Nutrients

Editorial

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Open AccessEditorial

Vitamin D and Human Health: Celebrating Diversity

by Simon Spedding

Nutrients 2014, 6(1), 11-14; https://doi.org/10.3390/nu6010011 - 19 Dec 2013

Cited by 6 | Viewed by 8162

Abstract

This Special Issue of Nutrients: Vitamin D and Human Health celebrates diversity in vitamin D research with articles from bench-to-bedside, examining mechanisms, epidemiology, and clinical issues in the management of non-skeletal disease following themes set by an earlier review in Nutrients [1]. [...] Read more.

This Special Issue of Nutrients: Vitamin D and Human Health celebrates diversity in vitamin D research with articles from bench-to-bedside, examining mechanisms, epidemiology, and clinical issues in the management of non-skeletal disease following themes set by an earlier review in Nutrients [1]. Vitamin D became synonymous with calcium and bone metabolism originating from Casimir Funk’s concept of “Vitamines”. This suggests that vitamin D is an amine found in food with a single mode of action affecting calcium and bone metabolism [2], whereas vitamin D is a secosteroid hormone derived from sunshine with a plethora of physiological functions (autocrine, paracrine, endocrine [3], and epigenetic [4]) associating vitamin D deficiency with many illnesses [1]. Deficiency is pandemic and most prevalent where sun exposure is limited by culture climate and skin colour [5]. Whilst reports have focused on diet and bone metabolism [6], this Special Issue of Nutrients about Vitamin D and Human Health focuses on non-skeletal disease, and research driven by industry and community health concerns. [...] Full article

(This article belongs to the Special Issue Vitamin D and Human Health)

Research

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Open AccessArticle

The Importance of Dose, Frequency and Duration of Vitamin D Supplementation for Plasma 25-Hydroxyvitamin D

by Yi-Sheng Chao, Ludovic Brunel, Peter Faris and Paul J. Veugelers

Nutrients 2013, 5(10), 4067-4078; https://doi.org/10.3390/nu5104067 - 11 Oct 2013

Cited by 24 | Viewed by 10260

Abstract

The importance of dose, frequency and duration of vitamin D supplementation for plasma 25(OH)D levels is not well described and rarely reported for supplementation that exceeds 2000 IU per day. The objective is to examine dose, frequency and duration of supplementation in relation [...] Read more.

The importance of dose, frequency and duration of vitamin D supplementation for plasma 25(OH)D levels is not well described and rarely reported for supplementation that exceeds 2000 IU per day. The objective is to examine dose, frequency and duration of supplementation in relation to plasma 25(OH)D in a large population-based sample. We accessed data on 2714 volunteers that contributed to 4224 visits and applied multilevel regression. Compared to not using supplements, a minimum regimen of 1000–2000 IU once or twice per week for one month was not effective in raising 25(OH)D. Compared to this minimum regimen, higher doses of 2000–3000, 3000–4000, and 5000 IU or more were associated with a 7.49, 13.19 and 30.22 nmol/L 25(OH)D increase, respectively; frequencies of three to four, five to six and seven times/week were associated with a 5.44, 16.52 and 30.69 nmol/L increase, respectively; and supplementation of five months or longer was associated with an increase of 6.68 nmol/L (p < 0.01 for all). Age, body weight, physical activity, smoking, and self-rated health were significantly associated with 25(OH)D. Whereas dose, frequency and duration of supplementation are important to healthy subjects committed to optimizing their nutritional status, to the design of clinical trials, individual characteristics and lifestyle contribute substantially to 25(OH)D. Full article

(This article belongs to the Special Issue Vitamin D and Human Health)

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Open AccessArticle

Increased Plasma Concentrations of Vitamin D Metabolites and Vitamin D Binding Protein in Women Using Hormonal Contraceptives: A Cross-Sectional Study

by Ulla K. Møller, Susanna Við Streym, Lars T. Jensen, Leif Mosekilde, Inez Schoenmakers, Shailja Nigdikar and Lars Rejnmark

Nutrients 2013, 5(9), 3470-3480; https://doi.org/10.3390/nu5093470 - 5 Sep 2013

Cited by 68 | Viewed by 8592

Abstract

Use of hormonal contraceptives (HC) may influence total plasma concentrations of vitamin D metabolites. A likely cause is an increased synthesis of vitamin D binding protein (VDBP). Discrepant results are reported on whether the use of HC affects free concentrations of vitamin D [...] Read more.

Use of hormonal contraceptives (HC) may influence total plasma concentrations of vitamin D metabolites. A likely cause is an increased synthesis of vitamin D binding protein (VDBP). Discrepant results are reported on whether the use of HC affects free concentrations of vitamin D metabolites. Aim: In a cross-sectional study, plasma concentrations of vitamin D metabolites, VDBP, and the calculated free vitamin D index in users and non-users of HC were compared and markers of calcium and bone metabolism investigated. Results: 75 Caucasian women aged 25–35 years were included during winter season. Compared with non-users (n = 23), users of HC (n = 52) had significantly higher plasma concentrations of 25-hydroxyvitamin D (25OHD) (median 84 interquartile range: [67–111] vs. 70 [47–83] nmol/L, p = 0.01), 1,25-dihydroxyvitamin D (1,25(OH)₂D) (198 [163–241] vs. 158 [123–183] pmol/L, p = 0.01) and VDBP (358 [260–432] vs. 271 [179–302] µg/mL, p < 0.001). However, the calculated free indices (FI-25OHD and FI-1,25(OH)₂D) were not significantly different between groups (p > 0.10). There were no significant differences in indices of calcium homeostasis (plasma concentrations of calcium, parathyroid hormone, and calcitonin, p > 0.21) or bone metabolism (plasma bone specific alkaline phosphatase, osteocalcin, and urinary NTX/creatinine ratio) between groups. In conclusion: Use of HC is associated with 13%–25% higher concentrations of total vitamin D metabolites and VDBP. This however is not reflected in indices of calcium or bone metabolism. Use of HC should be considered in the interpretation of plasma concentrations vitamin D metabolites. Full article

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Open AccessArticle

Association between Subcutaneous White Adipose Tissue and Serum 25-Hydroxyvitamin D in Overweight and Obese Adults

by Brian D. Piccolo, Gregory Dolnikowski, Elias Seyoum, Anthony P. Thomas, Erik R. Gertz, Elaine C. Souza, Leslie R. Woodhouse, John W. Newman, Nancy L. Keim, Sean H. Adams and Marta D. Van Loan

Nutrients 2013, 5(9), 3352-3366; https://doi.org/10.3390/nu5093352 - 26 Aug 2013

Cited by 43 | Viewed by 10304

Abstract

Cholecalciferol is known to be deposited in human adipose tissue, but it is not known whether 25-hydroxyvitamin D (25(OH)D) is found in detectable concentrations. Therefore, our objective was to determine whether 25(OH)D is detectable in subcutaneous white adipose tissue (SWAT) in overweight and [...] Read more.

Cholecalciferol is known to be deposited in human adipose tissue, but it is not known whether 25-hydroxyvitamin D (25(OH)D) is found in detectable concentrations. Therefore, our objective was to determine whether 25(OH)D is detectable in subcutaneous white adipose tissue (SWAT) in overweight and obese persons enrolled in a twelve week energy restricted diet. Baseline and post-intervention gluteal SWAT biopsies were collected from 20 subjects participating in a larger clinical weight loss intervention. LC-MS/MS was utilized to determine SWAT 25(OH)D concentrations. Serum 25(OH)D and 1,25(OH)₂D were measured by RIA. Body composition was assessed by dual energy x-ray absorptiometry. SWAT 25(OH)D concentrations were 5.8 ± 2.6 nmol/kg tissue and 6.2 ± 2.7 nmol/kg tissue pre- and post-intervention SWAT, respectively. There was a significant positive association between SWAT 25(OH)D concentration and serum 25(OH)D concentration (r = 0.52, P < 0.01). Both SWAT and serum 25(OH)D concentrations did not significantly change after a twelve-week period of energy restriction with approximately 5 kg of fat loss. In conclusion, we have demonstrated our LC-MS/MS method can detect 25(OH)D₃ in human subcutaneous fat tissue from overweight and obese individuals and is consistent with previously reported concentrations in swine. Additionally, our findings of no significant changes in SWAT 25(OH)D₃ or serum 25(OH)D after a 6% loss of total body weight and 13% reduction in total fat provides the first human evidence that adipose 25(OH)D does not likely contribute to serum 25(OH)D with moderate weight loss; whether this is also the case with larger amounts of weight loss is unknown. Weight loss alone is not sufficient to increase serum 25(OH)D and increases in dietary or dermal biosynthesis of vitamin D appear to be the most critical contributors to in vitamin D status. Full article

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Open AccessArticle

A Novel Role for a Major Component of the Vitamin D Axis: Vitamin D Binding Protein-Derived Macrophage Activating Factor Induces Human Breast Cancer Cell Apoptosis through Stimulation of Macrophages

by Lynda Thyer, Emma Ward, Rodney Smith, Maria Giulia Fiore, Stefano Magherini, Jacopo J. V. Branca, Gabriele Morucci, Massimo Gulisano, Marco Ruggiero and Stefania Pacini

Nutrients 2013, 5(7), 2577-2589; https://doi.org/10.3390/nu5072577 - 8 Jul 2013

Cited by 34 | Viewed by 12363

Abstract

The role of vitamin D in maintaining health appears greater than originally thought, and the concept of the vitamin D axis underlines the complexity of the biological events controlled by biologically active vitamin D (1,25(OH)(2)D3), its two binding proteins that are the vitamin [...] Read more.

The role of vitamin D in maintaining health appears greater than originally thought, and the concept of the vitamin D axis underlines the complexity of the biological events controlled by biologically active vitamin D (1,25(OH)(2)D3), its two binding proteins that are the vitamin D receptor (VDR) and the vitamin D-binding protein-derived macrophage activating factor (GcMAF). In this study we demonstrate that GcMAF stimulates macrophages, which in turn attack human breast cancer cells, induce their apoptosis and eventually phagocytize them. These results are consistent with the observation that macrophages infiltrated implanted tumors in mice after GcMAF injections. In addition, we hypothesize that the last 23 hydrophobic amino acids of VDR, located at the inner part of the plasma membrane, interact with the first 23 hydrophobic amino acids of the GcMAF located at the external part of the plasma membrane. This al1ows 1,25(OH)(2)D3 and oleic acid to become sandwiched between the two vitamin D-binding proteins, thus postulating a novel molecular mode of interaction between GcMAF and VDR. Taken together, these results support and reinforce the hypothesis that GcMAF has multiple biological activities that could be responsible for its anti-cancer effects, possibly through molecular interaction with the VDR that in turn is responsible for a multitude of non-genomic as well as genomic effects. Full article

(This article belongs to the Special Issue Vitamin D and Human Health)

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Open AccessArticle

Vitamin D Status Is Associated with Disease Activity among Rheumatology Outpatients

by Zohreh Sabbagh, Janet Markland and Hassanali Vatanparast

Nutrients 2013, 5(7), 2268-2275; https://doi.org/10.3390/nu5072268 - 26 Jun 2013

Cited by 24 | Viewed by 9265

Abstract

The co-existence of high prevalence of vitamin D inadequacy among Canadians and high prevalence of systematic autoimmune rheumatic diseases (SARDs) raise the question on relationship between the two situations. Objective: To determine vitamin D status in known cases of common SARDs and compare [...] Read more.

The co-existence of high prevalence of vitamin D inadequacy among Canadians and high prevalence of systematic autoimmune rheumatic diseases (SARDs) raise the question on relationship between the two situations. Objective: To determine vitamin D status in known cases of common SARDs and compare to those with non-autoimmune diseases; further, to evaluate the impact of vitamin D on disease activity in rheumatoid arthritis (RA) cases. Methods: In a retrospective case-control study design, we evaluated 116 patients in a community clinic classified in two groups, Control group: patients with non-rheumatic disease (n = 56), and Case group: those with rheumatic diseases (n = 60). We compared plasma vitamin D status (25(OH)D), indicators of disease activity and other potential confounders. Further, we determined factors associated with disease activity in RA cases. Results: The plasma 25(OH)D was significantly lower in Case group (64.8 ± 29.8) compared to Control group (86.8 ± 37.7). High number of SARDs outpatients 56%) had considerably low plasma 25(OH)D concentration. RA cases with low plasma 25(OH)D had over five times higher risk of disease activity (OR = 5.15 95% CI 1.16, 22.9; p = 0.031). Conclusion: Inadequate vitamin D status in SARDs cases, along with considerably strong association with disease activity in RA cases, indicate the need for proper evaluation of vitamin D status in this clinical population. Moreover, appropriate training should be given to the patients to ensure the intake of the recommended amount of vitamin D per day through diet or supplement. Full article

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

by Michelle C. Mann, Derek V. Exner, Brenda R. Hemmelgarn, Darlene Y. Sola, Tanvir C. Turin, Linda Ellis and Sofia B. Ahmed

Nutrients 2013, 5(6), 2114-2127; https://doi.org/10.3390/nu5062114 - 10 Jun 2013

Cited by 45 | Viewed by 9026

Abstract

Vitamin D deficiency (≤50nmol/L 25-hydroxy vitamin D) is a cardiovascular (CV) risk factor that affects approximately one billion people worldwide, particularly those affected by chronic kidney disease (CKD). Individuals with CKD demonstrate abnormal cardiac autonomic nervous system activity, which has been linked to [...] Read more.

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

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Open AccessArticle

Effects of Vitamin D₃ and Paricalcitol on Immature Cardiomyocytes: A Novel Role for Vitamin D Analogs in the Prevention of Cardiovascular Diseases

by Stefania Pacini, Gabriele Morucci, Jacopo J. V. Branca, Stefano Aterini, Marcello Amato, Massimo Gulisano and Marco Ruggiero

Nutrients 2013, 5(6), 2076-2092; https://doi.org/10.3390/nu5062076 - 7 Jun 2013

Cited by 10 | Viewed by 8793

Abstract

Cardiovascular diseases are more prevalent in patients with chronic kidney disease than in the general population and they are considered the leading cause of death in patients with end-stage renal disease. The discovery that vitamin D₃ plays a considerable role in cardiovascular [...] Read more.

Cardiovascular diseases are more prevalent in patients with chronic kidney disease than in the general population and they are considered the leading cause of death in patients with end-stage renal disease. The discovery that vitamin D₃ plays a considerable role in cardiovascular protection has led, in recent years, to an increase in the administration of therapies based on the use of this molecule; nevertheless, several studies warned that an excess of vitamin D₃ may increase the risk of hypercalcemia and vascular calcifications. In this study we evaluated the effects of vitamin D₃, and of its selective analog paricalcitol, on immature cardiomyocytes. Results show that vitamin D₃ induces cAMP-mediated cell proliferation and significant intracellular calcification. Paricalcitol, however, induces cell differentiation, morphological modifications in cell shape and size, and no intracellular calcification. Furthermore, vitamin D₃ and paricalcitol differently affect cardiomyoblasts responses to acetylcholine treatment. In conclusion, our results demonstrate that the effects of vitamin D₃ and paricalcitol on cardiomyoblasts are different and, if these in vitro observations could be extrapolated in vivo, they suggest that paricalcitol has the potential for cardiovascular protection without the risk of inducing intracellular calcification. Full article

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Vitamin D Insufficiency and Bone Mineral Status in a Population of Newcomer Children in Canada

by Hassanali Vatanparast, Christine Nisbet and Brian Gushulak

Nutrients 2013, 5(5), 1561-1572; https://doi.org/10.3390/nu5051561 - 14 May 2013

Cited by 20 | Viewed by 8464

Abstract

Background: Low levels of circulating vitamin D are more likely to be found in those with darker skin pigmentation, who live in areas of high latitude, and who wear more clothing. We examined the prevalence of vitamin D deficiency and inadequacy in newcomer [...] Read more.

Background: Low levels of circulating vitamin D are more likely to be found in those with darker skin pigmentation, who live in areas of high latitude, and who wear more clothing. We examined the prevalence of vitamin D deficiency and inadequacy in newcomer immigrant and refugee children. Methods: We evaluated circulating vitamin D status of immigrant children at the national level. Subsequently, we investigated vitamin D intake, circulating vitamin D status, and total body bone mineral content (TBBMC) in newcomer children living in Saskatchewan. Results: In the sample of newcomer children in Saskatchewan, the prevalence of inadequacy in calcium and vitamin D intakes was 76% and 89.4%, respectively. Vitamin D intake from food/supplement was significantly higher in immigrants compared to refugees, which accords with the significant difference in serum status. Circulating vitamin D status indicated that 29% of participants were deficient and another 44% had inadequate levels of serum 25(OH)D for bone health. Dietary vitamin D intake, sex, region of origin, and length of stay in Canada were significant predictors of serum vitamin D status. Results for TBBMC revealed that 38.6% were found to have low TBBMC compared to estimated values for age, sex, and ethnicity. In the regression model, after controlling for possible confounders, children who were taller and had greater circulating vitamin D also had greater TBBMC. Nationally, immigrant children, particularly girls, have significantly lower plasma 25(OH)D than non-immigrant children. Interpretation: Newcomer immigrant and refugee children are at a high risk of vitamin D deficiency and inadequacy, which may have serious negative consequences for their health. Full article

(This article belongs to the Special Issue Vitamin D and Human Health)

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Higher Serum 25-Hydroxyvitamin D Concentrations Associate with a Faster Recovery of Skeletal Muscle Strength after Muscular Injury

by Tyler Barker, Vanessa T. Henriksen, Thomas B. Martins, Harry R. Hill, Carl R. Kjeldsberg, Erik D. Schneider, Brian M. Dixon and Lindell K. Weaver

Nutrients 2013, 5(4), 1253-1275; https://doi.org/10.3390/nu5041253 - 17 Apr 2013

Cited by 95 | Viewed by 17675

Abstract

The primary purpose of this study was to identify if serum 25-hydroxyvitamin D (25(OH)D) concentrations predict muscular weakness after intense exercise. We hypothesized that pre-exercise serum 25(OH)D concentrations inversely predict exercise-induced muscular weakness. Fourteen recreationally active adults participated in this study. Each subject [...] Read more.

The primary purpose of this study was to identify if serum 25-hydroxyvitamin D (25(OH)D) concentrations predict muscular weakness after intense exercise. We hypothesized that pre-exercise serum 25(OH)D concentrations inversely predict exercise-induced muscular weakness. Fourteen recreationally active adults participated in this study. Each subject had one leg randomly assigned as a control. The other leg performed an intense exercise protocol. Single-leg peak isometric force and blood 25(OH)D, aspartate and alanine aminotransferases, albumin, interferon (IFN)-γ, and interleukin-4 were measured prior to and following intense exercise. Following exercise, serum 25(OH)D concentrations increased (p < 0.05) immediately, but within minutes, subsequently decreased (p < 0.05). Circulating albumin increases predicted (p < 0.005) serum 25(OH)D increases, while IFN-γ increases predicted (p < 0.001) serum 25(OH)D decreases. Muscular weakness persisted within the exercise leg (p < 0.05) and compared to the control leg (p < 0.05) after the exercise protocol. Serum 25(OH)D concentrations inversely predicted (p < 0.05) muscular weakness (i.e., control leg vs. exercise leg peak isometric force) immediately and days (i.e., 48-h and 72-h) after exercise, suggesting the attenuation of exercise-induced muscular weakness with increasing serum 25(OH)D prior to exercise. Based on these data, we conclude that pre-exercise serum 25(OH)D concentrations could influence the recovery of skeletal muscle strength after an acute bout of intense exercise. Full article

(This article belongs to the Special Issue Vitamin D and Human Health)

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Open AccessArticle

Total Vitamin D Assay Comparison of the Roche Diagnostics “Vitamin D Total” Electrochemiluminescence Protein Binding Assay with the Chromsystems HPLC Method in a Population with both D2 and D3 forms of Vitamin D

by Laila Abdel-Wareth, Afrozul Haq, Andrew Turner, Shoukat Khan, Arwa Salem, Faten Mustafa, Nafiz Hussein, Fasila Pallinalakam, Louisa Grundy, Gemma Patras and Jaishen Rajah

Nutrients 2013, 5(3), 971-980; https://doi.org/10.3390/nu5030971 - 22 Mar 2013

Cited by 58 | Viewed by 14402

Abstract

This study compared two methods of assaying the 25-hydroxylated metabolites of cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2). A fully automated electrochemiluminescence assay from Roche Diagnostics and an HPLC based method from Chromsystems were used to measure vitamin D levels in surplus sera [...] Read more.

This study compared two methods of assaying the 25-hydroxylated metabolites of cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2). A fully automated electrochemiluminescence assay from Roche Diagnostics and an HPLC based method from Chromsystems were used to measure vitamin D levels in surplus sera from 96 individuals, where the majority has the D2 form of the vitamin. Deming regression, concordance rate, correlation and Altman Bland agreement were performed. Seventy two subjects (75%) had a D2 concentration >10 nmol/L while the remaining twenty four subjects had vitamin D2 concentration of less than 10 nmol/L by HPLC. Overall, the Roche Diagnostics method showed a negative bias of −2.59 ± 4.11 nmol/L on the e602 as compared to the HPLC with a concordance rate of 84%. The concordance rate was 91% in samples with D2 of less than 10 nmol/L and 82% in those with D2 concentration >10 nmol/L. The overall correlation had an r value of 0.77. The r value was higher in samples with D2 levels of less than 10 nmol/L, r = 0.96, as compared to those with D2 values of greater than 10 nmol/L, r = 0.74. The observed bias had little impact on clinical decision and therefore is clinically acceptable. Full article

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Open AccessArticle

The ABC of Vitamin D: A Qualitative Study of the Knowledge and Attitudes Regarding Vitamin D Deficiency amongst Selected Population Groups

by Billie Bonevski, Jamie Bryant, Sylvie Lambert, Irena Brozek and Vanessa Rock

Nutrients 2013, 5(3), 915-927; https://doi.org/10.3390/nu5030915 - 15 Mar 2013

Cited by 27 | Viewed by 11734

Abstract

Objective: In Australia, vitamin D supply in food is limited, and sun exposure is the main source of vitamin D. However skin cancer risk is high, and the need to gain some sun exposure for adequate vitamin D is challenging public health messages [...] Read more.

Objective: In Australia, vitamin D supply in food is limited, and sun exposure is the main source of vitamin D. However skin cancer risk is high, and the need to gain some sun exposure for adequate vitamin D is challenging public health messages to use protection in the sun. The complex vitamin D public health message may be confusing the public and, in particular, those at highest risk for vitamin D deficiency. This study explored vitamin D and sun exposure attitudes, knowledge and practices of some groups considered at risk of vitamin D deficiency and those delivering healthy sun exposure messages to children. Method: 52 adults participated in six focus groups. Results: Results corroborated with previous research showing low levels of vitamin D knowledge. Individual and environmental barriers to receiving adequate sun exposure were also identified. Conclusions and Implications: The message advocating balanced sun exposure to produce adequate vitamin D needs to be made clearer and be more effectively communicated. Findings provide insights to aid development of appropriate public health messages for safe sun exposure and vitamin D, especially for vulnerable groups. Full article

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Pharmacokinetics of High-Dose Weekly Oral Vitamin D3 Supplementation during the Third Trimester of Pregnancy in Dhaka, Bangladesh

by Daniel E. Roth, Abdullah Al Mahmud, Rubhana Raqib, Evana Akhtar, Robert E. Black and Abdullah H. Baqui

Nutrients 2013, 5(3), 788-810; https://doi.org/10.3390/nu5030788 - 12 Mar 2013

Cited by 26 | Viewed by 10078

Abstract

A pharmacokinetic study was conducted to assess the biochemical dose-response and tolerability of high-dose prenatal vitamin D3 supplementation in Dhaka, Bangladesh (23°N). Pregnant women at 27–30 weeks gestation (n = 28) were randomized to 70,000 IU once + 35,000 IU/week vitamin D3 [...] Read more.

A pharmacokinetic study was conducted to assess the biochemical dose-response and tolerability of high-dose prenatal vitamin D3 supplementation in Dhaka, Bangladesh (23°N). Pregnant women at 27–30 weeks gestation (n = 28) were randomized to 70,000 IU once + 35,000 IU/week vitamin D3 (group PH: pregnant, higher dose) or 14,000 IU/week vitamin D3 (PL: pregnant, lower dose) until delivery. A group of non-pregnant women (n = 16) was similarly administered 70,000 IU once + 35,000 IU/week for 10 weeks (NH: non-pregnant, higher-dose). Rise (∆) in serum 25-hydroxyvitamin D concentration ([25(OH)D]) above baseline was the primary pharmacokinetic outcome. Baseline mean [25(OH)D] were similar in PH and PL (35 nmol/L vs. 31 nmol/L, p = 0.34). A dose-response effect was observed: ∆[25(OH)D] at modeled steady-state was 19 nmol/L (95% CI, 1 to 37) higher in PH vs. PL (p = 0.044). ∆[25(OH)D] at modeled steady-state was lower in PH versus NH but the difference was not significant (−15 nmol/L, 95% CI −34 to 5; p = 0.13). In PH, 100% attained [25(OH)D] ≥ 50 nmol/L and 90% attained [25(OH)D] ≥ 80 nmol/L; in PL, 89% attained [25(OH)D] ≥ 50 nmol/L but 56% attained [25(OH)D] ≥ 80 nmol/L. Cord [25(OH)D] (n = 23) was slightly higher in PH versus PL (117 nmol/L vs. 98 nmol/L; p = 0.07). Vitamin D3 was well tolerated; there were no supplement-related serious adverse clinical events or hypercalcemia. In summary, a regimen of an initial dose of 70,000 IU and 35,000 IU/week vitamin D3 in the third trimester of pregnancy was non-hypercalcemic and attained [25(OH)D] ≥ 80 nmol/L in virtually all mothers and newborns. Further research is required to establish the safety of high-dose vitamin D3 in pregnancy and to determine if supplement-induced [25(OH)D] elevations lead to maternal-infant health benefits. Full article

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Review

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Open AccessReview

Vitamin D and Depression: A Systematic Review and Meta-Analysis Comparing Studies with and without Biological Flaws

by Simon Spedding

Nutrients 2014, 6(4), 1501-1518; https://doi.org/10.3390/nu6041501 - 11 Apr 2014

Cited by 242 | Viewed by 32290

Abstract

Efficacy of Vitamin D supplements in depression is controversial, awaiting further literature analysis. Biological flaws in primary studies is a possible reason meta-analyses of Vitamin D have failed to demonstrate efficacy. This systematic review and meta-analysis of Vitamin D and depression compared studies [...] Read more.

Efficacy of Vitamin D supplements in depression is controversial, awaiting further literature analysis. Biological flaws in primary studies is a possible reason meta-analyses of Vitamin D have failed to demonstrate efficacy. This systematic review and meta-analysis of Vitamin D and depression compared studies with and without biological flaws. The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The literature search was undertaken through four databases for randomized controlled trials (RCTs). Studies were critically appraised for methodological quality and biological flaws, in relation to the hypothesis and study design. Meta-analyses were performed for studies according to the presence of biological flaws. The 15 RCTs identified provide a more comprehensive evidence-base than previous systematic reviews; methodological quality of studies was generally good and methodology was diverse. A meta-analysis of all studies without flaws demonstrated a statistically significant improvement in depression with Vitamin D supplements (+0.78 CI +0.24, +1.27). Studies with biological flaws were mainly inconclusive, with the meta-analysis demonstrating a statistically significant worsening in depression by taking Vitamin D supplements (−1.1 CI −0.7, −1.5). Vitamin D supplementation (≥800 I.U. daily) was somewhat favorable in the management of depression in studies that demonstrate a change in vitamin levels, and the effect size was comparable to that of anti-depressant medication. Full article

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Molecular Link between Vitamin D and Cancer Prevention

by Meis Moukayed and William B. Grant

Nutrients 2013, 5(10), 3993-4021; https://doi.org/10.3390/nu5103993 - 30 Sep 2013

Cited by 150 | Viewed by 23338

Abstract

The metabolite of vitamin D, 1α,25-dihydroxyvitamin D₃ (also known as calcitriol),is a biologically active molecule required to maintain the physiological functions of several target tissues in the human body from conception to adulthood. Its molecular mode of action ranges from immediate [...] Read more.

The metabolite of vitamin D, 1α,25-dihydroxyvitamin D₃ (also known as calcitriol),is a biologically active molecule required to maintain the physiological functions of several target tissues in the human body from conception to adulthood. Its molecular mode of action ranges from immediate nongenomic responses to longer term mechanisms that exert persistent genomic effects. The genomic mechanisms of vitamin D action rely on cross talk between 1α,25-dihydroxyvitamin D₃ signaling pathways and that of other growth factors or hormones that collectively regulate cell proliferation, differentiation and cell survival. In vitro and in vivo studies demonstrate a role for vitamin D (calcitriol) in modulating cellular growth and development. Vitamin D (calcitriol) acts as an antiproliferative agent in many tissues and significantly slows malignant cellular growth. Moreover, epidemiological studies have suggested that ultraviolet-B exposure can help reduce cancer risk and prevalence, indicating a potential role for vitamin D as a feasible agent to prevent cancer incidence and recurrence. With the preventive potential of this biologically active agent, we suggest that countries where cancer is on the rise—yet where sunlight and, hence, vitamin D may be easily acquired—adopt awareness, education and implementation strategies to increase supplementation with vitamin D in all age groups as a preventive measure to reduce cancer risk and prevalence. Full article

(This article belongs to the Special Issue Vitamin D and Human Health)

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Open AccessReview

Vitamin D: Deficiency, Sufficiency and Toxicity

by Fahad Alshahrani and Naji Aljohani

Nutrients 2013, 5(9), 3605-3616; https://doi.org/10.3390/nu5093605 - 13 Sep 2013

Cited by 214 | Viewed by 29380

Abstract

The plethora of vitamin D studies over the recent years highlight the pleomorphic effects of vitamin D outside its conventional role in calcium and bone homeostasis. Vitamin D deficiency, though common and known, still faces several challenges among the medical community in terms [...] Read more.

The plethora of vitamin D studies over the recent years highlight the pleomorphic effects of vitamin D outside its conventional role in calcium and bone homeostasis. Vitamin D deficiency, though common and known, still faces several challenges among the medical community in terms of proper diagnosis and correction. In this review, the different levels of vitamin D and its clinical implications are highlighted. Recommendations and consensuses for the appropriate dose and duration for each vitamin D status are also emphasized. Full article

(This article belongs to the Special Issue Vitamin D and Human Health)

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Open AccessReview

Vitamin D Intake and Risk of Type 1 Diabetes: A Meta-Analysis of Observational Studies

by Jia-Yi Dong, Weiguo Zhang, Jiong Jack Chen, Zeng-Li Zhang, Shu-Fen Han and Li-Qiang Qin

Nutrients 2013, 5(9), 3551-3562; https://doi.org/10.3390/nu5093551 - 12 Sep 2013

Cited by 152 | Viewed by 15944

Abstract

Vitamin D is suggested to have protective effects against type 1 diabetes. However, the results from observational studies have been inconsistent. We aimed to examine their association by conducting a meta-analysis of observational studies. Multiple databases were searched in June 2013 to identify [...] Read more.

Vitamin D is suggested to have protective effects against type 1 diabetes. However, the results from observational studies have been inconsistent. We aimed to examine their association by conducting a meta-analysis of observational studies. Multiple databases were searched in June 2013 to identify relevant studies including both case-control and cohort studies. Either a fixed- or random-effects model was used to calculate the pooled risk estimate. We identified eight studies (two cohort studies and six case-control studies) on vitamin D intake during early life and three studies (two cohort studies and one case-control study) on maternal vitamin D intake during pregnancy. The pooled odds ratio for type 1 diabetes comparing vitamin D supplementation with non-supplementation during early life was 0.71 (95% confidence interval [CI], 0.51–0.98). Similar results were observed in the case-control subgroup analysis but not in the cohort subgroup analysis. The pooled odds ratio with maternal intake of vitamin D during pregnancy was 0.95 (95% CI, 0.66–1.36). In conclusion, vitamin D intake during early life may be associated with a reduced risk of type 1 diabetes. However, there was not enough evidence for an association between maternal intake of vitamin D and risk of type 1 diabetes in the offspring. Full article

(This article belongs to the Special Issue Vitamin D and Human Health)

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Open AccessReview

The Role of Vitamin D in Blood Pressure, Endothelial and Renal Function in Postmenopausal Women

by Zhao-Min Liu, Jean Woo, Sheng-Hui Wu and Suzanne C. Ho

Nutrients 2013, 5(7), 2590-2610; https://doi.org/10.3390/nu5072590 - 9 Jul 2013

Cited by 25 | Viewed by 9421

Abstract

Background: Vitamin D is a pro-hormone that plays an essential role in the vasculature and in kidney function. Aims: To review the extra-skeletal effects of vitamin D on blood pressure, endothelial and renal function with emphasis on recent findings in postmenopausal [...] Read more.

Background: Vitamin D is a pro-hormone that plays an essential role in the vasculature and in kidney function. Aims: To review the extra-skeletal effects of vitamin D on blood pressure, endothelial and renal function with emphasis on recent findings in postmenopausal women. Methods: Included in this review was a PubMed database search for English language articles through March 2013. This review discussed the physiology and definition of vitamin D deficiency, the recent evidence for the role vitamin D in blood pressure, vascular and renal function. Results: Experimental and epidemiological data suggest that vitamin D plays an important role in the vasculature and in kidney function. Low vitamin D concentrations appear to significantly associate with hypertension, endothelial and renal dysfunction. However, the results of clinical trials have generally been mixed. Studies specifically conducted among postmenopausal women are limited and findings are still inconsistent. Conclusions: Definitive studies are warranted to elucidate the effects of vitamin D supplementation on vascular and renal function and a more detailed work is needed to outline the route, duration and optimal dose of supplementation. It is premature to recommend vitamin D as a therapeutic option in the improvement of vascular and renal function at the current stage. Full article

(This article belongs to the Special Issue Vitamin D and Human Health)

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Open AccessReview

Calcidiol Deficiency in End-Stage Organ Failure and after Solid Organ Transplantation: Status quo

by Ursula Thiem, Bartosz Olbramski and Kyra Borchhardt

Nutrients 2013, 5(7), 2352-2371; https://doi.org/10.3390/nu5072352 - 1 Jul 2013

Cited by 5 | Viewed by 7501

Abstract

Among patients with organ failure, vitamin D deficiency is extremely common and frequently does not resolve after transplantation. This review crystallizes and summarizes existing data on the status quo of vitamin D deficiency in patients with organ failure and in solid organ transplant [...] Read more.

Among patients with organ failure, vitamin D deficiency is extremely common and frequently does not resolve after transplantation. This review crystallizes and summarizes existing data on the status quo of vitamin D deficiency in patients with organ failure and in solid organ transplant recipients. Interventional studies evaluating different treatment strategies, as well as current clinical practice guidelines and recommendations on the management of low vitamin D status in these patients are also discussed. Full article

(This article belongs to the Special Issue Vitamin D and Human Health)

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Open AccessReview

The Role of Vitamin D in Hematologic Disease and Stem Cell Transplantation

by Aric C. Hall and Mark B. Juckett

Nutrients 2013, 5(6), 2206-2221; https://doi.org/10.3390/nu5062206 - 18 Jun 2013

Cited by 39 | Viewed by 10180

Abstract

Vitamin D is a steroid hormone with a broad range of biological effects ranging from the classical role as a mediator of calcium and phosphate balance to cellular differentiation and immune modulation. These effects impact normal and dysfunctional hematopoietic and immune function, which [...] Read more.

Vitamin D is a steroid hormone with a broad range of biological effects ranging from the classical role as a mediator of calcium and phosphate balance to cellular differentiation and immune modulation. These effects impact normal and dysfunctional hematopoietic and immune function, which may allow an avenue for improved treatment and support of patients suffering from hematologic disorders. In this review, we will summarize the role of vitamin D in normal hematopoiesis, discuss ways in which vitamin D may improve outcomes, and discuss a potential role of vitamin D for treating hematologic disorders and modulating the immune system to improve the outcome of allogeneic stem cell transplant. Full article

(This article belongs to the Special Issue Vitamin D and Human Health)

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Open AccessReview

Vitamin D and the Athlete: Risks, Recommendations, and Benefits

by Dana Ogan and Kelly Pritchett

Nutrients 2013, 5(6), 1856-1868; https://doi.org/10.3390/nu5061856 - 28 May 2013

Cited by 140 | Viewed by 29364

Abstract

Vitamin D is well known for its role in calcium regulation and bone health, but emerging literature tells of vitamin D’s central role in other vital body processes, such as: signaling gene response, protein synthesis, hormone synthesis, immune response, plus, cell turnover and [...] Read more.

Vitamin D is well known for its role in calcium regulation and bone health, but emerging literature tells of vitamin D’s central role in other vital body processes, such as: signaling gene response, protein synthesis, hormone synthesis, immune response, plus, cell turnover and regeneration. The discovery of the vitamin D receptor within the muscle suggested a significant role for vitamin D in muscle tissue function. This discovery led researchers to question the impact that vitamin D deficiency could have on athletic performance and injury. With over 77% of the general population considered vitamin D insufficient, it’s likely that many athletes fall into the same category. Research has suggested vitamin D to have a significant effect on muscle weakness, pain, balance, and fractures in the aging population; still, the athletic population is yet to be fully examined. There are few studies to date that have examined the relationship between vitamin D status and performance, therefore, this review will focus on the bodily roles of vitamin D, recommended 25(OH)D levels, vitamin D intake guidelines and risk factors for vitamin D insufficiency in athletes. In addition, the preliminary findings regarding vitamin D’s impact on athletic performance will be examined. Full article

(This article belongs to the Special Issue Vitamin D and Human Health)

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Open AccessReview

Vitamin D and Obesity

by Simon Vanlint

Nutrients 2013, 5(3), 949-956; https://doi.org/10.3390/nu5030949 - 20 Mar 2013

Cited by 283 | Viewed by 25669

Abstract

Obesity is a significant health problem world-wide, particularly in developed nations. Vitamin D deficiency is pandemic, and has been implicated in a wide variety of disease states. This paper seeks to examine the consistently reported relationship between obesity and low vitamin D concentrations, [...] Read more.

Obesity is a significant health problem world-wide, particularly in developed nations. Vitamin D deficiency is pandemic, and has been implicated in a wide variety of disease states. This paper seeks to examine the consistently reported relationship between obesity and low vitamin D concentrations, with reference to the possible underlying mechanisms. The possibility that vitamin D may assist in preventing or treating obesity is also examined, and recommendations for future research are made. There is a clear need for adequately-powered, prospective interventions which include baseline measurement of 25D concentrations and involve adequate doses of supplemental vitamin D. Until such studies have been reported, the role of vitamin D supplementation in obesity prevention remains uncertain. Full article

(This article belongs to the Special Issue Vitamin D and Human Health)

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Jump to: Editorial, Research, Review

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Open AccessCommentary

Does Vitamin D Sufficiency Equate to a Single Serum 25-Hydroxyvitamin D Level or Are Different Levels Required for Non-Skeletal Diseases?

by Simon Spedding, Simon Vanlint, Howard Morris and Robert Scragg

Nutrients 2013, 5(12), 5127-5139; https://doi.org/10.3390/nu5125127 - 16 Dec 2013

Cited by 84 | Viewed by 11589

Abstract

Objective: Clarify the concept of vitamin D sufficiency, the relationship between efficacy and vitamin D status and the role of Vitamin D supplementation in the management of non-skeletal diseases. We outline reasons for anticipating different serum vitamin D levels are required for different [...] Read more.

Objective: Clarify the concept of vitamin D sufficiency, the relationship between efficacy and vitamin D status and the role of Vitamin D supplementation in the management of non-skeletal diseases. We outline reasons for anticipating different serum vitamin D levels are required for different diseases. Method: Review the literature for evidence of efficacy of supplementation and minimum effective 25-hydroxyvitamin D (25-OHD) levels in non-skeletal disease. Results: Evidence of efficacy of vitamin supplementation is graded according to levels of evidence. Minimum effective serum 25-OHD levels are lower for skeletal disease, e.g., rickets (25 nmol/L), osteoporosis and fractures (50 nmol/L), than for premature mortality (75 nmol/L) or non-skeletal diseases, e.g., depression (75 nmol/L), diabetes and cardiovascular disease (80 nmol/L), falls and respiratory infections (95 nmol/L) and cancer (100 nmol/L). Conclusions: Evidence for the efficacy of vitamin D supplementation at serum 25-OHD levels ranging from 25 to 100 nmol/L has been obtained from trials with vitamin D interventions that change vitamin D status by increasing serum 25-OHD to a level consistent with sufficiency for that disease. This evidence supports the hypothesis that just as vitamin D metabolism is tissue dependent, so the serum levels of 25-OHD signifying deficiency or sufficiency are disease dependent. Full article

(This article belongs to the Special Issue Vitamin D and Human Health)

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