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Vitamin D in Health and the Prevention and Treatment of Disease

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Micronutrients and Human Health".

Deadline for manuscript submissions: closed (20 December 2019) | Viewed by 96361

Special Issue Editor

Prof. Dr. Igor Sergeev

E-Mail Website
Guest Editor
Health and Nutritional Sciences, South Dakota State University, Brookings, SD 57007, USA
Interests: vitamin D; calcium; bioactive food components; nutrient regulation of apoptosis; vitamin D, calcium, and bioactives in the prevention of obesity and cancer; vitamin D and cell calcium
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nutrients is planning a Special Issue on the role of vitamin D in health and disease. Vitamin D is essential for regulating a number of cellular and organismal functions. Mechanistic molecular, biochemical, cellular, and animal studies, epidemiological analyses, and clinical trials have linked vitamin D to various diseases and presented a possibility that vitamin D is required for maintaining good health throughout life. The definition of vitamin D status as deficient, sufficient, and optimal is actively debated. Physicians, dieticians, and other health professionals receive contradictory messages regarding optimal vitamin D status, vitamin D deficiency and toxicity, and the necessity of evaluating blood levels of vitamin D and promoting vitamin D supplementation. Vitamin D dietary requirements, food fortification, and regulatory issues are reevaluated by government agencies, which are under pressure to increase the recommended dietary vitamin D intake. Vitamin D analogues for treatment of various diseases have been clinically approved or are under development. These considerations warrant a Special Issue on vitamin D to include emerging basic and applied research and make an attempt to resolve controversial issues. Manuscripts presenting basic, applied, and clinical research, observational, and meta-analysis studies, and analytical reviews in the vitamin D area are encouraged for this Special Issue.

Prof. Dr. Igor Sergeev
Guest Editor

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Keywords

  • Vitamin D status
  • Vitamin D and health
  • Vitamin D and disease
  • Vitamin D functions
  • Vitamin D requirements
  • Vitamin D mechanism of action
  • Vitamin D analogues

Published Papers (17 papers)

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16 pages, 1248 KiB  
Article
Plasma 25-Hydroxyvitamin D Levels and VDR Gene Expression in Peripheral Blood Mononuclear Cells of Leukemia Patients and Healthy Subjects in Central Kazakhstan
by Assel G. Zhumina, Konstantin Li, Anna A. Konovalova, Yelena A. Li, Margarita Yu. Ishmuratova, Gayane P. Pogossyan and Michael Danilenko
Nutrients 2020, 12(5), 1229; https://doi.org/10.3390/nu12051229 - 26 Apr 2020
Cited by 5 | Viewed by 2650
Abstract
Low blood levels of the vitamin D metabolite 25-hydroxyvitamin D [25(OH)D] have been associated with an increased risk and poorer outcomes of various cancers, including hematological malignancies. The Central Kazakhstan area has a relatively high incidence rate of leukemia. However, the relationship between [...] Read more.
Low blood levels of the vitamin D metabolite 25-hydroxyvitamin D [25(OH)D] have been associated with an increased risk and poorer outcomes of various cancers, including hematological malignancies. The Central Kazakhstan area has a relatively high incidence rate of leukemia. However, the relationship between vitamin D status and leukemia or other types of cancer in Kazakhstan has not yet been addressed. Therefore, in this first pilot single-center study conducted in Central Kazakhstan, we compared plasma levels of 25(OH)D and the vitamin D receptor (VDR) gene expression levels in peripheral blood mononuclear cells of patients with leukemia and demographically matching healthy volunteers. The levels of 25(OH)D in patients were found to be significantly lower (10.8 ± 7.0 ng/mL; n = 31) than in healthy subjects (21.6 ± 7.8 ng/mL; n = 34; p < 0.0001). A similar difference was observed in both younger (<60 years old) and older (>60 years old) participants, though there was no association between 25(OH)D concentration and age within the patient group. In female patients, 25(OH)D levels were significantly lower than in male patients (p = 0.04). No significant seasonal variations of 25(OH)D were observed in either the patient or the control group. VDR gene expression levels appeared to be similar in leukemia patients and healthy subjects, and no correlation between the cellular VDR expression and plasma 25(OH)D concentrations was observed in either group of participants. We did not observe a significant association of 25(OH)D or VDR levels and overall survival of leukemia patients. This observational study conducted for the first time in Kazakhstan supports previous findings demonstrating reduced blood 25(OH)D levels in cancer (leukemia) patients. Larger studies are required to determine whether low 25(OH)D plasma concentrations represent a risk factor for leukemia development and/or progression. Full article
(This article belongs to the Special Issue Vitamin D in Health and the Prevention and Treatment of Disease)
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14 pages, 866 KiB  
Article
Infants’ Vitamin D Nutritional Status in the First Year of Life in Northern Taiwan
by Chiao-Ming Chen, Shu-Ci Mu, Yi-Ling Chen, Li-Yi Tsai, Yung-Ting Kuo, In-Mei Cheong, Mei-Ling Chang and Sing-Chung Li
Nutrients 2020, 12(2), 404; https://doi.org/10.3390/nu12020404 - 04 Feb 2020
Cited by 7 | Viewed by 3426
Abstract
Vitamin D deficiency (VDD) and insufficiency (VDI) are common among exclusively breastfeeding infants. However, epidemiological evidence for the prevalence of VDD in infants during their first year of life in Taiwan has never been found. This trial determined the prevalence of VDD and [...] Read more.
Vitamin D deficiency (VDD) and insufficiency (VDI) are common among exclusively breastfeeding infants. However, epidemiological evidence for the prevalence of VDD in infants during their first year of life in Taiwan has never been found. This trial determined the prevalence of VDD and VDI and the association between dietary vitamin D and vitamin D nutritional status in Northern Taiwan. A cross-sectional study was conducted on infants who returned to well-baby examinations from October 2012 to January 2014 in three hospitals: Shin Kong Wu Ho-Su Memorial Hospital, Taipei Medical University Hospital, and Shuang Ho Hospital. The specific vitamin D cut-off concentrations for VDD, VDI, and VDS are 25(OH)D3 levels ≤20, 21–29, and ≥30 (ng/mL). Overall, 481 infants’ parents completed a questionnaire comprising questions related to vitamin D nutritional status, including weekly time outdoors, breastfeeding status, anthropometric measurement, and assessment of dietary intake, including milk and complementary food. The results revealed that 197 (41%) and 212 (44%) of infants in their first year of life had VDI and VDD, respectively, by the Endocrine Society guidelines. Breastfed infants had a higher prevalence of VDI (86.1%) than did mixed-fed (51.9%) and formula-fed (38.5%) infants (p < 0.001). The prevalence of VDD was 55.4% in infants aged under six months but increased to 61.6% in infants aged over six months. Infants in the VDI and VDD groups had the same anthropometrics as those in the vitamin D sufficiency (VDS) group. Our results revealed that 25(OH)D3 had a negative correlation with the intact parathyroid hormone (iPTH) when the serum 25(OH)D3 level ≤20 ng/mL (r = −0.21, p = 0.001). The VDS group had a higher total vitamin D intake than did the VDI and VDD groups, which was mainly obtained from infant formula. Our data revealed that dietary vitamin D intake and birth season were major indicators in predicting VDD. Lower dietary vitamin D intake and born in winter and spring significantly increased the odds ratio (OR) for VDI by 1.15 (95% CI 1.09–1.20) and 2.02 (95% CI 1.10–3.70), respectively, and that for VDD by 1.23 (95% CI 1.16–1.31) and 2.37 (95% CI 1.35–4.17) without covariates adjustment, respectively. Furthermore, ORs for VDI and VDD significantly differed after adjustment for covariates. In conclusion, the prevalence of VDI and VDD were high in infants during the first year of life. Breastfeeding infants had difficulty in obtaining sufficient vitamin D from diet. In cases where the amount of sun exposure that is safe and sufficient to improve vitamin D status is unclear, breastfed infants aged below one year old are recommended to be supplemented with vitamin D. Full article
(This article belongs to the Special Issue Vitamin D in Health and the Prevention and Treatment of Disease)
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11 pages, 2407 KiB  
Article
Combined Treatment with Omega-3 Fatty Acid and Cholecalciferol Increases 1,25-Dihydroxyvitamin D Levels by Modulating Dysregulation of Vitamin D Metabolism in 5/6 Nephrectomy Rats
by Su Mi Lee, Mi Hwa Lee, Young Ki Son, Seong Eun Kim and Won Suk An
Nutrients 2019, 11(12), 2903; https://doi.org/10.3390/nu11122903 - 01 Dec 2019
Cited by 6 | Viewed by 3044
Abstract
The protein 1α-hydroxylase (CYP27B1) was expressed in liver and omega-3 fatty acid (FA) elevated 1,25-dihydroxyvitamin D [1,25(OH)2D] levels in dialysis patients. The aim of this study was to determine whether omega-3 FA and cholecalciferol have effects on vitamin D metabolism related [...] Read more.
The protein 1α-hydroxylase (CYP27B1) was expressed in liver and omega-3 fatty acid (FA) elevated 1,25-dihydroxyvitamin D [1,25(OH)2D] levels in dialysis patients. The aim of this study was to determine whether omega-3 FA and cholecalciferol have effects on vitamin D metabolism related to CYP27B1 and 24-hydroxylase (CYP24) activities in the kidney and liver of 5/6 nephrectomy (Nx) rats. Male Sprague–Dawley rats were divided into the following groups: sham control, 5/6 Nx, 5/6 Nx treated with cholecalciferol, 5/6 Nx treated with omega-3 FA, and 5/6 Nx treated with cholecalciferol/omega-3 FA. CYP27B1 and CYP24 expression were measured in the liver and kidney. Further, 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] levels were measured in serum. Among Nx groups, 1,25(OH)2D and 25(OH)D levels were lowest in the 5/6 Nx group. CYP24 expression was increased in the kidney of the 5/6 Nx rat model, which was found to be reversed by omega-3 FA or cholecalciferol/omega-3 FA supplementation. Decreased CYP27B1 expression was observed in the liver of the 5/6 Nx rats and its expression was recovered by supplementation with cholecalciferol/omega-3 FA. In conclusion, omega-3 FA and cholecalciferol may synergistically increase 1,25(OH)2D levels by inhibiting CYP24 expression in the kidney and liver and activating CYP27B1 expression in the liver of 5/6 Nx rats. Full article
(This article belongs to the Special Issue Vitamin D in Health and the Prevention and Treatment of Disease)
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13 pages, 2534 KiB  
Article
Effect of Vitamin D Supplementation on Faecal Microbiota: A Randomised Clinical Trial
by Negar Naderpoor, Aya Mousa, Luisa Fernanda Gomez Arango, Helen L. Barrett, Marloes Dekker Nitert and Barbora de Courten
Nutrients 2019, 11(12), 2888; https://doi.org/10.3390/nu11122888 - 27 Nov 2019
Cited by 56 | Viewed by 7054
Abstract
In animal studies, vitamin D supplementation has been shown to improve gut microbiota and intestinal inflammation. However, limited evidence exists on the effect of vitamin D supplementation on the human gut microbiota. We examined the effect of vitamin D supplementation on faecal microbiota [...] Read more.
In animal studies, vitamin D supplementation has been shown to improve gut microbiota and intestinal inflammation. However, limited evidence exists on the effect of vitamin D supplementation on the human gut microbiota. We examined the effect of vitamin D supplementation on faecal microbiota in 26 vitamin D-deficient (25-hydroxyvitamin D (25(OH)D) ≤50 nmol/L), overweight or obese (BMI ≥25 kg/m2) otherwise healthy adults. Our study was ancillary to a community based double-blind randomised clinical trial, conducted between 2014 and 2016. The participants provided stool samples at baseline and after 100,000 international units (IU) loading dose of cholecalciferol followed by 4000 IU daily or matching placebo for 16 weeks. Faecal microbiota was analysed using 16S rRNA sequencing; V6–8 region. There was no significant difference in microbiome α-diversity between vitamin D and placebo groups at baseline and follow-up (all p > 0.05). In addition, no clustering was found based on vitamin D supplementation at follow-up (p = 0.3). However, there was a significant association between community composition and vitamin D supplementation at the genus level (p = 0.04). The vitamin D group had a higher abundance of genus Lachnospira, and lower abundance of genus Blautia (linear discriminate analysis >3.0). Moreover, individuals with 25(OH)D >75 nmol/L had a higher abundance of genus Coprococcus and lower abundance of genus Ruminococcus compared to those with 25(OH)D <50 nmol/L. Our findings suggest that vitamin D supplementation has some distinct effects on faecal microbiota. Future studies need to explore whether these effects would translate into improved clinical outcomes. Full article
(This article belongs to the Special Issue Vitamin D in Health and the Prevention and Treatment of Disease)
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14 pages, 1916 KiB  
Article
Developmental Vitamin D Deficiency in the Rat Impairs Recognition Memory, but Has No Effect on Social Approach or Hedonia
by Kathie Overeem, Suzy Alexander, Thomas H. J. Burne, Pauline Ko and Darryl W. Eyles
Nutrients 2019, 11(11), 2713; https://doi.org/10.3390/nu11112713 - 08 Nov 2019
Cited by 12 | Viewed by 2767
Abstract
Developmental vitamin D (DVD) deficiency is a risk factor for schizophrenia. In rodents we show that DVD-deficiency alters brain development and produces behavioral phenotypes in the offspring of relevance to the positive symptoms of schizophrenia. The aims of this study are to examine [...] Read more.
Developmental vitamin D (DVD) deficiency is a risk factor for schizophrenia. In rodents we show that DVD-deficiency alters brain development and produces behavioral phenotypes in the offspring of relevance to the positive symptoms of schizophrenia. The aims of this study are to examine behavioral phenotypes specific to the cognitive and negative symptoms of schizophrenia in this model, and to vary the duration of vitamin D deficiency during gestation and beyond birth. We hypothesize that a longer duration of DVD-deficiency would result in greater behavioral impairments. Female vitamin D-deficient Sprague Dawley dams were mated at 10 weeks of age. Dietary vitamin D was reintroduced to dams and/or pups at different developmental time-points: Conception, Birth, Post-natal day (PND) 6 and PND21. Adult male and female offspring were assessed on a battery of behavioral tests, including sucrose preference, open field, novel object recognition (NOR), social approach and social novelty. We find that all windows of DVD-deficiency impaired NOR a cognitive measure that requires intact recognition memory. Sucrose consumption, social approach and social memory negative symptom-like phenotypes were unaffected by any maternal dietary manipulation. In addition, contrary to our hypothesis, we find that rats in the Conception group, that is the shortest duration of vitamin D deficiency, demonstrate increased locomotor activity, and decreased interaction time with novel objects. These findings have implications for the increasing number of studies examining the preclinical consequences of maternal vitamin D deficiency, and continue to suggest that adequate levels of maternal vitamin D are required for normal brain development. Full article
(This article belongs to the Special Issue Vitamin D in Health and the Prevention and Treatment of Disease)
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11 pages, 855 KiB  
Article
Early Rehabilitation Program and Vitamin D Supplementation Improves Sensitivity of Balance and the Postural Control in Patients after Posterior Lumbar Interbody Fusion: A Randomized Trial
by Wojciech Skrobot, Ewelina Liedtke, Katarzyna Krasowska, Katarzyna P. Dzik, Damian J. Flis, Anna Samoraj-Dereszkiewicz, Witold Libionka, Jakub Kortas, Wojciech Kloc, Jedrzej Antosiewicz and Jan J. Kaczor
Nutrients 2019, 11(9), 2202; https://doi.org/10.3390/nu11092202 - 12 Sep 2019
Cited by 6 | Viewed by 4045
Abstract
Background: The introduction of early rehabilitation exercise is the foundation of treatment post-Posterior lumbar interbody fusion (PLIF) surgery, and the search for additional sources of reinforcement physiotherapy seems to be very important. Methods: The patients were randomly divided into the vitamin D3 ( [...] Read more.
Background: The introduction of early rehabilitation exercise is the foundation of treatment post-Posterior lumbar interbody fusion (PLIF) surgery, and the search for additional sources of reinforcement physiotherapy seems to be very important. Methods: The patients were randomly divided into the vitamin D3 (n = 15; D3) supplemented group and received 3200 IU per day for five weeks before surgery and the placebo group (n = 18; Pl) received vegetable oil during the same time. The patients began the supervisor rehabilitation program four weeks after surgery. Results: The limits of stability (LOS) were significantly improved in the D3 group after 5 and 14 weeks (p < 0.05), while in the Pl group, progress was only observed after 14 weeks (p < 0.05). The LOS were also higher in the D3 group than in the Pl group after five weeks of supervised rehabilitation (p < 0.05). In the postural stability (PST) test, significant progress was observed in the D3 group after 14 weeks (p < 0.02). In addition, neither rehabilitation nor supplementation had significant effects on the risk of falls (RFT). Conclusions: Vitamin D supplementation seems to ameliorate the effects of an early postoperative rehabilitation program implemented four weeks after posterior lumbar interbody fusion. Early physiotherapy treatment after PLIF surgery combined with vitamin D supplementation appears to be a very important combination with regard to the patients’ recovery process. Full article
(This article belongs to the Special Issue Vitamin D in Health and the Prevention and Treatment of Disease)
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13 pages, 2417 KiB  
Article
Vitamin D Modulates the Response of Bronchial Epithelial Cells Exposed to Cigarette Smoke Extract
by Carolien Mathyssen, Jef Serré, Annelore Sacreas, Stephanie Everaerts, Karen Maes, Stijn Verleden, Lieve Verlinden, Annemieke Verstuyf, Charles Pilette, Ghislaine Gayan-Ramirez, Bart Vanaudenaerde and Wim Janssens
Nutrients 2019, 11(9), 2138; https://doi.org/10.3390/nu11092138 - 06 Sep 2019
Cited by 14 | Viewed by 4063
Abstract
In chronic obstructive pulmonary disease (COPD), the bronchial epithelium is the first immune barrier that is triggered by cigarette smoke. Although vitamin D (vitD) has proven anti-inflammatory and antimicrobial effects in alveolar macrophages, little is known about the direct role of vitD on [...] Read more.
In chronic obstructive pulmonary disease (COPD), the bronchial epithelium is the first immune barrier that is triggered by cigarette smoke. Although vitamin D (vitD) has proven anti-inflammatory and antimicrobial effects in alveolar macrophages, little is known about the direct role of vitD on cigarette smoke-exposed bronchial epithelial cells. We examined the effects of vitD on a human bronchial epithelial cell line (16HBE) and on air–liquid culture of primary bronchial epithelial cells (PBEC) of COPD patients and controls exposed for 24 h to cigarette smoke extract (CSE). VitD decreased CSE-induced IL-8 secretion by 16HBE cells, but not by PBEC. VitD significantly increased the expression of the antimicrobial peptide cathelicidin in 16HBE and PBEC of both COPD subjects and controls. VitD did not affect epithelial to mesenchymal transition or epithelial MMP-9 expression and was not able to restore impaired wound healing by CSE in 16HBE cells. VitD increased the expression of its own catabolic enzyme CYP24A1 thereby maintaining its negative feedback. In conclusion, vitD supplementation may potentially reduce infectious exacerbations in COPD by the upregulation of cathelicidin in the bronchial epithelium. Full article
(This article belongs to the Special Issue Vitamin D in Health and the Prevention and Treatment of Disease)
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18 pages, 1361 KiB  
Article
The Association between Cardiovascular Disease Risk Factors and 25-Hydroxivitamin D and Related Analytes among Hispanic/Latino Adults: A Pilot Study
by Ramon A. Durazo-Arvizu, Reyna L. Pacheco-Dominguez, Christopher T. Sempos, Holly Kramer, Andrew N. Hoofnagle, Amber Pirzada, Richard S. Cooper and Martha L. Daviglus
Nutrients 2019, 11(8), 1959; https://doi.org/10.3390/nu11081959 - 20 Aug 2019
Cited by 6 | Viewed by 3692
Abstract
Although the association of vitamin D levels with cardiovascular risk profiles among Hispanics/Latinos has been studied, little is known about this association among Hispanics/Latinos with chronic conditions. This pilot study determined serum vitamin D and parathyroid hormone (PTH) levels in a sample of [...] Read more.
Although the association of vitamin D levels with cardiovascular risk profiles among Hispanics/Latinos has been studied, little is known about this association among Hispanics/Latinos with chronic conditions. This pilot study determined serum vitamin D and parathyroid hormone (PTH) levels in a sample of participants from the University of Illinois at the Chicago Cohort of Patients, Family and Friends (UIC Cohort) and examined their association with traditional cardiovascular disease risk factors. From July 2012 to June 2016, the UIC Cohort study enrolled and conducted clinical examinations on men and women ages 18 years and older, who had one or more diagnosed chronic diseases/conditions (excluding cancer). This pilot study sample included 40 participants from the six main Hispanic/Latino background groups in the United States, namely Dominican, Cuban, Puerto Rican, Mexican, Central American, and South American, and were grouped by Caribbean or mainland origin. No substantial differences were noted in the vitamin D-related measures by Hispanic/Latino background, but the PTH levels were somewhat higher in the Caribbean vs. mainland group (43.0 ± 4.6 vs. 38.6 ± 2.7 pg/mL). The associations between selected CVD risk factors (systolic and diastolic blood pressure (SBP, DBP), total cholesterol, glucose) and PTH and vitamin D-related analytes were investigated using interval-censored multivariate regression models adjusted for age, sex, percent body fat, serum albumin/calcium, and Hispanic/Latino background. A negative association between total 25[OH]D and blood pressure was corroborated (SBP: β = −1.2, 95%CI = −2.0, −0.3; DBP: β = −0.7, 95% CI = −1.2, −0.1), whereas a positive association with total cholesterol was observed (β = 1.9, 95% CI = 0.02, 3.7). Levels of 1, 25[OH]2D were not associated with CVD risk factors, whereas 24, 25[OH]2D3 was associated with blood pressure (SBP: β = −13.0, 95% CI = −20.7, −5.2; DBP: β = −6.3, 95% CI = −11.6, −1.0). Estimated free 25[OH]D was inversely associated with both SBP (β = −3.5, 95% CI = −6.1, −0.9) and DBP (β = −2.1, 95% CI = −3.8, −0.3). Similarly, calculated bioavailable 25[OH]D was inversely associated with both SBP (β = −9.2, 95% CI = −15.9, −2.4) and DBP(β = −5.3, 95% CI = −9.8, −0.8). In conclusion, a negative association between 25[OH]D with BP was observed and a positive association with lipids is suggested. Due to the small sample size, most associations did not reach statistical significance. Full article
(This article belongs to the Special Issue Vitamin D in Health and the Prevention and Treatment of Disease)
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24 pages, 366 KiB  
Article
Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations
by Veronika Fedirko, Hannah B. Mandle, Wanzhe Zhu, David J. Hughes, Afshan Siddiq, Pietro Ferrari, Isabelle Romieu, Elio Riboli, Bas Bueno-de-Mesquita, Fränzel J.B. van Duijnhoven, Peter D. Siersema, Anne Tjønneland, Anja Olsen, Vittorio Perduca, Franck Carbonnel, Marie-Christine Boutron-Ruault, Tilman Kühn, Theron Johnson, Aleksandrova Krasimira, Antonia Trichopoulou, Periklis Makrythanasis, Dimitris Thanos, Salvatore Panico, Vittorio Krogh, Carlotta Sacerdote, Guri Skeie, Elisabete Weiderpass, Sandra Colorado-Yohar, Núria Sala, Aurelio Barricarte, Maria-Jose Sanchez, Ramón Quirós, Pilar Amiano, Björn Gylling, Sophia Harlid, Aurora Perez-Cornago, Alicia K. Heath, Konstantinos K. Tsilidis, Dagfinn Aune, Heinz Freisling, Neil Murphy, Marc J. Gunter and Mazda Jenabadd Show full author list remove Hide full author list
Nutrients 2019, 11(8), 1954; https://doi.org/10.3390/nu11081954 - 20 Aug 2019
Cited by 20 | Viewed by 7018
Abstract
Higher circulating 25-hydroxyvitamin D levels (25(OH)D) have been found to be associated with lower risk for colorectal cancer (CRC) in prospective studies. Whether this association is modified by genetic variation in genes related to vitamin D metabolism and action has not been well [...] Read more.
Higher circulating 25-hydroxyvitamin D levels (25(OH)D) have been found to be associated with lower risk for colorectal cancer (CRC) in prospective studies. Whether this association is modified by genetic variation in genes related to vitamin D metabolism and action has not been well studied in humans. We investigated 1307 functional and tagging single-nucleotide polymorphisms (SNPs; individually, and by gene/pathway) in 86 vitamin D-related genes in 1420 incident CRC cases matched to controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We also evaluated the association between these SNPs and circulating 25(OH)D in a subset of controls. We confirmed previously reported CRC risk associations between SNPs in the VDR, GC, and CYP27B1 genes. We also identified additional associations with 25(OH)D, as well as CRC risk, and several potentially novel SNPs in genes related to vitamin D transport and action (LRP2, CUBN, NCOA7, and HDAC9). However, none of these SNPs were statistically significant after Benjamini–Hochberg (BH) multiple testing correction. When assessed by a priori defined functional pathways, tumor growth factor β (TGFβ) signaling was associated with CRC risk (P ≤ 0.001), with most statistically significant genes being SMAD7 (PBH = 0.008) and SMAD3 (PBH = 0.008), and 18 SNPs in the vitamin D receptor (VDR) binding sites (P = 0.036). The 25(OH)D-gene pathway analysis suggested that genetic variants in the genes related to VDR complex formation and transcriptional activity are associated with CRC depending on 25(OH)D levels (interaction P = 0.041). Additional studies in large populations and consortia, especially with measured circulating 25(OH)D, are needed to confirm our findings. Full article
(This article belongs to the Special Issue Vitamin D in Health and the Prevention and Treatment of Disease)
12 pages, 235 KiB  
Article
Effects of Vitamin D Supplementation on Body Composition and Metabolic Risk Factors in Men: A Randomized Controlled Trial
by Elisabeth Lerchbaum, Christian Trummer, Verena Theiler-Schwetz, Martina Kollmann, Monika Wölfler, Stefan Pilz and Barbara Obermayer-Pietsch
Nutrients 2019, 11(8), 1894; https://doi.org/10.3390/nu11081894 - 14 Aug 2019
Cited by 21 | Viewed by 4623
Abstract
Vitamin D might play a role in metabolic processes and obesity. We therefore examined vitamin D effects on metabolic markers and obesity in a randomized controlled trial (RCT). This is a post-hoc analysis of the Graz Vitamin D&TT-RCT, a single-center, double-blind, randomized placebo-controlled [...] Read more.
Vitamin D might play a role in metabolic processes and obesity. We therefore examined vitamin D effects on metabolic markers and obesity in a randomized controlled trial (RCT). This is a post-hoc analysis of the Graz Vitamin D&TT-RCT, a single-center, double-blind, randomized placebo-controlled trial. We included 200 healthy men with serum 25-hydroxyvitamin D (25(OH) D) levels <75 nmol/L. Subjects received 20,000 IU of vitamin D3/week (n = 100) or placebo (n = 100) for 12 weeks. Outcome measures were metabolic markers, anthropometric measures, and body composition assessed by Dual-energy X-ray absorptiometry. One-hundred and ninety-two men completed the study. We found a significant treatment effect on fasting glucose/fasting insulin ratio (−5.3 (−10.4 to −0.2), p = 0.040), whereas we observed no significant effect on the remaining outcome parameters. In subgroup analyses of men with baseline 25(OH)D levels <50 nmol/L (n = 80), we found a significant effect on waist circumference (1.6 (0.3 to 2.9) cm, p = 0.012), waist-to-hip ratio (0.019 (0.002 to 0.036), p = 0.031), total body fat (0.029 (0.004 to 0.055) %, p = 0.026), and android fat (1.18 (0.11 to 2.26) %, p = 0.010). In middle-aged healthy men, vitamin D treatment had a negative effect on insulin sensitivity. In vitamin D deficient men, vitamin D has an unfavorable effect on central obesity and body composition. Full article
(This article belongs to the Special Issue Vitamin D in Health and the Prevention and Treatment of Disease)
9 pages, 460 KiB  
Article
Vitamin D Supplementation and Post-Stroke Rehabilitation: A Randomized, Double-Blind, Placebo-Controlled Trial
by Ryo Momosaki, Masahiro Abo and Mitsuyoshi Urashima
Nutrients 2019, 11(6), 1295; https://doi.org/10.3390/nu11061295 - 07 Jun 2019
Cited by 31 | Viewed by 6583
Abstract
Low vitamin D levels are associated with poorer outcomes after stroke. However, it is not clear whether post-stroke vitamin D supplementation can improve these outcomes. In this study, we investigated the effects of vitamin D supplementation on outcomes in hospitalized patients undergoing rehabilitation [...] Read more.
Low vitamin D levels are associated with poorer outcomes after stroke. However, it is not clear whether post-stroke vitamin D supplementation can improve these outcomes. In this study, we investigated the effects of vitamin D supplementation on outcomes in hospitalized patients undergoing rehabilitation after acute stroke. A multicenter, randomized, controlled, double-blind, parallel-group trial was conducted from January 2012 through July 2017. One hundred patients admitted to a convalescent rehabilitation ward after having an acute stroke were randomized, and each one received either vitamin D3 (2000 IU/day) or a placebo. The primary outcome was a gain in the Barthel Index scores at week 8. Secondary outcomes were seen in Barthel Index efficiency, hand grip strength, and calf circumference at week 8. Ninety-seven patients completed the study. There were no significant differences in the demographic characteristics between the groups. The mean (±standard deviation) gain in the Barthel Index score was 19.0 ± 14.8 in the supplementation group and 19.5 ± 13.1 in the placebo group (p = 0.88). The Barthel Index efficiency was 0.32 ± 0.31 in the supplementation group and 0.28 ± 0.21 in the placebo group (p = 0.38). There were no between-group differences in the other secondary outcomes. Our findings suggest that oral vitamin D3 supplementation does not improve rehabilitation outcomes after acute stroke. Full article
(This article belongs to the Special Issue Vitamin D in Health and the Prevention and Treatment of Disease)
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19 pages, 2305 KiB  
Article
Developmental Vitamin D Deficiency Produces Behavioral Phenotypes of Relevance to Autism in an Animal Model
by Asad Ali, Svetlina Vasileva, Mia Langguth, Suzanne Alexander, Xiaoying Cui, Andrew Whitehouse, John J. McGrath and Darryl Eyles
Nutrients 2019, 11(5), 1187; https://doi.org/10.3390/nu11051187 - 27 May 2019
Cited by 26 | Viewed by 5877
Abstract
Emerging evidence suggests that gestational or developmental vitamin D (DVD) deficiency is associated with an increased risk of autism spectrum disorder (ASD). ASD is a neurodevelopmental disorder characterized by impairments in social interaction, lack of verbal and non-verbal communications, stereotyped repetitive behaviors and [...] Read more.
Emerging evidence suggests that gestational or developmental vitamin D (DVD) deficiency is associated with an increased risk of autism spectrum disorder (ASD). ASD is a neurodevelopmental disorder characterized by impairments in social interaction, lack of verbal and non-verbal communications, stereotyped repetitive behaviors and hyper-activities. There are several other clinical features that are commonly comorbid with ASD, including olfactory impairments, anxiety and delays in motor development. Here we investigate these features in an animal model related to ASD—the DVD-deficient rat. Compared to controls, both DVD-deficient male and female pups show altered ultrasonic vocalizations and stereotyped repetitive behavior. Further, the DVD-deficient animals had delayed motor development and impaired motor control. Adolescent DVD-deficient animals had impaired reciprocal social interaction, while as adults, these animals were hyperactive. The DVD-deficient model is associated with a range of behavioral features of interest to ASD. Full article
(This article belongs to the Special Issue Vitamin D in Health and the Prevention and Treatment of Disease)
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Review

Jump to: Research

9 pages, 460 KiB  
Review
Vitamin D Status and Vitamin D-Dependent Apoptosis in Obesity
by Igor N. Sergeev
Nutrients 2020, 12(5), 1392; https://doi.org/10.3390/nu12051392 - 13 May 2020
Cited by 29 | Viewed by 6272
Abstract
The role of vitamin D in obesity appears to be linked to vitamin D insufficient/deficient status. However, mechanistic understanding of the role of vitamin D in obesity is lacking. We have shown earlier that the vitamin D hormonal form, 1,25-dihydroxyvitamin D3 (1,25(OH) [...] Read more.
The role of vitamin D in obesity appears to be linked to vitamin D insufficient/deficient status. However, mechanistic understanding of the role of vitamin D in obesity is lacking. We have shown earlier that the vitamin D hormonal form, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), induces cell death by apoptosis in mature adipocytes. This effect of the hormone is mediated by the cellular Ca2+ signaling pathway: a sustained increase of intracellular (cytosolic) Ca2+ concentration followed by activation of Ca2+-dependent initiators and effectors of apoptosis. In recent animal studies, we demonstrated that low vitamin D status is observed in diet-induced obesity (DIO). High intake of vitamin D3 in DIO decreased the weight of white adipose tissue and improved biomarkers related to adiposity and Ca2+ regulation. The anti-obesity effect of vitamin D (1,25(OH)2D3) in DIO was determined by the induction of Ca2+-mediated apoptosis in mature adipocytes executed by Ca2+-dependent apoptotic proteases (calpains and caspases). Thus, a high intake of vitamin D in obesity increases vitamin D nutritional status and normalizes vitamin D hormonal status that is accompanied by the reduction of adiposity. Overall, our findings imply that vitamin D may contribute to the prevention of obesity and obesity-related diseases and that the mechanism of the anti-obesity effect of 1,25(OH)2D3 includes induction of Ca2+-mediated apoptosis in adipocytes. Full article
(This article belongs to the Special Issue Vitamin D in Health and the Prevention and Treatment of Disease)
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29 pages, 792 KiB  
Review
Controversial Effects of Vitamin D and Related Genes on Viral Infections, Pathogenesis, and Treatment Outcomes
by Choongho Lee
Nutrients 2020, 12(4), 962; https://doi.org/10.3390/nu12040962 - 30 Mar 2020
Cited by 38 | Viewed by 7434
Abstract
Vitamin D (VD) plays an essential role in mineral homeostasis and bone remodeling. A number of different VD-related genes (VDRG) are required for the metabolic activation of VD and the subsequent induction of its target genes. They include a set of genes that [...] Read more.
Vitamin D (VD) plays an essential role in mineral homeostasis and bone remodeling. A number of different VD-related genes (VDRG) are required for the metabolic activation of VD and the subsequent induction of its target genes. They include a set of genes that encode for VD-binding protein, metabolic enzymes, and the VD receptor. In addition to its well-characterized skeletal function, the immunoregulatory activities of VD and the related polymorphisms of VDRG have been reported and linked to its therapeutic and preventive actions for the control of several viral diseases. However, in regards to their roles in the progression of viral diseases, inconsistent and, in some cases, contradictory results also exist. To resolve this discrepancy, I conducted an extensive literature search by using relevant keywords on the PubMed website. Based on the volume of hit papers related to a certain viral infection, I summarized and compared the effects of VD and VDRG polymorphism on the infection, pathogenesis, and treatment outcomes of clinically important viral diseases. They include viral hepatitis, respiratory viral infections, acquired immunodeficiency syndrome (AIDS), and other viral diseases, which are caused by herpesviruses, dengue virus, rotavirus, and human papillomavirus. This review will provide the most current information on the nutritional and clinical utilization of VD and VDRG in the management of the key viral diseases. This information should be valuable not only to nutritionists but also to clinicians who wish to provide evidence-based recommendations on the use of VD to virally infected patients. Full article
(This article belongs to the Special Issue Vitamin D in Health and the Prevention and Treatment of Disease)
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11 pages, 516 KiB  
Review
Hypovitaminosis D and Aging: Is There a Role in Muscle and Brain Health?
by Patrizia D’Amelio and Luca Quacquarelli
Nutrients 2020, 12(3), 628; https://doi.org/10.3390/nu12030628 - 27 Feb 2020
Cited by 18 | Viewed by 6255
Abstract
The older-adult population is constantly increasing, hence aging and mechanisms leading to aging are a topic raising increasing interest. Hypovitaminosis D is common amongst old patients and has been proposed as causative of several chronic diseases. Here we review the role of hypovitaminosis [...] Read more.
The older-adult population is constantly increasing, hence aging and mechanisms leading to aging are a topic raising increasing interest. Hypovitaminosis D is common amongst old patients and has been proposed as causative of several chronic diseases. Here we review the role of hypovitaminosis D and vitamin D supplementation in sarcopenia and dementia, from bench to bedside. Full article
(This article belongs to the Special Issue Vitamin D in Health and the Prevention and Treatment of Disease)
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17 pages, 802 KiB  
Review
The Role of Vitamin D in Primary Headache–from Potential Mechanism to Treatment
by Magdalena Nowaczewska, Michał Wiciński, Stanisław Osiński and Henryk Kaźmierczak
Nutrients 2020, 12(1), 243; https://doi.org/10.3390/nu12010243 - 17 Jan 2020
Cited by 31 | Viewed by 11301
Abstract
Some studies have suggested a link between vitamin D and headache; however, the underlying physiological mechanisms are unclear. We aimed to summarize the available evidence on the relationship between vitamin D and the various subtypes of primary headaches, including migraines and tension-type headaches. [...] Read more.
Some studies have suggested a link between vitamin D and headache; however, the underlying physiological mechanisms are unclear. We aimed to summarize the available evidence on the relationship between vitamin D and the various subtypes of primary headaches, including migraines and tension-type headaches. All articles concerning the association between primary headache and vitamin D published up to October 2019 were retrieved by searching clinical databases, including: EMBASE, MEDLINE, PubMed, Google scholar, and the Cochrane library. All types of studies (i.e., observational, cross-sectional, case-control, and clinical trials) were included. We identified 22 studies investigating serum vitamin D levels in association with headaches. Eight studies also evaluated the effect of vitamin D supplementation on the various headache parameters. Among them, 18 studies showed a link between serum vitamin D levels and headaches, with the strongest connection reported between serum vitamin D levels and migraine. Overall, there is not enough evidence to recommend vitamin D supplementation to all headache patients, but the current literature indicates that it may be beneficial in some patients suffering headaches, mainly migraineurs, to reduce the frequency of headaches, especially in those with vitamin D deficiency. Full article
(This article belongs to the Special Issue Vitamin D in Health and the Prevention and Treatment of Disease)
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22 pages, 1132 KiB  
Review
Potential Beneficial Effects of Vitamin D in Coronary Artery Disease
by Christian Legarth, Daniela Grimm, Marcus Krüger, Manfred Infanger and Markus Wehland
Nutrients 2020, 12(1), 99; https://doi.org/10.3390/nu12010099 - 30 Dec 2019
Cited by 30 | Viewed by 8973
Abstract
Vitamin D plays a pivotal role in bone homeostasis and calcium metabolism. However, recent research has indicated additional beneficial effects of vitamin D on the cardiovascular system. This review aims to elucidate if vitamin D can be used as an add-on treatment in [...] Read more.
Vitamin D plays a pivotal role in bone homeostasis and calcium metabolism. However, recent research has indicated additional beneficial effects of vitamin D on the cardiovascular system. This review aims to elucidate if vitamin D can be used as an add-on treatment in coronary artery disease (CAD). Large-scale epidemiological studies have found a significant inverse association between serum 25(OH)-vitamin D levels and the prevalence of essential hypertension. Likewise, epidemiological data have suggested plasma levels of vitamin D to be inversely correlated to cardiac injury after acute myocardial infarction (MI). Remarkably, in vitro trials have showed that vitamin D can actively suppress the intracellular NF-κB pathway to decrease CAD progression. This is suggested as a mechanistic link to explain how vitamin D may decrease vascular inflammation and atherosclerosis. A review of randomized controlled trials with vitamin D supplementation showed ambiguous results. This may partly be explained by heterogeneous study groups. It is suggested that subgroups of diabetic patients may benefit more from vitamin D supplementation. Moreover, some studies have indicated that calcitriol rather than cholecalciferol exerts more potent beneficial effects on atherosclerosis and CAD. Therefore, further studies are required to clarify these assumptions. Full article
(This article belongs to the Special Issue Vitamin D in Health and the Prevention and Treatment of Disease)
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