The undersigned, appointed by the Vice President of the Graduate School, have examined the dissertation entitled:

Iron Deficiency and Endurance Athletes by:

Jamin Swift

A candidate for the degree of Doctor of Education And hereby certify that in their opinion it is worthy of acceptance

April 2018

Approved:

Chair: ______(Dr. Paul Sturgis, Ed. D, Chair)

______(Dr. Doug Ebersold, Ed. D, Committee Member)

______(Dr. Lynn Hanrahan, Ed. D, Committee Member)

______(Dr. J. Michael Pragman, Ed. D, Committee Member)

Iron Deficiency and Endurance Athletes

by

Jamin Swift

A Dissertation Presented to the Faculty of the Graduate College William Woods University

in Partial Fulfillment of the Requirement for the Degree

Doctor of Education

May 2018

3

Abstract

The purpose of this study was to explore the various opinions concerning the importance of testing multiple markers of iron status while examining the current knowledge base in relation to the effects of iron depletion on endurance athletes. Contrasting beliefs exist pertaining to the differing methods for screening iron status as well as differing opinions regarding healthy ranges on those assessments.

This study utilized an exploratory research approach to determine which diagnostic tests physicians deem most beneficial in determining iron deficiency in endurance athletes. Employing semi-structured personal interviews to twelve coaches and six healthcare professionals along with open-ended surveys to eight athletes and eight parents, this study collected qualitative data from 34 participants regarding current doctor recommendations toward the diagnosis of non-anemic iron deficiency, the importance of tests, and effective forms of treatment.

Through a process of open and axial coding, four distinct themes emerged in relation to testing iron levels of fatigued endurance athletes: contact a healthcare professional, serum ferritin is an important test, creation of optimal ranges, and treatment options. According to this study, within the first two weeks of noticing persistent fatigue, athletes should seek the opinion of a healthcare professional due to the possibility of underlying disease and risks associated . Due to the prevalence of depleted iron stores within this demographic, participants in this study claimed that serum ferritin is an important test associated 4 with persistent fatigue reported by endurance athletes. Pertaining to blood tests associated with fatigue, participants in this study expressed that normal ranges need to be refined and optimal ranges need to be developed to promote optimal performance instead of minimal requirements. Lastly, participants in this study reported that treatment options are generally easy, affordable, and effective in the absence of underlying disorders or disease.

This study also confirmed a large disconnect between the opinions expressed by the healthcare professionals of this study and the experiences reported by the coaches, athletes, and parents with primary care physicians.

Many of the coaches, athletes, and parents reported poor experiences with their primary care physicians where they often had to self-advocate and demand additional iron tests not included with the standard CBC. The implications of this study will be extremely beneficial as it provides educational information and critical resources for use in conversations with primary care physicians related to iron depletion. 5

Dedication

This dissertation is dedicated to my closest friends and family, and to the memory of my grandparents: Virgil Thomas, Elsie Thomas, George Swift, and

Harriet Swift. Without their constant love, support, understanding, and virtues they’ve passed on to so many generations, I’m not sure I would have crossed this finish line. 6

Acknowledgements

An endeavor of this nature requires the assistance and support of numerous individuals. This research would not have been possible without the assistance and guidance from the professors at William Woods University and support from my incredible colleagues, friends, and family members. I am thankful for each and every individual that has impacted this study directly or indirectly. Words cannot express the true appreciation and love I have for each of you.

Specifically, I would like to thank my committee chair, Dr. Paul Sturgis, for his support and quick responses to my never-ending questions during this adventure. I would also like to thank Dr. Michael Pragman for his expertise and guidance pertaining to the challenges of qualitative analysis. I sincerely appreciate the continued support and timely feedback you both offered through all the difficulties posed in a study of this nature.

I would also like to thank my closest friends and family, near and far. I cannot express how important they have been to me in the pursuit of this endeavor. Your kind words in person and through social media have impacted me more than you will ever know. I would like to thank my parents for being great role models and always supporting me throughout all of life’s challenges. Most of all, I would like to thank my son, Tyler, for his constant encouragement, his incredible patience, and his understanding when this project monopolized my time and took me away from the person I love most. Love you most! 7

Table of Contents

List of Tables ...... 11

Chapter One - Introduction ...... 12

Background of Study ...... 12

Statement of Problem ...... 13

Purpose of Study ...... 13

Significance of Study ...... 14

Definition of Terms ...... 14

Research Questions ...... 16

Limitations ...... 16

Delimitations ...... 17

Assumptions ...... 17

Organization of the Study ...... 17

Chapter Two - Review of Literature ...... 19

Introduction ...... 19

Scientific Background and Definitions ...... 20

Iron and Its Importance to Endurance Athletes ...... 22

Relevance to endurance athletes ...... 22

Oxygen delivery and cellular respiration...... 22

Oxygen delivery and VO2 max...... 24

Iron depletion associated with endurance athletes ...... 26

Symptoms and effects of iron deficiency...... 31

Importance of monitoring dietary intake...... 32 8

Diagnosis of Iron Deficiency ...... 33

Importance of screening...... 33

Methods of diagnosis...... 36

Three stages of iron deficiency...... 43

Iron depletion...... 43

Iron deficient non-anemic...... 44

Iron deficiency anemia...... 45

Classifications of anemia...... 46

Need for standardization...... 48

Supplementation ...... 52

Determining the need for dietary supplements...... 52

Types of treatment...... 54

Benefits and risks associated with treatments...... 57

Conclusion ...... 60

Chapter Three - Research Methodology ...... 65

Introduction ...... 65

Selection of Participants ...... 65

Instrumentation ...... 66

Role of the Researcher ...... 67

Data Collection ...... 67

Data Analysis ...... 68

Summary ...... 68

Chapter Four - Results ...... 70 9

Introduction ...... 70

Description of Participants ...... 70

Research Findings ...... 72

Theme 1 – Seek the opinion of a healthcare professional...... 72

Theme 2 – Serum ferritin is an important test for fatigue...... 84

Theme 3 – Optimal ranges for serum ferritin...... 106

Theme 4 – Treatment options...... 113

Summary ...... 130

Chapter Five - Summary, Discussion, and Conclusions ...... 134

Introduction ...... 134

Summary of the Study ...... 134

Discussion of the Findings ...... 137

Research question one...... 137

Research question two...... 146

Knowledge of effects...... 149

Knowledge of diagnosis...... 150

Knowledge of treatment...... 154

Implications for Practice ...... 159

Recommendations for Further Research ...... 160

Conclusions ...... 165

References ...... 167

Appendix A: IRB Approval ...... 178

Appendix B: Consent Form ...... 179 10

Appendix C: Varying Opinions for Determining Iron Depletion ...... 180

Appendix D: Interview Questions for Healthcare Professionals ...... 181

Appendix E: Survey Questions for Parents ...... 183

Appendix F: Interview Questions for Coaches ...... 184

Appendix G: Survey Questions for Collegiate Athletes ...... 186

Appendix H: Healthcare Participants ...... 187

Appendix I: Coach Participants ...... 188

Appendix J: Parent Participants ...... 189

Appendix K: Collegiate Athlete Participants ...... 190

Appendix L: Letter for Physicians from Dr. Colter ...... 191

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List of Tables

Table 1: Varying Opinions for Determining Iron Depletion ...... 180

Table 2: Notable Demographics of Healthcare Participants ...... 187

Table 3: Notable Demographics of Coach Participants ...... 188

Table 4: Notable Demographics of Collegiate Athlete Participants ...... 189

Table 5: Notable Demographics of Parent Participants ...... 190

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Chapter One - Introduction

Background of Study

Athletes and coaches have long been intrigued by the effect of iron stores on the oxygen and energy delivery systems. Due to the strong correlation between iron levels and the body’s ability to carry needed oxygen to muscle tissue, many suspect that iron deficiency may have a stronger effect on endurance athletes. Oxygen depreciation allows fatigue to set in earlier than it should, causing measurable drops in both practice and competition performance. Athletes that cannot consistently train at high levels cannot compete at high levels. While it is widely known that iron deficiency is the single most common nutritional deficiency worldwide, recent findings and scientific contradictions have challenged the conventional processes in diagnosis and treatment of iron-related issues (Johnson-Wimbley & Graham, 2011). Many have begun to categorize iron deficiency into three significant stages, each with very specific characteristics: iron depleted (ID), iron deficient non-anemic (IDNA), and iron deficiency anemia

(IDA). However, a lack of standardized measures of iron stores and varying opinions by healthcare professionals, have made diagnosis within these stages very challenging and rather subjective. Studies have shown that delays in detection and misdiagnosis often lead to athletes missing up to a year of training and competing as iron levels require significant periods of rest and time for regeneration (Grinaker, 2014). Yet, there also seems to be a lack in educational programs designed to inform athletes, parents, and coaches of the effects of iron depletion on endurance athletes, and effective treatment plans. 13

Statement of Problem

It is a common recommendation that athletes struggling with persistent fatigue consult a healthcare professional. Healthcare professionals will often order a if anemia is suspected. A (CBC) is the universal blood test used to help diagnose disease and blood disorders. A CBC includes both of the accepted methods to test for IDA: and . Both of these tests show current levels of iron in the blood and are used to diagnose iron deficient anemia. However, a CBC test does not include a serum ferritin test which measures the amount of iron stores. The problem is that many coaches, athletes, parents, and family practitioners are not aware of the current theories and methodologies driving new research on iron deficiency.

Non-anemic athletes can still be iron depleted, but are rarely given the serum ferritin test (Weinstein, 2009). What constitutes an adequate level of ferritin is also commonly debated, as opinions often vary greatly. While the general population can usually function normally with depleted serum ferritin levels, low iron stores are suspected to have a more dramatic effect on endurance athletes.

Purpose of Study

The purpose of this study was to explore the differing opinions surrounding the importance of testing multiple markers of iron status concerning fatigue with endurance athletes. Athletes, parents, coaches, and healthcare professionals need to be educated not only on the side effects of iron deficiency, but also informed of the current best methods of diagnosis along with safe and effective methods to raise iron levels. 14

Significance of Study

Athletes suffering from abnormal levels of fatigue will often undergo CBC tests to measure red blood cells, hemoglobin, and hematocrit levels. These are considered the body’s current iron in the blood stream (National Institutes of

Health, 2016). Current research is placing additional value in measuring iron stored in the body through a serum ferritin test (Hill, 2014). Serum ferritin is currently a separate test and not considered part of the CBC test. Depending on the physician’s initial diagnosis, this test is often not covered by insurance. The purpose of this study was to examine the differing opinions toward the importance of monitoring iron stores, methods of diagnosing iron depletion, effects of iron depletion on endurance athletes, effective treatment options, and to determine the need for educational opportunities available for athletes, parents, and coaches.

Definition of Terms

To provide clarity, some medical terms specific to this study have been listed below. While commonly used in the medical field, athletes, coaches, and athletic trainers may need this for reference purposes.

Anemia. Anemia is simply having a low hemoglobin level which negatively

affects the body’s ability to carry oxygen (Weinstein, 2009).

Complete blood count (CBC). A complete blood count is a blood test used to

evaluate overall well-being through measures of red blood cells, white blood

cells, hemoglobin, hematocrit, and platelets (National Institutes of Health,

2016). 15

Erythrocyte. Erythrocytes are red blood cells which carry hemoglobin

(National Institutes of Health, 2016).

Hematocrit. An important piece of a CBC test, the hematocrit measure is the ratio of the total volume of red blood cells as compared to the total volume of blood (Peeling et al., 2008).

Hemoglobin. Hemoglobin is the protein molecule in red blood cells that carries oxygen from the lungs to the body's tissues and returns carbon dioxide from the tissues back to the lungs. Adult women should exhibit hemoglobin levels at or above 12.0 g/dL while men should be at or above 13.5 g/dL

(Weinstein, 2009).

Hemolysis. Hemolysis is the premature destruction of red blood cells and the release of their contents into the surrounding fluids (National Institutes of

Health, 2016).

Hepcidin. Hepcidin is a small protein secreted by the liver which regulates iron entry into the circulatory system (Peeling et al., 2008).

Iron. Found in hemoglobin, iron is essential in the transfer of oxygen from the lungs to cellular tissues (National Institutes of Health, 2016).

Iron depletion (ID). ID is defined as the decrease of the total content of iron in the body. This can happen for many reasons, therefore can be difficult to diagnose. This is best measured through serum ferritin levels, which are not considered part of a CBC test (Bermejo, 2009).

Iron deficiency anemia (IDA). IDA occurs when the iron deficiency is significant enough to slow production of red blood cells, causing 16

anemia. This is best measured through hemoglobin and hematocrit tests

(Bermejo, 2009).

Iron Deficient Non-Anemic (IDNA). IDNA is defined as having normal

hemoglobin levels but low serum ferritin levels. This is best measured

through ferritin and saturation tests (Tidy, 2008).

VO2 max. VO2 max is a measure of the maximum volume of oxygen that an

athlete can use (Weinstein, 2009).

Research Questions

This study focused the following research questions:

1. Why do varying opinions exist pertaining to healthy levels of serum

ferritin and its relevance toward endurance athletes?

2. What level of understanding do coaches, athletes, parents, and healthcare

professionals have regarding the effects, diagnosis, and treatment options

of iron deficiency?

Limitations

This study included the following limitations:

1. The sample of participants was selected regionally. Therefore, results may

not reflect knowledge base or perceptions outside of the region. Future

studies might consider expanding the selection to a broader audience.

2. In addition to iron deficiency, there are several other variables that can

impact the initial perception of fatigue. These additional variables may

include rest, diet, stress, genetics, disease, disorders, and general 17

motivation, all of which are beyond the control of the researcher. Future

studies might consider exploring the effects of these additional variables.

Delimitations

This study included the following delimitations:

1. The researcher does not have the credentials or certifications to administer

nor read blood tests.

2. The researcher does not have the credentials or certifications to diagnose

nor treat any symptoms of iron deficiency, inflammatory disease, or blood

disorder that participants may exhibit.

3. Therefore, the researcher will focus on establishing grounded theories

based on common perceptions through exploratory research gathered from

in-depth interviews.

Assumptions

This study included the following assumptions:

1. The selected participants understood the context and vocabulary associated

with the questions.

2. The selected participants accurately indicated their current knowledge and

perceptions on the effects of iron and ferritin levels.

3. The perception data from the participants was interpreted accurately.

Organization of the Study

This research study is presented in five chapters. Chapter one is an introduction and background of the study. This chapter also outlines the statement of the problem, purpose of the study, significance of the study, 18 definition of important terms, research questions, limitations, delimitations, and assumptions with the study. Chapter two presents a full review of the current literature pertaining to iron deficiency and endurance athletes. This chapter includes important background information relevant to this study, the effects of iron depletion on endurance athletes, methods of diagnosis, and effective treatments. Chapter three describes the methodology for this research including the selection of participants, instrumentation, data collection, and data analysis procedures. Chapter four presents the results of the study while chapter five summarizes and describes the implications of the results, and suggests recommendations for future research.

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Chapter Two - Review of Literature

Introduction

The purpose of this review of literature was to examine the effects of iron deficiency on endurance athletes, determine the best methods of diagnosis, and establish safe and effective treatments. While doctors have known for years that iron deficiency is the single most common nutritional deficiency worldwide, recent findings and scientific contradictions have challenged conventional processes in diagnosing and treating this deficiency (Johnson-Wimbley &

Graham, 2011). Found in red blood cells, iron plays a significant role by helping carry oxygen and nutrients to muscular tissue, then carrying carbon dioxide and other toxins away (Grinaker, 2014). Therefore, iron deficiency directly affects the efficiency of both the oxygen and energy delivery systems within the human body. Athletes with low iron levels have difficulty moving the needed oxygen to the cells, allowing fatigue to set in earlier than it should causing measurable drops in performance.

When a patient reports higher levels of fatigue than normal, conventional doctors often order general CBC tests (complete blood count) to measure red blood cells, hemoglobin, and hematocrit levels. These tests measure what is often considered as the body’s current iron levels within the bloodstream (National

Institutes of Health, 2016). Current research is placing more value on the body’s stored iron measures. However, these tests are not included in the commonly ordered CBC test. Even with the current knowledge of the importance of stored 20 iron, these tests are rarely ordered by family practitioners and are often not covered by insurance.

Several solutions currently exist to help raise iron levels in those who would suffer performance effects due to iron deficiency. Both oral and intravenous supplements are available, but can carry some significant side effects if not taken under the cautious care of a knowledgeable physician (Johnson-

Wimbley & Graham, 2011).

The following review of literature is organized into four subsections: (a) scientific background and definitions, (b) iron and its effect on endurance athletes,

(c) diagnosing low iron, and (d) supplementation. This information will be extremely important in helping athletes, parents, and coaches effectively communicate with their physicians concerning the physical effects of iron deficiency, delineating the best methods of diagnosis, and helping establish safe, yet effective treatments.

Scientific Background and Definitions

Iron deficiency is the single most common nutritional deficiency, affecting nearly two billion people worldwide (Johnson-Wimbley & Graham, 2011). In developed countries, disease, disorder, and side effects of certain medicines are the most common causes for ID while persons in developing countries are often plagued with parasites, malnutrition associated with poverty and cereal-based diets, and infectious disease such as malaria, HIV, and tuberculosis (Camaschella,

2015). 21

Hemoglobin is a complex protein found within red blood cells containing an iron molecule that carries oxygen from the lungs to the muscle tissues. As the tissues use up the oxygen, carbon dioxide (a toxic byproduct created in this exchange) is produced and must be carried away. The iron molecule within hemoglobin exchanges oxygen for carbon dioxide, then transports this toxin back to the lungs for elimination through respiration (National Institutes of Health,

2016).

When patients complain of frequent, heightened, or chronic fatigue and are not showing obvious symptoms of disease or infection, doctors often order a

CBC test to check for iron deficiency. Iron deficiency is often broken into three categories: iron depletion (ID), iron deficient but non-anemic (IDNA), and iron deficiency anemia (IDA). IDA refers to a patient diagnosed as anemic due to low (RBC) count or low hemoglobin levels while IDNA refers to patients falling in the normal ranges for red blood cell count and hemoglobin levels, but reporting low iron stores. IDNA has been found to be approximately three times more common than IDA (Jade, 2016; Tidy, 2014; Weinstein, 2009).

Anemia is a common condition associated with severe iron depletion in which the bloodstream does not have enough healthy red blood cells to carry sufficient amounts of hemoglobin to fatigued muscular tissue. Patients are often diagnosed as anemic when their hemoglobin levels fall below 12 g/dL for women and 13.5 g/dL for men (National Institutes of Health, 2016). When a patient has a circulatory system without an adequate supply of red blood cells and therefore cannot provide sufficient amounts of oxygen due to the limited levels of 22 hemoglobin, the patient typically reports symptoms of fatigue, lack of concentration, general weakness, unexplained loss of energy or motivation, and/or lack of work productivity as their aerobic capacity is greatly diminished due to tissue hypoxia (lack of oxygen). The challenge in correctly diagnosing iron deficiency, is that the measures within the blood tests can be affected by several different variables including disease, disorders, inflammation, diet, gastrointestinal bleeding, hemolysis, and hepcidin levels.

Iron and Its Importance to Endurance Athletes

Relevance to endurance athletes. Nearly 40 years ago, Clement Finch proved that iron stores can play a significant role in muscle fatigue, even when hemoglobin levels are reported to be normal. Often referred to as “The Iron

Man”, Dr. Finch designed an iron study involving two groups of rats. One group of rats were placed on a diet with insufficient intake of iron, while the control group enjoyed a normal diet. After a month on this diet, the iron-depleted rats were given transfusions that would ultimately raise their hemoglobin back to the same level as the control group, but would not influence their depleted iron stores. Both groups of rats were given treadmill tests to exhaustion. The iron- depleted, but non-anemic group exhausted much more quickly and with much higher levels of lactate in their muscle tissue indicating the importance of IDNA associated with muscle fatigue (Finch et al., 1979).

Oxygen delivery and cellular respiration. Iron deficiency has been shown to affect much more than just athletic performance. Iron deficiency has been shown to affect cognitive thinking, memory, mood, fatigue, work capacity, 23 and athletic performance which all depend greatly on the body’s ability to adequately and effectively transport oxygen for use in a metabolic process called cellular respiration (Rowland, 2012). Iron is an essential component of blood which is directly linked to the efficiency of this metabolic process due to its importance in the delivery of oxygen used in the production of cellular energy

(Peeling et al., 2008).

The Krebs cycle (also known as the citric acid cycle) is a series of chemical reactions that create a usable form of chemical energy converted from stored energy in foods: adenosine triphosphate (ATP). ATP is the main source for chemical energy that fuels muscular tissue. During a process called cellular respiration, ATP is produced by mitochondria which use large amounts of oxygen to convert glucose (stored energy in foods) into this chemical energy. Referred to as the powerhouse of the cell, each cell contains large numbers of these mitochondria. This particular method of energy metabolism relies heavily on the body’s ability to deliver sufficient amounts of oxygen while removing the byproduct (carbon dioxide). Due to its important role in hemoglobin’s ability to deliver oxygen and remove carbon dioxide, iron becomes an essential component to this process (Hinton, 2014; Orphardt, 2003; Scitable, 2014).

Once the cells exhaust their supply of oxygen, the aerobic energy metabolism (Krebs cycle) begins to switch over to anaerobic metabolism. This chemical transfer generally happens during intense exercise: activities requiring sustained sprinting. In the absence of oxygen, the Cori cycle (also known as the lactic acid cycle) can sustain ATP levels for a short time but consequently 24 produces a compound known as lactic acid. Excessive buildup of lactic acid in muscle tissue is known to cause pain and cramping (Orphardt, 2003). Iron is important in this process as well considering it is one of the important cofactors for the alpha glycerophosphate oxidase enzyme (also known as glycerol-3- phosphate oxidase). This enzyme, which is located in the mitochondria, is one of the key enzymes used in the Cori cycle during this anaerobic form of metabolism.

Especially in athletes, muscles must be able to synthesize this form of energy and efficiently transport the lactic acid to the liver to be converted back to glucose, or muscle activity will be severely limited and possibly shut down. Studies on both animals and humans diagnosed with iron deficiency have shown 30-70% reductions in mitochondrial proteins reflecting in significantly lowered aerobic capacity and VO2 max (Colter, 2017; Hinson, 2014; Orphardt, 2003).

Oxygen delivery and VO2 max. As performances in endurance sports are directly related to cardiovascular capacity, athletes and their coaches are constantly researching methods to increase the proficiency and effectiveness of their oxygen delivery systems. Because iron plays such a significant role in maximizing the efficiency of aerobic metabolism, superior endurance performances require an optimal iron balance (Reinke et al., 2012). VO2 max, also referred to as maximal oxygen uptake, is considered by most to be the best measure of cardiovascular endurance and is often used to calculate the various training paces for competitive runners (Davis, 2016). An athlete’s VO2 max is a numerical measurement of the body’s ability to consume oxygen. This measure is derived by calculating the volume of oxygen used while running at maximum 25 capacity. The best way to measure this volume of oxygen is to run at maximal effort for approximately 10 minutes on a treadmill. While on the treadmill, runners wear a breathing mask that is used to measure the amount of oxygen uptake required by the athlete to complete this intense exercise (Davis, 2016;

Friedman et al., 2001; Joyner & Coyle, 2008). Normal ranges are 30-50 ml/min/kg (milliliters per minute per kilogram of weight) for average participants while elite athletes often report measures upwards of 70-80 ml/min/kg. Although studies have shown that elite endurance athletes predictably have high VO2 max measures, VO2 max has not been shown to consistently predict actual athletic outcomes due to the multiple variables associated with competition. Distance events ranging from 3000 to 5000 meters (which are typical distances for high school races) usually require close to 100% of VO2 max while longer, slower- paced events (such as the marathon distance) rely more on efficient aerobic metabolism of stored energy (Davis, 2016; Joyner & Coyle, 2008).

As iron is an essential component of hemoglobin, multiple studies have shown that increased iron directly correlates to an increased VO2 max

(Hutchinson, 2014; Rowland 2012). However, as iron impacts the ability of the body to deliver oxygen to cells, iron depletion correlates directly to lower VO2 max (Joyner & Coyle, 2008). In a study using lab rats, researchers found that hemoglobin is directly proportional to VO2 max. Rats with the lowest hemoglobin levels also had the lowest V02 max measures and vice versa (Perkkio et al., 1985). In a study performed on elite athletes ranging in ages from 13 to 25, researchers found that both VO2 max and oxygen consumption increased in 26 athletes suffering from IDNA when supplements were used to replete iron stores

(Friedmann et al., 2001).

Athletes participating in sports associated with higher oxygen and energy expenditure rates have been shown to be at risk for iron depletion (Koehler et al.,

2012). As endurance athletes place higher demands on their oxygen delivery systems and energy metabolism mechanisms, monitoring and maintaining a proper balance of all related components is essential in reaching and sustaining peak performance. As iron plays an important role in both of those systems, it is crucial for these athletes to maintain appropriate iron stores to support the transfer of oxygen to muscular tissue. Therefore, athletes plagued with iron deficiency will suffer from limited production of ATP which will lower both the maximal

(VO2 max) and submaximal (aerobic) exercise capacities (Hinton, 2014).

Iron depletion associated with endurance athletes. While endurance sports in general are taxing on the body, distance running has been shown to deplete iron stores over time without rest or use of supplements (Auersperger et al., 2013). Although runners, cyclists, and triathletes report higher rates, 20-50% of all athletes are reported to suffer from iron depletion (Hinton, 2014). The higher prevalence for iron depletion in these athletes is often attributed to exercise-associated losses, destruction of red blood cells, reduced iron absorption, and insufficient diet routines (Auersperger et al., 2013; Camaschella, 2015;

Hinton, 2014; Pasricha et al., 2014; Telford et al., 2003). Female athletes are much more susceptible to iron depletion due to additional blood loss via menstruation and self-restricted diets to achieve or maintain a specific body 27 weight. Studies have reported nearly 70% of female athletes suffer from some form of iron deficiency (Grinaker, 2014; Pasricha et al., 2014). In a recent study of 14 female athletes, researchers investigated the effect of long-term sustained exercise on both iron deplete and iron replete runners. After 8 weeks, 71% of the participants reported reductions in serum ferritin (commonly used to measure the body’s stored iron) suggesting that distance running depletes iron stores over time without rest or supplementation (Auersperger et al., 2013). In a recent study of elite rowers and professional soccer players, researchers investigated the effects of a full competitive season on the athlete’s iron stores. At the end of the season,

70% of the athletes reported reductions in iron stores, with 20% of the athletes having ferritin levels leading to a diagnosis of IDNA. Additionally, 10% of those athletes reported hemoglobin dropping to the lowest acceptable level, suggesting mild cases of IDA (Reinke et al., 2012).

Iron deficiency is generally associated with inadequate absorption or exaggerated blood losses. The existence of IDNA is more common in competitive endurance athletes as compared to their sedentary counterparts. This is primarily due to the additional exertion placed on the body along with greater demands placed on their red blood cells and oxygen delivery systems (Hinton,

2014; Tidy, 2014). Under normal conditions and a balanced diet, the human body should be able to sustain the cycle of red blood cell erythropoiesis (cell production) and eryptosis (programmed cell death) with no signs of abnormal symptoms or fatigue. However, endurance athletes often put their bodies through extended periods of intense physical exertion that places higher demands on the 28 oxygen delivery and muscular systems. Due to this physical exertion, these athletes are reported to have higher rates of exaggerated blood loss through gastrointestinal bleeding, hemolysis, and are more susceptible to iron depletion through elevated levels of hepcidin, iron lost through excretion (sweat, urine, and feces), inadequate dietary intake, rapid growth spurts during adolescence, and frequent use of medicines designed to ease inflammation and calm agitated digestive systems (Camaschella, 2015; Hinton, 2014; Hutchinson, 2014; Pasricha et al., 2014; Weight et al., 1992).

Hemolysis is the early destruction of red blood cells which can be caused by bacteria, parasites, autoimmune disorders, genetic disorders, stress, overexertion of muscular tissue, and even footstrike. Exercise induced hemolysis has been associated with swimming, cycling, rowing, running, and strength training and has shown a positive correlation with the intensity of the activity

(Hinton, 2014). Due to long periods of muscle exertion with little rest, distance running in particular can lead to significant destruction of red blood cells, placing these athletes at an even higher risk for iron depletion (Hutchinson, 2014; Telford et al., 2003).

Red blood cells, which are generated in bone marrow, have a normal lifespan of approximately 120 days. As the red blood cells age and their plasma membranes weaken, they are attacked and recycled by macrophages within the liver and spleen. The hemoglobin within the dying cells is then processed and recirculated back into the bone marrow via a protein called transferrin. This recycled form of iron is then reused in the production of new red blood 29 cells. However, the life cycle of red blood cells can be shortened under heavy stress and exertion. Studies of long distance runners have shown red blood cell lifespans shortened to as few as 74 days (Weight et al, 1992).

Footstrike has also been linked to hemolysis in distance runners. As the red blood cells travel through the tiny capillary blood vessels located in the bottom of the foot, these fragile cells can be damaged or even crushed with each step. Reported to have a positive correlation with exercise intensity, studies have shown footstrike hemolysis can account for up to 4 times the amount of hemoglobin lost as compared to general exercise-induced hemolysis (Hutchinson,

2014; Telford et al., 2003). However, there are some who refute this theory, claiming the iron lost in dying cells is eventually recycled for use through the body’s natural iron cycle (Lippi et al., 2012).

Hepcidin is a small acute-phase protein secreted by the liver which regulates iron absorption and its entry into the circulatory system (Bermejo, 2009;

National Institutes of Health, 2016). Acute-phase proteins are a type of protein whose plasma concentrations increase or decrease in response to inflammation.

Because hepcidin is a positive acute-phase reactant, it increases with infection and inflammation in order to minimize the absorption of iron (Pasricha et al., 2014).

This immune system response is a defense mechanism designed to withhold iron from invading pathogens (Girelli et al., 2016). Studies have also shown that hepcidin levels will increase as a response to prolonged bouts of intense exercise which often cause inflammation as well. In a study of 14 runners (7 with normal iron levels), researchers found that hepcidin levels rose while iron stores fell after 30

8 weeks of intense training in all participants. Iron stores reportedly dropped by

50% across both groups, shifting 40% of participants of the normal group into the iron deficient group. These researchers concluded that exercise induced inflammation and its negative effects on absorption rates, can lead to iron deficiency in endurance athletes over time without the use of supplements

(Auersperger et al., 2013; Hinton, 2014; Peeling et al., 2008).

In addition to exercise-induced blood loss, hemolysis, and raised hepcidin levels, endurance athletes are also susceptible to iron depletion through inadequate dietary intake, iron absorption issues associated with some over-the- counter medicines, and additional strains placed on the energy systems during adolescent growth spurts. Unfortunately, many of these athletes become susceptible to iron deficiency as they rarely adapt their diets to reflect their heightened states of iron depletion (Loosli, 1993). Elite athletes are extremely attentive of their body composition. Distance athletes are particularly concerned with their body weight. While distance runners should be increasing their dietary intakes due to the large amounts of calories burned during exercise, they often restrict their diets in order to maintain a desired weight. This puts adolescent endurance athletes at particular risk due to their increased caloric needs associated with both exercise and growth spurts coupled with the risks related to limiting their dietary intake in order to maintain a certain weight through these years of growth (Camaschella, 2015; Koehler et al., 2012).

To combat constant muscle soreness, irritable bowels, and upset stomachs, endurance athletes use a multitude of readily available over-the-counter 31 medicines. Frequent use of nonsteroidal anti-inflammatory drugs (often referred to as NSAIDS) has been linked to enteropathy (malabsorption syndrome) and gastrointestinal bleeding. Familiar forms of NSAIDS often used by runners include aspirin (Bayer), ibuprofen (Motrin, Midol, Advil), and naproxen (Aleve,

Flanax), all of which are extremely harsh on the digestive system. Frequent use of proton pump inhibitors (often referred to as PPI’s) to reduce gastric acid has been linked to malabsorption of essential vitamins and minerals including iron.

Commonly used PPI’s include Nexium, Prevacid, and Prilosec (Bermejo, 2009;

Camaschella, 2015).

Symptoms and effects of iron deficiency. The effects of iron depletion can be subtle, especially in athletes plagued by IDNA. Therefore, symptoms can often go unnoticed or dismissed as general fatigue from training. Because of these obscure effects, iron deficiency frequently goes undiagnosed unless a blood test is requested (Camaschella, 2015). Symptoms of iron depletion can include hair loss, pica (craving non-food items such as chalk or ice), weakness, fatigue, poor work productivity, lack of concentration, loss of memory, and can lead to a dramatic effect on athletic performance due to the lowered VO2 max and decreased aerobic metabolism (Hinton, 2014; Tidy, 2014; Weinstein, 2009). In studies performed by Perkkio et al. (2015) and Rowland (1988), sharp declines in endurance performances were recorded when non-anemic athletes reported even small drops in iron stores. While there have been numerous studies with animals concluding that IDNA can have a huge impact on performance, most of the human studies have focused on the general health effects of IDA on average 32 participants. It is known that even slight reductions in hemoglobin can have a profound effect on both exercise and work capacity. IDA is also known to have a considerable effect on cognition which in turn has led researchers to contemplate the effects of iron depletion on the mental state of athletes. Many speculate that even a small decrease of iron stores can have a devastating effect on the determination and fortitude required by competitive endurance athletes (Rowland,

2012). However, the general scientific community hasn’t arrived at the same unequivocal conclusions on the effects of IDNA. To gain more scientific precedence and develop stronger outcomes, researchers in the medical fields yearn for more studies which focus directly on the effects of IDNA on human endurance athletes. The few existing studies are often debated due to the many uncontrollable variables involved in distance running: weather, motivation, competition, training groups, coaching, injury, and nutrition (Rowland, 2012).

Importance of monitoring dietary intake. Due to the extra calories required for exercise and the negative side effects of iron depletion, endurance athletes should routinely monitor and track their dietary intake (Loosli, 1993;

Reinke et al., 2012). While a healthy body presented with a healthy diet should be able regulate its own iron cycle, endurance athletes may need to consider supplementation of essential vitamins and minerals if their caloric intake or absorption rates aren’t sufficient (Hinton, 2014; Mandali, 2011; Reinke et al.,

2012). Finch’s monumental study of iron (1979) revealed that iron infusions given to iron depleted rats brought their performances back up to the same marks as the placebo rats. Consequently, Finch provided one of the first studies showing 33 the importance of iron supplementation on iron deplete subjects (Finch et al.,

1979). Friedmann (2001) found the same to be true concerning performance and young athletes. Athletes suffering from IDNA were given supplements to raise low iron stores, this led to increases in both aerobic capacity and athletic performance (Friedman, 2001).

Even though iron is an essential mineral, too much iron is known to be toxic to humans. While studies have shown that increased iron stores can raise both work and exercise performance, too much can lead to iron poisoning.

Athletes and coaches fearing iron depletion, should consult a physician and request a blood test before beginning any form of supplementation (Hutchinson,

2014; Weinstein, 2009).

Diagnosis of Iron Deficiency

Importance of screening. While iron deficiency is much more common in developing countries, women with heavy menstrual loss, and men with digestive disorders, these assumptions often lead to misdiagnosis and delays in treatment (Bermejo, 2009). Athletes with aggressive training programs should consider regular screenings of iron status. In separate consensus statements published in 2009 by both the American College of Sports Medicine and the

International Olympic Committee, researchers recommended routine hematological assessments as part of the pre-participation health examinations for competitive athletes (Ljungqvist et al, 2009; Rodriguez et al., 2009). The rationale for this statement is based on the higher-than-expected prevalence of iron depletion in athletes. Given the importance of iron in oxygen delivery and 34 energy metabolism required for endurance sports, routine screening is recommended for all athletes and strongly recommended for athletes considered to be at high risk. Athletes considered as high-risk for iron depletion include distance runners, vegetarian athletes, adolescent athletes, and especially female athletes of reproductive age (Koehler, 2016; Rodriguez et al, 2009; Rowland,

2012). Dating as far back as 1990, researchers have recommended that pre- participation physical evaluations (PPE) include hematological screening for iron status (Risser & Risser, 1990). While PPE’s are required by most high school and collegiate activity associations, hematology lab tests are generally not considered to be an essential piece of this health examination (Bernhardt & Roberts, 2010).

These periodic required screenings would be especially helpful in diagnosing

IDNA when symptoms aren’t obvious. While mild iron depletion may not be viewed as significant from a health perspective, it can still have dramatic effects on both work and athletic capacities (Ljungqvist et al, 2009; Rodriguez et al.,

2009; Weinstein, 2009). As iron stores often take three to six months to replete, early detection through screening can help athletes begin a safe routine of iron supplementation allowing them to continue training and competing at high levels

(Koehler, 2016).

Current research reveals that red blood cell count and hemoglobin level are believed to be the best measures for diagnosing anemia, while serum ferritin is arguably the best measure for assessing the body’s total iron stores (Chua, 1999;

Hinton, 2014). These tests are generally ordered when patients report unusual fatigue and weakness. Unfortunately, serum ferritin is a separate test and is often 35 not ordered when red blood cell count and hemoglobin levels are reported to be within acceptable ranges. However, contemporary research now suggests utilizing all three of the aforementioned methods along with measures of hepcidin, total iron-binding capacity (TIBC), transferrin, and soluble transferrin receptors in order to build a complete picture of total iron status (Burden et al.,

2014; Camaschella, 2015; Hinton, 2014; Koehler, 2016; Pasricha et al., 2014;

Rowland, 2012).

Frequent monitoring of iron status can greatly assist in the diagnosis of iron depletion and establish treatment options. While the American College of

Sports Medicine recommends screenings before competitive seasons, others recommend monitoring as often as every four to six weeks especially with at-risk athletes (Hinton, 2014; Rodriguez et al., 2009). The main symptom of iron deficiency (fatigue) can be difficult to measure. Diagnosis without a blood test can be further hampered as the athlete often becomes tolerant of the symptoms due to its gradual progression. Athletes often begin to accept the feelings as normal and may not regain awareness until iron stores are replete.

While elite and college athletes often have access to team physicians and diagnostic labs, high school and recreational athletes have fewer options for care and can be cost-prohibitive (Koehler, 2016). Depending on insurance coverage, office visits coupled with additional lab fees can cost several hundred dollars for each screening. Typically, an athlete reporting unusual fatigue would make an appointment to visit with their doctor to discuss medical history and current symptoms. If anemia was suspected, the doctor would take a blood sample and 36 deliver it to a local medical lab. The medical lab would run diagnostic tests on the sample and report their findings back to the doctor who would finally interpret the results for the patient during an additional office visit. Recently, labs have begun opening their doors to patients requesting lab work without physician requests. Companies such as Quest Diagnostics and LabCorp offer direct appointments at a fraction of the cost. Websites such as WalkinLab.com and

HealthcareBluebook.com offer assistance in locating and setting up affordable appointments at local medical labs. According to current pricing, these same diagnostic labs can range from $17 for an individual test to $100 for the complete iron panel, making this a much more affordable option for those with limited incomes or inadequate medical insurance (Healthcare Bluebook, 2017; Walk-In-

Lab, 2017).

Methods of diagnosis. When patients complain of fatigue, most doctors will order a CBC test to analyze white blood cells, red blood cells, and platelets.

White blood cell (WBC) evaluations can be helpful in detecting undiagnosed medical conditions and hidden infections. Because WBCs fight disease, levels will be elevated in patients suffering from infections or inflammatory disease.

Platelet evaluations are helpful in diagnosing various blood disorders and cancers.

Red blood cell (RBC) evaluations are helpful in detecting iron deficiency. These evaluations include assessments of hemoglobin and hematocrit levels along with analysis of the shape, size, and total count of the RBCs. These tests measure the body’s current iron within the bloodstream and its ability to carry oxygen throughout the circulatory system. Abnormally low measures within the RBC 37 evaluation lead to a diagnosis of anemia, requiring further testing to pinpoint the cause.

Early detection of iron deficiency is especially important to endurance athletes as treatment options generally require several months for even partial recovery. While RBC count, hemoglobin, and hematocrit are common measures for IDA, there are numerous factors that can affect overall iron status

(Camaschella, 2015; Hinton, 2014; Koehler et al., 2012). According to Dr. Scott

Koehler (2016), the aforementioned tests can lead to misdiagnosis in endurance athletes during periods of intense exercise. Due to the nature of their sport, these athletes often struggle with inflammation and dehydration, both of which can cause deceivingly elevated levels within the RBC evaluation. While generally not life-threatening, misdiagnosis is common with IDNA and can lead to months of treatment, recovery, and submaximal performance (Koehler, 2016). A recent study found that doctors can misdiagnose iron deficiency in females 34-82% of the time when only testing hematocrit and hemoglobin levels. While hemoglobin and hematocrit levels were generally within the acceptable ranges for these participants, their iron stores were often found to be deficient (Hill, 2014). In order to identify iron deficiency in its earliest stages, research suggests that athletes request additional tests of iron status (beyond the standard CBC) when visiting a physician (National Institutes of Health, 2016; Weinstein, 2009). Tests available for iron status include but are not limited to serum ferritin, hepcidin, total iron-binding capacity, , transferrin, , soluble transferrin receptors, and endoscopies when severe gastrointestinal bleeding is 38 suspected. (Bermejo, 2009; Girelli et al., 2016; Hinton, 2014; Koehler et al.,

2012; McClung et al., 2013; Rowland, 2012).

Ferritin is a storage vessel that provides additional iron when the body needs it. While very little ferritin circulates in the bloodstream, this tiny amount has been found to be proportional to the amount of ferritin stored within the liver

(Hinton, 2014; Rowland, 2012). When needed, the body signals the liver to release more ferritin into the bloodstream which binds with a protein called transferrin. Transferrin is the transport mechanism that delivers the additional ferritin to the iron deficient cells and tissues (Nall, 2015). As ferritin is an acute phase reactant, its levels can be misinterpreted during periods of infection or inflammation. Studies have shown that serum ferritin levels can rise in context to exercise-induced inflammation without improving iron status (McClung et al.,

2013; Schumacher et al., 2002). While acceptable values are often debated, serum ferritin continues to be the preferred method of measuring iron stores especially in the absence of infection or inflammation (Bermejo, 2009;

Camaschella, 2015; Chua, 1999; Rowland, 2012; Schumacher et al., 2002).

Discovered in 2001, hepcidin is a new addition to discussions on iron status and its molecular importance. Hepcidin is a peptide hormone secreted from the liver which plays a crucial role in iron homeostasis by regulating the absorption of iron and its entry into the bloodstream. To maintain iron homeostasis, levels of hepcidin decrease to allow more absorption of iron and increase when iron is plentiful. Because hepcidin is an acute phase reactant, its levels will also rise during episodes of inflammation and infection in order to 39 limit or block absorption. This process is believed to be a defense mechanism designed to deprive nutrients to invading pathogens (Girelli et al, 2016; Hinton,

2014; McClung et al., 2013).

Additional studies and further research are needed to unlock the full potential of hepcidin and its relationship to iron deficiency. Researchers have yet to fully decipher its mechanisms and its specific relationship in regard to inflammation. Due to muscular inflammation following intense, prolonged exercise, elevated hepcidin levels have been reported in athletes which complicates its relationship specific to distance runners (McClung et al., 2013).

Total iron binding capacity (TIBC), unsaturated iron binding capacity

(UIBC), serum iron, transferrin, and transferrin saturation (TSAT) are generally part of the same iron test. These measures are used to evaluate the body’s ability to bind and transport iron throughout the circulatory system. Iron is transported in the bloodstream bound to a protein called transferrin. The body produces transferrin based on its need for iron. When iron stores are low, transferrin numbers will increase indicating a deficiency of iron. Low transferrin levels can also be a sign of liver disease or diets that lack adequate amounts of protein

(Mangin, 2016).

The TIBC is used to evaluate the body’s ability to bind iron with transferrin. This test measures the maximum amount of iron that transferrin proteins can transport efficiently throughout the circulatory system. Because these proteins are the most dynamic carriers of iron, the TIBC test is a fairly accurate way to indirectly estimate the number of transferrin proteins available for 40 transport (Cirino, 2016). Under normal conditions, approximately one third of available transferrin are bound to iron molecules leaving two thirds available for reserves (Lab Tests Online, 2015).

Serum iron is a test that measures the total amount of iron in the blood, nearly all of which is bound to transferrin proteins. Because serum iron can fluctuate throughout the day, it is often used in conjunction with TIBC measurements and considered part of the iron-binding capacity assay. Also reported with TIBC, the UIBC a measure of the reserve amount of transferrin which are not bound to iron. The UIBC is calculated as the TIBC minus the total serum iron found in the blood (Iron Disorders Institute, 2017; Lab Tests Online,

2015).

While all of these tests can be useful in diagnosis of iron deficiency, test preference can vary greatly from lab to lab. Some labs prefer to test transferrin indirectly through TIBC panels (which include serum iron) due to its cost- efficiency, some labs prefer the direct measurement of transferrin, while others prefer to focus more on the transferrin saturation percentage (Iron Disorders

Institute, 2017).

Transferrin saturation (TSAT) is calculated by comparing the total available iron (serum iron) to the total iron-binding capacity (TIBC). Even though TSAT levels indicate the body’s ability to transport iron while serum ferritin levels indicate the body’s amount of stored iron, TSAT measures are viewed by some physicians as an alternative test to serum ferritin. However, as 41 both measures are directly affected by inflammation, physicians may not order both sets of tests (Mangin, 2016).

In a study of the effects of a 7-day military training exercise, McClung et al (2013) found that hepcidin and serum ferritin both increased as a result to the inflammatory response provoked by the release of proinflammatory proteins known as interleukin 6 (IL-6). IL-6 is primarily produced at the site of inflammation and is known to play a key role in defining the acute phase response. This 7-day study determined that serum ferritin and hepcidin measures both increased as a result from the increased levels of IL-6. However, the soluble transferrin receptors remained unchanged during this period of inflammation, leading the researcher to hypothesize its future importance towards iron status in the presence of inflammation (McClung et al., 2013).

Soluble transferrin receptors (TfRs) are carrier proteins for transferrin and offer physicians a relatively new test with a promising future. TfRs are present on all cell surfaces and mediate the import of iron into the cell. The concentration of

TfRs are regulated by iron stores, therefore inversely related to iron status (Lynch et al., 2005; Schumacher et al., 2002). Iron deficiency will cause an increase in

TfR concentrations as cells must be more competitive for iron requirements, while iron repletion will cause a decrease in this concentration (Hinton, 2014; Mayo

Clinic, 2017). A small percentage of TfRs can be found circulating in the bloodstream as a measurable soluble form. To estimate the number of TfRs available on each cell, researchers have found that concentrations of soluble transferrin receptors (sTfR) circulating in the blood stream are proportional to the 42 concentrations of TfRs found on the surface of cells. Because TfR concentrations are proportional to the cell’s need for iron, the concentration of sTfR proteins closely reflects the body’s iron stores and is considered a reliable marker for tissue iron deficiency (Schumacher et al., 2002; Skikne, 2008).

Unlike acute phase reactants, such as ferritin, hepcidin, and transferrin, sTfR concentrations are not affected by inflammation, infection, or chronic disease (Bermejo, 2009; Mangin, 2016; McClung et al., 2013; Schumacher et al.,

2002; Skikne, 2008). Therefore, these tests can be extremely beneficial in the diagnosis of iron deficiency especially in cases of elevated ferritin levels which may be falsely misinterpreted as healthy due to underlying inflammation, infection, or chronic disease (Hinton, 2014; Mangin, 2016; Mayo Clinic,

2017). In a study of thirty-nine human subjects spread out in three distinct groups

(non-athletes, leisure athletes, and highly-trained athletes), researchers found that hemoglobin, ferritin, and transferrin levels all rose immediately after exercise, while little to no change was noted in the sTfR concentrations. One specific participant was found to have subnormal ferritin levels before the study began. After exercise, this subject’s ferritin levels nearly doubled, completely disguising their iron deficiency (Schumacher et al., 2002). While this test still lacks an international standard of reference for comparison, physicians should consider sTfR concentration measures especially when differentiating between true iron deficiency, iron deficiency of athletes during strenuous training or competition cycles, and iron deficiency caused by chronic disease (Lynch et al.,

2005; McClung et al., 2013; Schumacher et al., 2002). However, measures of 43 sTfR concentrations are most beneficial when combined with other measures of iron status: hemoglobin, ferritin, TIBC, serum iron, and TSAT (Mangin,

2016). Each of these tests offer slightly different vantage points of iron metabolism, allowing the physician to form a comprehensive report of the patient’s complete iron status.

Three stages of iron deficiency. Iron deficiency develops in three distinct stages: depleted iron stores, iron deficiency, and iron deficiency anemia. First, a negative correlation between iron supply and iron demands causes iron stores to be depleted. Second, insufficient iron stores begin to negatively affect erythropoiesis (red blood cell production). Third, anemia develops due to the decline in hemoglobin and red blood cell production. When diagnosing iron status disorders, it is critical to distinguish between iron depletion

(ID), iron deficient but non-anemic (IDNA), and iron deficiency anemia (IDA).

This should be conducted not just through the standard CBC test, but through a complete iron panel including serum iron, TIBC, transferrin, and serum ferritin.

While early detection is advantageous, all three stages are generally treatable

(Bermejo, 2009; Braunstein, 2016; Camaschella, 2015; Carley, 2003; Koehler et al., 2012).

Iron depletion. Sometimes defined as functional iron depletion (ID), stage 1 is characterized by weakened iron transportation due to depleted iron stores within the body’s bone marrow. Generally having few noticeable symptoms, ID is caused by having an imbalance between iron requirements and iron supply. As demands on iron increase, iron stores will be depleted if iron 44 supply is not also increased via diet or supplementation. This stage is usually asymptomatic and generally does not cause a drop in hemoglobin nor hematocrit levels, therefore iron depletion often goes undetected without a serum ferritin test

(Camaschella, 2015; Carley, 2003). Unfortunately, increased ferritin levels in the presence of inflammation cannot rule out the possibility for iron deficiency though, as serum ferritin is an acute phase reactant (Bermejo, 2009). Continued iron depletion without an increase in iron supply will lead to an iron deficiency

(Carley, 2003).

Iron deficient non-anemic. Often referred to as IDNA, stage 2 occurs when the body has adequate levels of hemoglobin to carry oxygen, but impaired oxygen utilization due to inadequate iron stores and decreased total body iron.

Red blood cell production (erythropoiesis) slows due to the continued drop in iron stores, therefore starting to cause a decrease in the body’s total red blood cell count. Indicators of this stage often include a decrease in total available iron, decrease in serum ferritin, and an increase in transferrin levels as the body tries to mobilize as much circulating iron as possible. IDNA is commonly associated with inadequate absorption of iron or exaggerated blood losses. Due to the additional stresses placed on the body, the existence of IDNA appears to be even greater in competitive endurance athletes when compared to their sedentary counterparts (Hinton, 2014; Tidy, 2014). Due to dietary concerns, menstrual blood loss, and exaggerated losses related to strenuous endurance training, up to

33% of female endurance athletes may suffer from IDNA, many of which go undiagnosed (Rowland, 2012). Even with decreased erythropoiesis, symptoms 45 are generally mild for average patients while the iron components of a complete blood count test (CBC) will only show marginal results with hemoglobin levels near the bottom of the acceptable range. However, endurance athletes seem to be more prone to the effects of this stage and often complain of abnormal fatigue even with borderline hemoglobin levels (Goodnough, 2010; Rowland 2012). Due to low, but acceptable hemoglobin levels, serum ferritin and transferrin saturation tests are generally required for diagnosis of this stage (Hynes, 2016; Wade, 2014;

Weinstein, 2009). If this stage goes undiagnosed, production of red blood cells will continue to slow and patients will progress to the much more severe and final stage of iron depletion: iron deficiency anemia (IDA).

Iron deficiency anemia. The third and final stage of iron deficiency is characterized by continued iron depletion that results in damage to cell tissues caused by the deprivation of oxygen and nutrients caused by the decrease in red blood cell count. As IDA sets in, signs and symptoms of fatigue (weakness and shortness of breath) become evident and problematic as they dramatically affect the lifestyle of the patient (Braunstein, 2016; Camaschella, 2015). Physicians are often called upon during this stage, as patients become more aware and worried about this unexplained fatigue. Complete blood count tests will often reveal low hemoglobin and low hematocrit levels which should lead to further tests of iron status: serum iron, serum ferritin, TIBC, TSAT, and

(used to measure size of red blood cells). As IDA is not particularly common, anemic individuals should also be screened for chronic disease and disorders that accelerate iron depletion. Once diagnosed with anemia, patients will require 46 significant changes to their diets along with a treatment plan and iron supplements to accommodate immediate iron requirements and eventually replenish depleted iron stores (Carley, 2003; Rowland, 2012).

Classifications of anemia. Anemia is defined as a decrease in the body’s ability to transport and deliver oxygen usually marked by a deficient number of red blood cells. Once diagnosed with anemia, subjects must take immediate actions to regain the appropriate balance of iron intake, iron absorption, and iron transport to regain and restore a healthy erythropoiesis process. Physicians will need to run a variety of blood panels and possibly collect stool samples in order to determine the root cause of the low hemoglobin count. While there are several forms of anemia, most fall into one of two broad categories: decreased production or increased destruction of red blood cells.

Impaired erythropoiesis (decreased production of red blood cells) can be caused by chronic disease and disorders that affect absorption and transport of iron. Low red blood count and normal serum ferritin levels can be a sign of serious chronic diseases associated with malabsorption syndrome (Nall, 2015).

Directly affecting the absorption rates of iron and other nutrients into the bloodstream, malabsorption syndrome can be caused by several types of inherited blood disorders (such as sickle cell anemia, , and fanconi anemia), autoimmune diseases (such as celiac disease and Crohn’s disease), bacterial infections (such as Whipple’s disease and H. pylori bacteria), chronic inflammation (such as gastritis and irritable bowel disease), and even the overuse of NSAIDs (nonsteroidal anti-inflammatory drugs such as aspirin and ibuprofen) 47 which have been linked to ulcers, gastrointestinal bleeding, and liver problems

(Bermejo, 2009).

Inherited blood disorders can affect the shape, form, and ability for normal production of red blood cells. Sickle cell anemia affects the shape of the red blood cells. Due to their shape, these rigid, c-shaped cells cannot carry as much oxygen as healthy cells. Thalassemia blood disorders create abnormal forms of red blood cells which lead to early destruction. Fanconi anemia is a hereditary condition that causes bone marrow failure, which disrupts or eliminates the production of red blood cells (Macon & Lamoreux, 2017).

Celiac and Crohn’s disease are both autoimmune diseases notorious for causing intestinal inflammation and decreased iron absorption. Due to physical damage of the intestinal walls and inflammation of the surrounding tissues, patients can expect reduced absorption rates of iron, increased frequency of bowel movements, and increased intestinal blood loss, all of which will lead to decreased hemoglobin levels (Freeman, 2016; Murawska et al., 2013).

T. whipplei (Whipple’s disease) and H. pylori are both bacterial infections that manifest within the gastrointestinal system. While T. whipplei bacterial infections are rare, H. pylori bacteria are present in nearly half the world’s population. The prominent symptoms for both of these infections, gastritis and peptic ulcers, can accelerate gastric blood loss while significantly limiting the absorption or iron and other necessary minerals into the bloodstream (Colledge &

Cafasso, 2015). 48

Due to inflammation, irritable bowel disease, ulcers caused by gastritis, and digestive cancers, patients subjected to these chronic illnesses are likely to suffer from gastrointestinal bleeding and malabsorption of vitamins and minerals. When hemoglobin levels are low and ferritin levels are normal, physicians should order stool samples to test for these diseases as well (Bermejo,

2009).

In the presence of such inflammatory diseases or infections, the body will begin to sequester and withhold stored iron as a defense mechanism. While this mechanism significantly limits the bioavailability of iron to these pathogens, it also limits the iron available for iron transport, therefore limiting erythropoiesis as well. Consequently, the blood panels from subjects suffering from these diseases will often report decreased hemoglobin levels yet increased ferritin levels

(Bermejo, 2009; Burns et al., 2015; Parrow et al., 2013).

Need for standardization. Due to the severity of anemia, a simple

Google search can produce numerous medical studies concerning the various diseases and disorders associated with this condition. The results from these studies have helped researchers set universal standards of healthy ranges for each of the measures within the CBC test. Few practitioners will refute the CBC gold standards for hemoglobin, hematocrit, mean corpuscular volume (MCV), and red blood cell distribution width (RCD) when used in diagnosing IDA (Hinton, 2014;

National Institutes of Health, 2016). However, research directed towards the initial stages of iron deficiency (ID and IDNA) is scarce as these symptoms rarely pose an immediate health threat. While most agree that serum ferritin levels can 49 be used to reasonably predict the body’s iron stores, there are very conflicting views concerning the standardized healthy ranges of ferritin, general diagnosis of

IDNA, and iron status treatment for patients with acceptable hemoglobin levels

(Rowland, 2012).

As surveys continually find that up to 30% of athletes suffer from iron depletion, it is evident that practitioners need improved methods of screening for early stages of iron deficiency (Rowland, 2012). When diagnosing iron depletion of any stage, new research shows that practitioners should consider multiple tests of iron status, not just the standard CBC nor serum ferritin. Diagnosis of IDNA can be challenging for endurance athletes when CBC measures might fall within the lower limits of the acceptable healthy ranges while their ferritin levels may be deceitfully high due to inflammation (Camaschella, 2015; Hill, 2014).

Sports physicians have often viewed low ferritin as an early indicator for

IDA while also promoting its importance towards both general health conditions and endurance performance issues. In 2009, the International Olympic

Committee released a statement specifically requesting for further research directed towards the relationship between ferritin, the female athlete triad syndrome, and the onset of iron deficiency anemia. The IOC also recommended the creation of educational programs for athletes, coaches, and healthcare professionals aimed at early identification and treatment of iron deficiency (IOC,

2009).

Early diagnosis of iron deficiency is extremely important as treatment requires several months of iron supplements to replenish both serum iron levels 50 and iron stores. Misdiagnosis can result in exacerbated symptoms, delayed treatments, extended recovery time, and added medical costs (Hill, 2014; Risser &

Risser; 1990). In a study of females from various age groups, IDNA was misdiagnosed in up to 80% of females when CBC tests were the only measures used (Hill, 2014). Even when using the accepted tests for iron status and iron stores, there is still much debate surrounding the diagnosis of IDNA. While some consider serum ferritin, transferrin, transferrin saturation, soluble transferrin receptors, and hepcidin as indicators of iron stores, gold standards have yet to be determined for any of these measures. Additional research from diagnostic labs is recommended to aid in creating universal reference ranges that would greatly assist healthcare professionals in the diagnosis of IDNA (Girelli et al., 2016;

Hinton, 2014; Rowland, 2012; Wang et al., 2010).

While there is an accepted gold standard for measuring appropriate hemoglobin levels, measures of iron stores have not been standardized which complicates the findings of IDNA studies. Even though discovered in the 1930’s, various opinions exist for the healthy ranges of serum ferritin levels (Wang et al.,

2010). Some consider subjects to be at risk when their serum ferritin falls below

50 ng/ml while others do not view ferritin levels to be low until dropping below

10 ng/ml (Camaschella, 2015; Eckert, 2017; Hinton, 2014; Hynes, 2016; Peeling et al., 2008; Quest Diagnostics, 2017; Rowland, 2012; Vaucher et al., 2012).

Local medical labs independently determine their own diagnostic reference ranges for normal test measures. These ranges can vary greatly from one lab to the next, as these norms are based off of those receiving the tests within 51 their local regions (Eckert, 2017; Quest Diagnostics, 2017; Rowland, 2012).

Interestingly, mean values for ferritin are generally around 90 ng/ml for men, but only in the low 30’s for women. Utilizing the mean value to calculate normal ranges for females can prove to be inaccurately low considering their higher prevalence of iron deficiency (Hynes, 2016). Unhealthy specimens can also widen the acceptable ranges to include borderline or inadequate measures (Eckert,

2017). As these tests are often normed from subjects of questionable health, one could argue the validity for these healthy ranges causing some practitioners to use a more refined “optimal health range” (Eckert, 2017). However, if a patient falls within the lab’s for healthy individuals, then it doesn’t trigger the need for the expense of additional testing. If it doesn’t trigger the need, then insurance will not reimburse the practitioner requesting the additional testing, leaving the patient with expensive medical bills. Consequently, this forces the patient to reconsider their desire for additional iron assays due the expensive out- of-pocket costs associated with each test (Eckert, 2017). These widely varying opinions for acceptable values of serum ferritin can cause difficulty and confusion in the diagnosis of ID, IDNA, and IDA for athletes, parents, coaches, and even some physicians (see Table 1).

Studies of runners complaining of unexplained fatigue and loss of motivation suggest that practitioners often misdiagnose iron deficiency of runners complaining of fatigue, when not using multiple iron status assays (Hill, 2014;

Jade, 2014; Wade 2014). When these potential IDNA patients were tested for anemia, many of the CBC measures fell within acceptable ranges on those 52 particular assays and these runners would have been given a clean bill of health.

However, low measures of serum ferritin and transferrin saturation confirmed early onset of iron deficiency. When given iron supplements, most of these

IDNA patients reported significant improvements in areas of fatigue and motivation (Hill, 2014; Jade, 2014). To combat the extra fatigue that endurance athletes often endure, Dr. Scott Koehler recommends athletes supplement their iron intake when ferritin drops below 40 ng/mL (Koehler, 2016). There is no disagreement that IDA patients require supplementation. However, IDNA has been debatable leading to uncertainty regarding treatments (Rowland, 2012).

Supplementation

Determining the need for dietary supplements. Iron deficiency is the single most common nutritional deficiency affecting nearly one third of the world’s population (Johnson-Wimbley & Graham, 2011). While subjects diagnosed with IDA require iron supplementation, controversy exists as to whether or not IDNA subjects should consider supplementation as well (Rowland,

2012). Many sports physicians believe that young athletes, parents, and coaches should receive better information and more education about the risks of ID.

These physicians recommend regular blood testing especially for endurance athletes as ID can lead to a significant decrease in athletic performance, work capacity, and reduced VO2 max due to reduced oxygen transport and mitochondrial inefficiency (Hinton, 2014; Loosli & Rudd, 1998; Reinke et al.,

2012). Endurance athletes should consult their doctors about taking supplements based on the physical requirements of their sport, level of muscular stress, dietary 53 habits, and gender (Johnson-Wimbley & Graham, 2011). ID can be corrected slowly through several months of over-the-counter iron supplements. However, it is highly recommended these supplements are closely monitored by a healthcare professional as iron overload can be deadly (Hinton, 2014; Rowland, 2012;

Weinstein, 2009).

Under normal, healthy conditions, the body should be able to regulate its own cycle of iron through dietary intake due to its natural presence in many foods. Due to the risks associated with iron overload, athletes should always choose a healthy diet over iron treatment if possible (National Institutes of Health,

2016). However, young athletes are extremely susceptible to ID as they often do not adequately increase their intake of healthy calories to combat the increased need and losses of iron associated with exercise, menstruation, and growth spurts. This can create an imbalance of necessary nutrients such as iron and zinc. These nutrients are important for oxygen transport and injury healing, therefore intake needs to be monitored (Camaschella, 2015; Hinton, 2014; Loosli,

1993; Pasricha et al., 2014).

Vegetarian diets are becoming very common with endurance athletes.

However, these athletes must explore alternative nutritional sources for acquiring proteins through plant-based sources and carefully design their meal plans to prevent deficiencies in calcium, iron, zinc, and vitamin B12. Due to the reduced caloric intake, vegetarian diets are often connected to amenorrhea and eating disorders as well. Physicians recommend vegetarian athletes utilize pre- 54 participation examinations and seek dietary consultation from a certified dietitian

(Loosli & Ruud, 1998; Mandali, 2011).

Based on the physical requirements of the sport, endurance athletes should consider testing their iron levels every four to six weeks, especially females with questionable dietary habits. Iron supplementation is generally recommended for athletes whose ferritin is lower than 20 ng/mL, even when their hemoglobin levels are within healthy ranges. Athletes taking iron supplements should have their iron status reassessed every four weeks to determine if supplementation has been effective and is still warranted (Grinaker, 2014; Hinton, 2014). Labs can generally run these tests for around $50 plus the cost of the office visit for the attending physician to interpret the test results (Healthcare Bluebook, 2017).

Types of treatment. Due to the sustainable natural cycle of iron, dietitians recommend athletes seek healthier diets over supplementation if possible. The recommended daily allowance (RDA) for dietary iron is 8mg for men and 18mg for women of reproductive age. While most men consume more than enough iron, studies have shown female runners and swimmers often consume less than 40% of the RDA for dietary iron (Rowland, 2012). Dietitians also recommend athletes and their coaches research absorption rates of iron based on its bioavailability in plants versus meat. Plant based iron (nonheme) has a significantly lower absorption rate than animal based iron (heme) due to its bioavailability. Dietitians agree that nonheme iron is much more difficult to absorb than heme iron. Studies often report absorption rates as high as 35% for heme iron while nonheme iron can be as low as 2%, making it very difficult for 55 athletes on vegetarian diets to consume the recommended 18 mg of dietary iron

(Hinton, 2014; Rowland, 2012). Dietary absorption rates can also be adversely affected by foods which naturally cause inflammation. Foods which may cause inflammation that affects iron absorption include but are not limited to sugars, trans fats, oils made from vegetables and seeds, refined carbohydrates, alcohol, and processed meats. Diets filled with these foods may require even more intake of dietary iron, due to its negative correlation with absorption rates (Bhatia, 2017;

Eckert, 2017).

While athletes should not supplement without knowing their baselines first, oral supplementation is generally considered a cheap, safe, and effective method of treating iron deficiency in most patients (Camaschella, 2015; Johnson-

Wimbley & Graham, 2011; Hutchinson, 2014). Oral supplements include ferrous and ferric forms of iron sulfate as well as polypeptides such as Proferrin (Risser &

Risser, 1990). However, some patients have disorders which do not allow for adequate absorption of oral supplements and may require alternative methods such as iron infusions, intravenous (IV) iron therapy, or even blood transfusions in extreme cases of anemia. While IV therapy has historically been viewed as inefficient due to health risks and high costs, newer and safer IV iron treatments are now available though not commonly prescribed (Johnson-Wimbley &

Graham, 2011).

Oral doses of ferrous iron (+2 oxygen state) continues to be the treatment of choice given its effectiveness, acceptable tolerability, and affordability. Even though some argue ferric iron (+3 oxygen state) is more effective at raising 56 hemoglobin levels, it is rarely prescribed largely due to increased cost, lower absorption rates, and gastrointestinal intolerance. While recent studies show an insignificant difference in tolerance between the two forms of iron, there remains strong evidence towards ferrous iron’s ability to quickly resolve iron deficiencies in a cost-effective manner (Berber et al., 2014; Santiago, 2012).

When considering the purchase of iron supplements, consumers must note the amount of elemental iron in each tablet. For instance, ferrous iron generally consists of about 30% elemental iron while ferric iron is only around 10%, thus requiring larger doses. Ferrous iron is often sold in 325 mg tablets containing roughly 100 mg of elemental iron. A 3-month supply will cost roughly $10.

Research shows that appropriate daily oral doses of elemental iron can effectively and significantly increase both hemoglobin and serum ferritin levels over a period of four to twelve weeks. While treatments should be monitored by a physician, most recommend less than 100 mg of elemental iron per day for IDNA patients, and up to 200 mg of elemental iron per day for ADA patients. Many physicians also recommend taking zinc and vitamin C due to their positive influence on injury healing and absorption rates of other nutrients (Camaschella, 2015; Hinton,

2014; Lamanca, 1989).

While often considered controversial and high-risk, some physicians may prescribe IV iron treatments in severe cases of anemia. In a recent study of highly trained distance runners with low iron stores, participants were treated with either oral doses of iron or intravenous injections of iron. Researchers found that while ferrous iron substantially raised serum ferritin levels, the intravenous form of iron 57 carbohydrate (Ferinject) was significantly superior in its effectiveness. However, at a cost of $150 per dose plus the cost of a healthcare professional to administer the treatments, this remains a cost-prohibitive method for the average citizen

(Garvican et al., 2014).

Erythropoietin (EPO) is another controversial form of IV iron treatment.

Erythropoietin is a natural protein secreted by the kidney to stimulate red blood cell growth. This protein can now be synthesized in medical labs and injected as a treatment for severe anemia as well. However, there are severe risks associated with this method due to the common side effects of increased blood pressure and blood thickening. These side effects greatly increase the risk of stroke and heart disease. As a safeguard to athletes, most athletic associations have banned the use of EPO due to these health risks and its increasingly common misuse as a performance enhancing drug (Green, 1998).

Benefits and risks associated with treatments. Iron deficiency not in the presence of disease or disorder, can be cost effectively treated through simple over-the-counter oral supplementation of ferrous iron. Those suspecting iron depletion should consult their physician for appropriate testing measures and educate themselves on the benefits and risks associated with the various forms of iron treatment. Iron depleted athletes can generally maintain their training regimens while taking iron supplements provided their iron stores show continued growth (Hinton, 2014; Lamanca, 1989).

Unexplained fatigue in the presence of acceptable hemoglobin, but low ferritin levels has been the topic of several recent studies. In a 2003 study of 136 58 women with low ferritin levels, researchers found a 29% drop in reported fatigue levels after a four week period of 80 mg ferrous iron tablets administered daily

(Verdon, 2003). In a study of 20 women with low ferritin levels, six weeks of iron therapy resulted in a 27% improvement in self-reported muscular fatigue

(Brutsaert et al., 2003). In a 2012 study of nearly 200 women, researchers found that IDNA patients reported significant improvement in their fatigue over a 12- week period while taking daily doses of 80 mg of elemental iron via ferrous sulfate tablets (Vaucher et al., 2012).

Recent studies have also shown that iron treatments given to athletes suffering from IDNA may not only decrease fatigue, but may also increase both aerobic and anaerobic capacity via the oxygen delivery system (Waalen, 2003;

Hutchinson, 2014). In a study of 20 adolescent runners, participants were given ferrous sulfate tablets over a period of four weeks. During this treatment, average ferritin levels rose from 8.7 ng/mL to 26.6 ng/mL which revealed a direct correlation with treadmill endurance tests. Researchers noted these IDNA adolescent runners vastly increased their time on the treadmill, but reported no significant effect in their overall oxygen uptake or heart rate (Rowland, 1988). In a study of 20 active women with low ferritin levels, researchers found that 100 mg of daily iron supplements for eight weeks effectively improved their iron status, reduced blood lactate levels, and raised VO2 max (Lamanca, 1989). In a study of 42 IDNA active but untrained women, researchers found that six weeks of 100 mg ferrous sulfate tablets resulted in greater endurance improvements as compared to placebo (Hinton, 2000). In a 12-week study of 40 young athletes 59 with low ferritin levels, researchers found that 200 mg of elemental iron significantly raised both ferritin levels and VO2 max (Friedmann et al., 2001). In two separate studies of female college rowers, researchers found that IDNA athletes given 100 mg of ferrous sulfate daily were able to replete iron stores, lower blood lactate, and increase both their endurance threshold and aerobic capacity. Researchers also noted, participants with the lowest baseline scores, achieved the largest gains (Dellavalle & Haas, 2011; Dellavalle & Haas, 2014).

In 2014, two separate research teams performed a meta-analysis of studies involving differing variables of iron status and endurance capacity. Both studies confirmed strong positive correlations with serum ferritin and aerobic capacity at maximal and submaximal efforts. As ferritin measures climbed back to adequate levels, aerobic capacity and VO2 max were found to increase proportionately

(Burden et al., 2014; Pasricha et al., 2014). However, while there are numerous studies showing the benefits of supplementation, these studies generally have limited numbers of participants and are mostly females of reproductive age.

While studies show strong correlations with iron status, fatigue, and VO2 max, athletes should not supplement without knowing their baseline levels first. Hemoglobin levels can increase rapidly, while repletion of iron stores can take three to six months. During this timeline, frequent blood tests are recommended to ensure iron levels continue to rise throughout the treatment.

Unmonitored iron supplementation can lead to iron overload. As iron is a toxic mineral, excess iron can increase the risk of arthritis, liver cancer, diabetes and heart disease. Additionally, unsuccessful iron treatments are a sign of underlying 60 blood disorders or disease that may require further diagnosis by a physician

(Bermejo, 2009; Camaschella, 2015; Hinton, 2014; Rowland, 2012).

Conclusion

The purpose for this review of literature was to examine the differing viewpoints concerning the effects of iron deficiency on endurance athletes along with preferred methods of diagnosis and treatment. While research is very conclusive on the importance of screening, diagnosing, and treating IDA, differing opinions exist toward the significance of IDNA and its role in fatigue.

For years, many have suspected a correlation between low iron stores and aerobic metabolism due to the importance of iron within the oxygen delivery system.

While there are numerous studies concerning IDA, there is a lack of research supporting theories relating IDNA to work, aerobic, and performance capacities.

Due to the fact that endurance athletes make up such a small percentage of the overall population, the need for new studies regarding IDNA is often overlooked and even considered insignificant by researchers and physicians due to the much higher impact that IDA has on the general population. The studies of IDNA that do exist are often debated due to their small sample sizes, lack of diverse participants, and the large number of additional variables that can affect muscle fatigue, maximal effort, and general motivation. In a 2014 meta-analysis of the existing IDNA studies, researchers noted that many of the studies contained fewer than 20 participants and suggested future studies consider recruiting eight to ten times that number to ensure better reliability within the data (Pasricha et al.,

2014). 61

While research does confirm the significant role that circulating iron plays in maximizing the efficiency of aerobic metabolism, conflicting views exist concerning the role of iron stores. While the general population can often function normally with depleted serum ferritin levels, many speculate low iron stores may have a more dramatic effect on endurance athletes. According to Dr.

Kim Colter (personal communication, January 19, 2017):

The perspective many doctors seem to come from is the logical conclusion

that “red blood cells carry oxygen from the lungs to exercising muscle.

Iron deficiency is the most common cause of anemia, which means a

decreased number of red blood cells. If you have enough red blood cells,

you're fine, regardless of how much iron you have in your body. So all

that really counts is what your hemoglobin and hematocrit are. If those

are normal, you're fine. End of story. I don't care what the ferritin is, if

the hemoglobin and hematocrit are normal.” But iron does other things in

the body other than support the production of red blood cells. Iron is a

cofactor for an enzyme in the mitochondria in muscle called alpha

glycerophosphate oxidase. Alpha glycerophosphate oxidase is one of the

key enzymes in what is called the Cori cycle, which is a metabolic cycle in

muscle that metabolizes lactate. It is really important that athletes are

able to metabolize the lactate produced when they are exercising

anaerobically.

Research of aerobic capacity confirms maximal endurance efforts often require 90 to 100% of VO2 max, further indicating the impact IDNA may have on endurance 62 athletes. Any restriction of oxygen will allow fatigue to set in earlier, causing measurable drops in training and competition efforts. While some argue the impact of iron stores on VO2 max, others speculate that even a slight decrease in iron stores may create an early onset of fatigue causing a devastating effect on the determination and fortitude required by competitive endurance athletes (Davis

2016; Joyner & Coyle, 2008).

There is little argument that frequent monitoring of iron status can greatly assist in the diagnosis of iron depletion and support in establishing effective treatment options. Lack of early detection and misdiagnosis can lead to months of rest and treatment to replete iron levels, costing athletes upwards of a year of competition (Grinaker, 2014; Rowland, 2012). While the American College of

Sports Medicine recommends screenings before competitive seasons, others recommend monitoring as often as every four to six weeks especially with at-risk athletes. However, few athletic associations require any sort of blood screenings as part of their pre-participation evaluations (Hinton, 2014; Rodriguez et al.,

2009).

While standardized measures for diagnosing IDA have been created and accepted by healthcare professionals, gold standards have not been established for serum ferritin nor any of the alternative methods for screening iron stores. Even though current research is beginning to show support towards the importance of screening for full iron status, CBC tests still remain the standard measure given by most practitioners when suspecting iron deficiency. However, non-anemic athletes can still be iron deficient but often go undiagnosed without additional 63 tests of iron stores. Even though some tests can be greatly affected by the presence of inflammation, contemporary research suggests utilizing the CBC test along with serum ferritin, hepcidin, total iron-binding capacity, transferrin, and soluble transferrin receptors in order to build a complete picture of total iron status (Burden et al., 2014; Camaschella, 2015; Hinton, 2014; Koehler, 2016;

Pasricha et al., 2014; Rowland, 2012; Weinstein, 2009).

Varying options and opinions also exist concerning the methods and costs associated with screening and treatments. Depending on the individual's health insurance, multiple office visits and multiple blood tests can become costly.

Although seeking the assistance of a healthcare professional is advised, individuals can now seek out direct lab work on their own, cutting costs significantly. While few studies have assessed the effect of supplementation on overall performance, numerous studies conclude that oral doses of ferrous iron can greatly increase both hemoglobin and serum ferritin. At a cost of $3 per month, over-the-counter doses of ferrous iron can be an effective and economical method of treatment in the absence of disease or blood disorders. However, blind supplementation of iron is not advised as iron overload is associated with serious health risks (Healthcare Bluebook, 2017; Hinton, 2014; Rowland, 1988).

Due to the many risk factors associated with iron depletion, more information and improved educational opportunities should be made available to all athletes, their parents, and their coaches concerning both IDA and IDNA.

While the need for educational opportunities is clear, few programs of this nature currently exist to inform and educate these participants. With better education 64 regarding proper nutrition, importance of early detection, appropriate tests for iron status, and efficient methods of treatments, iron deficiency can be prevented or reversed (Hinton, 2014; Loosli & Rudd, 1998; Mandali, 2011).

Through the above review of literature, two rather important gaps in research have emerged. There are seemingly no studies rationalizing the wide array of subjective opinions of clearly objective measures of iron status. While many associations highly recommend participants receive education on the topic, there seems to be little action put into place ensuring that athletes, parents, and coaches receive the information and training surrounding the importance of iron deficiency. Through the qualitative exploration approach outlined in the following chapter, the researcher hopes to develop common conceptual categories and establish theories that can be used to drive future research.

65

Chapter Three - Research Methodology

Introduction

The purpose of this study was to explore the various opinions concerning the importance of testing multiple markers of iron status while examining the current knowledge base in relation to the effects of iron depletion on endurance athletes. As noted throughout the review of literature, there appears to be starkly contrasting beliefs surrounding the differing methods for screening iron status as well as differing opinions on what measurements are considered healthy. This study utilized an exploratory research approach to analyze which diagnostic tests physicians deem most beneficial in determining iron deficiency in endurance athletes as well as compiling data on current doctor recommendations toward non-anemic iron deficiency, importance of serum ferritin tests, and efficient forms of treatment. This study also explored the current depth of knowledge attained by parents and coaches concerning the effects of iron deficiency on endurance athletes. This chapter is broken into five subsections: selection of participants, instrumentation of the study, the role of the researcher in the study, how the data will be collected, how the data will be analyzed.

Selection of Participants

Participants for this study consist of healthcare professionals, parents of endurance athletes, collegiate athletes, and coaches of endurance sports.

Healthcare professionals were chosen locally through purposive and snowball sampling. Utilizing cluster sampling, parents of endurance athletes, collegiate athletes, and coaches of endurance sports were selected throughout the Kansas 66

City Metropolitan area. The Greater Kansas City Suburban Conference is comprised of 25 schools of various sizes, locations, and socioeconomics. Their members are very active and eager to provide support and cooperation related to their sports. From this database, schools were randomly selected with a request to volunteer at least one coach and one parent to participate in the study. In addition to these local high school coaches, one additional high school coach was chosen from rural Missouri along with one additional collegiate coach. The additional two participants were chosen via purposive sampling to gain a larger perspective from outside the Kansas City high school demographic.

Instrumentation

Because there is no current research of this nature, this study employed an exploratory research approach with the intent of establishing grounded theories to be used in future research of this topic. A mixture of structured and semi- structured interviews were administered to the healthcare professionals and coaches to provide insight towards underlying opinions towards the topic while identifying common perceptions and opinions throughout these participant groups. The structured interview questions were used to gather demographic and background information while the semi-structured questions were open-ended allowing the participant the freedom to expand upon the question and giving the interviewer the opportunity to explore particular perceptions in more detail.

Open-ended surveys were created in Google Forms and administered to the collegiate athletes and parents of endurance athletes. Four sets of interview prompts were utilized in this study: one set for healthcare professionals, one set 67 for coaches, one set for parents, and one set for collegiate athletes (see

Appendices D, E, F, and G for the interview questions and surveys). Common perceptions were then used to help develop themes for the basis of new hypotheses and grounded theories proposed for future studies in the final chapter.

Role of the Researcher

The researcher’s role was to create, administer, and facilitate all interviews and surveys in a manner that ensured the greatest opportunity for validity, reliability, and generalizability while monitoring and reducing the chance of bias. The researcher conducted the interviews and surveys according to the design of the study and acted as an objective observer throughout all interviews.

The researcher used appropriate field observations and was careful not to sway the discussions in any particular direction and did not utilize any current or past relationships to influence opinions or thoughts. The researcher has collected, analyzed, and presented the data in an appropriate manner consistent with the expectations of an exploratory research design.

Data Collection

The exploratory research method was used in this study to gather data from a mixture of structured and semi-structured interview questions and surveys with the intent of generating common perceptions and developing new hypotheses for future research. Healthcare professionals and coaches, were given individual interviews while the collegiate athletes and parents of endurance athletes were given open-ended surveys. The interviews and surveys were scheduled at their own convenience in order to obtain a high participation rate. All conversations 68 were voice-recorded and transcribed after completion. Once transcribed, all recordings are to be stored for five years, then discarded. Participants will remain anonymous throughout the study. Names have been replaced by numerical representation and all transcriptions of the interviews have been discarded to ensure privacy and anonymity. The researcher has pursued a theoretical saturation of data throughout as many different demographics as possible. Upon completion of the qualitative study, the researcher reviewed all of the collected data and investigated the repeated ideas, concepts, and perceptions. All correlations were extracted, coded, interpreted into concepts, and then grouped into categories that were used to develop themes and hypotheses for future research.

Data Analysis

This study utilized a grounded theory approach for data collection and analysis. Qualitative data collected via individual interviews and open-ended surveys were coded, organized, and then categorized to help show common connections and perceptions along with any stark differences throughout the various demographics. Through a process of theoretical sampling, inductive coding, and constant comparison, each interview was analyzed after completion in order to develop themes used to drive future interview questions. Once all the data was collected, the common themes and perceptions were used to develop additional hypotheses and theories to be recommended for use in future research of the topic.

Summary 69

The purpose of this study was to explore the differing viewpoints towards the importance of testing multiple markers for iron status of fatigued athletes.

Interviews utilizing a mixture of structured and semi-structured questions were administered to healthcare professionals and coaches, while parents of endurance athletes and collegiate athletes were presented with open-ended surveys. After the qualitative data was collected and sorted into categories through inductive coding, common perceptions and themes were analyzed in order to develop new theories and hypotheses recommended for future studies. The results of the data analysis are presented in the following chapter of this study.

70

Chapter Four - Results

Introduction

This chapter presents the results of the qualitative data collected throughout this exploratory study. The qualitative data collected via in-depth personal interviews and open-ended surveys was transcribed and coded by the researcher. Open coding was utilized initially to sort the data gathered from the participants’ responses into broad concepts and categories. Axial coding was then performed to confirm the accuracy of the categories identified through the open coding process and to provide a method of exploring deeper into the perceptions and relationships within each category. This was also beneficial in systematically narrowing the broad conceptual findings into specific concepts and categories.

The resulting concepts and categories were then sorted into common perceptions and recurring themes.

This coding process revealed four distinct themes in relation to testing iron levels of fatigued endurance athletes. The following themes were derived from the coded data: seek the opinion of a healthcare professional, serum ferritin is an important test for fatigue, optimal ranges need to be developed for serum ferritin levels, and treatment options are generally easy, affordable, and effective.

Description of Participants

Thirty-four participants were gathered from four distinct categories.

Participants included six healthcare professionals, twelve cross country and track coaches, eight collegiate cross country and track athletes, and eight parents of endurance athletes. 71

Due to the challenge of generating a reliable population of healthcare professionals, purposive sampling was used to develop the sample for this category. After expending a significant amount of time, the researcher was only able to interview six of the twelve participants originally chosen within this category. Of these six healthcare professionals, three participants were Doctors of

Medicine, one participant was a Doctor of Chiropractic, one participant was a

Certified Athletic Trainer, and one participant was a Certified Nutritionist. The three Doctors of Medicine held various board certifications including Internal

Medicine, Family Medicine, Sports Medicine, and General Surgery. Participant ages from this category ranged from 27 to 66. Of these six participants, three had previously competed in endurance sports (see Table 2, Appendix H).

Random sampling was used to identify ten high school coaches within the

Greater Kansas City Suburban Conference. One additional high school coach was chosen from a rural setting along with one additional collegiate coach. These additional coaches were chosen via purposive sampling to establish whether or not conflicting perspectives were observed outside the Kansas City high school demographic. All twelve of the identified subjects within this category chose to participate. This particular population sample represented a very diverse range of demographics. Participant ages ranged from 27 to 62. Of the ten male participants and two female participants, nine coaches worked with both male and female athletes, two coaches worked only with females, and one coach worked only with male athletes. Training volumes ranged from 15 miles per week to 80 miles per week. Of the twelve participants, only six claimed to have received 72 specific training or attended educational clinics pertaining to iron depletion (see

Table 3, Appendix I).

All eight parent participants were referred by their respective coaches.

Participant ages of the seven mothers and one father ranged from 40 to 58 as most have or recently had high school aged children. Three of the participants worked in healthcare: two registered nurses and one registered sleep technician. All eight participants have visited with a healthcare professional concerning their child and reported symptoms of persistent fatigue (see Table 4, Appendix J).

The eight collegiate athletes included five females and three males with ages ranging from 19 to 25 as many were still in college or recent graduates. The participants’ college experiences ranged from smaller NAIA schools up to larger

NCAA Division 1 Universities. Scholarships for the participants ranged from walk-on status to full scholarship. Of the eight participants, four have received treatment for iron depletion and only one has never received any information nor training pertaining to iron deficiency (see Table 5, Appendix K).

Even with the diverse backgrounds, assorted experience levels, and various sample sizes, theoretical saturation was achieved throughout each group of participants through their descriptions, explanations, and interpretations of the perceptions they hold pertaining to iron and its importance to endurance athletes.

Research Findings

Theme 1 – Seek the opinion of a healthcare professional. The first theme identified from the collected data was the common perception of seeking the advice and opinion of a healthcare professional for bouts of abnormal fatigue. 73

Within this theme, three very distinct concepts emerged including the prevalence of iron depletion especially in young female athletes, when to consult a physician concerning fatigue, and tests commonly used by healthcare professionals to diagnose symptoms of fatigue.

Pertaining to prevalence, participants in this study reported up to 30% of high school cross country athletes suffer from fatigue-related symptoms caused by iron depletion. Coach C10 stated, “Fatigue is my number one battle in coaching cross country and track.” Along with the high prevalence of iron depletion, strong correlations were found pertaining to gender and weekly training miles.

Higher instances of iron depletion were reported amongst the female athletes and programs with higher weekly training miles.

Of the twelve coaches interviewed, eight reported having numerous experiences of athletes diagnosed with iron deficiency, two coaches reported only a few instances, and two coaches reported no experience with iron-related issues.

All four of the coaches reporting few or no instances of iron deficiency considered themselves low-mileage programs, while the other eight coaches considered themselves as medium to high-mileage teams. Affiliated with a higher-mileage coed team, Coach C6 referenced this prevalence by stating:

Definitely more prevalent with the girls than guys in my experience. I’d

say in boys it’s 10% or less that I’ve had with chronic fatigue, being worn

down. For girls I’d say more in the 30-35% range. So about three and a

half more times more common for girls than boys. 74

Also affiliated with a higher-mileage coed team and agreeing with Coach C6 about higher prevalence amongst females, Coach C5 stated, “About 5% of the boys I’ve worked with and 15% of the girls have had iron issues”. Affiliated with higher-mileage teams consisting of only female athletes, Coach C1 and C7 also reported that approximately 15% of their female athletes are diagnosed and treated for low iron each year. Specifically, Coach 7 stated:

About 10 to 15% of our girls every year have issues with iron. Of our

seven varsity athletes this year, four of them have had issues with iron. I

think it is more prevalent with the varsity kids who run year round.

Affiliated with a lower-mileage coed team, Coach C12 shared:

I’ve only had three girls with iron deficiency in my 30 years of coaching.

We've not had any issues with the boys. I've done a lot of thinking about

this; we're a very low mileage program. With the varsity kids we start

around 30 miles a week. I don't think we've had too many issues because

we're a low mileage team. I can't get them out in the winter and I can't get

them out in the summer. I've heard stories about some schools running

every day. But my kids have only been running 30-40 miles a week.

Of the eight collegiate track athletes surveyed, five were females and three were males. Seven of those athletes considered themselves distance athletes, while one of the females considered herself a sprint athlete. All four female distance runners, who considered themselves as year-round athletes, were diagnosed and treated for iron deficiency during their high school and college 75 years. None of the three boys nor the lone female sprinter reported any iron- related fatigue issues.

The participating parents were all chosen because they’ve had children who have dealt with fatigue issues related to iron. The gender prevalence was once again evident through the parent surveys. Of those eight participants, six reported daughters being diagnosed with iron deficiency, while only two parents reported sons with the same diagnosis. Specifically, Parent P7 stated, “I had three daughters who all were endurance athletes . . . all three were [diagnosed and] treated for iron deficiency.”

The healthcare professionals also agreed on the prevalence of iron deficiency based on gender and activity level. All six healthcare professionals agreed that iron deficiency is more common with females in general and endurance athletes are more prone to iron depletion when compared to their sedentary counterparts. Healthcare Professional H6 stated, “Fatigue is a common complaint of many patients, whether athletes or not.” H5 confirmed this observation and added, “I always ask patients about their exercise levels. Any family practitioners with sports medicine training are certainly going to check ferritin when an athlete is coming in with fatigue.” Healthcare professional H4 also noted, “Females are much more prone to iron issues than boys as their menstruation cycles can fluctuate so dramatically, literally from week to week.

You need to check in a little bit more with the female athletes.” In reference to this same concept of prevalence, Healthcare Professional H2 stated: 76

Being an endurance athlete would definitely make a difference in my

opinion. If it's just your average 14-year-old teenager, maybe not. I

would definitely take gender into account as well . . . I would probably be

more prone to check a female athlete than a male just because you can

assess other aspects of their health, not just their exercise capacity. Is this

a manifestation of their exercise and endurance, nutritional status, or

having heavy periods?

Healthcare Professionals H1, H3, H5, and H6 also noted from experience that distance runners not only burn up energy sources quicker, they also tend to have inadequate diets even for a sedentary person. H3 offered his perspective by stating:

I direct these athletes to the foods they need to get incorporated into their

diets. But the caveat I run into, the biggest problem is, I’ll say “here are

the foods” and I’ll run down the list with them . . . “Hate it, won’t eat it,

shoot me, not going to do it, forget it.” And I’ll say, “No wonder you’re

deficient.”

Healthcare Professional H5 went on to elaborate by stating, “We see so many athletes with chronic injuries related to nutrition . . . it’s such an obvious and common deficiency in these demographics, especially once you start seeing their labs.”

Due to the prevalence of iron deficiency within this demographic, the second concept of this theme pertained to the timeliness of seeking out a professional opinion from a healthcare provider. Coaches, athletes, parents, and 77 healthcare professionals all agreed that investigating diet, sleep, stress, and workout patterns should be the focus of the initial investigation. However, if the conditions persist for a week or more, further investigation and diagnostic tests need to be conducted by a healthcare professional.

From the coaches’ perspective, many noted visible changes in performance as a key indicator to begin these initial investigations. Coach C1 stated, “When performances drop, we would investigate sleep, diet, back off workouts, then see a doctor after a week or two.” Coach C11 stated, “Investigate sleep, diet, daily stress . . . if persistent we’d speak with the parents and recommend seeing a physician.” Coach C5 added:

I’ll look at good fatigue vs bad fatigue. Your legs should be dead after a

hard workout. But typically on a recovery run, the first 800 might be

sluggish, but you start rolling and breathing and you’re fine. If on

recovery days, when you get to the point that you feel every step is a

struggle with undue fatigue and you can’t shake it, then we need to talk. I

probably err on sending them to a doctor earlier than later, and I’m almost

at a point that like I to see the girls get tested before the season and mid-

season no matter what. I’m much quicker to make the recommendation

[to seek a healthcare professional] for a female.

However, affiliated with a lower-mileage, coed team, from an urban setting,

Coach C2 shared a much different perspective by reporting:

While I go through a series of questions about what they are eating, how

much rest they are getting, and making adjustments to their workouts . . . 78

The honest answer is, very rarely in my world do I refer athletes to their

doctor because they typically don't have insurance or ever go to the doctor.

Our parents don't believe in bothering with that sort of thing, because they

have to work, or have no money, or no time, and no education. They

usually respond to these requests with “it's just in their head” or “they just

need to quit because they don't have time for all that.”

Coach C9 reported a unique perspective being the only collegiate coach and afforded with immediate access to team physicians. This participant stated:

First thing we do is look at their sleeping patterns, diet, daily stress, and

also their training schedule. We try to see if those are the reasons for their

abnormal fatigue first. If we decide those aren’t the reasons, then we look

at getting some bloodwork done. We have team doctors and trainers the

athletes can see on a daily basis. We don’t wait. We try to knock it out as

soon as possible.

Within in the athlete demographic, many shared the same sentiments.

Athletes A2, A6, and A8 cited the same philosophy of waiting one week before seeking medical advice pertaining to fatigue. However, Athletes A1, A3, A4, A5, and A7 each stated fatigue needed immediate attention when the athlete first notices a change in practice and/or race performances. Participant A1 elaborated by sharing, “It’s important to keep a detailed log to refer back to . . . when workout paces become slower, it’s time to see a doctor.” Athlete A4 also pointed out the importance of seeking immediate input from a physician by citing, “High levels [of fatigue] could be related to much more than just high levels of activity 79 and body strain [larger medical concerns].” Athlete A5 also noted, “From personal experience, it is much better to go sooner than later, as it can take several months to rebuild iron stores and feel back to your normal self.”

The parent participants also shared the same earlier-is-better perspective.

All eight parents used words and phrases such as “persistent fatigue”, “affecting performance”, and “when sleep and diet patterns do not correct the problem.”

Parent P1 stated, “It’s time to see the doctor when performances are declining and it’s not due to lack of sleep or diet.” Employed as a registered nurse, Parent P7 specified the importance of contacting a medical professional at the first onset of fatigue not associated with a recent illness. Parent P5 mirrored many of the other’s sentiments, but added:

As a parent you know your children. If they have been getting enough

sleep, staying hydrated, eating well, and still the fatigue persists, in my

opinion, it is time to seek out medical help and find out the underlying

cause of it.

Also employed as a registered nurse, Parent P8 noted the importance of conducting baseline lab work when they first start running. This parent participant stated that a baseline blood test can be an extremely valuable tool when compared to bloodwork after symptoms of fatigue arise.

The healthcare professional demographic also noted the importance of seeing a doctor within a week of noticing abnormal fatigue. Healthcare

Professional H1 stated, “If it was a persistent, abnormal fatigue . . . then I would suggest making an appointment with their primary care provider . . . within a 80 week.” Healthcare Professionals H2, H4, H5, and H6 all mentioned the importance of noting changes in performance capacities. Specifically, H2 stated,

“When routine workouts are becoming difficult, I’d have it looked into.” H5 elaborated by adding:

The red flag there is . . . when a light workout is more fatiguing than it

used to be. A lot of these athletes do routine workouts or the same kind of

running. And they’ll report, “I used to be able to do this, but now I can’t

do that anymore.”

Healthcare Professional H6, who works as a sports medicine doctor, added, “If an athlete is noticing a drop in performance with their increased training, despite trials of recovery [one week’s rest], we usually begin some basic lab tests.” From a unique perspective, H3 added the importance of visiting a physician based on some additional physical signs such as skin pallor, fingernail beds, hair loss, difficulty falling asleep, difficulty staying asleep, and pica.

A third concept that developed within this theme pertained to common tests healthcare professionals often use when diagnosing symptoms of persistent fatigue. A surprising number of participants in this study noted at least a basic knowledge of the tests available for iron status. Of the 34 participants, only two coaches and one athlete were not familiar with any of the basic tests (CBC, serum iron, and serum ferritin).

As noted, ten of the twelve coaches were able to name the basic tests that physicians often use, while three coaches were informed well enough to list several tests above and beyond what most practitioners would consider utilizing. 81

Coach C1 recommends athletes suffering from fatigue speak with their physicians about testing not just the standard CBC, but also requesting tests for serum ferritin, H. pylori, Epstein-Barr [mono], gluten intolerance, and celiac disease.

Coach C5 mentioned many of these same tests but also included serum iron,

Crohn’s disease, and thyroid [TSH] tests. Coach C7 also mentioned the importance of investigating gluten intolerance and gastrointestinal issues.

Within the collegiate athlete demographic, six of the eight participants recommended both the CBC and serum ferritin tests. Most of this demographic recommended further testing to rule out extenuating infections, disease, or allergies that might inhibit the body from self-regulating its own iron levels.

Athlete A1 recommended gluten tests if iron levels do not replete during treatment. Her iron deficiency was not initially corrected via supplementation and was later diagnosed with celiac disease due to gluten intolerance. Athlete A8 reported that her fatigue and low iron were later found to be related to adverse effects of an acne prescription.

Based on their personal experiences, all eight of the parents recommended pursuing both the CBC and ferritin tests simultaneously. Parent P5 also mentioned requesting thyroid tests along with testosterone based on her own research. Parent P7 stated:

I had three daughters who all were endurance athletes. They all had

normal CBC's and Hgb [hemoglobin]. I later requested iron studies and

ferritin [due to continued fatigue]. These studies [ferritin and serum iron] 82

were both found to be abnormal . . . all three were treated [successfully]

for iron deficiency.

From the healthcare professional standpoint, all six participants agreed on the following methods of assessing symptoms of fatigue: fill out a medical history survey, inquire about diet, sleep, stress, and exercise patterns, conduct a physical exam, then consider lab work deemed necessary but in accordance to their medical group’s standard-of-care. In a detailed response that summarized most of the participants’ opinions, Healthcare Professional H2 stated:

I would give a thorough history and physical examination of them. There

is a lack of studies to convince most doctors to add "endurance athletes" to

the medical history investigation. Now the thing is, most of these patients’

initial physical exams are totally stone-cold normal. Basically what they

tell you is, they are “more fatigued than usual” and are “not able to reach

my mile time or my 5K time.” Unfortunately, you don't get a lot of

information from that. As far as diagnostic testing, what I would pursue is

a complete blood count [CBC], metabolic profile, kidney function, thyroid

function, vitamin B12, and possibly vitamin D. And given the fact that I

am a runner and that I know physiological aspects of these patients, I will

check ferritin levels for these athletes as well. If you know they are

putting in the effort and they are not getting the results, I will check the

ferritin levels. If suspected to be nutritionally deficient I would potentially

think about vitamin B12 levels. And if they are having lots of stomach 83

upset and various food intolerances, I would consider testing for celiac

disease or gluten sensitivity as well.

Healthcare Professional H3 also stated:

I have a medical history that is about four pages long. After a physical

exam and investigating activity levels, sleep patterns, and diet, I do a lot of

testing. I prefer hard data. I like to see the numbers . . . my

recommendations are based on what I’ve seen in the blood values. Then

[after re-testing] I can see 3 months later down the road, to see if we’re

making any progress.

Healthcare Professional H4 noted additional inquiries pertaining to hydration levels for both genders and menstruation for the female athletes. Healthcare

Professional H5 recommended the largest scale of testing which included the previously noted assays plus a full nutritional panel consisting of amino acids, fatty acids, magnesium, zinc, copper, all of the B vitamins, vitamin D, and other assorted inflammatory markers. H5 furthered this point by stating:

Beyond CBC and full iron panel, we also screen for all nutrients that are

essential for proper biologic function. The body doesn’t work right in the

presence of inflammation . . . prevents healing, recovery, and [hinders]

performance. But the caveat for me, is that we don’t submit to insurance,

giving us the freedom to test as we see fit.

Participant H6 also noted the importance of exercise and dietary inquiry, specifically noting deficiencies commonly associated with vegetarian and vegan athletes. H6 stated, “If an athlete is dropping in performance . . . we try to 84 quantify how active they are and what is limiting them . . . medications they may be on, dietary intake, vegetarian, heavy periods, bloody [stools], and overtraining.” Healthcare Professional H1 cited a slightly different opinion stating:

After the medical history and physical exam, I’d order a CBC, chemistry

panel, renal panel [kidney function], , comprehensive

and metabolic panel that looks at too. If these were

normal, I wouldn’t order iron studies. But, I’m in [trauma and life-

support] surgery, so I don’t typically look at this stuff [simple complaints

of fatigue].

Theme 2 – Serum ferritin is an important test for fatigue. The second theme identified from the collected data was the common perception that serum ferritin is an important assessment for diagnosing abnormal fatigue, especially when dealing with endurance athletes. Within this theme, three very distinct concepts emerged including the importance of utilizing a serum ferritin test, reasons why primary care physicians might be reluctant to order serum ferritin tests, and the importance of researching this topic before visiting a family practitioner or pediatrician.

Of the 34 participants in this study, 29 agreed that serum ferritin was an important first-tier test when diagnosing symptoms of persistent fatigue with endurance athletes. Of the remaining five participants, two coaches and two athletes had not researched nor received any information pertaining to the blood 85 test, while one healthcare professional felt that serum ferritin was more of a second-tier test.

From the perspective of the coaches, 10 of the 12 participating coaches were both knowledgeable and supportive of their athletes seeking out this test when suspicions of iron depletion arise. Coach C11 simply stated, “If the fatigue were persistent, I would definitely inquire about ferritin.” Coach C1, C5, C7, and

C9 recommend their athletes have serum ferritin levels tested multiple times per year whether they are reporting fatigue or not. Coach C1 stated, “Once their ferritin levels drop, it takes months to rebuild those stores back up again. We try to be proactive and catch it before it’s too late.” Coach C5, shared the same sentiments, “I’m at a point that I like to see the girls get tested before the season and mid-season no matter what. When they need bloodwork, I’ll send them to the doctor and ask for those tests [serum ferritin] specifically.” Coach C7 also noted,

“I think it is more prevalent with the kids who run year round. I will call those athletes’ parents and suggest ferritin might be something you want to test for in your yearly checkup.” Coaches C1, C5, C6, C7, C9, and C12 all mentioned the importance of the athlete obtaining the full lab reports from the physician. These coaches specifically request the serum ferritin level from their athletes due to the clinical discrepancies in what some consider to be adequate levels. Participant C6 reported:

We let the doctors run all of the tests so that if there is something that is

alarming to them, that we aren’t familiar with, they can mention it as well,

like a hemoglobin count, or another type of thing in their blood that may 86

be low. But the ferritin test is what we are really after. We ask them to

specifically get the ferritin number. Don’t just let the doctor say “that

looks good”, or “your number is good”. We’ve had several athletes come

back to us who said their doctor said the number was good, and the

number was not in the sufficient range.

From the perspective of the collegiate athletes, fatigue is a commonly discussed team subject. Athlete A4 stated, “Fatigue [in relation to iron deficiency] is a frequent subject during team conversations.” While four of the five females were tested multiple times throughout their careers, all five actually recommended being tested for ferritin several times each year. Athlete A1 shared her experience by stating, “We get tested [for serum ferritin] every season, at a minimum.

Athletes who have had low levels [of ferritin], get tested more often. If [ferritin] levels aren’t increasing with treatment, athletes should consider testing for celiac disease as well.” Athlete A5 stated, “We had our ferritin levels tested twice a year to indicate our body’s iron stores and reveal whether or not we had an iron deficiency.” Athlete A8 also shared, “[our coach] pays for all the girls and any guy who wants to be tested for their ferritin levels at the health center.”

The parent participants were all very quick to note the importance of having their children’s iron stores tested. All eight parents noted their children’s

CBC levels were normal which causes hesitation from some doctors to test serum ferritin levels. Because of this, each parent specifically mentioned the serum ferritin test as a first-tier blood test along with the CBC when diagnosing symptoms of fatigue associated with distance runners. Parent P1 shared, “We 87 requested a ferritin test [along with the CBC]. My son’s CBC results were normal, but his ferritin was a 5 which I hear is really unusual for a male.” Parent

P2 recommends, “Run them both [CBC and serum ferritin tests] before and after each season of cross country and track.” Parent P3 added, “My daughter is tested regularly. She is a cross country runner, track athlete, and swimmer. She is tested after each season to monitor her levels [3 times per year].” Parent P7 shared, “All three of my daughters had low ferritin levels. They all had normal hemoglobin [CBC] but had low iron, low transferrin, and low TIBC as well.

They are all in their 20’s and still have the test run annually.” Parent P8 also noted the importance of requesting the ferritin test and reported, “I think ferritin levels should always be checked. Most physicians don’t even check ferritin levels specifically unless you ask for this test. It is not included with the basic blood work.” However, Parent P5 shared a different experience with their pediatrician.

In hindsight, she wished she had more knowledge, experience, and had asked the right questions when their doctor gave little importance in testing serum ferritin levels along with the CBC. In regard to this medical visit, this parent stated, “In my experience, the doctor’s office will often give the patient the hemoglobin level, but not the serum ferritin count. Since my son’s results were very close to normal, they stated he did not need any further testing, though his fatigue persisted.”

The healthcare participants of this study largely agreed with the beliefs of the other participants. All six of these healthcare professionals noted the importance of the serum ferritin test when CBC levels were low as well. Five of 88 these six participants also felt the test was a first-tier diagnostic marker for endurance athletes no matter what the levels from the CBC test. Healthcare

Professional H2 elaborated by reporting:

If I had an endurance athlete come in, I would probably test ferritin

immediately along with the CBC just because I'm aware of some of the

research on it. The CBC and metabolic profile, those are just quick and

easy crossing-things-off-a-checklist type tests. The others take more

thought and assessment. There are many things that can contribute to low

ferritin, iron absorption, and reasons you just can't get your iron up. Those

things would need to be appropriately assessed to make sure the iron is

getting absorbed into the system. It's usually just from exertion and just

not eating right, but if they truly can't raise their ferritin despite doing all

the right stuff, celiac disease would have to be ruled out.

Participant H2 continued this point, stating:

I see the ferritin test as being very essential. Red blood cells have a

lifespan of 120 days, so we are constantly needing to replace them. I

would like to see adequate supplies in the store house to manufacture

those cells as fast as possible. Iron is also mobilized during periods of

extreme stress. On some of the runners I’ve tested, I’ve noticed a little bit

of elevated serum iron, but low ferritin. And I’ve been asked, “We don’t

want to give them iron do we, if the serum iron is on the high range?” But

I’m like, “Look, this is the storage.” The serum iron is elevated due to the

stress on the body that has been mobilized to be available. But their 89

storage levels are low. With adequate rest, that serum iron will drop right

back down and ferritin will remain low. The savings account is the ferritin

in my mind, cash is the serum iron. We need savings to fall back on

during times of stress and exertion.

Healthcare Professional H5 also agreed with the importance of using serum ferritin as a first-tier test and gave a detailed response by claiming:

Ferritin is a basic nutritional screen. It should be screened anytime

someone is reporting fatigue and iron is suspected. Based on our

experiences with especially young girls, many of them have become vegan

or vegetarian for whatever reason. We find them lacking in nearly every

essential amino acid, every essential fatty acid, and B vitamins. Then you

just get this cycle of things, O2 capacity issues with the iron, energy for

conversion related to B vitamin, and other nutrients essential for proper

biological function. It’s such an obvious and common deficiency in these

demographics once you start seeing these labs.

If serum ferritin levels are found to be low, Participant H5 also added:

The standard-of-care for us after seeing low ferritin, is always to order the

full iron panel which includes TIBC, percent capacity, serum iron, and it

repeats ferritin. The reason you need all three of them [iron panel, serum

ferritin, and CBC] is because it tells the total story of iron, so that I can see

the impact of the iron on the body. The issue might not just be manifested

in the CBC. That full iron panel will tell how badly the body is looking

for iron. So even if you see a ferritin level that is kind of ok, not super 90

low, but you see the binding stats are near the top and the percent

saturation is really low, that’s actually reading what the body is wanting

and defines how bad the iron is needed. Even though it’s not manifested

in the CBC, it actually tempers that information and makes it more

important. So the ferritin is more of a screen while the blood count will

actually show its current effect on the body. That iron panel is the key to

linking those and showing how bad the body is actually looking for it

[elemental iron]. And I would say that using all three of those is a really

safe thing to do because you can see it all.

Healthcare Professional H6 also agreed with the previous statements about the importance of testing serum ferritin levels in athletes, but also noted:

Family practitioners with sports medicine training are certainly going to

check ferritin when an athlete is coming in with fatigue. As ferritin is

more of a pre-cursor to anemia, I still rely more on hemoglobin values for

a true diagnosis of anemia. [Additionally], ferritin levels can be falsely

elevated due to stress, infection, and recent strenuous workouts. Another

newer test, soluble transferrin receptors, may be a more accurate measure

of iron stores due to inflammation. Because ferritin is an acute phase

reactant [raises with inflammation], these newer tests like soluble

transferrin receptors may be a better option [not effected by

inflammation]. If someone has run a marathon, or after a strenuous long

workout, or an illness, you may have to wait a couple of weeks to get an

accurate measure of ferritin because it will spike up high [due to 91

inflammation]. I like to see them like two weeks after their big event or

after the cross country season to reassess their ferritin levels.

However, Healthcare Professional H1 reported a slightly different viewpoint working as a trauma surgeon who is often trying to maintain minimal levels for life-support versus enhancing optimal levels for performance. This participant stated:

If a patient that was an endurance athlete, their CBC was normal, had a

regular healthy diet, didn’t have a family history that made me suspect

something wrong with their iron, and I had a low clinical suspicion of

being iron deficient, then no, I would not order those iron panels. I would

pursue other workups. If the patient was persistent that I order an iron

test, I would probably order it.

Participant H1 clarified his stance on serum ferritin by adding:

If their CBC was normal, whether or not insurance would consider that

[ferritin test] as a proper use of medical resources, probably not.

[However] iron studies are pretty cheap, so it wouldn’t be problematic

when working up fatigue to just add those on and get it done. If it’s a cost

incurred by the patient and it will help you rule out other medical

problems, then I would definitely order it.

The second concept within this theme stemmed from the experiences with reluctance from some primary care physicians to administer the serum ferritin test. While this participant believes in the importance of this test, Healthcare

Professional H6 summed up this possible reluctance by stating: 92

While family practitioners with sports medicine training are certainly

going to check ferritin . . . the ferritin is more of a precursor to anemia,

[and little] evidence-based data exists that shows a correlation of low

ferritin with normal hemoglobin and fatigue. It is very subjective for now.

But certainly, if their ferritin stays low long enough, they can become

clinically anemic down the road.

While most of the coaches admitted to trusting the expertise of the healthcare professionals, many recommended being informed, educated, and prepared to discuss the different options for tests before visiting with their primary care physician. When asked about questions or tests they’d recommend their athletes discuss with a physician, Coach C2 confided, “I would just let the doctor be the professional.” However, several coaches expressed some concerns with experiences they’ve had pertaining to primary care physicians and what they perceived as a lack of experience within this category of iron deficiency. Coach

C12 stated, “I’d let them be the professional. But, I don't know if they ever check the ferritin levels. But that is one of the things I would have them checked for especially if they're running lots of miles.” Due to past experiences, Coaches C5 and C6 were not as trusting in the opinions of primary care physicians pertaining to the use of a serum ferritin test to diagnose persistent fatigue in athletes.

Participant C5 stated:

I’ve gotten to the point that I alert parents that ferritin and general

practitioners don’t really see eye to eye. I also alert the athlete that 99% of

general practitioners will not recognize the need for the ferritin test. There 93

is a huge disconnect between the competitive world and the general

practitioner stored-iron world. What is normal for a person out walking

around isn’t normal for an endurance athlete.

Participants C6 added:

Definitely not trusting of the doctors. We ask our athletes to get the full

workup blood-wise. And then specifically tell them to get the ferritin

number. Don’t just let the doctor say “That looks good”, or “Your number

is good.” We’ve had several [athletes] come back to us who said their

doctor said the number was good, and the number was not in [what we

considered] the sufficient range.

Coach C7 offered a detailed response, citing:

You know you have to specifically ask for it [ferritin]. You can't just

come in and ask for iron or anemia [tests]. You really need to name

ferritin so that they are actually tested for it. When I first started

researching it, I even talked to my own doctor about it, “What would you

say if a family came in and asked for ferritin?” I was trying to figure out

if they'd give the test or what they needed to hear from a coach. My

doctor stated that he would ask “Why or what is the purpose for this?” He

would ask if there was any support for ordering the test, such as a training

log. “But if they know of the ferritin test and are naming it, it’s hard for

me not to test it.” My doctor would do it, but it would be an issue of the

family knowing that insurance may or may not cover it. It’s shocking to

me. It’s no harm to them. They aren't that expensive. So I always ask 94

them to get a ferritin test along with [CBC]. Additionally, we have

doctors within our school district that are sponsored by the district that

will test our kids at a cheaper cost for the families. I put that out there for

the families and why this would be something that would benefit them.

The collegiate athletes expressed the same perceptions towards this reluctance to test. Most agreed they would trust the expertise and judgements from their primary care doctors. Athlete A7 stated, “I would decide to trust them based on the level of care, interest, and expertise they show in my care as a distance athlete. However, I would research common deficiencies in endurance athletes before discussing those deficiencies with a professional.” Athlete A5 agreed by adding, “I would trust their expertise, although I would ask about additional blood tests such as CBC, iron test, and ferritin level test. These tests could provide more information and confirmation of their judgement.” Athlete

A1 confided, “With most doctors, you have to request specific tests and remind them anything below 30 [ferritin level] is too low for college women [athletes].”

The parent participants observed a strong correlation with a reluctance from their primary care providers to utilize the serum ferritin test as a tool for diagnosing persistent fatigue of their children. Of the eight participants, seven were eventually granted the test for ferritin, but each had to specifically request it.

The other parent participant reported their primary care physician would not order the serum ferritin test due to healthy CBC ranges. Parents P1, P2, P3, P4, P6, P7, and P8 each reported specifically asking for the ferritin tests. Participant P1, 95 whose son was diagnosed and treated for iron deficiency due to a low ferritin level, but healthy CBC levels, reported:

Of course I would trust their expertise and judgement. However, you must

ask for ferritin and CBC tests for an endurance athlete. I had to

specifically request it [serum ferritin] as it wasn’t something she was

going to order. I had information from the cross country coach who

encouraged that I ask for that specific test. My son was a five which is

extremely low for ferritin.

Parent P6 simply stated, “We suggested the [ferritin] test and our physician was willing to give it.” Employed as a registered nurse, Parent P7 has been through this process with all three of her daughters. From her experiences, she reported:

I would not just trust their expertise or judgement. Our pediatrician had

no personal experience with endurance athletes, fatigue, or ferritin levels.

With the help of my daughter’s coach and my persistence I was able to

educate the doctor. I had three daughters who all were endurance athletes.

They all had normal CBC's and Hgb [hemoglobin]. I requested iron

studies and ferritin. These studies all were abnormal. However, I had to

request ferritin specifically. My physician did not disagree. I feel he was

very on board because his son happened to be running cross country as

well and was very open to learning. Due to his lack of knowledge on the

subject, he elected to refer my daughter to a hematologist.

Parent P8, also a registered nurse, shared her experience of visiting their primary care provider by confiding: 96

Specific blood tests are necessary to identify any deficiencies. I think

ferritin levels should be checked. Most physicians don't even check

ferritin levels unless you ask for this test. It is not included with basic

blood work like a CBC. We had to request ferritin levels specifically as

our pediatrician was not going to order this test. Our pediatrician is a very

good physician, but he was not familiar with low ferritin levels as it relates

to endurance athletes.

Noting a poor experience with their primary care provider, Parent P5 shared:

I had to take my son to the doctor due to unexplained fatigue and I asked

for his iron levels to be tested. I was afraid he could possibly have an iron

deficiency. The doctor's office agreed and days later I received a message

in regards to his test results. I was only told in a voicemail, "his

hemoglobin was within normal limits." I was not given the count. I had

to request a printed copy of his lab test results in order to get that

information.

Due to her disappointing experience, Parent P5 advised:

I would recommend for parents to specifically request a hemoglobin level

test and a serum ferritin test. In my experience the doctor’s office will

often give the patient the hemoglobin test and not a serum ferritin test. I

can only guess it is perhaps because a hemoglobin test is more commonly

known and more people are familiar with it. Since, per his doctor's office,

his results were normal for someone his age, they stated he did not need 97

any further testing. I must admit I was somewhat disappointed in the little

importance they gave to the matter in general.

To add another perspective to this concept, the healthcare participants were able to share first-hand knowledge of why certain blood tests are preferred due to the standard-of-care they are generally provided with. While this particular group of healthcare professionals largely favored serum ferritin tests, they shared speculations as to why some physicians may not be in favor of this particular test.

These participants mentioned various reasons ranging from their medical group’s standard-of-care, insurance coding regulations, and a general lack of education and experience within this particular demographic: distance runners reporting fatigue but with seemingly healthy ranges on their CBC tests. Healthcare

Professional H2 shared his belief:

It’s a patient population without a lot of studies involved. Quite honestly

they are probably looking at a healthy 15-year-old kid that looks healthy

and think “Why the heck would you be iron deficient?” They're basing it

off of, “You're not showing me a disease pathology, so why bother with

that test?” But it is a very critical thing if you ask me, to make sure you

have the appropriate iron and that your hemoglobin can carry the adequate

amount of oxygen. So it's not that they are bad doctors or anything, they

are just applying medical principles that are made for 60, 70, 80-year-olds

who have diabetes, high blood pressure, heart attacks, and stuff . . . to

what appears to be a healthy 15 or 16-year-old kid. So, applying those 98

medical principles to this population doesn't always quite lineup. I always

say that, “If you want good running health, find a good running doctor.”

From a chiropractic standpoint, Participant H3 first noted, “In my mind, it could be a bit more of a function of insurance reimbursement.” Participant H3 also added:

I don't see the caseload that medical doctors do. They are overwhelmed

with very sick people. The medical profession has evolved into

emergency medicine: car wrecks, heart attacks, disease management, and

things like that. It's almost like there is going to have to be a specialized

sports nutritionist. [For an endurance athlete] it might be important. But

if the physician isn’t trained in it, I don’t know how that would change his

opinion. If you put on the medical history, “I’m an endurance athlete,”

they are probably going to think, “Well, good for you, what’s wrong?”

Pertaining to the educational and experience level of the primary care physician,

Participant H4 added:

It's [ferritin testing] one of those things not on the mainstream, but it's

becoming more and more something that should be looked into.

Depending on the physician’s level of education and experience, I don't

think being an endurance athlete would be a trigger for them . . . I don't

think that would necessarily make them look at ferritin levels. If it’s a

physician you have personal experiences with and have worked with

before, that might make more of a difference in ensuring ferritin gets

tested. 99

From a licensed nutritionist’s standpoint, Healthcare Professional H5 noted:

The reason a family practitioner might not use this assessment, is right at

that line of lack of experience, lack of education, and insurance coverage.

Many doctors do not have extensive training in nutrition nor exercise

physiology. Doctors ask me a lot of questions about ferritin, for

somebody with just a masters in nutrition. It’s amazing how many doctors

are not trained to read iron tests correctly. Many doctors just run serum

iron on people. But serum iron is really more of an inflammatory marker

than anything else. It doesn’t tell much of the story without the ferritin,

the iron panel, and the CBC.

Participant H5 furthered his concerns about insurance by stating:

The other problem that most doctors have, and this is a problem with our

healthcare system, most doctors are restricted by insurance coding. So

unless they can justify ordering a lab by their standard-of-care, they won’t

get it.

Participant H5 also discussed ramifications associated with standard-of-care by reporting:

Doctors for the large part work in what the medical fields call standard-of-

care. If you operate within the box offered by the hospital or the group

you work with, you’ve got millions worth of pharmaceutical lawyers and

hospital lawyers to protect you. There’s a lot of danger and liability for

stepping outside of that box. They are liable for anything that is not in that

protected box of standard-of-care. We actually have a health system that 100

is designed to prevent anybody from free-thinking. Doctors these days get

a lot of nutrition questions from patients and it terrifies them because they

don’t want to do or say anything they might be liable for.

Furthering his point on how insurance can effect physicians’ decisions when faced with the complication of treating disease versus trying to optimize health,

Participant H5 also noted:

I will say the caveat for me is that we don’t submit to insurance. These

are cash labs. I want a nutritional screen that shows me nearly every

essential nutrient and insurance doesn’t have to dictate any of it. If you’ve

got a chronic disease and you’ve got something to get prescriptions and

procedures for, that’s what insurance is for. It is not for optimizing your

health. And this [testing serum ferritin with normal CBC measures] falls

under optimizing. So that girl who walks in here under her own power

and wants to improve her performance, there’s no insurance codes for that.

Offering advice for parents to seek out cheaper methods of testing, Participant H5 reported:

Cash labs are popping up everywhere now because people are kind of

taking over their own health in that regard. And they’ve gotten so much

cheaper. A $35 walk in lab billed to insurance could run close to $1,000

and that’s what makes our healthcare so expensive. Insurance is such a

scam.

Also noting a possible lack in training and experience, Healthcare Participant H6 stated: 101

I would say there is a lack of training and education about the value of it

[testing ferritin]. Family practitioners with sports medicine training are

certainly going to check ferritin when an athlete is coming in with fatigue,

probably more so than the regular primary care or pediatrician or family

practitioner who doesn’t have that background. A 65-year-old running a

5k is different than a college athlete trying to go professional.

Participant H6 also perceived the added costs associated with additional tests as a possible factor and reported:

Certainly cost may be another factor. Some doctors have a long list of lab

tests, but sometimes insurance doesn’t cover all of it that well. The

ferritin test is a lot more expensive than a CBC. A lot of doctors will do a

CBC for 10 to 15 dollars. We can run that test in our own office. [But]

once you start adding additional tests for fatigue you’re talking hundreds

of dollars. If they are getting ready for the Olympic trials, an elite athlete,

then you’re going to spend more money doing lab work, maybe getting

them on the treadmill and doing a stress test.

To further the discussion on standard-of-care and his perception toward the clinical discrepancies in utilizing this test, Participant H6 also noted:

It’s [ferritin testing] still more of a soft-science. There doesn’t seem to be

a real-well-done double blinded study on ferritin that I’m aware of

[pertaining to] general recommendations and guidelines that pediatricians

and family practice doctors are going to follow [as to] what blood tests we

should order. There isn’t a lot of evidence based data that shows a 102

correlation of low ferritin with normal hemoglobin and fatigue. [There

are] no studies that are conclusive that boosting just ferritin will increase

their VO2 max. It’s very subjective. But certainly if their ferritin stays

low long enough, they can become clinically anemic down the road.

Healthcare Professional H1 offered a slightly different viewpoint toward test preferences based on clinical suspicions and reported:

In the correct algorithm to appropriately order up tests, if someone came

in with low clinical suspicion of iron deficiency and a healthy CBC, I

would not order iron studies. Even if the patient was an endurance athlete

that had a regular healthy diet and I had a low clinical suspicion of being

iron deficient, then I would not order those tests [iron panel]. I would be

looking for another cause of their fatigue. I would probably order it [iron

panel] for people I would suspect to be iron deficient such as the elderly or

people without a good nutritional status that were anorexic or had eating

disorders. If it were an otherwise healthy person like you or I, then I

probably wouldn’t order it if the CBC was normal. Iron deficiency would

usually show up as an abnormal level in the CBC. However, if the patient

still complained of fatigue and I couldn’t find any other abnormalities and

I was suspecting an iron deficiency, I would probably order those tests.

Participant H1 also reported discrepancies and subjectivity in regard to the importance of serum ferritin pertaining to the physician’s background and certifications. This participant stated: 103

Sports medicine doctors might want their [patient’s] ferritin levels at the

high end of normal compared to a general internist that wants their patient

at a healthy maintenance level. If the patient was an endurance athlete and

I suspected the patient wasn’t eating healthy, had an incorrect body-

perception, and poor eating habits or eating disorders . . . If I were to pick

that up, I would probably order those iron panels.

Pertaining to insurance conflicts and costs associated with uncovered lab work,

Participant H1 also reported:

Iron studies are pretty cheap, so it wouldn’t be problematic when working

up fatigue to just add those on. If it’s a cost incurred by the patient and it

will help you in diagnosis, then definitely order it. If it’s a patient-ordered

test, one that the physician wouldn’t recommend as it would not fall

within the standard-of-care for the patient’s complaints . . . say a person is

complaining of fatigue and I went and ordered an MRI for their lower

back. They [insurance] are not going to cover that as it is not a proper

evaluation tool for fatigue. If the patient was persistent that I order an iron

test, and their CBC was normal, insurance would [probably not] consider

that as a proper use of medical resources.

The third concept within this theme was the commonly referenced importance of researching this topic ahead of time. Due to the discrepancies in healthcare opinions within this demographic, many participants recommended researching and acquiring as much information as possible pertaining to the 104 existing lab tests and possible causes for the symptoms of fatigue before visiting with a physician.

Coaches C1, C5, C6, C7, C8, C9, and C10 all mentioned the importance of educating not only their athletes about the effects of iron depletion, but their parents as well. Coach C1 reported, “Every year, we have a meeting before the season starts to discuss the importance of testing for iron stores and its effects on fatigue, especially for the girls.” Of the twelve coach participants, six mentioned using Dr. Kim Colter as an educational reference for any athlete reporting persistent fatigue. Dr. Colter is a primary care physician from the Midwest who advocates the importance tracking serum ferritin levels before and after each competitive season. Coach C8 stated, “I direct them toward the letter from Dr.

Colter’s study he published online, which had more detailed information than I’m certainly able to give.” Coach C7 also reported that her athletes keep running logs to aid in the accuracy of reporting fatigue.

The collegiate athletes also noted the importance of being proactive and researching the subject ahead of time. Of the eight collegiate athletes, six reported an importance of researching this subject ahead of time to better advocate for these tests during conversations with their physicians. Athlete A1 reported, “With most doctors you have to request specific tests and remind them that 30 [ferritin level] is too low for college women [athletes].” Athlete A6 shared, “My coach did discuss abnormal fatigue and its relationship to iron status.

It was understood that running could cause sluggish days, but a constant feeling of fatigue was likely an iron concern.” Athlete A7 reported, “It is likely that I would 105 research common deficiencies in endurance athletes before seeing a professional and discussing those deficiencies with a professional.” Participant A8 stated, “It is important to know what is being done. I would probably question them on what these tests are looking at.”

The parent participants also referred to the importance of researching beforehand. Parent P5 specifically noted in her case, “From my experience, the more you understand the subject, the more information the doctor’s office will provide you with. Be prepared to ask the right questions.” Participant P7 reported, “I have done a lot of research on iron deficiency. With the help of my daughter’s coach and my persistence, I was able to educate the doctor. He had no personal experience with endurance athletes, fatigue, or ferritin levels.”

Parallel to the findings of this study, the researcher also noted a striking contrast in terms of the willingness of participants to engage in a study of this nature. Participants with the most experience with iron deficiency, were the most willing to assist in this study and offered referrals with similar backgrounds and experiences. Contacts with the least amount of education and experience in this subject were more hesitant or unwilling to participate in this study. Of the 13 coaches that were contacted, 12 eagerly volunteered to participate. All sixteen of the athletes and parents that were contacted, responded quickly as well. Because athlete and parent names were submitted by the participating coaches, some of these coaches noted a hesitation to participate from parents and athletes with little or no experience with iron deficiency. However, a significant concern was noted by the researcher in the response level from the healthcare professionals contacted 106 in this study. Of the twelve contacted individuals within this demographic, only six were willing to participate. Of those six eager participants, all had backgrounds in sports medicine, sports nutrition, or extensive experience with endurance athletes. Five of these six knowledgeable participants voiced strong opinions toward the importance of testing serum ferritin levels. Of the six contacts not willing to participate, five were family practitioners. The lack of participation from these physicians is concerning, as they are generally the first point of contact for most parents and athletes. Summarizing the common responses from this group of nonparticipants, one family practitioner responded with, “I’ve been meaning to get back to you. It might be easier for me to answer your questions via email, if that would work.” After the interview questions were shared via email to this hesitant group in hopes of easing anxiety toward the interview, no more responses were received. Three more follow up emails were sent with no responses in return. Consistent with the experiences noted by the athletes and parents, this reluctance to participate suggests a lack of experience and discomfort from these physicians in regard to answering detailed questions about serum ferritin and its relevance toward iron depletion and endurance athletes.

Theme 3 – Optimal ranges for serum ferritin. The third theme identified from the collected data was the common request for more research to aid in refining the current ranges for healthy levels of serum ferritin. Within this theme, three very distinct concepts emerged including the lack of a gold standard for serum ferritin, concerns in regard to normalizing test ranges based off the 107 elderly and sickly, and the creation and utilization of optimal ranges for performance versus the bare minimum clinical ranges used to detect disease.

The first concept that emerged within this theme was the need for revised standards for healthy ranges of serum ferritin. While it is commonly noted that ferritin is an acute phase reactant which can cause complications of interpretation, there is a need for creating healthy ranges which are more clear and concise. As noted in Chapter Two, a very wide range exists for what many consider to be healthy levels of serum ferritin (typically measured in nanograms per milliliter).

The coaching participants had several varying opinions on healthy ranges, though most of which were at the higher end of the ranges reported in Chapter

Two. Of the twelve coaching participants, eight reported having knowledge of what they perceived were healthy ranges for serum ferritin levels. Coach C1 reported, “I believe normal ranges start at about 12 to 15. But we would rather our girls be above 30.” Coach C3 reported, “I believe it is close to 40.” Coach

C5 gave a more detailed response and reported:

I’ve kind of used the numbers that the college guys give me: 50. I’ll take

22 to 23. But when it gets under 20 or down to single digits, not only are

you not able to train, you’re lucky to make it through the school day.

Coach C9 agreed by stating, “We would like our kids to be above 30 on the ferritin scale, but ideally above 50.” Coach C7 also agreed with the previous comments based on her experience, but added:

Most doctors recommend 10 to 20. But I feel 30 or more is better based

on my experience. However, it depends on the kid. Some can still 108

perform in the upper teens. But [the athlete] notices that it is harder to

keep up with their usual pace groups when ferritin levels are in the upper

teens.

Coach C6 specifically reported on the discrepancies between what he has researched and what some primary care physicians have communicated to his athletes. Specifically, Coach C6 stated:

Healthy levels of ferritin for a distance runner are generally between 50

and 110 or 120. You want to start a season there, but as long as you are

above 30 you are going to be ok. I’ve had several doctors tell my kids

when they were at 20, “there’s no problem” and “they are healthy” . . . and

that is a problem.

Coach C11 agreed and also noted that healthy levels for one, may not be sufficient for another. Specifically, Participant C11 stated, “I feel there should be differing levels for different people. A kid staying home playing video games all night doesn't need the same levels of iron that a highly trained distance runner might.”

The athlete perceptions mirrored that of the coaching participants. Of the eight participating athletes, all five female distance runners were aware of typical healthy numbers, while both of the male distance runners and the lone female sprinter were not aware of such numbers. Athlete A1 reported, “Long distance runners typically need to be above 30. Most people don’t have problems with being too high. [But] it’s still possible to be fatigued when above 30 because athletes may have different thresholds.” Athlete A3 stated, “Ferritin levels should 109 be above 30 for runners.” Athlete A8 admitted, “While I have no clue on hemoglobin, I believe ferritin has to be about 30-ish.” Athlete A5 also added,

“Acceptable levels vary depending on genders. Ferritin should be 12 to 300 for males and 12 to 150 for females.”

The parent participants reported many of the same perceptions as the athletes and coaches. Of the eight parent participants, six parents were aware of the general standards for healthy serum ferritin. Parent P1 stated, “I believe

[ferritin should be] 30 for a runner. Parent P2 agreed, “Above 30 during racing season.” Parent P4 added, “Above 20 is normal, but distance runners need higher levels of ferritin.” Parent P7 noted that each clinical lab creates their own ranges for normal by stating, “Normal levels of ferritin vary by lab, usually ranging from

5 to 20.” And Parent P8 quoted a slightly higher number than most of the parent participants by reporting, “I think ferritin levels should be above 40 and less than

100.”

Many of the healthcare participants agreed with coach, parent, and athlete perceptions of healthy ferritin levels. However, while only four healthcare professionals were able to quote general healthy ranges of ferritin on the spot, those numbers were all much higher than the recommendations from the coaches, parents, and athletes. Healthcare Professional H3 was the lowest at 40 while both

Participants H5 and H6 recommended supplementing iron when serum ferritin levels drop below 60. Healthcare Professional H3 reported:

Because of my exposure to endurance athletes, the best I could come up

with is about 40, which is a nice target. I’m sure it would vary per 110

individual depending on their workload or their lifestyle. Whereas an

average young adult might do just fine with a lower level, your athletes are

going to want to bump that up.

Healthcare Professional H2 recommended the highest levels, stating:

I think in women all the way down to 20 is considered normal for females

all the way down to like 60 is considered normal for males by laboratory

definition. But for these patients I would want them to be closer to 100 or

higher.

From these perceptions, a second concept within this theme emerged pertaining to methods used to determine healthy ranges. When asked, only the healthcare professionals were able to describe the method in which labs determine healthy ranges for an individual’s blood work. However, each demographic noted that healthy ranges for a sedentary person may not be adequate for a highly trained athlete. Coach C1 stated, “While normal ranges for a regular person might be 15, in my opinion an elite athlete requires higher iron stores due to the levels of strain and exertion they place on their bodies.” Athlete A1 reported,

“It’s still possible to be fatigued when above 30 because athletes have different thresholds. You have to remind them, [doctors] that anything around or below 30 is too low for college women [athletes].” Parent P4 noted, “Above 20 is normal, but distance runners need higher levels of ferritin.”

All of the healthcare professionals confirmed those concerns when responding to the same question. Healthcare Professional H2 reported, “The laboratory definition of normal is not normal for this population of patients 111

[endurance athletes]. The lab numbers are often normed off of the sickly and elderly population.” Agreeing with these statements, Participant H3 also shared:

There are clinical values [lab values], which are based on what the

laboratory has been seeing. So that sample is heavily weighted with ill

and elderly people . . . to be diagnosed with a condition, you have to be

outside that clinical range, either above or below, before a diagnosis can

be made.

Concerning personal experience and research, Healthcare Professional H6 reported:

After looking at five or six guidelines, a normal ferritin level seems to be

above 20 ng/ml. But some people will recommend replacing iron if

ferritin is less than 60. Dietitians, chiropractors, and all sorts of people

have their own opinions of what those ranges should be. But probably the

most evidence based [healthy] ranges are going to be found by looking at

the American Hematology Association and studies they’ve done on it.

Participant H5 shared the same sentiments and added:

The range for iron is an incredibly huge range. That's because we define

healthy levels based on what causes a defect or disease, not what is

optimal. Medical ranges for nutrients are based on disease deficiency. In

other words, they all come from sick populations. So it’s just like our

BMI [body mass index]. Americans are getting heavier, so we just got

new classifications for BMI. 112

The concern of norming healthy ranges based on an elderly and sickly population was instrumental in developing a third concept within this theme: the importance of optimizing nutritional levels for peak performance of both athletes and the general population. All four demographics noted the tendencies to visit primary care physicians after observing or reporting symptoms related to fatigue.

Instead of investing all of the time and resources on the sickly, several participants of this study would like to see a new emphasis placed on optimizing health as a preventative measure. Through early detection, deficiencies can be easily treated and corrected in their beginning stages helping to prevent future disorders and disease.

This concept of optimizing nutritional levels to avoid disease while complementing performance was shared by several participants. Coach C5 shared his perception on the need for optimal ranges by stating, “[In terms of overall health] there is a huge disconnect between the competitive world and the general world. What is normal for a person out walking around isn’t optimal for an endurance athlete.” Disputing the current healthy ranges, Athlete A3 argued,

“Healthy ranges are for non-runners. My [ferritin] level may seem to be healthy for the average person, but it’s low for a competitive runner.” Healthcare

Professional H3 verified the previous statements while also advocating a need for optimal ranges by reporting:

In functional medicine or clinical nutrition, we’re looking at a much

narrower range. In other words, where are peak performances at, so we 113

can target that range. Physicians in this field put together a list of optimal

ranges for peak performance.

Referring to his beliefs toward deficient, healthy, and optimal ranges, Participant

H5 added:

We take our measurements from sick people so there comes your deficient

range. They [norm these ranges] based on the sick measured population.

So they just measure everybody that comes in needing bloodwork and

they make a healthy range out of that. We don’t have optimal ranges. It’s

not really a focus. Optimal ranges are calculated largely based on the

experiences of the doctors. They are not studied in large scales. You can

read up on the research and literature, but when it comes down to athletics,

there’s not much on that. We define healthy levels based on what causes a

defect or disease. What is optimal for a human is currently undefined. I

think the future of health depends on these athletes because there is a

reason to optimize. If we can define what is optimal for them, then we’ll

know what's good for the rest of us. I don’t know that we’ll ever have this

perfect range, but we’ll have something closer than what we’ve got right

now. For now, we’re just guessing what's best for everyone.

Theme 4 – Treatment options. The fourth theme identified from the collected data pertained to viable treatment options and recovery timelines.

Within this theme, three very distinct concepts emerged including the general ease in which iron depletion can be treated, diagnosing underlying issues which may be affecting nutrient absorption, and the importance of consulting a healthcare 114 professional before taking supplements due to the risks associated with iron overload.

Participants throughout each demographic of this study agreed that treatment of iron depletion is generally easy, affordable, and effective when diagnosed in its early stages and in the absence of disorders or disease which may be affecting the absorption of nutrients. When asked to share their experiences with diagnosis, treatment, and recovery, the coaching participants frequently reported serum ferritin tests used in diagnosis, iron pills for treatment, and approximately four weeks for the first noticeable improvements in regard to fatigue. Confirming several recent cases on his team, Coach C1 shared:

Most of our athletes were diagnosed with both the CBC and ferritin tests.

Treatment has generally been in the form of iron pills, usually

Proferrin. Recovery for these athletes has ranged from 4 weeks to 9

months. Most of these athletes were able to run aerobically [during

treatments], but workouts and races suffered until their ferritin levels were

back up, usually above 20. But I would rather see 30.

Expressing the same experiences, Coach C5 stated:

Our athletes have been diagnosed through CBC and ferritin tests. The first

girl I ever helped diagnose with iron deficiency was in 2008. I think she

ran 20 and change [as a freshman in a 5k race]. And the next year, can’t

keep up with any of my varsity runners. The most extreme treatment she

received was an iron transfusion. She’s the only one I’ve had receive a

transfusion. Her mom did exhaustive research, she took Proferrin, vitamin 115

C, cooking in a cast iron skillet, and started to increase red meat uptake.

[Pertaining to recovery] to be honest with you, I would say that as long as

we have enough time in the season for it to take effect, I’ve not seen a kid

not respond to the treatment. It’s just day and night when those levels

start going up. It usually takes two to three weeks for improvements,

maybe closer to a month depending upon the mental toughness of the kid.

Advocating for proactive measures before athletes visit their primary care physician, Coach C6 added:

When first noticing fatigue, we’ll ask about diet and sleeping correctly.

Then we’ll back them off and get a complete bloodwork deal. Then once

we get those numbers back, the number one go-to for us has been the

Proferrin ES for treatment. While we are waiting for that to happen, we

give the athlete a list of foods that is high in iron, start having them eating

things that are higher in iron if they haven’t been, and keep their training

lower until they start to feel better. Most of our kids were diagnosed

through ferritin tests. We never knew their hemoglobin, making me feel

like a bad coach right now. [Pertaining to recovery] I never had a kid not

get better. From my experience, I’d probably say it has taken about a

month to really start to see results. Starting to feel a little better, maybe a

couple of weeks, but to really see results, closer to one month. During that

time, we back off on intensity and how far they are going. But no time off

once they are on the pills.

As a supporter of multiple ferritin tests per year, Coach C7 recommended: 116

We try to get the parents on board to test the athletes [serum ferritin

levels] more than once a year to look for patterns. Does it matter the time

of the season? As the season goes on, does it get lower? [Pertaining to

treatments] I would say initially it’s under doctor’s advice, but I would

mention Proferrin because it’s easy to get and not too expensive. But of

course talk to your doctor, because "too much iron" is dangerous. One

girl, over the course of 4 years, learned to take more iron when upping the

miles, and less in the off season. Liquid iron has been more beneficial

with gluten and gastrointestinal issues. But their numbers never get to

what I think their numbers should be. We've had a few girls that have

gotten blood transfusions. One of them was pretty sick with anemia. She

played lots of sports so it really depleted her iron levels. It seems like the

Proferrin, for most girls, will do the trick for them and bring them up to a

level that makes a difference. But the girls with absorption issues, it

doesn't seem like a lot changes. Recovery usually takes at least two to

four weeks before I've ever seen something change. Performances stop

sagging and pick back up to where they have been. Especially with those

kids, I have them write down exactly how they feel so they can report it to

the doctor, and it's not just like "I think I feel better." We have shut kids

down and not raced them, trying to get them through the championship

season.

Coach C8 shared the same experience as many others, and stated: 117

Our latest case which is the most prevalent in my mind, had a kid that ran

track and cross-country as a freshman at the varsity level and were

expecting big things from his sophomore year in cross-country. But just

coming right out of the gate, he looked like he was struggling and wasn't

running what he had the year before. After a few more weeks, started

having conversations and wondering what was going on, “Have you been

sick or hurt?” Halfway through the season the conversation with his dad

turned to possibly getting tested [serum ferritin]. A couple weeks later it

came back that sure enough, he was suffering from iron deficiency. At

that time he did start taking some oral iron supplements. By the time he

started his treatment, we were in the last week or two of the season. There

wasn't enough time in the cross country season to see him bounce back.

But we did notice a big bounce back the following track season. He

started looking more like he did and was running better and continued on

and had a good cross country season for us this year. We definitely saw

an improvement once taking those supplements. Having conversations

with him, within the month he felt like he started feeling more normal.

Coach C9 recommends testing for absorption diseases when iron pills do not seem to be increasing iron stores. From his experience, this participant shared:

In my time coaching, I have only had three athletes that have been

diagnosed with iron deficiency. One girl was taking a liquid supplement

and everything seemed to come together. Another athlete had a big drop

off [in performance], had a transfusion, and ran really well a few weeks 118

later. Then, she had a big drop off in performance after another couple

weeks. Her ferritin numbers were all over the place. I think 17 before the

transfusion. Then after were up to like 127. Then tested again a week

later and was down around 60. The pills and liquids have seemed to be a

slower but more effective process, while the transfusions can be a really

quick fix. However, it doesn’t solve the [underlying] problem if there is

one.

Also confirming recovery times, Coach C11 stated, “It was years ago. I can't really remember how it was diagnosed nor the treatments she was on. She had a terrible diet. However, the athlete made significant progress after one month of whatever treatment she was on.”

When discussing their experiences with treatments, both the athlete and parent participants expressed strong sentiments pertaining to optimizing nutritional intake, oral iron treatments, iron transfusions, and additional supplements to aid in absorption of nutrients. Each participant noted the ease and general effectiveness of over-the-counter iron supplements. Athlete A1, also diagnosed with celiac disease, shared:

I've dealt with anemia and low ferritin since high school. I've taken iron

pills, received IV treatments, avoided dairy, increased vitamin C, avoided

caffeine, consumed more red meat, cooked in a cast iron skillet, and went

gluten free. I’m still currently receiving treatment, despite a lack of

consistent results [due to celiac]. 119

Athlete A3 shared her experiences with diagnosis, treatment, and recovery by stating:

During my junior year of high school, my times slowed down a lot from

the previous year. So I went and had blood drawn to test my iron. Mine

was low for a runner, so I began taking iron supplements and by my senior

year I was able to get it [ferritin] back up and set a personal record. I took

Proferrin once a day for the rest of my senior year once I got it [ferritin

results] and I improved a lot after about a month. Now, I take it

periodically when I feel like I need to.

Athlete A5 shared many of the same experiences with fatigue and reported:

I visited a physician for symptoms related to fatigue. I felt more tired than

usual while running as well as at home doing daily activities. My

performances in workouts were becoming worse and my legs felt heavy

all the time. I always took naps in college, but they were becoming longer

because I felt tired all the time. I was getting headaches a couple times a

week. I went to the physician where they took blood to check for

hemoglobin and ferritin levels. I took an iron supplement for a couple

months until my levels increased. I started with a heavier dose and slowly

decreased. Once I began taking iron supplements I felt better, but it took

about two to three months for levels to be back to normal range.

While it is highly recommended to consult a physician first, one athlete expressed that she has taken iron pills without the consent of a doctor during her bouts of fatigue. Participant A8 confided: 120

My senior year of high school track I struggled greatly with fatigue, but

my labs were normal. I have always been one to take iron supplements.

Not because I necessarily needed them, but simply because I knew they

were good for me. I usually take Vitron-C. It has vitamin C included in it

so I absorb it even better.

From the parent’s perspective, all eight participants had to specifically request a ferritin test to be used in diagnosis, though one was refused. Each of these parents recommended specific treatment plans and most commented on the recovery of their student-athlete as well. Adding to these common experiences with tests, treatment, and recovery, Parent P1 shared:

My son was diagnosed with a CBC and ferritin test. After he tested at a

ferritin level of five and was diagnosed as anemic [his CBC was normal],

he took two Vitron-C tablets per day for a couple of weeks and was

retested. His iron levels were increasing so we continued to take one

Vitron-C daily. Since treatment, he has completed one season of track and

one season of cross country with this daily regimen and has been

successful at keeping his iron levels within normal range.

Parent P2 reported, “While taking Proferrin three times per day, [Her] ferritin jumped from 19 to 26 to 55.” Parent P3 also noting that his daughter was diagnosed by a ferritin test he had to request, stated, “She takes iron tablets twice daily. Her levels have improved and stayed in the acceptable range.” Sharing her experience with a physician that would only give her son the CBC test, Parent P5 reported: 121

Even though he wasn’t diagnosed as anemic, I was advised by the nurse at

his doctor’s office to just increase iron intake in his diet if I was

concerned. And if we wanted to, a multivitamin with iron could also help.

[However], no specific treatment was needed in his case. I did some

research on my own and learned what foods are naturally rich in iron.

This helped me realize he was eating well, but he was missing that key

nutrient [iron] in his diet. Along with adding these types of foods to his

diet, I also started him on a daily multivitamin. I would say after a few

weeks I could see a difference.

Parent P7, who has dealt with the diagnosis, treatment, and recovery with all three of her daughters, shared:

I had to request it [serum ferritin test] specifically. Our pediatrician is a

very good physician, but he was not familiar with low ferritin levels as it

related to endurance athletes. Daughter one, first we tried ferrous sulfate

tablets, then she took liquid iron for several months. Finally, after seeing a

hematologist she was given an iron infusion. Daughter two, she took two

Proferrin capsules from Colorado Biolabs for two years. Daughter three,

she also took two Proferrin capsules from Colorado Biolabs for two years.

They are all in their 20’s and still have the test [ferritin] run as needed.

Sharing the same experiences, Parent P8 reported:

Our daughter took Proferrin oral supplements for several years when we

discovered her ferritin level to be low and she was suffering from running

fatigue. She took it intermittently during high school: before cross country 122

season, stopped in the off season, and resumed it again prior to track

season. She has continued to take it in college. Her ferritin levels are

checked yearly. It has helped her tremendously.

Many of the healthcare professionals expressed the same views toward the general ease, affordability, and effectiveness of oral iron treatments in the absence of disease or complications with absorption. In general terms of treating fatigue,

Healthcare Professional H1 stated:

I would suggest they optimize their diet first and ensure they have a good

source of iron within their diet: grain cereals for breakfast, lean protein

during the day and at night, and other high iron content foods. Ensure

they are meeting or exceeding their daily recommended amount of

iron. Lifestyle modifications are first before going to medical

supplementation.

Sharing his thoughts on iron supplements and the need to reassess regularly during iron treatments, Participant H2 reported:

Typically speaking these patients don't get down to a level where they

need a blood transfusion. The mainstay is oral iron therapy. Most people

are able to get adequate iron through their diet and possibly a

multivitamin. But the treatment dose [if needed] would be the ferrous

sulfate 325 mg twice-daily. I typically do that and tend to recheck their

numbers after a few weeks. We would test both CBC and ferritin to make

sure that both are going up. IV iron is not that effective by itself. It will

get the iron levels up quickly. But, if you are not supplementing, those 123

numbers will just drop right back down if the underlying problem isn't

fixed.

Healthcare Professional H3 shared some strong sentiments toward the inadequate diets that he often observes with his patients. Pertaining to this concept, this participant offered several recommendations on diet, types of available supplements, and recovery timelines, by reporting:

I recommend a good quality vitamin in a tablet form until we get the iron

stores built back up. Then I direct them to the foods to get incorporated

into their diets. But the caveat I run into is, I’ll run down the list of iron

rich foods with them, and they’ll say “hate it, won’t eat it, shoot me, not

going to do it, forget it.” And I’ll say, “No wonder you’re deficient.”

We’ve become too accustomed to living off of potato chips and Pepsi and

Snicker bars and McDonalds. At the same time, you have to take into

account their workload. Just like your bank account, if you make a

million dollars, but spend a million dollars, you’re broke. It's the same

concept, if you’re taking in this many milligrams and expending this many

milligrams, then you’ve gained nothing. [For iron treatment] I’ve had

good clinical results using Ferronyl with added vitamin C. It has all the

cofactors and the iron is micronized: very small and very clean. Plus, it’s

organic iron instead of elemental iron. We’re organic. Our bodies

assimilate the [iron] from a plant, much better than it can from [elemental

iron]. Which is why food is always better than supplements. When you

get into the nutraceutical world, what you start discovering is, what-you- 124

get is what-you-pay-for. [Due to] the manufacturing process and possible

contaminants, you might have something over here that is extremely

cheap, but is made in China with contaminants and your body can’t

process it and assimilate it. Ours [Ferronyl] is made by Douglas and I

prefer it because it is organic and the body can process it much more

efficiently. [Pertaining to recovery] I like to reassess them after about

three months, which is where we usually start seeing some real progress.

From a more simplistic approach, the lone certified athletic trainer, participant H4 stated, “I always recommend diet and sleep modifications first. I try not to prescribe a lot of stuff, even Tylenol. I will refer them to their doctors for treatments beyond diet.” Healthcare Professional H5 also agreed with many of the previous statements concerning diagnosis, treatment, and recovery.

Specifically, Participant H5 noted:

We prefer to correct all deficiencies through [dietary] intake in every case.

But, when you’re down to like 15 or under, we’ll refer them to

hematology because it will take forever to get that up even with an iron

infusion. [Because] we prefer to correct the intake first, we only give

supplements based on what their labs say are needed. We look at

supplements almost like pharmaceuticals; we shouldn’t be taking them

unless you need them. [Pertaining to recovery] people generally do start

to feel better pretty quickly. I’d say within a month or two, people report

their fatigue is better. Their energy is better, but they’re still not at normal 125

yet. I would say most of my iron patients aren’t getting back to normal,

until six months to a year, unfortunately.

Also noting the importance of a healthy diet and inquiring about menstruation,

Participant H6 added:

We’ll start off with their diet. I’ll print off a list of iron rich foods for

them. Talk with the girls about their menstrual cycles and their periods.

When needed, I will usually recommend 325 mg of iron once or twice a

day. Liquid forms are more expensive. Get them from Sam’s Club or

whatever, as long as it doesn’t constipate them too bad. Taking iron with

vitamin C has been shown to increase absorption as well as avoiding too

much coffee, tea and alcohol. I will recommend vitamin B12

supplementation to vegetarians, but there are many ways to get iron in

their diets without animal heme iron. I would retest in a month or so as I

usually see improvements after about 4 weeks.

A second concept within this theme emerged pertaining to recommendations for additional testing when diet and supplementation do not appear to be effectively elevating hemoglobin and serum ferritin values. Coaches

C1, C4, C5, and C7 each mentioned additional testing associated with absorption issues including gluten intolerance, celiac disease, Crohn’s disease, H. pylori infection, mono, and hyperthyroidism. Athlete A1 noted that some of her treatments were ineffective due to absorption issues associated with her celiac diagnosis. This participant stated, “If [ferritin] levels aren't changing with treatment, athletes should consider testing for celiac disease, especially if vitamin 126

D or vitamin B come back low as well.” Healthcare Professional H1, H2, H3, H5, and H6 also noted several of the same tests for absorption disease. Participant H1 reported that he would always attempt to modify diets or rule out chronic disease before suggesting supplements. Specifically pertaining to this concept,

Participant H2 reported:

There are many things that can contribute to low ferritin, iron absorption,

and the inability to get your iron up. Even though the iron may be getting

into the body, those things would need to be appropriately assessed to

determine why it's just not getting absorbed into the system. It's usually

just from exertion and not eating right. But if they truly can't [raise their

ferritin], despite doing all the right stuff, celiac would have to be ruled out.

If they are having lots of stomach upset and various food intolerances, I

would consider testing for gluten intolerance across the board along with

checking blood count, metabolic profile, and a thyroid test.

Concerning absorption issues, Participant H3 reported, “We also might look into chronic disease and absorption issues such as mono and celiac disease. That is a whole other ballgame, because it's not just iron they are having absorption issues with. It’s medical problems across the board.” Participant H5 shared the same beliefs, and reported:

Look at diet first, then supplement as needed. But we will also look for

absorption issues. You really have to look pretty hard at the diet, good or

bad. You have to find out if there’s any obvious gastrointestinal

symptoms. People will report poor hair, poor skin, migraines, and all 127

kinds of things. So you are matching all those symptoms up to anything

you may find in the lab work you do. One goal of the diet is actually just

to prevent or control inflammation.

Healthcare Professional H6 agreed that inflammation can cause absorption issues, stating:

We may also test for celiac and gluten allergies. I’ve had some high

school athletes with gluten allergies. If they eat items with gluten, they

get inflammation in their small intestine and they’ll lose some blood. So

one of the workups for anemia or low ferritin is to look for celiac disease

or gluten allergies, and do some confirmatory tests to see if they need to

avoid gluten in their diets.

Additionally, both Athlete A8 and Parent P4 noted experience with complications associated with acne prescriptions. Specifically, Parent P4 stated, “We think the acne medication blocked iron absorption causing a lower ferritin level.”

The third concept which emerged from this theme was the common suggestion of contacting a physician before attempting any self-diagnosis or self- prescribed treatments. When asked about blind supplementation, all twelve of the coaches agreed it would be best to visit with a physician before taking any medications or supplements. Participants expressed an importance of measuring baseline levels before considering any type of concentrated supplement.

However, most felt that taking a multivitamin probably would not cause any harm. Coach C7 reported, “I would not [blindly supplement iron] because I feel like I need that knowledge first, as too much iron can be detrimental. 128

Multivitamin? Sure, but hopefully they are eating enough [good foods] that a multivitamin isn’t needed.” Coach C8 stated, “I never have recommended

[athletes] take iron blindly. For me it would be a conversation with the parent, over-the-counter choices you might look into. Obviously let them make the decision.” Coach C9 added, “All athletes see the team doctor before any significant changes to diet or supplements.” Participant C10 also noted, “No, I wouldn’t recommend that [blind supplementation] for any student-athlete. I don’t feel I’m knowledgeable to make that referral.” Coach C11 elaborated on communication with parents and liabilities that coaches may endure if they are recommending supplements by stating:

There seems to be conflicting responses. Some say distance runners

should all be on iron supplements, some recommend seeing a doctor first.

I check into diet and sleep first, then recommend the parents consider

seeing a physician about supplements. The parent is then left with the

decision of whether to pursue testing and/or supplementation saving the

coaches from any liabilities that may come up.

Coach C12 also expressed concerns over dangers that are associated with too much iron in the blood, by sharing, “I would not recommend taking iron supplements blindly. Don't they say it’s toxic? But, I think I could tell a kid to take a multivitamin and eat healthy.”

Pertaining to blind supplementation, all six healthcare professional confirmed taking iron supplements can be potentially dangerous when a person does not know their baseline levels first. Healthcare Professional H1 clarified his 129 stance of “life style modifications are preferred over medical supplementation” by reporting:

If their diet is already rich in iron and they take too much, those

supplements contain a lot of iron, they may not realize the damage they

are doing to their bodies. One of the things that iron can cause is

constipation. It could really back them up and cause further issues. Over

a long period of time, too much iron can cause metabolic issues and

electrolyte abnormalities for a patient. There is a disease called

hemochromatosis, which is abnormally high levels of iron circulating in

the body. It shoots the pancreas. People develop liver cancer, eye issues,

and become diabetic. There is no nutritional benefit to supplementing iron

if someone is getting an adequate diet and doesn’t have any lab

abnormalities or disease. I definitely would not recommend they take iron

supplements, just because they are an endurance athlete.

Agreeing with this position, Participant H2 added:

If you are taking a concentrated elemental iron, that dosage typically is not

needed. Most people should be able to get enough iron from their diet or a

standard multivitamin. Multivitamins are fine, without requiring a doctor.

But if they're going to be taking concentrated iron, it would be

recommended to at least know where you are ferritin and iron level wise

first. There is iron toxicity and various conditions associated with iron

overload; one of them being called hemochromatosis. That's a pretty 130

uncommon condition but it exists enough in the world that iron levels

probably need to be checked first.

On the topic of blind supplementation, Healthcare Professional H3 reported:

As for blind supplementation of iron, I’d recommend seeing a physician

first. Myself, I rarely blindly take any supplement. We [my family] test

ourselves at least once a year. A multivitamin is fine, kind of covering A

to Z, and it's not a lot [per tablet].

Participant H4 reported, “What I do recommend to kids, is just a regular vitamin such as a multivitamin. But not an iron supplement. And if they can't fix it with diet and a multivitamin, then we need to visit with a physician.” Participant H5 agreed, adding:

Especially with iron, we would never, based on ascension, say, “Hey, you

should try iron just because it’s oxidative.” We look at the diet and lab

scans first, then supplement as needed. [However] you can argue that

taking a multivitamin isn’t going to hurt anything.

Participant H6 also agreed with the previous statements, reporting, “I have always been skeptical of supplementing with iron and trying to boost ferritin levels to supernormal amounts, mainly because of lack of evidence of it helping. But also because of the risk of iron overload and liver damage.”

Summary

This chapter focused on the creation and discussion of the common themes established from the qualitative data collected through a process of semi- structured interviews and open-ended surveys. Participants were described in 131 detail, noting important demographics within each category. Theoretical saturation was achieved throughout each group of participants by means of their descriptions, explanations, and interpretations of the perceptions they hold pertaining to iron and its importance to endurance athletes. Through a process of open and axial coding, four distinct themes emerged from this data in relation to testing iron levels of fatigued endurance athletes. The four identified themes were: seek the opinion of a healthcare professional, serum ferritin is an important test for fatigue, optimal ranges need to be developed for serum ferritin levels, and treatment options are generally easy, affordable, and effective.

From the first theme, all 34 participants noted a prevalence of iron depletion associated with endurance athletes and the importance of contacting a healthcare professional within one or two weeks of first noticing the abnormal fatigue. Coaches, athletes, and parents frequently mentioned the use of CBC and ferritin tests when diagnosing symptoms of fatigue. However, most of the healthcare professionals that were interviewed, widened that range of assessments to also include metabolic tests, kidney tests, thyroid tests, possibly iron panels as well.

From the second theme, 29 of the 34 participants noted the importance of utilizing serum ferritin as a first-tier test in the diagnosis of athletes reporting fatigue. While all six of the healthcare professionals participating in this study also agreed on the importance of testing ferritin levels, the majority of the coaches, athletes, and all eight parent participants reported conflicting experiences with their primary care providers. Due to her persistence and help from her 132 coach, Parent P7 reported, “I was able to educate the doctor . . . due to his lack of knowledge on the subject.” This became the premise of the third concept common to this theme: the importance of researching iron depletion before visiting a primary care physician.

The third theme which emerged from this study pertained to the apparent lack of clear and concise standards for what is considered to be healthy ranges of serum ferritin. Many of the coaches, athletes, and parents participating in this study argued that healthy ranges determined by clinical laboratories are too low for this demographic. The six healthcare professionals in this study agreed, reporting that clinical lab norms are averaged from the population that requires their blood to be checked most often: the sick and elderly. Several of these participating healthcare professionals stated the need for a revised set of ranges to include a list of “optimal ranges” needed to maximize the human body’s potential, versus the current ranges created for minimal functional health.

The fourth and final theme which emerged from these conversations centered on the general ease, affordability, and effectiveness of most iron treatments. Most of the 34 participants spoke in favor of lifestyle modifications as the first step in treatment before considering taking additional supplements. As the body should be able to moderate and sustain its own cycle of iron, the focus should be on improving and enhancing dietary intake. However, endurance athletes may need to consider an iron supplement due to the high levels of exertion placed on their bodies. Supplements are readily available and offered at affordable prices at nearly every convenience store. However, most of the 133 coaches, athletes, and parents, and all six healthcare professionals recommended visiting a physician before considering any form of concentrated iron supplements. Due to the dangers associated with iron overload, it is imperative to test hemoglobin and serum ferritin levels before starting any form of iron supplement.

The data collected from the interviews and surveys conducted in this explorative study allowed the researcher to organize and analyze the perspectives of each participant pertaining to the importance of iron and its effects on endurance athletes. Chapter Five will provide a summary of the study, discussion of the findings, implications for practice, recommendations for further research, and final conclusions.

134

Chapter Five - Summary, Discussion, and Conclusions

Introduction

Chapter Five consists of a summary of the study, a discussion of the findings, implications for practice, recommendations for further research, and a conclusion statement. The purpose of this chapter is to discuss, develop, and expand upon the themes which emerged from the qualitative data collected in the previous chapter. This chapter will provide a deeper analysis of those results in relation to the research questions posed in this study and present suggestions for further research of this topic. Final resolutions will be reported within the closing remarks of the conclusion statements.

Summary of the Study

Iron deficiency has been shown to affect cognitive thinking, memory, mood, fatigue, work capacity, and athletic performance which all depend greatly on the body’s ability to adequately and effectively transport oxygen (Rowland,

2012). Depletion of iron stores can lead to iron deficiency anemia if not identified and corrected in a timely manner (Carley, 2003). A complete blood count (CBC) is a universal blood test which measures on-hand iron levels via a hemoglobin count and is generally used in the diagnosis of anemia. However, the

CBC test does not include the serum ferritin level, which is used to measure the body’s amount of stored iron. Non-anemic athletes reporting healthy CBC tests can still suffer from the effects of being iron depleted, but are rarely given the serum ferritin test to measure iron stores (Weinstein, 2009). Additionally, what constitutes an adequate level of serum ferritin is also heavily debated and opinions 135 vary greatly pertaining to what is considered healthy or optimal. Adding to the complications, many coaches, athletes, parents, and family practitioners are not aware of the current theories and methodologies driving new research on iron deficiency.

The purpose of this study was to examine the differing opinions surrounding the importance of testing multiple markers of iron status and explore the current knowledge held by coaches, athletes, parents, and healthcare professionals. Due to their importance as first point of contacts, these four demographics need to be educated not only on the symptoms and side effects of iron deficiency, but also informed of the current best methods of diagnosis and treatment. By virtue of these concerns, this study included two primary research questions:

1. Why do varying opinions exist pertaining to healthy levels of serum

ferritin and its relevance toward endurance athletes?

2. What level of understanding do coaches, athletes, parents, and healthcare

professionals have regarding the effects, diagnosis, and treatment options

of iron deficiency?

This study utilized an exploratory research approach to analyze which diagnostic tests physicians deem most beneficial in determining iron deficiency in endurance athletes as well as compiling data on current doctor recommendations regarding diagnosis of iron depletion and efficient forms of treatment. This study also explored the current depth of knowledge held by coaches, athletes, and parents concerning the effects of iron depletion on endurance athletes. 136

The research approach used in this study was selected with the intent of establishing grounded theories to be used in future research of this topic.

Participants consisted of coaches, athletes, parents, and healthcare professionals.

Coaches were selected randomly throughout the Kansas City Metro area while athletes and parents were selected via cluster sampling. Healthcare professionals were chosen locally through purposive and snowball sampling. A mixture of structured and semi-structured interviews were administered to the healthcare professionals and coaches to examine their perceptions of iron depletion associated with endurance athletes. Open-ended surveys were administered to the collegiate athletes and parents of endurance athletes to gather input on their personal experiences with iron depletion. The researcher then examined the resulting qualitative data looking for repeated ideas, concepts, and perceptions.

All correlations were extracted, coded, interpreted into concepts, and then grouped into categories that were used to develop themes and hypotheses for future research.

From this coding process, four distinct themes emerged in relation to testing iron levels of fatigued endurance athletes. The four identified themes were: seek the opinion of a healthcare professional, serum ferritin is an important test for fatigue, optimal ranges need to be developed for serum ferritin levels, and treatment options are generally easy, affordable, and effective.

The first theme pertained to the prevalence of iron depletion associated with endurance athletes and the importance of contacting a healthcare professional within one or two weeks of first noticing the abnormal fatigue. The 137 second theme pertained to the varying opinions held by physicians in regard to using serum ferritin as a first-tier test in the diagnosis of athletes reporting fatigue.

The third theme developed around the need to better define both healthy and optimal ranges for serum ferritin levels. The fourth and final theme pertained to the general ease, affordability, and effectiveness of most iron treatments under a physician’s care.

Discussion of the Findings

The intent of this study was to develop common themes highlighting the best methods of diagnosing fatigue and exposing the current knowledge of the participants regarding diagnosis, treatment, and recovery times associated with iron depletion. The findings of these four themes have been summarized and applied to the research questions of the study. This section discusses the implications of the findings for each of the research questions.

Research question one. Why do varying opinions exist pertaining to healthy levels of serum ferritin and its relevance toward endurance athletes?

Research question one was proposed to explore the contrasting views many hold regarding the importance of testing serum ferritin and the healthy ranges associated with the test. Few physicians will refute the importance of a

CBC test when suspecting iron deficiency anemia (IDA) and most agree on the healthy standards which have been set for each component of this test. However, research directed toward the initial stages of IDA, iron depleted (ID), and iron deficient non-anemic (IDNA), is scarce as these symptoms rarely pose an immediate health threat. While most physicians agree that serum ferritin levels 138 can be used to reasonably predict the body’s iron stores in the absence of inflammation, there are very conflicting views concerning the standardized healthy ranges of ferritin, general diagnosis of IDNA, and iron status treatment for patients with acceptable hemoglobin levels. Even with acceptable CBC measures, some physicians consider patients to be at risk when their serum ferritin falls below 50 ng/ml while others do not view these levels to be inadequate until dropping below 10 ng/ml (see Table 1). While mild iron depletion may not be viewed as significant from a health perspective, it can still have dramatic effects on both work and athletic capacities (Ljungqvist et al, 2009; Rodriguez et al.,

2009; Weinstein, 2009). Additionally, endurance athletes seem to be more prone to the effects of these earlier stages of IDA and often complain of abnormal fatigue even with borderline hemoglobin levels (Goodnough, 2010; Rowland

2012).

In this particular study, 29 of the 30 participants with knowledge and experience of the serum ferritin test agreed it was an important first-tier test when diagnosing symptoms of persistent fatigue with endurance athletes. One participant considered this test as more of a second-tier test, used after ruling out other major forms of disorder and disease. Consistent with the research presented in Chapter Two, this study noted a strong correlation pertaining to the importance of testing ferritin across all four participating demographics.

Summarizing many participants’ opinions, Athlete A5 reported, “[Our coach] had our ferritin levels tested twice a year to indicate our body’s iron stores and reveal whether or not we had an iron deficiency.” Adding to the importance 139 of screening serum ferritin, Healthcare Professional H2 stated, “Red blood cells have a lifespan of 120 days, so we are constantly needing to replace them. I would like to see adequate supplies in the store house to manufacture those cells as fast as possible.” Addressing the specific benefit in testing serum ferritin along with the CBC test, Participant H5 noted, “Ferritin is a basic nutrition screen. It should be screened anytime someone is reporting fatigue and iron is suspected.

The issue might not just be manifested in the CBC.” Due to its high prevalence with endurance sports, Participant H6 added, “Family practitioners with sports medicine training are certainly going to check ferritin when an athlete is coming in with fatigue.”

As the lone healthcare professional in this study not considering serum ferritin as a first-tier test, Participant H1 reported he would not necessarily order an iron panel if the patient’s CBC was normal, the patient reported a healthy diet, and the patient had no red flags in their medical history that would trigger a clinical suspicion for iron deficiency. However, this participant also reported that he would accommodate the request, if the patient was adamant on ordering a serum ferritin test.

Concurring with this healthcare professional’s discretion, all eight parents shared a common experience with primary care physicians. When visiting their primary care physician for abnormal fatigue, all eight parents noted their child’s

CBC was found to be within the normal ranges and each had to specifically request the serum ferritin test as it wasn’t going to be ordered. Each parent noted their physician’s hesitance, but seven of the eight parents eventually convinced 140 the physician to order the additional test due to their persistence and individual research on its importance. All seven of the patients who were reluctantly given the serum ferritin test, were found to be iron deficient via this blood test and received treatments to correct their low iron stores. Without this additional test, all seven athletes would have been misdiagnosed. The other patient never received the serum ferritin test, but was able to correct his fatigue naturally through a multivitamin and major changes to his diet. However, this parent shared a strong disappointment in the lack of effort and care that she felt was provided in the diagnosis of her son’s reported fatigue.

While the participants in this study conveyed the importance of testing serum ferritin when endurance athletes complain of undue fatigue, most of the coaches, athletes, and parents also reported hesitation from their primary care physicians to order this test. Concerning this common reluctance to test, Parent

P8 reported, “We had to request ferritin levels specifically as our pediatrician was not going to order this test. Our pediatrician is a very good physician, but he was not familiar with low ferritin levels as it relates to endurance athletes.” Noting a particularly poor experience with her primary care provider, Parent P5 shared:

I would recommend for parents to specifically request a serum ferritin test.

In my experience the doctor’s office will often give the patient the

hemoglobin test and not a serum ferritin test. Since, per his doctor's

office, his results were normal for someone his age, they stated he did not

need any further testing. I must admit I was somewhat disappointed to the

little importance they gave to the matter in general. 141

Participant C5 summed up the opinions of many coaches stating, “I’ve gotten to the point that I alert the athlete that 99% of general practitioners will not recognize the need for the ferritin test.” Acknowledging a lack of education and experience from physicians when dealing with endurance sports, Athlete A1 reported, “With most doctors, you have to request specific tests [ferritin] and remind them anything below 30 is too low for college women [athletes].”

While five of the six of the healthcare professionals in this study deemed the serum ferritin a first-tier test, all six of these participants offered speculation as to why some family practitioners might be reluctant in suggesting and ordering this particular blood test. Participants mentioned various reasons including the standard-of-care as provided by their medical group, restrictions concerning medical insurance, and a possible lack of education and experience within this particular demographic of patient. Summarizing many of the participants beliefs,

Healthcare Professional H5 reported, “The reason a family practitioner might not use this assessment is right at that line of lack of experience, lack of education, and insurance coverage. Many doctors do not have extensive training in nutrition nor exercise physiology.”

Healthcare Professionals H2, H5, and H6 each mentioned a lack of existing medical studies physicians can use to educate themselves. Many physicians have minimal experience dealing with this patient demographic.

Unfortunately, most of their visual exams and medical history prompts will point toward great overall health. Healthcare Professional H2 shared, “It’s a patient population without a lot of studies involved. It's not that they are bad doctors or 142 anything, they are just applying medical principles [meant for the sick and elderly] to an otherwise healthy kid.” Pertaining to the experience and knowledge of the intricacies often associated with sport-specific injuries and disease, this physician also recommended, “If you want good running health, find a good running doctor.” Noting the importance of a sports medicine background when working with athletes, Participant H6 reported, “Family practitioners with sports medicine training are certainly going to check ferritin when an athlete is coming in with fatigue, probably more so than the primary care physician who doesn’t have that background.” Participant H6 added, “There is a lack of training and education about the value of testing ferritin. It’s still more of a soft-science.

There doesn’t seem to be a real-well-done double blinded study on ferritin that

I’m aware of [making diagnosis very subjective].” However, this participant was very adamant toward the importance of testing the ferritin levels of athletes when reporting persistent fatigue. This is concern stems from evidence that low iron stores will eventually lead to becoming clinically anemic if not found and treated in its early stages.

All six healthcare participants also noted that insurance companies often dictate the diagnosis and treatment for all types of disorders and disease no matter the level of experience or education the physician may have with a particular patient demographic. Participant H5 reported, “The other problem that most doctors have, they are restricted by insurance coding. So unless they can justify ordering a lab by their standard-of-care, they won’t get it.” Participant H6 agreed, and added that oftentimes the benefits of additional testing outweigh the 143 additional out-of-pocket costs. This participant stated, “The ferritin test is a lot more expensive than a CBC. Once you start adding [additional tests for fatigue] you’re talking hundreds of dollars. If they are getting ready for the Olympic trials, then you’re going to spend more money doing lab work.” Participant H1 clarified this position stating that if a patient demanded iron panels not suggested by the physician, the patient would probably be charged the full amount for any additional tests of iron status. As reported by participant H1, insurance may not view these additional iron panels as a “proper use of medical resources due to standard-of-care” especially if the CBC reported measurements within in the normal healthy ranges.

Speaking directly about standard-of-care ramifications and medical insurance regulations, Participant H5 added, “[Physicians] are liable for anything that is not in that protected box of standard-of-care. We actually have a health system that is designed to prevent anyone from free-thinking and stepping outside of that box.” This participant offered tremendous in-depth experience and knowledge about contrasting opinions and beliefs on treating disease versus optimizing health. Participant H5 also warned about the ramifications associated with allowing insurance and standard-of-care to dictate how we diagnose and treat all patients. This participant confided that standard-of-care and medical insurance are largely used to diagnose and treat the sick and elderly. However, there is a large population hovering at the minimal line of health, wishing for optimal health instead. To clarify his position on this, Participant H5 stated, “If you’ve got a chronic disease and you’ve got something to get prescriptions and procedures for, 144 that’s what insurance is for. It is not for optimizing your health. And this

[demographic] falls under optimizing.”

Consistent with the research presented in Chapter Two, there is a disappointing lack of clear and concise standards for what is considered to be minimal versus optimal levels for iron stores (see Table 1, Appendix C).

According to this particular study, all of the coaches, athletes, parents, and healthcare professionals with knowledge of the serum ferritin test agree that clinical laboratory norms are too low for this patient demographic. These clinically normed references for minimal standards of health are heavily weighted toward the population that requires their blood to be checked most often: the sick and elderly. Participant H2 reported, “The laboratory definition of normal is not normal for this population of patients [endurance athletes]. The lab numbers are often normed off of the sickly and elderly population.” Agreeing with these statements, Participant H3 also shared, “The clinical ranges are based on the average of what the laboratory has been seeing. So that sample is heavily weighted with ill and elderly people.” Participant H5 shared the same concerns for how these clinical ranges were determined and added, “The range for iron is incredibly huge because we define healthy based on what causes a defect or disease, not what is optimal. In other words, [these ranges] all come from sick populations.”

Many of the participants in this study also stated the need for a revised reference list to include optimal blood test ranges for maximal health as well as updating the current minimal ranges used to rule out disorder and disease. Instead 145 of investing all of the time and resources on the sickly, these participants would like to see an emphasis placed on optimizing health as a preventative measure by helping to correct deficiencies that might lead to future illness and disease.

Pertaining to this need for individualized and up-to-date ranges, many of the participants throughout all four demographics expressed not only concerns for current clinical references but also noted their own preferences for serum ferritin levels based on personal experience and individual research. Many of the participants involved in this study agreed on minimal levels of at least 30 ng/ml, optimal levels above 50 ng/ml, but also ensuring serum ferritin levels remain under 150 ng/ml to avoid the toxic effects of iron overload. To summarize the beliefs held by most coaches, Coach C7 reported, “Most doctors recommend 10 to

20. But, I feel 30 or more is better based on my experience.” Coach C6 agreed stating, “Healthy levels of ferritin for a distance runner is generally between 50 and 120. You want to start a season there, but as long as you are above 30 you are going to be ok.” Agreeing with the opinions from the coaches, Athlete A1 reported, “Long distance runners typically need to be above 30. But it’s still possible to be fatigued when above 30 because athletes may have different thresholds.”

While only four of the six healthcare professionals were able to quote general healthy ranges of ferritin during their interviews, those numbers were interestingly higher than the recommendations from the coaches, parents, and athletes. Healthcare Professional H3 was the lowest at 40 ng/ml while both

Participants H5 and H6 recommended supplementing iron if serum ferritin levels 146 dropped below 60 ng/ml. Recommending a minimum serum ferritin level of 40 ng/ml for endurance athletes, Healthcare Professional H3 also noted his stance on various lower limits in relation to the lifestyle of the individual patient. This participant stated, “I’m sure it would vary per individual depending on their workload or their lifestyle. Whereas an average young adult might do just fine with a lower level, your athletes are going to want to bump that up.” Discussing his beliefs toward deficient, healthy, and optimal ranges, Participant H5 added,

“We take our measurements from sick people so there comes your deficient range. What is optimal for a human is currently undefined and is calculated largely based on the experiences of the doctors.” However, this participant is optimistic that changes are on the horizon. Reporting that large amounts of insurance dollars are spent on treating the already-sick, he feels there may be a switch to preventative medicine and placing a higher priority on optimizing health. Specifically, Participant H5 stated, “Honestly, I think the future of health depends on these athletes because there is a reason to optimize performance and people are willing to pay for that. If we can define what is optimal for them, then we’ll know what’s good for the rest of us.”

Research question two. What level of understanding do coaches, athletes, parents, and healthcare professionals have regarding the effects, diagnosis, and treatment options of iron deficiency?

Research question two was proposed to gain perspective into the current levels of knowledge and opinions held by coaches, athletes, parents, and the healthcare profession regarding iron depletion and its importance to endurance 147 athletes. Consistent with the research presented in Chapter Two, several participants of this study recognized a lack of large-scale, long-term studies. This has led to conflicting beliefs and theories to exist pertaining to the overall importance of testing iron stores when endurance athletes complain of persistent, abnormal fatigue. While sports physicians and athletic associations have recommended the creation of educational programs designed specifically for athletes, coaches, and healthcare professionals, few programs of this nature currently exist to inform and educate these stakeholders. With better education regarding proper nutrition, importance of early detection, appropriate tests for iron status, and efficient methods of treatments, iron deficiency can be identified, treated, and reversed (IOC, 2009; Loosli & Rudd, 1998; Mandali 2011).

Due to the reported discrepancies in healthcare opinions on this topic, participants in this study also recommended researching and acquiring as much information as possible pertaining to the current tests used in diagnosis and the numerous causes of persistent fatigue before visiting with their primary care physician. While most of the coaches admitted to trusting the expertise of the healthcare professionals, many recommended being informed, educated, and prepared to discuss the different options for diagnosis before visiting with their primary care physician. Coaches C1, C5, C6, C7, C8, C9, and C10 reported the importance of educating both their athletes and parents about the effects of iron depletion. Of the twelve coach participants, six referenced Dr. Kim Colter and a letter he drafted specifically for physicians which helps clarify and justify the importance of testing serum ferritin with endurance athletes and references 148 several landmark studies (see Appendix L). Of the eight collegiate athletes, six reported the importance of researching this subject and referenced their primary care physician’s general lack of knowledge and lack of experience with endurance athletes. Also referencing poor experiences regarding the knowledge and expertise held by their primary care physicians, all eight of the parent participants reported the importance of researching this topic beforehand. Parent P7 spoke freely about her conversations with the family’s trusted pediatrician and how they collaborated with her daughter’s coach to better educate themselves about fatigue associated with iron stores. This participant shared, “I have done a lot of research on iron deficiency on my own. With the help of my daughter’s coach and my persistence, I was able to educate the doctor. He had no personal experience with endurance athletes, fatigue, or ferritin levels.” Parent P5 reported, “From my experience, the more you understand the subject, the more information the doctor’s office will provide you with. Be prepared to ask the right questions.”

This participant reported that her son’s CBC results were very close to the normal range for his age and his physician claimed he did not need any further testing.

Upset that she did not receive the care she had expected from her family doctor and concerned the serum ferritin test was refused, this participant was forced to research fatigue and treatments on her own. Participant P5 summarized this sadly common experience by stating, “I did some research on my own and learned what foods are naturally rich in iron. This helped me realize he was missing that key nutrient in his diet. I also started him on a daily multivitamin. After a few weeks

I could already see a difference.” 149

Knowledge of effects. Pertaining to the initial symptoms and first steps in diagnosis of iron depletion, all 34 participants were able to reference at least some basic knowledge in regard to persistent fatigue. All twelve coaches and all six healthcare professionals reported diet, sleep, and stress as first-steps in recognizing the symptoms of abnormal fatigue. Summarizing the information all participants of this study shared about dietary intake, Healthcare Professional H1 stated, “I would suggest they optimize their diet first. Make sure they are getting sufficient amounts of lean protein and ensure they have a good source of iron within their diet. Lifestyle modifications are first before going to medical supplementation.” However, Participant H3 reported some additional concerns based on his experience with dietary modifications of teenagers. This participant stated, “I’ll run down the list of iron rich foods with them, and they’ll say, ‘hate it, won’t eat it, shoot me, not going to do it, forget it.’ We’ve become too accustomed to living off of potato chips.”

In regard to the symptoms of iron depletion, coaches, athletes, and parents are often the first to recognize the initial stages of iron depletion and noted obvious drops in performance when referencing the effects of iron depletion. Of the 28 coaches, athletes, and parents involved in this study, 24 reported being able to recognize the effects of iron depletion in relation to endurance athletes. Several participants shared specific examples and experiences of the dramatic effects caused by low iron stores. Coach C5 agreed with most of the coach participants by reporting, “I can see obvious signs of it; just the old dead legs. There’s no middle ground. It is a night and day difference.” Coach C7 agreed by stating, 150

“Generally, I notice when they don't look very good, that complete flat-looking performance in practice and meets.” Athlete A5 summed up many of the athlete responses by reporting, “I felt more tired than usual while running as well as at home doing daily activities. My performances in workouts were becoming worse and my legs felt heavy all the time. I felt tired all the time.” Participant A5 agreed with the noticeable drop in performance and reported an obvious increase in performance as her iron stores returned to normal. In reference to this experience, this participant stated, “My times slowed down a lot from the previous year. I had blood drawn to test my iron [which] was low for a runner. So I began taking iron supplements and was able to get it [ferritin] back up and set a personal record.”

However, the participants of this study reported numerous personal experiences where the primary care physician did not view iron stores as being significant from a health perspective. As referenced by 29 of the 34 participants in this study, depleted iron stores have been observed to have a dramatic effect on aerobic capacity and athletic performance.

Knowledge of diagnosis. As iron depletion can lead to a significant drop in athletic performance, work capacity, and VO2 max, many sports physicians recommend regular screenings of iron status for endurance athletes (Hinton, 2014;

Loosli & Rudd, 1998; Reinke et al., 2012). In separate consensus statements published in 2009 by both the American College of Sports Medicine and the

International Olympic Committee, researchers recommended routine hematological assessments as part of the pre-participation physical evaluations

(PPE) for competitive athletes (Ljungqvist et al, 2009; Rodriguez et al., 2009). 151

While PPE’s are required by most high school and collegiate activity associations, hematology lab tests are still not considered to be an essential piece of this health examination (Risser & Risser, 1990; Bernhardt & Roberts, 2010).

Consistent with the research presented in Chapter Two, coaches with aggressive training programs reported higher instances of iron depletion.

However, only four of the twelve coaches in this study recommended regular screenings of iron status to their athletes. In hopes of further educating those involved with his program, Coach C1 stated, “Every year, we have a meeting before the season starts to discuss the importance of testing for iron stores and its effect on fatigue.” Also a supporter of testing serum ferritin multiple times per year, Coach C7 reported, “We try to get the parents on board to test the athletes more than once a year to look for patterns of fatigue.” Participant C5 agreed with the recommendation of multiple screenings each year stating, “I’m almost at a point that I like to see the girls get tested before the season and mid-season no matter what.”

While early detection via iron status screening is important, it may not be feasible for all coaches, athletes, and parents until the first symptoms of fatigue begin to arise. Of the 34 participants in this study, 29 reported being able to recognize symptoms of fatigue possibly caused by iron deficiency. When first noticing symptoms of fatigue, all 34 participants expressed a common routine of questioning dietary habits, sleeping patterns, and personal stress. Additionally, all

34 participants recognized the need for contacting a healthcare professional within 152 the first two weeks especially if the fatigue persists after attempting to correct diet, sleep, and stress.

After questioning diet habits, sleep patterns, and personal stress, participants from all four demographics frequently mentioned the use of CBC and serum ferritin tests used to diagnose a possible iron deficiency. Of the healthcare professionals that were interviewed, most widened that range of assessments to also include metabolic tests, kidney tests, thyroid tests, and full iron panels when a clinical suspicion for iron deficiency existed. However, none of the participants in this study mentioned use of hepcidin markers and only Healthcare Professional

H6 mentioned soluble transferrin receptors (sTfR).

Pertaining specifically to diagnosing iron deficiency, 29 of the 34 participants in this study expressed a basic knowledge of the blood tests often utilized by healthcare professionals to diagnose iron deficiency anemia. Seven of the twelve coaches, five of the eight athletes, six of the eight parents, and four of the six healthcare professionals were able to state the approximate healthy ranges for serum ferritin. Four of the eight athletes actually received one or more ferritin tests throughout their career while seven of the eight parents successfully convinced their primary care physician to order a serum ferritin test for one or more of their children.

Consistent with the research presented in Chapter Two, 29 of the 34 participants in this study referenced the importance of utilizing serum ferritin as a first-tier test in the diagnosis of athletes reporting persistent fatigue. While five of the six of the healthcare professionals participating in this study also agreed in the 153 importance of testing ferritin levels, the majority of the coaches, athletes, and all eight parent participants reported conflicting experiences with their primary care physicians. As reported by these participants, the unwillingness to order serum ferritin tests may suggest these primary care physicians have a lack of current knowledge and experience with these tests as they pertain to endurance athletes.

Due to the hesitation and reluctance of many family practitioners to order serum ferritin tests, Dr. Kim Colter has created a letter which he recommends parents present to their family practitioners during their initial visit. This letter is written for physicians and helps clarifies the importance of serum ferritin tests when diagnosing symptoms of persistent fatigue associated with endurance athletes.

Also consistent with the research presented in Chapter Two, several participants reported assessing more than just the CBC and serum ferritin levels, especially when athletes do not immediately respond to dietary changes and iron supplements. Coaches C1, C4, C5, and C7 each mentioned additional testing associated with absorption issues including gluten intolerance, celiac disease,

Crohn’s disease, H. pylori infection, mono, and hyperthyroidism. Athlete A1 noted that some of her treatments were ineffective due to absorption issues associated with her celiac diagnosis. Healthcare Professional H1, H2, H3, H5, and H6 also referenced these same tests for use in diagnosing underlying disorders or disease affecting nutrient absorption. Specifically pertaining to this concept, Participant H2 reported, “Even though the iron may be getting into the body, [underlying issues] would need to be appropriately assessed to determine why it's not getting absorbed into the system. If they truly can't raise the ferritin, 154 celiac would have to be ruled out.” Healthcare Professional H6 agreed that inflammation can also cause absorption issues, stating, “We also test for celiac and gluten allergies. I’ve had some high school athletes with gluten allergies. If they eat items with gluten, they get inflammation in their small intestine and they’ll lose blood.”

Several participants also mentioned the excessive costs associated with these additional tests that might not be covered by insurance. While none of the participants reported paying for tests, this seems to be one of the more common reasons for hesitance by healthcare professionals. Only one participant mentioned the possibility of self-ordering tests through a cash lab. Pertaining to this contemporary option, Healthcare Professional H5 reported, “Cash labs are popping up everywhere now, because people are kind of taking over their own health in that regard. And they’ve gotten so much cheaper. A $35 walk-in-lab billed to insurance could run close to $1,000.”

Knowledge of treatment. As iron stores often take three to six months to replete, early detection is important for determining the need for iron treatments which can allow the athlete to continue to train and compete at high levels

(Koehler, 2016). Consistent with the research presented in Chapter Two, participants in this study also noted the general ease, affordability, and effectiveness of most iron treatments. However, most of the 34 participants spoke in favor of lifestyle modifications before considering additional supplements. As the body should be able to moderate and sustain its own cycle of iron, improving dietary intake should be the priority (National Institutes of Health, 2016). 155

Also consistent with the research presented in Chapter Two, participants in this study reported sufficient recovery from iron depletion in the absence of disease when using over-the-counter iron supplements. Iron supplements are readily available and offered at affordable prices at most convenience stores.

However, most of the coaches, athletes, parents, and all six healthcare professionals in this study recommended visiting a physician before considering any forms of concentrated iron supplements due to the dangers associated with iron overload.

When asked to share their experiences with iron treatments, participants acknowledged each of the methods discussed in Chapter Two, including diet, oral iron therapy, intravenous iron therapy, and other assorted vitamins associated with bolstering metabolism, accelerating the healing process, and increasing nutrient absorption: vitamin C, vitamin B12, vitamin B6, magnesium, zinc, and folic acid

(Camaschella, 2015; Hinton, 2014; Lamanca, 1989). In addition to the previously mentioned treatments, three participants also advocated the use of cast iron cookware to naturally add iron to their food. The use of cast iron to increase intake of iron during meal preparation is supported by several studies (Geerligs et al., 2003).

From this particular study, all 34 participants reported diet modification as an important first step in treating depleted iron stores. Supporting this claim,

Participant H1 stated, “I would suggest they optimize their diet first and ensure they are meeting or exceeding their daily recommended amount of iron. Lifestyle modifications are first before going to medical supplementation.” 156

Most of the coaches and all six healthcare professionals in this study also advocated the use of multivitamins as a complement to a healthy diet, especially vitamins associated with benefitting nutrient absorption. Supporting this claim,

Participant H4 reported, “I recommend a regular vitamin such as a multivitamin, but not an iron supplement [initially]. If they can't fix it with diet and a multivitamin, then we need to visit with a physician about bloodwork.”

While most participants would recommend the use of a daily multivitamin to athletes, 31 of the 34 participants stated they would never blindly recommend concentrated iron supplements without testing current iron levels first. Of the other three participants, two coaches stated they might suggest the parents consider looking into over-the-counter supplements but would not personally recommend it to the athlete and one athlete participant was currently taking elemental iron without the knowledge of her baseline iron levels.

Pertaining to blind supplementation and consistent with the research presented in Chapter Two, all six healthcare professional confirmed taking iron supplements can be potentially dangerous when a person does not know their baseline numbers first. Specifically addressing the dangers associated with supplementing iron when not warranted, Healthcare Professional H1 reported, “It shoots the pancreas. People develop liver cancer, eye issues, and become diabetic. There is no nutritional benefit if someone is getting an adequate diet and doesn’t have any lab abnormalities.” Agreeing with the other healthcare participants as to the dangers associated with iron overload, Participant H6 shared, “I have always been skeptical of supplementing with iron and trying to 157 boost ferritin levels to supernormal amounts, mainly because of lack of evidence of it helping. But also, because of the risk of iron overload and liver damage.”

When blood tests warrant more than just diet modifications and multivitamins, oral iron therapy was the most commonly reported form of treatment by all participant demographics. Of the 34 participants, 24 communicated experiences with various iron pills. Of those 24 participants noting successful results with oral iron, 10 specifically mentioned Proferrin ES

(heme based iron), two participants mentioned Vitron-C (elemental iron with added vitamin C), and one participant mentioned Ferronyl (an organic form of iron with added vitamin C). Describing her experiences with abnormal fatigue, poor race performances, and oral iron therapy, Participant A3 shared, “I took

Proferrin once a day for the rest of my senior year and I improved a lot after about a month. I was able to get [my ferritin] back up and set a personal record.”

Sharing a similar experience, Parent P1 also noted, “My son took two Vitron-C tablets per day for a couple of weeks and was retested. His iron levels were increasing so we continued to take one Vitron-C daily. Since treatment, he has been successful at keeping his iron levels within the normal range.” Also supporting this claim, Healthcare Professional H6 reported, “When needed, I will usually recommend 325 mg of iron once or twice a day. Taking iron with vitamin

C has been shown to increase absorption.”

While oral iron supplements were the most common treatment, liquid iron was also suggested for patients diagnosed with absorption disorders or disease.

Five participants in this study specifically expressed positive experiences with 158 liquid forms of oral iron in the presence of an inflammatory disease. Dealing with an absorption disease, Parent P7 reported, “First we tried ferrous sulfate tablets, then she took liquid iron for several months.”

Often considered a more dramatic approach, seven participants in this study reported mixed experiences with intravenous iron infusions. While this method is noted for increasing iron levels rapidly, three participants noted rapid decreases in iron as well, especially when the underlying issues weren’t corrected.

In reference to this, Participant H2 reported, “IV iron is not that effective. It will get the iron levels up quickly. But, if you are not supplementing, those numbers will just drop right back down if the [underlying] problem isn't fixed.”

When asked about experiences with recovery timelines associated with iron treatments, coaches, athletes, and parents routinely reported the first noticeable improvements of fatigue occur after approximately four weeks of treatments. Communicating the same beliefs, Participant C6 shared, “From my experience, I’d probably say it has taken about a month to really start to see results. I’ve never had a kid not get better.” Agreeing, with the other participants, Coach C7 reported, “Recovery usually takes at least two to four weeks. Performances stop sagging and pick back up to where they have been.”

Expressing longer recovery times, the healthcare professionals often reported full recovery can take up to a year. Specifically addressing the longer recovery times,

Participant H5 stated, “I’d say within a month or two, people report their fatigue is better. Their energy is better. But they’re still not at normal yet. I would say 159 most of my iron patients aren’t getting back to normal until six months to a year, unfortunately.”

Implications for Practice

The findings of this study have significant implications for all persons involved with endurance sports as it provides crucial information which can increase awareness pertaining to contemporary methods of diagnosis and effective treatment options for iron depletion. Consistent with the research presented in

Chapter Two, participants in this study communicated a strong need for improved studies of iron depletion as well as the importance of creating educational programs designed for coaches, athletes, parents, and healthcare professionals.

The findings presented in this study offer resources and additional research which can be referenced when determining best methods of diagnosis and treatment options for symptoms related to persistent fatigue of endurance athletes.

For coaches, athletes, and parents, this study provides educational information and important resources for use in conversations with primary care physicians related to iron depletion. This study confirmed a large disconnect between the opinions expressed by the healthcare professionals within this study and the reported experiences with primary care physicians. Many of the coaches, athletes, and parents reported poor experiences with their primary care physicians where they often had to self-advocate and demand additional iron tests not included with the standard CBC test. While many participants reported eventually receiving the care they requested, they stated their physicians were uninformed and lacked experience with iron depleted athletes. Referring to the 160 experience levels of many family practitioners, Healthcare Professional H2 reported, “It's not that they are bad doctors, they are just applying medical principles that are made for 80-year-olds to what appears to be a healthy 16-year- old kid. If you want good running health, find a good running doctor.”

The implications of this study will also benefit healthcare professionals when seeking research to justify ordering additional tests for iron status of these athletes when it may not fit the usual standard-of-care. The initial process of diagnosis for any disease or disorder is often subjective and based on clinical suspicions held by the attending physician. Adding to the many challenges of diagnosing disease or disorder, early stages of iron depletion are often asymptomatic and rarely cause significant drops in hemoglobin or hematocrit levels which may not justify additional tests of iron status. When CBC levels are within normal ranges, many family practitioners lacking experience with endurance athletes will not advocate ordering a serum ferritin test. However, consistent with the research presented in Chapter Two and the experiences reported by the participants of this study, serum ferritin is extremely important in the diagnosis of the early stages of iron depletion. Continued iron depletion without an increase in iron supply will ultimately lead to iron deficiency anemia spawning a myriad of significant and severe health risks (Camaschella, 2015;

Carley, 2003).

Recommendations for Further Research

The purpose of this study was to explore the various opinions and beliefs concerning the importance of testing multiple markers of iron status while 161 examining the current knowledge base in relation to the effects of iron depletion on endurance athletes. As noted throughout this study, contrasting beliefs exist pertaining to the various methods for screening iron status as well as differing opinions on the healthy ranges of these measurements. This study utilized an exploratory research approach to analyze data collected from various stakeholders involved in the process of reporting and diagnosing persistent fatigue.

During this study, important limitations surfaced concerning the lack of participation from primary care physicians and the subjectivity often reported in diagnosis of fatigue. These limitations suggest the need for significant improvements to the population sample of this study by targeting more primary care physicians in future studies. These limitations also suggest extended opportunities for future research into the diverse causes of fatigue and ramifications when iron deficiency is not detected in its earliest stages.

A suggestion for future studies would be to increase the number of athletes, parents, and healthcare participants while also expanding this regional representation to include participants from across the United States. The data collected from the parents and healthcare professionals in this particular study was skewed due to the extensive experience and individual research acquired by these participants pertaining to the overall health and wellness of endurance athletes. Unfortunately, this study lacked participation from inexperienced individuals not comfortable with answering questions on this subject and primary care physicians, who are generally the first point of contact for most parents and athletes. While five of the six healthcare professionals in this study deemed the 162 serum ferritin test as a first-tier test in the diagnosis of fatigue, the findings of this study are unclear as to why many family practitioners argue against its importance. Gathering more input from physicians who reportedly refute the importance of testing iron stores will open up further dialogue and add more validity to this discretionary topic. Their opinions toward this subject are equally important as diagnosis of iron depletion will continue to be subjective until further research is conducted and healthy ranges are refined.

Being exploratory in nature, this study identifies several opportunities for future research possibilities. While this study has generated several useful conceptual themes and categories, additional research will be necessary to develop a better understanding of the ramifications associated with low iron stores, modify standard-of-care regulations to accommodate endurance athletes, confirm the correlation between levels of training and prevalence of iron depletion, and to refine the current clinical ranges for normal while creating optimal ranges for improved work capacity.

In addition to iron deficiency, several other variables exist which can impact the symptoms associated with fatigue. These additional variables include rest, diet, stress, genetics, disease, disorders, and general motivation. Future studies might consider exploring the effects of these additional variables and their impact in relation to persistent fatigue of endurance athletes. This research should also include studies on the psychological effects associated with unexplained fatigue. While reporting on the physical effects of iron depletion, Healthcare

Professional H5 also noted some serious psychological effects that undiagnosed 163 fatigue may have on adolescents. Burn-out is a phrase commonly used to describe athletes who have lost the mental fortitude and motivation to continue training and competing at high levels. Some participants noted the possibility that burn-out may be contributed to persistent fatigue manifesting itself as a decline in mental capacity and motivation. Considering the mental states of most teenagers when performances begin to drop, Participant H5 added, “I worry about the mental health issues that might arise as the minds of teenagers often go to deep dark places. The teenage mind deals with a lot of stress and trauma. You’ve got layer after layer of dangerous things.”

There is also a need for additional studies to justify and validate the need for testing serum ferritin, especially when CBC results are reported to be within normal ranges. While the participants of this study believed in the importance of testing serum ferritin, many reported conflicting experiences with primary care physicians. Even though diagnosis of any disorder or disease is subject to clinical suspicions held by the attending physician, participants of this study reported a strong reluctance from primary care physicians to test serum ferritin due to a perceived lack of conclusive and credible studies. The participants of this study speculated this was due to inexperience with endurance athletes along with insurance coding issues and liabilities associated with the standard-of-care provided by the physician’s medical group. With additional studies and improved research, all physicians will have the tools they need to justify and validate their reasons for ordering additional tests for iron status. 164

Further studies may also be beneficial in confirming the prevalence of iron depletion associated with higher-volume training programs. While not an intended outcome, this study found a strong positive correlation between reported prevalence and reported training miles. While most participants reported fatigue was common with endurance athletes, the coaches that reported higher-prevalence of iron depletion also claimed to be higher-mileage programs. A study comparing the prevalence of iron depletion to the volume of training would also help justify and validate the use of serum ferritin tests for use with these patients.

Further research is also needed to examine the process in which clinical labs determine ranges for normal health. While few participants offered solutions to this problem, many expressed their beliefs in the need for refining the current clinical ranges for normal and creating new ranges dedicated to optimizing work capacity and athletic performance. According to the perceptions reported in this study, the current clinical ranges provide minimal levels used to rule out disorders and disease. Most participants also felt these minimal values were created for the average, sedentary population. Endurance athletes may require a diet exceeding the recommended daily allowances and optimized results on their blood tests in order to complement their intense training programs. There is also a growing population of non-athletes who strive for better health and increased work capacity as well. According to several participants, business opportunities are developing in regard to this growing trend of optimization of health. Many of the healthcare professionals in this study suggested a higher emphasis on optimizing health as a preventative measure to combat deficiencies which might lead to 165 future illness and disease. Specifically addressing this need for further research,

Participant H5 reported:

I think the future of health depends on these athletes because there is a

reason to optimize. If we can define what is optimal for them, then we’ll

know what's good for the rest of us. This is becoming a huge business

opportunity for people in Kansas City right now. I just think that it would

be great for somebody to vet that, and I think your study would be good

for this.

Conclusions

The findings of this study revealed four common themes as reported by the coaches, athletes, parents, and healthcare professionals who participated in this research: seek the opinion of a healthcare professional, serum ferritin is an important test for fatigue, optimal ranges need to be developed for serum ferritin levels, and treatment options are generally easy, affordable, and effective. Most participants in this study were well-informed of the effects, current methods of diagnosis, and treatment options available for endurance athletes with depleted iron stores. However, most of these participants noted very different experiences when visiting with their primary care physicians about their concerns of persistent fatigue. These participants reported their primary care physicians were hesitant or reluctant to test iron stores even when requested by the patient. Participants often speculated this was due to the physician’s general lack of experience with endurance athletes and possible liabilities associated with the standard-of-care their medical group has provided. With additional studies and improved research, 166 all physicians will have the tools they need to justify and validate their reasons for ordering additional tests for iron status.

Due to the widely ranging opinions and beliefs surrounding the importance of testing iron stores, this study suggests a need for additional studies and research of iron depleted athletes. Most of the participants in this study reported their limited knowledge base stemmed from Google searches, Wikipedia, and discussions with colleagues. For this reason, most participants addressed the need for establishing credible and conclusive studies pertaining to both iron deficiency and iron depletion. A lack of studies of this nature has pressured sports medicine doctors to go above and beyond their standard-of-care and rely more on experience and personal research when diagnosing these fatigued athletes. Pursuing diagnosis based on experience versus standard-of-care has created conflicting beliefs and theories to develop pertaining to the overall importance of testing iron stores. By creating additional studies associated with iron depletion and developing educational opportunities regarding proper nutrition, early detection, and efficient treatments, all stakeholders will have the tools necessary to effectively address the symptoms of persistent fatigue in relation to iron depletion.

167

References

Auersperger, I., Škof, B., Leskošek, B., Knap, B., Jerin, A., & Lainscak, M. (2013).

Exercise-induced changes in iron status and hepcidin response in female runners.

PLOS ONE, 8(3). doi:10.1371/journal.pone.0058090

Bermejo, F. (2009). A guide to diagnosis of iron deficiency and iron deficiency anemia in

digestive diseases. World Journal of Gastroenterology WJG, 15(37), 4638.

doi:10.3748/wjg.15.4638

Bernhardt, D. T., & Roberts, W. O. (2010). PPE: preparticipation physical evaluation.

Elk Grove Village, IL: American Academy of Pediatrics.

Berber, I., Diri, H., Erkurt, M. A., Aydogdu, I., Kaya, E., & Kuku, I. (2014). Evaluation

of Ferric and Ferrous Iron Therapies in Women with Iron Deficiency Anaemia.

Advances in Hematology, 2014, 1-6. doi:10.1155/2014/297057

Bhatia, T. (2017, August 15). 11 Foods to Avoid for Anti-Inflammatory Eating.

Retrieved October 13, 2017, from https://www.rodalewellness.com/food/foods-

avoid-anti-inflammatory-eating

Braunstein, E. M. (2016, November). Iron Deficiency Anemia. Retrieved from

www.merckmanuals.com/professional/hematology-and-oncology/anemias-

caused-by-deficient-erythropoiesis/iron-deficiency-anemia

Bruner, A., Joffe, A., Duggan, A., Casella, J., & Brandt, J. (1996). Randomised study of

cognitive effects of iron supplementation in non-anaemic iron-deficient

adolescent girls. The Lancet,348, 992-996.

Brutsaert, T. D., Hernandez-Cordero, S., Rivera, J., Viola, T., & Hughes, A. G. (2003,

February 01). Iron supplementation improves progressive fatigue resistance 168

during dynamic knee extensor exercise in iron-depleted, nonanemic women.

Retrieved from http://ajcn.nutrition.org/content/77/2/441.full

Burden, R. J., Morton, K., Richards, T., Whyte, G. P., & Pedlar, C. R. (2014). Is iron

treatment beneficial in, iron-deficient but non-anaemic (IDNA) endurance

athletes? A systematic review and meta-analysis. British Journal of Sports

Medicine,49(21), 1389-1397. doi:10.1136/bjsports-2014-093624

Burns, M. A., Ge, Z., Muthupalani, S., Georgieff, M., & Fox, J. G. (2015). Helicobacter

pylori infection induces anemia, depletes serum iron storage, and alters local iron-

related and adult brain gene expression in male INS-GAS mice.

Gastroenterology,148(4). doi:10.1016/s0016-5085(15)31761-3

Camaschella, C. (2015, May 7). Iron-Deficiency Anemia. New England Journal of

Medicine,372(19), 1832-1843. doi:10.1056/nejmra1401038

Carley, A. (2003). Anemia: When is it iron deficiency? Journal of Nursing

Education,29(2).

Chua, E. (1999). Serum transferrin receptor assay in iron deficiency anaemia and

anaemia of chronic disease in the elderly. Qjm, 92(10), 587-594.

doi:10.1093/qjmed/92.10.587

Cirino, E. (2016, February 23). Total Iron Binding Capacity Test. Retrieved from

http://www.healthline.com/health/total-iron-binding-capacity#Overview1

Colledge, H., & Cafasso, J. (2015, October 13). H. pylori Infection. Retrieved from

http://www.healthline.com/health/helicobacter-pylori

Colter, K. (2017, January 20). Personal Communication. 169

Davis, J. (2016, May 23). How Important is VO2 Max? What Does Yours Actually

Mean? Retrieved from RunnersConnect website

www.runnersconnect.net/running-training-articles/is-vo2-max-worth-spending-for

Dellavalle, D. M., & Haas, J. D. (2011). The effects of iron depletion without anemia on

training and performance in female collegiate rowers. (Doctoral dissertation).

Cornell University. Retrieved from ProQuest. (3485151)

Dellavalle, D. M., & Haas, J. D. (2014). Iron Supplementation Improves Energetic

Efficiency in Iron-Depleted Female Rowers. Medicine & Science in Sports &

Exercise,46(6), 1204-1215. doi:10.1249/mss.0000000000000208

Eckert, C. (2017, February 2). Personal Communication.

Finch, C. A., Gollnick, P. D., Hlastala, M. P., Miller, L. R., Dillmann, E., & Mackler, B.

(1979). Lactic Acidosis as a Result of Iron Deficiency. Journal of Clinical

Investigation,64(1), 129-137. doi:10.1172/jci109431

Freeman, H. J. (2016). Anemia in Adult Celiac Disease; Presentation with Iron

Deficiency Anemia Masked by Colon Cancer. International Journal of Celiac

Disease,3(1), 33-36. doi:10.12691/ijcd-3-1-2

Friedmann, B., Weller, E., Mairbäurl, H., & Bärtsch, P. (2001). Effects of iron repletion

on blood volume and performance capacity in young athletes. Medicine and

Science in Sports and Exercise, 741-746. doi:10.1097/00005768-200105000-

00010

Gardner, G., Edgerton, V., & Senewirante, B. (1977). Physical work capacity and

metabolic stress in subjects with iron deficiency anemia. American Journal of

Clinical Nutrition,30, 910-917. 170

Garvican, L. A., Saunders, P. U., Cardoso, T., Macdougall, I. C., Lobigs, L. M.,

Fazakerley, R., . . . Gore, C. J. (2014). Intravenous Iron Supplementation in

Distance Runners with Low or Suboptimal Ferritin. Medicine & Science in Sports

& Exercise, 46(2), 376-385. doi:10.1249/mss.0b013e3182a53594

Geerligs, P. D., Brabin, B. J., & Omari, A. A. (2003). Food prepared in iron cooking pots

as an intervention for reducing iron deficiency anaemia in developing countries: a

systematic review. Journal of Human Nutrition and Dietetics, 16(4), 275-281.

doi:10.1046/j.1365-277x.2003.00447.x

Girelli, D., Nemeth, E., & Swinkels, D. W. (2016). Hepcidin in the diagnosis of iron

disorders. Blood,127(23), 2809-2813. doi:10.1182/blood-2015-12-639112

Goodnough, L. T., Nemeth, E., & Ganz, T. (2010). Detection, evaluation, and

management of iron-restricted erythropoiesis. Blood,116(23), 4754-4761.

doi:10.1182/blood-2010-05-286260

Green, H. J. (1998). Living high-training low. Clinical Journal of Sport Medicine, 8(2),

144. doi:10.1097/00042752-199804000-00018

Grinaker, Hanna Elisabet (2014). Iron supplementation and its effect on ferritin levels in

female collegiate track and field athletes. (Master’s thesis). North Dakota State

University. Retrieved from ProQuest. (1583998)

Healthcare Bluebook (2017). Retrieved from

https://www.healthcarebluebook.com

Hill, Brian P. (2014). Do current medical procedures sufficiently diagnose iron

deficiency? (Master’s thesis). University of Hawaii. Retrieved from ProQuest.

(1528264) 171

Hinton, P. S., Giordano, C., Brownlie, T., & Haas, J. (2000). Iron supplementation

improves endurance after training in iron-depleted, nonanemic women. Journal of

Applied Physiology, 88(3), 1103-1111.

Hinton, P. S. (2014). Iron and the endurance athlete. Applied Physiology, Nutrition, and

Metabolism,39(9), 1012-1018. doi:10.1139/apnm-2014-0147

Hutchinson, Alex (2014, April 16). Iron supplements and VO2 max. Retrieved from

Runners World website: http://www.runnersworld.com/sweat-science/iron-

supplements-and-vo2max

Hynes, H. (2016, June 27). Iron Supplementation For Athletes. Retrieved from

http://www.smscs.dreamhosters.com/wp-content/uploads/2016/06/PD2016-Iron-

and-the-Athlete.pdf

Iron Disorders Institute. (2017, March 10). Tests to Determine Iron Levels. Retrieved

from http://www.irondisorders.org/tests-to-determine-iron-levels/

Jade, Kathleen (2016, July 1). Iron Deficient But Not Anemic? A Simple Solution For

Fatigue. Retrieved from University Health News

website: http://universityhealthnews.com/daily/energy/iron-deficient-but-not-

anemic-a-simple-cause-of-chronic-fatigue-symptoms-with-a-simple-solution/

Johnson-Wimbley, T. D., & Graham, D. Y. (2011). Diagnosis and management of iron

deficiency anemia in the 21st century. Therapeutic Advances in Gastroenterology,

4(3), 177-184. doi: 10.1177/1756283X11398736

Joyner, M. J., & Coyle, E. F. (2008). Endurance exercise performance: The physiology of

champions. The Journal of Physiology, 586(1), 35-44.

doi:10.1113/jphysiol.2007.143834 172

Koehler, K., Braun, H., Achtzhen, S., Hildebrand, U., Predel, H., Mester, J., & Schanzer,

W. (2012). Iron status in elite young athletes: Gender-dependent influences of diet

and exercise. European Journal of Applied Physiology, 112(2), 513-523. doi:

10.1007/s00421-011-2002-4

Koehler, Scott (2016). Team physician statement on iron status screening. Retrieved from

St. Olaf College website: http://athletics.stolaf.edu/custompages/sports-

medicine/2016-17/ferritin.pdf

Kundrat, Susan (2017). Nutrition: fueling the distance runner. Retrieved from Track and

Field Toolbox website: http://trackandfieldtoolbox.net/distance/nutrition-fueling-

distance-runners

Lab Tests Online (2015, October 29). TIBC, UIBC, and Transferrin. Retrieved from Lab

Tests Online website:

https://labtestsonline.org/understanding/analytes/tibc/tab/sample/

Lamanca, John Joseph (1989). Effects of iron supplementation on aerobic power,

endurance performance, blood lactate, and body iron stores in women. (Doctoral

dissertation). Florida State University. Retrieved from ProQuest. (9002930)

Lippi, G., Schema, G., Salvagno, G., Aloe, R., Banfi, G., & Guidi, G. (2012). Foot Strike

Pattern and Gait Changes During a 161-km Ultramarathon. Blood Transfusion,3,

377-383. doi:10.2450/2012.0167-11

Ljungqvist, A., Jenoure, P., Engebretsen, L. (2009). International Olympic Committee

(IOC) Consensus Statement on Periodic Health Evaluation of Elite Athletes.

Journal of Athletic Training,44(5), 538-557. doi:10.4085/1062-6050-44.5.538 173

Loosli, Alvin R. (1993). Reversing sports-related iron and zinc deficiencies. Physician

and Sportsmedicine, 21(6), 70-78.

Loosli, Alvin R.; Ruud, Jaime S. (1998). Meatless diets in females: a red flag. Physician

and Sportsmedicine, 26(11), 45-48.

Lynch, S., Worwood, M., Beard, J., & Northrop-Clewes, C. (2005). Assessing the iron

status of populations. Geneva: World Health Organization, Dept. of Nutrition for

Health and Development.

Macon, B. L., & Lamoreux, K. (2017, June 19). Blood Diseases: White and Red Blood

Cells, Platelets and Plasma. Retrieved September 22, 2017, from

http://www.healthline.com/health/blood-cell-disorders

Mandali, S. L. (2011). Coaching the vegetarian athlete. Journal of Physical Education,

Recreation & Dance, 82(2), 44-56. doi:10.1080/07303084.2011.10598582

Mangin, M. (2016, December 14). Anemia. Retrieved from

https://chronicillnessrecovery.org/index.php?option=com_content&view=article&

id=192

Mayo Clinic (2017). Test ID: sTfR. Retrieved from Mayo Clinic website:

http://www.mayomedicallaboratories.com/test-

catalog/Clinical+and+Interpretive/84283

Mclean, E., Cogswell, M., Egli, I., Wojdyla, D., & Benoist, B. D. (2008). Worldwide

prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System,

1993–2005. Public Health Nutrition,12(04), 444.

doi:10.1017/s1368980008002401 174

Mcclung, J. P., Martini, S., Murphy, N. E., Montain, S. J., Margolis, L. M., Thrane, I.,

Pasiakos, S. M. (2013). Effects of a 7-day military training exercise on

inflammatory biomarkers, serum hepcidin, and iron status. Nutrition

Journal,12(1). doi:10.1186/1475-2891-12-141

Murawska, N., Fabisiak, A., & Fichna, J. (2016). Anemia of Chronic Disease and Iron

Deficiency Anemia in Inflammatory Bowel Diseases. Inflammatory Bowel

Diseases,22(5), 1198-1208. doi:10.1097/mib.0000000000000648

Nall, Rachel (2015, October 1). Ferritin Level Blood Test. Retrieved from Healthline

website: http://www.healthline.com/health/ferritin#Overview1

National Institutes of Health. (2016, February 11). Dietary supplement fact sheet: Iron.

Retrieved from National Institutes of Health website:

http://ods.od.nih.gov/factsheets/Iron-HealthProfessional/

Ophardt, C. (2003). Virtual ChemBook. Retrieved from

http://chemistry.elmhurst.edu/vchembook/index.html

Parrow, N. L., Fleming, R. E., & Minnick, M. F. (2013). Sequestration and Scavenging of

Iron in Infection. Infection and Immunity,81(10), 3503-3514.

doi:10.1128/iai.00602-13

Pasricha, S., Low, M., Thompson, J., Farrell, A., & De-Regil, L. (2014). Iron

Supplementation Benefits Physical Performance in Women of Reproductive Age:

A Systematic Review and Meta-Analysis. Journal of Nutrition,144(6), 906-914.

doi:10.3945/jn.113.189589

Peeling, P., Dawson, B., Goodman, C., Landers, G., & Trinder, D. (2008). Athletic

induced iron deficiency: new insights into the role of inflammation, cytokines and 175

hormones. European Journal of Applied Physiology, 103(4), 381-391. doi:

10.1007/s00421-008- 0726-6

Perkkio, M., Jansen, L., Brooks, G., Refino, C. & Dallman, P. (1985). Work performance

in iron deficiency of increasing severity. Journal of Applied Physiology, 58(5),

1477-1480.

Quest Diagnostics : Homepage. (n.d.). Retrieved October 06, 2017, from

http://www.questdiagnostics.com/

Reinke, S., Taylor, W. R., Duda, G. N., Haehling, S. V., Reinke, P., Volk, H., . . .

Doehner, W. (2012). Absolute and functional iron deficiency in professional

athletes during training and recovery. International Journal of Cardiology,156(2),

186-191. doi:10.1016/j.ijcard.2010.10.139

Risser, William L., Risser, Jan M. H. (1990). Iron deficiency in adolescents and young

adults. Physician and Sportsmedicine, 18(12), 87-101.

Rodriguez, N., DiMarco, N., & Langley, S. (2009). Position of the American Dietetic

Association, Dietitians of Canada, and the American College of Sports Medicine:

Nutrition and Athletic Performance. Journal of the American Dietetic

Association,109(3), 509-527. doi:10.1016/j.jada.2009.01.005

Rowland, T. (1988). The Effect of Iron Therapy on the Exercise Capacity of Nonanemic

Iron-Deficient Adolescent Runners. Archives of Pediatrics & Adolescent

Medicine,142(2), 165. doi:10.1001/archpedi.1988.02150020067030

Rowland, T. (2012). Iron Deficiency in Athletes. American Journal of Lifestyle

Medicine,6(4), 319-327. doi:10.1177/1559827611431541 176

Santiago, P. (2012). Ferrous versus ferric oral iron formulations for the treatment of iron

deficiency: a clinical overview. Scientific World Journal, 5. doi:

10.1100/2012/846824

Schumacher, Y. O., Schmid, A., Konig, D., & Berg, A. (2002). Effects of exercise on

soluble transferrin receptor and other variables of the iron status. British Journal

of Sports Medicine,36(3), 195-199. doi:10.1136/bjsm.36.3.195

Scitable. (2014). Mitochondria. Retrieved from Scitable by Nature Education website:

http://www.nature.com/scitable/topicpage/mitochondria-14053590

Skikne, B. S. (2008). Serum transferrin receptor. American Journal of

Hematology,83(11), 872-875. doi:10.1002/ajh.21279

Telford, R. D., Sly, G. J., Hahn, A. G., Cunningham, R. B., Bryant, C., & Smith, J. A.

(2003). Footstrike is the major cause of hemolysis during running. Journal of

Applied Physiology, 94(1), 38-42. doi: 10.1152/japplphysiol.00631.2001

Tidy, Collin. (2014, October 20). Non-Anemic Iron Deficiency. Retrieved from Patient

website: http://patient.info/doctor/non-anaemic-iron-deficiency#ref-1

Vaucher, P., Druais, P., Waldvogel, S., & Favrat, B. (2012). Effect of iron

supplementation on fatigue in nonanemic menstruating women with low ferritin: a

randomized controlled trial. Canadian Medical Association Journal,184(11),

1247-1254. doi:10.1503/cmaj.110950

Verdon, F. (2003). Iron supplementation for unexplained fatigue in non-anaemic women:

double blind randomised placebo controlled trial. Bmj,326(7399), 1124-0.

doi:10.1136/bmj.326.7399.1124 177

Waalen, Jill (2003, June 28). Retrieved from website:

http://www.bmj.com/content/326/7399/1124/rapid-responses

Walk-In-Lab (2017). Retrieved from http://www.walkinlab.com

Wade, A. (2014, November 10). Supplementation May Help with Non-Anemic Iron

Deficiency. Retrieved January 24, 2017, from

http://www.runnersworld.com/newswire/supplementation-may-help-with-non-

anemic-iron-deficiency

Wang, Wei, Knovich, Mary Ann, Coffman, Lan G., Torti, Frank M., & Torti, Suzy V.

(2010, August). Serum Ferritin: Past, Present and Future. BBA,1800(8), 760-9.

doi:10.1016/jbbagen2010.03.011

Weight, L., Byrne, M., & Jacobs, P. (1992). Haemolytic effects of exercise. Clinical

Journal of Sport Medicine,2(1), 74. doi:10.1097/00042752-199201000-00021

Weinstein, James L. (2009, August 6). Iron and the endurance athlete [Web log post].

Retrieved from Training Peaks

website: http://home.trainingpeaks.com/blog/article/iron-and-the-endurance-

athlete

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Appendix A: IRB Approval

To: Dr. Paul Sturgis

Cc: Jamin Swift

From: Tom Frankman, Ed.D. Chair, Institutional Review Board Associate Dean, Academic Services

Protocol Number: 122

Title: Effect of Iron Deficiency on Endurance Athletes

Date: January 10, 2018

On January 8, 2018, the William Woods University Institutional Review Board (IRB) reviewed and approved the above-cited protocol following expedited review procedures.

Please note the following: Please keep copies of the signed consent formed used for this research for three years after the completion of the research. Any modification to your research (including protocol, consent, advertising, instruments, funding, etc.) must be submitted to the Institutional Review Board for review and approval prior to implementation. Any adverse events or unanticipated problems involving risks to subjects including problems involving confidentiality of the data identifying the participants must be reported to the Institutional Review Board office.

The anniversary date of this study is January 8, 2019. You may not collect data beyond that date without WWU IRB approval. A continuing review form must be completed and submitted to the Institutional Review Board 30 days prior to the anniversary date or upon the completion of the project. You will be sent a reminder prior to the anniversary date.

If you have any questions, please contact me at [email protected]

179

Appendix B: Consent Form

Jamin Swift 415 Cheyenne Dr Raymore, MO 64083

January 10th, 2018

Dear Sir or Madam:

You are invited to participate in a study that will be conducted by Jamin Swift, who is a doctoral student at William Woods University working under the supervision of Dr. Paul Sturgis. The title of the project is, “Effect of Iron Deficiency on Endurance Athletes.” The purpose of this study will be to examine the perceptions and current knowledge concerning the use of multiple markers of iron status with endurance athletes.

If you decide to participate, your participation in this study will consist of taking part in an interview that is expected to last approximately 15 to 20 minutes. The interview questions will ask about your attitudes, opinions, and experiences concerning the use of various tests to determine the iron status of endurance athletes. Your participation in this study is voluntary, and if you decide to participate, you may withdraw from the interview at any point. There are no known risks that are likely to occur due to participation in this study.

Participants in this study will remain anonymous and will not be identified by name in any documents that discuss the results of the study.

If you have any questions about this study, feel free to contact Mr. Swift at (816) 786-6925 or Dr. Sturgis at (573) 592-4463.

Please sign and date below to indicate that you have been informed about the nature of the study and that you are willing to participate in the study.

Sincerely,

Jamin Swift

______(Signature) (Date) 180

Appendix C: Varying Opinions for Determining Iron Depletion

Table 1

Varying Opinions for Determining Iron Depletion Based on Serum Ferritin At Risk for ID Source Date <10 ng/mL Quest Diagnostics 2017 <12 ng/mL Braunstein 2016 <15 ng/mL British Columbia Medical Association 2015 <20 ng/mL Rowland 2012 <30 ng/mL Koehler 2016 <30 ng/mL Bermejo 2009 <30 ng/mL Camaschella 2015 <30 ng/mL (Women) International Olympic Committee 2009 <35 ng/mL Peeling et al. 2008 <40 ng/mL (Men) International Olympic Committee 2009 <40 ng/mL Eckert 2017 <40 ng/mL (Runners) Koehler 2016 <50 ng/mL (Women) Vaucher et al. 2012 181

Appendix D: Interview Questions for Healthcare Professionals

Structured - Demographics 1) What is your age and gender?

2) What is your educational level and years of experience?

3) Do you hold any special certifications (nutritionist, dietitian, physical therapy, medical, first responder, etc….)?

4) Have you researched or received any specific training on the following:  Strength and conditioning?  Injury prevention?  General health status of athletes?  Nutritional deficiencies?

Semi Structured – Open Ended Questions 1) Do you have any background in athletics/exercise?  If yes, ask participant to expand upon this.

2) Fatigue is pretty common with endurance athletes. Would you and at what point would you recommend seeing a healthcare professional for complaints of general fatigue?

3) If a person came to your office complaining of abnormal fatigue, how would you proceed in diagnosis?  If iron deficiency is brought up, ask about specific training or research they’ve sought on the topic.

4) If hemoglobin and hematocrit measures came back normal, under what conditions would you pursue further testing if the patient still reports fatigue?  Ask about different types of tests

5) There are widely varying opinions as to the importance of administering a serum ferritin test even when hemoglobin and hematocrit levels are within acceptable ranges. Through your research and personal experience, what are your general beliefs and thoughts in measuring ferritin levels in the general public?  If the patient was a highly trained endurance athlete, would that make any difference in your opinion?  If yes, why might some primary care physicians refute this test?  Off the top of your head, do you know what the acceptable levels of ferritin would be?  Where would a person find that information?  Ask how those numbers are determined. 182

6) If hemoglobin levels were low, what specific treatments would you generally propose?  What if their hemoglobin levels were acceptable, but ferritin levels were under 20 (or a little low if they aren’t aware of acceptable levels)?  When do you patients generally start to notice a positive change in fatigue?

7) Are there any other important items that should be considered in a study of this nature?

183

Appendix E: Survey Questions for Parents

Structured - Demographics 1) What is your age and gender?

2) What are the ages and genders of your children?

3) What is your educational level and occupation?

4) Do you hold any special certifications related to healthcare (nutritionist, dietitian, physical therapy, medical, first responder, etc….)?

5) Have you researched or received any specific training on the following:  Strength and conditioning?  Injury prevention?  General health status of athletes?  Nutritional deficiencies?

Semi Structured – Open Ended Questions 1) Do you have any background in athletics/exercise? If so, briefly describe your background.

2) Fatigue is pretty common with endurance athletes. At what point would you consider contacting a healthcare professional for complaints of general fatigue?

3) If visiting a healthcare professional due to symptoms of fatigue, would you simply trust their expertise, or are there specific questions and/or blood tests you would recommend discussing with the physician?

4) If the standard tests for fatigue were given (CBC – complete blood count) and results were within standard healthy ranges, under what conditions would you pursue further testing? Please list any additional tests related to fatigue you may be aware of?

5) Have you ever received or researched information pertaining to iron deficiency? If yes, briefly describe your experience.

6) Off the top of your head, do you know what the acceptable levels of hemoglobin and ferritin are?

7) Have any of your children been treated for low iron? If so, what blood tests did the physician use (if you can remember)? If a ferritin test was used, did your physician suggest it or did you have to specifically request it? If you had to request the test, was there any argument or disagreement from the physician? 184

Appendix F: Interview Questions for Coaches

Structured - Demographics 1) What is your age and gender?

2) Where do you coach and what sports do you coach?

3) Do you teach as well? If so, what grade levels and what subjects?

4) What is your educational level and years of experience?

5) Do you hold any special certifications related to healthcare (nutritionist, dietitian, physical therapy, medical, first responder, etc….)?

6) Which of the following best describes your training program:  Low Mileage (less than 15 miles for the girls, 20 miles for the boys)  Medium Low Mileage  Medium Mileage (30-35 miles for the girls, 40-45 miles for boys)  Medium High Mileage  High Mileage (over 50 miles for the girls, 65 miles for the boys)

7) Have you researched or received any specific training on the following:  Strength and conditioning?  Injury prevention?  General health status of athletes?  Nutritional deficiencies?

Semi Structured – Open Ended Questions 1) What was your background in athletics/exercise before entering the coaching field?  If yes, ask participant to expand upon this.

2) Fatigue is pretty common with endurance athletes. Have you ever worked with athletes that reported more-than-usual levels of fatigue?  If yes, briefly describe the athlete(s) and important detail(s) of the event(s).

3) When an athlete starts to complain or appears to be suffering from fatigue, what would you recommend?  Ask the participant to expand upon any specific answers.

4) At what point would you recommend consulting a healthcare professional?  Ask the participant to expand upon any specific answers.

185

5) If visiting a healthcare professional due to symptoms of fatigue, are there any specific questions or tests you would you would recommend the athlete discuss with their physician?  If yes, ask participant to expand upon this.

6) If the standard tests for fatigue were given and results were within the healthy ranges, under what conditions would you pursue further testing if your athlete still reports abnormal fatigue?  Ask participant to expand upon any specific answers.  Ask if the participant is aware of any different types of blood tests for fatigue.  Ask if the participant is aware of tests used to measure iron stores versus on-hand iron levels.

7) Have any of your athletes been diagnosed with iron depletion, iron deficiency, or anemia?  Ask participant to expand upon any specific answers.

8) Have you ever received or researched information pertaining to iron deficiency?  If yes, ask participant to expand upon this.

9) Off the top of your head, do you know what the acceptable levels of hemoglobin and ferritin are?

186

Appendix G: Survey Questions for Collegiate Athletes

Structured - Demographics 1) What is your age and gender?

2) How long have you been running?

3) Are you receiving a scholarship to run?

4) Have you researched or received any specific training on the following:  Strength and conditioning?  Injury prevention?  General health status of athletes?  Nutritional deficiencies?

Semi Structured – Open Ended Questions 1) Fatigue is pretty common with endurance athlete, did/does your coach/team ever discuss abnormal fatigue and its relationship to iron?

2) Would you recommend an athlete consult a healthcare professional reporting abnormal levels of fatigue? If so, at what point would you recommend this?

3) When visiting with a healthcare professional about fatigue, would you simply trust their expertise and judgement, or are there specific questions and/or blood tests you would recommend requesting more information about?

4) If the standard tests for fatigue were given and results were within the standard healthy ranges, under what conditions would you pursue further testing (list any additional tests of fatigue you may be aware of)?

5) Have you ever received or researched information pertaining to iron deficiency? If so, briefly describe your experience.

6) Do you have any knowledge of serum ferritin blood tests? If so, briefly describe your knowledge and experience.

7) Off the top of your head, do you know what the acceptable levels of hemoglobin and ferritin are?

8) Have you personally visited a physician for symptoms related to fatigue? If so, briefly describe your experience.

9) Have you ever received treatments for low iron? If so, briefly describe your treatments (type, amount, duration, effectiveness, etc…) 187

Appendix H: Healthcare Participants

Table 2

Notable Demographics of Healthcare Participants Endurance Ferritin used as a Preferred Ferritin Participant Certifications Background First-Tier Test Level (ng/ml) H1 Doctor of Medicine Yes Probably Not Unaware H2 Doctor of Medicine Yes Yes 60, but prefers 100 H3 Doctor of Chiropractic No Yes Above 40 H4 Athletic Trainer No Yes Unaware H5 Nutritionist No Yes 60 to 90 H6 Doctor of Medicine Yes Yes Above 60 188

Appendix I: Coach Participants

Table 3

Notable Demographics of Coach Participants Participant Gender Team Gender School Demographics Weekly Training Miles C1 Male Females Suburban Medium High C2 Female Coed Urban Low C3 Male Coed Rural Medium C4 Male Coed Suburban Medium Low C5 Male Coed Suburban Medium High C6 Male Coed Rural Medium C7 Female Females Suburban Medium High C8 Male Males Suburban Medium C9 Male Coed Collegiate High C10 Male Coed Rural Medium Low C11 Male Coed Suburban Medium C12 Male Coed Rural Medium Low

189

Appendix J: Parent Participants

Table 4

Notable Demographics of Parent Participants Participant Gender Background Information Ferritin test used in diagnosis? P1 Female Sleep Technician Yes, but had to request P2 Female Fitness Coordinator Yes, but had to request P3 Female Dance Team Yes, but had to request P4 Male Soccer Coach Yes, but had to request P5 Female CPR Training Requested but denied P6 Female High School Athletics Yes, but had to request P7 Female Registered Nurse Yes, but had to request P8 Female Registered Nurse Yes, but had to request 190

Appendix K: Collegiate Athlete Participants

Table 5

Notable Demographics of Collegiate Athlete Participants

Participant Gender Event College Classification Knowledge of Ferritin Ferritin Tested A1 Female Distance NCAA DI Yes Yes A2 Male Distance NCAA DI Yes No A3 Female Distance NAIA Yes Yes A4 Male Distance NCAA DII No No A5 Female Distance NCAA DII Yes Yes A6 Female Sprints NCAA DI No No A7 Male Distance NAIA No No A8 Female Distance NCAA DII Yes Yes 191

Appendix L: Letter for Physicians from Dr. Colter

Dear Doctor,

The runner you are seeing is requesting that serum ferritin be tested to assess total body iron stores. In my experience, there are many distance runners who are iron deficient without being anemic or microcytic and these runners are not able to perform optimally when their serum are below 30. Iron deficiency for runners is not simply an issue of having adequate hemoglobin. At least one muscle enzyme involved in lactate metabolism (Cori cycle), alpha glycerol phosphate oxidase, is an iron containing enzyme and inadequate levels of this enzyme make runners incapable of racing and doing hard training. The listed lower limits of "normal" for ferritin values vary from lab to lab, and are sometimes listed as low as single digits. Dr. Camaschella, a world authority on iron metabolism, stated in the May 2015 NEJM that ferritin was the most sensitive and specific test for iron deficiency and defined iron deficiency as less than 30. Runners with serum ferritins below 30 do not perform well. I encourage distance runners who are running year round to test their ferritin twice a year. Runners who are taking iron supplements must have ferritin tested to be sure no iron overload is occurring and to verify that replacement is adequate. Testing at the end of fall cross country season and after outdoor track season is over in late spring will allow identification of runners who are deficient in total body iron stores in time to allow replenishment of those iron stores by supplementation prior to the next season of hard running. Many runners require iron supplementation while running in order to prevent the development of iron deficiency. While iron deficiency is more common in female distance runners, male distance runners experience it as well. Hard running and racing lead to transient ischemia of distal colon and rectal mucosa with proven increased losses of iron in stool compared to sedentary controls.

In my experience, testing for the development of anemia is testing for the last thing that occurs in iron deficiency. Testing ferritin is much more helpful in the early detection of iron deficiency in runners than testing hemoglobin alone. Certainly, testing hemoglobin, HCT, and MCV may be useful in discovery of anemia that is due to factors other than iron deficiency.

If I can clarify my opinion regarding iron in runners please feel free to contact me at [email protected].

Kim Colter MD Washington, MO

Am J Dis Child. 1988;142(2):165-169. doi:10.1001/archpedi.1988.02150020067030 study showing that adolescent runners with normal hemoglobin and low ferritin demonstrate improved running performance with correction of iron deficiency as measured by serum ferritin concentration.

Finch CA, Miller LR, Inamdar AR. Iron deficiency in the rat. Physiological and biochemical studies of muscle dysfunction. J Clin Invest. 1976;58:447–552. rat study in which rats with normal hemoglobin and reduced total body iron stores have poorer exercise tolerance and higher rate of lactate production during treadmill exercise than iron replete group of rats with the same hemoglobin concentration.

Int J Sports Med. 1996 Oct;17(7):473-9. Iron deficiency in distance runners. A reinvestigation using Fe-labelling and non-invasive liver iron quantification. Study demonstrating the increased loss of iron in stool in runners who are racing and performing quality training.

Camaschella, Cara MD NEJM 2015:372:1832-1843 May 2015 “Serum ferritin level is most sensitive and specific test used for the identification of iron deficiency (indicated by a level of less than 30 micrograms per liter.)"