DOCSLIB.ORG

Genetic and Environmental Factors Influencing Circulating Concentration of Vitamin D Metabolites and Odds of Colorectal Neoplasia

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Genetic and Environmental Factors Influencing Circulating Concentration of Vitamin D Metabolites and Odds of Colorectal Neoplasia Genetic and Environmental Factors Influencing Circulating Concentration of Vitamin D Metabolites and Odds of Colorectal Neoplasia Item Type Electronic Dissertation; text Authors Hibler, Elizabeth Anne Publisher The University of Arizona. Rights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Download date 05/10/2021 11:50:32 Link to Item http://hdl.handle.net/10150/145300 GENETIC AND ENVIRONMENTAL FACTORS INFLUENCING CIRCULATING CONCENTRATION OF VITAMIN D METABOLITES AND ODDS OF COLORECTAL NEOPLASIA. by Elizabeth Anne Hibler ______________________ A Dissertation Submitted to the Faculty of the MEL AND ENID ZUCKERMAN COLLEGE OF PUBLIC HEALTH In Partial Fulfillment of the Requirements For the Degree of DOCTOR OF PHILOSOPHY WITH A MAJOR IN EPIDEMIOLOGY In the Graduate College THE UNIVERSITY OF ARIZONA 2011 2 THE UNIVERSITY OF ARIZONA GRADUATE COLLEGE As members of the Dissertation Committee, we certify that we have read the dissertation prepared by Elizabeth Anne Hibler entitled GENETIC AND ENVIRONMENTAL FACTORS INFLUENCING CIRCULATING CONCENTRATION OF VITAMIN D METABOLITES AND ODDS OF COLORECTAL NEOPLASIA. and recommend that it be accepted as fulfilling the dissertation requirement for the Degree of Doctor of Philosophy _______________________________________________________________________ Date: 3/21/2011 Elizabeth Jacobs, Ph.D. _______________________________________________________________________ Date: 3/21/2011 Maria Elena Martinez, Ph.D. _______________________________________________________________________ Date: 3/21/2011 Chengcheng Hu, Ph.D. _______________________________________________________________________ Date: 3/21/2011 Eugene Gerner, Ph.D. _______________________________________________________________________ Date: 3/21/2011 Patricia Thompson, Ph.D. Final approval and acceptance of this dissertation is contingent upon the candidate’s submission of the final copies of the dissertation to the Graduate College. I hereby certify that I have read this dissertation prepared under my direction and recommend that it be accepted as fulfilling the dissertation requirement. ________________________________________________ Date: 3/21/2011 Dissertation Director: Elizabeth Jacobs, Ph.D. 3 STATEMENT BY AUTHOR This dissertation has been submitted in partial fulfillment of requirements for an advanced degree at the University of Arizona and is deposited in the University Library to be made available to borrowers under rules of the Library. Brief quotations from this dissertation are allowable without special permission, provided that accurate acknowledgment of source is made. Requests for permission for extended quotation from or reproduction of this manuscript in whole or in part may be granted by the head of the major department or the Dean of the Graduate College when in his or her judgment the proposed use of the material is in the interests of scholarship. In all other instances, however, permission must be obtained from the author. SIGNED: Elizabeth Anne Hibler 4 ACKNOWLEDGEMENTS There are many individuals who supported me through this dissertation work and the years leading up to it. Dr. Howell and the staff of the Indiana State Department of Health showed me what it really means to work in public health and pushed me to take the next step. The staff of the supplement trial provided critical support and I could not have completed it without the help of Sibeso Namakando, Chad Wagoner, Marty Cisneroz, and the dedicated staff of the CaTS center at the University of Arizona. Bess LeRoy and Erin Ashbeck were central to my learning R and the statistical methods used for the genetic analysis. I am especially thankful for having had a committee that was so supportive of my ideas and tolerant of my questions. Thank you all for being so patient and always willing to help. I am grateful for the unwavering support of my family and friends, who tolerated my ramblings about vitamin D with patience and generous smiles. Shivani, thank you for always being ready with a pep talk and providing the words that I needed to stay focused. To my Tucson family, thank you for your willingness to help me whenever I need it and making sure that I stayed sane throughout this process. To my Indiana family, thank you for giving me the strength to fly the coop. To my sisters, thank you for the words of encouragement and always listening when I needed a break. To my father, thank you for always telling me how “smart” you think I am and for having the generous and kind spirit that taught me the value of choosing a career focused on helping others. Finally, to my mother, thank you for always insisting that your girls would go to college, making sure I had the confidence to make it through, and buying me my first microscope. 5 DEDICATION To Monnie Hibler and Jeff Peterson, who remind me every day of why I do this… 6 TABLE OF CONTENTS LIST OF TABLES .............................................................................................................. 8 LIST OF FIGURES……………...………………………………………………………10 ABSTRACT ...................................................................................................................... 11 I. INTRODUCTION ......................................................................................................... 13 A. EXPLANATION OF THE PROBLEM ............................................................................... 13 B. GOALS AND OBJECTIVES .......................................................................................... 14 C. ROLE OF THE AUTHOR IN THE RESEARCH .................................................................. 15 D. BACKGROUND .......................................................................................................... 17 1. Vitamin D: synthesis and metabolism ................................................................. 17 2. Vitamin D Receptor and Mechanism of Action ................................................... 22 3. Vitamin D and Calcium Homeostasis ................................................................... 27 4. Vitamin D deficiency ............................................................................................ 30 5. Epidemiology of vitamin D deficiency and factors influencing circulating concentrations of 25(OH)D....................................................................................... 32 6. Summary of evidence for effectiveness of cholecalciferol supplementation ...... 45 7. Evidence for the role of selected genes in etiology of vitamin D deficiency ...... 52 8. Vitamin D and cancer ........................................................................................... 59 9. Genetic variation in CASR and GC and colorectal neoplasia outcomes ............... 67 E. SUMMARY OF THE INTRODUCTION ............................................................................ 70 II. PRESENT STUDY ...................................................................................................... 72 A. INTRODUCTION ......................................................................................................... 72 B. VITAMIN D SUPPLEMENT CLINICAL TRIAL ................................................................ 72 1. Methods................................................................................................................. 72 2. Results .................................................................................................................. 80 C. ASSOCIATION BETWEEN POLYMORPHIC VARIATION IN VDR, RXR, GC, AND CASR AND CIRCULATING CONCENTRATIONS OF 25(OH)D ....................................................... 91 1. Methods for Aims 2 and 3 .................................................................................... 91 2. Results ................................................................................................................. 103 D. ASSOCIATION BETWEEN GENETIC VARIATION IN GC AND CASR AND ODDS OF METACHRONOUS COLORECTAL NEOPLASIA. ................................................................. 124 1. Methods............................................................................................................... 124 2. Results ................................................................................................................ 124 III. DISSERTATION CONCLUSIONS AND FUTURE DIRECTIONS ...................... 132 A. DISCUSSION AND CONCLUSIONS ............................................................................. 132 1. Specific Aim 1: pilot study to assess whether over-the-counter vitamin D supplements affect circulating concentrations of 25(OH)D in the blood. .............. 133 2. Specific aim 2: association between genetic variation in VDR, RXR, GC, and CASR and circulating concentrations of 25(OH)D ................................................ 139 7 TABLE OF CONTENTS- Continued 3. Specific aim 3: association between genetic variation in GC and CASR and odds of metachronous colorectal neoplasia ..................................................................... 147 4. Statistical methods for genetic analysis ............................................................. 152 5. Strengths and Limitations ..................................................................................
Load more

Recommended publications
  • Correction of Vitamin D Deficiency in Critically Ill Patients Study Protocol
    1 VITdAL@ICU - Correction of vitamin D deficiency in critically ill patients VITdAL@ICU Correction of vitamin D deficiency in critically ill patients Study Protocol Version 1.0, 19.02.2010 Original Version Version 2.0, 10.11.2010 Addition of personal variant for 6 – month – follow-up (including assessment of falls and fractures) and data safety review Version 3.0, 17.8.2012 Addition of 24-month follow-up Downloaded From: https://jamanetwork.com/ on 10/01/2021 2 VITdAL@ICU - Correction of vitamin D deficiency in critically ill patients SYNOPSIS Sponsor- Univ.-Prof. Dr. Harald Dobnig Investigator Department of Internal Medicine Division of Endocrinology and Nuclear Medicine Medical University of Graz Tel.: +43/316/385-80252 Email: [email protected] Correction of vitamin D deficiency in critically ill patients: a Title randomized, double-blind, placebo-controlled trial (“VITDAL@ICU”) Background Low vitamin D status is associated with increased mortality, cardiovascular events, diabetes, hypertension and impaired function of the immune and musculoskeletal system in cross-sectional and prospective cohort studies. Given that most critically ill patients are vitamin D deficient, treatment with sufficiently high doses of vitamin D may represent a promising and inexpensive intervention option. To date, no clinical trial has prospectively evaluated clinical outcomes in patients treated with vitamin D in an intensive care setting. Objectives/ Primary endpoint Outcome - hospital stay measures Secondary endpoints - ICU stay - mortality in
    [Show full text]
  • Hypervitaminosis - an Emerging Pathological Condition
    International Journal of Health Sciences and Research www.ijhsr.org ISSN: 2249-9571 Review Article Hypervitaminosis - An Emerging Pathological Condition J K Roop PG Department of Zoology, JC DAV College (Affiliated to Panjab University, Chandigarh), Dasuya-144205, District Hoshiarpur, Punjab, India ABSTRACT Vitamins are essential organic compounds that are required in small amounts to regulate various metabolic activities in the body. Prolonged and overconsumption of pharmaceutical forms of both water-soluble and fat-soluble vitamins may lead to toxicity and/or hypervitaminosis. Hypervitaminosis is an acute emerging pathological condition of the body due to excess accumulation of any of the vitamins. In case of acute poisoning with vitamin supplements/drugs, emergency assistance is required to detoxify the effects and restore the organization, structure and function of body’s tissues and organs. Sometimes death may occur due to intoxication to liver, kidney and heart. So, to manage any type of hypervitaminosis, proper diagnosis is essential to initiate eliminating the cause of its occurrence and accelerate the elimination of the supplement from the body. The present review discusses the symptoms of hypervitaminosis that seems to be a matter of concern today and management strategies to overcome toxicity or hypervitaminosis. Keywords: Hypervitaminosis, Toxicity, Vitamins, Vitamin pathology, Fat-soluble vitamin, Water- soluble vitamin. INTRODUCTION body, particularly in the liver. Vitamin B Vitamins are potent organic Complex and vitamin C are water- soluble. compounds present in small concentrations They are dissolved easily in food during in various fruits and vegetables. They cooking and a portion of these vitamins may regulate physiological functions and help in be destroyed by heating.
    [Show full text]
  • Simulation of Physicochemical and Pharmacokinetic Properties of Vitamin D3 and Its Natural Derivatives
    pharmaceuticals Article Simulation of Physicochemical and Pharmacokinetic Properties of Vitamin D3 and Its Natural Derivatives Subrata Deb * , Anthony Allen Reeves and Suki Lafortune Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL 33169, USA; [email protected] (A.A.R.); [email protected] (S.L.) * Correspondence: [email protected] or [email protected]; Tel.: +1-224-310-7870 or +1-305-760-7479 Received: 9 June 2020; Accepted: 20 July 2020; Published: 23 July 2020 Abstract: Vitamin D3 is an endogenous fat-soluble secosteroid, either biosynthesized in human skin or absorbed from diet and health supplements. Multiple hydroxylation reactions in several tissues including liver and small intestine produce different forms of vitamin D3. Low serum vitamin D levels is a global problem which may origin from differential absorption following supplementation. The objective of the present study was to estimate the physicochemical properties, metabolism, transport and pharmacokinetic behavior of vitamin D3 derivatives following oral ingestion. GastroPlus software, which is an in silico mechanistically-constructed simulation tool, was used to simulate the physicochemical and pharmacokinetic behavior for twelve vitamin D3 derivatives. The Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) Predictor and PKPlus modules were employed to derive the relevant parameters from the structural features of the compounds. The majority of the vitamin D3 derivatives are lipophilic (log P values > 5) with poor water solubility which are reflected in the poor predicted bioavailability. The fraction absorbed values for the vitamin D3 derivatives were low except for calcitroic acid, 1,23S,25-trihydroxy-24-oxo-vitamin D3, and (23S,25R)-1,25-dihydroxyvitamin D3-26,23-lactone each being greater than 90% fraction absorbed.
    [Show full text]
  • Question of the Day Archives: Monday, December 5, 2016 Question: Calcium Oxalate Is a Widespread Toxin Found in Many Species of Plants
    Question Of the Day Archives: Monday, December 5, 2016 Question: Calcium oxalate is a widespread toxin found in many species of plants. What is the needle shaped crystal containing calcium oxalate called and what is the compilation of these structures known as? Answer: The needle shaped plant-based crystals containing calcium oxalate are known as raphides. A compilation of raphides forms the structure known as an idioblast. (Lim CS et al. Atlas of select poisonous plants and mushrooms. 2016 Disease-a-Month 62(3):37-66) Friday, December 2, 2016 Question: Which oral chelating agent has been reported to cause transient increases in plasma ALT activity in some patients as well as rare instances of mucocutaneous skin reactions? Answer: Orally administered dimercaptosuccinic acid (DMSA) has been reported to cause transient increases in ALT activity as well as rare instances of mucocutaneous skin reactions. (Bradberry S et al. Use of oral dimercaptosuccinic acid (succimer) in adult patients with inorganic lead poisoning. 2009 Q J Med 102:721-732) Thursday, December 1, 2016 Question: What is Clioquinol and why was it withdrawn from the market during the 1970s? Answer: According to the cited reference, “Between the 1950s and 1970s Clioquinol was used to treat and prevent intestinal parasitic disease [intestinal amebiasis].” “In the early 1970s Clioquinol was withdrawn from the market as an oral agent due to an association with sub-acute myelo-optic neuropathy (SMON) in Japanese patients. SMON is a syndrome that involves sensory and motor disturbances in the lower limbs as well as visual changes that are due to symmetrical demyelination of the lateral and posterior funiculi of the spinal cord, optic nerve, and peripheral nerves.
    [Show full text]
  • Draft Vitamin D and Health Report
    Draft Vitamin D and Health report Scientific consultation: 22 July to 23 September 2015 Contents Page 1. Introduction 3 2. Biology and metabolism 5 3. Photobiology of vitamin D 16 4. Measuring vitamin D exposure (from diet and sunlight) 24 5. Relationship between vitamin D exposure and serum (25(OH)D concentration 29 6. Vitamin D and health outcomes 35 Musculoskeletal outcomes 37 Rickets 39 Osteomalacia 41 Pregnancy and lactation 42 Infants (up to 12 months) 44 Children (1-3y) 45 Children (4-8y) 45 Adults < 50 years 47 Adults > 50 years 50 Conclusions – vitamin D & musculoskeletal health outcomes 59 Non-musculoskeletal health outcomes 61 Pregnancy & lactation – non-musculoskeletal health outcomes 61 Cancers 67 Cardiovascular disease & hypertension 70 All-cause mortality 74 Autoimmune disease 76 Infectious disease 81 Neuropsychological functioning 85 Oral health 88 Age-related macular degeneration 90 Conclusions – non-musculoskeletal health outcomes 92 Selection of health outcomes to inform the setting of DRVs for vitamin D 93 7. Potential adverse effects of high vitamin D intakes/high serum 25(OH)D 95 concentration 8. Dietary vitamin D intakes and serum/plasma 25(OH)D concentrations of the UK 102 population 9. Review of DRVs 109 10. Overall summary & conclusions 121 11. Recommendations 130 12. References 131 2 1. Introduction Background 1. Vitamin D is synthesised in the skin by the action of sunlight. Skin synthesis is the main source of vitamin D for most people; dietary sources are essential when exposure to sunlight containing the appropriate wavelength is limited. The Committee on Medical Aspects of Food and Nutrition Policy (COMA), which set Dietary Reference Values (DRVs) for vitamin D in 1991 (DH1, 1991), did not set a Reference Nutrient Intake (RNI2) for groups in the population considered to receive adequate sunlight exposure.
    [Show full text]
  • Vitamins in Animal and Human Nutrition
    Lee Russell McDowell Vitamins in Animal and Human Nutrition SECOND EDITION Iowa State University Press / Ames VITAMINS IN ANIMAL AND HUMAN NUTRITION Lee Russell McDowell Vitamins in Animal and Human Nutrition SECOND EDITION Iowa State University Press / Ames Lee Russell McDowell, PhD, is a professor of animal science in the Department of Animal Science, University of Florida, Gainesville. His research interests center pri- marily on minerals for grazing livestock, vitamins for livestock, and feed composition. Dr. McDowell also collaborates with numerous animal nutritionists in tropical coun- tries of Latin America, Africa, and Southeast Asia. © 2000 Iowa State University Press; 1989 Academic Press All rights reserved Iowa State University Press 2121 South State Avenue, Ames, Iowa 50014 Orders: 1-800-862-6657 Office: 1-515-292-0140 Fax: 1-515-292-3348 Web site: www.isupress.edu Authorization to photocopy items for internal or personal use, or the internal or per- sonal use of specific clients, is granted by Iowa State University Press, provided that the base fee of $.10 per copy is paid directly to the Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923. For those organizations that have been granted a photocopy license by CCC, a separate system of payments has been arranged. The fee code for users of the Transactional Reporting Service is 0-8138-2630-6/2000 $.10. Printed on acid-free paper in the United States of America First edition, 1989 (© Academic Press) Second edition, 2000 Library of Congress Cataloging-in-Publication Data McDowell, L. R. Vitamins in animal and human nutrition/Lee Russell McDowell—2nd ed.
    [Show full text]
  • ACVPM Toxicology Review
    Top 20 Toxicology Review “I always keep a supply of stimulant handy in case I see a snake………..which I also keep handy. “ - WC Fields The Top 10 (in no particular order….) 1. Bracken fern Pteridium aquilinum –THINK bloody urine cows, ataxic horse 2. Copper –THINK hemolytic crisis, port wine urine, gunmetal kidneys 3. Cyanide—THINK Bright red blood, like bright red cherries 4. Anticoagulant rodenticides--–THINK hemolytic crisis 5. Ethylene glycol (antifreeze) –THINK kidney failure 6. Insecticides (esp. OPPs, carbamates) –THINK miosis, drool, vomiting, diarrhea, seizure 7. Lead--–THINK GI signs + Neuro Sx (blindness) 8. NITRATE / NITRITE Toxicity –THINK Dark Chocolate blood 9. Mycotoxins Aflatoxins –THINK hepatotoxic, carcinogenic Zearalonone / moldy corn –THINK estrogenism, repro dysfunction 10. Nonprotein nitrogen (NPN) ‘Ammonia tox‘ (urea, ammonia, etc) –THINK Bov Bonkers 1 www.zukureview.com © Zuku LLC, All Rights Reserved I. Pathognomonics, weird names, weird smells, NOEL 1. Gunmetal grey kidneys-Cu tox Trifolium subterraneum, cz mineral imbal Senecio, Heliotropum damage liver cz Cu tetention 2. Port wine urine-Cu tox see above 3. Cherry-red blood-Cyanide pitted fruits 4. Chocolate-brown blood- Nitrates 5. “SPECTACLES” Depigmentation around eyes- molybdenul tox 6. Smells a. Garlicky breath- selenium tox b. Bitter almonds in rumen-cyanide c. “Mouse-like odor” to crushed leaves- Conium maculatum (poison hemlock) 7. Diseases a. “Alkali disease”- selenium toxicity (Astragalus, Oxytropis) b. “Blind staggers”-selenium tox c. “Cracker heels” clicking dewclaws w/ Astragalus-miserotoxin d. “Milk sickness” in early American settlers- Eupatorium (white snakeroot) e. “Crooked calf” syndrome- torticollis, carpal flexure, scoliosis in calves exposed in utero d. 40-70 to Lupinus (Lupine, bluebonnet) f.
    [Show full text]
  • Can Vitamin D3 Supplementation Reduce the Time to Severe Asthma Exacerbations in Children with Asthma?
    Idan Bokobza1, Nour El Hadi1, Andrew Bush2,3, Heidi Makrinioti1,2 [email protected] Journal club Can vitamin D3 supplementation reduce the time to severe asthma exacerbations in children with asthma? Although the protective levels of vitamin D for Cite as: Bokobza I, El Hadi N, Commentary on: bone health have been well described, we do Bush A, et al. Can vitamin Forno E, et al. Effect of Vitamin D 3 not know what levels of vitamin D are needed for D3 supplementation reduce supplementation on severe asthma optimal immune responses to respiratory viral the time to severe asthma exacerbations in children with asthma and low infections [8]. Vitamin D deficiency is defined as exacerbations in children vitamin D levels: the VDKA randomized clinical with asthma? Breathe 2021; measurable levels of 25-hydroxyvitamin D below trial. JAMA 2020; 324: 752–760. 17: 210071. 20 ng·mL−1 and vitamin D insufficiency is defined as measurable levels of 25-hydroxyvitamin D below Context 30 ng·mL−1 [9], but these are based solely on bone markers. There is considerable evidence that the prevalence There is evidence from observational cohort of asthma is increasing in industrialised countries, studies linking low 25-hydroxyvitamin D levels with particularly in children and young adults [1]. asthma incidence in children [10, 11]. A systematic Exacerbations of asthma constitute the main review of the literature on studies examining the burden of the disease for children and their impact of vitamin D supplementation in children families. The majority of asthma exacerbations are with early diagnosed asthma failed to show triggered by respiratory viruses, most commonly clear positive impact [12].
    [Show full text]
  • Vitamin D in Plants – Occurrence, Analysis and Biosynthesis
    Vitamin D in plants – occurrence, analysis and biosynthesis Rie Bak Jäpelt PhD Thesis 2011 Vitamin D in plants Occurrence, analysis and biosynthesis PhD thesis Rie Bak Jäpelt Division of Food Chemistry National Food Institute Technical University of Denmark 2011 Vitamin D in plants – occurrence, analysis and biosynthesis December 2011 Copyright: National Food Institute, Technical University of Denmark Photo: Colourbox ISBN: 978-87-92763-15-0 This PhD Thesis is available at www.food.dtu.dk National Food Institute Technical University of Denmark Mørkhøj Bygade 19 DK-2860 Søborg Tel: +45 35 88 70 00 Fax: +45 35 88 70 01 Preface This PhD study was conducted from 2008 to 2011 at the Division of Food Chemistry, National Food Institute, Technical University of Denmark. The project was financially supported by Ministry of Food, Agriculture and Fisheries, Directorate for Food, Fisheries and Agri Business (3304-FVFP-07-774-02) and Technical University of Denmark. I will start by expressing my gratitude to everyone who has helped during my PhD study. In particular, I would like to thank my principal supervisor Senior Scientist Jette Jakobsen. Jette has been an invaluable support both in ups and downs. Thank you for giving me diverse and varying tasks and responsibilities and for believing in me. I would also like to thank my co- supervisor, Head of Division Jørn Smedsgaard, for introducing me to mass spectrometry and for valuable discussions on method development. I thank current and former colleagues at Division of Food Chemistry and especially the group of Bioactive Compounds for creating a comfortable work atmosphere.
    [Show full text]
  • Vitamin D: Current Status and Perspectives1)
    Article in press - uncorrected proof Clin Chem Lab Med 2009;47(2):120–127 ᮊ 2009 by Walter de Gruyter • Berlin • New York. DOI 10.1515/CCLM.2009.036 2009/165 Review Vitamin D: current status and perspectives1) Etienne Cavalier1,*, Pierre Delanaye2, Jean-Paul Introduction Chapelle1 and Jean-Claude Souberbielle3 1 Department of Clinical Chemistry, University The discovery of vitamin D may have begun in Bel- Hospital of Liege, University of Liege, Belgium gium in 1900 when Professor Wildiers from the Uni- versity of Louvain studied the ‘‘bios’’, an organic 2 Department of Nephrology, University Hospital of extract of self-autolyzed yeast. This substance stimu- Liege, University of Liege, Belgium lated the proliferation of yeast (1). In 1912, Casimir 3 Universite´Paris Descartes, Inserm U845, and Funk suggested the name ‘‘vitamine’’ for ‘‘nitroge- Hoˆpital Necker, Service d’explorations nous substances, minute quantities of which are fonctionnelles, Paris, France essential in the diet of birds, man and some other ani- mals’’ (2). In 1921, Funk and Dubin showed that there were two different vitamins present in yeast: the absence of one of these, vitamin B, caused polyneur- itis in birds (beri-beri), while the other, which they Abstract called vitamin D, was the ‘‘bios’’, necessary for the activity of low concentrations of yeast cells. Both vita- The role of vitamin D in maintaining bone health has mins were necessary for the proper growth of rats (3, been known for decades. Recently, however, the dis- 4). At the same time the interest for rickets was covery that many tissues expressed the vitamin D renewed.
    [Show full text]
  • Vitamin D Toxicity
    Post N Med 2016; XXIX(10): 756-759 ©Borgis *Ewa Marcinowska-Suchowierska1, Paweł Płudowski2 Vitamin D toxicity Zatrucie witaminą D 1Department of Geriatric, Internal Medicine and Metabolic Bone Disease, Centre of Postgraduate Medical Education, Warsaw Head of Department: Professor Marek Tałałaj, MD, PhD 2Department of Biochemistry, Radioimmunology and Experimental Medicine, The Children’s Memorial Health Institute, Warsaw Head of Department: Professor Roman Janas, PhD Keywords Summary vitamin D, 25(OH)D, toxicity, clinical Vitamin D toxicity (VDT), also called hypervitaminosis D, is a rare but potentially serious symptoms and management condition that occurs when an individual has excessive 25(OH)D levels in the bloodstream. Vitamin D toxicity is usually caused by extremely high doses of vitamin D supplements, not by diet or skin exposure to the sun. The main clinical consequence of VDT is elevated Słowa kluczowe serum calcium level (hypercalcemia) and a variety of nonspecific symptoms. The literature witamina D, 25(OH)D, toksyczność, reports that hypercalcemia due to overdosed vitamin D may appear if serum 25(OH)D objawy kliniczne, leczenie levels are higher than 150-200 ng/ml. Many different mechanisms have been proposed to account for VDT, including the vitamin D metabolite itself, VDR number, activity of 1 al- fa-hydroxylase, inhibition of vitamin D catabolism, and the capacity of VDBP. Mounting evidence that higher levels of vitamin D may have beneficial effects on bone and cellular health may predispose to enhanced administration of vitamin D and increased frequency of VDT. Hypercalcemia from VDT is rare, but a dangerous state for the organism and should receive adequate and sensible treatment.
    [Show full text]
  • Vitamin D and Asthma: What Is the Connection? Disclosure
    Vitamin D and Asthma: What is the Connection? Disclosure Monaghan Medical Corporation – speaker Norvartis – speaker Genetech – speaker Thank you Monaghan! Learning Objectives Discuss basic physiology of vitamin D and the potential consequences of vitamin D deficiency. Describe the potential impact of vitamin D and asthma. Evaluate the emerging role of vitamin D as an adjunctive therapy in asthma management. Vitamin D- The Facts . Vitamin D deficiency is public health problem for adults and children worldwide. Many epidemiological studies have shown that vitamin D deficiency increases the risk of asthma and allergies. Low levels of vitamin D have been associated with asthma severity, poor control with recurrent exacerbations. Rochester Epidemiology Project National Institutes of Health-funded Mayo Clinic 2002 – 2011 Geographic population identifying health trends N = 20,308 8% of subjects vitamin D levels > 50 ng/mL 16,246 people were vitamin D deficient Mayo Clinic, 2015 What is vitamin D deficiency? Deficiency < 20 ng/ml25(OH)D concentration Insufficiency: 20-30 mg/ml Sufficiency: 30-50 ng/ml Toxic: > 150 ng/ ml Endocrine Society Clinical Practice Guideline Vitamin D Deficiency Increase Risk Osteoporosis Osteoporotic fracture Osteomalacia Rickets Heart disease Autoimmune disease Multiple sclerosis Alzheimers Type 1 Diabetes Some cancers Depression Cardiovasular disease Vitamin D Deficiency Increase Risk Asthma Cystic fibrosis Chronic Obstructive Pulmonary Disease (COPD) Interstitial pneumonia Factors Influencing Vitamin D Age Body fat Level of skin melanin Latitude Amount of sun exposures Use of sunscreen Health status Latitude and vitamin D production in the skin Except during the summer months, the skin makes little if any vitamin D from the sun at latitudes above 37 degrees north (in the United States, the shaded region in the map) or below 37 degrees south of the equator.
    [Show full text]