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B
Workshop Papers
Concerns About the Effects of Military Environments on
Mineral Metabolism and Consequences of Marginal
Deficiencies to Performance
Karl E. Friedl
U.S. Army Research Institute of Environmental Medicine,
Natick, Massachusetts
OVERVIEW
Statement of the Problem
Mineral requirements to sustain soldier performance in stressful conditions
have been considered in military nutrition studies for many decades but rarely as
the primary focus of the studies (Johnson, 1986; Sauberlich, 1984). These stud-
ies, which were often underpowered, only descriptive, or not designed to address
specific hypotheses in this area, raised questions that remained unresolved. The
primary concern is the inability to-date to determine if there is a problem related
to mineral metabolism (especially iron, calcium, zinc, and magnesium) that im-
pairs health and performance in some soldiers in any field conditions. This should
be considered from at least the following two perspectives: (a) does the military
environment produce somewhat unique derangements or specifically change min-
eral intake requirements that affect performance? and (b) are marginally defi-
cient individuals (regardless of the reason for their deficiency) impaired relative
to the demands of military performance? Answers to these questions are also
240
OCR for page 241
APPENDIX B 241
important as they will help the Army address persistent suggestions about using
mineral supplemention for soldiers that arise from health advocates and inter-
ested entrepreneurs.
Military Stressors
Key stressors in the military environment include thermoregulatory chal-
lenges, hard work and exercise, inadequate rest and energy intakes, and psycho-
logical stress. Inadequate food intake is a problem in field environments, where
soldiers typically underconsume by 25 percent of their energy requirements, and
it can be worsened by the loss of appetite in hot or hypoxic environments;
underconsumption is also a consequence of strictly enforced body fat standards,
possibly with a larger effect on service women than men because women are
more likely to exceed the standards and restrict their food intake. High sweat rate
and water turnover is an important feature of hot work environments. Psycho-
logical stressors range from trauma (e.g., exposure to traumatic injuries and
death, exposures to populations living in poverty and ruin, and feelings of help-
lessness in some peacekeeping operations) and anxiety (e.g., worry about per-
sonal safety and family separation), to information overload (e.g., managing
complex data from multiple sources). The extent to which these exposures are
manifested in various stress responses depend on the resilience of the individual
as well as leadership, unit cohesion, and other stress mitigators.
Some unique environments and exposures (e.g., cold, altitude, enclosed en-
vironments, blast overpressure in field artillery units, noise and toxic chemicals
around military vehicles and aircraft, radiofrequency radiation in communica-
tions centers) may also have to be considered when recommending optimal min-
eral intakes. A previous Committee on Military Nutrition Research (CMNR)
concluded that none of these special environments had been adequately charac-
terized as producing higher oxidative stress burdens to soldiers than that for the
healthy active U.S. population (IOM, 1999).
Health and Performance Outcomes
Soldiers are likely to be involved in demanding physical tasks that require
strength and endurance; most physical tasks require lifting and carrying heavy
loads. There are also significant mental demands that come with increased speed,
complexity, and lethality of modern warfare; in this regard, every individual
soldier may be called upon for rapid decision making and judgment calls, may
require fine psychomotor performance (e.g., marksmanship), spatial mapping
ability, pattern recognition, etc. Mood and motivation are important underlying
aspects of soldier mental performance at all times. Even momentary lapses in
mental and physical performance may have catastrophic effects in today's mili-
tary environment.
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242 MINERAL REQUIREMENTS FOR MILITARY PERSONNEL
Practical tests that adequately reflect militarily-relevant performance have
been elusive but various test paradigms have provided useful measures in mili-
tary studies, such as repeated box lifts (strength endurance), simulated sentry
duty (vigilance, judgment, psychomotor performance), and simulated mission
control center (multiple cognitive domains). The Army is increasingly turning to
realistic training simulators that include electronic "combat" games and new
markmanship trainers; these systems can also be converted to research tools that
unobtrusively assess performance.
In addition to cognition abilities, a fully responsive immune system is criti-
cal to maintain the health and optimal health needed to face the demands of
military lifestyle. Regardless of how good our vaccines may be, soldiers are not
likely to be protected against all the endemic and deliberate infectious threats
that may determine success or failure of a mission, nor will they have equipment
and drugs to fully prevent inflammatory responses to physical demands and
other physical and chemical threats. This highlights one more broad outcome of
interest to the Army, optimizing a soldier's resistance to disease and injury.
Some of the host defense systems that determine immunological and inflamma-
tory responses appear to be importantly affected by mineral status.
RANGER TRAINING AS A STRESS MODEL
In the early 1990s, the Army had concerns about the high prevalence of
infectious illnesses (pneumococcal pneumonia and soft tissue infections such as
cellulitis) occurring in healthy young men undergoing 65 days of Ranger train-
ing with multiple stressors, including extreme food and sleep restriction and hot
humid conditions. This concern led to a request to determine if we could just
provide "an iron pill or a vitamin" to prevent soldiers from getting sick while
subjected to the same high level of stressful training. Initially we conducted a
descriptive study to quantify the stressors (1,000 kcal/day energy deficits; 3.6 hr/
day sleep) and their effects; this was followed by a study that increased feeding
by only 400 kcal/day, which was associated with marked improvement in im-
mune function and reduction in infection rates (Kramer et al., 1997). Most of the
men lost all of their fat reserves and the main adverse outcomes due to the
semistarvation were in the cognitive and immune function (Friedl, 2003; Friedl
et al., 2001). In addition, soldiers were hyperphagic and had sleep disturbances
for several weeks after the course but were fully recovered six months later.
During the initial planning of these experiments, we worried repeatedly
about what would happen to iron and hematological parameters in association
with the extreme privation. It was assumed that at some point hemoglobin and
hematocrit would become low enough that it would not be safe or ethical to
continue to draw blood from the test volunteers. This never happened and the
significant changes in iron status that were observed occurred in the first few
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APPENDIX B 243
weeks of the course and corrected by the end of the course (Figure B-1). The
observed changes were ascribed to acute phase responses, with no changes in
iron, zinc, or copper status between baseline and the end of the course (Moore et
al., 1993; Shippee et al., 1993). One possible explanation for the absence of a
progressive decline in iron status is that periodic re-feeding that occurred at the
end of each two week phase through the four training phases of this course
replenished any deficiencies (sampling was done at the end of each phase of
restriction and before the re-feeding began). The loss of muscle mass in this
study would have also provided a steady supply of minerals and nutrients into
the circulation. These findings matched those in the 1973 biomedical studies of
Ranger training, with comparable weight loss and also no significant changes in
hematological parameters and iron status across the training period. Thus, we did
not detect overt mineral deficiencies in one of the most stressful models we
could ethically study. However, only iron was targeted for study a priori and
periodic re-feeding provided a less challenging intermittent replenishment.
MILITARY QUESTIONS
Is There a Problem (#1)?: Stress of Initial Entry Training
and Iron Status in Young Women
Iron became a subject of interest after a 1979 study identified deficiencies in
female West Point cadets; this was observed again in the decennial 1989 study,
despite the high prevalence of mineral and vitamin supplement use (Friedl et al.,
1991; Kretsch et al., 1986). The observation was attributed to "just part of the
stress of West Point," rather than being considered a medical concern, a treatable
condition, or an important performance issue. However, in 1993, a comprehen-
sive study of womens' health and performance in the last gender-segregated
Army basic training class also suggested a high incidence of iron deficiency
anemia compared to the U.S. population (Westphal et al., 1995). We noted inad-
equate intakes of several minerals compared to established RDAs, a slight wors-
ening of iron status through the course, and a correspondence between poor iron
status and physical fitness test run time (Westphal et al., 1995). Several subse-
quent studies attempted to followup on these findings as part of the 1994 De-
fense Women's Health Research Program (DWHRP). One followed a select
population of new female officers, comparing iron and hematological status to
treadmill measured aerobic performance at the beginning and end of their officer
basic course. This group was uniformly well nourished and fit, and offered no
significant correlation between measures of iron and hematological status and
aerobic performance (Cline et al., 1998); this sample was probably not represen-
tative of the majority of female soldiers. The second study was a cross sectional
examination of three populations of female soldiers, with iron and hematological
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244 MINERAL REQUIREMENTS FOR MILITARY PERSONNEL
Hemoglobin Hematocrit
160
40
140
35
120
(g/L)
100 30
80
25
Hemoglobin 60
40 20
Baseline wk 2 wk 4 wk 6 wk 8 Baseline wk 2 wk 4 wk 6 wk 8
Ferritin Iron
240 14
12
190
10
(ug/L) 8
140 (umol/L)
6
Ferritin Iron
90 4
2
40
0
Baseline wk 2 wk 4 wk 6 wk 8
Baseline wk 2 wk 4 wk 6 wk 8
FIGURE B-1 Changes in iron status indicators status during Ranger training under
severe food restriction and other stressors.
SOURCE: Moore et al. (1993).
B-1 new
data that suggested a worsening status through their initial training (IOM, 1995).
The cross sectional design presented a significant weakness in this study, and
because of different locations, feeding regimens, and stressors, it was difficult to
draw conclusions about the nature of this apparent decline in health status. A
clinical study investigated the prevalence of iron deficiency in women referred
to a military gastroenterology clinic, concluding that the majority of asymptom-
atic iron deficiency anemia cases, including several already diagnosed by spe-
cialists as having excess blood loss related to menstrual flow, actually had a high
prevalence of significant endoscopy findings (Kepzyk et al., 1999). A fourth
study funded in the DWHRP examined the benefits to neurocognitive perfor-
mance from zinc and iron repletion in marginal deficiency. In preliminary analy-
ses, many cognitive and psychometric tests were apparently improved
(Sandstead, 2001); however, the results have not yet been reported.
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APPENDIX B 245
Is There a Problem (#2)?:
Calcium Requirements and Bone Health
Calcium intakes have been given more attention in military studies in the
past decade because of research initiatives on prevention of stress fractures,
particularly in female recruits. As part of the DHWRP, the CMNR convened a
special review of women's body composition, nutrition and health which in-
cluded a major review of stress fractures in the military (IOM, 1998). The subse-
quent Bone Health and Military Medical Readiness (BHMMR) research pro-
gram was shaped by the recommendations from this review and from the DRI
report on calcium, vitamin D, and related nutrients (IOM, 1997).
One important DWHRP project demonstrated that energy deficit, not in-
tense exercise, was a key determinant of menstrual disturbances (Loucks and
Thuma, 2003), refuting earlier concepts of a "female athlete triad" of intense
exercise, menstrual abnormalities and osteoporosis. This was consistent with
findings that high functioning women, such as Olympic athletes, exercising in-
tensively but not restricting their diet had normal rates of oligomenorrhea. As a
follow up effort supported by the BHMMR, experimental manipulations of the
energy deficit that exceeded thresholds and caused alterations in LH (luteinized
hormone) pulsatility, produced changes in bone mineral metabolism consistent
with demineralization (Ihle and Loucks, 2004).
Another important study, currently underway, is testing the hypothesis that
2,000 mg of calcium along with 800 IU of Vitamin D can substantially reduce
the acute occurrence of stress fracture in a study of 5,200 young women during
eight weeks of recruit training at the Great Lakes Naval Base. Part of the hypoth-
esis and assumptions are that young women still have not attained peak bone
mass, recruit training stimulates new bone formation, calcium intakes are nor-
mally low in this population, and substantial sweat calcium losses occur in this
training (Lappe, 2003).
Special populations such as submariners living for extended periods in closed
environments and away from sunlight have reduced plasma levels of 25-(OH)
Vitamin D and special challenges in calcium metabolism (Sack et al., 1986).
Two studies in progress in the BHMMR program are defining Vitamin D needs
in relation to ethnicity and skin pigmentation, following up on a research gap
identified in the review of calcium, vitamin D, and related nutrients (IOM, 1997).
Are We Missing a Performance Enhancing Benefit
(Or Are Some Supplements a Health or Performance Risk)?
Some military studies have raised questions about the effects of stressors on
mineral requirements and/or effects of supplementation on mitigation of stress
responses. For example, as part of an important series of starvation and limited
intake studies to determine minimum requirements for 10-day patrols, the 1968
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246 MINERAL REQUIREMENTS FOR MILITARY PERSONNEL
Panama study measured intakes and losses for sodium, potassium, calcium, and
magnesium, including sweat and urine excretion rates (Consolazio et al., 1979).
The authors concluded that magnesium intakes were deficient but there was no
biomedical evidence of a decline in magnesium levels. In a study at the Uni-
formed Services University of Health Sciences (USUHS), magnesium balance in
anaerobic exercise was considered. Another study tested specific performance
benefits of zinc combined with Vitamin E on exhaustive running in women,
based on hypothesized antioxidant actions, but found no effect of acute dosing
(Singh et al., 1999). However, there has been no concerted effort through a
carefully planned program of studies to determine benefits and risks of mineral
supplements in military populations.
Most service members report using supplements of some kind; this is cur-
rently being resurveyed to improve estimates of specific supplement use. Young
soldiers are at high risk for the use of supplements with putative performance
enhancement because of the ready availability of these products in military com-
missaries and stores, and because of perceptions that military training and opera-
tional demands somehow drive a higher intake requirement, as well as the strate-
gically seeded suggestions of performance enhancement in popular fitness
magazines and the prevalent belief that such claims could not be made if they
were not true (Friedl et al., 1992). A potentially important question that has
never been addressed in military research studies is whether or not higher than
usual intakes of certain supplements, including minerals, produce a deficiency
state from withdrawal that is likely to occur when soldiers leave them behind for
a field exercise or operational deployment. Another concern would be individual
and population bases of upper limits of intakes, such as the obvious problem of
iron overload if supplements are provided across military groups, for men and
women or to all women regardless of their iron status.
SUMMARY
Constant discoveries of new roles of minerals in integrated physiological
processes, where a mineral deficiency may have far reaching consequences on
stress responses and susceptibility to disease makes this an important and rel-
evant line of inquiry for military medical research. The key question that has
never been properly addressed in military or other relevant studies is "can we
achieve a sizeable improvement in mental or physical functioning, especially in
stressful operational or training conditions, by improving the mineral status of
young men and women in the military?" This area of investigation has been
hindered by the absence of (1) practical and validated tools to definitely assess
outcomes including neuropsychological outcomes and changes in disease sus-
ceptibility, (2) adequate indices of mineral status, not confused by stress states
including acute phase responses, and (3) clear indications of health and perfor-
mance deficiencies.
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APPENDIX B 247
Research conducted under the special performance demands and conditions
in which soldiers have to operate will not be addressed elsewhere and needs to
be conducted by the Army. In fact, there is no other federal agency with a
primary focus on biomedical aspects of performance; more typically the research
is focused purely on health outcomes. This work is primarily centered at the U.S.
Army Research Institute of Environmental Medicine in the Military Nutrition
Division in collaboration with the Pennington Biomedical Research Center and
with scientific guidance from the Institute of Medicine's CMNR.
The key question(s) can also be framed by a pragmatic question: Should the
Department of Defense consider the addition of a mineral supplement pack in
every ration with instructions on use for "health and performance optimization,"
or perhaps other strategies on the use of whole foods?
DISCLAIMER
The opinions and assertions in this paper are those of the authors and do not
necessarily reflect the official views of the Department of the Army.
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intake, performance, and mood state of female Army officers in a basic training population.
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Institute of Environmental Medicine.
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combat soldier. Minimal calorie intake during combat patrols in a hot humid environment
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Friedl KE, Marchitelli LJ, Sherman DE, Tulley R. 1991. Nutritional Assessment of Cadets at the
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Friedl KE, Moore LJ, Marchitelli LJ. 1992. Physiology of nutritional supplements. "Steroid replac-
ers": Let the athlete beware! Natl Strength Conditioning Assoc J 14:1419.
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function in U.S. Army Ranger students in a multistressor field environment. In: The Effect
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Ihle R, Loucks AB. 2004. Dose-response relationships between energy availability and bone turn-
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Army Basic Combat Training. Letter Report to BG Russ Zajtchuk, December 19, 1995.
IOM. 1997. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluo-
ride. Washington, DC: National Academy Press.
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IOM. 1998. Reducing Stress Fracture in Physically Active Military Women. Washington, DC: Na-
tional Academy Press.
IOM. 1999. Letter Report to the Office of the Surgeon General United States Army on Antioxidants
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Johnson HL. 1986. Practical military implications of fluid and nutritional imbalances for perfor-
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ington DC: National Academy Press. Pp. 5568.
Kepczyk T, Cremins JE, Long BD, Bachinski MB, Smith LR, McNally PR. 1999. A prospective,
multidisciplinary evaluation of premenopausal women with iron deficiency anemia. Am J
Gastroenterol 94:109115.
Kramer TR, Moore RJ, Shippee RL, Friedl KE, Martinez-Lopez L, Chan MM, Askew EW (1997).
Effects of food restriction in military training on T-lymphocyte responses. Int J Sportsmed
18:S84S90.
Kretsch MJ, Conforti PM, Sauberlich HE. 1986. Nutrient intake evaluation of male and female
cadets at the United States Military Academy, West Point, New York. Technical Report
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Lappe JM. 2003. Efficacy of calcium and Vitamin D supplementation for the prevention of stress
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October 2003. Omaha, NE: Creighton University.
Loucks AB, Thuma JR. 2003. Luteinizing hormone pulsatility is disrupted at a threshold of energy
availability in regularly menstruating women. J Clin Endocr Metab 88:297311.
Moore RJ, KE Friedl, RT Tulley, EW Askew. 1993. Maintenance of iron status in healthy men
during an extended period of stress and physical activity. Am J Clin Nutr 58:923927.
Sack DM, Holick M, Bondi KR. 1986. Calcium and Vitamin D metabolism in submariners--carbon
dioxide, sunlight, and absorption considerations. Technical Report NSMRL-1037. January
1986. ADA166292. Groton, CT: Naval Submarine Medical Research Laboratory.
Sandstead HH. 2001. Repletion of zinc and iron deficiencies improve cognition of premenopausal
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of Texas Medical Branch.
Sauberlich HE. 1984. Implications of nutritional status on human biochemistry, physiology and
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Shippee RL, Friedl KE, Tulley R, Christensen E, Arsenault J. 1993. Changes in plasma iron, copper,
and zinc concentrations of young males during 8 weeks of extreme physiological and psycho-
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Singh A, Papanicolaou DA, Lawrence LL, Howel EA, Chrousos GP, Deuster PA. 1999. Neuroendo-
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APPENDIX B 249
Derivation of the Military Dietary Reference Intakes
and the Mineral Content of Military Rations
Carol J. Baker-Fulco
U.S. Army Research Institute of Environmental Medicine,
Natick, Massachusetts
This paper presents the nutritional standards for military rations and the
mineral composition of military field rations. In addition, it summarizes the
findings of a few studies that have estimated mineral intakes of soldiers in the
field and in garrison. This paper focuses on operational rations, which are rations
intended for military operations, whether combat or field training. A ration is
one day's food supply for a group or an individual. The type of ration provided is
based upon the unit's mission, tactical scenario, location, and availability of food
service equipment and personnel. The operational rations examined in this paper
are the Meal, Ready-to-Eat (MRE); Meal, Cold Weather (MCW); one of the
Unitized Group Rations (UGR), the Heat-and-Serve (H&S); and the First Strike
Ration (FSR).
DESCRIPTIONS OF OPERATIONAL RATION
The MRE is the standard individual operational ration and consists of heat-
processed entrees and other food components that require no preparation. Each
meal contains an entrée/starch, crackers, a spread (cheese, peanut butter, jam or
jelly), a dessert or snack, beverages, and an accessory packet that contains cof-
fee, tea or cider and condiments. The MRE is issued at three menu bags per day
for a complete ration with an average of 3,900 kcal. For variety, there are twenty-
four different meal menus in the inventory.
The MCW is a higher calorie ration intended for arctic feeding. This ration
contains freeze-dried, cooked entrees and other low-moisture foods that will not
freeze. Meal bags for each of the twelve menus contain the entrée and a variety
of spreads and crackers, cookies, sports bars, nuts, candy, and powdered drink
mixes. The MCW is issued at three menu bags per day for a provision of roughly
4,500 kcal. The MCW menus are identical to those of the Food Packet, Long
Range Patrol (LRP) which is a restricted ration issued as one menu bag per day
during special operations when weight and volume of the ration are critical
factors.
Another restricted calorie ration considered in this report is the FSR. The
FSR is a new, individual combat ration developed for forward deployed ground
forces engaged in high-intensity operations. This ration is smaller and lighter
than a full day's ration of MREs and is comprised of foods that can be eaten "on
the move." The FSR as currently configured provides about 2,800 kcal.
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250 MINERAL REQUIREMENTS FOR MILITARY PERSONNEL
The UGR is a group of rations in which all the components for 50 complete
meals are packaged as one unit to streamline the ordering and delivery process.
There are seven breakfast and fourteen lunch and dinner menus for each type of
UGR; however, the lunch meal is often a MRE. The UGR-Heat & Serve (UGR-
H&S) is comprised of shelf-stable, ready-to-eat entrees, starches, vegetables,
and desserts packaged in short, rectangular plastic trays. It is the more common
(hot) group feeding ration for the field and is used when neither cooking nor
refrigeration are possible. Each meal, including the mandatory supplement of
milk, provides an average of 1,400 kcal. UGR menus may be enhanced with cold
breakfast cereal, bread, fresh fruits and salad. There are other UGR options that
comprise perishable and frozen ingredients (UGR-A) or are cook-prepared from
canned and dehydrated foods (UGR-B), but these will not be discussed in this
paper.
MILITARY DIETARY AND RATION STANDARDS
Nutritional standards for operational and restricted rations (NSOR), i.e., what
the rations must contain, are presented in the tri-service regulation, Nutritional
Standards and Education, which for the Army is Army Regulation (AR) 40-25
(U.S. Departments of the Army, Navy, and Air Force, 2001). The NSORs are
based on the Military Dietary Reference Intakes (MDRI) presented in the same
regulation (see Table B-1). The MDRIs are, in turn, based on the Dietary Refer-
ence Intakes (DRIs) (IOM, 1997, 1998, 2000a) or earlier Recommended Dietary
Allowances (RDA) (National Research Council, 1989). Since the current regula-
tion was prepared prior to the 2001 DRI publication (IOM, 2001)--which up-
dated the RDAs for iron, iodine and zinc, and established DRIs for chromium,
copper, manganese and molybdenum--current MDRIs are based on the 1989
RDAs for iron, iodine, and zinc, and there are no MDRIs for chromium, copper,
manganese and molybdenum. A soon to be drafted change to the regulation will
update the MDRIs and include additional MDRIs based on the more recent IOM
publications.
The MDRIs are applicable to healthy, 17 to 50 year old, physically active
military men and non-lactating, non-pregnant women. This age range covers the
majority of military personnel on active or reserve duty. The 17 to 50 year age
range incorporates three of the age classes for which DRIs have been set (14 to
18, 19 to 30, and 31 to 50 years) and three of the age classes used in the 10th
edition of the RDA (15 to 18, 19 to 24, and 25 to 50 years). For most nutrients,
the MDRI is the highest gender-specific reference value or RDA. However, the
MDRIs for calcium, phosphorus, and iron for males and calcium, phosphorus,
and magnesium for females, are not based on the highest reference intake or
allowance, which is for 14 to 18 year old individuals. Only 23 percent of the
military population is 17 to 18 years old; thus, inflating the MDRIs to meet the
needs of relatively so few individuals is not warranted. The regulation advises
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APPENDIX B 451
U.S. Departments of Army, Navy, and Air Force. 2001. Nutrition Standards and Education. AR 40-
25/BUMEDINST 10110.6/AFI 44-141. Washington, DC: U.S. Department of Defense
Headquarters.
Van Beaumont W, Strand JC, Petrofsky JS, Hipskind SG, Greenleaf JE. 1973. Changes in total
plasma content of electrolytes and proteins with maximal exercise. J Appl Physiol 34:102106.
Van Loan MD, Sutherland B, Lowe NM, Turnlund JR, King JC. 1999. The effects of zinc depletion
on peak force and total work of knee and shoulder extensor and flexor muscles. Int J Sport Nutr
9(2):125135.
Van Rij AM, Hall MT, Dohm GL, Bray JT, Pories WJ. 1986. Changes in zinc metabolism following
exercise in human subjects. Biol Trace Elem Res 10:99105.
Weight LM, Myburgh KH, Noakes TD. 1988a. Vitamin and mineral supplementation: Effect on the
running performance of trained athletes. Am J Clin Nutr 47:192195.
Weight LM, Noakes TD, Labadarios D, Graves J, Jacobs P, Berman PA. 1988b. Vitamin and mineral
status of trained athletes including the effects OF SUPPLEMENTation. Am J Clin Nutr 47:186191.
The Effects of Iron Deficiency on Physical Performance
Jere D. Haas
Cornell University, Ithaca, New York
INTRODUCTION
Iron deficiency is the most prevalent micronutrient deficiency in both the
industrialized and non-industrialized world. In the United States iron deficiency
affects approximately 34 percent of men and 1214 percent of women between
18 and 45 years, the age of the majority of military personnel in the U.S. (Looker
et al., 1997). While the most common consequence of iron deficiency is anemia,
or blood hemoglobin concentration below a specified level, the prevalence of
anemia underestimates the amount of iron deficiency in the population. WHO
(2001) estimates that the prevalence of iron deficiency is more than twice the
prevalence of anemia in any given population. Also, while iron deficiency ac-
counts for the majority of anemia in the U.S. population, there are numerous
additional causes of anemia, including other micronutrient deficiencies.
Numerous studies of the effect of iron deficiency on physical performance
have been conducted over the past 35 years with conclusive evidence for a
causal relationship (Haas and Brownlie, 2001). Most of the evidence from these
studies indicates that low hemoglobin concentration and consequent reduced
oxygen transport to working muscles is the primary mechanism for reduced
performance due to iron deficiency. However, evidence from animal studies and
more recently in human studies of non-anemic human subjects suggest that iron
deficiency may affect physical performance through other mechanisms. This
review addresses the evidence for the effects of iron depletion in non-anemic
individuals.
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452 MINERAL REQUIREMENTS FOR MILITARY PERSONNEL
ASSESSING MODERATE IRON DEFICIENCY
There are a number of indicators of iron nutritional status that when used
together can reveal a fairly comprehensive picture of the various body iron pools
that are significant for understanding the functional consequences of iron defi-
ciency. Figure B-31 shows the progress of iron status from normal to deficient
states and the course taken by the major indicators of iron status in common use.
The body iron stores reflect the functional iron status of an individual. With
increased iron loss or decreased iron intake to compensate for losses, the body
iron stores decline to a point indicated as "deficient." The best single indicator of
the depletion of iron stores is serum ferritin. Hemoglobin concentration does not
start to fall until after iron stores are depleted, and anemia is defined as a hemo-
globin level that is achieved during the decline in hemopoiesis. There is a stage
of body iron depletion when the iron stores are completely depleted but hemo-
globin has not yet reached a level that indicates anemia; this is the iron deficient,
non-anemic state (IDNA). Another indicator of iron status that is not represented
in Figure B-31 is the blood plasma concentration of the soluble transferrin recep-
tor (sTfR). It follows a course similar to that for free erythrocyte protoporphyrin
(FEP), and increasing levels indicate a increased demand for iron at the muscle
Hemoglobin FEP
Ferritin
TS
Fe stores IDNA
anemia
IDNA=Iron Deficient Non-Anemic
FIGURE B-31 Relationship between various indicators of iron status and the body's
level of iron stores.
SOURCE: Modified from Guthrie and Picciano (1995).
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APPENDIX B 453
tissue level which is not being met by circulating iron in the iron depleted indi-
vidual. This indicator appears to identify non-anemic individuals who will ben-
efit from iron supplementation as it affects physical performance (Brownlie et
al., 2004). Cook and colleagues (Cook et al., 2003) have developed an algorithm
to estimate total body iron from the log of the ratio of soluble transferrin receptor
and serum ferritin.
EVIDENCE FOR THE EFFECT OF IRON DEFICIENCY ON
PHYSICAL PERFORMANCE IN ANEMIC SUBJECTS
Most of the research on iron deficiency effects on physical performance has
focused on anemic subjects. This literature has been reviewed extensively by
Haas and Brownlie (2001) who conclude that there is considerable evidence to
support a direct causal relationship. One of the more recent studies that used an
experimental design that included randomization of subjects to consume either
an iron supplement or a placebo was conducted by Li and colleagues (Li, 1993;
Li et al., 1995), who studied the effects of iron deficiency on work capacity in
female Chinese factory workers. They assessed changes in physical performance
with the VO2max test, an assessment of aerobic power, after 12 weeks of con-
suming either an iron supplement or a placebo. The results are summarized in
Figure B-32. Li (1993) reported a 5 percent improvement in VO2max in the iron
supplemented group which corresponded to a 13g/L increase in hemoglobin con-
centration. There was a range of hemoglobin values in this sample and the great-
2
* * different from
1.95
placebo, p < .05
1.9
/min)
Before After
(L
1.85
max
2 1.8
VO
1.75
1.7
114 127 Hb (g/L) 115 113
Iron Supplemented Placebo Control
FIGURE B-32 VO2max in Chinese female cotton mill workers before and after 12
weeks of iron supplementation.
SOURCE: Li (1993, unpublished thesis).
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454 MINERAL REQUIREMENTS FOR MILITARY PERSONNEL
est effects of iron supplementation on VO2max were seen in the anemic women.
The authors also reported an increase in productivity in the workplace after 12
weeks of iron supplementation (Li et al., 1995).
There have been a large number of studies of the effects of iron deficiency
on physical performance using experimental animals. One of the most interest-
ing was conducted by Davies et al. (1982) with post-weaning rats that developed
iron deficiency after consuming a low-iron diet and then repleted rapidly by iron
therapy. The results are summarized in Figure B-33. This study confirmed previ-
ous studies in animals and humans of an improvement in VO2max, which paral-
leled an increase in hemoglobin concentration following iron therapy. This study
is significant because it also followed changes in another measure of physical
performance, endurance capacity, and a measure of tissue oxidative capacity,
muscle pyruvate oxidase, throughout the 7-day period following iron repletion.
The course of change in endurance lagged behind that of VO2max and paralleled
the increase in pyruvate oxidase. These findings indicate that physical perfor-
mance may be only partially mediated by the effect of iron deficiency on oxygen
transport in the blood, and that tissue iron depletion may also limit performance.
FIGURE B-33 The relationship of iron repletion to hemoglobin response, maximal
aerobic capacity (VO2max), muscle pyruvate oxidase activity and endurance capacity in
rats made iron deficient post-weaning.
SOURCE: Davies et al. (1982). Used with permission.
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APPENDIX B 455
They also indicate that different types of physical performance tests need to be
considered when studying severe compared to moderate iron deficiency.
PHYSICAL PERFORMANCE IN IRON DEPLETED
NON-ANEMIC SUBJECTS
This section reviews evidence for the effects of iron deficiency on physical
performance, focused primarily on non-anemic individuals. Before the evidence
is described, a brief review is presented of the rationale for why these affects
should be observable and important.
Rationale
The animal experiments represented by Davies et al. (1982) provide partial
rationale for exploring relationships between iron depletion and performance in
non-anemic human subjects. Further justification exists when one considers that
iron plays an import role in muscle metabolism beyond the transport of oxygen
by hemoglobin to the tissue sites for energy conversion to muscular work. Figure
B-34 presents a list of iron-containing compounds that are affected by body iron
depletion. Approximately 5 percent of the body iron is found in iron-containing
enzymes and 10 percent is found in myoglobin. Many of these compounds are
involved in transformation of chemical to mechanical energy. A second rationale
FIGURE B-34 Iron containing compounds that are affected by iron deficiency.
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456 MINERAL REQUIREMENTS FOR MILITARY PERSONNEL
Tissue oxidative
Diet capacity Endurance
capacity
Depletion Functional Maximal
of iron iron Anemia Oxygen
power output
stores deficiency Transport
(VO2max)
Blood
loss Energetic
Tissue oxidative efficiency
capacity
FIGURE B-35 Conceptual model of iron deficiency effects on physical performance.
is the relatively large number of individuals in a population that may be affected
by iron deficiency. This is a number that exceeds the prevalence of anemia in the
population (WHO, 2001). While the effects of iron depletion without anemia
may be less severe than the effects of iron deficiency, there is growing evidence
that the impact on physical performance is not trivial.
The proposed mechanisms for the action of iron deficiency on physical
performance are summarized in Figure B-35. Body iron stores become depleted
due to an imbalance of iron loss and dietary gain. When levels of body iron
become too low there is the beginning of a functional iron deficiency which
affects compounds associated with muscle metabolism but probably does not
affect hemoglobin synthesis and oxygen transport in the blood. Under conditions
of more severe depletion, hemoglobin synthesis is compromised along with skel-
etal muscle compounds resulting iron deficiency anemia (IDA). Under IDA a
broad range of physical performance measures are affected. The anemia results
in reduced oxygen transport that limits aerobic power, endurance, and muscular
energetic efficiency. The reduced levels and activity of iron-dependant, muscu-
lar tissue compounds seen in non-anemic, iron deficiency (IDNA) contribute to
reduced endurance and energetic efficiency, but do not limit aerobic power,
since blood oxygen transport is not compromised.
Evidence for Effects of Iron Depletion
in Non-Anemic Women
While the functional effects of iron deficiency have been well documented
in those individuals who are anemic, the effects of IDNA have only recently
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APPENDIX B 457
been examined in some detail (Haas and Brownlie, 2001). Three recent iron
supplementation trials with iron deficient non-anemic women provided evidence
that supports the general conceptual model presented in Figure B-35 (Brutsaert
et al., 2003; Hinton et al., 2000; Zhu and Haas, 1998). All of the studies used a
similar research design. Female subjects between 18 and 45 years were identi-
fied through population screening to be non-anemic (hemoglobin > 120 g/L), but
iron depleted (serum ferritin < 20 µg/L). Subjects were randomly assigned to
consume either supplemental iron (100 to 135 mg FeSO4/day) or a placebo daily
for 6 or 8 weeks, following a double blind protocol. A battery of measures of
iron status and various measures of physical performance were assessed at base-
line and at the end of the supplementation period. The results of these studies are
summarized as follows.
Metabolic Response to Exercise
Zhu and Haas (1998) studied thirty-seven non-anemic, iron-deficient (fer-
ritin < 16 µg/L) university women who consumed 135 mg/day of FeSO4 (50 mg
Fe/day) or a placebo for 8 weeks. Physical performance was assessed by VO2max
and time to complete a simulated 15-km time trial with a cycle ergometer, an
indicator of endurance. Serum ferritin values increased in the supplemented group
but hemoglobin did not change, and there was no group difference in VO2max at
the end of the trial. While the iron supplemented group did not complete the time
trial in less time than the placebo group, they completed the task at a lower
percentage of their VO2max (82 versus 88 percent) and with 5.1 percent less
energy expended than the placebo group. While one can conclude that iron defi-
cient women are less efficient at doing heavy work, it is not known whether
these effects of iron deficiency on performance can be observed under less rigor-
ous levels of exertion. The next study addresses this question.
Energetic Efficiency in Mexican Women
The studies described here (Brutsaert et al., 2003; Haas et al., 2002; Seymour,
2002) investigated the effects of iron supplementation for women on outcomes
of physical performance while cycling at different intensities. Forty-three non-
anemic, iron deficient (ferritin < 20 mg/L), female Mexican office workers and
students consumed 18 mg/day of elemental iron as FeSO4 or a placebo for
6 weeks (Haas et al., 2002). Serum ferritin increased while hemoglobin did not
change in the iron supplemented group when compare to the placebo group, and
estimated VO2max did not differ between the groups after supplementation.
Energy cost of performing 30 and 60 watts of work on a cycle ergometer was
assessed at baseline and after 6 weeks. At 60 watts the iron supplemented women
showed a 5.2 percent lower energy cost to perform the work after 6 weeks of
supplementation (Seymour, 2002). As shown in Figure B-36 this resulted in a
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458 MINERAL REQUIREMENTS FOR MILITARY PERSONNEL
31
Placebo p < .05
(%) 30.5 iron
30
29.5
Efficiency 29
28.5
Work
28
Baseline Final
kcal of external work performed at 60W
WE =
(kcal expended at 60W) - (kcal expended at 0W)
FIGURE B-36 Work efficiency (WE) at 60 watts in Mexican women before and after 6
weeks of iron supplementation.
SOURCE: Seymour (2002, unpublished thesis).
significantly higher net work efficiency which was related to increased iron in-
take and decreases in tissue iron status, based on the soluble transferrin receptor
concentration (sTfR). In a sub-sample of 20 women from this study, an addi-
tional test of a maximal voluntary static contraction (MVC) on a dynamic knee
extension exercise was administered to assess local muscle fatigue (Brutsaert et
al., 2003). The iron supplemented women performed the task with significantly
less muscle fatigue than the placebo group after 6 weeks of supplementation.
Adaptation to Physical Training
Several papers have reported on a study of the effects of iron status and
supplementation on improvements on performance outcomes due to adaptation
to physical training (Brownlie et al., 2002, 2004; Hinton et al., 2000). In this
study, 42 non-anemic, iron-deficient university women were randomly assigned
to consume either 100mg/day of FeSO4 or a placebo for 6 weeks. In addition, an
additional exercise intervention for all subjects consisted on 20 days of aerobic
training during the final 4 weeks of the supplementation trial. It was reported
that both groups benefited from the training by increasing their VO2max and
reducing their times on a simulated 15-km time trial with a cycle ergometer. As
shown in Figure B-37, the iron supplemented group improved its time in the
time trial by 3.4 minutes compared to a 1.6 minute improvement in the placebo
group (Hinton et al., 2000). The effect of iron treatment was mediated by changes
in serum ferritin but not by changes in hemoglobin. VO2max also improved
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APPENDIX B 459
33 Placebo Iron
32
31
Time trial
30 *
Minutes
29
28
27
Baseline Final
FIGURE B-37 Improvements in times for women to complete a 15 km bicycle time trial
after 4 weeks training while consuming supplemental iron or placebo. Iron group com-
pleted final trial 1.6 min faster than placebo group, after adjusting for differences in initial
times and work rate, p < 0.05.
SOURCE: Hinton et al. (2000).
more in the iron supplemented group and the greatest improvement in time-trial
time and work efficiency was seen in the iron supplemented women who were
most depleted in tissue iron (sTfR) at baseline (Brownlie et al., 2004). From this
study one can conclude that iron deficiency reduces the potential benefits of
aerobic training in both endurance and VO2max. It remains to be tested whether
the effects of iron deficiency on adaptation to aerobic training can be observed in
individuals who are already physically fit.
CONCLUSIONS
We can draw several conclusions from the research literature on physical
performance in iron deficiency anemia and from the recent experiments described
in this paper on iron depleted non-anemic women:
· Iron deficiency anemia (IDA) has clear functional consequences across a
wide range of tests of physical work capacity and productivity
· The mechanisms for IDA effects on performance include compromise to
both oxygen transport and tissue level oxidative capacity
· Iron deficiency without anemia (IDNA) is more prevalent than IDA in
the general population and carries measurable but less severe consequences to
human performance
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460 MINERAL REQUIREMENTS FOR MILITARY PERSONNEL
· The impact of IDNA is observed for physical endurance rather than aerobic
power, and on reducing the ability to adapt to aerobic training.
For relevance to physical performance of military personnel, one can conclude:
· The results on the effects of iron deficiency anemia on physical perfor-
mance should apply to all individuals
· The results on moderate iron deficiency without anemia in females should
be extrapolated to males who experience a similar degree of iron deficiency and
level of fitness
· Military personnel should be screened for anemia and body iron status
· Iron deficiency should be corrected in the long term by dietary adjust-
ments and by mineral and vitamin supplementation in the short term, as condi-
tions warrant.
Future research should consider assessing the effects of moderate iron defi-
ciency on energetic efficiency and adaptation to training in more physically fit
subjects and under conditions such as basic training. Additional research should
consider assessing dietary iron requirements for military personnel which are
based on potential iron loss from heavy exertion as well as additional demands to
support physical training and maintenance of high levels of endurance.
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Representative terms from entire chapter:
mineral requirements
