Special Issue "Changing Times for Vitamin D and Health"

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

Deadline for manuscript submissions: closed (15 March 2018).

Special Issue Editors

Prof. Dr. Robyn Lucas
E-Mail Website
Guest Editor
ANU College of Medicine, Biology and Environment, Australian National University
Interests: environmental effects on immune function; epidemiology; developmental origins of health and disease; autoimmune diseases; climate change; ultraviolet radiation; vitamin D
Special Issues and Collections in MDPI journals
Dr. Lucinda Black
E-Mail Website
Guest Editor
School of Public Health, Curtin University, PO Box U1987, Perth, WA 6845, Australia
Tel. +61-8-9266-2523
Interests: vitamin D; nutritional epidemiology; diet and risk of multiple sclerosis
Dr. Rachel Neale
E-Mail Website
Co-Guest Editor
1. QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia
2. Royal Brisbane Hospital, Brisbane, QLD 4029, Australia
Interests: cancer epidemiology; pancreatic cancer; skin cancer; ultraviolet radiation; vitamin D

Special Issue Information

Dear Colleagues,

Adequate vitamin D is essential to human health. Over the last twenty years, there has been an explosion of research into the possible health benefits of maintaining higher and higher blood levels of vitamin D. This has been accompanied by controversy around the level that should be considered “adequate”. This level is critical to determining the prevalence of vitamin D deficiency, and thus whether the “epidemic of vitamin D deficiency” is real. More recently, the focus has returned to the well-accepted requirement of vitamin D for bone health, as clinical trials do not demonstrate major benefits of vitamin D supplementation for amelioration of a range of non-bone disease outcomes. However, deficits in the design of clinical trials to date – particularly that the participants have not been vitamin D deficient at baseline – mean that there is still some doubt about links between vitamin D and many health outcomes. This Special Issue will explore the most recent research and critically evaluate the evidence.

Keywords

  • vitamin D
  • human health
  • immunology
  • infections
  • cardiovascular disease
  • diabetes
  • cancer

Published Papers (22 papers)

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Research

Jump to: Review

Open AccessArticle
Vitamin D Content of Australian Native Food Plants and Australian-Grown Edible Seaweed
Nutrients 2018, 10(7), 876; https://doi.org/10.3390/nu10070876 - 06 Jul 2018
Cited by 2
Abstract
Vitamin D has previously been quantified in some plants and algae, particularly in leaves of the Solanaceae family. We measured the vitamin D content of Australian native food plants and Australian-grown edible seaweed. Using liquid chromatography with triple quadrupole mass spectrometry, 13 samples [...] Read more.
Vitamin D has previously been quantified in some plants and algae, particularly in leaves of the Solanaceae family. We measured the vitamin D content of Australian native food plants and Australian-grown edible seaweed. Using liquid chromatography with triple quadrupole mass spectrometry, 13 samples (including leaf, fruit, and seed) were analyzed in duplicate for vitamin D2, vitamin D3, 25-hydroxyvitamin D2, and 25-hydroxyvitamin D3. Five samples contained vitamin D2: raw wattleseed (Acacia victoriae) (0.03 µg/100 g dry weight (DW)); fresh and dried lemon myrtle (Backhousia citriodora) leaves (0.03 and 0.24 µg/100 g DW, respectively); and dried leaves and berries of Tasmanian mountain pepper (Tasmannia lanceolata) (0.67 and 0.05 µg/100 g DW, respectively). Fresh kombu (Lessonia corrugata) contained vitamin D3 (0.01 µg/100 g DW). Detected amounts were low; however, it is possible that exposure to ultraviolet radiation may increase the vitamin D content of plants and algae if vitamin D precursors are present. Full article
(This article belongs to the Special Issue Changing Times for Vitamin D and Health)
Open AccessFeature PaperArticle
Meeting Vitamin D Requirements in White Caucasians at UK Latitudes: Providing a Choice
Nutrients 2018, 10(4), 497; https://doi.org/10.3390/nu10040497 - 17 Apr 2018
Cited by 9
Abstract
The body gains vitamin D through both oral intake (diet/supplementation) and synthesis in skin upon exposure to ultraviolet radiation (UVR). Sun exposure is the major source for most people even though sun exposure is complex and limited by climate and culture. We aimed [...] Read more.
The body gains vitamin D through both oral intake (diet/supplementation) and synthesis in skin upon exposure to ultraviolet radiation (UVR). Sun exposure is the major source for most people even though sun exposure is complex and limited by climate and culture. We aimed to quantify the sun exposure required to meet vitamin D targets year-round and determine whether this can be safely achieved in a simply defined manner in the UK as an alternative to increasing vitamin D oral intake. Data from observation (sun exposure, diet, and vitamin D status) and UVR intervention studies performed with white Caucasian adults were combined with modeled all-weather UVR climatology. Daily vitamin D effective UVR doses (all-weather) were calculated across the UK based on ten-year climatology for pre-defined lunchtime exposure regimes. Calculations then determined the time necessary to spend outdoors for the body to gain sufficient vitamin D levels for year-round needs without being sunburnt under differing exposure scenarios. Results show that, in specified conditions, white Caucasians across the UK need nine minutes of daily sunlight at lunchtime from March to September for 25(OH)D levels to remain ≥25 nmol/L throughout the winter. This assumes forearms and lower legs are exposed June-August, while in the remaining, cooler months only hands and face need be exposed. Exposing only the hands and face throughout the summer does not meet requirements. Full article
(This article belongs to the Special Issue Changing Times for Vitamin D and Health)
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Open AccessFeature PaperArticle
Colour Counts: Sunlight and Skin Type as Drivers of Vitamin D Deficiency at UK Latitudes
Nutrients 2018, 10(4), 457; https://doi.org/10.3390/nu10040457 - 07 Apr 2018
Cited by 14
Abstract
Sunlight exposure, with resulting cutaneous synthesis, is a major source of vitamin D for many, while dietary intake is low in modern diets. The constitutive pigment in skin determines skin type, observed as white, brown, or black skin. The melanin pigment absorbs ultraviolet [...] Read more.
Sunlight exposure, with resulting cutaneous synthesis, is a major source of vitamin D for many, while dietary intake is low in modern diets. The constitutive pigment in skin determines skin type, observed as white, brown, or black skin. The melanin pigment absorbs ultraviolet radiation (UVR) and protects underlying skin from damage caused by UVR. It also reduces the UVR available for vitamin D synthesis in the skin. It has been shown that the white-skinned population of the UK are able to meet their vitamin D needs with short, daily lunchtime exposures to sunlight. We have followed the same methodology, based on a 10-year UK all-weather UVR climatology, observation (sun exposure, diet, vitamin D status), and UVR intervention studies with Fitzpatrick skin type V (brown) adults, to determine whether sunlight at UK latitudes could provide an adequate source of vitamin D for this section of the population. Results show that to meet vitamin D requirements, skin type V individuals in the UK need ~25 min daily sunlight at lunchtime, from March to September. This makes several assumptions, including that forearms and lower legs are exposed June–August; only exposing hands and face at this time is inadequate. For practical and cultural reasons, enhanced oral intake of vitamin D should be considered for this population. Full article
(This article belongs to the Special Issue Changing Times for Vitamin D and Health)
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Open AccessArticle
Does Vitamin D Deficiency Affect the Immunogenic Responses to Influenza Vaccination? A Systematic Review and Meta-Analysis
Nutrients 2018, 10(4), 409; https://doi.org/10.3390/nu10040409 - 26 Mar 2018
Cited by 1
Abstract
Influenza virus infection is a major global public health problem, and the efficacy of influenza vaccination is not satisfactory. Vitamin D is involved in many immune-mediated inflammatory processes. The impact of vitamin D levels on the immunogenic response to influenza vaccination is not [...] Read more.
Influenza virus infection is a major global public health problem, and the efficacy of influenza vaccination is not satisfactory. Vitamin D is involved in many immune-mediated inflammatory processes. The impact of vitamin D levels on the immunogenic response to influenza vaccination is not clear. We performed a comprehensive literature search and systematic review of studies that investigated vitamin D and influenza vaccination. Data pertaining to study population, vaccine components, vitamin D levels, and immunogenic response were analyzed. Nine studies, with a combined study population of 2367 patients, were included in the systematic review. Four studies were included in the meta-analysis to investigate the influence of vitamin D deficiency (VDD) on the seroprotection (SP) rates and seroconversion (SC) rates following influenza vaccination. We found no significant association between vitamin D level and the immunogenic response to influenza vaccination. However, strain-specific differences may exist. We observed lower SP rates of influenza A virus subtype H3N2 (A/H3N2) and B strain in VDD patients than patients with normal vitamin D levels (A/H3N2: 71.8% vs. 80.1%, odds ratio (OR): 0.63, 95% confidence interval (CI): 0.43–0.91, p = 0.01; B strain: 69.6% vs. 76.4%, OR: 0.68, 95% CI: 0.5–0.93, p = 0.01). However, the SP rates of A/H1N1 and SC rates of all three strains were not significantly different in VDD and control groups. In conclusion, no association was observed between VDD and immunogenic response to influenza vaccination. Full article
(This article belongs to the Special Issue Changing Times for Vitamin D and Health)
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Open AccessArticle
Randomised Controlled Trial Comparing Daily Versus Depot Vitamin D3 Therapy in 0–16-Year-Old Newly Settled Refugees in Western Australia Over a Period of 40 Weeks
Nutrients 2018, 10(3), 348; https://doi.org/10.3390/nu10030348 - 13 Mar 2018
Cited by 4
Abstract
Vitamin D deficiency is highly prevalent in newly settled refugees in Western Australia (WA). If adherence to daily vitamin D therapy is problematic, depot therapy is a therapeutic alternative. The aim of this study was to compare daily versus depot treatment and factors [...] Read more.
Vitamin D deficiency is highly prevalent in newly settled refugees in Western Australia (WA). If adherence to daily vitamin D therapy is problematic, depot therapy is a therapeutic alternative. The aim of this study was to compare daily versus depot treatment and factors influencing the therapeutic outcome. Newly settled refugees (n = 151) with 25(OH)D levels less than 78 nmol/L were randomised to receive daily or depot vitamin D therapy with eight weekly interval follow up to 40 weeks. Biochemical and clinical parameters were collected at each visit. Generalized Linear Mixed Models (GLMM) examined the longitudinal changes over time controlling for confounders including age, gender, treatment arm, season, country of refuge/origin and sun exposure score. Participants were aged 5.5 months to 16.0 years (75 males, 83 females). Both treatment groups achieved vitamin D sufficiency. The daily treatment group had significantly higher 25(OH)D levels at each visit post baseline and a higher proportion of participants with levels above 50 nmol/L at all time points. Time, treatment group, calcium and sun exposure score were significant predictors of 25(OH)D serum levels. Depot vitamin D therapy is an alternative to daily treatment in this at-risk group of children and adolescents in whom treatment adherence is problematic. Full article
(This article belongs to the Special Issue Changing Times for Vitamin D and Health)
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Open AccessArticle
MS Sunshine Study: Sun Exposure But Not Vitamin D Is Associated with Multiple Sclerosis Risk in Blacks and Hispanics
Nutrients 2018, 10(3), 268; https://doi.org/10.3390/nu10030268 - 27 Feb 2018
Cited by 15
Abstract
Multiple sclerosis (MS) incidence and serum 25-hydroxyvitamin D (25OHD) levels vary by race/ethnicity. We examined the consistency of beneficial effects of 25OHD and/or sun exposure for MS risk across multiple racial/ethnic groups. We recruited incident MS cases and controls (blacks 116 cases/131 controls; [...] Read more.
Multiple sclerosis (MS) incidence and serum 25-hydroxyvitamin D (25OHD) levels vary by race/ethnicity. We examined the consistency of beneficial effects of 25OHD and/or sun exposure for MS risk across multiple racial/ethnic groups. We recruited incident MS cases and controls (blacks 116 cases/131 controls; Hispanics 183/197; whites 247/267) from the membership of Kaiser Permanente Southern California into the MS Sunshine Study to simultaneously examine sun exposure and 25OHD, accounting for genetic ancestry and other factors. Higher lifetime ultraviolet radiation exposure (a rigorous measure of sun exposure) was associated with a lower risk of MS independent of serum 25OHD levels in blacks (adjusted OR = 0.53, 95% CI = 0.31–0.83; p = 0.007) and whites (OR = 0.68, 95% CI = 0.48–0.94; p = 0.020) with a similar magnitude of effect that did not reach statistical significance in Hispanics (OR = 0.66, 95% CI = 0.42–1.04; p = 0.071). Higher serum 25OHD levels were associated with a lower risk of MS only in whites. No association was found in Hispanics or blacks regardless of how 25OHD was modeled. Lifetime sun exposure appears to reduce the risk of MS regardless of race/ethnicity. In contrast, serum 25OHD levels are not associated with MS risk in blacks or Hispanics. Our findings challenge the biological plausibility of vitamin D deficiency as causal for MS and call into question the targeting of specific serum 25OHD levels to achieve health benefits, particularly in blacks and Hispanics. Full article
(This article belongs to the Special Issue Changing Times for Vitamin D and Health)
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Open AccessArticle
Vitamin D-Binding Protein Polymorphisms, 25-Hydroxyvitamin D, Sunshine and Multiple Sclerosis
Nutrients 2018, 10(2), 184; https://doi.org/10.3390/nu10020184 - 07 Feb 2018
Cited by 11
Abstract
Blacks have different dominant polymorphisms in the vitamin D-binding protein (DBP) gene that result in higher bioavailable vitamin D than whites. This study tested whether the lack of association between 25-hydroxyvitamin D (25OHD) and multiple sclerosis (MS) risk in blacks and Hispanics is [...] Read more.
Blacks have different dominant polymorphisms in the vitamin D-binding protein (DBP) gene that result in higher bioavailable vitamin D than whites. This study tested whether the lack of association between 25-hydroxyvitamin D (25OHD) and multiple sclerosis (MS) risk in blacks and Hispanics is due to differences in these common polymorphisms (rs7041, rs4588). We recruited incident MS cases and controls (blacks 116 cases/131 controls; Hispanics 183/197; whites 247/267) from Kaiser Permanente Southern California. AA is the dominant rs7041 genotype in blacks (70.0%) whereas C is the dominant allele in whites (79.0% AC/CC) and Hispanics (77.1%). Higher 25OHD levels were associated with a lower risk of MS in whites who carried at least one copy of the C allele but not AA carriers. No association was found in Hispanics or blacks regardless of genotype. Higher ultraviolet radiation exposure was associated with a lower risk of MS in blacks (OR = 0.06), Hispanics and whites who carried at least one copy of the C allele but not in others. Racial/ethnic variations in bioavailable vitamin D do not explain the lack of association between 25OHD and MS in blacks and Hispanics. These findings further challenge the biological plausibility of vitamin D deficiency as causal for MS. Full article
(This article belongs to the Special Issue Changing Times for Vitamin D and Health)
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Open AccessArticle
Maternal Vitamin D Status and Infant Infection
Nutrients 2018, 10(2), 111; https://doi.org/10.3390/nu10020111 - 23 Jan 2018
Cited by 2
Abstract
Maternal vitamin D status during pregnancy may modulate fetal immune system development and infant susceptibility to infections. Vitamin D deficiency is common during pregnancy, particularly among African American (AA) women. Our objective was to compare maternal vitamin D status (plasma 25(OH)D concentration) during [...] Read more.
Maternal vitamin D status during pregnancy may modulate fetal immune system development and infant susceptibility to infections. Vitamin D deficiency is common during pregnancy, particularly among African American (AA) women. Our objective was to compare maternal vitamin D status (plasma 25(OH)D concentration) during pregnancy and first-year infections in the offspring of African American (AA) and non-AA women. We used medical records to record frequency and type of infections during the first year of life of 220 term infants (69 AA, 151 non-AA) whose mothers participated in the Kansas University DHA Outcomes Study. AA and non-AA groups were compared for maternal 25(OH)D by Mann–Whitney U-test. Compared to non-AA women, AA women were more likely to be vitamin D deficient (<50 nmol/L; 84 vs. 37%, p < 0.001), and more of their infants had at least one infection in the first 6 months (78.3% and 59.6% of infants, respectively, p = 0.022). We next explored the relationship between maternal plasma 25(OH)D concentration and infant infections using Spearman correlations. Maternal 25(OH)D concentration was inversely correlated with the number of all infections (p = 0.033), eye, ear, nose, and throat (EENT) infections (p = 0.043), and skin infection (p = 0.021) in the first 6 months. A model that included maternal education, income, and 25(OH)D identified maternal education as the only significant predictor of infection risk in the first 6 months (p = 0.045); however, maternal education, income, and 25(OH)D were all significantly lower in AA women compared to non-AA women . The high degree of correlation between these variables does not allow determination of which factor is driving the risk of infection; however, the one that is most easily remediated is vitamin D status. It would be of value to learn if vitamin D supplementation in this at-risk group could ameliorate at least part of the increased infection risk. Full article
(This article belongs to the Special Issue Changing Times for Vitamin D and Health)
Open AccessArticle
A Longitudinal Study of 25-Hydroxy Vitamin D and Parathyroid Hormone Status throughout Pregnancy and Exclusive Lactation in New Zealand Mothers and Their Infants at 45° S
Nutrients 2018, 10(1), 86; https://doi.org/10.3390/nu10010086 - 13 Jan 2018
Cited by 8
Abstract
Vitamin D status and associated metabolism during pregnancy and lactation have been assessed in only a limited number of longitudinal studies, all from the northern hemisphere, with no infant data concurrently reported. Therefore, we aimed to describe longitudinal maternal and infant 25-hydroxy vitamin [...] Read more.
Vitamin D status and associated metabolism during pregnancy and lactation have been assessed in only a limited number of longitudinal studies, all from the northern hemisphere, with no infant data concurrently reported. Therefore, we aimed to describe longitudinal maternal and infant 25-hydroxy vitamin D (25OHD) and parathyroid hormone (PTH) status during pregnancy and up to 5 months postnatal age, in New Zealand women and their infants living at 45° S latitude. Between September 2011 and June 2013, 126 pregnant women intending to exclusively breastfeed for at least 20 weeks were recruited. Longitudinal data were collected at three time-points spanning pregnancy, and following birth and at 20 weeks postpartum. Vitamin D deficiency (25OHD < 50 nmol/L) was common, found at one or more time-points in 65% and 76% of mothers and their infants, respectively. Mean cord 25OHD was 41 nmol/L, and three infants exhibited secondary hyperparathyroidism by postnatal week 20. Maternal late pregnancy 25OHD (gestation 32–38 weeks) was closely correlated with infant cord 25OHD, r2 = 0.87 (95% CI (Confidence interval) 0.8–0.91), while no correlation was seen between early pregnancy (<20 weeks gestation) maternal and cord 25OHD, r2 = 0.06 (95% CI −0.16–0.28). Among other variables, pregnancy 25OHD status, and therefore infant status at birth, were influenced by season of conception. In conclusion, vitamin D deficiency in women and their infants is very common during pregnancy and lactation in New Zealand at 45° S. These data raise questions regarding the applicability of current pregnancy and lactation policy at this latitude, particularly recommendations relating to first trimester maternal vitamin D screening and targeted supplementation for those “at risk”. Full article
(This article belongs to the Special Issue Changing Times for Vitamin D and Health)
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Open AccessArticle
Effect of Monthly, High-Dose, Long-Term Vitamin D on Lung Function: A Randomized Controlled Trial
Nutrients 2017, 9(12), 1353; https://doi.org/10.3390/nu9121353 - 13 Dec 2017
Cited by 12
Abstract
Although observational studies suggest positive vitamin D-lung function associations, randomized trials are inconsistent. We examined effects of vitamin D supplementation on lung function. We recruited 442 adults (50–84 years, 58% male) into a randomized, double-blinded, placebo-controlled trial. Participants received, for 1.1 years (median; [...] Read more.
Although observational studies suggest positive vitamin D-lung function associations, randomized trials are inconsistent. We examined effects of vitamin D supplementation on lung function. We recruited 442 adults (50–84 years, 58% male) into a randomized, double-blinded, placebo-controlled trial. Participants received, for 1.1 years (median; range = 0.9–1.5 years), either (1) vitamin D3 200,000 IU, followed by monthly 100,000 IU doses (n = 226); or (2) placebo monthly (n = 216). At baseline and follow-up, spirometry yielded forced expiratory volume in 1 s (FEV1; primary outcome). Mean (standard deviation) 25-hydroxyvitamin D increased from 61 (24) nmol/L at baseline to 119 (45) nmol/L at follow-up in the vitamin D group, but was unchanged in the placebo group. There were no significant lung function improvements (vitamin D versus placebo) in the total sample, vitamin D-deficient participants or asthma/chronic obstructive pulmonary disease (COPD) participants. However, among ever-smokers (n = 217), the mean (95% confidence interval) FEV1 increase in the vitamin D versus placebo was 57 (4, 109) mL (p = 0.03). FEV1 increases were larger among vitamin D-deficient ever-smokers (n = 54): 122 (8, 236) mL (p = 0.04). FEV1 improvements were largest among ever-smokers with asthma/COPD (n = 60): 160 (53, 268) mL (p = 0.004). Thus, vitamin D supplementation did not improve lung function among everyone, but benefited ever-smokers, especially those with vitamin D deficiency or asthma/COPD. Full article
(This article belongs to the Special Issue Changing Times for Vitamin D and Health)
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Open AccessArticle
Maternal Vitamin D Status and the Relationship with Neonatal Anthropometric and Childhood Neurodevelopmental Outcomes: Results from the Seychelles Child Development Nutrition Study
Nutrients 2017, 9(11), 1235; https://doi.org/10.3390/nu9111235 - 11 Nov 2017
Cited by 8
Abstract
Vitamin D has an important role in early life; however, the optimal vitamin D status during pregnancy is currently unclear. There have been recent calls for pregnant women to maintain circulating 25-hydroxyvitamin D (25(OH)D) concentrations >100 nmol/L for health, yet little is known [...] Read more.
Vitamin D has an important role in early life; however, the optimal vitamin D status during pregnancy is currently unclear. There have been recent calls for pregnant women to maintain circulating 25-hydroxyvitamin D (25(OH)D) concentrations >100 nmol/L for health, yet little is known about the long-term potential benefits or safety of achieving such high maternal 25(OH)D concentrations for infant or child health outcomes. We examined maternal vitamin D status and its associations with infant anthropometric and later childhood neurocognitive outcomes in a mother-child cohort in a sun-rich country near the equator (4.6° S). This study was conducted in pregnant mothers originally recruited to the Seychelles Child Development Nutrition Study. Blood samples (n = 202) taken at delivery were analysed for serum 25-hydroxyvitamin D (25(OH)D) concentrations. Multiple linear regression models assessed associations between maternal 25(OH)D and birth weight, infant head circumference, and neurocognitive outcomes in the children at age 5 years. Mothers were, on average, 27 years of age, and the children’s average gestational age was 39 weeks. None of the women reported any intake of vitamin D supplements. Maternal 25(OH)D concentrations had a mean of 101 (range 34–218 nmol/L) and none were deficient (<30 nmol/L). Maternal 25(OH)D concentrations were not associated with child anthropometric or neurodevelopmental outcomes. These findings appear to indicate that a higher vitamin D status is not a limiting factor for neonatal growth or neurocognitive development in the first 5 years of life. Larger studies with greater variability in vitamin D status are needed to further explore optimal cut-offs or non-linear associations (including for maternal health) that might exist among populations with sub-optimal exposure. Full article
(This article belongs to the Special Issue Changing Times for Vitamin D and Health)

Review

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Open AccessReview
Development of Vitamin D Toxicity from Overcorrection of Vitamin D Deficiency: A Review of Case Reports
Nutrients 2018, 10(8), 953; https://doi.org/10.3390/nu10080953 - 24 Jul 2018
Cited by 11
Abstract
Over the past two decades, vitamin D level measurements have become some of the most frequently ordered tests in the laboratory. This increase is due to a growing awareness of widespread vitamin D deficiency and scientific data suggesting the beneficial effects of vitamin [...] Read more.
Over the past two decades, vitamin D level measurements have become some of the most frequently ordered tests in the laboratory. This increase is due to a growing awareness of widespread vitamin D deficiency and scientific data suggesting the beneficial effects of vitamin D in various diseases. A literature search was carried out in PubMed for cases reporting vitamin D intoxication and overdose. Thirteen articles were included in this review. Intoxication was severe in the reported cases. Patients presented with serum vitamin D concentrations ranging between 150 and 1220 ng/mL and serum calcium concentrations between 11.1 and 23.1 mg/dL. Most of the reported patients showed symptoms of vitamin D toxicity such as vomiting, dehydration, pain, and loss of appetite. The underlying causes included manufacturing errors, overdosing by patients or prescribers, and combinations of these factors. Our literature search highlights the fact that even though vitamin D intoxication is rare, it does occur and therefore patients and prescribers should be more cognizant of the potential dangers of vitamin D overdose. Full article
(This article belongs to the Special Issue Changing Times for Vitamin D and Health)
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Open AccessFeature PaperReview
Associations of Maternal Vitamin D Deficiency with Pregnancy and Neonatal Complications in Developing Countries: A Systematic Review
Nutrients 2018, 10(5), 640; https://doi.org/10.3390/nu10050640 - 18 May 2018
Cited by 6
Abstract
Pregnant women in Asia, the Middle East, Africa and Latin America are at risk of vitamin D deficiency (VDD) and prevalence throughout these regions are among the highest, globally. Maternal VDD has been associated with increased risk of a number of adverse maternal [...] Read more.
Pregnant women in Asia, the Middle East, Africa and Latin America are at risk of vitamin D deficiency (VDD) and prevalence throughout these regions are among the highest, globally. Maternal VDD has been associated with increased risk of a number of adverse maternal and neonatal health outcomes, yet research from developing countries is limited. We assessed the associations of maternal VDD during pregnancy with adverse health outcomes by synthesizing the literature from observational studies conducted in developing countries. Six electronic databases were searched for English-language studies published between 2000 and 2017. Thirteen studies from seven countries were included in the review. Prevalence of VDD ranged from 51.3% to 100%. Six studies assessed both maternal and neonatal outcomes, four studies assessed only maternal outcomes and three studies assessed only neonatal outcomes. Ten studies showed at least one significant association between VDD and adverse maternal and/or neonatal health outcomes including pre-eclampsia (n = 3), gestational diabetes mellitus (n = 1), postpartum depression (n = 1), emergency cesarean section delivery (n = 1), low birth weight babies (n = 4), small for gestational age (n = 2), stunting (n = 1). However most of these studies (n = 6) also showed no association with multiple health outcomes. Vitamin D assessment methods, criteria applied to define VDD, season and trimester in which studies were conducted varied considerably across studies. In conclusion, this study highlights the need to improve maternal vitamin D status in developing countries in an effort to support best maternal and child health outcomes across these regions. Future research should focus on more unified approaches to vitamin D assessment and preventative approaches that may be embedded into already existing antenatal care settings. Full article
(This article belongs to the Special Issue Changing Times for Vitamin D and Health)
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Open AccessReview
Emerging Evidence of Thresholds for Beneficial Effects from Vitamin D Supplementation
Nutrients 2018, 10(5), 561; https://doi.org/10.3390/nu10050561 - 03 May 2018
Cited by 22
Abstract
Publications from clinical trials of vitamin D supplementation have increased substantially over the last 15 years. Yet, despite the growing number of randomized controlled trials, meta-analyses of these studies have drawn inconsistent conclusions. Many meta-analyses assume that vitamin D is a pharmacological agent, [...] Read more.
Publications from clinical trials of vitamin D supplementation have increased substantially over the last 15 years. Yet, despite the growing number of randomized controlled trials, meta-analyses of these studies have drawn inconsistent conclusions. Many meta-analyses assume that vitamin D is a pharmacological agent, and give scant consideration of it being a nutrient. This limits their potential to detect beneficial effects in participants with vitamin D deficiency. An increasing body of evidence from both observational studies and clinical trials supports the presence of thresholds in vitamin D status below which disease risk increases and vitamin supplementation has beneficial effects. Future supplementation trials which seek to replicate these findings should recruit sufficient numbers of participants with low vitamin D levels, and not give low-dose vitamin D to the placebo group. If the presence of vitamin D thresholds for beneficial effects is confirmed, this would strengthen the need for vitamin D fortification of foods. Full article
(This article belongs to the Special Issue Changing Times for Vitamin D and Health)
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Open AccessReview
The Vitamin D–Folate Hypothesis as an Evolutionary Model for Skin Pigmentation: An Update and Integration of Current Ideas
Nutrients 2018, 10(5), 554; https://doi.org/10.3390/nu10050554 - 30 Apr 2018
Cited by 8
Abstract
Vitamin D is unique in being generated in our skin following ultraviolet radiation (UVR) exposure. Ongoing research into vitamin D must therefore always consider the influence of UVR on vitamin D processes. The close relationship between vitamin D and UVR forms the basis [...] Read more.
Vitamin D is unique in being generated in our skin following ultraviolet radiation (UVR) exposure. Ongoing research into vitamin D must therefore always consider the influence of UVR on vitamin D processes. The close relationship between vitamin D and UVR forms the basis of the “vitamin D–folate hypothesis”, a popular theory for why human skin colour has evolved as an apparent adaption to UVR environments. Vitamin D and folate have disparate sensitivities to UVR; whilst vitamin D may be synthesised following UVR exposure, folate may be degraded. The vitamin D–folate hypothesis proposes that skin pigmentation has evolved as a balancing mechanism, maintaining levels of these vitamins. There are several alternative theories that counter the vitamin D–folate hypothesis. However, there is significant overlap between these theories and the now known actions of vitamin D and folate in the skin. The focus of this review is to present an update on the vitamin D–folate hypothesis by integrating these current theories and discussing new evidence that supports associations between vitamin D and folate genetics, UVR, and skin pigmentation. In light of recent human migrations and seasonality in disease, the need for ongoing research into potential UVR-responsive processes within the body is also discussed. Full article
(This article belongs to the Special Issue Changing Times for Vitamin D and Health)
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Open AccessFeature PaperReview
Vitamin D Requirements for the Future—Lessons Learned and Charting a Path Forward
Nutrients 2018, 10(5), 533; https://doi.org/10.3390/nu10050533 - 25 Apr 2018
Cited by 9
Abstract
Estimates of dietary requirements for vitamin D or Dietary Reference Values (DRV) are crucial from a public health perspective in providing a framework for prevention of vitamin D deficiency and optimizing vitamin D status of individuals. While these important public health policy instruments [...] Read more.
Estimates of dietary requirements for vitamin D or Dietary Reference Values (DRV) are crucial from a public health perspective in providing a framework for prevention of vitamin D deficiency and optimizing vitamin D status of individuals. While these important public health policy instruments were developed with the evidence-base and data available at the time, there are some issues that need to be clarified or considered in future iterations of DRV for vitamin D. This is important as it will allow for more fine-tuned and truer estimates of the dietary requirements for vitamin D and thus provide for more population protection. The present review will overview some of the confusion that has arisen in relation to the application and/or interpretation of the definitions of the Estimated Average Requirement (EAR) and Recommended Dietary Allowance (RDA). It will also highlight some of the clarifications needed and, in particular, how utilization of a new approach in terms of using individual participant-level data (IPD), over and beyond aggregated data, from randomised controlled trials with vitamin D may have a key role in generating these more fine-tuned and truer estimates, which is of importance as we move towards the next iteration of vitamin D DRVs. Full article
(This article belongs to the Special Issue Changing Times for Vitamin D and Health)
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Open AccessReview
Vitamin D and the Liver—Correlation or Cause?
Nutrients 2018, 10(4), 496; https://doi.org/10.3390/nu10040496 - 16 Apr 2018
Cited by 9
Abstract
Vitamin D is becoming increasingly accepted as an important physiological regulator outside of its classical role in skeletal homeostasis. A growing body of evidence connects vitamin D with hepatic disease. This review summarises the role of vitamin D in liver homeostasis and disease [...] Read more.
Vitamin D is becoming increasingly accepted as an important physiological regulator outside of its classical role in skeletal homeostasis. A growing body of evidence connects vitamin D with hepatic disease. This review summarises the role of vitamin D in liver homeostasis and disease and discusses the therapeutic potential of vitamin D-based treatments to protect against hepatic disease progression and to improve response to treatment. While pre-clinical experimental data is promising, clinical trials around liver diseases have mostly been under-powered, and further studies will be required to clarify whether vitamin D or vitamin D analogues have beneficial effects on liver disease. Full article
(This article belongs to the Special Issue Changing Times for Vitamin D and Health)
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Open AccessReview
Clinical Management of Low Vitamin D: A Scoping Review of Physicians’ Practices
Nutrients 2018, 10(4), 493; https://doi.org/10.3390/nu10040493 - 16 Apr 2018
Cited by 10
Abstract
The role of vitamin D in the prevention and treatment of non-skeletal health issues has received significant media and research attention in recent years. Costs associated with clinical management of low vitamin D (LVD) have increased exponentially. However, no clear evidence supports vitamin [...] Read more.
The role of vitamin D in the prevention and treatment of non-skeletal health issues has received significant media and research attention in recent years. Costs associated with clinical management of low vitamin D (LVD) have increased exponentially. However, no clear evidence supports vitamin D screening to improve health outcomes. Authoritative bodies and professional societies do not recommend population-wide vitamin D screening in community-dwelling adults who are asymptomatic or at low risk of LVD. To assess patterns of physicians’ management of LVD in this conflicting environment, we conducted a scoping review of three electronic databases and the gray literature. Thirty-eight records met inclusion criteria and were summarized in an evidence table. Thirteen studies published between 2006 and 2015 across seven countries showed a consistent increase in vitamin D lab tests and related costs. Many vitamin D testing patterns reflected screening rather than targeted testing for individuals at high risk of vitamin D deficiency or insufficiency. Interventions aimed at managing inappropriate clinical practices related to LVD were effective in the short term. Variability and controversy were pervasive in many aspects of vitamin D management, shining a light on physicians’ practices in the face of uncertainty. Future research is needed to inform better clinical guidelines and to assess implementation practices that encourage evidence-based management of LVD in adult populations. Full article
(This article belongs to the Special Issue Changing Times for Vitamin D and Health)
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Open AccessReview
The When, What & How of Measuring Vitamin D Metabolism in Clinical Medicine
Nutrients 2018, 10(4), 482; https://doi.org/10.3390/nu10040482 - 13 Apr 2018
Cited by 9
Abstract
We now have the ability to measure a number of different vitamin D metabolites with very accurate methods. The most abundant vitamin D metabolite, 25-hydroxyvitamin D, is currently the best marker for overall vitamin D status and is therefore most commonly measured in [...] Read more.
We now have the ability to measure a number of different vitamin D metabolites with very accurate methods. The most abundant vitamin D metabolite, 25-hydroxyvitamin D, is currently the best marker for overall vitamin D status and is therefore most commonly measured in clinical medicine. The added value of measuring metabolites beyond 25-hydroxyvitamin D, like 1,25-, and 24,25-dihydroxyvitamin D is not broadly appreciated. Yet, in some more complicated cases, these metabolites may provide just the information needed for a legitimate diagnosis. The problem at present, is knowing when to measure, what to measure and how to measure. For 25-hydroxyvitamin D, the most frequently used automated immunoassays do not meet the requirements of today’s standards for certain patient groups and liquid chromatography-tandem mass spectrometry is the desired method of choice in these individuals. The less frequently measured 1,25-dihydroxyvitamin D metabolite enables us to identify a number of conditions, including 1α-hydroxylase deficiency, hereditary vitamin D-resistant rickets and a number of granulomatous diseases or lymphoproliferative diseases accompanied by hypercalcaemia. Furthermore, it discriminates between the FGF23-mediated and non-FGF23-mediated hypophosphatemic syndromes. The 24,25-dihydroxyvitamin D metabolite has proven its value in the diagnosis of idiopathic infantile hypercalcaemia and has the potential of having value in identifying other diseases. For both metabolites, the understanding of the origin of differences between assays is limited and requires further attention. Nonetheless, in every way, appropriate measurement of vitamin D metabolism in the clinical laboratory hinges eminently on the comprehension of the value of the different metabolites, and the importance of the choice of method. Full article
(This article belongs to the Special Issue Changing Times for Vitamin D and Health)
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Open AccessReview
Vitamin D Deficiency and Antenatal and Postpartum Depression: A Systematic Review
Nutrients 2018, 10(4), 478; https://doi.org/10.3390/nu10040478 - 12 Apr 2018
Cited by 11
Abstract
Vitamin D has been implicated in antenatal depression (AD) and postpartum depression (PPD) in many studies; however, results have been inconsistent due to the complexity of this association. We searched the MEDLINE, Embase, PsycINFO, and Maternity and Infant Care databases for literature addressing [...] Read more.
Vitamin D has been implicated in antenatal depression (AD) and postpartum depression (PPD) in many studies; however, results have been inconsistent due to the complexity of this association. We searched the MEDLINE, Embase, PsycINFO, and Maternity and Infant Care databases for literature addressing associations between vitamin D and AD and PPD. Two independent authors reviewed titles and abstracts of the search results and selected studies for full review. Data were extracted, and a quality rating was done using the Newcastle–Ottawa Scale (NOS) on the selected studies. A total of 239 studies were identified; 14 were included in the review. The quality assessment of the included studies ranged from moderate to high. Of the studies on PPD, five of nine (55%) showed a significant association between vitamin D and PPD. Five of seven (71%) studies on AD showed a significant association with vitamin D status. As the included studies used different effect estimates and statistical analyses to report the association, it was not possible to transform the existing data into one single effect measure to employ meta-analytic techniques. While results of this systematic review vary, they indicate a significant association between vitamin D status and AD and PD. Full article
(This article belongs to the Special Issue Changing Times for Vitamin D and Health)
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Open AccessReview
Vitamin D, Hypercalciuria and Kidney Stones
Nutrients 2018, 10(3), 366; https://doi.org/10.3390/nu10030366 - 17 Mar 2018
Cited by 9
Abstract
The estimated lifetime risk of nephrolithiasis is growing nowadays, and the formation of kidney stones is frequently promoted by hypercalciuria. Vitamin D, and especially its active metabolite calcitriol, increase digestive calcium absorption—as urinary calcium excretion is directly correlated with digestive calcium absorption, vitamin [...] Read more.
The estimated lifetime risk of nephrolithiasis is growing nowadays, and the formation of kidney stones is frequently promoted by hypercalciuria. Vitamin D, and especially its active metabolite calcitriol, increase digestive calcium absorption—as urinary calcium excretion is directly correlated with digestive calcium absorption, vitamin D metabolites could theoretically increase calciuria and promote urinary stone formation. Nevertheless, there was, until recently, low evidence that 25-hydroxyvitamin D serum levels would be correlated with kidney stone formation, even if high calcitriol concentrations are frequently observed in hypercalciuric stone formers. Low 25-hydroxyvitamin D serum levels have been associated with a broad spectrum of diseases, leading to a huge increase in vitamin D prescription in the general population. In parallel, an increased frequency of kidney stone episodes has been observed in prospective studies evaluating vitamin D alone or in association with calcium supplements, and epidemiological studies have identified an association between high 25-hydroxyvitamin D serum levels and kidney stone formation in some groups of patients. Moreover, urinary calcium excretion has been shown to increase in response to vitamin D supplements, at least in some groups of kidney stone formers. It seems likely that predisposed individuals may develop hypercalciuria and kidney stones in response to vitamin D supplements. Full article
(This article belongs to the Special Issue Changing Times for Vitamin D and Health)
Open AccessReview
Vitamin D and Age-Related Macular Degeneration
Nutrients 2017, 9(10), 1120; https://doi.org/10.3390/nu9101120 - 13 Oct 2017
Cited by 4
Abstract
In recent years, the relationship between vitamin D and health has received growing attention from the scientific and medical communities. Vitamin D deficiencies have been repeatedly associated with various acute and chronic diseases, including age-related macular degeneration (AMD). Its active metabolite, 1α,25-dihydoxy vitamin [...] Read more.
In recent years, the relationship between vitamin D and health has received growing attention from the scientific and medical communities. Vitamin D deficiencies have been repeatedly associated with various acute and chronic diseases, including age-related macular degeneration (AMD). Its active metabolite, 1α,25-dihydoxy vitamin D, acts as a modulator of cell proliferation, differentiation and apoptosis, and cumulative data from experimental and observational studies suggest that relatively a lower vitamin D status could be a potential risk factor for the development of early and/or late AMD. Herein, we made a narrative review of the mechanisms linking a potential role of vitamin D with the current concepts of AMD pathophysiology. Full article
(This article belongs to the Special Issue Changing Times for Vitamin D and Health)
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