UUnniivveerrssiittyy ooff MMaassssaacchhuusseettttss AAmmhheerrsstt SScchhoollaarrWWoorrkkss@@UUMMaassss AAmmhheerrsstt Masters Theses 1911 - February 2014 2011 IIrroonn SSttaattuuss,, IInnflflaammmmaattiioonn aanndd AAnneemmiiaa iinn BBaannggllaaddeesshhii WWoommeenn EExxppoosseedd ttoo AArrsseenniicc Joycelyn M. Faraj University of Massachusetts Amherst Follow this and additional works at: https://scholarworks.umass.edu/theses Part of the International Public Health Commons, and the Maternal and Child Health Commons Faraj, Joycelyn M., "Iron Status, Inflammation and Anemia in Bangladeshi Women Exposed to Arsenic" (2011). Masters Theses 1911 - February 2014. 562. Retrieved from https://scholarworks.umass.edu/theses/562 This thesis is brought to you for free and open access by ScholarWorks@UMass Amherst. It has been accepted for inclusion in Masters Theses 1911 - February 2014 by an authorized administrator of ScholarWorks@UMass Amherst. For more information, please contact [email protected]. IRON STATUS, INFLAMMATION AND ANEMIA IN BANGLADESHI WOMEN EXPOSED TO ARSENIC A Thesis Presented by JOYCELYN M. FARAJ Submitted to the Graduate School of the University of Massachusetts Amherst in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE February 2011 Nutrition © Copyright by Joycelyn M. Faraj 2011 All Rights Reserved IRON STATUS, INFLAMMATION AND ANEMIA IN BANGLADESHI WOMEN EXPOSED TO ARSENIC A Thesis Presented by JOYCELYN M. FARAJ Approved as to style and content by: _____________________________________ Alayne Ronnenberg, Chair _____________________________________ Richard Wood, Member _____________________________________ J. Richard Pilsner, Member _____________________________________ Carol Bigelow, Member __________________________ Nancy Cohen, Department Head Nutrition DEDICATION To my family for giving me their invaluable support. ACKNOWLEDGEMENTS I would like to thank my advisor, Dr. Alayne Ronneberg, for her indispensable guidance, support and motivation throughout my academic career. I would also like to thank my committee members: Dr. Richard Wood, Dr. Carol Bigelow, Dr. Edward Calabrese for their guidance throughout my thesis. Special thanks to Dr. J. Richard Pilsner for his participation in this process. I thank all my friends and colleagues who were directly or indirectly involved in the project. v ABSTRACT IRON STATUS, INFLAMMATION AND ANEMIA IN BANGLADESHI WOMEN EXPOSED TO ARSENIC FEBRUARY 2011 JOYCELYN FARAJ, B.S. UNIVERSITY OF MASSACHUSETTS AMHERST M.S., UNIVERSITY OF MASSACHUSETTS AMHERST Directed by: Dr. Alayne Ronnenberg Iron depletion is the most common nutrient deficiency worldwide and is the leading cause of anemia. The prevalence of anemia in Bangladeshi women has been estimated by others at 45%, but the prevalence of iron depletion (ID) and iron deficiency anemia (IDA) in these women remains unknown. Chronic arsenic (As) exposure, which is a major public health problem in Bangladesh, is associated with increased risk of anemia. Arsenic exposure also triggers inflammatory responses that alter iron parameters, including serum ferritin, rendering IDA assessment more challenging. We assessed the prevalence of ID and IDA in 147 Bangladeshi women, ages 18-33 years, who participated in a larger study of arsenic exposure and skin lesions. The current study includes 75 women with skin lesions (cases) and 72 women without lesions (controls). Blood samples, anthropometric, sociodemographic and dietary data were collected at enrollment. Hb, ferritin and hs-c-reactive protein (CRP) were measured in serum. Overall, the prevalence of anemia (Hb < 120 g/L) was 18%. Although the prevalence of ID (ferritin ≤12mcg/L) did not differ between cases and controls, vi the prevalence of anemia was almost three times higher among women with arsenic-related skin lesions compared with controls (25% vs 10%, respectively; p=0.02). Of the women with anemia, 27% (N=7) also had ID (Hb<120g/L and ferritin ≤12 mcg/L), indicating IDA. Women with normal iron status had double the concentration of toenail arsenic compared to iron-depleted women (2.9 vs 1.4 µg As/g toenail; p=0.00). In addition, the arsenic concentration of their water source was three-times higher than that of iron-depleted women (18.8 vs 6.2 µg As/L; p=0.03). Mean CRP was higher in cases than controls (p=0.04) as well as in those with serum ferritin >12mcg/L compared to those who were iron deplete (p=0.02). In multivariable logistic regression,. the risk of ID was 84% lower in women ages 29-33 compared to women ages 18-22 (OR=0.16, 95% CI=0.04, 0.56); every 1µg increase in toenail As level was associated with a 45% lower d risk of ID (OR=0.55 , 95% CI=0.33, 0.94).The presence of inflammation decreased the odds of being classified as ID by 80% (OR=0.20, 95% CI=0.04, 0.96). Much of the anemia in this cohort appears unrelated to iron deficiency, but could be linked to other nutrients, such as folate and vitamin B , which are 12 involved in both hematopoiesis and arsenic metabolism. It is possible that arsenic exposure in this cohort compromised folate and vitamin B status. 12 Because these vitamins are also important during pregnancy, additional studies are needed to assess B-vitamin status in arsenic-exposed women and to determine whether B-vitamin status influences reproductive outcomes in these women. vii TABLE OF CONTENTS Page ACKNOWLEDGEMENTS ..................................................................................... V ABSTRACT ......................................................................................................... VI LIST OF TABLES ................................................................................................. X LIST OF FIGURES .............................................................................................. XI CHAPTER 1 INTRODUCTION ........................................................................................... 1 2 IRON ............................................................................................................ 4 2.1 Introduction and Biological Functions ................................................... 4 2.1.1 Iron-containing Proteins .............................................................. 5 2.2 Iron Absorption ..................................................................................... 9 2.2.1 Non-heme Iron Absorption .......................................................... 9 2.2.2 Heme Iron Absorption ................................................................ 11 2.3 Iron Stores and Mobilization ............................................................... 12 2.4 Iron Homeostasis ................................................................................. 13 2.5 Iron Deficiency ..................................................................................... 18 2.6 Assessment of Iron Status ................................................................... 19 3 IRON DEFICIENCY AS A PUBLIC HEALTH PROBLEM ........................... 23 3.1 Epidemiology of Iron Deficiency .......................................................... 24 3.2 Etiology of Iron Deficiency ................................................................... 25 3.3 Iron Deficiency and Reproductive Health ............................................. 25 vii 4 ARSENIC .................................................................................................... 27 4.1 Arsenic: Properties ............................................................................. 27 4.2 Arsenic Contamination ........................................................................ 28 4.3 Arsenic Metabolism ............................................................................ 28 4.4 Arsenic Toxicity and Carcinogenicity .................................................. 30 4.4.1 Possible Mechanisms of Arsenic Carcinogenesis ....................... 32 4.4.2 Animal Toxicity Studies .............................................................. 32 4.4.3 Dietary Influences on Arsenic Toxicity ....................................... 34 4.5 Effects of Arsenic on Human Health ................................................... 35 4.5.1 Effects of Arsenic on Femal Reproductive Health ....................... 37 4.5.2 Gender Differences in Arsenic Toxicity ....................................... 38 5 BANGLADESH ............................................................................................ 40 6 PURPOSE OF THE STUDY ....................................................................... 44 6.1 Hypotheses ......................................................................................... 45 6.2 Specific Aims ...................................................................................... 45 7 MATERIALS AND METHODS .................................................................... 47 7.1 Subjects .............................................................................................. 47 7.2 Data Collection ................................................................................... 48 7.2.1 Blood Sample Collection ............................................................. 48 7.2.2 Laboratory Measurements .......................................................... 48 7.3 Statistical Analysis .............................................................................. 50 8 RESULTS .................................................................................................... 51 viii
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