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IRON DEFICIENCY IS PREVALENT IN FEMALE ATHLETES AND CAN IMPEDE ENDURANCE PERFORMANCE (I.E., SLOWER TIME TRIAL), AND WITH ANEMIA CAN REDUCE ENDURANCE CAPACITY. LEVELS OF HEPCIDIN ARE ELEVATED AFTER EXERCISE SECOND TO INFLAMMATORY STIMULI (INTERLEUKIN-6) AND MAY CONTRIBUTE TO THE DEVELOPMENT OF IRON DEFICIENCY. HEPCIDIN ACTS TO INTERNALIZE AND DEGRADE FERROPORTIN (CELLULAR CHANNEL RESPONSIBLE FOR IRON EFFLUX). THIS RESULTS IN SEQUESTRATION OF IRON WITHIN MACROPHAGES, WHICH RECYCLE IRON FROM AGED AND DAMAGED ERYTHROCYTES. PROLONGED HIGH-INTENSITY TRAINING, ESPECIALLY A MODALITY THAT INCLUDES REPETITIVE FOOT STRIKES, CAN CAUSE HEMOLYSIS RESULTING IN UPREGULATION OF HEPCIDIN AND MAY CONTRIBUTE TO THE DEVELOPMENT OF IRON DEFICIENCY.
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Exercise-Associated Iron
Deficiency: A Review and
Recommendations for
Practice
Erica R. Goldstein, MS, RDN, LD/N, CSCS, CISSN
Mayo Clinic, Jacksonville, Florida
ABSTRACT
IRON DEFICIENCY IS PREVALENT
IN FEMALE ATHLETES AND CAN
IMPEDE ENDURANCE PERFOR-
MANCE (I.E., SLOWER TIME TRIAL),
AND WITH ANEMIA CAN REDUCE
ENDURANCE CAPACITY. LEVELS
OF HEPCIDIN ARE ELEVATED
AFTER EXERCISE SECOND TO
INFLAMMATORY STIMULI (INTER-
LEUKIN-6) AND MAY CONTRIBUTE
TO THE DEVELOPMENT OF IRON
DEFICIENCY. HEPCIDIN ACTS TO
INTERNALIZE AND DEGRADE FER-
ROPORTIN (CELLULAR CHANNEL
RESPONSIBLE FOR IRON EFFLUX).
THIS RESULTS IN SEQUESTRATION
OF IRON WITHIN MACROPHAGES,
WHICH RECYCLE IRON FROM
AGED AND DAMAGED ERYTHRO-
CYTES. PROLONGED HIGH-
INTENSITY TRAINING, ESPECIALLY
A MODALITY THAT INCLUDES
REPETITIVE FOOT STRIKES, CAN
CAUSE HEMOLYSIS RESULTING IN
UPREGULATION OF HEPCIDIN AND
MAY CONTRIBUTE TO THE DEVEL-
OPMENT OF IRON DEFICIENCY.
INTRODUCTION
Maintenance of adequate levels
of dietary iron consumption,
absorption, storage, and cellu-
lar uptake (e.g., incorporation into
hemoglobin and developing red blood
cells [RBCs]) is critical to endurance
performance. Oxygen transport is
most commonly associated with
endurance sports, but iron is also
required for mitochondria iron-
dependent oxidative enzymes that
support aerobic metabolism and gen-
eration of adenosine triphosphate
(ATP) through the Krebs cycle and
cytochrome activity necessary for the
transfer of electrons in the electron
transport chain (8,18,33). Iron defi-
ciency, inadequate body iron stores,
and iron deficiency anemia, depleted
iron stores with decreased hemoglobin
synthesis, can impede endurance per-
formance by dampening muscle tissue
oxidative capacity and cytochrome
activity (e.g., slower time trial perfor-
mance) and by diminishing V
̇
O
2
max or
oxygen transport (reduced endurance
capacity), respectively (8,18).
Inadequate total daily energy intake
and dietary iron consumption in addi-
tion to menstrual blood loss in
endurance-trained women increase
the risk of iron deficiency, with pro-
gression to anemia, if diet is not cor-
rected and/or supplementation is not
initiated (34). Nutrition education with
attention to type and combination of
animal and plant sources of iron in
addition to individualized needs (i.e.,
total daily required energy intake, rec-
ommended dietary allowance [RDA]
per population) is necessary for
reducing the risk of iron deficiency
and for helping to reverse the occur-
rence (34). Supplementation as war-
ranted (8,20,28,30) should be closely
supervised and is commonly provided
in the form of ferrous sulfate with 20–
105 g provided as elemental iron (i.e.,
amount that is absorbed) (8,30).
Finally, through a series of investiga-
tions (2,32,39,40,43), scientists have
begun to examine the hormone, hepci-
din, which is elevated 3 hours after exer-
cise secondary to inflammatory stimuli,
namely, the cytokine interleukin-6
(IL-6). Prolonged high-intensity train-
ing, especially modalities that include
repetitive foot strikes, can cause hemo-
lysis resulting in upregulation of hepci-
din and may contribute to the
development of iron deficiency. It has
been shown, however, that hepcidin
will be downregulated in athletes who
initiate training with already clinically
deficient iron stores (41).
It is important that allied health pro-
fessionals have an understanding of
both the dietary iron needs of the ath-
lete and how certain aspects of training
(type, intensity, and duration) can con-
tribute to physiological disturbances of
KEY WORDS:
iron; iron deficiency; anemia; hemolysis;
inflammation; hepcidin; red blood
cells
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24
Copyright © National Strength and Conditioning Association Unauthorized reproduction of this article is prohibited.
iron handling, disruption of homeosta-
sis, and how this can ultimately
impede performance, particularly in
trained endurance athletes.
REVIEW OF PHYSIOLOGY
Iron is obtained from both plant and
animal sources and is largely absorbed
into intestinal cells (enterocytes) at the
duodenum or first portion of the small
intestine (13). Ferric iron must undergo
a change in oxidative state to its diva-
lent form (ferrous, Fe
2+
) to enable
movement across the brush border
and absorption into the intestinal cell
through the divalent metal transporter
(DMT1). However, once absorbed,
iron can be used by the cell or stored
through the protein ferritin in entero-
cytes, hepatocytes, and macrophages
(13,47). Enterocytes have a high turn-
over, so iron stored in these cells will be
lost to excretion approximately every 2
days (13,16,48). Iron exits the cell as
ferric (Fe
3+
) iron, where it binds to
the protein transferrin, and is circulated
to various tissues to be used, chiefly by
developing RBCs (36).
Mitochondria support hemoglobin
synthesis in developing RBCs, which
are produced in bone marrow
(13,16,26,48,49). Within the mitochon-
dria, free iron is used to synthesize
heme (36,48,49). Therefore, heme con-
tains iron bound to it, which is then
used to form the protein hemoglobin.
Other locations of iron storage are
macrophages (reticuloendothelial cells)
in the liver and spleen (13,36,48). After
120 days, RBCs undergo various phys-
iological changes that essentially mark
aged erythrocytes for phagocytosis,
principally by macrophages of the
spleen (13). Macrophages are then able
to store iron from degraded hemoglo-
bin, which can ultimately be excreted
and recycled to supply demand by other
cells (14). In particular to athletes,
hemolysis, or the destruction of RBCs,
is often induced by chronic mechanical
trauma, such as high impact repetitive
foot striking, generally associated with
running. Hemoglobin escapes from the
ruptured membrane of a RBC, is
released into plasma, and is captured
by macrophages (16). The iron is then
either stored through ferritin or recycled
in a process similar to the aging
erythrocyte.
Hepcidin is a protein synthesized by
the liver that has been well described
as the master regulator of systemic
iron homeostasis (13,14,36). Hepcidin
acts as a hormone that controls iron
export from macrophages, liver, and
intestinal cells (13,14). Movement of
iron from the cell to the bloodstream
is blocked because of the action of hep-
cidin on ferroportin (13,14). Ferropor-
tin has a dual purpose as it serves as the
cell receptor for hepcidin and is also
a transmembrane transporter responsi-
ble for the efflux of iron from the cell to
plasma (13,14). Hepcidin stimulates
the internalization and degradation of
ferroportin, which traps iron within the
cell (13,14). It seems that hepcidin is
downregulated in response to elevated
erythrocyte production in the bone
marrow or increased use of serum
and tissue iron (13,14,35).
Hepcidin is upregulated in response to
inflammatory stimuli, namely, IL-6,
and promotes sequestration of iron
within the cell (31). One theory is that
bacteria uses nonbound iron to thrive;
therefore, the action of hepcidin is
a protective mechanism from the pro-
liferation of pathogens (14,16). Inflam-
mation and elevated hepcidin activity
will stimulate the endocytosis and deg-
radation of the ferroportin channels of
the major iron storage and exporting
sites (enterocytes, hepatocytes, and
macrophages) (13). This will cause
a buildup of stored iron in ferritin
within the cytoplasm. As the demand
for iron by developing erythrocytes
continues, a subsequent decrease in
available circulating iron ensues, lead-
ing to iron deficiency (13,14).
Iron deficiency represents inadequate
body iron stores by macrophages in
the liver, spleen, and bone marrow
and is clinically defined as a ferritin lab-
oratory value ,12 mg/L (1,8). How-
ever, there is some variance in the
literature as ferritin is often reported as
some value .12 mg/L but ,20 mg/L,
depending on the investigation (8). A
continual decline of iron stores results
in impaired iron transport with insuffi-
cient supply for developing RBCs (1).
Iron deficiency anemia is the end result
and represents depleted iron stores
with decreased hemoglobin synthesis,
defined as hemoglobin ,12 g/
dL (1,8,27).
Serum ferritin (SF) alone does not accu-
rately reflect iron status because SF will
increaseconsiderablyinresponseto
inflammation (21). In fact, results of
one study (34) did not find a significant
relationship between ferritin level and
duration of training (hours per week).
Therefore, more sensitive laboratory
testingbeyondSFshouldbeusedto
assess for iron status, including hemoglo-
bin and soluble transferrin receptor con-
centration. The relationship between
these indices exists such that SF repre-
sents iron storage, and hemoglobin and
soluble transferrin receptor reflect iron
deficiency anemia or inadequate iron
supply for hemoglobin synthesis as
a result of insufficient stores and absorp-
tion (4,27).
Transferrin receptors are expressed on
the surface of all cells, especially devel-
oping RBCs. As previously mentioned
in this article, iron circulates bound to
transferrin, and when iron is trans-
ported to a cell, it is internalized and
released into the cytoplasm. The solu-
ble transferrin receptor is the end
product of this process (4), which is
then left to circulate in plasma. The
soluble transferrin receptor is not
affected by inflammation and therefore
will be elevated in response to the
increased demand by iron-deficient
cells, specifically erythropoiesis (4,27).
In summary, there are fundamental
physiological functions of iron specific
to exercise that include generation of
hemoglobin, important for oxygen
transport to tissues throughout the
body; myoglobin, an intermediate stor-
age site for oxygen in muscle tissue;
cytochromes, a series of complexes
necessary for the transfer of electrons
in the electron transport chain, which
contributes to the generation of ATP;
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and mitochondria iron-dependent oxi-
dative enzymes that support aerobic
metabolism and generation of ATP
through the Krebs cycle
(8,13,16,18,26,33,36,48,49).
Iron deficiency can present as lethargy,
weakness, vulnerability to infection,
dyspnea, and palpitations (16), and
both iron deficiency and iron defi-
ciency anemia can impede an athlete’s
performance. Iron deficiency can neg-
atively affect endurance performance
by dampening muscle tissue oxidative
capacity and cytochrome activity,
which can manifest as prolonged time
to complete a competitive event, such
as a slower time trial (8,18). If iron defi-
ciency is not corrected with an
improvement in energy intake and iron
supplementation, progression to ane-
mia can develop. With iron deficiency
anemia, an athlete’s endurance capac-
ity is diminished as V
̇
O
2
max or oxygen
transport is impaired, because of
reduced hemoglobin synthesis.
Decreased energetic efficiency and
increased energy expenditure are also
part of this paradigm contributing to
decrements in an endurance athlete’s
performance within the range of iron
deficiency and anemia (8,18).
INFLAMMATION, HEPCIDIN, AND
EXERCISE-ASSOCIATED IRON
DEFICIENCY
Inflammation results in what is known
as an acute-phase response that pro-
motes the production and circulation
of acute-phase proteins, usually as
a response to injury or infection (38).
Interleukin-6 is a cytokine that is both
produced and released into circulation
by contracting skeletal muscle during
exercise (23,37). Duration and intensity
of exercise seem to determine the mag-
nitude of the IL-6 response, and running
in particular seems to result in a signifi-
cant production of IL-6 (10,37). Varying
factors associated with endurance exer-
cise, particularly duration and muscle
glycogen content, can affect the IL-6
response. Exercise duration has been
posited as having the greatest effect on
the magnitude of the IL-6 response (10).
It has been suggested that IL-6 func-
tions to regulate glucose metabolism
and enhance lipolysis during exercise
(11,37). Moreover, it has been pro-
posed that IL-6 acts as an energy sen-
sor during exercise and is markedly
increased in response to low intramus-
cular glycogen content, especially dur-
ing periods of extended duration
(22,23,37). Results of one study, how-
ever, indicated that the magnitude of
the IL-6 mRNA expression in response
to 3 hours of exercise was significantly
reduced with higher absolute work
intensity, in response to 10 weeks of
knee extensor endurance training
(11). This study represents a training
adaptation to endurance exercise in
that the magnitude of the IL-6
response will decrease in response to
consistent exercise (11).
Interleukin-6 has been shown to be the
main mediator of hepcidin production
(31,38,43). In fact, the main finding of
an animal model investigation showed
hepcidin levels peaked at 2 hours after
exhaustive exercise in both the group
treated with a pharmacological agent
used to blunt plasma IL-6 levels during
exercise and the control group (3).
However, hepcidin mRNA levels were
significantly reduced in the treatment
group, which displayed 50% lower
plasma IL-6 levels (3). Therefore, re-
sults of this study provide evidence that
the level of hepcidin rises in response
to plasma IL-6, and as such, the hep-
cidin expression was inhibited as
a result of blunted IL-6 (3).
The relationship of carbohydrate
intake during prolonged endurance
exercise and subsequent IL-6 and hep-
cidin response has been examined. Re-
sults from a 2011 study (42) found that
even though carbohydrate ingestion
during endurance exercise (120 minutes
followed by 5-km time trial) resulted in
a significant decrease in the IL-6
response, as compared with placebo,
hepcidin was still significantly
increased immediately after exercise
(blood samples were taken before,
after, and 24 hours later), with no sig-
nificant difference between trials. Fur-
thermore, plasma iron concentrations
were significantly decreased from base-
line at 24 hours after exercise, and there
was no significant difference between
groups.
Newlin et al. (32) examined the acute
postexercise response of both IL-6
and hepcidin in women. Female run-
ners participated in both 60-min and
120-minute treadmill runs at 65% of
V
̇
O
2
max. Interleukin-6 was significantly
increased immediately after exercise as
compared with before exercise, but not
for any other time points (3, 6, 9, 24
hours), and with no significant effect
between trials. Hepcidin levels peaked
at 3 hours, and concentrations were
significantly higher at 120 minutes than
at 60 minutes. Serum iron was signifi-
cantly decreased at 9 hours after exer-
cise in both the 60- and 120-min
trials (32).
Individual data from the 12 participants
included in the Newlin et al. (32) inves-
tigation indicated a range in the magni-
tude of the hepcidin response, varying
from 7 subjects with a small-to-
moderate concentration (,2.4 nmol/
L) to 5 with a large concentration (.5
nmol/L). Furthermore, participants
with a large hepcidin response were
noted to have a higher mean serum iron
concentration, as compared with the
subjects with both a lower mean serum
and hepcidin response (32).
This observation has been reported
elsewhere in the literature. More
recently, Auersperger et al. (2) exam-
ined the effects of 8 weeks of endur-
ance training in female runners.
Fourteen females were recruited and
divided into 2 groups: 7 defined as iron
deficient (ferritin levels #20 mg/L) and
7 as iron normal (ferritin levels .20
mg/L). The protocol consisted of two
3-week progressive overload periods
followed by 1-week tapers. Participants
completed either a competitive 6-mile
or 13-mile distance run in a marathon
after the second taper. Blood samples
were drawn at baseline, at the comple-
tion of training and after a 10-day
recovery phase. Of significance, the
number of females with iron deficiency
increased to 10 of 14, such that 3 of the
Exercise-Associated Iron Deficiency
VOLUME 38 | NUMBER 2 | APRIL 2016
26
Copyright © National Strength and Conditioning Association Unauthorized reproduction of this article is prohibited.
participants originally identified as hav-
ing normal iron stores advanced to iron
deficiency after training. In contrast to
previous studies discussed in this article
(39,40,43), IL-6 plasma values were re-
ported as undetectable at each time
point, with no change in hepcidin
except for a significant decrease at
recovery. For both groups, the percent-
age of hypochromic RBCs was signif-
icantly increased at training and
recovery, whereas the mean hemoglo-
bin content of RBCs and reticulocytes
(immature RBCs) was significantly
decreased. Even though there was
a slight increase in total iron binding
capacity (TIBC) from the training to
recovery time point, at recovery, TIBC
still remained significantly decreased
from baseline. In addition, the concen-
tration of soluble transferrin receptor
significantly increased during training
and recovery, representative of iron
deficiency. These results are interest-
ing, and the authors of this study (2)
posit that the hormone hepcidin is also
regulated by iron demand such that in
periods of low iron stores, hepcidin will
not be influenced in the same manner
as a state of normal iron capacity (2). In
conclusion, it would seem counterpro-
ductive that hepcidin would act to
restrict iron efflux in the presence of
low iron stores.
Peeling et al. (41) have expanded on
this theory of a suppressed hepcidin
response in the presence of decreased
iron stores. Data were pooled from 5
different investigations and were used
to stratify athletes into 4 different
groups based on levels of SF. Group-
ing was as follows: iron depleted, ,30
mg/L; suboptimal, 30–50 mg/L;
healthy, 100 mg/L; and high, .100
mg/L. Of particular interest, 13 of 16
trained females (runners, triathletes)
included in this study were identified
as either iron depleted or having sub-
optimal iron stores.
As expected, IL-6 was significantly
increased after exercise as compared
with baseline for all groups (41). Novel
findings of this study (41) demon-
strated a significantly greater hepcidin
response 3 hours after exercise for high
SF (.100 mg/L) participants than for
all other groups. Moreover, hepcidin
was significantly increased 3 hours
after exercise as compared with base-
line for all groups, except the iron-
depleted (SF ,30 mg/L) participants.
These results therefore indicate
a sequential increase in hepcidin 3
hours after exercise based on iron sta-
tus. Of greatest concern is the fact that
hepcidin was still significantly
increased after exercise in the SF sub-
optimal group (30–50 mg/L), which
makes these athletes at greatest risk
for advancing to iron deficiency.
Finally, the suboptimal group consisted
of an n58, of which 5 were fe-
males (41).
Other training variables have been
explored in relation to IL-6 and hepci-
din production. For example, IL-6 was
significantly elevated immediately after
exercise, and hepcidin was significantly
increased 3 hours after exercise (for all
trials) in one study that examined the
effects of exercise intensity and modal-
ity (high-intensity interval versus
low-intensity continuous cycling and
running) on markers of inflammation
(43); Table 3. Of interest, serum iron
levels (related to hemolysis) were signif-
icantly elevated in all trials of this study
except low-intensity continuous cycling,
which lacks the force and impact of
running and associated mechanical
hemolysis (43). In addition, significantly
elevated IL-6 levels after high-intensity
cycling demonstrate that exercise which
requires high power output irrespective
of impact (repetitive foot strikes) will
stimulate an inflammatory response of
contracting skeletal muscle (43).
It is common that athletes train twice
per day and at varying intensities (e.g.,
conditioning, speed and agility, prac-
tice, etc.). In a study published by Peel-
ing et al. (39), participants completed
a continuous slow 10-km distance run
(70% peak V
̇
O
2
velocity) followed by
a subsequent bout of exercise 12 hours
later that consisted of 10 31-km inter-
val repeats (90% peak V
̇
O
2
velocity).
On a different day, participants com-
pleted 1 session of the 10 31-km inter-
val repeats (90% peak V
̇
O
2
velocity).
Results indicated that levels of IL-6
were significantly elevated after each
bout of exercise but 12 hours was suf-
ficient for this marker of inflammation
to return to baseline. Results of this
study (39) also demonstrated signifi-
cantly increased free hemoglobin and
hepcidin (3 hours post) after all exer-
cise trials. Similar to IL-6, hepcidin re-
turned to baseline values after a 12-
hour rest period. Taken together, these
results indicate elevations in hepcidin 3
hours after exercise coupled with train-
ing days that require multiple exercise
bouts do not elicit an exaggerated
effect but instead 12 hours is an accept-
able recovery period to allow for these
markers to return to baseline (39).
In a different investigation by Peeling
et al. (40), the question of training
intensity (continuous versus interval)
and its effects on levels of inflammation
and hepcidin were further investigated,
as was training surface (grass versus
road). Trained male athletes (n510)
participated in 3 separate trials: 2 con-
tinuous 10-km runs on grass versus
a bitumen road surface (75–80% peak
V
̇
O
2
velocity) and a 10 31-km interval
running session on a grass surface. The
interval session on grass was compared
with the continuous running trial on
grass. Results indicated significantly
increased free hemoglobin levels for
all 3 trials but no significant difference
between training surfaces. Levels of
IL-6 were significantly increased after
exercise for all 3 trials. However, IL-6
values were significantly greater for
interval than for continuous, indicating
a heightened level of inflammation for
training intensity. Finally, hepcidin was
significantly increased 3 hours after
training for all 3 trials, but there was
no significant effect between trials.
Therefore, although the severity of
inflammation was increased after a bout
of high-intensity training, the hepcidin
response despite an increase from
baseline was not equally exaggerated.
In conclusion, this study (40) indicates
that the training surface does not fur-
ther induce hemolysis, but inflamma-
tion and subsequent hepcidin response
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do occur with heel-strike activity
regardless.
In summary, high-intensity exercise,
particularly a mode that involves run-
ning or heel-strike activity, will stimu-
late an immediate postexercise release
of IL-6 and subsequent hepcidin
response. The hepcidin response has
been shown to be increased with lon-
ger duration endurance exercise (32),
which may have an implication for
women involved in triathlon training
and competition. Studies, however,
have also shown that the magnitude
of the inflammatory response may be
reduced as a result of training adapta-
tion. Therefore, the possibility exists
that because of a training adaptation,
the reduction in inflammatory stimuli
during exercise, namely, IL-6, may
result in a decreased hepcidin response.
However, this concept, and whether it
translates to a decreased prevalence of
iron deficiency, is a topic that warrants
further research and clarification. More-
over, it has been demonstrated that car-
bohydrate intake during 120 minutes of
endurance exercise was sufficient to
blunt the IL-6 response but not
hepcidin.
The occurrence of iron deficiency does
seem to be evident in women participat-
ing in endurance sport (29,34,45). It is
therefore prudent that athletes (females
in particular) should be monitored at all
time points of a competitive season
because maintenance of iron stores is
crucial to endurance performance as
any decrement in time to complete an
event can negatively affect an athlete’s
competitive advantage.
IRON LOSS AND FEMALE
ATHLETES
Female athletes of reproductive age are
at an increased risk of iron loss due to
menstruation, with total iron loss esti-
mated to be approximately 1.3–1.4
mg/d or 17.5 mg per cycle (16,25,48).
In fact, results of one study (n590
premenopausal women) indicated that
regardless of type of diet (lacto-ovo-
vegetarian versus poultry versus red
meat), menstrual blood loss had the
greatest influence on iron status (17).
Research indicates that women who
have used an oral contraceptive pill
are more likely to have sufficient iron
stores and associated iron markers (SF
and iron) because of decreased men-
strual blood loss, albeit the physiolog-
ical mechanisms have yet to be
elucidated (44). A comprehensive
review has been published on this
topic; for more details, please refer to
the study by Sim et al. (44).
In addition, there is a high risk for the
development of iron deficiency in fe-
males when insufficient energy intake
to replace iron loss, common to the
female athlete triad, is coupled with
high-intensity training that includes
repetitive foot striking, as discussed
previously (25,34). Therefore, men-
strual blood loss (especially heavy or
frequent) in combination with
decreased dietary iron intake likely
contributes to the scenario of increased
risk for the development of iron defi-
ciency in female athletes.
Research indicates an increased inci-
dence of iron depletion in women par-
ticipating in endurance sports. Results
examining iron status in male and
female recreational marathon runners
demonstrated iron depletion in 12 of
43 women (28%) of which 6 were ane-
mic (29). However, only 2 of 127 men
(1.6%) were iron deficient, with only
one male reported as anemic (29). In
a different study of iron deficiency in
121 recreationally active adults (72 fe-
males and 49 males), 36% of female
participants and 6% of male partici-
pants were identified as iron deficient
without anemia (45). Finally, of a sam-
ple of 165 female collegiate rowers,
30% (n544) were identified as either
iron depleted or clinically iron deficient
at the start of the season, which em-
phasizes the need for preseason screen-
ing to identify female athletes at risk of
iron deficiency and to prevent progres-
sion to iron deficiency anemia (9).
In a 2010 investigation of women
undergoing basic combat training,
female soldiers were provided either
a fortified iron bar (2 bars daily; 55.8
mg/d ferrous sulfate) or placebo
during a 9-week basic training course
(20). Results indicated that supplemen-
tation was beneficial for soldiers with
iron deficiency anemia but not for iron-
deficient or iron-normal female mili-
tary personnel (20). Specifically,
hemoglobin concentration signifi-
cantly increased from baseline for the
iron deficiency anemia group after
treatment. Moreover, soluble transfer-
rin receptor concentration (biomarker
of iron deficiency) was significantly
increased after training for the iron
deficiency anemia participants, who
received the placebo, but not for the
iron-supplemented participants within
the same group (20).
In a different study (28) that examined
the effects of basic combat training on
iron status in female soldiers, iron sup-
plementation in the form of 100-mg
capsules (ferrous sulfate) was provided
over the course of 8 weeks. Fourteen
iron-deficient ($2 of 3 indicators: SF
,12 ng/mL, transferrin saturation
,16%, RBC distribution width
.15%) participants were identified in
both the placebo and iron-
supplemented groups. At the conclu-
sion of the study (28), results indicated
the number of iron-deficient partici-
pants doubled in the placebo group
from 14 to 28 (100% increase), whereas
the number of iron-deficient persons in
the treatment group only climbed
from 14 to 19 (36% increase). Results
for the iron deficiency anemia group
(same classification as iron deficiency
plus hemoglobin concentrations ,12
g/dL) indicated a significant increase
in ferritin for the treatment group as
compared with baseline and placebo,
with a significant decrease in ferritin
for the placebo group as compared
with baseline. In addition, soluble
transferrin receptor concentration for
iron-deficient anemia participants was
significantly increased from baseline
for the placebo group (28).
Finally, results of a 2-mile run time test
demonstrated a significantly faster
mean time of 110 seconds for the
iron-deficient anemia participants in
the treatment group, but not for the
placebo group (28). In conclusion, iron
Exercise-Associated Iron Deficiency
VOLUME 38 | NUMBER 2 | APRIL 2016
28
Copyright © National Strength and Conditioning Association Unauthorized reproduction of this article is prohibited.
supplementation was effective for
attenuating the decline in iron status
in female soldiers over an 8-week
period during basic combat training
that involves road marching, running,
and sprinting, and also periods of pro-
longed standing in formation, and
obstacle course completion, among
other activities (28).
RECOMMENDATIONS FOR
PRACTICE
DIETARY SOURCES OF IRON
Athletes participating in high-intensity
sports that involve repetitive foot
strikes are particularly susceptible to
the development of iron deficiency.
Female athletes in particular may pose
a higher risk because of varying sce-
narios of menstrual blood loss and
inadequate energy intake. Monitoring
these athletes requires the work of
a multidisciplinary team including
sports medicine physicians, athletic
trainers, strength and conditioning
coaches, and sports dietitians.
As discussed in this article (39–41),
exercise-induced inflammation will
likely stimulate a subsequent elevation
in hepcidin for at least a 3-hour period.
Therefore, consuming iron-rich foods
during this period may not contribute
to recovery of iron stores. Athletes
should be educated to understand the
type and combination of foods to sup-
port recovery and maintenance of iron
status.
For example, nonheme iron obtained
from plant sources is less bioavailable
because it presents in the ferric form.
A duodenal redox enzyme at the surface
of the enterocyte fronting the intestinal
lumen enables the absorption of non-
heme iron. Vitamin C plays an essential
role in this process of reducing ferric
iron to ferrous (24,36,48). Many com-
pounds in food such as phytates (black
beans, lentils, chickpeas), polyphenols
(coffee, tea), and oxalates (spinach, swiss
chard, chocolate) bind nonheme iron
and can prevent its absorption (16,46).
Conversely, heme iron, in the form of
hemoglobin and myoglobin, is obtained
from animal sources (meat, fish, poul-
try) and is exceedingly bioavailable,
although how it enters the cell is less
understood (48). It seems that heme
iron enters the cell intact and is subse-
quently catabolized (36). Regardless,
absorption of nonheme iron (plant
based) is improved by the presence of
heme iron. Therefore, it is advisable to
consume meat, fish, or poultry with
plant sources of iron to enhance absorp-
tion of nonheme containing foods.
Athletes should be cautioned against
drinking tea with iron-rich meals as
Table 1
Dietary sources of iron
Milligrams of iron per 3 ounces Milligrams per 1/2 cup Milligrams per 1 cup
Heme
Beef, ground, 97% lean meat 2.46
Chicken, breast 0.38
Eggs, scrambled 1.11
Fish, salmon, Atlantic, wild 0.88
Tuna fish, white, canned in water,
drained solids
0.82 — —
Nonheme
Almonds, dry roasted 3.17 2.57 5.15
Lentils 3.30 6.59
Beans, black 1.81 3.61
Cashews, dry roasted 5.10 4.11 8.22
Raisins 1.36 2.73
Seeds, sunflower 3.23 2.43 4.86
Seeds, pumpkin and squash seeds,
whole, roasted
2.82 1.06 2.12
Spinach, raw 0.41 0.81
Spinach, cooked 3.21 6.43
Data obtained from the USDA National Nutrient Database for Standard Reference Release 27.
Strength and Conditioning Journal | www.nsca-scj.com 29
Copyright © National Strength and Conditioning Association Unauthorized reproduction of this article is prohibited.
the former can interfere with the
absorption of the latter. Moreover,
although green leafy vegetables such
as chard and spinach are a rich source
of iron, they have a high tannin and
phytate content, respectively (46),
which can bind with iron and inhibit
absorption. Phytate is heat stable and
cooking is not effective in decreasing
the phytate content of spinach or the
tannin content of chard, which greatly
reduces the bioavailability (46). That
being said consuming a plant-based
dietary source of iron in combination
with other foods rich in vitamin C and/
or animal protein will help reduce
inhibitory effects and act to enhance
overall absorption (1).
Training tables in a university or simi-
lar athletic setting should provide
foods that readily combine iron-rich
plant sources with meat, fish, or poul-
try. Chili is an excellent example of this
because it combines beans with lean
red meat or lentil soup with chicken;
a breakfast option is an iron-fortified
cereal that can be combined with rai-
sins or strawberries. Moreover,
a review article found iron-fortified
foods (e.g., ferrous sulfate or fumarate)
to be an effective strategy for improv-
ing iron status (15). Table 1 provides
a list of both heme and nonheme die-
tary sources, and Table 2 provides a list
of foods rich in vitamin C.
Vegetarian athletes can meet daily iron
needs through a plant-based diet.
However, the daily RDA is higher.
Vegetarians require 1.8 times the daily
iron requirement or 33 mg because of
the reduced bioavailability of nonheme
dietary sources, which is 10% as com-
pared with 18% for consumption of
combined heme (animal) and non-
heme (plants) foods (19). The RDA
for adults aged 19–50 years who con-
sume a mixed diet (heme and non-
heme) is 8 mg per day for males and
18 mg per day for females (19).
Finally, female athletes will benefit
from nutrition education related to
both total energy intake and dietary
sources of iron. This is especially true
for vegetarian athletes because their
daily dietary iron needs are higher
because of reduced absorption, so
insufficient total daily calorie intake
can put these athletes at particular risk.
Female athletes who have already pro-
gressed to iron deficiency or iron defi-
ciency anemia may benefit from
supplementation as warranted, in addi-
tion to nutrition education.
IRON SUPPLEMENTATION
There is no distinct physiological
mechanism for iron excretion, espe-
cially in the case of overload. There-
fore, the body must regulate iron
homeostasis through absorption, and
the hormone hepcidin acts as the mas-
ter regulator. The major concern for
iron supplementation in any popula-
tion is iron overload, which is toxic
and can cause cellular damage because
of iron’s ability to generate reactive
oxygen species. Moreover, individuals
with a hereditary predisposition for
developing hemochromatosis are at
an increased risk, because this disorder
is associated with a high efficiency for
dietary iron absorption and storage in
the heart, liver, and pancreas, which
can lead to organ damage (6,16,50).
Conversely, unwarranted iron supple-
mentation can mask iron deficiency or
iron deficiency anemia, which in a clin-
ical setting can serve as a valuable indi-
cator for a more significant underlying
condition, such as celiac disease or
occult gastrointestinal bleeding, among
others (5,12).
Physically active men, as compared
with women, seem to have a decreased
incidence of iron deficiency and seem
to be more at risk of iron overload
because of the absence of menstrual
blood loss (8,29,45). In a 2010 study
of recreational runners participating
in a Switzerland-based marathon,
15% (19 of 127) of men were identified
to have iron overload, as compared
with 4.7% (2 of 43) of women (29).
These results (29) should be interpreted
with caution because runners in this
study did not provide data through
a questionnaire related to supplement
use or iron intake. However, excessively
high SF levels (.300 ng/mL) have
Table 2
Dietary sources of vitamin C
Serving size Milligrams
Fruit
Cantaloupe 1 cup, cubes 0.34
Mango 1 cup, pieces 0.26
Oranges, navels 1 medium 0.18
Raisins 1/2 cup 1.7
Tangerines 1 medium 0.13
Strawberries 1 cup, whole 0.59
Vegetables
Broccoli 1 cup, chopped 0.66
Brussels sprouts 1 cup 1.87
Peppers, sweet, green 1 cup, sliced 0.31
Peppers, sweet, red 1 cup, sliced 0.40
Tomatoes, red, ripe 1 cup, cherry tomatoes 0.40
Tomatoes, canned sauce 1 cup 2.35
Data obtained from the USDA National Nutrient Database for Standard Reference Release 27.
Exercise-Associated Iron Deficiency
VOLUME 38 | NUMBER 2 | APRIL 2016
30
Copyright © National Strength and Conditioning Association Unauthorized reproduction of this article is prohibited.
been documented in elite male cyclists,
in addition to reported use of iron sup-
plementation through repeated intrave-
nous administration (51). It should
therefore be underscored that uncon-
trolled or unnecessary iron supplemen-
tation in the absence of clinical
biomarkers of iron deficiency with or
without anemia does not enhance per-
formance and so the risk does not out-
weigh the benefit (7).
Supplementation guidelines are still
being developed within the literature
in terms of screening, when to initiate
supplementation, and adequate dose
and form. Ferrous sulfate (FeSO
4
)is
a common oral iron supplement and
because it is prepared in the ferrous form,
absorption is enhanced, as compared
with ferric (8). One hundred milligrams
of ferrous sulfate provides 20 mg or 20%
Table 3
Comparison of exercise protocols, IL-6, hepcidin, and iron response
Study Subjects Baseline iron status Protocol Findings
Auersperger
et al. (2)
14, F,
moderately
physically
active
n57, ferritin
.20 mg/L; n57,
ferritin ,20 mg/L
3-wk progressive overload periods
followed by 1-wk tapers;
completed either competitive
6- or 13-mile distance run in
a marathon after second taper;
labs assessed at baseline,
completion of training, and after
10-d recovery phase
IL-6: undetectable at all time
points; HEP: SIG Yat recovery;
[in females with ID (10 /14)
after training
Sim et al. (43) 10, M, well-
trained
triathletes
n510, ferritin,
67.1 610.8 mg/L
High-intensity (85% velocity and
power output V
̇
O
2
peak) INT versus
low-intensity (85% velocity and
power output V
̇
O
2
peak) CONT
cycling and running
IL-6: SIG [immediately after
exercise, all trials; HEP: SIG [
3 h after exercise, all trials; sFe:
SIG [all trials except low-
intensity cycling
Peeling
et al. (39)
10, M, highly
trained
triathletes,
endurance
runners
n510, ferritin, 82.8
mg/L (average);
range, 37.3–173.1
mg/L
CONT slow 10-km distance run (70%
peak V
̇
O
2
velocity) /10 31-km
INT repeats (90% peak V
̇
O
2
velocity) 12 h later; different day:
1 session of 10 31-km INT repeats
(90% peak V
̇
O
2
velocity)
IL-6: SIG [immediately after
exercise 3each bout of
exercise, Yto baseline 12 h
later; HEP: SIG [3 h after
exercise, all trials, Yto baseline
12 h later; free HGB: SIG [3h
after exercise, all trials
Peeling
et al. (40)
10, M, highly
trained
endurance
athletes
n510, ferritin
.60 mg/L
3 separate trials: 2 CONT 10-km runs
—grass versus bitumen road
surface (75–80% peak V
̇
O
2
velocity); 10 31-km INT running
session on grass; INT session on
grass compared with CONT
running on grass
IL-6: SIG [immediately after
exercise, all trials, SIG [interval
versus continuous; HEP: SIG [
3 h after exercise, all trials, not
between trials; free HGB: SIG [
all trials, no SIG trial effect
between training surfaces
Newlin
et al. (32)
12, F, active
runners
NR 60- and 120-min treadmill run, 65%
V
̇
O
2
max, blood samples before,
immediately after, 3, 6, 9, 24 h
IL-6: SIG [immediately after
exercise, all trials but no other
time points, no SIG between
trials; HEP: SIG [3 h after
exercise and for 120-min trial;
sFe: SIG Y9 h after exercise
Robson-Ansley
et al. (42)
9, M, runners,
40 618
km weekly
NR 120-min treadmill run, 60% velocity
V
̇
O
2
max followed by 5-km time
trial; blood samples baseline,
immediately after, 24 h; Tx group
58% CHO solution at 20-min
intervals
IL-6: SIG [immediately after
exercise, all trials, SIG Yfor CHO
compared with placebo; HEP:
SIG [after exercise, all trials,
not between trials; sFe: SIG Y
24 h after exercise, no SIG
between trials
F5female; M 5male; NR 5not reported; ID 5iron deficiency; IL-6 5interleukin-6; HEP 5hepcidin; SIG 5significant; HGB 5hemoglobin;
CONT 5continuous; INT 5interval; sFe 5serum iron; CHO 5carbohydrate; Tx 5treatment.
Strength and Conditioning Journal | www.nsca-scj.com 31
Copyright © National Strength and Conditioning Association Unauthorized reproduction of this article is prohibited.
elemental iron or the amount that can be
absorbed (8). Supplemental forms vary in
the level of elemental iron because fer-
rous fumarate contains 33% and ferrous
gluconate 12% (8). The same guidelines
provided to improve dietary iron absorp-
tion also apply to supplementation such
that vitamin C will enhance absorption
and polyphenols in coffee and tea will
exert an inhibitory effect (8,18).
As previously discussed in this article,
100 mg of ferrous sulfate both as a food
supplement and in capsule form was
effective for improving various clinical
markers related to poor iron status in
female soldiers participating in basic
combat training (20,28). This level of
supplementation (100 mg of ferrous
sulfate) has been suggested to be effec-
tive for both improving and preventing
a decline in iron status (8); however,
whether supplementation in an iron-
deficient or anemic athlete (especially
female) translates to positive perfor-
mance outcomes, such as improved
endurance times, has continued to be
a focus in the literature (8,28).
In the investigation of McClung et al.
(28), supplementation was associated
with a significantly faster run time for
females with iron deficiency anemia.
An earlier investigation (18) examined
the effect of 100-mg ferrous sulfate and
the ability to complete a 15-km time
trial in a group of iron-depleted non-
anemic (SF ,16 mg/L) females partici-
pating in an endurance training
protocol. Results demonstrated a signif-
icantly faster time to completion for
the iron treatment group, as compared
with placebo, specifically in the second
and third 5-km segments, which repre-
sents an increase in endurance capac-
ity. Moreover, increases in hemoglobin
were associated with improvements in
energetic efficiency and decreased
energy expenditure, and increased
work rate (18).
Although the primary focus in the
literature has been iron status and
endurance athletes, a recent 2015 pub-
lication (30) examined the effects of 11
weeks of oral iron supplementation on
elite female volleyball players during
a competitive season, and the results
warrant discussion. Initial iron status
in both the control and treatment
groups ranged from ferritin ,30 to
.100 mg/L. Athletes (n522) received
either 325-mg ferrous sulfate, through
a product that provided the equivalent
of 105-mg elemental iron, or placebo.
Average weekly training consisted of
morning and afternoon sessions com-
prised of jogging, strength training,
sport-specific drills, power and speed
drills, and interval sessions. All athletes
were coached by trained dietitians on
how to track their dietary intake, and
results indicated that both the control
and treatment groups met the RDA for
iron intake (30).
There are several other major findings
of this study (30). First was a significant
decline in iron status over an 11-week
training period in the control group, as
compared with treatment. In terms of
performance outcomes, there was a sig-
nificantly greater increase in the per-
cent change for strength for the
treatment group for the clean and jerk,
power clean, and total mean strength,
as compared with placebo. In addition,
changes in hemoglobin were signifi-
cantly associated with the aforemen-
tioned increases in strength, for the
treatment group (30).
Finally, of concern is the fact that these
female athletes met the RDA for die-
tary iron intake and the women in the
control group still developed a decline
in iron status over an 11-week training
period (25 hours training weekly),
which warrants further consideration
for the development of conclusive sup-
plementation guidelines. Finally, it
seems that the development of iron
deficiency in female athletes is preva-
lent in both endurance and anaerobic
sports (18,28,30). In fact, prevalence of
iron depletion in a group of 84 female
professional endurance and team sport
athletes has been previously reported
(34). Iron depletion (ferritin ,30
mg/L) and iron deficiency with anemia
were found to be more frequent in
female distance runners as compared
with team sport athletes; however,
no statistical difference was found
between groups of athletes for preva-
lence of iron depletion, iron deficiency,
and iron-deficiency anemia (34).
In conclusion, recommendations for
practice include nutrition education
related to individual total daily energy
needs, daily RDA for iron intake, dietary
sources of iron, and approaches for
enhancing absorption. Furthermore,
iron absorption may be temporarily in-
hibited for approximately 3 hours after
training because of exercise-stimulated
inflammation and subsequent hepcidin
response. Athletes should therefore be
encouraged to consume dietary sources
of iron regularly throughout the day,
with all meals, to ensure adequate intake
and absorption. In addition to nutrition
education, iron supplementation (e.g.,
ferrous sulfate), mostly likely in the
range of 20–105 mg/d (elemental iron),
may be necessary in both endurance and
team sport female athletes (18,20,28,30),
and this should be clinically established
and appropriately monitored through
a multidisciplinary approach.
Conflicts of Interest and Source of Funding:
The author reports no conflicts of interest
and no source of funding.
Erica R.
Goldstein is
a clinical dieti-
tian at Mayo
Clinic in Jack-
sonville, Florida.
REFERENCES
1. Alaunyte I, Stojceska V, and Plunkett A. Iron
and the female athlete: A review of dietary
treatment methods for improving iron status
and exercise performance. J Int Soc Sports
Nutr 12: 1–7, 2015.
2. Auersperger I, Skof B, Leskosek B, Knap B,
Jerin A, and Lainscak M. Exercise-induced
changes in iron status and hepcidin
response in female runners. PLoS One 8:
1–7, 2013.
3. Banzet S, Sanchez H, Chapot R, Bigard X,
Vaulont S, and Koulmann N. Interleukin-6
contributes to hepcidin mRNA increase in
Exercise-Associated Iron Deficiency
VOLUME 38 | NUMBER 2 | APRIL 2016
32
Copyright © National Strength and Conditioning Association Unauthorized reproduction of this article is prohibited.
response to exercise. Cytokine 58: 158–
161, 2012.
4. Beguin Y. Soluble transferrin receptor for
the evaluation of erythropoiesis and iron
status. Clin Chim Acta 329: 9–22, 2003.
5. Bull-Henry K and Al-Kawas FH. Evaluation
of occult gastrointestinal bleeding. Am Fam
Physician 87: 430–436, 2013.
6. Casu C and Rivella S. Iron age: Novel
targets for iron overload. Hematol Am Soc
Hematol Educ Program 1: 216–221,
2014.
7. Deldicque L and Francaux M.
Recommendations for healthy nutrition in
female endurance runners: An update.
Front Nutr 2: 1–7, 2015.
8. DellaValle DM. Iron supplementation for
female athletes: Effects on iron status and
performance outcomes. Curr Sports Med
Rep 12: 234–239, 2013.
9. DellaValle DM and Haas JD. Impact of iron
depletion without anemia on performance
in trained endurance athletes at the
beginning of a training season: A study of
female collegiate rowers. Int J Sport Nutr
Exerc Metab 21: 501–506, 2011.
10. Fischer CP. Interleukin-6 in acute exercise
and training: What is the biological
relevance? Exerc Immunol Rev 12: 6–33,
2006.
11. Fischer CP, Plomgaard P, Hansen AK,
Pilegaard H, Saltin B, and Pedersen BK.
Endurance training reduce the contraction-
induced interleukin-6 mRNA expression in
human skeletal muscle. Am J Physiol
Endocrinol Metab 287: E1189–E1194,
2004.
12. Freeman HJ. Iron deficiency anemia in
celiac disease. World J Gastroenterol 21:
9233–9238, 2015.
13. Ganz T. Molecular control of iron transport.
J Am Soc Nephrol 18: 394–400, 2007.
14. Ganz T and Nemeth E. Iron metabolism:
Interactions with normal and disordered
erythropoiesis. Cold Spring Harb Perspect
Med 2: 1–13, 2012.
15. Gera T, Sachdev HS, and Boy E. Effect of
iron-fortified foods on hematologic and
biological outcomes: Systematic review of
randomized controlled trials. Am J Clin
Nutr 96: 309–324.
16. Gropper SS, Smith JL, and Groff JL.
Microminerals. In: Advanced Nutrition and
Human Metabolism (5th ed). Belmont, CA:
Wadsworth, Cengage Learning, 2009. pp.
469–487.
17. Harvey LJ, Armah CN, Dainty JR, Foxall RJ,
Lewis DJ, Langford NJ, and Fairweather-
Tait SJ. Impact of menstrual blood loss and
diet on iron deficiency among women in the
UK. Br J Nutr 94: 557–564, 2005.
18. Hinton PS, Giordano C, Brownlie T, and
Haas JD. Iron supplementation improves
endurance after training in iron-depleted,
nonanemic women. J Appl Physiol (1985)
88: 1103–1111, 2000.
19. Institute of Medicine, Food and Nutrition
Board. Dietary Reference Intakes for
Vitamin A, Arsenic, Boron, Chromium,
Copper, Iodine, Iron, Manganese,
Molybdenum, Nickel, Silicon, Vanadium,
and Zince. Washington, DC: National
Academies Press, 2001. pp. 351.
20. Karl JP, Lieberman HR, Cable SJ,
Williams KW, Young AJ, and McClung JP.
Randomized, double-blind, placebo-
controlled trial of an iron-fortified food
product in female soldiers during military
training: Relations between iron status,
serum hepcidin, and inflammation. Am J
Clin Nutr 92: 93–100, 2010.
21. Kell D and Pretorius E. Serum ferritin is an
important inflammatory disease marker, as
it is mainly a leakage product from
damaged cells. Metallomics 6: 748–773,
2014.
22. Keller C, Steensberg A, Hansen AK,
Fischer CP, Plomgaard P, and
Pedersen BK. Effect of exercise, training,
and glycogen availability on IL-6 receptor
expression in human skeletal muscle.
J Appl Physiol (1985) 99: 2075–2079,
2005.
23. Keller C, Steensberg A, Pilegaard H,
OsadaT,SaltinB,PedersenBK,and
Neufer PD. Transcriptional activation of
theIL-6geneinhumancontracting
skeletal muscle: Influence of muscle
glycogen content. FASEB J 15: 2748–
2750, 2001.
24. Lane DJR, Bae DH, Merlot AM, Sahni S,
and Richardson DR. Duodenal cytochrome
b(DCYTB) in iron metabolism: An update
on function and regulation. Nutrients 7:
2274–2296, 2015.
25. Latunde-Dada GO. Iron-metabolism in
athletes—Achieving a gold standard. Eur J
Haematol 90: 10–15, 2013.
26. Levi S and Rovida E. The role of iron in
mitochondrial function. Biochim Biophys
Acta 1790: 629–636, 2009.
27. Lynch S. The rationale for selecting and
standardizing iron status indicators. In:
World Health Organization. Report:
Priorities in the Assessment of Vitamin
a and Iron Status in Populations. Panama,
Geneva: World Health Organization, 2012.
28. McClung JP, Karl JP, Cable SJ,
Williams KW, Nindl BC, Young AJ, and
Lieberman HR. Randomized, double-blind,
placebo-controlled trial of iron
supplementation in female soldiers during
military training: Effects on iron status,
physical performance, and mood. Am J
Clin Nutr 90: 124–131, 2009.
29. Mettler S and Zimmerman MB. Iron excess
in recreational marathon runners. Eur J Clin
Nutr 64: 490–494, 2010.
30. Mielgo-Ayuso J, Zourdos MC, Calleja-
Gonza
´lez J, Urdampilleta A, and Ostojic S.
Iron supplementation prevents a decline in
iron stores and enhances strength
performance in elite female volleyball
players during the competitive season.
Appl Physiol Nutr Metab 40: 615–622,
2015.
31. Nemeth E, Rivera S, Gabayan V, Keller C,
Taudorf S, Pedersen BK, and Ganz T. IL-6
mediates hypoferremia of inflammation by
inducing the synthesis of the iron regulatory
hormone hepcidin. J Clin Invest 113:
1271–1276, 2004.
32. Newlin MK, Williams S, McNamara T,
Tjalsma H, Swinkels DW, and Haymes EM.
The effects of acute exercise bouts on
hepcidin in women. Int J Sport Nutr Exerc
Metab 22: 79–88, 2012.
33. Oexle H, Gnaiger E, and Weiss G. Iron-
dependent changes in cellular energy
metabolism: Influence on citric acid cycle
and oxidative phosphorylation. Biochim
Biophys Acta 1413: 99–107, 1999.
34. Ostojic SM and Ahmetovic Z. Weekly
training volume and hematological status in
female top-level athletes of different sports.
J Sports Med Phys Fitness 48: 398–403,
2008.
35. Pak M, Lopez MA, Gabayan V, Ganz T, and
Rivera S. Suppression of hepcidin during
anemia requires erythropoietic activity.
Blood 108: 3730–3735.
36. Pantopoulos K, Porwal SK, Tartakoff A, and
Devireddy L. Mechanisms of mammalian
iron homeostasis. Biochemistry 51: 5705–
5724, 2012.
37. Pedersen BK. Muscular interleukin-6 and
its role as an energy sensor. Med Sci
Sports Exerc 44: 392–396, 2012.
38. Pedersen BK, Steensberg A, and
Schjerling P. Exercise and interleukin-6.
Curr Opin Hematol 8: 137–141, 2001.
39. Peeling P, Dawson B, Goodman C,
Landers G, Wiegerinck ET, Swinkels DW,
and Trinder D. Cumulative effects of
consecutive running sessions on
hemolysis, inflammation and hepcidin
activity. Eur J Appl Physiol 106: 51–59,
2009.
Strength and Conditioning Journal | www.nsca-scj.com 33
Copyright © National Strength and Conditioning Association Unauthorized reproduction of this article is prohibited.
40. Peeling P, Dawson B, Goodman C,
Landers G, Wiegerinck ET, Swinkels DW,
and Trinder D. Training surface and
intensity: Inflammation, hemolysis, and
hepcidin expression. Med Sci Sports Exerc
41: 1138–1145, 2009.
41. Peeling P, Sim M, Badenhorst CE,
Dawson B, Govus AD, Abbiss CR,
Swinkels DW, and Trinder D. Iron status and
theacutepost-exercisehepcidinresponse
in athletes. PLoS One 9: 1–6, 2014.
42. Robson-Ansley P, Walshe I, and Ward D.
The effect of carbohydrate ingestion on
plasma interleukin-6, hepcidin and iron
concentrations following prolonged
exercise. Cytokine 53: 196–200, 2011.
43. Sim M, Dawson B, Landers G,
Swinkels DW, Tjalsma H, Trinder D, and
Peeling P. Effect of exercise modality
and intensity on postexercise interleukin-6
and hepcidin levels. Int J Sport Nutr Exerc
Metab 23: 178–186, 2013.
44. Sim M, Dawson B, Landers G, Trinder D,
and Peeling P. Iron regulation in athletes:
Exploring the menstrual cycle and effects
of different exercise modalities on hepcidin
production. Int J Sport Nutr Exerc Metab
24: 177–187, 2014.
45. Sinclair LM and Hinton PS. Prevalence of
iron deficiency with and without
anemia in recreationally active men and
women. JAmDietAssoc105: 975–978,
2005.
46. Sotelo A, Gonzalez-Osnaya L, Sanchez-
Chinchillas A, and Trejo A. Role of oxalate,
phytate, tannins and cooking on iron
bioavailability from foods commonly
consumed in mexico. Int J Food Sci Nutr
61: 29–39, 2010.
47. Takami T and Sakaida I. Iron regulation by
hepatocytes and free radicals. J Clin
Biochem Nutr 48: 103–106, 2011.
48. Tandara L and Salamunic I. Iron
metabolism: Current facts and future
directions. Biochem Med (Zagreb) 22:
311–328, 2012.
49. Xu W, Barrientos T, and Andrews NC. Iron
and copper in mitochondrial diseases. Cell
Metab 17: 31–328, 2013.
50. Zoller H and Vogel W. Iron
supplementation in athletes–first do no
harm. Nutrition 20: 615–619, 2004.
51. Zotter H, Robinson N, Zorzoli M,
Schattenberg L, Saugy M, and Mangin P.
Abnormally high serum ferritin levels among
professional road cyclists. Br J Sports Med
38: 704–708, 2004.
Exercise-Associated Iron Deficiency
VOLUME 38 | NUMBER 2 | APRIL 2016
34
Copyright © National Strength and Conditioning Association Unauthorized reproduction of this article is prohibited.
... Exercise practice can modify aforementioned hepcidin regulators [5][6][7][8][9] . Specifically, running shows a powerful capacity to increase hepcidin expression due to IL-6 production, chiefly owing to the higher foot strike haemolysis befallen in this modality 10 and/or its production as a myokine in the muscle during aerobic exercise 11 . ...
... Only Peeling et al. 21 tested men and women´s response, but the results were presented as a whole, ignoring the possible influence of female sex hormones1 [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] . It is unknown the hepcidin response to endurance exercise of the active females in different menstrual cycle phases, depending on their pre-exercise ferritin concentrations. ...
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Serum ferritin has been proposed as a predictor of hepcidin concentrations in response to exercise. However, this fact has not been studied in physically-active women. Therefore, the main objective of this study was to analyse the hepcidin response at different ferritin status before and after running exercise in physically active females. Fifteen eumenorrheic women performed a 40-min running protocol at 75% of VO2peak speed in different menstrual cycle phases (early-follicular phase, mid-follicular phase and luteal phase). Blood samples were collected pre-exercise, 0h post-exercise and 3h post-exercise. For statistics, participants were divided into two groups according to their pre-exercise ferritin levels (<20 and ≥20 μg/L). Through menstrual cycle, hepcidin was lower in both early follicular phase (p=0.024; 64.81±22.48 ng/ml) and mid-follicular phase (p=0.007; 64.68±23.91 ng/ml) for <20 μg/L ferritin group, in comparison with ≥20 μg/L group (81.17±27.89 and 79.54±22.72 ng/ml, respectively). Hepcidin showed no differences between both ferritin groups in either pre-exercise, 0h post-exercise and 3h post-exercise. Additionally, no association between pre-exercise ferritin and hepcidin levels 3h post-exercise (r=-0.091; p=0.554) was found. Menstrual cycle phase appears to influence hepcidin levels depending on ferritin reserves. In particular, physically-active females with depleted ferritin reserves seems to present lower hepcidin levels during the early-follicular phase and mid-follicular phase. However, no association between ferritin and hepcidin levels was found in this study. Hence, ferritin levels alone may not be a good predictor of hepcidin response to exercise in this population. Multiple factors such as sexual hormones, training loads and menstrual bleeding must be taken into account.
... Defisiensi zat besi mengakibatkan terjadinya penurunan hemoglobin pada atlet wanita, yang dikenal dengan anemia defisiensi besi. Anemia defisiensi besi dapat mengurangi kapasitas daya tahan atlet karena terganggunya transportasi oksigen akibat berkurangnya sintesis hemoglobin (Goldstein, 2016). Salah satu faktor yang memengaruhi nilai VO 2 maks adalah hemoglobin (Sinaga et al., 2017). ...
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Prolonged physical exercise has the risk of increasing free radicals which will affect the breakdown of red blood cells and promote the risk of decreased hemoglobin. Adolescent female athletes have a risk of decreasing hemoglobin due to menstruation. This situation can get worse if the athletes have iron defi-ciency or anemia as the result of poor diet choice. Increased radicals and anemia affect the amount of oxygen carried to the tissues and the maximum volume of oxygen an individual can use to produce energy (VO2 max). Beets have benefits for athlete's performance and have been developed into an instant drink. The purpose of this study was to determine the effect of an instant FeSO4 fortified beet juice (BeeFe juice) in overcoming anemia on female adolescent athletes. This research using an experimental study with controlled trial pre-posttest design. Twenty-nine adolescent female athletes, aged 13-19 years, were divided into two groups. Fe tablet supplementation (containing Fe 60 mg) was given to 15 athletes in the control group and BeeFe juice (containing Fe 17 mg) was given to 14 athletes in the treatment group du-ring the luteal and menstruation phase (±14 days). Hemoglobin levels, Malondialdehyde (MDA) and maxi-mal oxygen volume (VO2 max) were examined before and after the intervention. Data were analyzed using paired t-test and independent t-test IBM SPSS version 22. This research has obtained Ethical Appro-val with number KE/FK/0633/EC/2018 from the Ethical Commission of FKKMK UGM. The results showed no significant difference between the group given Fe tablets and the group given BeeFe juice on hemo-globin levels (P>0.05), MDA levels (P>0.05), and VO2 max levels (P>0.05) in the menstrual and luteal phases of menstruation. It can be concluded that BeeFe juice has the same effectiveness as commercial Fe tablets. BeeFe juice can be an alternative food ingredient in iron supplementation.
... Iron is one of the key micronutrients in an athlete's diet. In the human body, it is responsible for oxygen transport and energy production [65], and its adequate intake through diet, absorption, and cellular use is crucial for endurance performance [66]. Anaemia, caused by iron deficiency, can result in decrease of performance; furthermore, depletion of iron stores affects aerobic training adaptation, increases muscle fatigue, and decreases energetic efficiency during submaximal exercise [67]. ...
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Soccer is one of the most popular sports in the world. As its number of players is increasing, the number of female players is also on the rise. However, there are limited data about how the diets of female soccer players should be designed. Thus, the aim of our work is to deliver concise nutritional recommendations for women practicing this sport. Based on a literature review, we emphasize that individual adjustment of the energy value of the diet is the key factor for the physical performance of female soccer players. Appropriate macronutrient intake makes it possible to achieve the proper energy value of the diet (5–10 g/kg body mass/day carbohydrates; 1.2–1.7 g/kg body mass/day proteins; <30% fats from energy). The micronutrients should be consumed in amounts corresponding to individual values recommended in national standards. Soccer players should pay special attention to the proper consumption of such micronutrients, as well as vitamins such as iron, calcium, and vitamin D. The right amount of fluid intake, consistent with the player’s needs, is crucial in maximizing exercise performance. The diet of a female practicing soccer is usually characterized with low energy values, which increases the risk of various health consequences related to low energy availability. Monitoring the diets of female soccer players is, therefore, necessary.
... Iron also influences on other biological functions, such as breathing, DNA synthesis and cells proliferation [2]. Proper dietary intake, absorption and cellular use of iron is crucial for endurance performance [3]. ...
Article
Objectives The aim of the study was to evaluate dietary iron intake by professional female soccer players and to estimate the possible risk of iron deficiency. Equipment and methods The research was completed by 38 professional soccer players of the three soccer leagues: Ekstraleague, I League, and II League. The participants had their height and body mass measured. The data food consumption and iron intake was obtained through the method of a systematic recording of results conducted throughout a 3-day long period and food frequency questionnaire, adapted to evaluation of intake of this particular micronutrients (IRONIC-FFQ). Results The age of the participants was 21 ± 5 years, the height was 167 ± 5 cm, and the body mass median was 59,2 kg. Most common iron sources in study group were cereal products (31,8%), meats (14,1%) and vegetables (9,9%). Iron intake with using IRONIC-FFQ method was 8,06 mg, while using 3-day dietary food record method was 8,8 mg. After comparing both method with each other we found a correlation (P < 0,001, r = 0,568) and Bland-Altman index of 7,89%. Conclusion In conclusion, iron intake in study group was sufficient. Validation of IRONIC-FFQ with Spearman test gives positive results, but failed with Bland-Altman plot.
... The explanation could be based on the sportsmen´s higher intakes of air, food and drinking water. Besides, the increased demands in oxidative metabolism, antioxidant protection, and aerobic physiological demands may induce low Iron (Fe) levels or anemia [25], which is common among sportsmen. In recent surveys it has been associated low Fe concentrations with higher Pb and Cd blood levels [26,27]. ...
Article
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Iron is a functional component of oxygen transport and energy production in humans and therefore is a critically important micronutrient for sport and exercise performance. Athletes, particularly female athletes participating in endurance sport, are at increased risk of compromised iron status due to heightened iron losses through menstruation and exercise-induced mechanisms associated with endurance activity. Conventionally oral iron supplementation is used in prevention or/and treatment of iron deficiency. However, this approach has been criticised because of the side effects and increased risk of iron toxicity associated with the use of supplements. Thus, more recently there has been a growing interest in using dietary modification rather than the use of supplements to improve iron status of athletes. Dietary iron treatment methods include the prescription of an iron-rich diet, or/and haem iron-based diet, dietary advice counselling and inclusion of novel iron-rich products into the daily diet. Although studies using dietary modification are still scarce, current literature suggests that dietary iron interventions can assist in maintaining iron status in female athletes, especially during intensive training and competition. Future research should focus on the most efficient method(s) of dietary modification for improvement of iron status and whether these approaches can have a favourable impact on sports and exercise performance.
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The purpose of this review is to present the basic principles of a healthy nutrition in female endurance runner enriched by the latest scientific recommendations. Female endurance runners are a specific population of athletes who need to take specifically care of daily nutrition due to the high load of training and the necessity to keep a rather low body mass. This paradoxical situation can create some nutritional imbalances and deficiencies. Female endurance athletes should pay attention to their total energy intake, which is often lower than their energy requirement. The minimal energy requirement has been set to 45kcal/kg fat free mass/day plus the amount of energy needed for physical activity. The usual recommended amount of 1.2-1.4g protein/kg/day has recently been questioned by new findings suggesting that 1.6g/kg/day would be more appropriate for female athletes. Although a bit less sensitive to carbohydrate loading than their male counterparts, female athletes can benefit from this nutritional strategy before a race if the amount of carbohydrates reaches 8g/kg/day and if their daily total energy intake is sufficient. A poor iron status is a common issue in female endurance runners but iron-enriched food as well as iron supplementation may help to counterbalance this poor status. Finally, they should also be aware that they may be at risk for low calcium and vitamin D levels.
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Iron and ascorbate are vital cellular constituents in mammalian systems. The bulk-requirement for iron is during erythropoiesis leading to the generation of hemoglobin-containing erythrocytes. Additionally; both iron and ascorbate are required as co-factors in numerous metabolic reactions. Iron homeostasis is controlled at the level of uptake; rather than excretion. Accumulating evidence strongly suggests that in addition to the known ability of dietary ascorbate to enhance non-heme iron absorption in the gut; ascorbate regulates iron homeostasis. The involvement of ascorbate in dietary iron absorption extends beyond the direct chemical reduction of non-heme iron by dietary ascorbate. Among other activities; intra-enterocyte ascorbate appears to be involved in the provision of electrons to a family of trans-membrane redox enzymes; namely those of the cytochrome b561 class. These hemoproteins oxidize a pool of ascorbate on one side of the membrane in order to reduce an electron acceptor (e.g., non-heme iron) on the opposite side of the membrane. One member of this family; duodenal cytochrome b (DCYTB); may play an important role in ascorbate-dependent reduction of non-heme iron in the gut prior to uptake by ferrous-iron transporters. This review discusses the emerging relationship between cellular iron homeostasis; the emergent “IRP1-HIF2α axis”; DCYTB and ascorbate in relation to iron metabolism.
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The primary aim of this study was to examine the effects of 11 weeks of iron supplementation on hematological and strength markers in elite female volleyball players. Twenty-Two volleyballers (27.0±5.6yrs.) from two Spanish First National League teams participated and were counterbalanced into one of two groups based upon iron status: 1) Control Group (CG, n=11) or 2) Iron Treatment Group (ITG, n=11), which received 325mg/d of ferrous sulphate daily. Everyday subjects performed their team’s regimen of training or match play. Both groups were tested for hematological and strength levels at two points, 1) baseline (T0-before preseason); and 2) 11 weeks later (T11-post-testing). Hematological parameters were: [serum iron (sFe), serum ferritin (FER), transferrin saturation index (TSI), and Hemoglobin (Hb)]; strength assessments were: (bench press, military press, back squat, power clean, clean and jerk and pull-over). CG, experienced a significant decrease (p<0.05) for SFe (T0: 112.7±31.5 - T11: 69.0±20.5 μg•dL−1.-33.9%), FER (T0: 60.2±28.6 - T11: 38.2±16.4 ng•mL−1,-34.6%), TSI (T0: 29.4±9.5 - T11: 17.4±5.1 %,-35.3%), and Hb (T0: 14.1±1.0 - T11:13.0±0.8 g•L−1,-7.44%), however ITG experienced no changes (p>0.05). Consequently, in ITG all hematological parameters were significantly greater (p<0.05) than CG at T11. There was greater (p<0.05) percent increase in the clean and jerk (CG: +5.1±20.9 vs. ITG: +29.0±21.3 %), power clean (CG: -5.8±30.3 vs. ITG: +44.6±56.6%) and total mean strength (CG: +10.9±3.2 vs. ITG: +26.2±3.6%) in ITG. Our findings suggest that oral iron supplementation prevents iron loss and enhances strength in female volleyballers during the competitive season.
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Excess iron deposition in vital organs is the main cause of morbidity and mortality in patients affected by β-thalassemia and hereditary hemochromatosis. In both disorders, inappropriately low levels of the liver hormone hepcidin are responsible for the increased iron absorption, leading to toxic iron accumulation in many organs. Several studies have shown that targeting iron absorption could be beneficial in reducing or preventing iron overload in these 2 disorders, with promising preclinical data. New approaches target Tmprss6, the main suppressor of hepcidin expression, or use minihepcidins, small peptide hepcidin agonists. Additional strategies in β-thalassemia are showing beneficial effects in ameliorating ineffective erythropoiesis and anemia. Due to the suppressive nature of the erythropoiesis on hepcidin expression, these approaches are also showing beneficial effects on iron metabolism. The goal of this review is to discuss the major factors controlling iron metabolism and erythropoiesis and to discuss potential novel therapeutic approaches to reduce or prevent iron overload in these 2 disorders and ameliorate anemia in β-thalassemia. © 2014 by The American Society of Hematology. All rights reserved.
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The cardio-metabolic and antioxidant health benefits of caffeinated green tea (GT) relate to its catechin polyphenol content. Less is known about decaffeinated extracts, particularly in combination with exercise. The aim of this study was therefore to determine whether a decaffeinated green tea extract (dGTE) positively influenced fat oxidation, body composition and exercise performance in recreationally active participants. Fourteen, recreationally active males participated in a double-blind, placebo-controlled, parallel design intervention (mean ± SE; age = 21.4 ± 0.3 yrs; weight = 76.37 ± 1.73 kg; body fat = 16.84 ± 0.97%, peak oxygen consumption [[Formula: see text]] = 3.00 ± 0.10 L·min(-1)). Participants were randomly assigned capsulated dGTE (571 mg·d(-1); n = 7) or placebo (PL; n = 7) for 4 weeks. Following body composition and resting cardiovascular measures, participants cycled for 1 hour at 50% [Formula: see text], followed by a 40 minute performance trial at week 0, 2 and 4. Fat and carbohydrate oxidation was assessed via indirect calorimetry. Pre-post exercise blood samples were collected for determination of total fatty acids (TFA). Distance covered (km) and average power output (W) were assessed as exercise performance criteria. Total fat oxidation rates increased by 24.9% from 0.241 ± 0.025 to 0.301 ± 0.009 g·min(-1) with dGTE (P = 0.05; ηp(2) = 0.45) by week 4, whereas substrate utilisation was unaltered with PL. Body fat significantly decreased with dGTE by 1.63 ± 0.16% in contrast to PL over the intervention period (P < 0.001; ηp(2) = 0.84). No significant changes for FFA or blood pressure between groups were observed. dGTE resulted in a 10.9% improvement in performance distance covered from 20.23 ± 0.54 km to 22.43 ± 0.40 km by week 4 (P < 0.001; ηp(2) = 0.85). A 4 week dGTE intervention favourably enhanced substrate utilisation and subsequent performance indices, but did not alter TFA concentrations in comparison to PL. The results support the use of catechin polyphenols from dGTE in combination with exercise training in recreationally active volunteers.
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This study explored the relationship between serum ferritin and hepcidin in athletes. Baseline serum ferritin levels of 54 athletes from the control trial of five investigations conducted in our laboratory were considered; athletes were grouped according to values <30 μg/L (SF<30), 30-50 μg/L (SF30-50), 50-100 μg/L (SF50-100), or >100 μg/L (SF>100). Data pooling resulted in each athlete completing one of five running sessions: (1) 8×3 min at 85% vVO2peak; (2) 5×4 min at 90% vVO2peak; (3) 90 min continuous at 75% vVO2peak; (4) 40 min continuous at 75% vVO2peak; (5) 40 min continuous at 65% vVO2peak. Athletes from each running session were represented amongst all four groups; hence, the mean exercise duration and intensity were not different (p>0.05). Venous blood samples were collected pre-, post- and 3 h post-exercise, and were analysed for serum ferritin, iron, interleukin-6 (IL-6) and hepcidin-25. Baseline and post-exercise serum ferritin levels were different between groups (p<0.05). There were no group differences for pre- or post-exercise serum iron or IL-6 (p>0.05). Post-exercise IL-6 was significantly elevated compared to baseline within each group (p<0.05). Pre- and 3 h post-exercise hepcidin-25 was sequentially greater as the groups baseline serum ferritin levels increased (p<0.05). However, post-exercise hepcidin levels were only significantly elevated in three groups (SF30-50, SF50-100, and SF>100; p<0.05). An athlete's iron stores may dictate the baseline hepcidin levels and the magnitude of post-exercise hepcidin response. Low iron stores suppressed post-exercise hepcidin, seemingly overriding any inflammatory-driven increases.
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Iron is an important micronutrient that may be depleted in celiac disease. Iron deficiency and anemia may complicate well-established celiac disease, but may also be the presenting clinical feature in the absence of diarrhea or weight loss. If iron deficiency anemia occurs, it should be thoroughly evaluated, even if celiac disease has been defined since other superimposed causes of iron deficiency anemia may be present. Most often, impaired duodenal mucosal uptake of iron is evident since surface absorptive area in the duodenum is reduced, in large part, because celiac disease is an immune-mediated disorder largely focused in the proximal small intestinal mucosa. Some studies have also suggested that blood loss may occur in celiac disease, sometimes from superimposed small intestinal disorders, including ulceration or neoplastic diseases, particularly lymphoma. In addition, other associated gastric or colonic disorders may be responsible for blood loss. Rarely, an immune-mediated hemolytic disorder with increased urine iron loss may occur that may respond to a gluten-free diet. Reduced expression of different regulatory proteins critical in iron uptake has also been defined in the presence and absence of anemia. Finally, other rare causes of microcytic anemia may occur in celiac disease, including a sideroblastic form of anemia reported to have responded to a gluten-free diet.