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Berry SPDG, Honkpèhedji YJ, Ludwig E, Mahmoudou S, Prodjinotho UF, Adamou R, Nouatin OP, Adégbitè BR, Dejon-Agobe JC, Mba RB, Maloum M, Nkoma AMM, Zinsou JF, Luty AJF, Esen M, Adégnika AA, Prazeres da Costa C. Impact of helminth infections during pregnancy on maternal and newborn Vitamin D and on birth outcomes. Sci Rep 2024; 14:14845. [PMID: 38937587 PMCID: PMC11211496 DOI: 10.1038/s41598-024-65232-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 06/18/2024] [Indexed: 06/29/2024] Open
Abstract
Poor birth outcomes in low- and middle income countries are associated with maternal vitamin D deficiency and chronic helminth infections. Here, we investigated whether maternal Schistosoma haematobium affects maternal or cord vitamin D status as well as birth outcomes. In a prospective cross-sectional study of pregnant women conducted in Lambaréné, Gabon, we diagnosed maternal parasitic infections in blood, urine and stool. At delivery we measured vitamin D in maternal and cord blood. S. haematobium, soil-transmitted helminths, and microfilariae were found at prevalences of 30.2%, 13.0%, and 8.8%, respectively. Insufficient vitamin D and calcium levels were found in 28% and 15% of mothers, and in 11.5% and 1.5% of newborns. Mothers with adequate vitamin D had lower risk of low birthweight babies (aOR = 0.11, 95% CI 0.02-0.52, p = 0.01), whilst offspring of primipars had low cord vitamin D levels, and low vitamin D levels increased the risk of maternal inflammation. Maternal filariasis was associated with low calcium levels, but other helminth infections affected neither vitamin D nor calcium levels in either mothers or newborns. Healthy birth outcomes require maintenance of adequate vitamin D and calcium levels. Chronic maternal helminth infections do not disrupt those levels in a semi-rural setting in sub-Saharan Africa.
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Affiliation(s)
- Sèyigbéna P Déo-Gracias Berry
- Institute for Medical Microbiology, Immunology and Hygiene, TUM School of Medicine and Health, Technical University of Munich (TUM), Trogerstrasse 30, 81675, Munich, Germany
- Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon
- Center for Global Health, TUM School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany
| | - Yabo Josiane Honkpèhedji
- Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon
- Department of Parasitology, Leiden University Medical Centre, Leiden, The Netherlands
- Institut Für Tropenmedizin, Universität Tübingen, Tübingen, Germany
- Fondation Pour La Recherche Scientifique (FORS), Cotonou, Benin
| | - Esther Ludwig
- Institute for Medical Microbiology, Immunology and Hygiene, TUM School of Medicine and Health, Technical University of Munich (TUM), Trogerstrasse 30, 81675, Munich, Germany
- Center for Global Health, TUM School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany
| | | | - Ulrich Fabien Prodjinotho
- Institute for Medical Microbiology, Immunology and Hygiene, TUM School of Medicine and Health, Technical University of Munich (TUM), Trogerstrasse 30, 81675, Munich, Germany
- Center for Global Health, TUM School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany
| | - Rafiou Adamou
- Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon
| | - Odilon P Nouatin
- Institut de Recherche Clinique du Bénin (IRCB), Abomey-Calavi, Benin
| | - Bayode R Adégbitè
- Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon
- Institut Für Tropenmedizin, Universität Tübingen, Tübingen, Germany
| | - Jean Claude Dejon-Agobe
- Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon
- Institut Für Tropenmedizin, Universität Tübingen, Tübingen, Germany
| | - Romuald Beh Mba
- Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon
| | | | | | - Jeannot Fréjus Zinsou
- Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon
- Institut Für Tropenmedizin, Universität Tübingen, Tübingen, Germany
- Fondation Pour La Recherche Scientifique (FORS), Cotonou, Benin
| | | | - Meral Esen
- Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon
- Institut Für Tropenmedizin, Universität Tübingen, Tübingen, Germany
- German Center for Infection Research (DZIF), Partner site Tübingen, Tübingen, Germany
| | - Ayôla Akim Adégnika
- Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon
- Institut Für Tropenmedizin, Universität Tübingen, Tübingen, Germany
- Fondation Pour La Recherche Scientifique (FORS), Cotonou, Benin
- German Center for Infection Research (DZIF), Partner site Tübingen, Tübingen, Germany
| | - Clarissa Prazeres da Costa
- Institute for Medical Microbiology, Immunology and Hygiene, TUM School of Medicine and Health, Technical University of Munich (TUM), Trogerstrasse 30, 81675, Munich, Germany.
- Center for Global Health, TUM School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany.
- German Center for Infection Research (DZIF), Partner site Munich, Munich, Germany.
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Lautatzis ME, Keya FK, Al Mahmud A, Tariq U, Lam C, Morris SK, Stimec J, Zlotkin S, Ahmed T, Harrington J, Roth DE. Maternal Vitamin D Supplementation and Infantile Rickets: Secondary Analysis of a Randomized Trial. Pediatrics 2024; 153:e2023063263. [PMID: 38726565 DOI: 10.1542/peds.2023-063263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 02/08/2024] [Accepted: 02/09/2024] [Indexed: 06/02/2024] Open
Abstract
BACKGROUND The role of maternal vitamin D supplementation in the prevention of infantile rickets is unknown, particularly in low- and middle-income countries without routine infant vitamin D supplementation. Through secondary analysis of a randomized, placebo-controlled trial in Bangladesh, we examined the dose-ranging effects of maternal vitamin D supplementation on the risk of biochemical rickets at 6 to 12 months of age. METHODS Pregnant women (n = 1300) were randomized into 5 groups: placebo, or vitamin D 4200 IU/week, 16 800 IU/week, or 28 000 IU/week from second trimester to delivery and placebo until 6 months postpartum; or 28 000 IU/week prenatally and until 6 months postpartum. Infants underwent biochemical rickets screening from 6 to 12 months of age (n = 790). Relative risks (RR) and 95% confidence intervals (95% CI) of biochemical rickets were estimated for each group versus placebo. RESULTS Overall, 39/790 (4.9%) infants had biochemical rickets. Prevalence was highest in the placebo group (7.8%), and the risk was significantly lower among infants whose mothers received combined prenatal and postpartum vitamin D at 28 000 IU/week (1.3%; RR, 0.16; 95% CI, 0.03-0.72). Risks among infants whose mothers received only prenatal supplementation (4200 IU, 16 800 IU, 28 000 IU weekly) were not significantly different from placebo: 3.8% (RR, 0.48; 95% CI, 0.19-1.22), 5.8% (RR, 0.74; 95% CI, 0.33-1.69), and 5.7% (RR, 0.73; 95% CI, 0.32-1.65), respectively. CONCLUSIONS Maternal vitamin D supplementation (28 000 IU/week) during the third trimester of pregnancy until 6 months postpartum reduced the risk of infantile biochemical rickets. Further research is needed to define optimal postpartum supplementation dosing during lactation.
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Affiliation(s)
- Maria-Elena Lautatzis
- Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
- The Centre for Global Child Health, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Farhana K Keya
- Technical Training Unit, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
| | - Abdullah Al Mahmud
- Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
| | - Ulaina Tariq
- The Centre for Global Child Health, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Carol Lam
- Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
| | - Shaun K Morris
- Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
- The Centre for Global Child Health, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Jennifer Stimec
- Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
| | - Stanley Zlotkin
- Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
- The Centre for Global Child Health, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Tahmeed Ahmed
- Centre for Nutrition and Food Security, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh
| | - Jennifer Harrington
- Division of Endocrinology, Women's and Children's Health Network, North Adelaide, Australia
- Department of Paediatrics, University of Adelaide, Adelaide, Australia
| | - Daniel E Roth
- Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
- The Centre for Global Child Health, The Hospital for Sick Children, Toronto, Ontario, Canada
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Naik M, Kamath U S, Uppangala S, Adiga SK, Patil A. Vitamin D metabolites and analytical challenges. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2023; 15:399-410. [PMID: 36628933 DOI: 10.1039/d2ay01692c] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
Vitamin D is an essential micronutrient for bone health and the general cellular functions of the body. Its insufficiency/deficiency leads to the pathophysiology of disorders like diabetes, cancer, autoimmune, neurodegenerative, and cardiovascular diseases. Clinical interest in Vitamin D metabolites and their role in various medical disorders have contributed to an increase in laboratory demands for vitamin D measurements. For clinical and research laboratories worldwide, analysis of vitamin D and associated metabolites is a significant problem. The best way for determining vitamin D levels is constantly being debated. Various methods such as immunoassays and chromatographic techniques are available for determining vitamin D levels. Additionally, biosensors have recently been considered promising options for routine vitamin D analysis. The existing methods and other developments in the measurement of vitamin D metabolites and associated analytical challenges are discussed in this review.
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Affiliation(s)
- Megha Naik
- Department of Atomic and Molecular Physics, Manipal Academy of Higher Education (MAHE), India-576 104.
| | - Saritha Kamath U
- Department of Medical Laboratory Technology, Manipal College of Health Professions, Manipal Academy of Higher Education (MAHE), Manipal, India-576 104
| | - Shubhashree Uppangala
- Division of Reproductive Genetics, Department of Reproductive Science, Kasturba Medical College, Manipal Academy of Higher Education (MAHE), Manipal, India-576 104
| | - Satish Kumar Adiga
- Division of Clinical Embryology, Department of Reproductive Science, Kasturba Medical College, Manipal Academy of Higher Education (MAHE), Manipal, India-576 104
| | - Ajeetkumar Patil
- Department of Atomic and Molecular Physics, Manipal Academy of Higher Education (MAHE), India-576 104.
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Vitamin A- and D-Deficient Diets Disrupt Intestinal Antimicrobial Peptide Defense Involving Wnt and STAT5 Signaling Pathways in Mice. Nutrients 2023; 15:nu15020376. [PMID: 36678247 PMCID: PMC9863741 DOI: 10.3390/nu15020376] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 12/14/2022] [Accepted: 01/04/2023] [Indexed: 01/15/2023] Open
Abstract
Vitamin A and D deficiencies are associated with immune modulatory effects and intestinal barrier impairment. However, the underlying mechanisms remain unclear. C57BL/6J mice were fed either a diet lacking in vitamin A (VAd), vitamin D (VDd) or a control diet (CD) for 12 weeks. Gut barrier function, antimicrobial peptide (AMP) defense and regulatory pathways were assessed. VAd mice compared to CD mice showed a reduced villus length in the ileum (p < 0.01) and decreased crypt depth in the colon (p < 0.05). In both VAd- and VDd-fed mice, ileal α-defensin 5 (p < 0.05/p < 0.0001 for VAd/VDd) and lysozyme protein levels (p < 0.001/p < 0.0001) were decreased. Moreover, mRNA expression of lysozyme (p < 0.05/p < 0.05) and total cryptdins (p < 0.001/p < 0.01) were reduced compared to controls. Furthermore, matrix metalloproteinase-7 (Mmp7) mRNA (p < 0.0001/p < 0.001) as well as components of the Wnt signaling pathway were decreased. VAd- and VDd-fed mice, compared to control mice, exhibited increased expression of pro-inflammatory markers and β-defensins in the colon. Organoid cell culture confirmed that vitamins A and D regulate AMP expression, likely through the Jak/STAT5 signaling pathway. In conclusion, our data show that vitamin A and D regulate intestinal antimicrobial peptide defense through Wnt and STAT5 signaling pathways.
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Giannini S, Giusti A, Minisola S, Napoli N, Passeri G, Rossini M, Sinigaglia L. The Immunologic Profile of Vitamin D and Its Role in Different Immune-Mediated Diseases: An Expert Opinion. Nutrients 2022; 14:473. [PMID: 35276834 PMCID: PMC8838062 DOI: 10.3390/nu14030473] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 01/11/2022] [Accepted: 01/18/2022] [Indexed: 02/06/2023] Open
Abstract
Historically, vitamin D is recognized as an essential component for the maintenance of the musculoskeletal system. The immunomodulatory role of vitamin D in health and disease has gained much interest in recent years due to the many pathologies that share underlying immunological features where vitamin D has been shown to exert a potential role. Evidence from pre-clinical studies show that vitamin D elicits biological effects on both the innate and adaptive immune systems. Furthermore, in vivo studies have shown that administration of vitamin D can lead to changes in or the development of a range of immune-related diseases. This encourages the hypothesis that data derived from clinical and epidemiological studies connect vitamin D with the incidence and severity of many immune-mediated disorders such as rheumatoid arthritis, diabetes, and infectious diseases. Since some other immune-mediated diseases share similar features to that of viral infection such as COVID-19, in this review, we examined these other areas and the role of vitamin D in these diseases.
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Affiliation(s)
- Sandro Giannini
- Clinica Medica 1, Department of Medicine, University of Padova, 35128 Padova, Italy
| | - Andrea Giusti
- Metabolic Bone Disease Unit & Fracture Liaison Service, Department of Medical Specialties, Regional Health Trust 3, 16125 Genova, Italy;
| | - Salvatore Minisola
- Department of Clinical, Internal, Anaesthesiology, and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy;
| | - Nicola Napoli
- Division of Endocrinology and Diabetes, Universita Campus Bio-Medico di Roma, 00128 Rome, Italy;
| | - Giovanni Passeri
- Unit of Clinica e Terapia Medica, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy;
| | - Maurizio Rossini
- Rheumatology Unit, Department of Medicine, University of Verona, 37134 Verona, Italy;
| | - Luigi Sinigaglia
- Division of Rheumatology, ASST Gaetano Pini-CTO, 20122 Milano, Italy;
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Low Serum 25-Hydroxy Vitamin D (25-OHD) and Hepatic Encephalopathy in HCV-Related Liver Cirrhosis. Int J Hepatol 2021; 2021:6669527. [PMID: 33628512 PMCID: PMC7896845 DOI: 10.1155/2021/6669527] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 01/19/2021] [Accepted: 01/29/2021] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Patients with liver cirrhosis experience a large variety of metabolic disorders associated with more hepatic decompensation. Hepatic encephalopathy (HE) is a significant complication in liver cirrhosis patients, presenting a wide spectrum of neuropsychological symptoms. A deficiency of 25-hydroxy vitamin D (25-OHD) in the general population is associated with a loss of cognitive function, dementia, and Alzheimer's disease. Aim of the Study. Our study aims to check the relationship between low serum 25-OHD and HE in patients with HCV-related liver cirrhosis and assess its link with patient mortality. Patients and Methods. This study was observationally carried out on 100 patients with HCV-related liver cirrhosis. The patients were divided into 2 groups: Group A-included 50 HCV-related cirrhotic patients with HE, and Group B-included 50 HCV-related cirrhotic patients without HE. Assessment of disease severity using the end-stage liver disease (MELD) model and Child Turcotte Pugh (CTP) scores were done, and 25-OHD levels were measured. Comparison of vitamin D levels in different etiologies and different CTP categories was made using one-way ANOVA. Pearson's correlation between the level of vitamin D and other biomarkers was applied. RESULTS There was a statistically significant Vitamin D level difference between the two groups. A lower level of vitamin D was observed in the HE group where the severe deficiency was 16%, while it was 6% in the other group and the moderate deficiency was 24% in HE group as compared to 10% in the other group. The insufficient vitamin D level represented 46% of the non-HE group while none of the HE group falls in this category. Vitamin D level was statistically higher in Grade 1 HE than in Grade 2 which is higher than in Grades 3 to 4. Vitamin D level was also significantly higher in those who improved from HE as compared to those who died. CONCLUSION The lower levels of 25-OHD were associated with the higher incidence of HE in cirrhotic HCV patients. The worsening vitamin D deficiency was associated with increased severity of the liver disease, so vitamin D may be considered a prognostic factor for the severity of liver cirrhosis and high mortality rate in HE patients.
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Validation and Determination of 25(OH) Vitamin D and 3-Epi25(OH)D3 in Breastmilk and Maternal- and Infant Plasma during Breastfeeding. Nutrients 2020; 12:nu12082271. [PMID: 32751196 PMCID: PMC7469027 DOI: 10.3390/nu12082271] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Revised: 07/23/2020] [Accepted: 07/27/2020] [Indexed: 12/22/2022] Open
Abstract
Vitamin D deficiency in pregnant women and their offspring may result in unfavorable health outcomes for both mother and infant. A 25hydroxyvitamin D (25(OH)D) level of at least 75 nmol/L is recommended by the Endocrine Society. Validated, automated sample preparation and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were used to determine the vitamin D metabolites status in mother-infant pairs. Detection of 3-Epi25(OH)D3 prevented overestimation of 25(OH)D3 and misclassification of vitamin D status. Sixty-three percent of maternal 25(OH)D plasma levels were less than the recommended level of 25(OH)D at 3 months. Additionally, breastmilk levels of 25(OH)D decreased from 60.1 nmol/L to 50.0 nmol/L between six weeks and three months (p < 0.01). Furthermore, there was a positive correlation between mother and infant plasma levels (p < 0.01, r = 0.56) at 3 months. Accordingly, 31% of the infants were categorized as vitamin D deficient (25(OH)D < 50 nmol/L) compared to 25% if 3-Epi25(OH)D3 was not distinguished from 25(OH)D3. This study highlights the importance of accurate quantification of 25(OH)D. Monitoring vitamin D metabolites in infant, maternal plasma, and breastmilk may be needed to ensure adequate levels in both mother and infant in the first 6 months of infant life.
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O'Callaghan KM, Taghivand M, Zuchniak A, Onoyovwi A, Korsiak J, Leung M, Roth DE. Vitamin D in Breastfed Infants: Systematic Review of Alternatives to Daily Supplementation. Adv Nutr 2020; 11:144-159. [PMID: 31552417 PMCID: PMC7442322 DOI: 10.1093/advances/nmz098] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Revised: 08/19/2019] [Accepted: 08/23/2019] [Indexed: 01/09/2023] Open
Abstract
Daily oral vitamin D supplementation (400 IU) is recommended for breastfeeding infants (≤1 y). Recent studies have examined alternative approaches to preventing vitamin D deficiency in this population. This systematic review and meta-analysis aimed to estimate the effects of maternal postpartum (M-PP) or infant intermittent (I-INT) vitamin D supplementation on infant 25-hydroxyvitamin D [25(OH)D] concentrations in comparison to routine direct infant daily (I-D) oral supplementation (400 IU). MEDLINE, MEDLINE In-Process, Embase, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched up to December 2018. Inclusion criteria consisted of published, peer-reviewed, vitamin D intervention trials involving lactating women and/or exclusively or partially breastfed term infants. Two reviewers independently extracted study characteristics (e.g., sample size, intervention dose, and duration and mode of administration) and related biochemical and clinical outcomes. Of 28 included trials, 5 randomized controlled trials were incorporated in meta-analyses examining infant 25(OH)D. Overall, M-PP supplementation resulted in modestly lower infant 25(OH)D compared with I-D supplementation (weighted mean difference = -8.1 nmol/L; 95% CI: -15.4, -0.9; I2 = 45%; P = 0.14; 3 trials), but the 2 most recent trials found M-PP to achieve similar infant 25(OH)D as I-D. Comparison of I-INT with I-D was confined to 2 trials with contradictory findings, and it was considered inappropriate for pooled analysis. Meta-analysis was therefore limited by a small number of eligible trials with variable quality of analytically derived 25(OH)D data and inconsistent reporting of safety outcomes, including effects on calcium homeostasis. Considering all 28 included trials, this systematic review highlights M-PP and I-INT regimens as plausible substitutes for routine daily infant vitamin D supplementation, but evidence remains too weak to support a policy update. Dose-ranging, adequately powered trials are required to establish the efficacy, safety, and feasibility of alternative strategies to prevent vitamin D deficiency in breastfeeding infants. This review was registered with PROSPERO as CRD42017069905.
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Affiliation(s)
- Karen M O'Callaghan
- Centre for Global Child Health and SickKids Research Institute, Hospital for Sick Children, Toronto, Canada
| | - Mahgol Taghivand
- Centre for Global Child Health and SickKids Research Institute, Hospital for Sick Children, Toronto, Canada
- Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Canada
| | - Anna Zuchniak
- Centre for Global Child Health and SickKids Research Institute, Hospital for Sick Children, Toronto, Canada
- Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Canada
| | - Akpevwe Onoyovwi
- Centre for Global Child Health and SickKids Research Institute, Hospital for Sick Children, Toronto, Canada
| | - Jill Korsiak
- Centre for Global Child Health and SickKids Research Institute, Hospital for Sick Children, Toronto, Canada
| | - Michael Leung
- Centre for Global Child Health and SickKids Research Institute, Hospital for Sick Children, Toronto, Canada
| | - Daniel E Roth
- Centre for Global Child Health and SickKids Research Institute, Hospital for Sick Children, Toronto, Canada
- Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Canada
- Department of Pediatrics, Hospital for Sick Children and University of Toronto, Toronto, Canada
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Mollahosseini A, Kamankesh M, Mohammadi A. Central Composite Design for Dispersive Liquid-liquid Microextraction of 25-hydroxy-cholecalciferol in Human Serum. J Chromatogr Sci 2019; 57:575-581. [PMID: 31095673 DOI: 10.1093/chromsci/bmz016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2018] [Revised: 01/09/2019] [Indexed: 11/12/2022]
Abstract
The human body's vitamin D levels are determined by measuring the level of 25-hydroxy-vitamin D3 (25-OH-vitamin D3) in human serum. In this research, a fast, simple, efficient and highly sensitive low-density solvent based on dispersive liquid-liquid microextraction (DLLME) was employed for the successful determination of 25-OH-vitamin D3 from complex human serum matrices. Reversed phase high-performance liquid chromatography was used as a powerful technique. The important parameters in the low-density solvent-DLLME method were optimized using response surface methodology based on central composite design. The calibration curves displayed a high level of linearity (R2 > 0.997) for 25-OH-vitamin D3 in the range of 2-500 ng mL-1. The limit of detection and limit of quantitation were 0.6 ng mL-1 and 1.9 ng mL-1, respectively. The relative standard deviation for the seven analyses was 7.1%. The relative recoveries of vitamin D3 in spiked human serum samples were between 85% and 97%. The amount of 25-OH-vitamin D3 in samples was determined using the proposed method and acceptable results were reported.
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Affiliation(s)
- Afsaneh Mollahosseini
- Research Laboratory of Spectroscopy & Micro and Nano Extraction, Department of Chemistry, Iran University of Science and Technology, Tehran, Iran
| | - Marzieh Kamankesh
- Research Laboratory of Spectroscopy & Micro and Nano Extraction, Department of Chemistry, Iran University of Science and Technology, Tehran, Iran.,Department of Food Science and Technology, Faculty of Nutrition Science, Food Science and Technology/National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abdorreza Mohammadi
- Department of Food Science and Technology, Faculty of Nutrition Science, Food Science and Technology/National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Cantorna MT, Snyder L, Arora J. Vitamin A and vitamin D regulate the microbial complexity, barrier function, and the mucosal immune responses to ensure intestinal homeostasis. Crit Rev Biochem Mol Biol 2019; 54:184-192. [PMID: 31084433 DOI: 10.1080/10409238.2019.1611734] [Citation(s) in RCA: 139] [Impact Index Per Article: 23.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Diet is an important regulator of the gastrointestinal microbiota. Vitamin A and vitamin D deficiencies result in less diverse, dysbiotic microbial communities and increased susceptibility to infection or injury of the gastrointestinal tract. The vitamin A and vitamin D receptors are nuclear receptors expressed by the host, but not the microbiota. Vitamin A- and vitamin D-mediated regulation of the intestinal epithelium and mucosal immune cells underlies the effects of these nutrients on the microbiota. Vitamin A and vitamin D regulate the expression of tight junction proteins on intestinal epithelial cells that are critical for barrier function in the gut. Other shared functions of vitamin A and vitamin D include the support of innate lymphoid cells that produce IL-22, suppression of IFN-γ and IL-17 by T cells, and induction of regulatory T cells in the mucosal tissues. There are some unique functions of vitamin A and D; for example, vitamin A induces gut homing receptors on T cells, while vitamin D suppresses gut homing receptors on T cells. Together, vitamin A- and vitamin D-mediated regulation of the intestinal epithelium and mucosal immune system shape the microbial communities in the gut to maintain homeostasis.
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Affiliation(s)
- Margherita T Cantorna
- a Department of Veterinary and Biomedical Science , The Pennsylvania State University , University Park , PA , USA.,b Center for Molecular Immunology and Infectious Disease , The Pennsylvania State University , University Park , PA , USA
| | - Lindsay Snyder
- a Department of Veterinary and Biomedical Science , The Pennsylvania State University , University Park , PA , USA.,b Center for Molecular Immunology and Infectious Disease , The Pennsylvania State University , University Park , PA , USA
| | - Juhi Arora
- a Department of Veterinary and Biomedical Science , The Pennsylvania State University , University Park , PA , USA.,b Center for Molecular Immunology and Infectious Disease , The Pennsylvania State University , University Park , PA , USA
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Abstract
The last decade has seen a dramatic increase in general interest in and research into vitamin D, with many athletes now taking vitamin D supplements as part of their everyday dietary regimen. The most recognized role of vitamin D is its regulation of calcium homeostasis; there is a strong relationship between vitamin D and bone health in non-athletic individuals. In contrast, data have consistently failed to demonstrate any relationship between serum 25[OH]D and bone health, which may in part be due to the osteogenic stimulus of exercise. Vitamin D may interact with extra-skeletal tissues such as muscle and the immune system to modulate recovery from damaging exercise and infection risk. Given that many athletes now engage in supplementation, often consuming extreme doses of vitamin D, it is important to assess whether excessive vitamin D can be detrimental to health. It has been argued that toxic effects only occur when serum 25[OH]D concentrations are greater than 180 nmol·l-1, but data from our laboratory have suggested high-dose supplementation could be problematic. Finally, there is a paradoxical relationship between serum 25[OH]D concentration, ethnicity, and markers of bone health: Black athletes often present with low serum 25[OH]D without physiological consequences. One explanation for this could be genetic differences in vitamin D binding protein due to ethnicity, resulting in greater concentrations of bioavailable (or free) vitamin D in some ethnic groups. In the absence of any pathology, screening may be unnecessary and could result in incorrect supplementation. Data must now be re-examined, taking into consideration bioavailable or "free" vitamin D in ethnically diverse groups to enable new thresholds and target concentrations to be established; perhaps, for now, it is time to "set vitamin D free".
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Affiliation(s)
- Daniel J Owens
- Research Institute for Sport and Exercise Science, Liverpool John Moores University, Tom Reilly Building, Byrom Street, Liverpool, L3 3AF, UK
| | - Richard Allison
- Research Institute for Sport and Exercise Science, Liverpool John Moores University, Tom Reilly Building, Byrom Street, Liverpool, L3 3AF, UK.,Exercise and Sport Science Department, ASPETAR, Orthopaedic and Sports Medicine Hospital, Doha, Qatar.,Arsenal Football Club, Bell Lane, London Colney, St Albans, Shenley, AL2 1DR, UK
| | - Graeme L Close
- Research Institute for Sport and Exercise Science, Liverpool John Moores University, Tom Reilly Building, Byrom Street, Liverpool, L3 3AF, UK.
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12
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Abstract
Tuberculosis (TB) has troubled mankind for millennia, but current treatment strategies are long and complicated and the disease remains a major global health problem. The risk of Mycobacterium tuberculosis (Mtb) infection or progression of active TB disease is elevated in individuals with vitamin D deficiency. High-dose vitamin D was used to treat TB in the preantibiotic era, and in vitro experimental data show that vitamin D supports innate immune responses that restrict growth of Mtb. Several randomized controlled trials have tested whether adjunctive vitamin D supplementation enhances the clinical and microbiological response to standard antimicrobial chemotherapy for pulmonary TB. The effects have been modest at best, and attention is turning to the question of whether vitamin D supplementation might have a role in preventing acquisition or reactivation of latent Mtb infection. In this article, we describe the effects of vitamin D on host immune responses to Mtb in vitro and in vivo and review the results of clinical trials in the field. We also reflect on the findings of clinical trials of vitamin D supplementation for the prevention of acute respiratory tract infections, and discuss how these findings might influence the design of future trials to evaluate the role of vitamin D in the prevention and treatment of TB.
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Affiliation(s)
- S Brighenti
- Department of Medicine, Center for Infectious Medicine (CIM), Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - P Bergman
- Department of Laboratory Medicine (LABMED), Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - A R Martineau
- Blizard Institute, Centre for Immunobiology, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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13
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Vidot H, Potter A, Cheng R, Allman-Farinelli M, Shackel N. Serum 25-hydroxyvitamin D deficiency and hepatic encephalopathy in chronic liver disease. World J Hepatol 2017; 9:510-518. [PMID: 28443156 PMCID: PMC5387363 DOI: 10.4254/wjh.v9.i10.510] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2016] [Revised: 02/05/2017] [Accepted: 03/13/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the relationship between 25-hydroxyvitamin D (25-OHD) deficiency and hepatic encephalopathy (HE) in patients with chronic liver disease (CLD).
METHODS A retrospective analysis of the results of 392 adult patients with chronic liver disease who were assessed for liver transplantation between 2006 and 2010 was undertaken. HE, severity of CLD, nutritional status and 25-OHD were analysed in patients assessed for liver transplantation between 2006 and 2010. Patients who presented with acute, fulminant or subacute disease, with a primary diagnosis of liver cancer, were assessed for re-transplantation or who did not have a 25-OHD measurement were excluded from the analysis.
RESULTS One hundred and sixty-five patients were included in this analysis. The mean age of all patients was 53 ± 8 years. Moderate to severe 25-OHD deficiency was identified in 49 patients of whom 36 had grade 2-3 HE compared with 13 patients who were not encephalopathic (P ≤ 0.0001). Mild 25-OHD deficiency was not associated with HE. There was a significant correlation between the severity of 25-OHD deficiency and the severity of liver disease (r = 0.39, P ≤ 0.0001) and disease severity and the presence of HE (P ≤ 0.0001). Importantly, individuals with 25-OHD deficiency were more likely to have a diagnosis of overt HE (OHE) at a significantly lower model for end stage liver disease (MELD) score than individuals without OHE (P ≤ 0.0001). This significant difference was observed with MELD scores from 10 to 38.
CONCLUSION 25-OHD deficiency was observed in the majority of patients with CLD and for the first time was found to be significantly worse in patients with OHE.
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14
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Aggarwal R, Akhthar T, Jain SK. Coronary artery disease and its association with Vitamin D deficiency. J Midlife Health 2016; 7:56-60. [PMID: 27499590 PMCID: PMC4960940 DOI: 10.4103/0976-7800.185334] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Coronary artery disease (CAD) has become the latest scourge of humankind and referred to in this article as CAD, is the end result of the accumulation of atheromatous plaques within the walls of coronary arteries that supply the myocardium, a process also known as atherosclerosis and manifests mostly in the form of chronic stable angina or acute coronary syndrome. Vitamin D has attracted considerable interest recently due to its role in a number of extraskeletal disease processes including multiple sclerosis, malignancies, diabetes mellitus, and CAD. It is also known as sunshine vitamin due to its production in the body following exposure to ultraviolet rays, and it is a unique vitamin as it acts like a hormone with its receptor present in a wide range of tissues including endothelium, which is the important mediator of atherosclerosis and subsequent CAD. A large number of studies conducted in the past have provided the basic scientific framework and this article attempts to explore the role of Vitamin D deficiency in the pathogenesis of CAD and stresses the need for further research to fill up gap in our knowledge.
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Affiliation(s)
- Ramesh Aggarwal
- Department of Medicine, Lady Hardinge Medical College and Dr. Ram Manohar Lohia Hospital, New Delhi, India
| | - Tauseef Akhthar
- Department of Medicine, Lady Hardinge Medical College and SSK Hospital, New Delhi, India
| | - Sachin Kumar Jain
- Department of Medicine, Lady Hardinge Medical College and Dr. Ram Manohar Lohia Hospital, New Delhi, India
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15
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Abstract
PTH and Vitamin D are two major regulators of mineral metabolism. They play critical roles in the maintenance of calcium and phosphate homeostasis as well as the development and maintenance of bone health. PTH and Vitamin D form a tightly controlled feedback cycle, PTH being a major stimulator of vitamin D synthesis in the kidney while vitamin D exerts negative feedback on PTH secretion. The major function of PTH and major physiologic regulator is circulating ionized calcium. The effects of PTH on gut, kidney, and bone serve to maintain serum calcium within a tight range. PTH has a reciprocal effect on phosphate metabolism. In contrast, vitamin D has a stimulatory effect on both calcium and phosphate homeostasis, playing a key role in providing adequate mineral for normal bone formation. Both hormones act in concert with the more recently discovered FGF23 and klotho, hormones involved predominantly in phosphate metabolism, which also participate in this closely knit feedback circuit. Of great interest are recent studies demonstrating effects of both PTH and vitamin D on the cardiovascular system. Hyperparathyroidism and vitamin D deficiency have been implicated in a variety of cardiovascular disorders including hypertension, atherosclerosis, vascular calcification, and kidney failure. Both hormones have direct effects on the endothelium, heart, and other vascular structures. How these effects of PTH and vitamin D interface with the regulation of bone formation are the subject of intense investigation.
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Affiliation(s)
- Syed Jalal Khundmiri
- Department of Medicine, University of Louisville, Louisville, Kentucky, USA
- Department of Physiology and Biophysics, University of Louisville, Louisville, Kentucky, USA
| | - Rebecca D. Murray
- Department of Medicine, University of Louisville, Louisville, Kentucky, USA
- Department of Physiology and Biophysics, University of Louisville, Louisville, Kentucky, USA
| | - Eleanor Lederer
- Department of Medicine, University of Louisville, Louisville, Kentucky, USA
- Department of Physiology and Biophysics, University of Louisville, Louisville, Kentucky, USA
- Robley Rex VA Medical Center, University of Louisville, Louisville, Kentucky, USA
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16
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Demir K, Kattan WE, Zou M, Durmaz E, BinEssa H, Nalbantoğlu Ö, Al-Rijjal RA, Meyer B, Özkan B, Shi Y. Novel CYP27B1 Gene Mutations in Patients with Vitamin D-Dependent Rickets Type 1A. PLoS One 2015; 10:e0131376. [PMID: 26132292 PMCID: PMC4489500 DOI: 10.1371/journal.pone.0131376] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2015] [Accepted: 05/31/2015] [Indexed: 12/30/2022] Open
Abstract
The CYP27B1 gene encodes 25-hydroxyvitamin D-1α-hydroxylase. Mutations of this gene cause vitamin D-dependent rickets type 1A (VDDR-IA, OMIM 264700), which is a rare autosomal recessive disorder. To investigate CYP27B1 mutations, we studied 8 patients from 7 unrelated families. All coding exons and intron-exon boundaries of CYP27B1 gene were amplified by PCR from peripheral leukocyte DNA and subsequently sequenced. Homozygous mutations in the CYP27B1 gene were found in all the patients and heterozygous mutations were present in their normal parents. One novel single nucleotide variation (SNV, c.1215 T>C, p.R379R in the last nucleotide of exon 7) and three novel mutations were identified:, a splice donor site mutation (c.1215+2T>A) in intron 7, a 16-bp deletion in exon 6 (c.1022-1037del16), and a 2-bp deletion in exon 5 (c.934_935delAC). Both c.1215 T>C and c.1215+2T>A were present together in homozygous form in two unrelated patients, and caused exon 7 skipping. However, c.1215 T>C alone has no effect on pre-mRNA splicing. The skipping of exon 7 resulted in a shift of downstream reading frame and a premature stop codon 57 amino acids from L380 (p.L380Afs*57). The intra-exon deletions of c.1022-1037del16 and c.934_935delAC also resulted in a frameshift and the creation of premature stop codons at p.T341Rfs*5, and p.T312Rfs*19, respectively, leading to the functional inactivation of the CYP27B1 gene. Clinically, all the patients required continued calcitriol treatment and the clinical presentations were consistent with the complete loss of vitamin D1α-hydroxylase activity. In conclusion, three novel mutations have been identified. All of them caused frameshift and truncated proteins. The silent c.1215 T>C SNV has no effect on pre-mRNA splicing and it is likely a novel SNP. The current study further expands the CYP27B1 mutation spectrum.
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Affiliation(s)
- Korcan Demir
- Division of Pediatric Endocrinology, Dr. Behçet Uz Children's Hospital, İzmir, Turkey
| | - Walaa E Kattan
- College of Science and General Studies, Alfaisal University, Riyadh, Saudi Arabia; Department of Genetics, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - Minjing Zou
- Department of Genetics, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - Erdem Durmaz
- Department of Pediatric Endocrinology, Sifa University, Bornova Health Application and Research Center, İzmir, Turkey
| | - Huda BinEssa
- Department of Genetics, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - Özlem Nalbantoğlu
- Division of Pediatric Endocrinology, Dr. Behçet Uz Children's Hospital, İzmir, Turkey
| | - Roua A Al-Rijjal
- Department of Genetics, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - Brian Meyer
- Department of Genetics, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - Behzat Özkan
- Division of Pediatric Endocrinology, Dr. Behçet Uz Children's Hospital, İzmir, Turkey
| | - Yufei Shi
- Department of Genetics, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
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17
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Suárez-Martínez EB, Pérez CM, Cruz SK, Khorsandi S, Chardón C, Ferder L. Importance of vitamin D and vitamin D levels status in Puerto Ricans. J Health Care Poor Underserved 2014; 24:38-47. [PMID: 24241259 DOI: 10.1353/hpu.2014.0000] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
There is growing and compelling evidence demonstrating the extra-skeletal role of vitamin D and the importance of maintaining adequate levels of this nutrient. Currently, there is very limited information available on the vitamin D status in children and adults in underserved groups, including Puerto Ricans. We assessed the vitamin D status of 4,090 Puerto Ricans living in six geographical regions in the island. Only 31.5% of the studied population had sufficient vitamin D levels (>30 ng/ml). The 18-39 year age group and the females showed inadequate (<30 ng/ml) levels of vitamin D (76.9% and 69.8%, respectively). Participants aged 60 or older showed the highest mean values of serum 25(OH)D (28.8 ng/ml) and the highest percentage (37.1%) of sufficient levels (>30 ng/ml). Future studies are certainly warranted to understand the prevalence of vitamin D deficiency and influencing factors (including obesity) in Puerto Ricans.
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18
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Stubbs JR, Zhang S, Friedman PA, Nolin TD. Decreased conversion of 25-hydroxyvitamin D3 to 24,25-dihydroxyvitamin D3 following cholecalciferol therapy in patients with CKD. Clin J Am Soc Nephrol 2014; 9:1965-73. [PMID: 25183657 DOI: 10.2215/cjn.03130314] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
BACKGROUND AND OBJECTIVES Elevated concentrations of fibroblast growth factor 23 (FGF23) are postulated to promote 25-hydroxyvitamin D (25[OH]D) insufficiency in CKD by stimulating 24-hydroxylation of this metabolite, leading to its subsequent degradation; however, prospective human studies testing this relationship are lacking. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS An open-label prospective study was conducted from October 2010 through July 2012 to compare the effect of 8 weeks of oral cholecalciferol therapy (50,000 IU twice weekly) on the production of 24,25(OH)2D3 in vitamin D-insufficient patients with CKD (n=15) and controls with normal kidney function (n=15). Vitamin D metabolites were comprehensively profiled at baseline and after treatment, along with FGF23 and other mineral metabolism parameters. RESULTS Vitamin D3 and 25(OH)D3 concentrations increased equivalently in the CKD and control groups following cholecalciferol treatment (median D3 change, 8.6 ng/ml [interquartile range, 3.9-25.6 ng/ml] for controls versus 12.6 ng/ml [6.9-41.2 ng/ml] for CKD [P=0.15]; 25(OH)D3 change, 39.2 ng/ml [30.9-47.2 ng/ml] for controls versus 39.9 ng/ml [31.5-44.1 ng/ml] for CKD [P=0.58]). Likewise, the absolute increase in 1α,25(OH)2D3 was similar between CKD participants and controls (change, 111.2 pg/ml [64.3-141.6 pg/ml] for controls versus 101.1 pg/ml [74.2-123.1 pg/ml] for CKD; P=0.38). Baseline and post-treatment 24,25(OH)2D3 concentrations were lower in the CKD group; moreover, the absolute increase in 24,25(OH)2D3 after therapy was markedly smaller in patients with CKD (change, 2.8 ng/ml [2.3-3.5 ng/ml] for controls versus 1.2 ng/ml [0.6-1.9 ng/ml] for patients with CKD; P<0.001). Furthermore, higher baseline FGF23 concentrations were associated with smaller increments in 24,25(OH)2D3 for individuals with CKD; this association was negated after adjustment for eGFR by multivariate analysis. CONCLUSIONS Patients with CKD exhibit an altered ability to increase serum 24,25(OH)2D3 after cholecalciferol therapy, suggesting decreased 24-hydroxylase activity in CKD. The observed relationship between baseline FGF23 and increments in 24,25(OH)2D3 further refutes the idea that FGF23 directly contributes to 25(OH)D insufficiency in CKD through stimulation of 24-hydroxylase activity.
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Affiliation(s)
- Jason R Stubbs
- The Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas;
| | - Shiqin Zhang
- The Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas
| | - Peter A Friedman
- Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and
| | - Thomas D Nolin
- Department of Pharmacy and Therapeutics, Center for Clinical Pharmaceutical Sciences, and Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh Schools of Pharmacy and Medicine, Pittsburgh, Pennsylvania
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19
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Abstract
Interest in Vitamin D has risen considerably recently with many athletes now advised to take daily vitamin D supplements. The reason for this interest is partly not only attributed to the resurgence of the Vitamin D-deficient disease rickets but also due to the discovery of a Vitamin D receptor in many tissues suggesting a more global role for Vitamin D than previously considered. Unlike the other vitamins that are obtained through the diet, Vitamin D is unique since endogenous synthesis following ultraviolet B (UVB) exposure is the predominant route of entry into systemic circulation. Moreover, Vitamin D could be better classed as a seco-steroid, given that its structure is similar to that of a steroid, and its production is derived from a cholesterol precursor (7-dehydrocholesteol) in the skin. The classification of Vitamin D status is currently subject to considerable debate with many authors opposing governing body recommendations. Regardless of the suggested optimal concentration, there is now growing evidence to suggest that many athletes are in fact Vitamin D deficient, especially in the winter months largely as a consequence of inadequate sun exposure, combined with poor dietary practices, although the consequences of such deficiencies are still unclear in athletic populations. Impaired muscle function and reduced regenerative capacity, impaired immune function, poor bone health and even impaired cardiovascular function have all been associated with low Vitamin D in athletes, however, to date, the majority of studies on Vitamin D have described associations and much more research is now needed examining causation.
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Affiliation(s)
- Daniel J Owens
- a Research Institute for Sport and Exercise Sciences , Liverpool John Moores University , Liverpool , UK
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20
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Abu el Maaty MA, Hanafi RS, Aboul-Enein HY, Gad MZ. Design-of-Experiment Approach for HPLC Analysis of 25-Hydroxyvitamin D: A Comparative Assay with ELISA. J Chromatogr Sci 2014; 53:66-72. [DOI: 10.1093/chromsci/bmu017] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
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Cantorna MT, McDaniel K, Bora S, Chen J, James J. Vitamin D, immune regulation, the microbiota, and inflammatory bowel disease. Exp Biol Med (Maywood) 2014; 239:1524-30. [PMID: 24668555 DOI: 10.1177/1535370214523890] [Citation(s) in RCA: 108] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The inflammatory bowel diseases are complex diseases caused by environmental, immunological, and genetic factors. Vitamin D status is low in patients with inflammatory bowel diseases, and experimental inflammatory bowel diseases are more severe in vitamin D-deficient or vitamin D receptor knockout animals. Vitamin D is beneficial in inflammatory bowel diseases because it regulates multiple checkpoints and processes essential for homeostasis in the gut. Vitamin D inhibits IFN-γ and IL-17 production while inducing regulatory T cells. In addition, vitamin D regulates epithelial cell integrity, innate immune responses, and the composition of the gut microbiota. Overall, vitamin D regulates multiple pathways that maintain gastrointestinal homeostasis. The data support improving vitamin D status in patients with inflammatory bowel diseases.
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Affiliation(s)
- Margherita T Cantorna
- Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, PA 16802, USA Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, PA 16802, USA
| | - Kaitlin McDaniel
- Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, PA 16802, USA
| | - Stephanie Bora
- Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, PA 16802, USA
| | - Jing Chen
- Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, PA 16802, USA
| | - Jamaal James
- Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, PA 16802, USA
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22
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Development of a validated UPLC method for simultaneous estimation of both free and entrapped (in solid lipid nanoparticles) all-trans retinoic acid and cholecalciferol (vitamin D3) and its pharmacokinetic applicability in rats. J Pharm Biomed Anal 2014; 91:73-80. [DOI: 10.1016/j.jpba.2013.12.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2013] [Revised: 11/30/2013] [Accepted: 12/12/2013] [Indexed: 11/21/2022]
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Yang L, Weaver V, Smith JP, Bingaman S, Hartman TJ, Cantorna MT. Therapeutic effect of vitamin d supplementation in a pilot study of Crohn's patients. Clin Transl Gastroenterol 2013; 4:e33. [PMID: 23594800 PMCID: PMC3636524 DOI: 10.1038/ctg.2013.1] [Citation(s) in RCA: 136] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVES Low vitamin D status may be associated with Crohn's disease. A pilot study was performed in patients with mild-to-moderate Crohn's disease to determine the dose of vitamin D needed to raise serum vitamin D levels above 40 ng/ml. METHODS Patients were evaluated for severity of symptoms using the Crohn's disease activity index (CDAI) and patients with mild-to-moderate (150-400 CDAI scores) Crohn's disease were entered into the study (n=18). Vitamin D3 oral therapy was initiated at 1,000 IU/d and after 2 weeks, the dose was escalated incrementally until patients' serum concentrations reached 40 ng/ml 25(OH)D3 or they were taking 5,000 IU/d. Patients continued on the vitamin D supplements for 24 weeks. CDAI, quality of life measures, bone mineral density, dietary analyses, cytokines, parathyroid hormone, calcium, and several other laboratory measurements were evaluated at baseline and after 24 weeks supplementation. RESULTS Fourteen of eighteen patients required the maximal vitamin D supplement of 5,000 IU/d. Vitamin D oral supplementation significantly increased serum 25(OH)D3 levels from 16±10 ng/ml to 45±19 ng/ml (P<0.0001) and reduced the unadjusted mean CDAI scores by 112±81 points from 230±74 to 118±66 (P<0.0001). Quality-of-life scores also improved following vitamin D supplementation (P=0.0004). No significant changes in cytokine or other laboratory measures were observed. CONCLUSIONS Twenty-four weeks supplementation with up to 5,000 IU/d vitamin D3 effectively raised serum 25(OH)D3 and reduced CDAI scores in a small cohort of Crohn's patients suggesting that restoration of normal vitamin D serum levels may be useful in the management of patients with mild-moderate Crohn's disease.
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Affiliation(s)
- Linlin Yang
- Department of Veterinary and Biomedical Science, Center for Molecular Immunology and Infectious Disease, University Park, Pennsylvania, USA
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24
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Fraser WD, Milan AM. Vitamin D assays: past and present debates, difficulties, and developments. Calcif Tissue Int 2013; 92:118-27. [PMID: 23314742 DOI: 10.1007/s00223-012-9693-3] [Citation(s) in RCA: 115] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2012] [Accepted: 11/30/2012] [Indexed: 11/28/2022]
Abstract
Clinical interest in Vitamin D and its purported roles not only in calcium and bone metabolism but in several other medical conditions (diabetes, cardiovascular disease, multiple sclerosis, cancer, psychiatric disorders, neuro-muscular disease) has led to a surge in laboratory requests for 25 hydroxy vitamin D and 1,25 dihydroxy vitamin D measurement. Circulating 25 hydroxy vitamin D concentration is routinely used as the best indicator of vitamin D status, but measurement of other metabolites, especially the physiologically active 1,25 dihyroxy vitamin D, are of clinical value. Over the last 40 years the development of assays for vitamin D and its metabolites from early competitive binding assays through to immunoassay and liquid chromatography aligned to mass spectrometry have demonstrated various analytical challenges, the advantages and disadvantages of each method are constantly changing with new technological developments. Immunoassay remains the predominant mode of measurement for 25-hydroxy vitamin D although problems with equimolar recovery of the D2 and D3 metabolites remain an issue. Standardisation of all assays has been improved but not resolved with the currently available reference materials as evidenced by the international vitamin D external quality assurance scheme, DEQAS. The choice of method for each laboratory remains a balance mainly between turn around time, convenience, cost and the specificity and accuracy of the information obtained. With increasing discussion and clinical interest surrounding other vitamin D metabolites the vitamin D assay debate is set to continue.
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25
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Vandevijvere S, Amsalkhir S, Van Oyen H, Moreno-Reyes R. High prevalence of vitamin D deficiency in pregnant women: a national cross-sectional survey. PLoS One 2012; 7:e43868. [PMID: 22937114 PMCID: PMC3427250 DOI: 10.1371/journal.pone.0043868] [Citation(s) in RCA: 96] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2012] [Accepted: 07/26/2012] [Indexed: 12/21/2022] Open
Abstract
An increasing number of studies suggest that vitamin D deficiency during pregnancy is associated with multiple adverse health outcomes in mothers, neonates and children. There are no representative country data available on vitamin D status of pregnant women in Europe. The aim of this study was to estimate the prevalence of vitamin D deficiency among Belgian pregnant women and to assess the determinants of vitamin D status in the first and third trimester of pregnancy. The women were selected via a multi-stage proportionate-to-size sampling design. Blood samples were collected and a questionnaire was completed face-to-face. 55 obstetric clinics were randomly selected and 1311 pregnant women participated in the study. The median serum 25-hydroxyvitamin D [25-(OH)D] concentration was significantly lower in the first trimester (20.4 ng/ml) than in third trimester (22.7 ng/ml). Of all women, 74.1% (95%CI = 71.8–76.5%) were vitamin D insufficient (25-(OH)D <30 ng/ml), 44.6% (95%CI = 41.9–47.3%) were vitamin D deficient (25-(OH)D <20 ng/ml), while 12.1% (95%CI = 10.3–13.8%) were severely vitamin D deficient (25-(OH)D <10 ng/ml). Of all women included, 62.0% reported taking vitamin D-containing multivitamins, of which only 24.2% started taking those before pregnancy. The risk of vitamin D deficiency (25-(OH)D <20 ng/ml) was significantly higher for less educated women and women who reported not going on holidays to sunny climates. The risk of severe vitamin D deficiency (25-(OH)D <10 ng/ml) decreased for women who reported alcohol consumption during pregnancy, decreased with more frequent use of sunscreen lotion and increased for smokers and women who reported preference for shadow. In conclusion, vitamin D deficiency is highly prevalent among pregnant women in Belgium and this raises concerns about the health consequences for the mother and the offspring. A targeted screening strategy to detect and treat women at high risk of severe vitamin D deficiency is needed in Belgium and in Europe.
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Affiliation(s)
- Stefanie Vandevijvere
- Department of Public Health and Surveillance, Scientific Institute of Public Health, Brussels, Belgium.
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26
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Xie W, Chavez-Eng C, Fang W, Constanzer M, Matuszewski B, Mullett W, Pawliszyn J. Quantitative liquid chromatographic and tandem mass spectrometric determination of vitamin D3 in human serum with derivatization: A comparison of in-tube LLE, 96-well plate LLE and in-tip SPME. J Chromatogr B Analyt Technol Biomed Life Sci 2011; 879:1457-66. [DOI: 10.1016/j.jchromb.2011.03.018] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2010] [Revised: 01/14/2011] [Accepted: 03/07/2011] [Indexed: 10/18/2022]
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Pei FH, Wang YJ, Gao SL, Liu BR, DU YJ, Liu W, Yu HY, Zhao LX, Chi BR. Vitamin D receptor gene polymorphism and ulcerative colitis susceptibility in Han Chinese. J Dig Dis 2011; 12:90-8. [PMID: 21401893 DOI: 10.1111/j.1751-2980.2011.00483.x] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Specific polymorphisms in the vitamin D receptor (VDR) gene have been associated with genetic susceptibility to inflammatory bowel disease (IBD) in different ethnic populations. METHODS A total of 218 ulcerative colitis (UC) patients and 251 healthy controls were genotyped for VDR gene polymorphisms using PCR-restriction fragment length polymorphism (PCR-RFLP) assay. VDR gene polymorphisms (Apa I, Taq I, Bsm I and Fok I) were analyzed for both genotypic and phenotypic susceptibilities. RESULTS Among the four examined VDR gene polymorphisms, the Bsm I polymorphism showed a slightly higher distribution in our study population than that in the previous studies. We also found that the increased frequency of the Bb genotype of the Bsm I VDR gene polymorphism was associated with UC in Han Chinese, as compared with healthy controls (28.4% vs. 18.7%, χ(2) = 6.044, P = 0.014, OR = 1.739, 95% CI = 1.122-2.697). Moreover, Bsm I polymorphic allele (B) frequency was significantly increased in the UC cases, as compared to the healthy controls (14.7% vs. 7.8% χ(2) = 6.222, P = 0.013; OR = 1.670, 95% CI = 1.113-2.506). In contrast, the other three VDR gene polymorphisms (Apa I, Taq I and Fok I) were not associated with UC susceptibility in the Han Chinese cohort. In addition, none of these four VDR polymorphisms had statistical association with clinicopathological parameters of these UC patients. CONCLUSION This study demonstrated a probable association of the Bsm I polymorphism of the VDR gene with ulcerative colitis susceptibility in Han Chinese.
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Affiliation(s)
- Feng Hua Pei
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, Jilin Province, China
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Abstract
Vitamin D and the vitamin D receptor (VDR) have been shown to be important regulators of the immune system. In particular, vitamin D and VDR deficiency exacerbates experimental autoimmune diseases such as inflammatory bowel disease (IBD). IBD develops due to an immune-mediated attack by pathogenic T-cells that overproduce IL-17 and IFN-gamma and a few regulatory cells. VDR knockout mice have twice as many T-cells making IL-17 and IFN-gamma than wild-type mice. In addition, vitamin D and the VDR are required for normal numbers of regulatory T-cells (iNKT and CD8alphaalpha) that have been shown to suppress experimental IBD. In the absence of vitamin D and the VDR, autoimmunity occurs in the gastrointestinal tract due to increased numbers of IL-17 and IFN-gamma secreting T-cells and a concomitant reduction in regulatory T-cells.
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Affiliation(s)
- Margherita T Cantorna
- Center for Molecular Immunology and Infectious Disease, Department of Veterinary and Biomedical Science, The Pennsylvania State University, 115 Henning Bldg, University Park, PA 16802, USA.
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Abstract
PURPOSE OF REVIEW To understand the basis for current recommendations for vitamin D supplementation in childhood and the differences between the recommendations published by major expert committees, using the Medline engine of the US National Library of Medicine and the National Institutes of Health. RECENT FINDINGS Recent recommendations published by major national expert committees are essentially based on expert opinion (a relatively low level of evidence). Randomized controlled trials are very few, and there are no systematic reviews or meta-analyses on the topic. Most trials have examined the question of whether a specific daily vitamin D dose is capable or not to prevent rickets (by studying surrogate markers of rickets). There are no trials that have systematically attempted to determine the upper limit of daily vitamin D dose beyond which its toxic effects may appear. Whether or not outcomes such as osteoporosis (or low bone mass) and specific types of cancer may be prevented by 'generous' vitamin D supplementation is unclear and mostly based on indirect epidemiologic data not clearly substantiated by randomized controlled trials SUMMARY The dose of daily vitamin D supplements needed to prevent rickets is probably much lower than that recommended by most expert committees. Whether higher doses of daily vitamin D supplements may or may not prevent other poor outcomes such as adult osteoporosis or specific types of cancer is not yet known.
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Affiliation(s)
- Francis B Mimouni
- Department of Pediatrics, Shaare Zedek Medical Center, Jerusalem, Israel.
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Wu T, Willett WC, Giovannucci E. Plasma C-peptide is inversely associated with calcium intake in women and with plasma 25-hydroxy vitamin D in men. J Nutr 2009; 139:547-54. [PMID: 19141703 PMCID: PMC2646217 DOI: 10.3945/jn.108.089920] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2008] [Revised: 04/22/2008] [Accepted: 12/10/2008] [Indexed: 02/05/2023] Open
Abstract
The consumption of calcium, vitamin D, and dairy products may be associated with a reduced risk of type 2 diabetes mellitus. However, whether this reduction is due to calcium, vitamin D, or other components of dairy products is not clear. We examined intakes of total calcium and vitamin D, and plasma concentrations of 25 hydroxyvitamin D [25(OH)D] in relation to fasting plasma concentrations of C-peptide in 2 cross-sectional studies among healthy men from the Health Professionals Follow-up Study and among healthy women from the Nurses' Health Study I. Intake of total calcium was modestly inversely associated with C-peptide concentration in women (P-trend = 0.05); however, the inverse association was not significant in men (P = 0.7). Concentrations of C-peptide were 20% lower among men who had plasma concentrations of 25(OH)D in the highest quartile compared with those in the lowest quartile (P-trend = 0.08); there was no association in women (P = 0.3). The inverse association between calcium intake and the plasma C-peptide concentration was stronger in hypertensive individuals of both sexes. The difference in the C-peptide concentrations between extreme quartiles of calcium intake was 17% in men and 20% in women. Plasma concentrations of C-peptide for the combination of the highest tertiles of calcium intake and plasma 25(OH)D compared with the opposite extreme were 35% lower (P = 0.03) in men and 12% lower (P = 0.01) in women. The results suggest that calcium intake or systemic vitamin D status, after adjustment for intake of dairy products, is associated with decreased insulin secretion.
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Affiliation(s)
- Tianying Wu
- Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.
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31
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Cantorna MT, Yu S, Bruce D. The paradoxical effects of vitamin D on type 1 mediated immunity. Mol Aspects Med 2008; 29:369-75. [PMID: 18561994 PMCID: PMC2633636 DOI: 10.1016/j.mam.2008.04.004] [Citation(s) in RCA: 98] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2008] [Revised: 04/18/2008] [Accepted: 04/22/2008] [Indexed: 12/19/2022]
Abstract
Low vitamin D status is associated with an increased risk of Th1 mediated autoimmune diseases like inflammatory bowel disease. 1,25(OH)(2)D(3) treatments have been shown to suppress Th1 mediated immunity and protect animals from experimental autoimmunity. Th1 mediated immunity is important for clearance of a number of different infectious diseases. For tuberculosis 1,25(OH)(2)D(3) treatment is associated with decreased Th1 mediated immunity but increased bactericidal activity. Systemic candidiasis is unaffected by 1,25(OH)(2)D(3) treatment. The seemingly paradoxical effects of 1,25(OH)(2)D(3) and vitamin D on Th1 mediated autoimmunity versus infectious immunity point to a broad array of vitamin D targets in the immune system. The interplay of these vitamin D targets and their impact on the host-immune response then dictate the outcome.
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Affiliation(s)
- Margherita T Cantorna
- Department of Veterinary and Biomedical Sciences, Center for Molecular Immunology and Infectious Diseases, The Pennsylvania State University, University Park, PA 16802, USA.
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32
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Abstract
In the past quarter century, more than 50 metabolites of vitamin D have been described. To date, only a few of these have been quantified in blood, but this has widened our understanding of the pathologic role that altered vitamin D metabolism plays in the development of diseases of calcium homeostasis. Currently, awareness is growing of the prevalence of vitamin D insufficiency in the general population in association with an increased risk of several diseases. However, for many researchers, it is not clear which vitamin D metabolites should be quantified and what the information gained from such an analysis tells us. Only 2 metabolites, namely, 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D], have received the greatest attention. Of these, the need for measuring serum 1,25(OH)2D is limited, and this metabolite should therefore not be considered as part of the standard vitamin D testing regimen. On the other hand, serum 25(OH)D provides the single best assessment of vitamin D status and thus should be the only vitamin D assay typically performed. Currently, numerous formats exist for measuring serum 25(OH)D concentrations, each with its own advantages and disadvantages. This article reviews the currently available methods for serum 25(OH)D quantitation and considers important issues such as whether both the D2 and the D3 forms of the vitamin should be assayed, whether total or free concentrations are most important, and what measures should be taken to ensure the fidelity of the measurements.
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Affiliation(s)
- Joseph E Zerwekh
- Charles and Jane Pak Center for Mineral Metabolism and Clinical Research and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-8885, USA.
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33
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Vitamin D and cancer incidence in the Harvard cohorts. Ann Epidemiol 2008; 19:84-8. [PMID: 18291673 DOI: 10.1016/j.annepidem.2007.12.002] [Citation(s) in RCA: 120] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2007] [Revised: 07/11/2007] [Accepted: 12/14/2007] [Indexed: 12/12/2022]
Abstract
Since the hypothesis that vitamin D reduces the risk of some cancers was initiated in 1980, this hypothesis has been studied in the Harvard cohort studies, including the Nurses' Health Study (NHS), the Health Professionals Follow-Up Study (HPFS), and the Physicians' Health Study (PHS). Three approaches have been used, the study of circulating 25(OH)vitamin D (25(OH)D) level, of dietary and supplementary intake, and of predicted 25(OH)D. These cohorts strongly support an inverse association with colorectal cancer, because this association has been viewed in both the NHS and HPFS cohorts, for cancers and adenomas, and for plasma, diet, and predicted 25(OH)D analyses. In the NHS, about a 30% reduction in risk was observed for breast cancer comparing the highest with lowest quintiles of 25(OH)D levels. Vitamin D intake also was associated with a lower risk of pancreatic cancer in both men and women, but studies of plasma or predicted 25(OH)D level or dietary intake have generally not been supportive of a major role of vitamin D status in middle-age or elderly men on prostate cancer risk. Results from the HPFS also suggest that the poor vitamin D status generally in African-Americans contributes to their higher incidence and mortality from various malignancies.
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Gorham ED, Mohr SB, Garland CF, Chaplin G, Garland FC. Do Sunscreens Increase Risk of Melanoma in Populations Residing at Higher Latitudes? Ann Epidemiol 2007; 17:956-63. [DOI: 10.1016/j.annepidem.2007.06.008] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2006] [Revised: 05/17/2007] [Accepted: 06/10/2007] [Indexed: 12/21/2022]
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Young AR, Walker SL. UV radiation, vitamin D and human health: an unfolding controversy introduction. Photochem Photobiol 2006; 81:1243-5. [PMID: 16354109 DOI: 10.1562/2005-10-16-ra-716] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Antony R Young
- St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, King's College London School of Medicine at Guy's, St. Thomas' Hospitals, London, England.
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36
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Cantorna MT, Zhu Y, Froicu M, Wittke A. Vitamin D status, 1,25-dihydroxyvitamin D3, and the immune system. Am J Clin Nutr 2004; 80:1717S-20S. [PMID: 15585793 DOI: 10.1093/ajcn/80.6.1717s] [Citation(s) in RCA: 447] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Vitamin D is an important immune system regulator. The active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], has been shown to inhibit the development of autoimmune diseases, including inflammatory bowel disease (IBD). Paradoxically, other immune system-mediated diseases (experimental asthma) and immunity to infectious organisms were unaffected by 1,25(OH)2D3 treatment. There are similar paradoxical effects of vitamin D deficiency on various immune system functions. Vitamin D and vitamin D receptor (VDR) deficiency resulted in accelerated IBD. Experimental asthma was unaffected by 1,25(OH)2D3 treatment and was less severe among VDR-deficient mice. Vitamin D is a selective regulator of the immune system, and the outcome of 1,25(OH)2D3 treatment, vitamin D deficiency, or VDR deficiency depends on the nature of the immune response (eg, infectious disease, asthma, or autoimmune disease). An additional factor that determines the effect of vitamin D status on immune function is dietary calcium. Dietary calcium has independent effects on IBD severity. Vitamin D-deficient mice on low-calcium diets developed the most severe IBD, and 1,25(OH)2D3 treatment of mice on low-calcium diets improved IBD symptoms. However, the best results for IBD were observed when the calcium concentration was high and 1,25(OH)2D3 was administered. Both the type of immune response and the calcium status of the host determine the effects of vitamin D status and 1,25(OH)2D3 on immunity.
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Affiliation(s)
- Margherita T Cantorna
- Department of Nutritional Sciences, Pennsylvania State University, University Park, PA 16802, USA.
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37
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Abstract
A comparison was made of the ability of ergocalciferol and cholecalciferol to elevate plasma concentrations of vitamin D and 25-hydroxyvitamin D in cats. Cholecalciferol, given as an oral bolus in oil, resulted in a rapid elevation of plasma concentration of cholecalciferol followed by a rapid decline. In contrast, 25-hydroxyvitamin D concentration in plasma increased until day 3 after administration and remained elevated for a further 5 days. When 337 microg of both cholecalciferol and ergocalciferol in oil were given as an oral bolus to 10 cats, the peak plasma concentrations of cholecalciferol and ergocalciferol occurred at 8 or 12 h after administration. Peak concentrations of cholecalciferol were over twice those of ergocalciferol (570 +/- 80 vs. 264 +/- 42 nmol/l). The area under the curve 0-169 h for cholecalciferol was also more than twice that for ergocalciferol. When ergocalciferol and cholecalciferol were administered in a parenteral oil-based emulsion, higher concentrations of 25-hydroxyvitamin D3 than 25-hydroxyvitamin D2 were maintained in plasma. When both vitamins were included in the diet in the nutritional range, plasma concentrations of 25-hydroxyvitamin D2 were 0.68 of those of 25-hydroxyvitamin D3. Discrimination against ergocalciferol by cats appears to result from differences in affinity of the binding protein for the metabolites of the two forms of vitamin D. These results indicate that cats discriminate against ergocalciferol, and use it with an efficiency of 0.7 of that of cholecalciferol to maintain plasma 25-hydroxyvitamin D concentration.
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Affiliation(s)
- J G Morris
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
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38
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Cantorna MT, Munsick C, Bemiss C, Mahon BD. 1,25-Dihydroxycholecalciferol prevents and ameliorates symptoms of experimental murine inflammatory bowel disease. J Nutr 2000; 130:2648-52. [PMID: 11053501 DOI: 10.1093/jn/130.11.2648] [Citation(s) in RCA: 348] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Anecdotal data suggest that the amount of vitamin D available in the environment either from sunshine exposure or diet may be an important factor affecting the development of inflammatory bowel disease (IBD) in humans. We tested the vitamin D hypothesis in an experimental animal model of IBD. Interleukin (IL)-10 knockout (KO) mice, which spontaneously develop symptoms resembling human IBD, were made vitamin D deficient, vitamin D sufficient or supplemented with active vitamin D (1,25-dihydroxycholecalciferol). Vitamin D-deficient IL-10 KO mice rapidly developed diarrhea and a wasting disease, which induced mortality. In contrast, vitamin D-sufficient IL-10 KO mice did not develop diarrhea, waste or die. Supplementation with 50 IU of cholecalciferol (5.0 microgram/d) or 1, 25-dihydroxycholecalciferol (0.005 microgram/d) significantly (P < 0. 05) ameliorated symptoms of IBD in IL-10 KO mice. 1, 25-Dihydroxycholecalciferol treatment (0.2 microgram/d) for as little as 2 wk blocked the progression and ameliorated (P < 0.05) symptoms in IL-10 KO mice with already established IBD.
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Affiliation(s)
- M T Cantorna
- Department of Nutrition, College of Health and Human Development, The Pennsylvania State University, University Park, PA 16802, USA
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39
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Kinetic and thermodynamic studies of the conversion of previtamin D3 to vitamin D3 in human skin. J Biol Chem 1993. [DOI: 10.1016/s0021-9258(18)82416-4] [Citation(s) in RCA: 91] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
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Watson D, Setchell KD, Ross R. Analysis of vitamin D and its metabolites using thermospray liquid chromatography/mass spectrometry. Biomed Chromatogr 1991; 5:153-60. [PMID: 1655127 DOI: 10.1002/bmc.1130050404] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
A new method is described for the analysis of vitamin D and its metabolites utilizing thermospray (TSP) mass spectrometry as an on-line detector for high performance liquid chromatography. Ionization conditions were optimized for use with isocratic reversed phase chromatography. TSP mass spectrometry was employed in series with a UV absorbance detector to facilitate comparisons between the two methods of detection. Positive ion TSP mass spectra were recorded for vitamin D2, vitamin D3, 25-hydroxyvitamin D3 (25(OH)D3), 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3). The spectra contained protonated molecular ions, ammonium adduct ions and fragment ions due to the loss of one or more molecules of water. A comparison of quantitative precision was made by determining UV absorbance and TSP standard curves for vitamin D3 using two different methods: (1) External standard method with post-column (post UV detector) addition of ammonium acetate. (2) As (1) but using the method of internal standards with a closely eluting internal standard (vitamin D2). In each case the quantitative precision (correlation coefficient) for UV absorbance detection was superior owing to intrinsic instability of the TSP ion beam. A stable isotopically labelled internal standard was employed in the development of an assay for 1,25(OH)2D3. The assay was used to quantify in vitro enzymic conversion of 25(OH)D3 to 1,25(OH)2D3 in guinea pig and sheep renal mitochondrial incubations. TSP LC/MS was also applied to analysis of an extract of human blood plasma in which D3 and each of its principal metabolites were identified in a single analysis.
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Affiliation(s)
- D Watson
- Mass Spectrometry Laboratory, Children's Hospital Medical Center, Cincinnati, Ohio 45229
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41
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Abstract
The HMG-CoA reductase inhibitors, a new class of lipid-lowering agents being used with increasing frequency, inhibit synthesis of cholesterol in vivo. Thus, one potential side effect of these drugs is alteration of other metabolic pathways requiring intermediates in the cholesterol biosynthetic pathway. We hypothesized that pravastatin, a new HMG-CoA reductase inhibitor, may impair vitamin D3 synthesis in the skin and alter mineral homeostasis by diminishing the availability of vitamin D precursors. Basal serum levels of calcium, phosphorus, parathyroid hormone (PTH), vitamin D3, and 1,25-dihydroxyvitamin D were measured, and dietary intakes of calcium and vitamin D were calculated in a control hypercholesterolemic group and an experimental group treated with pravastatin 10, 20, and/or 40 mg orally twice daily for at least 3 months. Basal parameters of mineral metabolism were similar in the two groups. To assess the capacity of the skin to synthesize vitamin D3 and as an indirect measure of its precursors, all subjects received whole body ultraviolet irradiation (UVI) in a phototherapy chamber for varying time intervals. Subjects in both groups showed significant (P less than .001) dose-dependent increases in vitamin D3 production after equivalent UVI exposures. However, for equivalent UVI exposure, the serum vitamin D3 response was identical in controls versus pravastatin-treated subjects. We conclude that hypercholesterolemic patients have normal mineral metabolism and the use of pravastatin at these doses for up to 3 months does not alter vitamin D3 synthesis in the skin.
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Affiliation(s)
- A S Dobs
- Johns Hopkins University School of Medicine, Baltimore, MD 21205
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42
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Holmberg I, Aksnes L, Berlin T, Lindbäck B, Zemgals J, Lindeke B. Absorption of a pharmacological dose of vitamin D3 from two different lipid vehicles in man: comparison of peanut oil and a medium chain triglyceride. Biopharm Drug Dispos 1990; 11:807-15. [PMID: 2176898 DOI: 10.1002/bdd.2510110908] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
The absorption of a pharmacological dose of vitamin D3 from two different lipid vehicles, peanut oil, containing long chain fatty acids, and a medium chain triglyceride was compared. Serial measurements of the serum concentration of vitamin D3 after dosage were made. The serum levels of 25-hydroxyvitamin D3, the major circulating vitamin D3 metabolite, were also determined. The analytical methods used were based on HPLC. In the fasting state, the serum levels of vitamin D3 were significantly higher after administration in peanut oil than after administration in the medium chain triglyceride. When the vitamin D3 dose was ingested together with food no difference between the two formulations was observed. Only small inter-formulation differences in serum 25-hydroxyvitamin D3 levels were detected. The results indicate that the presence of long chain fatty acids facilitates the absorption of vitamin D3.
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Chen TC, Turner AK, Holick MF. A method for the determination of the circulating concentration of vitamin D. J Nutr Biochem 1990; 1:272-6. [PMID: 15539215 DOI: 10.1016/0955-2863(90)90078-y] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Affiliation(s)
- T C Chen
- Vitamin D, Skin, and Bone Research Laboratory, Boston University School of Medicine, Boston, MA 02118, USA
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44
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45
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Garland CF, Comstock GW, Garland FC, Helsing KJ, Shaw EK, Gorham ED. Serum 25-hydroxyvitamin D and colon cancer: eight-year prospective study. Lancet 1989; 2:1176-8. [PMID: 2572900 DOI: 10.1016/s0140-6736(89)91789-3] [Citation(s) in RCA: 419] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Blood samples taken in 1974 in Washington County, Maryland, from 25 620 volunteers were used to investigate the relation of serum 25-hydroxyvitamin D (25-OHD) with subsequent risk of getting colon cancer. 34 cases of colon cancer diagnosed between August, 1975, and January, 1983, were matched to 67 controls by age, race, sex, and month blood was taken. Risk of colon cancer was reduced by 75% in the third quintile (27-32 ng/ml) and by 80% in the fourth quintile (33-41 ng/ml) of serum 25-OHD. Risk of getting colon cancer decreased three-fold in people with a serum 25-OHD concentration of 20 ng/ml or more. The results are consistent with a protective effect of serum 25-OHD on colon cancer.
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Affiliation(s)
- C F Garland
- Department of Community and Family Medicine, School of Medicine, University of California, San Diego, La Jolla
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46
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Griffiths AP, Fairney A. Effect of phototherapy on serum 25-hydroxyvitamin D in the Antarctic. EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY AND OCCUPATIONAL PHYSIOLOGY 1989; 59:68-72. [PMID: 2583152 DOI: 10.1007/bf02396582] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
The hypothesis that sunlight may induce the enzymes involved in the vitamin D pathway has been tested by comparing the ability to synthesize vitamin D3 and its 25 hydroxy metabolite (25-OHD) in 2 groups of male volunteers resident at the British Antarctic base at Rothera Point (67 degrees 34'S.). One group endured the UV depleted winter and the other group received regular phototherapy throughout the winter. Both groups then received a course of 14 days phototherapy in October (Southern Hemisphere spring). The group receiving regular phototherapy had a trend towards a higher level of serum 25-OHD, and the October phototherapy course produced a further small increase in serum 25-OHD values. In the previously non irradiated group the October phototherapy produced a much larger increase in serum 25-OHD so that they attained the previously higher values of the pre-iradiated group. There was a negative correlation between the pre October phototherapy serum concentration of 25-OHD and the subsequent increment (r-0.78, p less than 0.01) but no relationship between the serum 25-OHD and D3 after phototherapy. These results provide evidence against the existence of enzyme induction of vitamin D 25 hydroxylase by light.
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Affiliation(s)
- A P Griffiths
- Department of Chemical Pathology, St. Marys Hospital Medical School, Paddington, London
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47
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Sanchez Perez A, Delgado Zamarreño M, Hernandez Mendez J, Sanchez Rodriguez R. Flow-injection analysis of vitamin D3 and 25-hydroxy-vitamin D3 by amperometric detection. Anal Chim Acta 1989. [DOI: 10.1016/s0003-2670(00)84613-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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48
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Abstract
Previous studies demonstrated decreases in serum 25-hydroxyvitamin D in obese subjects. Studies were carried out to determine whiter serum vitamin D is low in obesity. The results indicate that serum vitamin D is significantly lower in obese than in nonobese individuals and may contribute to lower serum 25-hydroxyvitamin D in obesity.
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Affiliation(s)
- Y Liel
- Veterans Administration Medical Center, Charleston, South Carolina, 29403
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49
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De Leenheer AP, Nelis HJ, Lambert WE, Bauwens RM. Chromatography of fat-soluble vitamins in clinical chemistry. JOURNAL OF CHROMATOGRAPHY 1988; 429:3-58. [PMID: 3062023 DOI: 10.1016/s0378-4347(00)83866-9] [Citation(s) in RCA: 41] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
A review is presented of current gas and liquid chromatographic methods for the determination of the fat-soluble vitamins A, D, E and K and the provitamin A beta-carotene in biological samples of human origin. For each vitamin, the discussion successively focuses on procedures for sample preparation, gas and liquid chromatographic systems and principles of detection. The emphasis is on liquid chromatography, which is gradually becoming a standard technique in fat-soluble vitamin assays. New trends in the liquid chromatography of these compounds include the use of smaller particles and shorter columns, to improve speed, and the advance of electrochemical detection as an alternative to absorbance and fluorescence detection. Bonded phases, both normal and reversed phase, tend to be preferred over underivatized silica as column supports. Gas chromatography remains of particular value in combination with mass spectrometry, a technique which may form the basis of reference methods. In general, despite the availability of well established analytical methods for fat-soluble vitamins, the wealth of recent literature in this area indicates that there continues to be a need for new assays with enhanced speed, specificity and sensitivity.
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Affiliation(s)
- A P De Leenheer
- Laboratoria voor Medische Biochemie, Klinische Analyse, Ghent, Belgium
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Porteous CE, Coldwell RD, Trafford DJ, Makin HL. Recent developments in the measurement of vitamin D and its metabolites in human body fluids. JOURNAL OF STEROID BIOCHEMISTRY 1987; 28:785-801. [PMID: 3320575 DOI: 10.1016/0022-4731(87)90413-4] [Citation(s) in RCA: 58] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Affiliation(s)
- C E Porteous
- Department of Chemical Pathology, London Hospital Medical College, England
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