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Giustina A, Bilezikian JP, Adler RA, Banfi G, Bikle DD, Binkley NC, Bollerslev J, Bouillon R, Brandi ML, Casanueva FF, di Filippo L, Donini LM, Ebeling PR, Fuleihan GEH, Fassio A, Frara S, Jones G, Marcocci C, Martineau AR, Minisola S, Napoli N, Procopio M, Rizzoli R, Schafer AL, Sempos CT, Ulivieri FM, Virtanen JK. Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows. Endocr Rev 2024; 45:625-654. [PMID: 38676447 PMCID: PMC11405507 DOI: 10.1210/endrev/bnae009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Indexed: 04/28/2024]
Abstract
The 6th International Conference, "Controversies in Vitamin D," was convened to discuss controversial topics, such as vitamin D metabolism, assessment, actions, and supplementation. Novel insights into vitamin D mechanisms of action suggest links with conditions that do not depend only on reduced solar exposure or diet intake and that can be detected with distinctive noncanonical vitamin D metabolites. Optimal 25-hydroxyvitamin D (25(OH)D) levels remain debated. Varying recommendations from different societies arise from evaluating different clinical or public health approaches. The lack of assay standardization also poses challenges in interpreting data from available studies, hindering rational data pooling and meta-analyses. Beyond the well-known skeletal features, interest in vitamin D's extraskeletal effects has led to clinical trials on cancer, cardiovascular risk, respiratory effects, autoimmune diseases, diabetes, and mortality. The initial negative results are likely due to enrollment of vitamin D-replete individuals. Subsequent post hoc analyses have suggested, nevertheless, potential benefits in reducing cancer incidence, autoimmune diseases, cardiovascular events, and diabetes. Oral administration of vitamin D is the preferred route. Parenteral administration is reserved for specific clinical situations. Cholecalciferol is favored due to safety and minimal monitoring requirements. Calcifediol may be used in certain conditions, while calcitriol should be limited to specific disorders in which the active metabolite is not readily produced in vivo. Further studies are needed to investigate vitamin D effects in relation to the different recommended 25(OH)D levels and the efficacy of the different supplementary formulations in achieving biochemical and clinical outcomes within the multifaced skeletal and extraskeletal potential effects of vitamin D.
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Affiliation(s)
- Andrea Giustina
- Institute of Endocrine and Metabolic Sciences, San Raffaele Vita-Salute University and IRCCS Hospital, Milan 20132, Italy
| | - John P Bilezikian
- Department of Medicine, Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
| | - Robert A Adler
- Richmond Veterans Affairs Medical Center and Virginia Commonwealth University, Richmond, VA 23284, USA
| | - Giuseppe Banfi
- IRCCS Galeazzi Sant’Ambrogio Hospital, Milano 20161, Italy
- San Raffaele Vita–Salute University, Milan 20132, Italy
| | - Daniel D Bikle
- Department of Medicine, University of California and San Francisco Veterans Affairs Health Center, San Francisco, CA 94121-1545, USA
- Department of Endocrinology, University of California and San Francisco Veterans Affairs Health Center, San Francisco, CA 94121-1545, USA
| | - Neil C Binkley
- School of Medicine and Public Health, University of Wisconsin–Madison, Madison, WI 53726, USA
| | | | - Roger Bouillon
- Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, 3000 Leuven, Belgium
| | - Maria Luisa Brandi
- Italian Foundation for the Research on Bone Diseases (F.I.R.M.O.), Florence 50129, Italy
| | - Felipe F Casanueva
- Department of Medicine, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario and CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Santiago de Compostela University, Santiago de Compostela 15706, Spain
| | - Luigi di Filippo
- Institute of Endocrine and Metabolic Sciences, San Raffaele Vita-Salute University and IRCCS Hospital, Milan 20132, Italy
| | - Lorenzo M Donini
- Department of Experimental Medicine, Sapienza University, Rome 00161, Italy
| | - Peter R Ebeling
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton 3168, Australia
| | - Ghada El-Hajj Fuleihan
- Calcium Metabolism and Osteoporosis Program, WHO CC for Metabolic Bone Disorders, Division of Endocrinology, American University of Beirut, Beirut 1107 2020, Lebanon
| | - Angelo Fassio
- Rheumatology Unit, University of Verona, Verona 37129, Italy
| | - Stefano Frara
- Institute of Endocrine and Metabolic Sciences, San Raffaele Vita-Salute University and IRCCS Hospital, Milan 20132, Italy
| | - Glenville Jones
- Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, ON K7L 3N6, Canada
| | - Claudio Marcocci
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa 56126, Italy
| | - Adrian R Martineau
- Faculty of Medicine and Dentistry, Queen Mary University of London, London E1 4NS, UK
| | - Salvatore Minisola
- Department of Clinical, Internal, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome 00161, Italy
| | - Nicola Napoli
- Unit of Endocrinology and Diabetes Campus Bio-Medico, University of Rome, Rome 00128, Italy
| | - Massimo Procopio
- Division of Endocrinology, Diabetology and Metabolic Diseases, “Molinette” Hospital, University of Turin, Turin 10126, Italy
| | - René Rizzoli
- Geneva University Hospitals and Faculty of Medicine, Geneva 1205, Switzerland
| | - Anne L Schafer
- Department of Medicine, University of California and San Francisco Veterans Affairs Health Center, San Francisco, CA 94121-1545, USA
| | | | - Fabio Massimo Ulivieri
- Institute of Endocrine and Metabolic Sciences, San Raffaele Vita-Salute University and IRCCS Hospital, Milan 20132, Italy
| | - Jyrki K Virtanen
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio FI-70211, Finland
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Yilmaz R. Efficacy and safety of single or consecutive double high-dose oral cholecalciferol supplementation in adult patients with vitamin D deficiency. Steroids 2023; 199:109308. [PMID: 37673409 DOI: 10.1016/j.steroids.2023.109308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 08/28/2023] [Accepted: 09/03/2023] [Indexed: 09/08/2023]
Abstract
BACKGROUND AND AIM Enhancing vitamin D levels as a crucial modifiable risk factor may provide a critical contribution to prevent susceptibility to various diseases, including musculoskeletal, autoimmune, and inflammatory rheumatic diseases as well as promoting overall health. However, adherence to daily vitamin D supplementation is generally poor, and there are some concerns regarding the high-dose vitamin D supplementation's safety. We aimed to investigate whether a single oral dose of 300,000 IU or consecutive two-day dosing of 300,000 IU each day of cholecalciferol could sufficiently and safely elevate vitamin D levels. METHODS This cross-sectional study was conducted on 160 inpatients with vitamin D deficiency and various musculoskeletal diseases.Subjects with serum 25(OH)D levels between 10 and 20 ng/mL (mild to moderate deficiency) received a single oral dose of 300,000 IU cholecalciferol, while those with severe vitamin D deficiency (<10 ng/mL) were supplemented with consecutive two-day doses of 300,000 IU cholecalciferol (a total of 600,000 IU). RESULTS After one week of replacement therapy, the 25(OH)D levels increased from 6.3 (4.0-9.9) ng/mL to 53.3 (8.3-84.4) ng/mL and from 15.0 (10.1-19.6) ng/mL to 38.4 (16.3-67.7) in the group with severe and those with the mild-to-moderate vitamin D deficiency, respectively. Except for three patients, nearly all patients (98%) achieved levels above 20 ng/mL. No signs of toxicity were observed in any of the patients. During the 6-month follow-up, falls were observed in 3 patients (2.8%), but no fractures were reported. CONCLUSION A single dose of 300,000 IU of oral cholecalciferol or two consecutive doses with a total dose of 600,000 IU cholecalciferol can effectively and reliably increase the 25(OH)D serum levels within one week in nearly all patients. The results may contribute to optimizing treatment strategies for vitamin D deficiency and re-evaluating the potential negative impact of high-dose vitamin D supplementation.
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Affiliation(s)
- Ramazan Yilmaz
- Department of Physical Medicine and Rehabilitation, Konya Beyhekim Training and Research Hospital, University of Health Sciences, 42060, Konya, Turkiye.
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Efficacy and Safety of a Personalized Vitamin D 3 Loading Dose Followed by Daily 2000 IU in Colorectal Cancer Patients with Vitamin D Insufficiency: Interim Analysis of a Randomized Controlled Trial. Nutrients 2022; 14:nu14214546. [PMID: 36364809 PMCID: PMC9658724 DOI: 10.3390/nu14214546] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 10/18/2022] [Accepted: 10/19/2022] [Indexed: 11/23/2022] Open
Abstract
A personalized vitamin D3 loading dose has not yet been tested in cancer patients. This interim analysis of the randomized, placebo-controlled VICTORIA trial analyzed the first recruited 74 German adults with nonmetastatic colorectal cancer, a tumor surgery within the past year, and 25-hydroxyvitamin D levels (25(OH)D) < 50 nmol/L. Study participants received a loading dose tailored for a baseline 25(OH)D level and BMI in the first 11 days, followed by a maintenance dose of 2000 IU of vitamin D3 daily until end of trial week 12. The mean 25(OH)D levels were 27.6, 31.0, and 34.1 nmol/L in the placebo group and 25.9, 63.1, and 75.5 nmol/L in the verum group during screening, visit 1 (end of loading dose), and visit 2 (end of maintenance dose), respectively. The prevalence of 25(OH)D) ≥ 50 nmol/L at visits 1 and 2 was 3.5% and 17.4% in the placebo group and 80.0% and 100% in the verum group. No events of 25(OH)D > 150 nmol/L or hypercalcemia were observed. Hypercalciuria events at visit 1 (n = 5 in verum and n = 1 in the placebo group; p = 0.209) receded after discontinuation of the study medication. The personalized loading dose effectively and safely increased the 25(OH)D levels, and 2000 IU of vitamin D3 daily sustained the achieved levels.
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Li B, Xu Y, Zhang X, Zhang L, Wu Y, Wang X, Zhu C. The effect of vitamin D supplementation in treatment of children with autism spectrum disorder: a systematic review and meta-analysis of randomized controlled trials. Nutr Neurosci 2022; 25:835-845. [PMID: 32893747 DOI: 10.1080/1028415x.2020.1815332] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Objective: The effect of vitamin D supplementation on the risk of Autism Spectrum Disorder (ASD) is conflicting. The aim of this study was to estimate the efficacy of vitamin D supplementation on ASD in children.Methods: We conducted a meta-analysis of randomized controlled trials (RCTs) in which vitamin D supplementation was used as a therapy in children with ASD. The PubMed, PsychINFO, Cochrane CENTRAL library, Web of Science, and Cinahl databases were searched from inception to March 20, 2019, for all publications on vitamin D and ASD with no restrictions. Studies involving individuals aged <18 years diagnosed with ASD and with all functional outcomes assessed by measurement scales for ASD were included. Mean differences were pooled, and a meta-analysis was performed using a random-effects model due to differences between the individual RCTs.Results: There were five RCTs with 349 children with ASD in the review, of which three RCTs were included in the meta-analysis. Vitamin D supplementation indicated a small but significant improvement in hyperactivity scores (pooled MD: -3.20; 95% CI: [-6.06, -0.34]) with low heterogeneity (I2 = 10%, p = 0.33), but there were no other statistically significant differences in ASD symptoms between groups as measured by validated scales.Conclusion: Vitamin D supplementation appears to be beneficial for hyperactivity but not for core symptoms or other co-existing behaviors and conditions of ASD. Future RCTs with large sample sizes examining the effect of vitamin D supplementation on ASD among individuals with low serum vitamin D levels at baseline are needed.
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Affiliation(s)
- Bingbing Li
- Henan Key Laboratory of Child Brain Injury, Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Yiran Xu
- Henan Key Laboratory of Child Brain Injury, Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Xiaoli Zhang
- Henan Key Laboratory of Child Brain Injury, Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Lingling Zhang
- Henan Key Laboratory of Child Brain Injury, Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Yanan Wu
- Henan Key Laboratory of Child Brain Injury, Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Xiaoyang Wang
- Henan Key Laboratory of Child Brain Injury, Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, People's Republic of China
- Center of Perinatal Medicine and Health, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Changlian Zhu
- Henan Key Laboratory of Child Brain Injury, Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, People's Republic of China
- Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
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Balachandar R, Pullakhandam R, Kulkarni B, Sachdev HS. Relative Efficacy of Vitamin D 2 and Vitamin D 3 in Improving Vitamin D Status: Systematic Review and Meta-Analysis. Nutrients 2021; 13:nu13103328. [PMID: 34684328 PMCID: PMC8538717 DOI: 10.3390/nu13103328] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 09/17/2021] [Accepted: 09/20/2021] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Widespread prevalence of vitamin D deficiency has been documented globally. Commonly used interventions to address this deficiency include supplementation and/or fortification with either ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3), but the relative efficacy of these two vitamers is unclear. The current study aimed to evaluate the relative efficacy of ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) for raising the serum levels of vitamin D metabolites and functional indicators including serum parathyroid (PTH) levels, isometric muscle strength, hand grip strength and bone mineral density. METHODS Randomized and non-randomized controlled studies evaluating relative efficacy of ergocalciferol and cholecalciferol were systematically reviewed to synthesize quantitative and qualitative evidence as per the recommendations of according to "Preferred Reporting Items for Systematic reviews and Meta-analysis" guidelines. Search terms were constructed on the basis of the "participants", "intervention", "control", "outcome" and "study type" (PICOS) strategy to systematically search the popular electronic databases. Relevant data from studies meeting inclusion and exclusion criteria were extracted and analyzed. Meta-regression, subgroup and sensitivity analyses were performed to investigate the influence of study-level characteristics including intervention dosage, frequency of dosing, interval between the last dose and test for outcome assessment, participant characteristics and analytical methods. RESULTS Apparently healthy human participants (n = 1277) from 24 studies were included for meta-analysis. The quantitative analysis suggested higher efficacy of cholecalciferol than ergocalciferol in improving total 25(OH)D (mean difference: 15.69, 95%CI: 9.46 to 21.93 nmol/L) and reducing PTH levels, consistently across variable participant demographics, dosage and vehicle of supplementation. Meta-regression suggested smaller differences in the efficacy of cholecalciferol and ergocalciferol at lower doses. Average daily dose was the single significant predictor of effect size, as revealed by multivariate meta-regression analysis. CONCLUSIONS Compared to ergocalciferol, cholecalciferol intervention was more efficacious in improving vitamin D status (serum levels of total 25(OH)D and 25(OH)D3) and regulating PTH levels, irrespective of the participant demographics, dosage and vehicle of supplementation.
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Affiliation(s)
- Rakesh Balachandar
- ICMR-National Institute of Occupational Health, Ahmedabad 380016, India;
| | | | - Bharati Kulkarni
- ICMR-National Institute of Nutrition, Hyderabad 500007, India;
- Correspondence:
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Chang Villacreses MM, Karnchanasorn R, Panjawatanan P, Ou HY, Chiu KC. Conundrum of vitamin D on glucose and fuel homeostasis. World J Diabetes 2021; 12:1363-1385. [PMID: 34630895 PMCID: PMC8472505 DOI: 10.4239/wjd.v12.i9.1363] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 05/10/2021] [Accepted: 08/05/2021] [Indexed: 02/06/2023] Open
Abstract
As an endocrine hormone, vitamin D plays an important role in bone health and calcium homeostasis. Over the past two decades, the non-calcemic effects of vitamin D were extensively examined. Although the effect of vitamin D on beta cell function were known for some time, the effect of vitamin D on glucose and fuel homeostasis has attracted new interest among researchers. Yet, to date, studies remain inconclusive and controversial, in part, due to a lack of understanding of the threshold effects of vitamin D. In this review, a critical examination of interventional trials of vitamin D in prevention of diabetes is provided. Like use of vitamin D for bone loss, the benefits of vitamin D supplementation in diabetes prevention were observed in vitamin D-deficient subjects with serum 25-hydroxyvitamin D < 50 nmol/L (20 ng/mL). The beneficial effect from vitamin D supplementation was not apparent in subjects with serum 25-hydroxyvitamin D > 75 nmol/L (30 ng/mL). Furthermore, no benefit was noted in subjects that achieved serum 25-hydroxyvitamin D > 100 nmol/L (40 ng/mL). Further studies are required to confirm these observations.
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Affiliation(s)
- Maria Mercedes Chang Villacreses
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA 91010, United States
- Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, CA 90509, United States
| | - Rudruidee Karnchanasorn
- Division of Endocrinology, Department of Medicine, University of Kansas Medical Center, Kansas City, KS 66160, United States
| | - Panadeekarn Panjawatanan
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA 91010, United States
- Department of Internal Medicine, Bassett Medical Center, Cooperstown, NY 13326, United States
| | - Horng-Yih Ou
- Department of Internal Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan 700, Taiwan
| | - Ken C Chiu
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA 91010, United States
- Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, CA 90509, United States
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Neill HR, Gill CIR, McDonald EJ, McRoberts WC, Pourshahidi LK. The future is bright: Biofortification of common foods can improve vitamin D status. Crit Rev Food Sci Nutr 2021; 63:505-521. [PMID: 34291674 DOI: 10.1080/10408398.2021.1950609] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Vitamin D deficiency is a global concern, linked to suboptimal musculoskeletal health and immune function, with status inadequacies owing to variations in UV dependent cutaneous synthesis and limited natural dietary sources. Endogenous biofortification, alongside traditional fortification and supplement usage is urgently needed to address this deficit. Evidence reviewed in the current article clearly demonstrates that feed modification and UV radiation, either independently or used in combination, effectively increases vitamin D content of primary produce or ingredients, albeit in the limited range of food vehicles tested to date (beef/pork/chicken/eggs/fish/bread/mushrooms). Fewer human trials have confirmed that consumption of these biofortified foods can increase circulating 25-hydroxyvitamin D [25(OH)D] concentrations (n = 10), which is of particular importance to avoid vitamin D status declining to nadir during wintertime. Meat is an unexplored yet plausible food vehicle for vitamin D biofortification, owing, at least in part, to its ubiquitous consumption pattern. Consumption of PUFA-enriched meat in human trials demonstrates efficacy (n = 4), lighting the way for exploration of vitamin D-biofortified meats to enhance consumer vitamin D status. Response to vitamin D-biofortified foods varies by food matrix, with vitamin D3-enriched animal-based foods observing the greatest effect in maintaining or elevating 25(OH)D concentrations. Generally, the efficacy of biofortification appears to vary dependent upon vitamer selected for animal feed supplementation (vitamin D2 or D3, or 25(OH)D), baseline participant status and the bioaccessibility from the food matrix. Further research in the form of robust human clinical trials are required to explore the contribution of biofortified foods to vitamin D status.
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Affiliation(s)
- Holly R Neill
- Nutrition Innovation Centre for Food and Health (NICHE), School of Biomedical Sciences, Ulster University, Coleraine, UK
| | - Chris I R Gill
- Nutrition Innovation Centre for Food and Health (NICHE), School of Biomedical Sciences, Ulster University, Coleraine, UK
| | | | | | - L Kirsty Pourshahidi
- Nutrition Innovation Centre for Food and Health (NICHE), School of Biomedical Sciences, Ulster University, Coleraine, UK
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Wang R, DeGruttola V, Lei Q, Mayer KH, Redline S, Hazra A, Mora S, Willett WC, Ganmaa D, Manson JE. The vitamin D for COVID-19 (VIVID) trial: A pragmatic cluster-randomized design. Contemp Clin Trials 2021; 100:106176. [PMID: 33045402 PMCID: PMC7547023 DOI: 10.1016/j.cct.2020.106176] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 10/03/2020] [Accepted: 10/06/2020] [Indexed: 12/27/2022]
Abstract
OBJECTIVES To determine the effect of vitamin D supplementation on disease progression and post-exposure prophylaxis for COVID-19 infection. We hypothesize that high-dose vitamin D3 supplementation will reduce risk of hospitalization/death among those with recently diagnosed COVID-19 infection and will reduce risk of COVID-19 infection among their close household contacts. METHODS We report the rationale and design of a planned pragmatic, cluster randomized, double-blinded trial (N = 2700 in total nationwide), with 1500 newly diagnosed individuals with COVID-19 infection, together with up to one close household contact each (~1200 contacts), randomized to either vitamin D3 (loading dose, then 3200 IU/day) or placebo in a 1:1 ratio and a household cluster design. The study duration is 4 weeks. The primary outcome for newly diagnosed individuals is the occurrence of hospitalization and/or mortality. Key secondary outcomes include symptom severity scores among cases and changes in the infection (seroconversion) status for their close household contacts. Changes in vitamin D 25(OH)D levels will be assessed and their relation to study outcomes will be explored. CONCLUSIONS The proposed pragmatic trial will allow parallel testing of vitamin D3 supplementation for early treatment and post-exposure prophylaxis of COVID-19. The household cluster design provides a cost-efficient approach to testing an intervention for reducing rates of hospitalization and/or mortality in newly diagnosed cases and preventing infection among their close household contacts.
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Affiliation(s)
- Rui Wang
- Department of Population Medicine, Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, MA, USA; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
| | - Victor DeGruttola
- Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA
| | | | - Kenneth H Mayer
- Fenway Health, and Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Susan Redline
- Division of Sleep Medicine and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Aditi Hazra
- Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Samia Mora
- Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Walter C Willett
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Davaasambuu Ganmaa
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - JoAnn E Manson
- Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
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Bian P, Jin X, Shou Z. Effects of Monthly Intramuscular High-Dose Vitamin D2 on Serum 25-Hydroxyvitamin D and Immune Parameters in Very Elderly Chinese Patients with Vitamin D Deficiency. Int J Endocrinol 2021; 2021:1343913. [PMID: 34707657 PMCID: PMC8545514 DOI: 10.1155/2021/1343913] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Revised: 10/02/2021] [Accepted: 10/07/2021] [Indexed: 11/18/2022] Open
Abstract
PURPOSE Vitamin D deficiency is highly prevalent among the very elderly and is associated with a wide variety of clinical conditions other than musculoskeletal diseases. This study aims to ascertain the efficacy and safety of high-dose intramuscular vitamin D2 in very elderly Chinese patients with vitamin D deficiency. METHODS Very elderly (aged 80 years or over) Chinese patients with vitamin D deficiency were recruited to receive monthly intramuscular injections of 600,000 IU vitamin D2 until their serum 25-hydroxyvitamin D (25(OH)D) reached ≥30 ng/mL. The serum levels of 25(OH)D2, 25(OH)D3, iPTH, BTMs, immune parameters, and other biochemical parameters were measured at baseline and one month after each dose. RESULTS Of the 30 very elderly Chinese patients who had been recruited into the study, 27 (90.0%) had their vitamin D deficiency corrected, and 26 (86.7%) reached vitamin D sufficiency. The mean time (±SD) was 3.1 (±1.3) months for vitamin D deficiency to be corrected, and 6.1 (±0.8) months for vitamin D sufficiency to be reached. The mean (±SD) serum level of 25(OH)D2 increased from 0.69 (±1.51) ng/mL to 29.07 (±5.68) ng/mL, while the mean (±SD) serum level of 25(OH)D3 decreased from 9.82 (±2.75) ng/mL to 5.30 (±3.09) ng/mL (both P < 0.001). The total T cells in serum remained unchanged (P > 0.05), and the CD4 and B cells (CD19+) were increased significantly (both P < 0.05). In addition, no significant change was observed in the serum levels of iPTH and BTMs. CONCLUSION Monthly intramuscular injection of 600,000 IU vitamin D2 is an effective and safe dosing regimen to reach vitamin D sufficiency and enhances immune function in the very elderly Chinese patients with vitamin D deficiency.
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Affiliation(s)
- Pingda Bian
- Department of Geriatrics, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Xue Jin
- Clinical Pharmacy Center, Department of Pharmacy, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Zhangxuan Shou
- Department of Pharmacy, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
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Čečrle M, Černý D, Sedláčková E, Míková B, Dudková V, Drncová E, Pokusová M, Skalský I, Tamášová J, Halačová M. Vitamin D for prevention of sternotomy healing complications: REINFORCE-D trial. Trials 2020; 21:1018. [PMID: 33308291 PMCID: PMC7731517 DOI: 10.1186/s13063-020-04920-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 11/19/2020] [Indexed: 11/29/2022] Open
Abstract
Background Most cardiac surgery patients undergo median sternotomy during open heart surgery. Sternotomy healing is an arduous, very complex, and multifactorial process dependent on many independent factors affecting the sternum and the surrounding soft tissues. Complication rates for median sternotomy range from 0.5 to 5%; however, mortality rates from complications are very variable at 7–80%. Low calcidiol concentration below 80 nmol/L results in calcium absorptive impairment and carries a risk of bone loss, which is considered as a risk factor in the sternotomy healing process. The primary objective of this clinical trial is to compare the incidence of all postoperative sternotomy healing complications in two parallel patient groups administered cholecalciferol or placebo. The secondary objectives are focused on general patient recovery process: sternal bone healing grade at the end of the trial, length of hospitalization, number of days spent in the ICU, number of days spent on mechanical lung ventilation, and number of hospital readmissions for sternotomy complications. Methods This clinical trial is conducted as monocentric, randomized, double-blind, placebo-controlled, with planned enrollment of 600 patients over 4 years, approximately 300 in the placebo arm and 300 in the treatment arm. Males and females from 18 to 95 years of age who fulfill the indication criteria for undergoing cardiac surgery with median sternotomy can be included in this clinical trial, if they meet the eligibility criteria. Discussion REINFORCE-D is the first monocentric trial dividing patients into groups based on serum calcidiol levels, and with dosing based on serum calcidiol levels. This trial may help to open up a wider range of postoperative healing issues. Trial registration EU Clinical Trials Register, EUDRA CT No: 2016-002606-39. Registered on September 8, 2016.
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Affiliation(s)
- Michal Čečrle
- Department of Clinical Pharmacy, Na Homolce Hospital, Prague, Czech Republic.,Institute of Pharmacology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Dalibor Černý
- Department of Clinical Pharmacy, Na Homolce Hospital, Prague, Czech Republic. .,Institute of Pharmacology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
| | - Eva Sedláčková
- Department of Cardiac Surgery, Na Homolce Hospital, Prague, Czech Republic
| | - Barbora Míková
- Department of Radiology, Na Homolce Hospital, Prague, Czech Republic
| | - Vlasta Dudková
- Department of Clinical Biochemistry, Hematology and Immunology, Na Homolce Hospital, Prague, Czech Republic
| | - Eva Drncová
- Department of Clinical Biochemistry, Hematology and Immunology, Na Homolce Hospital, Prague, Czech Republic
| | | | - Ivo Skalský
- Department of Cardiac Surgery, Na Homolce Hospital, Prague, Czech Republic
| | - Jana Tamášová
- Department of Medical Physics, Na Homolce Hospital, Prague, Czech Republic
| | - Milada Halačová
- Department of Clinical Pharmacy, Na Homolce Hospital, Prague, Czech Republic.,Department of Pharmacology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic
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11
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Wyon MA, Wolman R, Martin C, Galloway S. The efficacy of different vitamin D supplementation delivery methods on serum 25(OH)D: A randomised double-blind placebo trial. Clin Nutr 2020; 40:388-393. [PMID: 32703720 DOI: 10.1016/j.clnu.2020.05.040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 05/20/2020] [Accepted: 05/24/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND The use of vitamin D supplementation has increased due to greater recognition of widespread deficiency. AIMS There has been little research on the effectiveness of different delivery methods and therefore the aim of was to test the efficacy of different delivery methods on serum 25(OH)D. METHODS Using a randomised repeated measures double-blind placebo design (registered under ClinicalTrials.gov Identifier no. NCT03463642), changes in serum 25(OH)D over a 4-week period using a capillary spot method were monitored. 62 female participants blindly chose a number related to a supplementation delivery method: pill placebo, pill, oral liquid, oral liquid placebo, Skin oil application (SOA) placebo, SOA plus vitamin D3 suspension, or SOA plus vitamin D3 suspension with essential oil enhancer; active vitamin D supplements contained 100,000IU. Participants took their allocated supplements over a 24-hr period with serum 25(OH)D retested 4 weeks later. Liquid chromatography-tandem mass spectrometry method was applied to dried blood spot samples by an independent laboratory. RESULTS ANCOVA reported a significant difference between the groups (F1,6 = 146.68; p < 0.001, eta2 = 0.51). Separate analysis within the delivery methods (pill, SOA, oral liquid) indicated significant differences between the active and placebo supplementation groups (p < 0.01). Post hoc analysis of absolute changes indicated vit D pill and SOA + vit D + essential oil had significant increases (p < 0.05) in serum 25(OH)D compared to all other interventions with no significant difference between them. CONCLUSIONS In human participants vitamin D oral pill has the greatest effect on serum 25(OH)D levels. Skin oil application delivery of vitamin D using a penetrator enhancer has also been shown to be an effective method of delivery.
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Affiliation(s)
- M A Wyon
- Sport and Physical Activity Research Centre, Institute of Sport and Health Sciences, University of Wolverhampton, UK
| | - R Wolman
- Department of Rheumatology and Sport and Exercise Medicine, Royal National Orthopaedic Hospital, Stanmore, UK
| | - C Martin
- Worcester Biomedical Science Research Group, Institute of Science and the Environment, St. John's Campus, University of Worcester, Henwick Grove, Worcester, WR2 6AJ, UK.
| | - S Galloway
- Sport and Physical Activity Research Centre, Institute of Sport and Health Sciences, University of Wolverhampton, UK
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12
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Jensen ME, Ducharme FM, Alos N, Mailhot G, Mâsse B, White JH, Sadatsafavi M, Khamessan A, Tse SM, Alizadehfar R, Bock DE, Daigneault P, Lemire C, Yang C, Radhakrishnan D. Vitamin D in the prevention of exacerbations of asthma in preschoolers (DIVA): protocol for a multicentre randomised placebo-controlled triple-blind trial. BMJ Open 2019; 9:e033075. [PMID: 31892662 PMCID: PMC6955525 DOI: 10.1136/bmjopen-2019-033075] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
INTRODUCTION Preschoolers have the highest rate of emergency visits and hospitalisations for asthma exacerbations of all age groups, with most triggered by upper respiratory tract infections (URTIs) and occurring in the fall or winter. Vitamin D insufficiency is highly prevalent in Canadian preschoolers with recurrent asthma exacerbations, particularly in winter. It is associated with more URTIs and, in patients with asthma, more oral corticosteroid (OCS) use. Although evidence suggests that vitamin D supplements significantly decrease URTIs and asthma exacerbations requiring OCS, there is insufficient data in preschoolers. This study aims to determine the impact of vitamin D3 supplementation on exacerbations requiring OCS, in preschoolers with recurrent URTI-induced asthma exacerbations. METHODS AND ANALYSIS This is a phase III, randomised, triple-blind, placebo-controlled, parallel-group multicentre trial of vitamin D3 supplementation in children aged 1-5 years, with asthma triggered by URTIs and a recent history of frequent URTIs and OCS use. Children (n=865) will be recruited in the fall and early winter and followed for 7 months. They will be randomised to either the (1) intervention: two oral boluses of 100 000 international unit (IU) vitamin D3 (3.5 months apart) with 400 IU vitamin D3 daily; or (2) control: identical placebo boluses with daily placebo. The primary outcome is the number of exacerbations requiring OCS per child, documented by medical and pharmacy records. Secondary outcomes include number of laboratory-confirmed viral URTIs, exacerbation duration and severity, parent functional status, healthcare use, treatment deintensification, cost and safety. ETHICS AND DISSEMINATION This study has received ethical approval from all sites. Results will be disseminated via international conferences and manuscripts targeting paediatricians and respirologists, and to families of asthmatic children via our Quebec parents-partners outreach programme. If proven effective, findings may markedly influence the management of URTI-induced asthma in high-morbidity preschoolers and could be directly implemented into practice with an update to clinical guidelines. TRIAL REGISTRATION NUMBER NCT03365687.
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Affiliation(s)
- Megan E Jensen
- Priority Research Centre Grow Up Well, School of Medicine & Public Health, Faculty of Health, The University of Newcastle, Callaghan, New South Wales, Australia
| | - Francine M Ducharme
- Department of Social & Preventive Medicine, University of Montreal, Montreal, Québec, Canada
- Clinical Research and Knowledge Transfer Unit on Childhood Asthma, Research Centre, CHU Sainte-Justine, Montreal, Québec, Canada
- Department of Pediatrics, University of Montreal, Montreal, Québec, Canada
| | - Nathalie Alos
- Department of Social & Preventive Medicine, University of Montreal, Montreal, Québec, Canada
- Pediatric Endocrinology Service, CHU Sainte-Justine, Montreal, Québec, Canada
| | - Geneviève Mailhot
- Department of Nutrition, Faculty of Medicine, University of Montreal, Montreal, Québec, Canada
| | - Benoît Mâsse
- Research Centre, CHU Sainte-Justine, Montreal, Québec, Canada
- School of Public Health, University of Montreal, Montreal, Québec, Canada
| | - John H White
- Department of Physiology, McGill University, Montreal, Québec, Canada
| | - Mohsen Sadatsafavi
- Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada
| | - Ali Khamessan
- Euro-Pharm International Canada Inc, Montreal, Québec, Canada
| | - Sze Man Tse
- Department of Social & Preventive Medicine, University of Montreal, Montreal, Québec, Canada
- Clinical Research and Knowledge Transfer Unit on Childhood Asthma, Research Centre, CHU Sainte-Justine, Montreal, Québec, Canada
| | - Reza Alizadehfar
- Department of Pediatrics, Montreal Children's Hospital, Montreal, Québec, Canada
| | - Dirk E Bock
- Department of Pediatrics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
| | - Patrick Daigneault
- Department of Pediatrics, Centre Mère-Enfant du CHU de Québec, Quebec City, Quebec, Canada
| | - Chantal Lemire
- Division of Allergy and Immunology, Department of Pediatrics, Université de Sherbrooke, Sherbrooke, Quebec, Canada
| | - Connie Yang
- Department of Pediatrics, British Columbia Children's Hospital, Vancouver, British Columbia, Canada
| | - Dhenuka Radhakrishnan
- Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
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13
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Li XX, Liu Y, Luo J, Huang ZD, Zhang C, Fu Y. Vitamin D deficiency associated with Crohn's disease and ulcerative colitis: a meta-analysis of 55 observational studies. J Transl Med 2019; 17:323. [PMID: 31547829 PMCID: PMC6757415 DOI: 10.1186/s12967-019-2070-5] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Accepted: 09/17/2019] [Indexed: 12/13/2022] Open
Abstract
PURPOSE To investigate the association of serum levels of 25(OH)D and 1,25(OH)2D3 in healthy and non-healthy controls with Crohn's disease (CD) and ulcerative colitis (UC). METHODS Three electronic databases: PubMed, EMbase and EBSCOhost CINAHL, were searched for observational studies to measure the relationship between serum levels of vitamin D (VitD) and CD (or UC). RESULTS Fifty-five studies were included in the meta-analysis. We found that mean serum 25(OH)D levels in patients with CD were significantly lower than those in healthy controls (MD: - 3.17 ng/mL; 95% CI - 4.42 to - 1.93). Results from the meta-analysis examining 1,25(OH)2D3 levels in Crohn's patients revealed higher levels in the CD group than in healthy (MD: 3.47 pg/mL; 95% CI - 7.72 to 14.66) and UC group (MD: 5.05 pg/mL; 95% CI - 2.42 to 12.52). Serum 25(OH)D levels were lower in the UC group than in the healthy control group (MD: - 2.52 ng/mL; 95% CI - 4.02 to - 1.02). In studies investigating the level of 1,25(OH)2D3 in UC and healthy control groups, the level of 1,25(OH)2D3 in the UC groups were found to be higher than that in the control groups (MD: 3.76 pg/mL; 95% CI - 8.36 to 15.57). However, the 1,25(OH)2D3 level in patients with UC was lower than that in CD groups (MD: - 6.71 pg/mL; 95% CI - 15.30 to 1.88). No significant difference was noted between CD patients and UC patients in terms of average serum 25(OH)D levels. CONCLUSIONS This study found that VitD levels were inversely related to CD and UC. Serum levels of 25(OH)D were lower in patients with CD and UC than in healthy people, and more than half of the patients had insufficient vitamin D levels. The serum level of 1,25(OH)2D3 in both the CD and UC groups was higher than that in healthy people.
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Affiliation(s)
- Xi-Xi Li
- Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, No. 32, South Renmin Road, Shiyan, 442000, China.,Zhejiang Chinese Medical University, No. 548, Binwen Road, Zhengjiang, 310053, China
| | - Yang Liu
- Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, No. 32, South Renmin Road, Shiyan, 442000, China
| | - Jie Luo
- Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, No. 32, South Renmin Road, Shiyan, 442000, China
| | - Zhen-Dong Huang
- Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, No. 32, South Renmin Road, Shiyan, 442000, China
| | - Chao Zhang
- Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, No. 32, South Renmin Road, Shiyan, 442000, China.
| | - Yan Fu
- Department of General Surgery, Taihe Hospital, Hubei University of Medicine, No. 32, South Renmin Road, Shiyan, 442000, China.
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14
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Bozkurt S, Alkan BM, Ural FG, Aksekili H, Fidan F, Sezer N, Aktekin L, Ardıçoğlu Ö, Akkuş S. The Effect of Bolus Vitamin D Supplementation. ANKARA MEDICAL JOURNAL 2019. [DOI: 10.17098/amj.582000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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15
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Malihi Z, Lawes CMM, Wu Z, Huang Y, Waayer D, Toop L, Khaw KT, Camargo CA, Scragg R. Monthly high-dose vitamin D supplementation does not increase kidney stone risk or serum calcium: results from a randomized controlled trial. Am J Clin Nutr 2019; 109:1578-1587. [PMID: 31005969 DOI: 10.1093/ajcn/nqy378] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Accepted: 12/10/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND A growing number of randomized controlled trials (RCTs) are investigating the potential health benefits of high-dose vitamin D supplementation. However, there are limited RCT data on the safety of calcium-related adverse effects. OBJECTIVE We investigated the incidence of kidney stone and hypercalcemia events in a large, population-based RCT of vitamin D supplementation. DESIGN The Vitamin D Assessment (ViDA) study was a randomized, double-blind, placebo-controlled trial of vitamin D supplementation in 5110 participants in Auckland, New Zealand. This trial investigated the impact of monthly 100,000 IU vitamin D3 supplementation over several years on cardiovascular events, respiratory infections, and falls/fractures. Participants provided information about recent kidney stone events in regular questionnaires sent to them with study capsules. Hospitalization data for kidney stones were collected from health authorities. Serum calcium was measured in an 8% subsample of participants who returned annually for blood tests. HRs of time to the first kidney stone event were calculated by Cox regression. RESULTS During a median follow-up of 3.3 y, 158 participants reported a kidney stone event (76 vitamin D, 82 placebo). The HR of reporting the first kidney stone event was 0.90 (95% CI: 0.66, 1.23; P = 0.51) for participants in the vitamin D arm compared with the placebo arm. There were 18 urolithiasis events in the hospitalization records: 7 in the vitamin D arm and 11 from the placebo arm. The HR to the first hospitalization urolithiasis event was 0.62 (95% CI: 0.24, 1.26; P = 0.30) in the vitamin D arm compared with the placebo arm. From the subsample annual blood test, there was no case of hypercalcemia in the vitamin D arm, compared with 1 in the placebo arm. CONCLUSION Over a median of 3.3 y, monthly supplementation with 100,000 IU vitamin D3 did not affect the incidence rate of kidney stone events, or hypercalcemia. This study was registered at clinicaltrials.gov as ACTRN12611000402943.
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Affiliation(s)
- Zarintaj Malihi
- School of Population Health, University of Auckland, Auckland, New Zealand
| | - Carlene M M Lawes
- School of Population Health, University of Auckland, Auckland, New Zealand
| | - Zhenqiang Wu
- School of Population Health, University of Auckland, Auckland, New Zealand
| | - Ying Huang
- School of Population Health, University of Auckland, Auckland, New Zealand
| | - Debbie Waayer
- School of Population Health, University of Auckland, Auckland, New Zealand
| | - Les Toop
- Department of General Practice, University of Otago, Christchurch, New Zealand
| | - Kay-Tee Khaw
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Carlos A Camargo
- Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Robert Scragg
- School of Population Health, University of Auckland, Auckland, New Zealand
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Slobogean GP, Sprague S, Bzovsky S, Heels-Ansdell D, Thabane L, Scott T, Bhandari M. Fixation using alternative implants for the treatment of hip fractures (FAITH-2): design and rationale for a pilot multi-centre 2 × 2 factorial randomized controlled trial in young femoral neck fracture patients. Pilot Feasibility Stud 2019; 5:70. [PMID: 31161044 PMCID: PMC6540373 DOI: 10.1186/s40814-019-0458-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Accepted: 05/13/2019] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND Femoral neck fractures in patients ≤ 60 years of age are often very different injuries compared to low-energy, hip fractures in elderly patients and are difficult to manage because of inherent problems associated with high-energy trauma mechanisms and increased functional demands for recovery. Internal fixation, with multiple cancellous screws or a sliding hip screw (SHS), is the most common treatment for this injury in young patients. However, there is no clinical consensus regarding which surgical technique is optimal. Additionally, there is compelling rationale to use vitamin D supplementation to nutritionally optimize bone healing in young patients. This pilot trial will determine feasibility and provide preliminary clinical data for a larger definitive trial. METHODS We will conduct a multicenter, concealed randomized controlled pilot study, using a 2 × 2 factorial design in 60 patients aged 18-60 years with a femoral neck fracture. Eligible patients will be randomized in equal proportions to one of four groups: 1) SHS and vitamin D supplementation (4000 international units (IU) daily dose) for 6 months, 2) cancellous screws and vitamin D supplementation (4000 IU daily dose) for 6 months, 3) SHS and placebo, and 4) cancellous screws and placebo. Participants will be followed for 12 months post-fracture. Feasibility outcomes include initiation of clinical sites, recruitment, follow-up, data quality, and protocol adherence. Clinical outcomes, for both the pilot and planned definitive trials, include a composite of patient-important outcomes (re-operation, femoral head osteonecrosis, severe femoral neck malunion, and nonunion), health-related quality of life and patient-reported function, fracture healing complications, and radiographic fracture healing. A priori success criteria have been established. If the pilot study is deemed successful, study participants will be included in the definitive trial and clinical outcomes for the pilot will not be analyzed. If the pilot study is not deemed successful, clinical outcome data will be analyzed. DISCUSSION Results of this study will inform the feasibility of a definitive trial. If clinical outcome data are analyzed, they will be disseminated through a publication and presentations. TRIAL REGISTRATION The FAITH-2 trial, described as a definitive trial, was registered at ClinicalTrials.gov (NCT01908751) prior to enrollment of the first participant.
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Affiliation(s)
- Gerard P. Slobogean
- R Adams Cowley Shock Trauma Center, Department of Orthopaedics, University of Maryland School of Medicine, 22 South Greene Street, Baltimore, MD 21201 USA
| | - Sheila Sprague
- Division of Orthopaedic Surgery, Department of Surgery, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8 Canada
- Department of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8 Canada
| | - Sofia Bzovsky
- Division of Orthopaedic Surgery, Department of Surgery, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8 Canada
| | - Diane Heels-Ansdell
- Department of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8 Canada
| | - Lehana Thabane
- Department of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8 Canada
| | - Taryn Scott
- Division of Orthopaedic Surgery, Department of Surgery, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8 Canada
| | - Mohit Bhandari
- Division of Orthopaedic Surgery, Department of Surgery, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8 Canada
- Department of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8 Canada
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17
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Rowe CW, Arthurs S, O'Neill CJ, Hawthorne J, Carroll R, Wynne K, Bendinelli C. High-dose preoperative cholecalciferol to prevent post-thyroidectomy hypocalcaemia: A randomized, double-blinded placebo-controlled trial. Clin Endocrinol (Oxf) 2019; 90:343-350. [PMID: 30387163 DOI: 10.1111/cen.13897] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2018] [Revised: 10/08/2018] [Accepted: 10/29/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Post-thyroidectomy hypocalcaemia is a significant cause of morbidity and prolonged hospitalization, usually due to transient parathyroid gland damage, treated with calcium and vitamin D supplementation. We present a randomized, double-blinded placebo-controlled trial of preoperative loading with high-dose cholecalciferol (300 000 IU) to reduce post-thyroidectomy hypocalcaemia. PATIENTS AND MEASUREMENTS Patients (n = 160) presenting for thyroidectomy at tertiary hospitals were randomized 1:1 to cholecalciferol (300 000 IU) or placebo 7 days prior to thyroidectomy. Ten patients withdrew prior to surgery. The primary outcome was post-operative hypocalcaemia (corrected calcium <2.1 mmol/L in first 180 days). RESULTS The study included 150 patients undergoing thyroidectomy for Graves' disease (31%), malignancy (20%) and goitre (49%). Mean pre-enrolment vitamin D was 72 ± 26 nmol/L. Postoperative hypocalcaemia occurred in 21/72 (29%) assigned to cholecalciferol and 30/78 (38%) participants assigned to placebo (P = 0.23). There were no differences in secondary end-points between groups. In pre-specified stratification, baseline vitamin D status did not predict hypocalcaemia, although most individuals were vitamin D replete at baseline. Post-hoc stratification by day 1 parathyroid hormone (PTH) (<10 pg/mL, low vs ≥10 pg/mL, normal) was explored due to highly divergent rates of hypocalcaemia in these groups. Using a Cox regression model, the hazard ratio for hypocalcaemia in the cholecalciferol group was 0.56 (95%CI 0.32-0.98, P = 0.04) after stratification for Day 1 PTH. Further clinical benefits were observed in these subgroups. CONCLUSIONS Pre-thyroidectomy treatment with high-dose cholecalciferol did not reduce the overall rate of hypocalcaemia following thyroidectomy. In subgroups stratified by day 1 PTH status, improved clinical outcomes were noted.
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Affiliation(s)
- Christopher W Rowe
- Department of Endocrinology, John Hunter Hospital, Newcastle, New South Wales, Australia
- School of Medicine and Public Health, University of Newcastle, New South Wales, Australia
| | - Sam Arthurs
- Department of Rehabilitation, John Hunter Hospital, Newcastle, New South Wales, Australia
| | - Christine J O'Neill
- School of Medicine and Public Health, University of Newcastle, New South Wales, Australia
- Department of Surgery, John Hunter Hospital, Newcastle, New South Wales, Australia
| | - Jacqueline Hawthorne
- Department of Surgery, John Hunter Hospital, Newcastle, New South Wales, Australia
| | - Rosemary Carroll
- Department of Surgery, John Hunter Hospital, Newcastle, New South Wales, Australia
| | - Katie Wynne
- Department of Endocrinology, John Hunter Hospital, Newcastle, New South Wales, Australia
- School of Medicine and Public Health, University of Newcastle, New South Wales, Australia
| | - Cino Bendinelli
- Department of Surgery, John Hunter Hospital, Newcastle, New South Wales, Australia
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Bellan M, Marzullo P. New Insights on Low Vitamin D Plasma Concentration as a Potential Cardiovascular Risk Factor. Open Rheumatol J 2018. [DOI: 10.2174/1874312901812010261] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
The role of Vitamin D hormone in human health and disease is still debated. Recently, growing attention has been paid to its putative role in cardiovascular system homeostasis with several studies that suggested a correlation between low vitamin D levels and increased cardiovascular risk. Several mechanisms are involved in the development of cardiovascular diseases: systemic inflammation, endothelial dysfunction, arterial hypertension and insulin resistance. In the present paper, we have revised the current literature supporting a role for vitamin D in the development of these pathogenetic processes. Finally, we have evaluated the current evidence linking vitamin D to atherosclerosis and its natural consequence, cardiovascular diseases.
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Gupta R, Behera C, Paudwal G, Rawat N, Baldi A, Gupta PN. Recent Advances in Formulation Strategies for Efficient Delivery of Vitamin D. AAPS PharmSciTech 2018; 20:11. [PMID: 30560516 DOI: 10.1208/s12249-018-1231-9] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Accepted: 10/26/2018] [Indexed: 12/14/2022] Open
Abstract
Deficiency of vitamin D is a global concern affecting a huge number of human populations. This deficiency has a serious impact on human health not only affecting bone mineral density but also becoming the reason for cardiovascular disorders, infectious diseases, autoimmune diseases and cancers. Exposure to sunlight is the major source of vitamin D, but due to the present day-to-day lifestyle of working in a shade arouses the need for exogenous sources of vitamin D. Ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) are the two major forms of vitamin D, which are hydrophobic in nature and highly susceptible to environmental conditions, like temperature and light. Therefore, novel drug delivery systems could be explored for efficient delivery of vitamin D. In this review, a brief account of vitamin D is provided followed by a detailed description of recent advances in various delivery systems, including solid lipid nanoparticles, nanoemulsion, self-emulsifying drug delivery systems, polymeric nanoparticles and solid dispersion, for the efficient delivery of vitamin D.
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Apaydin M, Can AG, Kizilgul M, Beysel S, Kan S, Caliskan M, Demirci T, Ozcelik O, Ozbek M, Cakal E. The effects of single high-dose or daily low-dosage oral colecalciferol treatment on vitamin D levels and muscle strength in postmenopausal women. BMC Endocr Disord 2018; 18:48. [PMID: 30031389 PMCID: PMC6054843 DOI: 10.1186/s12902-018-0277-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Accepted: 07/11/2018] [Indexed: 12/14/2022] Open
Abstract
INTRODUCTION Vitamin D deficiency is a common health problem. Vitamin D supplements are used to improve vitamin D status; however, there are contradictory data related to what doses to give and how often they should be given. Many studies have investigated the effects of vitamin D supplementation on muscle strength, but the results remain controversial. We aimed to compare the effects and safety of single high-dose with daily low-dose oral colecalciferol on 25(OH)D levels and muscle strength in postmenopausal women with vitamin D deficiency or insufficiency. METHODS AND DESIGN Sixty healthy postmenopausal women who had serum vitamin D levels < 20 ng/mL (50 nmol/L) were enrolled in the study. Group 1 (n = 32) was given daily oral dosages of 800 IU vitamin D3, and group 2 (n = 28) was given a single oral dose of 300,000 IU vitamin D3. Serum vitamin D levels and muscle strengths were measured at the beginning, 4th, and 12th week. Muscle strength tests were performed at 60° using a Biodex system 3 isokinetic dynamometer. RESULTS Pretreatment vitamin D levels did not differ between the two groups (10.2 ± 4.4 ng/mL (25,4 ± 10,9 nmol/L); 9.7 ± 4.4 ng/mL (24,2 ± 10,9 nmol/L), p > 0.05). A significant increase in vitamin D levels was observed in both groups at 4 and 12 weeks after vitamin D3 treatment. The increase in the single-dose group was significantly higher than the daily low-dosage group at the 4th week (35.9 ± 9.6 ng/mL (89,6 ± 23,9 nmol/L), 16.9 ± 5.8 ng/mL (42,1 ± 14,4 nmol/L), p = 0.01). The increase in the single-dose group was significantly higher than in the daily low dosage group at the 12th week (23.4 ± 4.7 ng/mL (58,4 ± 11,7 nmol/L), 19.8 ± 7.2 ng/mL (49,4 ± 17,9 nmol/L), p = 0.049). The quadriceps muscle strength score increased significantly in the daily group at the 4th week (p = 0.038). The hamstring muscle strength score increased significantly in the daily group at the 12th week (p = 0.037). CONCLUSION Although daily administration routes are more effective in improving muscle strength, a single administration is more effective in increasing vitamin D levels. TRIAL REGISTRATION NUMBER ISRCTN14226530 (04.07.2018), Name of the registry: ISRCTN registry, The study was retrospectively registered.
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Affiliation(s)
- Mahmut Apaydin
- Department of Endocrinology and Metabolism, Diskapi Training and Research Hospital, Ankara, Turkey.
| | - Asli Gencay Can
- Department of Physical Medicine and Rehabilitation, Diskapi Training and Research Hospital, Ankara, Turkey
| | - Muhammed Kizilgul
- Department of Endocrinology and Metabolism, Diskapi Training and Research Hospital, Ankara, Turkey
| | - Selvihan Beysel
- Department of Endocrinology and Metabolism, Diskapi Training and Research Hospital, Ankara, Turkey
| | - Seyfullah Kan
- Department of Endocrinology and Metabolism, Diskapi Training and Research Hospital, Ankara, Turkey
| | - Mustafa Caliskan
- Department of Endocrinology and Metabolism, Diskapi Training and Research Hospital, Ankara, Turkey
| | - Taner Demirci
- Department of Endocrinology and Metabolism, Diskapi Training and Research Hospital, Ankara, Turkey
| | - Ozgur Ozcelik
- Department of Endocrinology and Metabolism, Diskapi Training and Research Hospital, Ankara, Turkey
| | - Mustafa Ozbek
- Department of Endocrinology and Metabolism, Diskapi Training and Research Hospital, Ankara, Turkey
| | - Erman Cakal
- Department of Endocrinology and Metabolism, Diskapi Training and Research Hospital, Ankara, Turkey
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Vitamin D deficiency as a public health issue: using vitamin D2 or vitamin D3 in future fortification strategies. Proc Nutr Soc 2017; 76:392-399. [PMID: 28347378 DOI: 10.1017/s0029665117000349] [Citation(s) in RCA: 103] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
The role of vitamin D in supporting the growth and maintenance of the skeleton is robust; with recent research also suggesting a beneficial link between vitamin D and other non-skeletal health outcomes, including immune function, cardiovascular health and cancer. Despite this, vitamin D deficiency remains a global public health issue, with a renewed focus in the UK following the publication of Public Health England's new Dietary Vitamin D Requirements. Natural sources of vitamin D (dietary and UVB exposure) are limited, and thus mechanisms are needed to allow individuals to achieve the new dietary recommendations. Mandatory or voluntary vitamin D food fortification may be one of the mechanisms to increase dietary vitamin D intakes and subsequently improve vitamin D status. However, for the food industry and public to make informed decisions, clarity is needed as to whether vitamins D2 and D3 are equally effective at raising total 25-hydroxyvitamin D (25(OH)D) concentrations as the evidence thus far is inconsistent. This review summarises the evidence to date behind the comparative efficacy of vitamins D2 and D3 at raising 25(OH)D concentrations, and the potential role of vitamin D food fortification as a public health policy to support attainment of dietary recommendations in the UK. The comparative efficacy of vitamins D2 and D3 has been investigated in several intervention trials, with most indicating that vitamin D3 is more effective at raising 25(OH)D concentrations. However, flaws in study designs (predominantly under powering) mean there remains a need for a large, robust randomised-controlled trial to provide conclusive evidence, which the future publication of the D2-D3 Study should provide (BBSRC DRINC funded: BB/I006192/1). This review also highlights outstanding questions and gaps in the research that need to be addressed to ensure the most efficacious and safe vitamin D food fortification practices are put in place. This further research, alongside cost, availability and ethical considerations (vitamin D3 is not suitable for vegans), will be instrumental in supporting government, decision-makers, industry and consumers in making informed choices about potential future vitamin D policy and practice.
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Gupta N, Farooqui KJ, Batra CM, Marwaha RK, Mithal A. Effect of oral versus intramuscular Vitamin D replacement in apparently healthy adults with Vitamin D deficiency. Indian J Endocrinol Metab 2017; 21:131-136. [PMID: 28217512 PMCID: PMC5240054 DOI: 10.4103/2230-8210.196007] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
CONTEXT A number of controversies exist regarding appropriate treatment strategy for Vitamin D deficiency. AIMS The aim of this study was to investigate the efficacy of equivalent doses of oral cholecalciferol (60,000 IU weekly for 5 weeks) versus intramuscular (IM) cholecalciferol (300,000 IU) in correcting Vitamin D deficiency in apparently healthy volunteers working in a hospital. SETTINGS AND DESIGN Prospective randomized open-label single institution study. SUBJECTS AND METHODS This study enrolled 40 apparently healthy adults with Vitamin D deficiency into 2 arms. The oral cholecalciferol group (n = 20) received oral cholecalciferol 60,000 IU weekly for 5 weeks while the IM cholecalciferol group (n = 20) received a single injection of cholecalciferol 300,000 IU. The main outcome measure was serum 25-hydroxyvitamin D (25OHD) levels at baseline, 6 and 12 weeks after the intervention. STATISTICAL ANALYSIS USED Differences in serum 25OHD and other biochemical parameters at baseline and follow-up were analyzed using general linear model. RESULTS Mean 25OHD level at baseline was 5.99 ± 1.07 ng/mL and 7.40 ± 1.13 ng/mL (P = 0.332) in the oral cholecalciferol and IM cholecalciferol group, respectively. In the oral cholecalciferol group, serum 25OHD level was 20.20 ± 1.65 ng/mL at 6 weeks and 16.66 ± 1.36 ng/mL at 12 weeks. The corresponding serum 25OHD levels in the IM cholecalciferol group were 20.74 ± 1.81 ng/mL and 25.46 ± 1.37 ng/mL at 6 and 12 weeks, respectively. At 12 weeks, the mean 25OHD levels in IM cholecalciferol group was higher as compared to the oral cholecalciferol group (25.46 ± 1.37 vs. 16.66 ± 1.36 ng/mL; P < 0.001). CONCLUSIONS Both oral and IM routes are effective for the treatment of Vitamin D deficiency. 25-hydroxyvitamin D levels in the IM cholecalciferol group showed a sustained increase from baseline.
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Affiliation(s)
- Nitin Gupta
- Department of Endocrinology, Fortis Escorts Hospital, Amritsar, Punjab, India
| | - Khalid J. Farooqui
- Division of Endocrinology and Diabetes, Medanta the Medicity, Gurgaon, Haryana, India
| | - Chandar M. Batra
- Department of Endocrinology, Indraprastha Apollo Hospitals, New Delhi, India
| | - Raman K. Marwaha
- Senior Consultant Endocrinology and Scientific Advisor (Projects), ILSI-India, New Delhi, India
| | - Ambrish Mithal
- Division of Endocrinology and Diabetes, Medanta the Medicity, Gurgaon, Haryana, India
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Mihos CG, De La Cruz JA, Hernandez A, Santana O. Vitamin D Deficiency and Supplementation in Cardiovascular Disorders. Cardiol Rev 2017; 25:189-196. [PMID: 28574937 DOI: 10.1097/crd.0000000000000138] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Cardiovascular disease (CVD) is the leading cause of death in developed countries. Similarly, the frequency of vitamin D deficiency is increasing, and a number of epidemiologic and clinical studies have suggested that there is an increased risk of CVD among people with depletion of this vitamin. This has raised much interest in the potential pathogenic and therapeutic role of vitamin D in CVD. However, randomized trials and meta-analyses have not shown a clear benefit of vitamin D supplementation with respect to cardiovascular events. Herein, we provide a comprehensive review of the most relevant evidence to date regarding vitamin D deficiency and supplementation, and their respective impact on CVD prevention and treatment.
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Affiliation(s)
- Christos G Mihos
- From the *Cardiac Ultrasound Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA; †The Department of Internal Medicine, Mount Sinai Medical Center, Miami Beach, FL; and ‡Cardiology Department, Columbia University Division of Cardiology, Mount Sinai Heart Institute, Miami Beach, FL
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24
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Vitamin D status in patients attending a Danish migrant health clinic: a clinical retrospective study. J Immigr Minor Health 2016; 17:474-81. [PMID: 24791701 DOI: 10.1007/s10903-014-0031-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Non-western migrants and ethnic minority populations in western countries are particularly at risk of vitamin D deficiency due to darker skin color and low sun exposure. The aim of this study was to examine levels of 25-OH vitamin D in patients attending a Danish health clinic for migrants. Patients attending the clinic represent a distinct group of migrants with longstanding, unresolved symptoms and often multiple illnesses. In this retrospective study, data on patient demographics and vitamin D levels were extracted from the medical records of 156 patients attending a Migrant Health Clinic in 2008-2011 who were considered at-risk for low vitamin D, mainly due to symptoms of diffuse pain in the muscles, bones or joints. Over the follow-up period of 1 year, the number of patients with vitamin D below 50 nmol/L decreased from 80 to 56%. The median vitamin D level increased from 27 nmol/L [(interquartile ranges (IQR 14.5-45.0)] at baseline to 45 nmol/L (IQR 26.5-64.5) at follow-up. Patient consultations with a holistic approach and close follow-up can help patients with complex symptoms and language barriers to overcome barriers to treatment and adherence, thus leading to improved levels of vitamin D.
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25
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Agarwal M, Phan A, Willix R, Barber M, Schwarz ER. Is Vitamin D Deficiency Associated With Heart Failure? A Review of Current Evidence. J Cardiovasc Pharmacol Ther 2016; 16:354-63. [DOI: 10.1177/1074248410390214] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
An estimated 1 billion people worldwide have deficient or insufficient levels of vitamin D. Even more alarming is the association of vitamin D deficiency with many types of diseases, particularly heart failure (HF). Hypovitaminosis D has been observed to be highly prevalent in the HF community with rates varying from approximately 80% to 95%. Higher rates of deficiency have been linked to winter months, in patients with protracted decompensated HF, darker skin pigmentation, and higher New York Heart Association (NYHA) classes. In fact, some data suggest vitamin D deficiency may even be an independent predictor of mortality in patients with HF. Traditionally obtained through UV exposure and activated in the liver and then the kidneys, vitamin D is classified as a vitamin but functions as a steroid hormone. The hormone acts through the vitamin D receptor (VDR), which is expressed in vascular smooth muscle cells, renal juxtaglomerular cells, and most interestingly, cardiac myocytes. Studies have shown that the association between vitamin D deficiency and HF often manifests in the structural components of cardiac myocytes and/or through alterations of the neurohormonal cascade. In addition, vitamin D may also act rapidly through intracellular nongenomic receptors that alter cardiac contractility. Unfortunately, prospective vitamin D supplementation trials show mixed results. In rat models, successful correction of deficiency was associated with reductions in ventricular hypertrophy. In humans, however, echocardiographic dimensions did not change significantly. These results bring into questions whether vitamin D is a risk factor for HF, a marker of HF disease severity, or has a true pathologic role. This article provides a thorough review of vitamin D deficiency etiology, prevalence, and possible pathophysiologic role in HF. Furthermore, we carefully review prospective trials on vitamin D therapy in HF. We believe more trials on vitamin D therapy in HF need to be conducted before any conclusions can be drawn.
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Affiliation(s)
- Megha Agarwal
- Cedars Sinai Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Anita Phan
- Cedars Sinai Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | | | | | - Ernst R. Schwarz
- Cedars Sinai Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA, The University of California Los Angeles, Los Angeles, CA, USA
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26
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Nowak A, Boesch L, Andres E, Battegay E, Hornemann T, Schmid C, Bischoff-Ferrari HA, Suter PM, Krayenbuehl PA. Effect of vitamin D3 on self-perceived fatigue: A double-blind randomized placebo-controlled trial. Medicine (Baltimore) 2016; 95:e5353. [PMID: 28033244 PMCID: PMC5207540 DOI: 10.1097/md.0000000000005353] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Vitamin D deficiency is frequent and has been associated with fatigue in uncontrolled trials. METHODS This is the first double-blind placebo-controlled clinical trial to investigate the efficacy of per os vitamin D3 (cholecalciferol) in treating fatigue among otherwise healthy persons with low serum 25-hydroxyvitamin D (25(OH)D) levels. We enrolled 120 individuals (mean age 29 ± 6 years, 53% women) presenting with fatigue and vitamin D deficiency (serum 25(OH)D < 20 μg/L). Participants were randomized to a single oral dose of 100,000 units of vitamin D or placebo. The primary endpoint was intra-individual change in the fatigue assessment scale (FAS) at 4 weeks after treatment. RESULT The mean age of the participants was 29 ± 6 years, 53% were women. Mean FAS decreased significantly more in the vitamin D group (-3.3 ± 5.3; 95% confidence interval [CI] for change -14.1 to 4.1) compared with placebo (-0.8 ± 5.3; 95% CI for change -9.0 to 8.7); (P = 0.01). Amelioration of fatigue was reported more frequently in vitamin D than in placebo group (42 [72%] vs. 31 [50%]; P = 0.01; odds ratio [OR] 2.63, 95% CI for OR 1.23-5.62). Among all participants, improvement in fatigue score correlated with the rise in 25(OH)D level (R = -0.22, P = 0.02). CONCLUSION Vitamin D treatment significantly improved fatigue in otherwise healthy persons with vitamin D deficiency.This study was registered at the www.ClinicalTrials.gov Protocol ID NCT02022475.
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Affiliation(s)
| | | | | | | | - Thorsten Hornemann
- Institute for Clinical Chemistry, University Hospital Zurich and University of Zurich
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27
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Limketkai BN, Mullin GE, Limsui D, Parian AM. Role of Vitamin D in Inflammatory Bowel Disease. Nutr Clin Pract 2016; 32:337-345. [PMID: 28537516 DOI: 10.1177/0884533616674492] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Vitamin D is a secosteroid hormone that possesses immunomodulatory properties and has been demonstrated to potentially influence inflammatory bowel disease (IBD) pathogenesis and activity. Epidemiologic data have associated vitamin D deficiency with an increased risk of IBD, hospitalizations, surgery, and loss of response to biologic therapy. Conversely, IBD itself can lead to vitamin D deficiency. This bidirectional relationship between vitamin D and IBD suggests the need for monitoring and repletion of vitamin D, as needed, in the IBD patient. This review discusses the role of vitamin D in IBD and provides practical guidance on vitamin D repletion.
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Affiliation(s)
- Berkeley N Limketkai
- 1 Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA.,2 Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Gerard E Mullin
- 2 Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - David Limsui
- 1 Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA
| | - Alyssa M Parian
- 2 Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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28
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Kearns MD, Alvarez JA, Tangpricha V. Large, single-dose, oral vitamin D supplementation in adult populations: a systematic review. Endocr Pract 2016; 20:341-51. [PMID: 24246341 DOI: 10.4158/ep13265.ra] [Citation(s) in RCA: 89] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVE Daily vitamin D supplementation is often inadequate in treating vitamin D deficiency due to poor compliance. A single, large dose of vitamin D given at timed intervals may be an alternative strategy. METHODS We conducted a systematic literature review to investigate the efficacy of a single large bolus dose to treat vitamin D deficiency. We identified 2,243 articles in PubMed using the terms "high dose vitamin D," "single dose vitamin D," "bolus vitamin D," or "annual dose vitamin D." Review articles, cross-sectional studies, non-human studies, responses to other articles, and non-English articles were excluded. Manuscripts were also excluded if the study: (1) did not use oral cholecalciferol or ergocalciferol, (2) used vitamin D analogs, (3) enrolled participants under age 18 years, (4) administered doses <100,000 international units (IU) (2.5 mg), or (5) administered >1 dose per year. References of eligible manuscripts and the Cochrane databases were also searched. Two independent reviewers identified eligible manuscripts, and a third reviewer evaluated disagreements. Thirty manuscripts were selected using these criteria. RESULTS Large, single doses of vitamin D consistently increased serum/plasma 25-hydroxyvitamin D (25[OH]D) concentrations in several vitamin D-sufficient and -deficient populations. Vitamin D3 doses ≥300,000 IU provided optimal changes in serum/plasma 25(OH)D and parathyroid hormone (PTH) concentrations. Vitamin D supplementation also impacted bone health and extraskeletal endpoints. CONCLUSION This review recommends that vitamin D3 be used for supplementation over vitamin D2 and concludes that single vitamin D3 doses ≥300,000 IU are most effective at improving vitamin D status and suppressing PTH concentrations for up to 3 months. Lower doses, however, may be sufficient in certain populations. Vitamin D doses >500,000 IU should be used judiciously in order to minimize adverse events.
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Affiliation(s)
- Malcolm D Kearns
- Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, Georgia
| | - Jessica A Alvarez
- Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, Georgia
| | - Vin Tangpricha
- Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, Georgia Atlanta Veterans Affairs Medical Center, Section of Endocrinology, Atlanta, Georgia
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Abou El Hassan M, Lin DCC, Earle T, Spencer M, Blasutig IM. Analytical evaluation of the BioPlex® 2200 25-OH vitamin D total assay. Clin Biochem 2016; 49:723-725. [PMID: 27112381 DOI: 10.1016/j.clinbiochem.2016.03.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2016] [Revised: 03/16/2016] [Accepted: 03/18/2016] [Indexed: 11/18/2022]
Abstract
BACKGROUND Testing for 25-hydroxyvitamin D (25(OH)D) has increased dramatically over the past decade and several automated immunoassays exist to measure serum 25(OH)D. Here we assess the performance of the recently released automated Bio-Rad BioPlex® 2200 25-OH vitamin D immunoassay, claimed to equally detect 25(OH)D2 and 25(OH)D3, and compare its results against a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method and the well-established DiaSorin LIAISON® 25-OH vitamin D total immunoassay. METHODS Imprecision was determined using third party controls over 20days. Linearity over the claimed measuring range was assessed using admixtures of a high and a low patient pool. Correlation between the BioPlex and LC-MS/MS (n=137) or the LIAISON (n=56) was assessed using patient samples with varying amounts of 25(OH)D3 and/or 25(OH)D2. RESULTS The total imprecision was 9.4%, 6.9% and 4.5% at concentrations of 39.4nmol/L, 70.6nmol/L and 242.8nmol/L, respectively. The assay was linear from 33.1-375.0nmol/L with a R(2) of 0.993. Method comparison revealed a strong correlation between the BioPlex assay and LC-MS/MS for samples containing 25(OH)D2 alone (n=5; R(2)=0.999), 25(OH)D3 alone (n=119; R(2)=0.935) and both (n=13; R(2)=0.919). In samples tested by all three methods (n=56), the correlation between the BioPlex and the LIAISON (R(2)=0.853) was poorer than that of the BioPlex and LC-MS/MS (R(2)=0.942). CONCLUSION The BioPlex assay is suitable for the measurement of total serum 25(OH)D. The strong correlation between the BioPlex assay and LC-MS/MS in detecting 25(OH)D2 and 25(OH)D3 provides evidence that the BioPlex assay is capable of the equivalent detection of both forms.
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Affiliation(s)
- Mohamed Abou El Hassan
- Department of Clinical Biochemistry, University Health Network, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Clinical Chemistry Division, Provincial Laboratory Services, Queen Elizabeth Hospital, Charlottetown, Prince Edward Island, Canada; Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada
| | - Dan C C Lin
- Department of Clinical Biochemistry, University Health Network, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
| | - Tammy Earle
- Department of Clinical Biochemistry, University Health Network, Toronto, ON, Canada
| | - Megan Spencer
- Department of Clinical Biochemistry, University Health Network, Toronto, ON, Canada
| | - Ivan M Blasutig
- Department of Clinical Biochemistry, University Health Network, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
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Performance evaluation of four 25-hydroxyvitamin D assays to measure 25-hydroxyvitamin D2. Clin Biochem 2015; 48:1097-104. [DOI: 10.1016/j.clinbiochem.2015.05.021] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Revised: 05/27/2015] [Accepted: 05/28/2015] [Indexed: 02/07/2023]
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Zhang YV, Stolla M, Kwong TC. Prevalence of 25-hydroxyvitamin D₂ in Western New York: a 3-year study. Clin Chim Acta 2015; 444:3-8. [PMID: 25659294 DOI: 10.1016/j.cca.2015.01.029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2014] [Revised: 01/06/2015] [Accepted: 01/22/2015] [Indexed: 10/24/2022]
Abstract
BACKGROUND We evaluated the distribution of 25OH-D2 and 25OH-D3 in a general patient population in Western New York to provide insights into how common detectable vitamin D2 is among samples from a general patient population. METHODS Serum 25OH-D2 and 25OH-D3 results measured by LC-MS/MS from June 2009 to December 2012 were retrospectively analyzed. RESULTS A total of 266,269 serum tests were included for analysis. The percentage of tests with 25OH-D2 levels above the assay limit of quantitation (LoQ) decreased from 32% to 17% over the course of the study period. The percentage of tests with 25OH-D2 levels higher than those of 25OH-D3 decreased from 21% to 12%. Sixty-seven percent of the test results with 25OH-D2 levels above the LoQ had serum concentrations of 25OH-D2 higher than those of 25OH-D3. CONCLUSION Prevalence of tests with quantifiable 25OH-D2 decreased over time and yet 17% of them still had detectable levels of 25OH-D2, 67% of which had 25OH-D2 levels higher than 25OH-D3. To achieve accurate 25-hydroxyvitamin D measurement, clinical laboratories should assess the accuracy of their assays, and if necessary, determine the local prevalence of 25OH-D2 to determine if mass spectrometry is the platform of choice to assess vitamin D deficiency.
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Affiliation(s)
- Yan Victoria Zhang
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Strong Memorial Hospital, Rochester, NY, United States.
| | - Moritz Stolla
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Strong Memorial Hospital, Rochester, NY, United States
| | - Tai C Kwong
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Strong Memorial Hospital, Rochester, NY, United States
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Vestergaard P. Effects of antiepileptic drugs on bone health and growth potential in children with epilepsy. Paediatr Drugs 2015; 17:141-50. [PMID: 25567416 DOI: 10.1007/s40272-014-0115-z] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
BACKGROUND Bone health may be impaired in children with epilepsy. OBJECTIVES Our objective was to characterize bone mineral density (BMD) and bone growth in children receiving antiepileptic drugs (AEDs) and to assess the effects of co-morbidity, vitamin D deficiency, and type of drugs used. DATA SOURCES Data were sourced from PubMed, Embase, and Web of Science. ELIGIBILITY CRITERIA Cross-sectional, cohort, case-control, or randomized controlled trials reporting BMD or parameters of bone growth. PARTICIPANTS Children with epilepsy compared with controls. INTERVENTIONS AEDS or ketogenic diet. STUDY APPRAISAL The studies were evaluated by one author. SYNTHESIS METHODS Studies were categorized as reporting reduced BMD or not at any skeletal site as outcome. A logistic regression was performed for age, percent boys, study design, type of AED, co-morbidity or not, and signs of vitamin D deficiency/osteomalacia or not. RESULTS Carbamazepine and valproate were analyzed as monotherapy in 11 studies, and for both drugs a limited decrease in BMD seemed present. For oxcarbazepine, levetiracetam, phenytoin, phenobarbital, and topiramate, only one study with monotherapy was found for each drug, none of which reported decreased bone density. Polytherapy with AEDs seemed to be associated with a larger decrease in bone density than was monotherapy. Although few studies were available on bone growth, these did indicate that bone growth may be impaired among users of AEDs. Ketogenic diet may be associated with decreased bone density. The main determinant of normal BMD was absence of vitamin D deficiency/osteomalacia. LIMITATIONS The studies differed in skeletal sites studied and most were cross-sectional. No head-to-head comparisons of AEDs were performed. Children treated with polytherapy or ketogenic diet may have more complicated and severe disease than those treated with monotherapy. The underlying cause of epilepsy and vitamin D deficiency may contribute to impaired bone growth and density. CONCLUSIONS Reduced bone density, impaired bone growth, and vitamin D deficiency may be seen in children treated with drugs against epilepsy. IMPLICATIONS Measures to correct vitamin D deficiency, calcium intake should be taken.
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Affiliation(s)
- Peter Vestergaard
- Departments of Clinical Medicine and Endocrinology, Aalborg University Hospital, Mølleparkvej 4, 9100, Aalborg, Denmark,
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Vitamin D3 seems more appropriate than D2 to sustain adequate levels of 25OHD: a pharmacokinetic approach. Eur J Clin Nutr 2015; 69:697-702. [PMID: 25782422 DOI: 10.1038/ejcn.2015.16] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2014] [Revised: 11/16/2014] [Accepted: 01/16/2015] [Indexed: 12/31/2022]
Abstract
BACKGROUND/OBJECTIVES The superiority of cholecalciferol (D3) over ergocalciferol (D2) in sustaining serum 25-hydroxy vitamin D (25OHD) levels is controversial. To compare D2 with D3 we performed a single-blind, placebo-controlled randomized trial spanning 11 weeks. SUBJECTS/METHODS Healthy volunteers (n=33, aged 33.4±6 years) were divided into three groups (n=11, each): D2, D3 and placebo. Treatment started with a loading dose (100,000 IU) followed by 4800 IU/day (d) between d7 and d20 and follow-up until d77. Serum samples were obtained at baseline and at days 3, 7, 14, 21, 35, 49, 63 and 77. RESULTS Baseline 25OHD values in the D2 group were lower than those in the D3 and placebo groups (P<0.01). Placebo 25OHD levels never changed. As after the loading dose both D2 and D3 groups had reached similar 25OHD levels, we tested equivalence of the area under the concentration × time curve (AUC) between d7 and d77. The AUC was 28.6% higher for D3 compared with D2, and both were higher with respect to placebo. At d77, D2 25OHD levels were higher than those at baseline, but similar to placebo; both were lower than D3 (P<0.04). According to raw data, the elimination half-life of 25OHD was 84 and 111 days under D2 and D3 supplementation, respectively; after subtracting the placebo values, the corresponding figures were 33 and 82 days. CONCLUSIONS D2 and D3 were equally effective in elevating 25OHD levels after a loading dose. In the long term, D3 seems more appropriate for sustaining 25OHD, which could be relevant for classic and non-classic effects of vitamin D.
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Abstract
This review summarises evidence for an association between vitamin D status and CVD and the mechanisms involved. Vitamin D3 is predominantly provided by the action of UVB from sunlight on skin. Average UK diets supply 2-3 μg/d vitamin D but diets containing at least one portion of oily fish per week supply about 7 μg/d. Pharmacological doses of vitamin D2 (bolus injection of 7500 μg or intakes >50 μg/d) result in a smaller increase in plasma 25(OH)D than those of D3 but physiological doses 5-25 μg/d seem equivalent. Plasma 25(OH)D concentrations are also influenced by clothing, obesity and skin pigmentation. Up to 40 % of the population have plasma 25(OH)D concentrations <25 nmol/l in the winter compared with <10 % in the summer. The relative risk of CVD death is 1·41 (95 % CI 1·18, 1·68) greater in the lowest quintile of plasma 25(OH)D according to meta-analysis of prospective cohort studies. Acute deficiency may inhibit insulin secretion and promote inflammation thus increasing the risk of plaque rupture and arterial thrombosis. Chronic insufficiency may increase arterial stiffness. There is no evidence to support claims of reduced CVD from existing trials with bone-related health outcomes where vitamin D was usually co-administered with calcium. Although several trials with cardiovascular endpoints are in progress, these are using pharmacological doses. In view of the potential toxicity of pharmacological doses, there remains a need for long-term trials of physiological doses of D2 and D3 with CVD incidence as the primary outcome.
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Hlavaty T, Krajcovicova A, Payer J. Vitamin D therapy in inflammatory bowel diseases: who, in what form, and how much? J Crohns Colitis 2015; 9:198-209. [PMID: 26046136 DOI: 10.1093/ecco-jcc/jju004] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND The north–south geographical gradient of inflammatory bowel disease (IBD) prevalence, its epidemiology, the genetic association of vitamin D receptor polymorphisms, and results in animal models suggest that vitamin D plays an important role in the pathogenesis of IBD. AIMS The purpose of this review was to critically appraise the effectiveness and safety of vitamin D therapy in patients with IBD. METHODS MEDLINE, Scopus and Google Scholar were searched from inception to May 20, 2014 using the terms ‘Crohn’s disease’, ‘ulcerative colitis’ and ‘vitamin D’. Results: Vitamin D deficiency is common in patients with IBD. Limited clinical data suggest an association between low vitamin D concentration and increased disease activity in both ulcerative colitis (UC) and Crohn’s disease (CD). To date, only two small open label trials and one randomized controlled trial have shown a positive effect of vitamin D supplementation on disease activity in patients with CD; no effect has been shown for UC. An optimal vitamin D supplementation protocol for patients with IBD remains undetermined, but targeting serum 25-hydroxy vitamin D [25(OH)D] levels between 30 and 50 ng/mL appears safe and may have benefits for IBD disease activity. Depending on baseline vitamin D serum concentration, ileal involvement in CD, body mass index, and perhaps smoking status, daily vitamin D doses between 1800–10,000 international units/day are probably necessary. CONCLUSION Increasing preclinical and clinical evidence suggests a role for vitamin D deficiency in the development and severity of IBD. The possible therapeutic role of vitamin D in patients with IBD merits continued investigation.
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Hoffmann MR, Senior PA, Mager DR. Vitamin D supplementation and health-related quality of life: a systematic review of the literature. J Acad Nutr Diet 2015; 115:406-418. [PMID: 25573654 DOI: 10.1016/j.jand.2014.10.023] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2014] [Accepted: 10/16/2014] [Indexed: 01/10/2023]
Abstract
Vitamin D deficiency and insufficiency are highly prevalent worldwide and thought to potentiate a variety of chronic disease states, including diabetes, cancer, and depression. Routine vitamin D supplementation is often needed to meet vitamin D requirements. Little is known regarding the effect of vitamin D supplementation on quality of life. The purpose of this article was to systematically review the literature regarding quality-of-life outcomes from vitamin D supplementation in healthy and clinical populations. Clinical trials of vitamin D supplementation, where quality-of-life outcomes were reported, were selected from Medline and Web of Science databases. Inclusion criteria were English language articles available online (published between 1950 and May 2014), primary research articles, studies conducted on human beings, and treatment/supplementation with vitamin D. Articles were excluded if they involved topical vitamin D application or implicit cotreatment with other vitamins (eg, multivitamins). Articles selected for review were examined for process and methodologic quality using validated methodologies. A total of 15 articles met the inclusion criteria for review. Interventions were highly variable in terms of study population (eg, healthy/diseased, children/elderly, and baseline vitamin D status) vitamin D dose, and duration of follow-up. Vitamin D supplementation ranged from 400 IU/day for an average of 7.1 years, to a single 300, 000 IU dose. The main tools used to capture quality of life were adaptations of validated, questionnaires (Medical Outcomes Study Short Form 36-item questionnaire and EuroQOL five dimension questionnaire). Vitamin D supplementation was not associated with significant changes in quality of life. Studies that reported changes in quality of life as a result of vitamin D supplementation were in clinical populations on short-term vitamin D. Most articles reviewed displayed poor methodologic quality (eg, no randomization/blinding, dropout description, or vitamin D assessment). Current evidence indicates that vitamin D supplementation may have a small to moderate effect on quality of life when used on a short-term basis in diseased populations. However, the evidence for a beneficial effect of long-term vitamin D supplementation on health-related quality of life is lacking.
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McNally JD, Iliriani K, Pojsupap S, Sampson M, O'Hearn K, McIntyre L, Fergusson D, Menon K. Rapid normalization of vitamin D levels: a meta-analysis. Pediatrics 2015; 135:e152-66. [PMID: 25511115 DOI: 10.1542/peds.2014-1703] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Vitamin D deficiency may represent a modifiable risk factor to improve outcome in severe illness. The efficacy of high-dose regimens in rapid normalization of vitamin D levels is uncertain. METHODS We conducted a systematic review of pediatric clinical trials administering high-dose vitamin D to evaluate 25-hydroxyvitamin D (25[OH]D) response and characteristics associated with final 25(OH)D levels by using Medline, Embase, and the Cochrane Central Register of Controlled Trials, including reference lists of systematic reviews and eligible publications. Uncontrolled and controlled trials reporting 25(OH)D levels after high-dose (≥1000 IU) ergocalciferol or cholecalciferol were selected. Two reviewers independently extracted and verified predefined data fields. RESULTS We identified 88 eligible full-text articles. Two of 6 studies that administered daily doses approximating the Institute of Medicine's Tolerable Upper Intake Level (1000-4000 IU) to vitamin D-deficient populations achieved group 25(OH)D levels >75 nmol/L within 1 month. Nine of 10 studies evaluating loading therapy (>50 000 IU) achieved group 25(OH)D levels >75 nmol/L. In meta-regression, baseline 25(OH)D, regimen type, dose, age, and time factors were associated with final 25(OH)D levels. Adverse event analysis identified increased hypercalcemia risk with doses >400 000 IU, but no increased hypercalcemia or hypercalciuria with loading doses <400 000 IU (or 10 000 IU/kg). Few studies in adolescents evaluated loading dose regimens >300 000 IU. CONCLUSIONS Rapid normalization of vitamin D levels is best achieved by using loading therapy that considers disease status, baseline 25(OH)D, and age (or weight). Loading doses >300 000 IU should be avoided until trials are conducted to better evaluate risk and benefit.
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Affiliation(s)
- J Dayre McNally
- Department of Pediatrics, Faculty of Medicine, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Research Institute, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada;
| | - Klevis Iliriani
- Research Institute, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; School of Medicine, Trinity College, Dublin, Ireland
| | - Supichaya Pojsupap
- Department of Pediatrics, Faculty of Medicine, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Division of Critical Care, Department of Pediatrics, Phramonghutklao Hospital, Bangkok, Thailand; and
| | - Margaret Sampson
- Department of Pediatrics, Faculty of Medicine, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
| | - Katie O'Hearn
- Department of Pediatrics, Faculty of Medicine, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Research Institute, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
| | | | - Dean Fergusson
- Department of Epidemiology and Community Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada
| | - Kusum Menon
- Department of Pediatrics, Faculty of Medicine, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Research Institute, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
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Krajcovicova A, Hlavaty T, Killinger Z, Miznerova E, Toth J, Letkovsky J, Nevidanska M, Cierny D, Koller T, Zelinkova Z, Huorka M, Payer J. Combination therapy with an immunomodulator and anti-TNFα agent improves bone mineral density in IBD patients. J Crohns Colitis 2014; 8:1693-1701. [PMID: 25175812 DOI: 10.1016/j.crohns.2014.08.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2014] [Revised: 08/06/2014] [Accepted: 08/08/2014] [Indexed: 02/08/2023]
Abstract
OBJECTIVE There is a high prevalence of low bone mineral density (BMD) among patients with inflammatory bowel disease (IBD) although there is a lack of clinical data on the impact of IBD specific medications and recommended vitamin D (VD) and calcium (Ca) supplements on it. DESIGN The cohort consisted of 150 IBD patients. The average change in BMD at the lumbar spine per year (∆BMDL/year) was calculated and the impact of clinical characteristics, medications and VD and Ca supplements was analysed. RESULTS The prevalence of osteopenia was 69/150 (46%) and osteoporosis was identified in 15/150 (10%) patients at baseline. The presence of osteoporosis was associated with the disease duration OR=1.07 per year of disease duration (95% CI=1.01-1.14), p=0.03. The average ∆BMDL/year was 0.010 g/cm(2)/year. Among patients with no IS the ∆BMDL/year was -0.001±0.010 g/cm(2)/year, with AZA -0.001±0.013 g/cm(2)/year, with anti-TNFα 0.003±0.006 g/cm(2)/year and with COMBO 0.027±0.004 g/cm(2)/year; p<0.05 COMBO vs any other subgroup. ∆BMDL/year among patients treated with CS was -0.031±0.012 g/cm(2)/year versus CS free patients 0.013±0.004 g/cm(2)/year; p<0.001. There was no effect of VD/Ca supplementation on BMDL. CONCLUSIONS The prevalence of low BMD was 55%. Duration of disease was the only independent predictor of low BMD. The BMDL was reduced by high cumulative dose of CS and improved by combined anti-TNFα/AZA therapy. The supplementation with recommended doses of VD and Ca had no effect on BMDL.
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Affiliation(s)
- Anna Krajcovicova
- Gastroenterology and Hepatology Unit, University Hospital Bratislava, Slovakia.
| | - Tibor Hlavaty
- Gastroenterology and Hepatology Unit, University Hospital Bratislava, Slovakia
| | | | - Ema Miznerova
- Gastroenterology and Hepatology Unit, University Hospital Bratislava, Slovakia
| | - Jozef Toth
- Gastroenterology and Hepatology Unit, University Hospital Bratislava, Slovakia
| | - Juraj Letkovsky
- Gastroenterology and Hepatology Unit, University Hospital Bratislava, Slovakia
| | - Monika Nevidanska
- Gastroenterology and Hepatology Unit, University Hospital Bratislava, Slovakia
| | - Daniel Cierny
- Osteocenter, University Hospital Bratislava, Slovakia
| | - Tomas Koller
- Gastroenterology and Hepatology Unit, University Hospital Bratislava, Slovakia
| | - Zuzana Zelinkova
- Gastroenterology and Hepatology Unit, University Hospital Bratislava, Slovakia
| | - Martin Huorka
- Gastroenterology and Hepatology Unit, University Hospital Bratislava, Slovakia
| | - Juraj Payer
- Osteocenter, University Hospital Bratislava, Slovakia
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Kearns MD, Binongo JNG, Watson D, Alvarez JA, Lodin D, Ziegler TR, Tangpricha V. The effect of a single, large bolus of vitamin D in healthy adults over the winter and following year: a randomized, double-blind, placebo-controlled trial. Eur J Clin Nutr 2014; 69:193-7. [PMID: 25271011 PMCID: PMC4318716 DOI: 10.1038/ejcn.2014.209] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2014] [Accepted: 08/22/2014] [Indexed: 12/18/2022]
Abstract
BACKGROUND/OBJECTIVES Although single, high doses of vitamin D effectively maintain vitamin D sufficiency in several populations, no studies have evaluated healthy adults over winter, during which vitamin D status declines. This study investigated whether high-dose vitamin D3 given once to healthy adults before winter will (1) prevent the wintertime decline in vitamin D status, (2) promote vitamin D sufficiency 1 year following the dose and (3) prevent the rise of parathyroid hormone (PTH) concentrations. SUBJECTS/METHODS In this double-blind, placebo-controlled trial, we assessed plasma 25(OH)D and PTH concentrations at baseline, 5, 90 and 365 days after drug administration in 28 healthy adults. In all, >80% of subjects returned at each time point. RESULTS At baseline, the young, healthy participants had a mean plasma 25(OH)D concentration of 17.5±6.1 ng/ml. Only two subjects exhibited plasma 25(OH)D concentrations >30 ng/ml. At 5 days, subjects randomized to vitamin D3 had a higher mean plasma 25(OH)D concentration compared with the placebo group (39.1 vs 19.1 ng/ml, P<0.001). Plasma 25(OH)D concentrations returned to baseline at 90 and 365 days in the vitamin D3 group and remained unchanged in the placebo group. PTH and calcium concentrations were unrelated to changes in 25(OH)D levels and similar between groups over time. CONCLUSIONS A dose of 250,000 IU of vitamin D3 given once in November resulted in a robust increase in plasma 25(OH)D after 5 days, but it was unable to sustain this increase after 90 days. A larger or more frequent dosing regimen may be needed for long-term vitamin D sufficiency.
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Affiliation(s)
- M D Kearns
- Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA, USA
| | - J N G Binongo
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, GA, USA
| | - D Watson
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, GA, USA
| | - J A Alvarez
- Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA, USA
| | - D Lodin
- Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA, USA
| | - T R Ziegler
- Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA, USA
| | - V Tangpricha
- 1] Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA, USA [2] Atlanta Veterans Affairs Medical Center, Section of Endocrinology, Atlanta, GA, USA
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Traub ML, Finnell JS, Bhandiwad A, Oberg E, Suhaila L, Bradley R. Impact of vitamin D3 dietary supplement matrix on clinical response. J Clin Endocrinol Metab 2014; 99:2720-8. [PMID: 24684456 PMCID: PMC4121030 DOI: 10.1210/jc.2013-3162] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
CONTEXT As a result of research suggesting increased health risk with low serum 25-hydroxycholecalciferol (25(OH)D), health care providers are measuring it frequently. Providers and patients are faced with treatment choices when low status is identified. OBJECTIVE To compare the safety and efficacy of three vitamin D3 dietary supplements with different delivery matrices. SETTING AND DESIGN A 12-week, parallel group, single-masked, clinical trial was conducted in Seattle, Washington and Kailua Kona, Hawaii. Sixty-six healthy adults with (25(OH)D) <33 ng/mL were randomly assigned to take one of three D3 supplements, ie, a chewable tablet (TAB), an oil-emulsified drop (DROP), or an encapsulated powder (CAP) at a label-claimed dose of 10,000 IU/day. Actual D3 content was assessed by a third party and the results adjusted based on the actual D3 content administered. Mean change in 25(OH)D/mcg D3 administered; difference in the proportion of D3 insufficient participants (ie, 25(OH)D ≤30 ng/mL) reaching sufficiency (ie, 25(OH)D ≥30 ng/mL); and mean change in serum 1, 25-dihydroxycholecalciferol were measured. RESULTS In two of the three products tested, the measured vitamin D3 content varied considerably from the label-claimed dose. Differences in 25(OH)D/mcg D3 administered were significantly different between groups (P = .04; n = 55). Pairwise comparisons demonstrated DROP resulted in a greater increase than TAB (P < .05) but not than CAP. TAB was not different from CAP. The proportions reaching sufficiency were: 100% (TAB and CAP) and 80% (DROP) (P = .03 between groups; n = 55). 1, 25-Dihydroxycholecalciferol did not change significantly in any group. CONCLUSIONS Oil-emulsified vitamin D3 supplements resulted in a greater mean change in serum 25(OH)D concentration, but fewer patients reaching vitamin D sufficiency, than chewable or encapsulated supplements.
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Affiliation(s)
- Michael L Traub
- Lokahi Health Center (M.L.T.), Kailua Kona, Hawaii 96740; AOMA Graduate School of Integrative Medicine, (J.S.F.) Austin, Texas 78745; Wayne State University (A.B.), Detroit, Michigan 48202; Pacific Pearl Center for Health and Healing (E.O.), La Jolla, California 92037; Cancer Treatment Centers of America Western Regional Medical Center (L.S.), Phoenix, Arizona 85338; and Bastyr University Research Institute (R.B.), San Diego, California 98028
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Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Krstic G, Wetterslev J, Gluud C, Cochrane Metabolic and Endocrine Disorders Group. Vitamin D supplementation for prevention of cancer in adults. Cochrane Database Syst Rev 2014; 2014:CD007469. [PMID: 24953955 PMCID: PMC11285304 DOI: 10.1002/14651858.cd007469.pub2] [Citation(s) in RCA: 91] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND The evidence on whether vitamin D supplementation is effective in decreasing cancers is contradictory. OBJECTIVES To assess the beneficial and harmful effects of vitamin D supplementation for prevention of cancer in adults. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, Science Citation Index Expanded, and the Conference Proceedings Citation Index-Science to February 2014. We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials. SELECTION CRITERIA We included randomised trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention in adults who were healthy or were recruited among the general population, or diagnosed with a specific disease. Vitamin D could have been administered as supplemental vitamin D (vitamin D₃ (cholecalciferol) or vitamin D₂ (ergocalciferol)), or an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol), or 1,25-dihydroxyvitamin D (calcitriol)). DATA COLLECTION AND ANALYSIS Two review authors extracted data independently. We conducted random-effects and fixed-effect model meta-analyses. For dichotomous outcomes, we calculated the risk ratios (RRs). We considered risk of bias in order to assess the risk of systematic errors. We conducted trial sequential analyses to assess the risk of random errors. MAIN RESULTS Eighteen randomised trials with 50,623 participants provided data for the analyses. All trials came from high-income countries. Most of the trials had a high risk of bias, mainly for-profit bias. Most trials included elderly community-dwelling women (aged 47 to 97 years). Vitamin D was administered for a weighted mean of six years. Fourteen trials tested vitamin D₃, one trial tested vitamin D₂, and three trials tested calcitriol supplementation. Cancer occurrence was observed in 1927/25,275 (7.6%) recipients of vitamin D versus 1943/25,348 (7.7%) recipients of control interventions (RR 1.00 (95% confidence interval (CI) 0.94 to 1.06); P = 0.88; I² = 0%; 18 trials; 50,623 participants; moderate quality evidence according to the GRADE instrument). Trial sequential analysis (TSA) of the 18 vitamin D trials shows that the futility area is reached after the 10th trial, allowing us to conclude that a possible intervention effect, if any, is lower than a 5% relative risk reduction. We did not observe substantial differences in the effect of vitamin D on cancer in subgroup analyses of trials at low risk of bias compared to trials at high risk of bias; of trials with no risk of for-profit bias compared to trials with risk of for-profit bias; of trials assessing primary prevention compared to trials assessing secondary prevention; of trials including participants with vitamin D levels below 20 ng/mL at entry compared to trials including participants with vitamin D levels of 20 ng/mL or more at entry; or of trials using concomitant calcium supplementation compared to trials without calcium. Vitamin D decreased all-cause mortality (1854/24,846 (7.5%) versus 2007/25,020 (8.0%); RR 0.93 (95% CI 0.88 to 0.98); P = 0.009; I² = 0%; 15 trials; 49,866 participants; moderate quality evidence), but TSA indicates that this finding could be due to random errors. Cancer occurrence was observed in 1918/24,908 (7.7%) recipients of vitamin D₃ versus 1933/24,983 (7.7%) in recipients of control interventions (RR 1.00 (95% CI 0.94 to 1.06); P = 0.88; I² = 0%; 14 trials; 49,891 participants; moderate quality evidence). TSA of the vitamin D₃ trials shows that the futility area is reached after the 10th trial, allowing us to conclude that a possible intervention effect, if any, is lower than a 5% relative risk reduction. Vitamin D₃ decreased cancer mortality (558/22,286 (2.5%) versus 634/22,206 (2.8%); RR 0.88 (95% CI 0.78 to 0.98); P = 0.02; I² = 0%; 4 trials; 44,492 participants; low quality evidence), but TSA indicates that this finding could be due to random errors. Vitamin D₃ combined with calcium increased nephrolithiasis (RR 1.17 (95% CI 1.03 to 1.34); P = 0.02; I² = 0%; 3 trials; 42,753 participants; moderate quality evidence). TSA, however, indicates that this finding could be due to random errors. We did not find any data on health-related quality of life or health economics in the randomised trials included in this review. AUTHORS' CONCLUSIONS There is currently no firm evidence that vitamin D supplementation decreases or increases cancer occurrence in predominantly elderly community-dwelling women. Vitamin D₃ supplementation decreased cancer mortality and vitamin D supplementation decreased all-cause mortality, but these estimates are at risk of type I errors due to the fact that too few participants were examined, and to risks of attrition bias originating from substantial dropout of participants. Combined vitamin D₃ and calcium supplements increased nephrolithiasis, whereas it remains unclear from the included trials whether vitamin D₃, calcium, or both were responsible for this effect. We need more trials on vitamin D supplementation, assessing the benefits and harms among younger participants, men, and people with low vitamin D status, and assessing longer duration of treatments as well as higher dosages of vitamin D. Follow-up of all participants is necessary to reduce attrition bias.
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Affiliation(s)
- Goran Bjelakovic
- Medical Faculty, University of NisDepartment of Internal MedicineZorana Djindjica 81NisSerbia18000
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University HospitalThe Cochrane Hepato‐Biliary GroupBlegdamsvej 9CopenhagenDenmarkDK‐2100
| | - Lise Lotte Gluud
- Copenhagen University Hospital HvidovreGastrounit, Medical DivisionKettegaards AlleHvidovreDenmark2650
| | - Dimitrinka Nikolova
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University HospitalThe Cochrane Hepato‐Biliary GroupBlegdamsvej 9CopenhagenDenmarkDK‐2100
| | - Kate Whitfield
- Rigshospitalet, Copenhagen University HospitalCopenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812CopenhagenDenmark
| | - Goran Krstic
- Environmental Health ServicesFraser Health Authority#218 ‐ 610 Sixth StreetNew WestminsterBCCanadaV3L 3C2
| | - Jørn Wetterslev
- Rigshospitalet, Copenhagen University HospitalCopenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812CopenhagenDenmark
| | - Christian Gluud
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University HospitalThe Cochrane Hepato‐Biliary GroupBlegdamsvej 9CopenhagenDenmarkDK‐2100
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Sansanayudh N, Wongwiwatthananukit S, Phetkrajaysang N, Krittiyanunt S. Comparative efficacy and safety of different doses of ergocalciferol supplementation in patients with metabolic syndrome. Int J Clin Pharm 2014; 36:771-8. [PMID: 24853094 DOI: 10.1007/s11096-014-9958-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2013] [Accepted: 05/09/2014] [Indexed: 11/26/2022]
Abstract
BACKGROUND Vitamin D deficiency is a common problem worldwide. Several studies have shown an association between vitamin D deficiency and the increased risk of metabolic syndrome. No previous study has compared the efficacy and safety of ergocalciferol at 40,000 versus 20,000 IU/week in patients with metabolic syndrome. OBJECTIVE To evaluate the efficacy of ergocalciferol supplementation on serum 25-hydroxyvitamin D [25(OH)D] concentrations and to examine safety parameters in metabolic syndrome patients. SETTING Outpatient department of Phramongkutklao Hospital, Bangkok, Thailand. METHOD A randomized, double-blinded, parallel study was conducted in metabolic syndrome patients with vitamin D deficiency [25(OH)D <20 ng/mL]. Ninety patients were randomly assigned into three groups of 30 patients each. Group 1 was given two capsules of placebo/week, group 2 was given ergocalciferol 20,000 IU/week, and group 3 was given ergocalciferol 40,000 IU/week for 8 weeks. MAIN OUTCOME MEASURE serum 25(OH)D concentrations, serum calcium, safety, and corrected QT (QTc) interval. RESULTS Of the 90 patients enrolled, 84 patients completed the study. At the end of the study, the mean serum 25(OH)D in groups 2 and 3 significantly increased from the baseline (15.1 and 14.3 to 26.8 and 30.0 ng/mL, respectively). The increase in serum 25(OH)D in groups 2 and 3 were comparable and significantly greater than that of the placebo group. The percentage number of patients achieving normal vitamin D levels in groups 1, 2 and 3 were 3.3, 33.3, and 60.0 %, respectively, which were significantly different between groups (p < 0.001). Adverse reactions in both ergocalciferol treatment groups were not different from the placebo group (p > 0.05). Serum calcium levels did not change within and between groups of treatment. No significant change in QTc was observed in any patient. CONCLUSIONS Both 20,000 and 40,000 IU/week of ergocalciferol supplementation for 8 weeks were able to increase serum 25(OH)D concentrations significantly. However, more patients in the ergocalciferol 40,000 IU/week treatment group achieved a normal serum 25(OH)D level than in the group which received 20,000 IU/week. Clinicians would have informed of choosing the dosing regimen of ergocalciferol in metabolic syndrome patients.
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Affiliation(s)
- Nakarin Sansanayudh
- Department of Internal Medicine, Phramongkutklao Hospital, Bangkok, Thailand
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Impact of vitamin D supplementation on arterial vasomotion, stiffness and endothelial biomarkers in chronic kidney disease patients. PLoS One 2014; 9:e91363. [PMID: 24646518 PMCID: PMC3960127 DOI: 10.1371/journal.pone.0091363] [Citation(s) in RCA: 81] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2013] [Accepted: 02/06/2014] [Indexed: 01/03/2023] Open
Abstract
Background Cardiovascular events are frequent and vascular endothelial function is abnormal in patients with chronic kidney disease (CKD). We demonstrated endothelial dysfunction with vitamin D deficiency in CKD patients; however the impact of cholecalciferol supplementation on vascular stiffness and vasomotor function, endothelial and bone biomarkers in CKD patients with low 25-hydroxy vitamin D [25(OH)D] is unknown, which this study investigated. Methods We assessed non-diabetic patients with CKD stage 3/4, age 17–80 years and serum 25(OH)D <75 nmol/L. Brachial artery Flow Mediated Dilation (FMD), Pulse Wave Velocity (PWV), Augmentation Index (AI) and circulating blood biomarkers were evaluated at baseline and at 16 weeks. Oral 300,000 units cholecalciferol was administered at baseline and 8-weeks. Results Clinical characteristics of 26 patients were: age 50±14 (mean±1SD) years, eGFR 41±11 ml/min/1.73 m2, males 73%, dyslipidaemia 36%, smokers 23% and hypertensives 87%. At 16-week serum 25(OH)D and calcium increased (43±16 to 84±29 nmol/L, p<0.001 and 2.37±0.09 to 2.42±0.09 mmol/L; p = 0.004, respectively) and parathyroid hormone decreased (10.8±8.6 to 7.4±4.4; p = 0.001). FMD improved from 3.1±3.3% to 6.1±3.7%, p = 0.001. Endothelial biomarker concentrations decreased: E-Selectin from 5666±2123 to 5256±2058 pg/mL; p = 0.032, ICAM-1, 3.45±0.01 to 3.10±1.04 ng/mL; p = 0.038 and VCAM-1, 54±33 to 42±33 ng/mL; p = 0.006. eGFR, BP, PWV, AI, hsCRP, von Willebrand factor and Fibroblast Growth Factor-23, remained unchanged. Conclusion This study demonstrates for the first time improvement of endothelial vasomotor and secretory functions with vitamin D in CKD patients without significant adverse effects on arterial stiffness, serum calcium or FGF-23. Trial Registration ClinicalTrials.gov NCT02005718
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Oral postdialysis cholecalciferol supplementation in patients on maintenance hemodialysis: a dose-response approach. Int J Nephrol 2014; 2014:597429. [PMID: 24579049 PMCID: PMC3918706 DOI: 10.1155/2014/597429] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2013] [Accepted: 11/02/2013] [Indexed: 12/19/2022] Open
Abstract
The aim of the present study was to evaluate the dose of postdialysis cholecalciferol needed to maintain the 25-hydroxyvitamin D [25(OH)D] levels in the optimal range of 75–150 nmol/L. Twenty-six patients who had low baseline 25(OH)D levels (mean 27.5 ± 14.9 nmol/L) were studied. The 25(OH)D levels were measured every 2 months for one year. During the first two months, all the patients received 2000 IU of cholecalciferol after each hemodialysis (=6000 IU/wk). Thereafter, the dose was individualized and adapted every 2 months by administering 1 to 6 cholecalciferol tablets (2000 IU each) per week (total weekly dose = 2000–12000 IU/wk). During cholecalciferol supplementation, the 25(OH)D concentrations rapidly increased from baseline to 140.1 ± 28.3 nmol/L at month 6 and 95.6 ± 20.9 nmol/L at month 12. At month twelve, 86% of the patients had 25(OH)D levels within the target range with a mean dose of 5917 ± 4106 IU/wk of cholecalciferol; however, the amount needed to maintain these levels varied widely from 0 (n = 2) to 12000 IU/wk (n = 5). In conclusion, postdialysis cholecalciferol prescription is quite effective in correcting vitamin D deficiency/insufficiency, but the amount of cholecalciferol needed to maintain the 25(OH)D levels within the optimal range over the long-term varies widely among patients and must be individualized.
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Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Wetterslev J, Simonetti RG, Bjelakovic M, Gluud C, Cochrane Metabolic and Endocrine Disorders Group. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev 2014; 2014:CD007470. [PMID: 24414552 PMCID: PMC11285307 DOI: 10.1002/14651858.cd007470.pub3] [Citation(s) in RCA: 217] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Available evidence on the effects of vitamin D on mortality has been inconclusive. In a recent systematic review, we found evidence that vitamin D3 may decrease mortality in mostly elderly women. The present systematic review updates and reassesses the benefits and harms of vitamin D supplementation used in primary and secondary prophylaxis of mortality. OBJECTIVES To assess the beneficial and harmful effects of vitamin D supplementation for prevention of mortality in healthy adults and adults in a stable phase of disease. SEARCH METHODS We searched The Cochrane Library, MEDLINE, EMBASE, LILACS, the Science Citation Index-Expanded and Conference Proceedings Citation Index-Science (all up to February 2012). We checked references of included trials and pharmaceutical companies for unidentified relevant trials. SELECTION CRITERIA Randomised trials that compared any type of vitamin D in any dose with any duration and route of administration versus placebo or no intervention in adult participants. Participants could have been recruited from the general population or from patients diagnosed with a disease in a stable phase. Vitamin D could have been administered as supplemental vitamin D (vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol)) or as an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol) or 1,25-dihydroxyvitamin D (calcitriol)). DATA COLLECTION AND ANALYSIS Six review authors extracted data independently. Random-effects and fixed-effect meta-analyses were conducted. For dichotomous outcomes, we calculated the risk ratios (RRs). To account for trials with zero events, we performed meta-analyses of dichotomous data using risk differences (RDs) and empirical continuity corrections. We used published data and data obtained by contacting trial authors.To minimise the risk of systematic error, we assessed the risk of bias of the included trials. Trial sequential analyses controlled the risk of random errors possibly caused by cumulative meta-analyses. MAIN RESULTS We identified 159 randomised clinical trials. Ninety-four trials reported no mortality, and nine trials reported mortality but did not report in which intervention group the mortality occurred. Accordingly, 56 randomised trials with 95,286 participants provided usable data on mortality. The age of participants ranged from 18 to 107 years. Most trials included women older than 70 years. The mean proportion of women was 77%. Forty-eight of the trials randomly assigned 94,491 healthy participants. Of these, four trials included healthy volunteers, nine trials included postmenopausal women and 35 trials included older people living on their own or in institutional care. The remaining eight trials randomly assigned 795 participants with neurological, cardiovascular, respiratory or rheumatoid diseases. Vitamin D was administered for a weighted mean of 4.4 years. More than half of the trials had a low risk of bias. All trials were conducted in high-income countries. Forty-five trials (80%) reported the baseline vitamin D status of participants based on serum 25-hydroxyvitamin D levels. Participants in 19 trials had vitamin D adequacy (at or above 20 ng/mL). Participants in the remaining 26 trials had vitamin D insufficiency (less than 20 ng/mL).Vitamin D decreased mortality in all 56 trials analysed together (5,920/47,472 (12.5%) vs 6,077/47,814 (12.7%); RR 0.97 (95% confidence interval (CI) 0.94 to 0.99); P = 0.02; I(2) = 0%). More than 8% of participants dropped out. 'Worst-best case' and 'best-worst case' scenario analyses demonstrated that vitamin D could be associated with a dramatic increase or decrease in mortality. When different forms of vitamin D were assessed in separate analyses, only vitamin D3 decreased mortality (4,153/37,817 (11.0%) vs 4,340/38,110 (11.4%); RR 0.94 (95% CI 0.91 to 0.98); P = 0.002; I(2) = 0%; 75,927 participants; 38 trials). Vitamin D2, alfacalcidol and calcitriol did not significantly affect mortality. A subgroup analysis of trials at high risk of bias suggested that vitamin D2 may even increase mortality, but this finding could be due to random errors. Trial sequential analysis supported our finding regarding vitamin D3, with the cumulative Z-score breaking the trial sequential monitoring boundary for benefit, corresponding to 150 people treated over five years to prevent one additional death. We did not observe any statistically significant differences in the effect of vitamin D on mortality in subgroup analyses of trials at low risk of bias compared with trials at high risk of bias; of trials using placebo compared with trials using no intervention in the control group; of trials with no risk of industry bias compared with trials with risk of industry bias; of trials assessing primary prevention compared with trials assessing secondary prevention; of trials including participants with vitamin D level below 20 ng/mL at entry compared with trials including participants with vitamin D levels equal to or greater than 20 ng/mL at entry; of trials including ambulatory participants compared with trials including institutionalised participants; of trials using concomitant calcium supplementation compared with trials without calcium; of trials using a dose below 800 IU per day compared with trials using doses above 800 IU per day; and of trials including only women compared with trials including both sexes or only men. Vitamin D3 statistically significantly decreased cancer mortality (RR 0.88 (95% CI 0.78 to 0.98); P = 0.02; I(2) = 0%; 44,492 participants; 4 trials). Vitamin D3 combined with calcium increased the risk of nephrolithiasis (RR 1.17 (95% CI 1.02 to 1.34); P = 0.02; I(2) = 0%; 42,876 participants; 4 trials). Alfacalcidol and calcitriol increased the risk of hypercalcaemia (RR 3.18 (95% CI 1.17 to 8.68); P = 0.02; I(2) = 17%; 710 participants; 3 trials). AUTHORS' CONCLUSIONS Vitamin D3 seemed to decrease mortality in elderly people living independently or in institutional care. Vitamin D2, alfacalcidol and calcitriol had no statistically significant beneficial effects on mortality. Vitamin D3 combined with calcium increased nephrolithiasis. Both alfacalcidol and calcitriol increased hypercalcaemia. Because of risks of attrition bias originating from substantial dropout of participants and of outcome reporting bias due to a number of trials not reporting on mortality, as well as a number of other weaknesses in our evidence, further placebo-controlled randomised trials seem warranted.
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Affiliation(s)
- Goran Bjelakovic
- Medical Faculty, University of NisDepartment of Internal MedicineZorana Djindjica 81NisSerbia18000
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University HospitalThe Cochrane Hepato‐Biliary GroupBlegdamsvej 9CopenhagenDenmarkDK‐2100
| | - Lise Lotte Gluud
- Copenhagen University Hospital HvidovreGastrounit, Medical DivisionKettegaards AlleHvidovreDenmark
| | - Dimitrinka Nikolova
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University HospitalThe Cochrane Hepato‐Biliary GroupBlegdamsvej 9CopenhagenDenmarkDK‐2100
| | - Kate Whitfield
- Rigshospitalet, Copenhagen University HospitalCopenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812CopenhagenDenmark
| | - Jørn Wetterslev
- Rigshospitalet, Copenhagen University HospitalCopenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812CopenhagenDenmark
| | - Rosa G Simonetti
- Ospedali Riuniti Villa Sofia‐CervelloU.O. di Medicina 2Via Trabucco 180PalermoItalyI‐90146
| | - Marija Bjelakovic
- Medical Faculty, University of NisInstitute of AnatomyBoulevard Dr Zorana Djindjica 81NisSerbia18000
| | - Christian Gluud
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University HospitalThe Cochrane Hepato‐Biliary GroupBlegdamsvej 9CopenhagenDenmarkDK‐2100
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Menon RK, Rickard AP, Mannan N, Timms PM, Sharp SJ, Martineau A, Boucher BJ, Chowdhury TA, Griffiths CJ, Griffin SJ, Hitman GA, Forouhi NG. The effects of vitamin D₂ or D₃ supplementation on glycaemic control and related metabolic parameters in people at risk of type 2 diabetes: protocol of a randomised double-blind placebo-controlled trial. BMC Public Health 2013; 13:999. [PMID: 24152375 PMCID: PMC3819003 DOI: 10.1186/1471-2458-13-999] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2012] [Accepted: 10/14/2013] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND The global prevalence of type 2 diabetes is increasing. Effective strategies to address this public health challenge are currently lacking. A number of epidemiological studies have reported associations between low concentrations of 25-hydroxy vitamin D and the incidence of diabetes, but a causal link has not been established. We investigate the effect of vitamin D supplementation on the metabolic status of individuals at increased risk of developing type 2 diabetes. METHODS/DESIGN In a randomised double-blind placebo-controlled trial individuals identified as having a high risk of type 2 diabetes (non-diabetic hyperglycaemia or positive diabetes risk score) are randomised into one of three groups and given 4 doses of either placebo, or 100,000 IU Vitamin D₂ (ergocalciferol) or 100,000 IU Vitamin D₃ (cholecalciferol) at monthly intervals. The primary outcome measure is the change in glycated haemoglobin level between baseline and 4 months. Secondary outcome measures include blood pressure, lipid levels, apolipoproteins, highly sensitive C-reactive protein, parathyroid hormone (PTH) and safety of supplementation. and C-reactive protein. The trial is being conducted at two sites (London and Cambridge, U.K.) and a total of 342 participants are being recruited. DISCUSSION Trial data examining whether supplementation of vitamin D improves glycaemic status and other metabolic parameters in people at risk of developing type 2 diabetes are sparse. This trial will evaluate the causal role of vitamin D in hyperglycaemia and risk of type 2 diabetes. Specific features of this trial include recruitment of participants from different ethnic groups, investigation of the relative effectiveness and safety of vitamin D₂ and D₃ and an evidence based approach to determination of the dose of supplementation. TRIAL REGISTRATION EudraCT2009-011264-11; ISRCTN86515510.
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Affiliation(s)
- Ravi K Menon
- Blizard Institute, Queen Mary University of London, London, UK
| | - Anna P Rickard
- Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge, UK
| | - Nasima Mannan
- Blizard Institute, Queen Mary University of London, London, UK
| | - Peter M Timms
- Homerton University Hospital NHS Foundation Trust, London, UK
| | - Stephen J Sharp
- Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge, UK
| | - Adrian Martineau
- Centre for Health Sciences, Queen Mary University of London, London, UK
| | | | | | | | - Simon J Griffin
- Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge, UK
| | - Graham A Hitman
- Blizard Institute, Queen Mary University of London, London, UK
- Blizard Institute, Barts and The London School of Medicine and Dentistry, 4 Newark Street, London E1 2AT, UK
| | - Nita G Forouhi
- Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge, UK
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[Vitamin D and breast cancer: physiopathology, biological and clinical implications]. Bull Cancer 2013; 101:266-82. [PMID: 24103818 DOI: 10.1684/bdc.2013.1826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
There is a recent increase in interest of vitamin D and breast cancer, facing the number of publications on the subject. This increase have several reasons, on the one hand, vitamin D deficiency is more and more prevalent and, on the other hand, there are new data that highlights the extra-bone effects of vitamin D, especially in breast cancer, the vitamin D is involved in the breast cancer risk factor, the prognosis, and the interaction with breast cancer treatments. This combination between vitamin D deficiency and breast cancer is extremely usual, and combined with all cancer clinical parameters: the incidence, the tumour biology, the clinical presentation, the prognosis, and the antineoplastic treatment tolerance. This vitamin D deficiency is increased after adjuvant cancer treatments. And yet, this problem increases bone metabolism disruptions in breast cancer patients, inducing osteoporotic risk at long time, even though this population is curable. This problem is therefore serious in the adjuvant breast cancer treatment. Unfortunately, in this population, the current recommendations are clearly insufficient, and the current randomized clinical trial results would contribute to define the best way to correct the vitamin D deficiency, quickly and secure.
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Evidence for the treatment of osteoporosis with vitamin D in residential care and in the community dwelling elderly. BIOMED RESEARCH INTERNATIONAL 2013; 2013:463589. [PMID: 24058907 PMCID: PMC3766590 DOI: 10.1155/2013/463589] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/30/2013] [Accepted: 07/12/2013] [Indexed: 12/31/2022]
Abstract
Introduction. Vitamin D is common treatment for osteoporosis. Both age >70 years and living in residential care are associated with increased fracture risk. Community dwelling elderly are a heterogeneous group who may have more similatiry with residential care groups than younger community dwelling counterparts. Aims. To review the evidence for cholecalciferol or ergocalciferol tretment of osteoporosis in either community dwelling patients aged ≥70 years of age, or redidential care patients. Secondly endpoints were changes in bone mineral denisty, and in bone turnover markers. Methods. We performed a literature search using search terms for osteoporosis and vitamin D. Treatment for at least one year was required. Results. Only one residential care study using cholecalciferol, showed non-vertebral and hip fracture reduction in vitamin D deficient subjects. In the community setting one quasi randomised study using ergocalciferol showed reduction in total but not hip or non-vertebral fracture, and a second randomised study showed increased hip fracture risk. Three studies reported increases in hip bone mineral denisty. Discussion. A minority of studies demonstrated a fracture benefit form vitamin D and one suggested possible harm in a community setting. Current practice should be to only offer this treatment to subjects identified as deficient.
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Jones G. Extrarenal Vitamin D Activation and Interactions Between Vitamin D2, Vitamin D3, and Vitamin D Analogs. Annu Rev Nutr 2013; 33:23-44. [DOI: 10.1146/annurev-nutr-071812-161203] [Citation(s) in RCA: 77] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Glenville Jones
- Department of Biomedical & Molecular Sciences, and Department of Medicine, Queen's University, Kingston, Ontario, Canada K7L 3N6;
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Reddy SVB, Ramesh V, Bhatia E. Double blind randomized control study of intramuscular vitamin D3 supplementation in tropical calcific pancreatitis. Calcif Tissue Int 2013; 93:48-54. [PMID: 23564348 DOI: 10.1007/s00223-013-9726-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2012] [Accepted: 02/10/2013] [Indexed: 11/30/2022]
Abstract
Vitamin D deficiency is prevalent in chronic pancreatitis (CP), but the optimal route and dose of vitamin D supplementation are unknown. We evaluated the relative efficacy of two different doses of intramuscular (i.m.) vitamin D(3) in patients with CP and vitamin D insufficiency. In a double-blind randomized study, 40 patients with tropical calcific pancreatitis with serum 25-hydroxyvitamin D (25OHD) <75 nmol/L (mean 27.0 ± 14.5 nmol/L, <50 nmol/L in 90 %) were divided into three groups. Groups 1 and 2 received 600,000 IU (15,000 μg) and 300,000 IU (7,500 μg) i.m. cholecalciferol, respectively, while group 3 received i.m. saline. All groups received 1 g calcium and 500 IU (12.5 μg) vitamin D(3) orally daily and were studied for 9 months. The primary outcome was the proportion of patients with vitamin D sufficiency (25OHD >75 nmol/L) at 6 months. Vitamin D sufficiency was significantly different in the three groups (85, 29, and 0 % in groups 1, 2, and 3, respectively; p < 0.001). Mean 25OHD remained >75 nmol/L in months 1-6 in group 1 but reached a lower level (50-75 nmol/L) at these time points in group 2. At 6 months, serum alkaline phosphatase decreased significantly only in group 1 (230 ± 73 vs 165 ± 39 IU/L, p = 0.004). No patient in any group developed hypervitaminosis D or hypercalcemia. In conclusion, in patients with CP, a single i.m. injection of 600,000 IU was more effective at achieving vitamin D sufficiency over 6 months compared with 300,000 IU vitamin D(3). (Clinical Trials.gov number NCT00956839).
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Affiliation(s)
- Sagili Vijaya Bhaskar Reddy
- Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
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