = 0.02) independent of age, sex, smoking and cholesterol and negatively associated with 25 hydroxy vitamin D (p = 0.002) independent of age, sex and season. In contrast, there was no association between baroreflex sensitivity and 25 hydroxy vitamin D (p = 0.54). Treatment with vitamin D increased 25 hydroxy vitamin D from 43 ± 5 to 96 ± 24 nmol/L (p < 0.0001) but there was no significant change in plasma metanephrine (115 ± 25 vs. 99 ± 39 pmol/L, p = 0.12). We conclude that as plasma metanephrine was negatively associated with 25 hydroxy vitamin D and positively with AIx, it could mediate an association between these two variables. This hypothesis should be tested in larger interventional studies. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)
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Open AccessArticle
Seasonal Changes in Vitamin D-Effective UVB Availability in Europe and Associations with Population Serum 25-Hydroxyvitamin D
Nutrients 2016, 8(9), 533; https://doi.org/10.3390/nu8090533 - 30 Aug 2016
Cited by 46
Abstract
Low vitamin D status is common in Europe. The major source of vitamin D in humans is ultraviolet B (UVB)-induced dermal synthesis of cholecalciferol, whereas food sources are believed to play a lesser role. Our objectives were to assess UVB availability (Jm−2 [...] Read more.
Low vitamin D status is common in Europe. The major source of vitamin D in humans is ultraviolet B (UVB)-induced dermal synthesis of cholecalciferol, whereas food sources are believed to play a lesser role. Our objectives were to assess UVB availability (Jm−2) across several European locations ranging from 35° N to 69° N, and compare these UVB data with representative population serum 25-hydroxyvitamin D (25(OH)D) data from Ireland (51–54° N), Iceland (64° N) and Norway (69° N), as exemplars. Vitamin D-effective UVB availability was modelled for nine European countries/regions using a validated UV irradiance model. Standardized serum 25(OH)D data was accessed from the EC-funded ODIN project. The results showed that UVB availability decreased with increasing latitude (from 35° N to 69° N), while all locations exhibited significant seasonal variation in UVB. The UVB data suggested that the duration of vitamin D winters ranged from none (at 35° N) to eight months (at 69° N). The large seasonal fluctuations in serum 25(OH)D in Irish adults was much dampened in Norwegian and Icelandic adults, despite considerably lower UVB availability at these northern latitudes but with much higher vitamin D intakes. In conclusion, increasing the vitamin D intake can ameliorate the impact of low UVB availability on serum 25(OH)D status in Europe. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)
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Open AccessArticle
The Association of Vitamin D Status with Dyslipidaemia and Biomarkers of Endothelial Cell Activation in Older Australians
Nutrients 2016, 8(8), 457; https://doi.org/10.3390/nu8080457 - 28 Jul 2016
Cited by 4
Abstract
Background/Aims: Vitamin D has been investigated for many non-skeletal effects. The objective of this study was to determine whether circulating lipids, systemic inflammation, and biomarkers of endothelial cell activation varied with the vitamin D status of older Australians. Methods: One hundred and one [...] Read more.
Background/Aims: Vitamin D has been investigated for many non-skeletal effects. The objective of this study was to determine whether circulating lipids, systemic inflammation, and biomarkers of endothelial cell activation varied with the vitamin D status of older Australians. Methods: One hundred and one participants were proportionately and randomly sampled across tertiles of 25 hydroxy vitamin D (25(OH)D) from a larger cohort of free living older adults (T1 median = 97; T2 median = 74.5; T3 median = 56.8 nmol/L). Overnight fasting blood samples were assayed for 25(OH)D, parathyroid hormone (PTH), insulin, triacylglycerol (TAG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C). Markers of systemic inflammation (high sensitivity C-reactive protein (hsCRP), tumour necrosis factor-α (TNF-α)) and endothelial activation (hepatocyte growth factor (HGF), P-selectin and soluble vascular cell adhesion molecule (sVCAM), soluble intracellular adhesion molecule (sICAM)) were determined. A general linear model multivariate analysis with a backward elimination procedure was performed. Results: Eighty-three participants (48 women, 35 men), aged 65 ± 7.7 years, BMI 28 ± 4.5 kg/m2, with complete data were analyzed. The final parsimonious model controlled for age, gender, BMI, and McAuley’s index, but excluded season, medications, and PTH. There were significant differences across 25(OH)D tertiles in TC (T1 < T3, p = 0.003; T2 < T3, p = 0.001), LDL-C (T1 < T3, p = 0.005; T2 < T3, p = 0.001), TAG (T2 < T3, p = 0.026), HGF (T1 > T3, p = 0.009) and sVCAM (T1 > T3, P = 0.04). Conclusions: Higher vitamin D status may protect the endothelium through reduced dyslipidaemia and increased HGF. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)

Review

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Open AccessReview
Association between Circulating Vitamin D Level and Urolithiasis: A Systematic Review and Meta-Analysis
Nutrients 2017, 9(3), 301; https://doi.org/10.3390/nu9030301 - 18 Mar 2017
Cited by 11
Abstract
Many studies compared the serum/plasma 1,25 dihydroxyvitamin D3 (1,25(OH)2D) and 25 hydroxyvitamin D3 (25(OH)D) between people with and without nephrolithiasis, and their results were conflicting. After systematically searching PubMed, Web of Science, The Cochrane Library, CNKI, and the Wanfang [...] Read more.
Many studies compared the serum/plasma 1,25 dihydroxyvitamin D3 (1,25(OH)2D) and 25 hydroxyvitamin D3 (25(OH)D) between people with and without nephrolithiasis, and their results were conflicting. After systematically searching PubMed, Web of Science, The Cochrane Library, CNKI, and the Wanfang Database, we conducted a meta-analysis. Thirty-two observational studies involving 23,228 participants were included. Meta-analysis of these studies showed that of stone formers (SFs), calcium SFs had significantly higher concentrations of 1,25(OH)2D (weighted mean difference (WMD), 10.19 pg/mL; 95% confidence interval (CI), 4.31–16.07; p = 0.0007 and WMD, 11.28 pg/mL; 95% CI, 4.07–18.50; p = 0.002, respectively) than non-stone formers, while the levels of 25(OH)D (WMD, 0.88 ng/mL; 95% CI, −1.04–2.80; p = 0.37 and WMD, −0.63 ng/mL; 95% CI, −2.72–1.47; p = 0.56, respectively) are similar. Compared with controls and normocalciuria SFs, hypercalciuria SFs had increased circulating 1,25(OH)2D (WMD, 9.41 pg/mL; 95% CI, 0.15–18.67; p = 0.05 and WMD, 2.75 pg/mL; 95% CI, −0.20–5.69; p = 0.07, respectively) and markedly higher 25(OH)D (WMD, 5.02 ng/mL; 95% CI, 0.99–9.06; p = 0.01 and WMD, 5.02 ng/mL; 95% CI, 2.14–7.90; p = 0.0006, respectively). Normocalciuria SFs had elevated 1,25(OH)2D level (WMD, 6.85 pg/mL; 95% CI, −5.00–18.71; p = 0.26) and comparable 25(OH)D (WMD, 0.94 ng/mL; 95% CI, −3.55–5.43; p = 0.68). Sensitivity analysis generated similar results. Current evidence suggests that increased circulating 1,25(OH)2D is associated with urinary stones and a higher level of circulating 25(OH)D is significantly associated with hypercalciuria urolithiasis. Further studies are still needed to reconfirm and clarify the role of vitamin D in the pathogenesis of stones. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)
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Open AccessReview
Serum Parathyroid Hormone Responses to Vitamin D Supplementation in Overweight/Obese Adults: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Nutrients 2017, 9(3), 241; https://doi.org/10.3390/nu9030241 - 06 Mar 2017
Cited by 14
Abstract
Obesity is often associated with vitamin D deficiency and secondary hyperparathyroidism. Vitamin D supplementation typically leads to the reductions in serum parathyroid hormone (PTH) levels, as shown in normal weight individuals. Meanwhile, the dose of vitamin D supplementation for the suppression of PTH [...] Read more.
Obesity is often associated with vitamin D deficiency and secondary hyperparathyroidism. Vitamin D supplementation typically leads to the reductions in serum parathyroid hormone (PTH) levels, as shown in normal weight individuals. Meanwhile, the dose of vitamin D supplementation for the suppression of PTH may differ in overweight and obese adults. We conducted a systematic review and meta-analysis of randomized controlled trials to determine the dose of vitamin D supplementation required to suppress PTH levels in overweight/obese individuals. We identified 18 studies that examined overweight or obese healthy adults who were supplemented with varying doses of vitamin D3. The primary outcomes examined were changes in PTH and serum 25-hydroxyvitamin D (25OHD) levels from baseline to post-treatment. The results of the meta-analysis showed that there was a significant treatment effect of vitamin D supplementation on PTH, total standardized mean difference (SMD) (random effects) = −0.38 (95% CI = −0.56 to −0.20), t = −4.08, p < 0.001. A significant treatment effect of vitamin D supplementation was also found on 25OHD, total SMD (random effects) = 2.27 (95% CI = 1.48 to 3.06) t = 5.62, p < 0.001. Data from available clinical trials that supplemented adults with D3 ranging from 400 IU to 5714 IU, showed that 1000 IU of vitamin D supplementation best suppressed serum PTH levels, total SMD = −0.58, while vitamin D supplementation with 4000 IU showed the greatest increase in serum 25OH levels. Vitamin D and calcium supplementation of 700 IU and 500 mg, respectively, also showed a significant treatment effect on the suppression of PTH with a total SMD = −5.30 (95% CI = −9.72 to −0.88). In conclusion, the meta analysis of available clinical trials indicates that 1000 IU vitamin D supplementation can suppress serum PTH levels, while 4000 IU of vitamin D was associated with the largest increase in serum 25OHD levels in the overweight and obese population. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)
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Open AccessReview
Effects of 1,25(OH)2D3 on Cancer Cells and Potential Applications in Combination with Established and Putative Anti-Cancer Agents
Nutrients 2017, 9(1), 87; https://doi.org/10.3390/nu9010087 - 23 Jan 2017
Cited by 9
Abstract
The diverse effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the bio-active form of vitamin D, on cancer cell metabolism and proliferation has made it an interesting candidate as a supporting therapeutic option in cancer treatment. An important strategy in cancer [...] Read more.
The diverse effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the bio-active form of vitamin D, on cancer cell metabolism and proliferation has made it an interesting candidate as a supporting therapeutic option in cancer treatment. An important strategy in cancer therapy is the use of combination chemotherapy to overcome drug resistance associated with numerous anti-cancer agents and to provide better means of avoiding undesirable side effects. This complex strategy is widely adopted by oncologists and several established “cocktails” of chemotherapeutics are routinely administered to cancer patients. Among the principles followed in designing such treatment regimens is the use of drugs with different mechanisms of action to overcome the issue of tumor heterogeneity and to evade resistance. In light of the profound and diverse effects of 1,25(OH)2D3 reported by in vitro and in vivo studies, we discuss how these effects could support the use of this molecule in combination with “classical” cytotoxic drugs, such as platins and anti-metabolites, for the treatment of solid and hematological tumors. We also examine recent evidence supporting synergistic activities with other promising anti-cancer drug candidates, and postulate mechanisms through which 1,25(OH)2D3 may help evade chemoresistance. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)
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Open AccessReview
“English Disease”: Historical Notes on Rickets, the Bone–Lung Link and Child Neglect Issues
Nutrients 2016, 8(11), 722; https://doi.org/10.3390/nu8110722 - 15 Nov 2016
Cited by 10
Abstract
Nutritional or classical rickets (here labeled as “rickets”) is a worldwide disease involving mostly infants and young children having inadequate sunlight exposure, often associated with a low dietary intake of Vitamin D. Rickets targets all layers of society independently of economic status with [...] Read more.
Nutritional or classical rickets (here labeled as “rickets”) is a worldwide disease involving mostly infants and young children having inadequate sunlight exposure, often associated with a low dietary intake of Vitamin D. Rickets targets all layers of society independently of economic status with historical information spanning more than two millennia. Vitamin D is critical for the absorption of calcium and prevention of rickets in children as well as osteomalacia in adults. The initial and misleading paradigm of the 19th and 20th centuries that rickets may have been the consequence of infection has been, indeed, reversed following the identification of the Vitamin D molecule’s important role in the function of the immune system. Although traditionally considered limited to osteopathology, Vitamin D deficiency is now known to be linked to infection, inflammation, and carcinogenesis. In this review, we consider the key historical (Whistler, pre-Whistler and post-Whistler descriptors) and social facts around rickets; highlight the osteo-pathological features of rickets and the pathology of the upper and lower respiratory tract, stressing the fact that lungs remain the main secondary organ affected by Vitamin D deficiency; and emphasize the public health role in identifying the cases of child neglect or abuse based on the evaluation of the costochondral region. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)
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Open AccessReview
Crucial Role of Vitamin D in the Musculoskeletal System
Nutrients 2016, 8(6), 319; https://doi.org/10.3390/nu8060319 - 01 Jun 2016
Cited by 53
Abstract
Vitamin D is well known to exert multiple functions in bone biology, autoimmune diseases, cell growth, inflammation or neuromuscular and other immune functions. It is a fat-soluble vitamin present in many foods. It can be endogenously produced by ultraviolet rays from sunlight when [...] Read more.
Vitamin D is well known to exert multiple functions in bone biology, autoimmune diseases, cell growth, inflammation or neuromuscular and other immune functions. It is a fat-soluble vitamin present in many foods. It can be endogenously produced by ultraviolet rays from sunlight when the skin is exposed to initiate vitamin D synthesis. However, since vitamin D is biologically inert when obtained from sun exposure or diet, it must first be activated in human beings before functioning. The kidney and the liver play here a crucial role by hydroxylation of vitamin D to 25-hydroxyvitamin D in the liver and to 1,25-dihydroxyvitamin D in the kidney. In the past decades, it has been proven that vitamin D deficiency is involved in many diseases. Due to vitamin D’s central role in the musculoskeletal system and consequently the strong negative impact on bone health in cases of vitamin D deficiency, our aim was to underline its importance in bone physiology by summarizing recent findings on the correlation of vitamin D status and rickets, osteomalacia, osteopenia, primary and secondary osteoporosis as well as sarcopenia and musculoskeletal pain. While these diseases all positively correlate with a vitamin D deficiency, there is a great controversy regarding the appropriate vitamin D supplementation as both positive and negative effects on bone mineral density, musculoskeletal pain and incidence of falls are reported. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)
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Other

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Open AccessCommentary
In Pursuit of Vitamin D in Plants
Nutrients 2017, 9(2), 136; https://doi.org/10.3390/nu9020136 - 13 Feb 2017
Cited by 5
Abstract
Vitamin D deficiency is a global concern. Much research has concentrated on the endogenous synthesis of vitamin D in human skin following exposure to ultraviolet‐B radiation (UV‐B, 280–315 nm). In many regions of the world there is insufficient UV‐B radiation during winter months [...] Read more.
Vitamin D deficiency is a global concern. Much research has concentrated on the endogenous synthesis of vitamin D in human skin following exposure to ultraviolet‐B radiation (UV‐B, 280–315 nm). In many regions of the world there is insufficient UV‐B radiation during winter months for adequate vitamin D production, and even when there is sufficient UV‐B radiation, lifestyles and concerns about the risks of sun exposure may lead to insufficient exposure and to vitamin D deficiency. In these situations, dietary intake of vitamin D from foods or supplements is important for maintaining optimal vitamin D status. Some foods, such as fatty fish and fish liveroils, certain meats, eggs, mushrooms, dairy, and fortified foods, can provide significant amounts of vitamin D when considered cumulatively across the diet. However, little research has focussed on assessing edible plant foods for potential vitamin D content. The biosynthesis of vitamin D in animals, fungi and yeasts is well established; it is less well known that vitamin D is also biosynthesised in plants. Research dates back to the early 1900s, beginning with in vivo experiments showing the anti‐rachitic activity of plants consumed by animals with induced rickets, and in vitro experiments using analytical methods with limited sensitivity. The most sensitive, specific and reliable method for measuring vitamin D and its metabolites is by liquid chromatography tandem mass spectrometry (LC‐MS/MS). These assays have only recently been customised to allow measurement in foods, including plant materials. This commentary focuses on the current knowledge and research gaps around vitamin D in plants, and the potential of edible plants as an additional source of vitamin D for humans. Full article
(This article belongs to the Special Issue Vitamin D: Current Issues and New Perspectives)
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