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da Silva AD, Oliveira JS, de Castro IC, Paiva WC, Gomes JMG, Pimenta LCJP. Association of vitamin D and cognition in people with type 2 diabetes: a systematic review. Nutr Rev 2024; 82:622-638. [PMID: 37403328 DOI: 10.1093/nutrit/nuad085] [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] [Indexed: 07/06/2023] Open
Abstract
CONTEXT There is a high prevalence of vitamin D deficiency and impaired cognitive function in people with type 2 diabetes mellitus (T2DM). OBJECTIVE To critically and systematically review the literature on the association between vitamin D status and cognitive performance in people with type 2 diabetes. DATA SOURCES This review was conducted according to PRISMA recommendations. MEDLINE, SCOPUS, the Cochrane Library, and Web of Science databases were searched using the terms "Diabetes Mellitus, Type 2", "Cognitive Function", and "Vitamin D". DATA EXTRACTION Eight observational and 1 randomized study were included, containing data of 14 648 adult and elderly individuals (19-74 y). All extracted data were compiled, compared, and critically analyzed. DATA ANALYSIS There is no strong evidence that lower serum concentrations of vitamin D and vitamin D-binding protein are associated with worsening cognitive function in individuals with T2DM. Vitamin D supplementation (12 wk) improved the scores of some executive functioning tests, although there was no difference between low doses (5000 IU/wk) and high doses (50 000 IU/wk). CONCLUSIONS There is no high-quality evidence demonstrating an association between vitamin D status and cognitive function, or clinical benefits on cognition from vitamin D supplementation in individuals with T2DM. Future studies are needed. Systematic Review Registration: PROSPERO registration no. CRD42021261520.
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Affiliation(s)
- Alice D da Silva
- Department of Nutrition, Universidade Federal de Lavras, Minas Gerais, Brazil
| | - Julia S Oliveira
- Department of Nutrition and Health, Universidade Federal de Viçosa, Minas Gerais, Brazil
| | - Isabela C de Castro
- Department of Nutrition, Universidade Federal de Lavras, Minas Gerais, Brazil
| | - Wanderléia C Paiva
- Instituto Federal de Educação, Ciência e Tecnologia do Sudeste de Minas Gerais, Minas Gerais, Brazil
| | - Júnia M G Gomes
- Instituto Federal de Educação, Ciência e Tecnologia do Sudeste de Minas Gerais, Minas Gerais, Brazil
| | - Laura C J P Pimenta
- Department of Nutrition, Universidade Federal de Lavras, Minas Gerais, Brazil
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Starck C, Cassettari T, Wright J, Petocz P, Beckett E, Fayet-Moore F. Mushrooms: a food-based solution to vitamin D deficiency to include in dietary guidelines. Front Nutr 2024; 11:1384273. [PMID: 38660061 PMCID: PMC11039838 DOI: 10.3389/fnut.2024.1384273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Accepted: 03/29/2024] [Indexed: 04/26/2024] Open
Abstract
Vitamin D deficiency and insufficiency is a public health issue, with low dietary vitamin D intakes a contributing factor. Rates of vitamin D deficiency are 31% in Australia, and up to 72% in some regions globally. While supplementation is often prescribed as an alternative to additional sun exposure, complementary approaches including food-based solutions are needed. Yet, food-centric dietary guidelines are not always adequate for meeting vitamin D needs. Edible mushrooms such as Agaricus bisporus can produce over 100% of vitamin D recommendations (10 μg/day, Institute of Medicine) per 75 g serve (18 μg) on exposure to UV-light, with the vitamin D2 produced showing good stability during cooking and processing. However, mushrooms are overlooked as a vitamin D source in dietary guidelines. Our dietary modelling shows that four serves/week of UV-exposed button mushrooms can support most Australian adults in meeting vitamin D recommendations, and UV-exposed mushrooms have been found to increase vitamin D status in deficient individuals. While recent evidence suggests some differences between vitamin D2 and vitamin D3 in physiological activities, vitamin D2 from mushrooms can be part of a larger solution to increasing dietary vitamin D intakes, as well as an important focus for public health policy. Mushrooms exposed to UV represent an important tool in the strategic toolkit for addressing vitamin D deficiency in Australia and globally. Health authorities lead the recognition and promotion of mushrooms as a natural, vegan, safe, and sustainable vitamin D food source.
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Affiliation(s)
| | | | | | | | - Emma Beckett
- FOODiQ Global, Sydney, NSW, Australia
- School of Health Sciences, The University of New South Wales, Kensington, NSW, Australia
| | - Flavia Fayet-Moore
- FOODiQ Global, Sydney, NSW, Australia
- School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW, Australia
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Kotwan J, Kühn J, Baur AC, Stangl GI. Oral Intake of Lumisterol Affects the Metabolism of Vitamin D. Mol Nutr Food Res 2021; 65:e2001165. [PMID: 34061442 DOI: 10.1002/mnfr.202001165] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 04/16/2021] [Indexed: 01/01/2023]
Abstract
SCOPE The treatment of food with ultraviolet-B (UV-B) light to increase the vitamin D content is accompanied by the formation of photoisomers, such as lumisterol2 . The physiological impact of photoisomers is largely unknown. METHODS AND RESULTS Three groups of C57Bl/6 mice are fed diets containing 50 µg kg-1 deuterated vitamin D3 with 0, 50 (moderate-dose) or 2000 µg kg-1 (high-dose) lumisterol2 for four weeks. Considerable quantities of lumisterol2 and vitamin D2 are found in the plasma and tissues of mice fed with 2000 µg kg-1 lumisterol2 but not in those fed 0 or 50 µg kg-1 lumisterol2 . Mice fed with 2000 µg kg-1 lumisterol2 showed strongly reduced deuterated 25-hydroxyvitamin D3 (-50%) and calcitriol (-80%) levels in plasma, accompanied by downregulated mRNA abundance of cytochrom P450 (Cyp)27b1 and upregulated Cyp24a1 in the kidneys. Increased tissue levels of vitamin D2 were also seen in mice in a second study that are kept on a diet with 0.2% UV-B exposed yeast versus those fed 0.2% untreated yeast containing iso-amounts of vitamin D2 . CONCLUSION High doses of lumisterol2 can enter the body, induce the formation of vitamin D2 , reduce the levels of 25(OH)D3 and calcitriol and strongly impact the expression of genes involved in the degradation and synthesis of bioactive vitamin D.
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Affiliation(s)
- Julia Kotwan
- Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany
- Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Jena, Germany
| | - Julia Kühn
- Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany
| | - Anja C Baur
- Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany
- Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Jena, Germany
| | - Gabriele I Stangl
- Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany
- Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Jena, Germany
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Papadimitriou DT, Vassaras AK, Holick MF. Association between population vitamin D status and SARS-CoV-2 related serious-critical illness and deaths: An ecological integrative approach. World J Virol 2021; 10:111-129. [PMID: 34079693 PMCID: PMC8152454 DOI: 10.5501/wjv.v10.i3.111] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Revised: 02/21/2021] [Accepted: 04/07/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Vitamin D population status may have possible unappreciated consequences to the coronavirus disease 2019 (COVID-19) pandemic. Α significant association between vitamin D sufficiency and reduction in clinical severity and inpatient mortality from COVID-19 disease has recently been shown, while a recent study has claimed lower COVID-19 cases in European countries with a better vitamin D status. Low serum 25-hydroxyvitamin-D [25(OH)D] was identified as an independent risk factor for COVID-19 infection and hospitalization, and administration of 0.532 mg (21280 IU) of calcifediol or 25(OH)D, followed by 0.266 mg on days 3 and 7 and then weekly until discharge or intensive care unit admission significantly reduced the need for intensive care unit treatment. AIM To elucidate the role of vitamin D European population status in the COVID-19 pandemic, data from the Worldometer were analyzed. METHODS Linear regression explored the correlation between published representative-standardized population vitamin D concentrations and the number of total cases/million (M), recovered/M, deaths/M and serious-critically ill/M from COVID-19 for 26 European countries populated > 4 M (Worldometer). Life expectancy was analyzed with semi-parametric regression. Weighted analysis of variance/analysis of covariance evaluated serious-critical/M and deaths/M by the vitamin D population status: Deficient < 50, insufficient: 50-62.5, mildly insufficient > 62.5-75 and sufficient > 75 nmol/L, while controlling for life expectancy for deaths/M. Statistical analyses were performed in XLSTAT LIFE SCIENCE and R (SemiPar Library). RESULTS Linear regression found no correlation between population vitamin D concentrations and the total cases-recovered/M, but negative correlations predicting a reduction of 47%-64%-80% in serious-critical illnesses/M and of 61%-82%-102.4% in deaths/M further enhanced when adapting for life expectancy by 133-177-221% if 25(OH)D concentrations reach 100-125-150 nmol/L, sustained on August 15, 2020, indicating a truthful association. Weighted analysis of variance was performed to evaluate serious-critical/M (r 2 = 0.22) by the vitamin D population status and analysis of covariance the deaths/M (r 2 = 0.629) controlling for life expectancy (r 2 = 0.47). Serious-critical showed a decreasing trend (P < 0.001) from population status deficient (P < 0.001) to insufficient by 9.2% (P < 0.001), to mildly insufficient by 47.6% (P < 0.044) and to sufficient by 100% (reference, P < 0.001). For deaths/M the respective decreasing trend (P < 0.001) was 62.9% from deficient (P < 0.001) to insufficient (P < 0.001), 65.15% to mildly insufficient (P < 0.001) and 78.8% to sufficient (P = 0.041). CONCLUSION Achieving serum 25(OH)D 100-150 nmol/L (40-60 ng/mL) (upper tolerable daily doses followed by maintenance proposed doses not requiring medical supervision, Endocrine Society) may protect from serious-critical illness/death from COVID-19 disease.
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Affiliation(s)
- Dimitrios T Papadimitriou
- Pediatric - Adolescent Endocrinology and Diabetes, Athens Medical Center, Marousi 15125, Greece
- Endocrine Unit, Aretaieion University Hospital, Athens 11528, Greece
| | - Alexandros K Vassaras
- Neurology Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, Thessaloniki 56429, Greece
- Neuroimmunology Department, Democritus University of Thrace, Alexandroupoli 68100, Greece
| | - Michael F Holick
- Section Endocrinology, Nutrition and Diabetes, Department of Medicine, Boston University Medical Center, Boston, MA 02118, United States
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Holick MF. A call for action: standard of care guidelines to assess vitamin D status are needed for patients with hip fracture. Am J Clin Nutr 2020; 112:507-509. [PMID: 32710753 PMCID: PMC7458764 DOI: 10.1093/ajcn/nqaa202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Affiliation(s)
- M F Holick
- Address correspondence to MFH (e-mail: )
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Rubin SJ, Park JH, Pearce EN, Holick MF, McAneny D, Noordzij JP. Vitamin D Status as a Predictor of Postoperative Hypocalcemia after Thyroidectomy. Otolaryngol Head Neck Surg 2020; 163:501-507. [PMID: 32312160 DOI: 10.1177/0194599820917907] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
OBJECTIVE To determine whether perioperative vitamin D levels are predictive of postoperative hypocalcemia in patients receiving thyroidectomy. STUDY DESIGN Single center retrospective study. SUBJECTS AND METHODS This study included all patients receiving total or completion thyroidectomy between January 2007 and March 2017 at a single tertiary care hospital. 25-Hydroxyvitamin D (25[OH]D) levels were measured within 42 days prior to surgery or 1 day postoperatively. Hypocalcemia was defined as an adjusted serum calcium <8.0 mg/dL (based on albumin levels) or symptomatic hypocalcemia. Univariate analysis was performed with a 2-sample t test and chi-square test, while multivariate analysis was performed with logistic regression analysis to determine whether perioperative 25(OH)D level is a predictor of postoperative hypocalcemia. RESULTS A total of 517 subjects were included in the study, 15.7% (n = 81) of whom experienced postoperative hypocalcemia with a mean ± SD serum calcium level of 7.6 ± 0.5 mg/dL as compared with 8.9 ± 0.5 mg/dL in the normocalcemic population (P < .01). The mean 25(OH)D level for patients with hypocalcemia was 24.4 ± 12.0 ng/mL as compared with 27.5 ± 12.2 ng/mL in patients with normocalcemia (P = .038). Subjects who were hypocalcemic experienced a significantly longer hospital stay (2.9 ± 2.5 vs 1.4 ± 1.1 days, P < .01). After adjusting for preoperative calcium, age, and performance of a neck dissection, subjects with a 25(OH)D level <30 ng/mL were significantly associated with postoperative hypocalcemia (odds ratio, 1.9; P = .041; 95% CI, 1.0-3.3). CONCLUSION Using a single-center retrospective study design, we demonstrated that 25(OH)D level is a significant predictor of postoperative hypocalcemia after thyroidectomy.
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Affiliation(s)
- Samuel J Rubin
- Department of Otolaryngology-Head and Neck Surgery, Boston University Medical Center, Boston, Massachusetts, USA
| | - Jong H Park
- School of Medicine, Boston University, Boston, Massachusetts, USA
| | - Elizabeth N Pearce
- Section of Endocrinology, Diabetes, and Nutrition, Boston University Medical Center, Boston, Massachusetts, USA
| | - Michael F Holick
- Section of Endocrinology, Diabetes, and Nutrition, Boston University Medical Center, Boston, Massachusetts, USA
| | - David McAneny
- Department of Surgery, Boston University Medical Center, Boston, Massachusetts, USA
| | - J Pieter Noordzij
- Department of Otolaryngology-Head and Neck Surgery, Boston University Medical Center, Boston, Massachusetts, USA
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Hammami MM, Abuhdeeb K, Hammami S, Yusuf A. Vitamin-D2 treatment-associated decrease in 25(OH)D3 level is a reciprocal phenomenon: a randomized controlled trial. BMC Endocr Disord 2019; 19:8. [PMID: 30658603 PMCID: PMC6339397 DOI: 10.1186/s12902-019-0337-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Accepted: 01/09/2019] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Vitamin-D2 (D2) treatment has been associated with a decrease in 25-hydroxy (25(OH)) vitamin-D3 (D3) level, suggesting that D3 treatment would be preferred to raise total 25(OH) vitamin-D (D) level. We postulated that D2 treatment-associated decrease in 25(OH)D3 level is related to the increase in 25(OH)D level rather than being D2-specific, and thus there would be a similar D3 treatment-associated decrease in 25(OH)D2 level. METHODS Fifty volunteers were block-randomized to 50,000 IU D2 or placebo orally once (study-1) and fifty volunteers received 50,000 IU D2 orally once and 4 days later block-randomized to 50,000 IU D3 or placebo orally once (study-2). Interventions were concealed from volunteers and research coordinators and blindly-administered. Serum 25(OH)D2 and 25(OH)D3 levels were blindly-determined at baseline and days 14, 28, 42, and 56, post-randomization by high performance liquid chromatography assay. Results of 97 participants were analyzed. Primary outcome measure was day-28 D2-associated change in 25(OH)D3 level in study-1 and D3-associated change in 25(OH)D2 level in study-2, adjusted for baseline levels. RESULTS Mean (95% confidence interval) difference between the active and placebo arms in the decrease in day-28 25(OH)D3 (study-1) and 25(OH)D2 (study-2) levels was 13.2 (9.7 to 16.6) and 9.8 (5.2 to 14.4) nmol/L, respectively. Corresponding differences at day-56 were 10.8 (6.8 to 14.8) and 1.7 (- 7.6 to 11.1) nmol/L, respectively. The difference between the placebo and active arms in area-under-the-curve at day-28 (AUC28) and day-56 (AUC56) were 262.3 (197.8 to 326.7) and 605.1 (446.3 to 784.0) for 25(OH)D3 (study-1) and 282.2 (111.2 to 453.3) and 431.2 (179.3 to 683.2) nmol.d/L for 25(OH)D2 (study-2), respectively. There were significant correlations between day-28 changes in 25(OH)D2 and 25(OH)D3 levels in study-1 (rho = - 0.79, p < 0.001) and study-2 (rho = - 0.36, p = 0.01), and between day-28 changes in 25(OH)D2 level and baseline 25(OH)D level in study-2 (rho = - 0.42, p = 0.003). CONCLUSIONS Compared to placebo, D3 treatment is associated with a decrease in 25(OH)D2 level similar in magnitude to D2-treatment associated decrease in 25(OH)D3 level; however, the D3-placebo difference in 25(OH)D2 level is shorter-lasting. Changes in 25(OH)D2 and 25(OH)D3 levels are correlated with each other and with baseline 25 (OH) D levels, suggesting a common regulatory mechanism. TRIAL REGISTRATION ClinicalTrial.gov identifier: NCT03035084 (registered January 27, 2017).
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Affiliation(s)
- Muhammad M. Hammami
- Department King Faisal Specialist Hospital and Research Center, Clinical Studies and Empirical Ethics, P O Box # 3354, Riyadh, 11211 Saudi Arabia
- Alfaisal University College of Medicine, Riyadh, Saudi Arabia
| | - Kafa Abuhdeeb
- Department King Faisal Specialist Hospital and Research Center, Clinical Studies and Empirical Ethics, P O Box # 3354, Riyadh, 11211 Saudi Arabia
| | - Safa Hammami
- St. Mary Medical Center, San Francisco, California USA
| | - Ahmed Yusuf
- Department King Faisal Specialist Hospital and Research Center, Clinical Studies and Empirical Ethics, P O Box # 3354, Riyadh, 11211 Saudi Arabia
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Rafii DC, Ali F, Farag A, Iyer B, Otterbeck PE, Chaudhari R, Potter N, Stefanov DG, Guber HA. A PROSPECTIVE STUDY OF COMMONLY UTILIZED REGIMENS OF VITAMIN D REPLACEMENT AND MAINTENANCE THERAPY IN ADULTS. Endocr Pract 2018; 25:6-15. [PMID: 30383486 DOI: 10.4158/ep-2018-0219] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE To determine which vitamin D dose, formulation, and schedule most effectively and safely achieves a 25-hydroxyvitamin D (25[OH]D) level of >30 ng/mL (75 nmol/L). METHODS In this prospective study, 100 subjects from the NY Harbor HCS Brooklyn Campus, ages 25 to 85 years, with 25(OH)D <30 ng/mL (<75 nmol/L), were randomized into four groups: cholecalciferol (D3) 2,000 international units (IU) daily; D3 3,000 IU daily; ergocalciferol (D2) 50,000 IU weekly; and D2 50,000 IU twice weekly. All were supplemented with 500 mg calcium carbonate daily. 25(OH)D, parathyroid hormone (PTH), urinary calcium, urinary creatinine, and other variables were measured during 7 visits over 12 months. RESULTS All groups achieved a mean vitamin D level >30 ng/mL (>75 nmol/L) by visit 4 (5 months). Those receiving 50,000 IU D2 twice weekly displayed the most rapid and robust response, with 25(OH)D reaching >30 ng/mL (>75 nmol/L) after only 1 month and plateauing at 60 ng/mL (150 nmol/L) by 7 months. Although no statistically significant difference was seen in mean 25(OH)D levels between groups 1 through 3, subjects on 50,000 IU D2 weekly more consistently showed higher mean levels than either groups 1 or 2. No episodes of significant hypercalcemia occurred. There was a negative correlation in mean PTH levels and mean vitamin D levels in group 4 and all groups combined. CONCLUSION All four schedules of vitamin D replacement were effective in safely achieving and maintaining 25(OH)D >30 ng/mL (>75 nmol/L). D2 50,000 IU twice weekly provided the most rapid attainment and highest mean levels of vitamin D. ABBREVIATIONS 25(OH)D = 25-hydroxyvitamin D; BMI = body mass index; BUN = blood urea nitrogen; Ca/Cr = calcium/creatinine; D2 = ergocalciferol; D3 = cholecalciferol; IU = international units; PTH = parathyroid hormone.
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Cesareo R, Attanasio R, Caputo M, Castello R, Chiodini I, Falchetti A, Guglielmi R, Papini E, Santonati A, Scillitani A, Toscano V, Triggiani V, Vescini F, Zini M. Italian Association of Clinical Endocrinologists (AME) and Italian Chapter of the American Association of Clinical Endocrinologists (AACE) Position Statement: Clinical Management of Vitamin D Deficiency in Adults. Nutrients 2018; 10:nu10050546. [PMID: 29702603 PMCID: PMC5986426 DOI: 10.3390/nu10050546] [Citation(s) in RCA: 101] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Revised: 04/09/2018] [Accepted: 04/23/2018] [Indexed: 01/08/2023] Open
Abstract
Vitamin D deficiency is very common and prescriptions of both assay and supplementation are increasing more and more. Health expenditure is exponentially increasing, thus it is timely and appropriate to establish rules. The Italian Association of Clinical Endocrinologists appointed a task force to review literature about vitamin D deficiency in adults. Four topics were identified as worthy for the practicing clinicians. For each topic recommendations based on scientific evidence and clinical practice were issued according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) System. (1) What cut-off defines vitamin D deficiency: even though 20 ng/mL (50 nmol/L) can be considered appropriate in the general population, we recommend to maintain levels above 30 ng/mL (75 nmol/L) in categories at risk. (2) Whom, when, and how to perform screening for vitamin D deficiency: categories at risk (patients with bone, liver, kidney diseases, obesity, malabsorption, during pregnancy and lactation, some elderly) but not healthy people should be screened by the 25-hydroxy-vitamin D assay. (3) Whom and how to treat vitamin D deficiency: beyond healthy lifestyle (mostly sun exposure), we recommend oral vitamin D (vitamin D2 or vitamin D3) supplementation in patients treated with bone active drugs and in those with demonstrated deficiency. Dosages, molecules and modalities of administration can be profitably individually tailored. (4) How to monitor the efficacy of treatment with vitamin D: no routine monitoring is suggested during vitamin D treatment due to its large therapeutic index. In particular conditions, 25-hydroxy-vitamin D can be assayed after at least a 6-month treatment. We are confident that this document will help practicing clinicians in their daily clinical practice.
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Affiliation(s)
- Roberto Cesareo
- Department of Internal Medicine, "S. M. Goretti" Hospital, 04100 Latina, Italy.
| | - Roberto Attanasio
- Endocrinology Service, Galeazzi Institute IRCCS, 20161 Milan, Italy.
| | - Marco Caputo
- Ospedale Classificato Villa Salus, 30174 Venezia Mestre, Italy.
| | - Roberto Castello
- General Medicine and Endocrinology, University Hospital, 37126 Verona, Italy.
| | - Iacopo Chiodini
- Unit for Bone Metabolism Diseases and Diabetes & Lab of Endocrine and Metabolic Research, IRCCS Istituto Auxologico Italiano, 20149 Milan, Italy.
- Department of Clinical Sciences and Community Health, University of Milan, 20149 Milan, Italy.
| | - Alberto Falchetti
- Centro Hercolani and Villa Alba (GVM), 40123 Bologna and EndOsMet, Villa Donatello Private Hospital, 50132 Florence, Italy.
| | - Rinaldo Guglielmi
- Department of Endocrinology and Metabolic Diseases, Regina Apostolorum Hospital, Albano Laziale, 00041 Rome, Italy.
| | - Enrico Papini
- Department of Endocrinology and Metabolic Diseases, Regina Apostolorum Hospital, Albano Laziale, 00041 Rome, Italy.
| | - Assunta Santonati
- Department of Endocrinology, San Giovanni Addolorata Hospital, 00184 Rome, Italy.
| | - Alfredo Scillitani
- Endocrinology Unit, Department of Medical Science, Ospedale Casa Sollievo della Sofferenza IRCCS, 71013 San Giovanni Rotondo (FG), Italy.
| | - Vincenzo Toscano
- Endocrinology, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, 00189 Roma, Italy.
| | - Vincenzo Triggiani
- Interdisciplinary Department of Medicine, Endocrinology and Metabolic Diseases, University of Bari "Aldo Moro", 70124 Bari, Italy.
| | - Fabio Vescini
- Department of Endocrinology and Diabetes, Santa Maria della Misericordia Hospital, 33010 Udine, Italy.
| | - Michele Zini
- Endocrinology Unit, Arcispedale S. Maria Nuova IRCCS, 42123 Reggio Emilia, Italy.
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Tamblyn JA, Jenkinson C, Larner DP, Hewison M, Kilby MD. Serum and urine vitamin D metabolite analysis in early preeclampsia. Endocr Connect 2018; 7:199-210. [PMID: 29217650 PMCID: PMC5793806 DOI: 10.1530/ec-17-0308] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2017] [Accepted: 12/07/2017] [Indexed: 12/18/2022]
Abstract
Vitamin D deficiency is common in pregnant women and may contribute to adverse events in pregnancy such as preeclampsia (PET). To date, studies of vitamin D and PET have focused primarily on serum concentrations vitamin D, 25-hydroxyvitamin D3 (25(OH)D3) later in pregnancy. The aim here was to determine whether a more comprehensive analysis of vitamin D metabolites earlier in pregnancy could provide predictors of PET. Using samples from the SCOPE pregnancy cohort, multiple vitamin D metabolites were quantified by liquid chromatography-tandem mass spectrometry in paired serum and urine prior to the onset of PET symptoms. Samples from 50 women at pregnancy week 15 were analysed, with 25 (50%) developing PET by the end of the pregnancy and 25 continuing with uncomplicated pregnancy. Paired serum and urine from non-pregnant women (n = 9) of reproductive age were also used as a control. Serum concentrations of 25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 24,25(OH)2D3 and 3-epi-25(OH)D3 were measured and showed no significant difference between women with uncomplicated pregnancies and those developing PET. As previously reported, serum 1,25(OH)2D3 was higher in all pregnant women (in the second trimester), but serum 25(OH)D2 was also higher compared to non-pregnant women. In urine, 25(OH)D3 and 24,25(OH)2D3 were quantifiable, with both metabolites demonstrating significantly lower (P < 0.05) concentrations of both of these metabolites in those destined to develop PET. These data indicate that analysis of urinary metabolites provides an additional insight into vitamin D and the kidney, with lower urinary 25(OH)D3 and 24,25(OH)2D3 excretion being an early indicator of a predisposition towards developing PET.
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Affiliation(s)
- J A Tamblyn
- Institute of Metabolism and Systems Research (IMSR)College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
- Birmingham Women's Foundation HospitalEdgbaston, Birmingham, UK
- Centre for EndocrinologyDiabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
| | - C Jenkinson
- Birmingham Women's Foundation HospitalEdgbaston, Birmingham, UK
| | - D P Larner
- Birmingham Women's Foundation HospitalEdgbaston, Birmingham, UK
| | - M Hewison
- Institute of Metabolism and Systems Research (IMSR)College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
- Centre for EndocrinologyDiabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
| | - M D Kilby
- Institute of Metabolism and Systems Research (IMSR)College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
- Birmingham Women's Foundation HospitalEdgbaston, Birmingham, UK
- Centre for EndocrinologyDiabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
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Abstract
Vitamin D deficiency and insufficiency is a global health issue that afflicts more than one billion children and adults worldwide. The consequences of vitamin D deficiency cannot be under estimated. There has been an association of vitamin D deficiency with a myriad of acute and chronic illnesses including preeclampsia, childhood dental caries, periodontitis, autoimmune disorders, infectious diseases, cardiovascular disease, deadly cancers, type 2 diabetes and neurological disorders. This review is to put into perspective the controversy surrounding the definition for vitamin D deficiency and insufficiency as well as providing guidance for how to treat and prevent vitamin D deficiency.
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Affiliation(s)
- Michael F Holick
- Endocrinology, Nutrition and Diabetes, Department of Medicine, Boston University Medical Center, Boston, MA, 02118, USA.
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Hammami MM, Yusuf A. Differential effects of vitamin D2 and D3 supplements on 25-hydroxyvitamin D level are dose, sex, and time dependent: a randomized controlled trial. BMC Endocr Disord 2017; 17:12. [PMID: 28231782 PMCID: PMC5324269 DOI: 10.1186/s12902-017-0163-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2016] [Accepted: 02/17/2017] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Vitamin D (D) supplements are indispensable for its world-wide deficiency. Controversy continues on ergocalciferol (D2) and cholecalciferol (D3) relative potency as well as on dosing-schedule and sex role in raising 25-hydroxy D (25(OH)D) level, the best indicator of D status. METHODS We randomized 279 adults to daily D2, D3, D2/D3, or placebo; 2-weekly D2 or D3; or 4-weekly D2 or D3 (250,000 IU over/140 days). Randomization sequence, stratified by body-mass-index (BMI) and sex, was concealed from study coordinators and participants who were then blinded to capsules' content. D2, D3, 25(OH)D2, and 25(OH)D3 Serum levels were determined blindly on days 0,1,2,3,4,7,14, and 2-weekly thereafter by high performance liquid chromatography assay. The results of 269 participants were available for analysis. Primary endpoint was area-under-the-curve (AUC) of 25(OH)D (25(OH)D2 + 25(OH)D3) adjusted for sex, BMI, and baseline 25(OH)D level. RESULTS Mean(SD) age was 33.0(8.5) year, 41% were males, and 85% completed follow-up. Baseline 25(OH)D level was 39.8(11.9) and increased by 3.3(11.6) and 28.6(16.3) nmol/L, in the placebo and active-treatment groups, respectively. AUC from day 0 to 140 (AUC140) of 25(OH)D was 40% (D3 daily) to 55% (D3 2-weekly) higher with active-treatment than placebo (p < 0.001). 25(OH)D2 AUC140 was higher in daily than 2-weekly (17%, p = 0.006) and 4-weekly (20%, p = 0.001) D2-treated groups. 25(OH)D3 AUC140 was lower in daily than 2-weekly (11%, p = 0.002) and 4-weekly D3-treated groups (10%, p = 0.008). In D2-treated groups, there was 16.4 nmol/L decrease in 25(OH)D3 level that correlated (p < 0.001) with 25(OH)D2 level increase (r = 0.48) and baseline 25(OH)D level (r = 0.58), in one participant with measurable baseline 25(OH)D2 level, D3 caused a similar decrease in 25(OH)D2 level, while in the D2/D3-treated group, 25(OH)D3 level didn't increase. Incremental AUC from day 0 to 7 (AUC7) of D3 and 25(OH)D3 in D3-treated groups were 118-243% higher and 31-39% lower, respectively, than incremental AUC7 of D2 and 25(OH)D2 in D2-treated groups. Incremental AUC7 of D3 and 25(OH)D3 in D3-treated groups and D2 and 25(OH)D2 in D2-treated groups were higher in females than males (55, 13, 64, and 28%, respectively). Baseline 25(OH)D level predicted response to D2 and D3 (p < 0.001), whereas, BMI was significant predictor only for early response to D2. CONCLUSIONS Effects of D2 and D3 supplements on 25 (OH)D level may be dosing-schedule and sex-dependent. D2-associated reduction in 25(OH)D3 level may be related to total 25(OH)D level rather than being D2-specific. D2 may be 25-hydroxylated faster than D3. TRIAL REGISTRATION ClinicalTrial.gov identifier: NCT01170494 (registered July 25, 2010).
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Affiliation(s)
- Muhammad M. Hammami
- Clinical Studies and Empirical Ethics Department, King Faisal Specialist Hospital and Research Center, P O Box # 3354 (MBC 03), Riyadh, 11211 Saudi Arabia
- Alfaisal University College of Medicine, Riyadh, Saudi Arabia
| | - Ahmed Yusuf
- Clinical Studies and Empirical Ethics Department, King Faisal Specialist Hospital and Research Center, P O Box # 3354 (MBC 03), Riyadh, 11211 Saudi Arabia
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13
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Forouhi NG, Menon RK, Sharp SJ, Mannan N, Timms PM, Martineau AR, Rickard AP, Boucher BJ, Chowdhury TA, Griffiths CJ, Greenwald SE, Griffin SJ, Hitman GA. Effects of vitamin D2 or D3 supplementation on glycaemic control and cardiometabolic risk among people at risk of type 2 diabetes: results of a randomized double-blind placebo-controlled trial. Diabetes Obes Metab 2016; 18:392-400. [PMID: 26700109 PMCID: PMC4950066 DOI: 10.1111/dom.12625] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2015] [Revised: 11/30/2015] [Accepted: 12/17/2015] [Indexed: 11/29/2022]
Abstract
AIMS To investigate the effect of short-term vitamin D supplementation on cardiometabolic outcomes among individuals with an elevated risk of diabetes. METHODS In a double-blind placebo-controlled randomized trial, 340 adults who had an elevated risk of type 2 diabetes (non-diabetic hyperglycaemia or positive diabetes risk score) were randomized to either placebo, 100,000 IU vitamin D2 (ergocalciferol) or 100,000 IU vitamin D3 (cholecalciferol), orally administered monthly for 4 months. The primary outcome was change in glycated haemoglobin (HbA1c) between baseline and 4 months, adjusted for baseline. Secondary outcomes included: blood pressure; lipid levels; apolipoprotein levels; C-reactive protein levels; pulse wave velocity (PWV); anthropometric measures; and safety of the supplementation. RESULTS The mean [standard deviation (s.d.)] 25-hydroxyvitamin D [25(OH)D]2 concentration increased from 5.2 (4.1) to 53.9 (18.5) nmol/l in the D2 group, and the mean (s.d.) 25(OH)D3 concentration increased from 45.8 (22.6) to 83.8 (22.7) nmol/l in the D3 group. There was no effect of vitamin D supplementation on HbA1c: D2 versus placebo: -0.05% [95% confidence interval (CI) -0.11, 0.02] or -0.51 mmol/mol (95% CI -1.16, 0.14; p = 0.13); D3 versus placebo: 0.02% (95% CI -0.04, 0.08) or 0.19 mmol/mol (95% CI -0.46, 0.83; p = 0.57). There were no clinically meaningful effects on secondary outcomes, except PWV [D2 versus placebo: -0.68 m/s (95% CI -1.31, -0.05); D3 versus placebo -0.73 m/s (95% CI -1.42, -0.03)]. No important safety issues were identified. CONCLUSIONS Short-term supplementation with vitamin D2 or D3 had no effect on HbA1c. The modest reduction in PWV with both D2 and D3 relative to placebo suggests that vitamin D supplementation has a beneficial effect on arterial stiffness.
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Affiliation(s)
- N G Forouhi
- Medical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK
| | - R K Menon
- Blizard Institute, Queen Mary University of London, London, UK
| | - S J Sharp
- Medical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK
| | - N Mannan
- Blizard Institute, Queen Mary University of London, London, UK
| | - P M Timms
- Homerton University Hospital NHS Foundation Trust, London, UK
| | - A R Martineau
- Blizard Institute, Queen Mary University of London, London, UK
| | - A P Rickard
- Medical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK
| | - B J Boucher
- Blizard Institute, Queen Mary University of London, London, UK
| | - T A Chowdhury
- Blizard Institute, Queen Mary University of London, London, UK
- Barts Healthcare NHS Trust, London, UK
| | - C J Griffiths
- Blizard Institute, Queen Mary University of London, London, UK
| | - S E Greenwald
- Blizard Institute, Queen Mary University of London, London, UK
| | - S J Griffin
- Medical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK
| | - G A Hitman
- Blizard Institute, Queen Mary University of London, London, UK
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Factors Affecting 25-Hydroxyvitamin D Concentration in Response to Vitamin D Supplementation. Nutrients 2015; 7:5111-42. [PMID: 26121531 PMCID: PMC4516990 DOI: 10.3390/nu7075111] [Citation(s) in RCA: 147] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2015] [Revised: 06/05/2015] [Accepted: 06/12/2015] [Indexed: 12/27/2022] Open
Abstract
Sun exposure is the main source of vitamin D. Due to many lifestyle risk factors vitamin D deficiency/insufficiency is becoming a worldwide health problem. Low 25(OH)D concentration is associated with adverse musculoskeletal and non-musculoskeletal health outcomes. Vitamin D supplementation is currently the best approach to treat deficiency and to maintain adequacy. In response to a given dose of vitamin D, the effect on 25(OH)D concentration differs between individuals, and it is imperative that factors affecting this response be identified. For this review, a comprehensive literature search was conducted to identify those factors and to explore their significance in relation to circulating 25(OH)D response to vitamin D supplementation. The effect of several demographic/biological factors such as baseline 25(OH)D, aging, body mass index(BMI)/body fat percentage, ethnicity, calcium intake, genetics, oestrogen use, dietary fat content and composition, and some diseases and medications has been addressed. Furthermore, strategies employed by researchers or health care providers (type, dose and duration of vitamin D supplementation) and environment (season) are other contributing factors. With the exception of baseline 25(OH)D, BMI/body fat percentage, dose and type of vitamin D, the relative importance of other factors and the mechanisms by which these factors may affect the response remains to be determined.
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Grant WB, Wimalawansa SJ, Holick MF, Cannell JJ, Pludowski P, Lappe JM, Pittaway M, May P. Emphasizing the health benefits of vitamin D for those with neurodevelopmental disorders and intellectual disabilities. Nutrients 2015; 7:1538-64. [PMID: 25734565 PMCID: PMC4377865 DOI: 10.3390/nu7031538] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2014] [Revised: 01/16/2015] [Accepted: 02/05/2015] [Indexed: 02/06/2023] Open
Abstract
People with neurodevelopmental disorders and intellectual disabilities have much greater health care needs. Mainly staying indoors, such people generally have low 25-hydroxyvitamin D (25(OH)D) concentrations. The Vitamin D Task Force of the American Academy of Developmental Medicine and Dentistry (AADMD) reviewed the evidence of 25(OH)D concentrations that benefit the health of persons with developmental disabilities. Maintaining recommended optimal serum 25(OH)D concentrations year long will benefit skeletal development in infants, children, and adolescents, and benefit musculoskeletal health and neuromuscular coordination in adult patients, and decrease risk of falls. Maintaining optimal concentrations decreases risks and severities of autoimmune diseases, cardiovascular disease, many types of cancer, dementia, types 1 and 2 diabetes mellitus, and respiratory tract infections. Other benefits include improved dental and oral health and improved physical performance. The Task Force recommends that 25(OH)D concentrations for optimal health to be in the range of 75 to 125 nmol/L, which can be achieved using between 800 and 4000 IU/day vitamin D3 and sensible exposure to solar UVB radiation. The paper also discusses the potential risks of higher 25(OH)D concentrations, the evidence from and limitations of randomized controlled trials, and the recommendations by various groups and agencies.
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Affiliation(s)
- William B Grant
- Sunlight, Nutrition, and Health Research Center, PO Box 641603, San Francisco, CA 94164-1603, USA.
| | - Sunil J Wimalawansa
- Department of Medicine & Endocrinology, Cardio Metabolic Institute, Somerset, NJ 08873, USA.
| | - Michael F Holick
- Department of Medicine, Section of Endocrinology, Nutrition, and Diabetes, and the Vitamin D, Skin, and Bone Research Laboratory, Boston University Medical Center, Boston, MA 02118, USA.
| | - John J Cannell
- Vitamin D Council and San Luis Obispo Integrative Medicine, San Luis Obispo, CA 93401, USA.
| | - Pawel Pludowski
- Department of Biochemistry, Radioimmunology, and Experimental Medicine, The Children's Memorial Health Institute, 04-730 Warsaw, Poland.
| | - Joan M Lappe
- Creighton University School of Medicine, Omaha, NE 68131, USA.
| | - Mary Pittaway
- Global Clinical Advisor-Health Promotion, Special Olympics International and Affiliate Faculty, College of Education and Human Sciences, University of Montana, Missoula, MT 59812, USA.
| | - Philip May
- International Foundation for Chronic Disabilities, Inc., PO Box 166, Oxford, NJ 07863, USA.
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Volmer DA, Mendes LRBC, Stokes CS. Analysis of vitamin D metabolic markers by mass spectrometry: current techniques, limitations of the "gold standard" method, and anticipated future directions. MASS SPECTROMETRY REVIEWS 2015; 34:2-23. [PMID: 24318020 DOI: 10.1002/mas.21408] [Citation(s) in RCA: 102] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2013] [Revised: 07/18/2013] [Accepted: 07/18/2013] [Indexed: 05/10/2023]
Abstract
Vitamin D compounds belong to a group of secosteroids, which occur naturally as vitamin D3 in mammals and D2 in plants. Vitamin D is vital for bone health but recent studies have shown a much wider role in the pathologies of diseases such as diabetes, cancer, autoimmune, neurodegenerative, mental and cardiovascular diseases. Photosynthesis of vitamin D in the human skin and subsequent hepatic and renal metabolism generate a wide range of transformation products occurring over a large dynamic range spanning from picomolar to nanomolar levels. This necessitates selective and sensitive analytical methods to quantitatively capture these low concentration levels in relevant tissues such as blood. Ideally, vitamin D assessment would be performed using a universal and standardized analytical method available to clinical laboratories that provides reliable and accurate quantitative results for all relevant vitamin D metabolites with sufficiently high throughput. At present, LC-MS/MS assays are the most promising techniques for vitamin D analysis. The present review focuses on developments in mass spectrometry methodologies of the past 12 years. It will highlight detrimental influences of the biological matrix, epimer contributions, pitfalls of specific mass spectrometry data acquisition routines (in particular multiple reaction monitoring, MRM), influence of ionization source, derivatization reactions, inter-laboratory comparisons on precision, accuracy, and application range of vitamin D metabolites.
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Affiliation(s)
- Dietrich A Volmer
- Institute of Bioanalytical Chemistry, Saarland University, Saarbrücken, Germany
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Jones KS, Assar S, Harnpanich D, Bouillon R, Lambrechts D, Prentice A, Schoenmakers I. 25(OH)D2 half-life is shorter than 25(OH)D3 half-life and is influenced by DBP concentration and genotype. J Clin Endocrinol Metab 2014; 99:3373-81. [PMID: 24885631 PMCID: PMC4207933 DOI: 10.1210/jc.2014-1714] [Citation(s) in RCA: 186] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
CONTEXT There is uncertainty over the equivalence of vitamins D2 and D3 to maintain plasma 25-hydroxyvitamin D (25(OH)D). OBJECTIVE The objective of the study was to compare the plasma half-lives of 25(OH)D2 and 25(OH)D3 in two distinct populations with different dietary calcium intake and 25(OH)D status. PARTICIPANTS Healthy men (aged 24 and 39 y), resident in The Gambia (n = 18) or the United Kingdom (n = 18) participated in the study. INTERVENTIONS The intervention included an oral tracer dose of deuterated-25(OH)D2 and deuterated-25(OH)D3 (both 40 nmol). Blood samples were collected over 33 days. MAIN OUTCOME MEASURES 25(OH)D2 and 25(OH)D3 plasma half-lives, concentrations of 25(OH)D, and vitamin D binding protein (DBP) and DBP genotypes were measured. RESULTS 25(OH)D2 half-life [mean (SD)] [13.9 (2.6) d] was shorter than 25(OH)D3 half-life [15.1 (3.1) d; P = .001] for countries combined, and in Gambians [12.8 (2.3) d vs 14.7 (3.5) d; P < .001], but not in the United Kingdom [15.1 (2.4) d vs 15.6 (2.5) d; P = .3]. 25(OH)D concentration was 69 (13) and 29 (11) nmol/L (P < .0001), and the DBP concentration was 259 (33) and 269 (23) mg/L (P = .4) in The Gambia and United Kingdom, respectively. Half-lives were positively associated with plasma DBP concentration for countries combined [25(OH)D2 half-life: regression coefficient (SE) 0.03 (0.01) d per 1 mg/L DBP, P = .03; 25(OH)D3 half-life: 0.04 (0.02) d, P = .02] and in Gambians [25(OH)D2 half-life: 0.04 (0.01) d; P = .02; 25(OH)D3 half-life: 0.06 (0.02) d, P = .01] but not in UK participants. The DBP concentration × country interactions were not significant. DBP Gc1f/1f homozygotes had shorter 25(OH)D2 half-lives compared with other combined genotypes (P = .007) after correction for country. CONCLUSIONS 25(OH)D2 half-life was shorter than 25(OH)D3 half-life, and half-lives were affected by DBP concentration and genotype. The stable isotope 25(OH)D half-life measurements provide a novel tool to investigate vitamin D metabolism and vitamin D expenditure and aid in the assessment of vitamin D requirements.
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Affiliation(s)
- K S Jones
- Medical Research Council Human Nutrition Research (K.S.J., S.A., D.H., A.P., I.S.), Cambridge CB1 9NL, United Kingdom; Medical Research Council Keneba (K.S.J., A.P.), The Gambia; Clinic and Laboratory of Experimental Medicine and Endocrinology (R.B.) and Laboratory for Translational Genetics (D.L.), Katholieke Universiteit, B-3000 Leuven, Belgium; and Vesalius Research Center (D.L.), VIB, Katholieke Universiteit, B-3000, Leuven, Belgium
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Swanson CM, Nielson CM, Shrestha S, Lee CG, Barrett-Connor E, Jans I, Cauley JA, Boonen S, Bouillon R, Vanderschueren D, Orwoll ES. Higher 25(OH)D2 is associated with lower 25(OH)D3 and 1,25(OH)2D3. J Clin Endocrinol Metab 2014; 99:2736-44. [PMID: 24828488 PMCID: PMC4121037 DOI: 10.1210/jc.2014-1069] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
CONTEXT Despite common use of supplemental vitamin D2 in clinical practice, the associations of serum vitamin D2 concentrations with other vitamin D metabolites and total vitamin D are unclear. OBJECTIVE The aim of the study was to measure vitamin D2 and D3 levels and examine their associations with each other and with total vitamin D. DESIGN We performed a cross-sectional analysis of 679 randomly selected participants from the Osteoporotic Fractures in Men Study. 25-Hydroxyvitamin D2 [25(OH)D2], 25(OH)D3, 1,25-dihydroxyvitamin D2 [1,25(OH)2D2], and 1,25(OH)2D3 were measured using liquid chromatography-tandem mass spectrometry and were summed to obtain total 25(OH)D and 1,25(OH)2D. Associations between all metabolites (D2, D3, and total levels) were examined using Wilcoxon rank-sum tests and Spearman correlations. RESULTS 25(OH)D2 and 1,25(OH)2D2 were detectable in 189 (27.8%) and 178 (26.2%) of the men, respectively. Higher 25(OH)D2 levels did not correlate with higher total 25(OH)D (r = 0.10; P = .17), although median total 25(OH)D was slightly higher in those with detectable vs undetectable 25(OH)D2 (25.8 vs 24.3 ng/mL; P < .001). 25(OH)D2 was not positively associated with total 1,25(OH)2D levels (r = -0.11; P = .13), and median 1,25(OH)2D level was not higher in those with detectable vs undetectable 25(OH)D2. Higher 25(OH)D2 was associated with lower 25(OH)D3 (r = -0.35; P < .001) and 1,25(OH)2D3 (r = -0.32; P < .001), with median levels of both D3 metabolites 18-35% higher when D2 metabolites were undetectable. CONCLUSIONS In a cohort of older men, 25(OH)D2 is associated with lower levels of 25(OH)D3 and 1,25(OH)2D3, suggesting that vitamin D2 may decrease the availability of D3 and may not increase calcitriol levels.
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Affiliation(s)
- Christine M Swanson
- Division of Endocrinology (C.M.S., C.G.L., E.S.O.), Bone and Mineral Unit (C.M.S., C.M.N., S.S., C.G.L., E.S.O.), and Department of Public Health and Preventive Medicine (C.M.N.), Oregon Health & Science University, Portland, Oregon 97239; Research Service (C.G.L.), Portland Veterans Affairs Medical Center, Portland, Oregon 97239; Division of Epidemiology (E.B.-C.), Department of Family & Preventive Medicine, University California San Diego, La Jolla, California 92093-0607; Laboratory of Diagnostic Medicine (I.J., D.V.), KU Leuven, University of Leuven, 3000 Leuven, Belgium; Department of Epidemiology (J.A.C.), Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261; and Division of Geriatric Medicine and Centre for Metabolic Bone Diseases (S.B.), and Laboratory of Clinical and Experimental Endocrinology (R.B., D.V.), KU Leuven, University of Leuven, 3000 Leuven, Belgium
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Mao X, Zheng H, Liu Z, Wu Y, Na R, Wang C, Zheng X, Gao J, Wu L, Shi X, Liu C, Sheng H. Analysis of 25(OH)D serum concentrations of hospitalized elderly patients in the Shanghai area. PLoS One 2014; 9:e90729. [PMID: 24599155 PMCID: PMC3944708 DOI: 10.1371/journal.pone.0090729] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2013] [Accepted: 02/03/2014] [Indexed: 12/29/2022] Open
Abstract
OBJECTIVE To find an association between basic characteristics, seasons as well as disease types and 25-Hydroxyvitamin D serum concentrations in Chinese patients. METHODS We randomly selected 5470 Chinese patients with various diseases, who were hospitalized between May 2012 and August 2013 in Shanghai and analyzed their serum 25-Hydroxyvitamin D2 (25 (OH)D2) and 25-Hydroxyvitamin D3 (25(OH)D3) concentrations with liquid chromatography-tandem mass spectrometry (LC-MS/MS) as well as their parathyroid hormone (PTH) and serum creatinine blood levels. The resulting data were analyzed by linear regression and variance analyses or multivariate analysis with covariance. RESULTS The 25(OH)D serum concentrations were lowest in December. Among the subjects with a median age of 83.0 ± 16.0, the median 25(OH)D2, 25(OH)D3 and total 25(OH)D serum concentrations were 1.00 ± 1.80 ng/ml, 12.20 ± 8.50 ng/ml and 14.80 ± 9.80 respectively, indicating a prevalent 25(OH)D deficiency. According to our multivariate analysis of covariance, the factors affecting 25(OH)D2 and 25(OH)D3 serum concentrations included age, creatinine, PTH, season and type of disease, whereas gender correlated only with 25(OH)D2 and 25(OH)D2 and D3 values correlated negatively with each other. Our results further revealed that 25(OH)D3 levels were low while 25(OH)D2 levels were high among patients with lung diseases, dyskinesia and coronary heart diseases. In addition, participants with diabetes and cerebral infarction had higher 25(OH)D3 serum concentrations compared with lung disease patients. CONCLUSION Vitamin D intake particularly during winter and summer seasons is important especially for elderly lung disease, dyskinesia and coronary heart disease patients to improve their quality of life.
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Affiliation(s)
- Xudong Mao
- Department of Endocrinology, Xuhui District Central Hospital, Shanghai, China
- * E-mail: (XM); (HZ)
| | - Hongchao Zheng
- Department of Cardiology, Xuhui District Central Hospital, Shanghai, China
- * E-mail: (XM); (HZ)
| | - Zhiwen Liu
- Department of Endocrinology, Xuhui District Central Hospital, Shanghai, China
| | - Yan Wu
- Department of Psychiatry, Shanghai Mental Health Center, Shanghai, China
| | - Risu Na
- Department of Endocrinology, Xuhui District Central Hospital, Shanghai, China
| | - Chunping Wang
- Department of Endocrinology, Xuhui District Central Hospital, Shanghai, China
| | - Xulei Zheng
- Department of Endocrinology, Xuhui District Central Hospital, Shanghai, China
| | - Jing Gao
- Department of Information, Xuhui District Central Hospital, Shanghai, China
| | - Liming Wu
- Department of Endocrinology, Xuhui District Central Hospital, Shanghai, China
| | - Xiaohong Shi
- Department of Endocrinology, Xuhui District Central Hospital, Shanghai, China
| | - Cong Liu
- Department of Endocrinology, Xuhui District Central Hospital, Shanghai, China
| | - Hongguang Sheng
- Department of Endocrinology, Xuhui District Central Hospital, Shanghai, China
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Keegan RJH, Lu Z, Bogusz JM, Williams JE, Holick MF. Photobiology of vitamin D in mushrooms and its bioavailability in humans. DERMATO-ENDOCRINOLOGY 2014; 5:165-76. [PMID: 24494050 PMCID: PMC3897585 DOI: 10.4161/derm.23321] [Citation(s) in RCA: 89] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/06/2012] [Accepted: 12/18/2012] [Indexed: 01/30/2023]
Abstract
Mushrooms exposed to sunlight or UV radiation are an excellent source of dietary vitamin D2 because they contain high concentrations of the vitamin D precursor, provitamin D2. When mushrooms are exposed to UV radiation, provitamin D2 is converted to previtamin D2. Once formed, previtamin D2 rapidly isomerizes to vitamin D2 in a similar manner that previtamin D3 isomerizes to vitamin D3 in human skin. Continued exposure of mushrooms to UV radiation results in the production of lumisterol2 and tachysterol2. It was observed that the concentration of lumisterol2 remained constant in white button mushrooms for up to 24 h after being produced. However, in the same mushroom tachysterol2 concentrations rapidly declined and were undetectable after 24 h. Shiitake mushrooms not only produce vitamin D2 but also produce vitamin D3 and vitamin D4. A study of the bioavailability of vitamin D2 in mushrooms compared with the bioavailability of vitamin D2 or vitamin D3 in a supplement revealed that ingestion of 2000 IUs of vitamin D2 in mushrooms is as effective as ingesting 2000 IUs of vitamin D2 or vitamin D3 in a supplement in raising and maintaining blood levels of 25-hydroxyvitamin D which is a marker for a person's vitamin D status. Therefore, mushrooms are a rich source of vitamin D2 that when consumed can increase and maintain blood levels of 25-hydroxyvitamin D in a healthy range. Ingestion of mushrooms may also provide the consumer with a source of vitamin D3 and vitamin D4.
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Affiliation(s)
- Raphael-John H Keegan
- Department of Medicine; Section of Endocrinology, Nutrition, and Diabetes; Vitamin D, Skin and Bone Research Laboratory; Boston University Medical Center; Boston, MA USA
| | - Zhiren Lu
- Department of Medicine; Section of Endocrinology, Nutrition, and Diabetes; Vitamin D, Skin and Bone Research Laboratory; Boston University Medical Center; Boston, MA USA
| | - Jaimee M Bogusz
- Department of Medicine; Section of Endocrinology, Nutrition, and Diabetes; Vitamin D, Skin and Bone Research Laboratory; Boston University Medical Center; Boston, MA USA
| | - Jennifer E Williams
- Department of Medicine; Section of Endocrinology, Nutrition, and Diabetes; Vitamin D, Skin and Bone Research Laboratory; Boston University Medical Center; Boston, MA USA
| | - Michael F Holick
- Department of Medicine; Section of Endocrinology, Nutrition, and Diabetes; Vitamin D, Skin and Bone Research Laboratory; Boston University Medical Center; Boston, MA USA
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Alam U, Chan AWS, Buazon A, Van Zeller C, Berry JL, Jugdey RS, Asghar O, Cruickshank JK, Petropoulos IN, Malik RA. Differential effects of different vitamin D replacement strategies in patients with diabetes. J Diabetes Complications 2014; 28:66-70. [PMID: 24139562 DOI: 10.1016/j.jdiacomp.2013.09.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2013] [Revised: 08/02/2013] [Accepted: 09/06/2013] [Indexed: 01/28/2023]
Abstract
BACKGROUND The optimal treatment regimen for correcting vitamin D insufficiency in diabetic patients has not been established. METHODS Two hundred and forty four adult diabetic patients with vitamin D insufficiency were enrolled to receive: Ergocalciferol (D2) 50,000 IU daily over 10 days (500,000 IU) followed by Calcichew D3 (calcium carbonate/Cholecalciferol) BID (~24,000 IU cholecalciferol/month) (ECC) (n=53); Cholecalciferol (D3) 40,000 IU daily over 10 days (400,000 IU) followed by Calcichew D3 BID (~24,000 IU cholecalciferol/month) (CCC) (n=94) or Cholecalciferol 40,000 IU daily over 10 days (400,000 IU) followed by Cholecalciferol 40,000 IU monthly (CC) (n=97). The 25(OH)D, HbA1c, lipids, blood pressure and eGFR were assessed at baseline and after a mean follow up of 8.0±4.0 months. RESULTS Treatment increased 25(OH)D concentrations significantly in ECC (17.4±13.8 vs 29.9±9.6 ng/ml, P<0.0001), CCC (14.2±6.6 vs 30.9±13.1 ng/ml, p<0.0001) and CC (13.5±8.4 vs 33.9±14.4 ng/ml, P<0.0001). The relative increase in 25(OH)D was significantly lower with ECC compared to CC (+14.6±12.2 vs +20.6±15.0, P=0.01) and the majority of subjects in the ECC group (63%) remained vitamin D deficient (25(OH)D <30 ng/ml) compared to CCC (46%) and CC (36%) (P=0.0005). CONCLUSION This study demonstrates that relatively aggressive treatment regimens of both vitamin D2 and D3 increase 25(OH)D concentrations in diabetic patients, but the ability to raise 25(OH)D status to 'sufficient' levels is inadequate in a large proportion of individuals.
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Affiliation(s)
- Uazman Alam
- Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and the Central Manchester University Hospitals Foundation Trust, Manchester, UK
| | | | - April Buazon
- Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and the Central Manchester University Hospitals Foundation Trust, Manchester, UK
| | - Cristiano Van Zeller
- Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and the Central Manchester University Hospitals Foundation Trust, Manchester, UK
| | - Jacqueline L Berry
- Vitamin D Research Group, School of Biomedicine, University of Manchester, UK
| | | | - Omar Asghar
- Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and the Central Manchester University Hospitals Foundation Trust, Manchester, UK
| | - John Kennedy Cruickshank
- Department of Diabetes and Nutritional Sciences, King's College and St Thomas' and Guy's Hospitals, UK
| | - Ioannis N Petropoulos
- Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and the Central Manchester University Hospitals Foundation Trust, Manchester, UK
| | - Rayaz A Malik
- Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and the Central Manchester University Hospitals Foundation Trust, Manchester, UK.
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Hossein-nezhad A, Holick MF. Vitamin D for health: a global perspective. Mayo Clin Proc 2013; 88:720-55. [PMID: 23790560 PMCID: PMC3761874 DOI: 10.1016/j.mayocp.2013.05.011] [Citation(s) in RCA: 773] [Impact Index Per Article: 64.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2013] [Revised: 05/21/2013] [Accepted: 05/23/2013] [Indexed: 02/09/2023]
Abstract
It is now generally accepted that vitamin D deficiency is a worldwide health problem that affects not only musculoskeletal health but also a wide range of acute and chronic diseases. However, there remains cynicism about the lack of randomized controlled trials to support the association studies regarding the nonskeletal health benefits of vitamin D. This review was obtained by searching English-language studies published up to April 1, 2013, in PubMed, MEDLINE, and the Cochrane Central Register of Controlled Trials (search terms: vitamin D and supplementation) and focuses on recent challenges regarding the definition of vitamin D deficiency and how to achieve optimal serum 25-hydroxyvitamin D concentrations from dietary sources, supplements, and sun exposure. The effect of vitamin D on fetal programming epigenetics and gene regulation could potentially explain why vitamin D has been reported to have such wide-ranging health benefits throughout life. There is potentially a great upside to increasing the vitamin D status of children and adults worldwide for improving musculoskeletal health and reducing the risk of chronic illnesses, including some cancers, autoimmune diseases, infectious diseases, type 2 diabetes mellitus, neurocognitive disorders, and mortality.
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Affiliation(s)
- Arash Hossein-nezhad
- Department of Medicine, Section of Endocrinology, Nutrition, and Diabetes, Vitamin D, Skin, and Bone Research Laboratory, Boston University Medical Center, Boston, MA
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Cipriani C, Romagnoli E, Pepe J, Russo S, Carlucci L, Piemonte S, Nieddu L, McMahon DJ, Singh R, Minisola S. Long-term bioavailability after a single oral or intramuscular administration of 600,000 IU of ergocalciferol or cholecalciferol: implications for treatment and prophylaxis. J Clin Endocrinol Metab 2013; 98:2709-15. [PMID: 23766519 DOI: 10.1210/jc.2013-1586] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
CONTEXT We previously showed that a single high dose of oral (po) cholecalciferol (D₃) sharply increases serum 25-hydroxyvitamin D [25(OH)D]. OBJECTIVE We evaluated the long-term bioavailability and metabolism of a single po or intramuscular (im) high dose of ergocalciferol (D₂) or D₃. DESIGN This was a prospective intervention study. SETTING The study was conducted in an ambulatory care setting. PATIENTS Participants were 24 subjects with hypovitaminosis D. INTERVENTIONS A single dose of 600,000 IU of po or im D₂ or D₃ was administered. MAIN OUTCOME MEASURES Serum 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)₂D] were measured at baseline and at days 30, 60, 90, and 120 by RIA. Serum 1,25(OH)₂D₂, 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃], 24,25-hydroxyvitamin D₂ [24,25(OH)D₂], and 24,25-hydroxyvitamin D₃ [24,25(OH)D₃] were measured by liquid chromatography-tandem mass spectrometry in a subgroup of patients receiving the po formulations. RESULTS The areas under the curve of 25(OH)D after D₃ were significantly higher than those after D₂ (P < .0001). Serum 25(OH)D basal difference significantly increased at day 30 with po D₂ and D₃ (P < .01 and P < .0001) and up to day 90 with po D₃ (P < .01). The im formulations produced a slow increased, and values peaked at day 120 relative to the other time points (P < .0001). We found a decrease in 1,25(OH)₂D at day 30 (P < .05) and up to day 120 (P < .001) and an increase in 1,25(OH)₂D₂ at day 30 (P < .01) and up to day 120 (P < .01) after po D₂. Oral D₂ and D₃ produced increases in 24,25(OH)D₂ and 24,25(OH)D₃, respectively, at day 30 (P < .001). CONCLUSIONS A po dose of 600,000 IU of D₂ or D₃ is initially more effective in increasing serum 25(OH)D than the equivalent im dose and is rapidly metabolized. Our RIA assay for 1,25(OH)₂D may not recognize 1,25(OH)₂D₂.
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Affiliation(s)
- Cristiana Cipriani
- Department of Internal Medicine and Medical Disciplines, Sapienza Rome University, 00161 Rome, Italy.
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Nimitphong H, Saetung S, Chanprasertyotin S, Chailurkit LO, Ongphiphadhanakul B. Changes in circulating 25-hydroxyvitamin D according to vitamin D binding protein genotypes after vitamin D₃ or D₂supplementation. Nutr J 2013; 12:39. [PMID: 23556437 PMCID: PMC3637219 DOI: 10.1186/1475-2891-12-39] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2012] [Accepted: 03/18/2013] [Indexed: 11/10/2022] Open
Abstract
Background It is not known whether genetic variation in the vitamin D binding protein (DBP) influences 25-hydroxyvitamin D levels [25(OH)D] after vitamin D supplementation. We aimed to investigate the changes of total 25(OH)D, 25(OH)D3 and 25(OH)D2 in a Thai cohort, according to type of vitamin D supplement (vitamin D3 or D2) and DBP genotype, after receiving vitamin D3 or D2 for 3 months. Methods Thirty-nine healthy subjects completed the study. All subjects received 400 IU of either vitamin D3 or D2, plus a calcium supplement, every day for 3 months. Total serum 25(OH)D, 25(OH)D3 and 25(OH)D2 were measured by LC-MS/MS. Individual genotyping of rs4588 in the DBP gene was performed using real-time PCR. Results Vitamin D3 supplementation of 400 IU/d increased 25(OH)D3 significantly (+16.2 ± 4.2 nmol/L, p <0.001). Vitamin D2 (400 IU/d) caused increased 25(OH)D2 levels (+22.0 ± 2.11 nmol/L, p <0.001), together with a decrease of 25(OH)D3 (−14.2 ± 2.0 nmol/L, p <0.001). At 3 month, subjects in vitamin D3 group tended to have higher total 25(OH)D levels than those in vitamin D2 (67.8 ± 3.9 vs. 61.0 ± 3.0 nmol/L; p = 0.08). Subjects were then classified into two subgroups: homozygous for the DBP rs4588 C allele (CC), and the rest (CA or AA). With D3 supplementation, subjects with CA or AA alleles had significantly less increase in 25(OH)D3 and total 25(OH)D when compared with those with the CC allele. However, no difference was found when the supplement was vitamin D2. Conclusion Genetic variation in DBP (rs4588 SNP) influences responsiveness to vitamin D3 but not vitamin D2.
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Affiliation(s)
- Hataikarn Nimitphong
- Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Rama 6 Rd, Rajthevi, Bangkok 10400, Thailand.
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