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Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Our objective was to investigate the effects of iron depletion on adaptation to aerobic exercise, assessed by time to complete a 15-km cycle ergometer test. Forty-two iron-depleted (serum ferritin <16 µg/l), nonanemic (Hb >12 g/dl) women (18-33 yr old) received 100 mg of ferrous sulfate (S) or placebo (P) per day for 6 wk in a randomized, double-blind trial. Subjects trained for 30 min/day, 5 days/wk at 75-85% of maximum heart rate for the final 4 wk of the study. There were no group differences in baseline iron status or in 15-km time. Iron supplementation increased serum ferritin and decreased transferrin receptors in the S compared with the P group. The S and P groups decreased 15-km time and respiratory exchange ratio and increased work rate during the 15-km time trial after training. The decrease in 15-km time was greater in the S than in the P group (P = 0.04) and could be partially attributed to increases in serum ferritin and Hb. These results indicate that iron deficiency without anemia impairs favorable adaptation to aerobic exercise.
iron deficiency; endurance capacity; aerobic training; serum transferrin receptors
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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THE PREVALENCE OF IRON DEFICIENCY anemia in US women 18-44 yr of age has been estimated to be 3-5%, whereas the prevalence of iron deficiency without anemia is much higher, ranging from 11 to 13% (18). Furthermore, regular aerobic exercise results in depletion of body iron stores (4, 14, 19), placing a significant number of young women at risk for iron deficiency as they engage in regular physical activity, which is recommended as part of a healthy lifestyle.
Decreased work capacity [i.e., maximal O2 utilization
(
O2 max)] due to
iron deficiency anemia in humans has been well documented (5, 6, 11,
29) and is attributed to insufficient O2 transport by Hb to
peripheral tissues. In contrast, the effects of iron depletion without
anemia on physical performance have not been well characterized.
With moderate iron deficiency, iron stores are depleted but Hb remains
above a specified cutoff point for anemia, and neither O2-carrying capacity of the blood nor
O2 max is compromised (15, 23, 32). However, animal studies have shown that the activities of
iron-containing muscle mitochondrial oxidative enzymes and respiratory
proteins are decreased during iron deficiency without anemia (7, 8,
30). Because of the role of these iron-dependent enzymes and proteins
in oxidative metabolism, it is expected that iron deficiency without
anemia would impair the ability to sustain physical performance at
65-85% of maximal capacity, i.e., endurance. Iron-deficient rats
with Hb concentrations normalized by transfusion of erythrocytes have
compromised endurance capacity in conjunction with decreased oxidative
capacity of skeletal muscle (7, 8). In addition, aerobic training
induces increases in iron-dependent mitochondrial enzyme and
respiratory chain cytochrome activities (12, 13). Thus iron deficiency
may also impair the adaptive response to aerobic training.
Studies in experimental animals have demonstrated that iron deficiency
severe enough to impair Hb production alters heme and nonheme iron
adaptations to training. Tobin et al. (28) showed that iron deficiency,
sufficient to reduce Hb ~50% compared with control rats, prevented
improvements in O2 max
after 12 wk of endurance training (1.5 h/day, 4 days/wk at 65%
O2 max). The effects of iron deficiency on nonheme iron responses to training were
not reported in this investigation. After a more moderate 4-wk training
regimen (1.0 h/day, 6 days/wk at 65%
O2 max), Willis et al.
(31) found that iron-deficient rats (Hb ~50% of controls) improved
O2 max and endurance
but iron-sufficient rats did not. These adaptations in the
iron-deficient animals were associated with increased activities of
tricarboxylic acid cycle enzymes in skeletal muscle and heart and NADH
oxidase in liver, which were absent in iron-sufficient animals. After a
similar training protocol, Willis et al. (30) also reported increased cytochrome c, tricarboxylic acid cycle enzymes, and manganese superoxide dismutase activities in skeletal muscle of iron-deficient, but not iron-sufficient, animals (30). These studies demonstrate that
heme and nonheme iron responses to training are altered by iron deficiency.
The effects of iron depletion without anemia on adaptation to training
in young women have not been fully characterized. Iron supplementation
of iron-deficient, but not anemic (Hb >120 g/l), women who were
physically active (16) or who underwent a prescribed training program
(20) significantly increased Hb, serum ferritin (sFer), and
O2 max compared with
placebo. In both studies, change in
O2 max was
significantly and positively associated with change in Hb in the
iron-supplemented women. Newhouse et al. (23) found that iron
supplementation increased sFer in iron-depleted, nonanemic female
runners but did not alter Hb or
O2 max. These studies are consistent with the idea that O2 delivery to the
peripheral tissues is the primary determinant of
O2 max (26). Because Hb
concentration was increased in the iron-treated women in these studies,
the authors were unable to assess the effects of iron deficiency
independent of O2-carrying capacity on performance. Rowland
et al. (25) found that iron supplementation of iron-depleted runners
who continued their normal training regimen resulted in significant
improvements in treadmill running times and sFer concentrations but did
not alter Hb or O2 max.
However, there was a significant, positive association between changes
in treadmill running time and changes in sFer. Klingshirn et al. (15),
in a similar supplementation trial of iron-deficient women runners,
demonstrated significant increases in sFer but no effect on Hb,
O2 max, or endurance after supplementation compared with placebo.
The results of the animal and human studies, taken together, suggest that iron deficiency impairs the adaptive response to training at maximal levels by preventing attainment of optimal Hb and at submaximal levels by impairing oxidative capacity of peripheral tissues. However, the effects of iron deficiency without anemia on the response to endurance training and on submaximal work capacity in previously untrained women have yet to be elucidated.
Previous work from this laboratory has demonstrated that iron depletion
without anemia reduces the endurance capacity of untrained women by
increasing energy expenditure and fractional O2 utilization (%O2 max)
after controlling for work rate (34). The goal of this follow-up study
was to determine whether iron depletion impairs the ability of
nonanemic, previously untrained women to increase endurance capacity in
response to 4 wk of aerobic training on a cycle ergometer. The specific
objectives of this investigation were 1) to study the effects
of iron supplementation on endurance capacity as assessed by
performance during a 15-km time trial on a cycle ergometer, 2)
to test the effects of iron supplementation on metabolic adaptations to
training during the time trial, including ventilation, gas exchange,
and plasma lactate concentrations, and 3) to investigate the
relation of iron status indicators to endurance capacity and energy
metabolism during the time trial after 4 wk of physical training.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Subjects. Two hundred seventy-one physically active, untrained 19- to 35-yr-old women were recruited from the local community. Forty-nine women were identified as iron-depleted without anemia on the basis of Hb concentrations >120 g/l and sFer concentrations <16 µg/l in preliminary screenings. After physical examination, including a medical history, no subjects were found to possess the following exclusion criteria: current pregnancy or pregnancy within the previous year, recent infectious illness or fever, hemolytic anemia, asthma, musculoskeletal problems, recent history of eating disorders, smoking, excess alcohol consumption, recent use of recreational drugs, consumption of prescription medications that may interfere with dietary iron absorption, or participation in competitive athletics.
Data from four women were excluded from data analysis because of high baseline ferritin concentrations, indicating that their screening ferritins misclassified them as iron depleted, and three women dropped out for personal reasons unrelated to the study. Thus 42 women qualified and were willing to participate in the study. Signed informed consent was obtained from each subject. This study was approved by the Cornell University Committee on Human Subjects.Study design. The experimental design of the study was a randomized, double-blind, placebo-controlled intervention trial. Subjects were randomly assigned to two groups, receiving an iron supplement or a placebo; all subjects completed 4 wk of aerobic training. Subjects took an iron supplement of 50 mg of ferrous sulfate (10 mg of elemental iron) or an identical placebo capsule two times a day for 6 wk. Previous work in our laboratory demonstrated that iron status is improved after 4 wk of iron supplementation by use of a similar dose of ferrous sulfate (33). The capsules were prepared in our laboratory with the use of gelatin capsules (Apothecary Products, Minneapolis, MN), ferrous sulfate, and lactose filler. The iron content of the capsules was determined from a random sample of 20 capsules [49.4 ± 4.2 (SD) mg of ferrous sulfate]. The subjects were instructed to consume the capsules with citrus juice to enhance iron absorption and with meals to reduce side effects. They were also instructed to avoid consumption of any other multivitamin and mineral supplements during the entire study period. Subjects recorded capsule ingestion, consumption of medication, illness, menstrual status, gastrointestinal symptoms, physical activity, and musculoskeletal problems in a daily log. Unsolicited verbal reports from the subjects indicated that they were unable to detect whether they received iron or placebo.
After 2 wk of iron or placebo treatment, exercise training was initiated. The 4-wk training regimen (5 sessions/wk) was performed on a cycle ergometer (Cateye ergociser E-3200) equipped with a heart rate (HR) monitor and digital output of cadence and work (in W). The training sessions included a 4-min warm-up followed by a 25-min cycling session divided between workloads that allowed subjects to achieve a target HR of 75% of maximum HR (HRmax) and 85% HRmax. Over the course of the 4-wk training program, the time spent at 75% HRmax was decreased from 20 to 10 min, with a corresponding increase in the duration of cycling at 85% HRmax (i.e., 20 min at 75% HRmax and 5 min at 85% HRmax in week 1 and 10 min at 75% HRmax and 15 min at 85% HRmax in week 4). Previous studies have demonstrated that aerobic exercise of similar intensity and duration is sufficient to produce measurable improvements in endurance capacity (3). Subjects recorded HR, average cadence, and work (in W) for each training session in a training log. Prestudy habitual physical activity levels were assessed by a frequency questionnaire, which was analyzed using the method described previously (32) to obtain a physical activity score for each subject. This was done to confirm similar habitual physical activity between groups after randomization. To ensure that the prescribed training regimen was the only additional source of physical activity, subjects were asked to maintain their prestudy activity level during the entire study period. To maximize the potential to respond to physical training, highly trained women and competitive athletes were excluded from the study. For all subjects, body composition and physical performance were measured immediately before and after the 6-wk treatment period. In addition, baseline dietary iron intake was assessed by a dietary record over 4 consecutive days, including 1 weekend day. The dietary records were analyzed using Nutritionist IV (Hearst, San Bruno, CA) to quantify dietary iron intake.Physiological measurements.
Exercise tests
(O2 max and 15-km
time trial) were conducted on a mechanically braked and calibrated
cycle ergometer (model 818E, Monark, Varberg, Sweden) with a
computerized metabolic cart (Physiodyne, Quogue, NY) in the Human
Bioenergetics Laboratory at Cornell University. The ergometer was
equipped with a digital readout of cadence (in rpm) or distance (in km)
pedaled. Concentrations of O2 and CO2 in
expired air and respiratory volume were analyzed with gas analyzers
(Ametek, Pittsburgh, PA) and a respiratory pneumotachograph (Fitco
Micro Flow, Fitness Instrument Technologies, Farmingdale, NY) through a
breathing valve (Hans Rudolph, Kansas City, MO). Data output from the
instruments was directed to an IBM 386 computer for the
breath-by-breath calculation of O2 consumption (O2), CO2
production (CO2),
respiratory exchange ratio (RER, CO2/O2),
and minute ventilation. HR was monitored throughout the tests with an
electrocardiograph (Burdick, Milton, WI).
O2 max, maximal aerobic capacity was determined. The protocol was a modification of
that described by McArdle and Magel (22) for the cycle ergometer. Testing began with a 5-min warm-up at 30 W and a pedaling cadence of 60 rpm. The workload was increased by 30-W intervals every 2 min until
O2 stopped increasing or
the subject could not continue. O2 max was achieved
if two of three of the following criteria were met:
O2 increased by <150 ml
with an increase in workload, RER was >1.10, or HRmax was
within ±10 beats of age-predicted maximum (220 
age in yr).
Test-retest reliability for the
O2 max test
for similar subjects in our laboratory is r = 0.91.
Endurance capacity was tested by a 15-km time trial administered 2 days
after the O2 max
test. Performance was measured as time to complete the 15-km time
trial. Subjects were asked to finish the time trial as quickly as
possible, against a predetermined resistance. The level of the
resistance allowing the subject to achieve 70% of
O2 max while pedaling
at 60 rpm was determined for each individual on the basis of her
pretreatment O2 max test. The same resistance level was used at the posttreatment endurance
test. Standardized words of encouragement were used by the investigator
throughout the test. During the test,
O2, CO2, and HR were
continuously monitored. Cadence was recorded each minute and was used
to calculate absolute work rate. Test-retest reliability of this
protocol determined in our laboratory is r = 0.93 for average
O2 during the time trial
and r = 0.99 for average work rate during the time trial.
Blood samples were obtained by finger punctures immediately before the
time trial, after 5, 10, and 15 km, and 10 min after completion of the
time trial. Blood samples were drawn into 100-µl heparinized
capillary tubes, sealed, stored on ice, centrifuged immediately after
the test, and stored at 20°C for determination of lactate
concentration. Lactate concentration in plasma was determined
enzymatically (Sigma Diagnostics, St. Louis, MO). Pre- and
posttreatment samples for each subject were analyzed concurrently at
the completion of the study to eliminate variation in assay conditions.
Body size and composition were measured in the Human Body Composition
Laboratory at Cornell University. Anthropometry (weight and height) was
assessed using standard procedures described in Lohman et al. (17).
Body fat (i.e., fat mass) and fat-free mass were assessed by
densitometry following the technique described by Aker and Buskirk (1).
The Siri equation adapted for women was used, with the assumption that
the density of fat-free mass is 1.096 g/ml.
Iron status measurements.
Iron status was assessed at screening and before, at the midpoint (3 wk), and after iron treatment (6 wk). Blood samples were obtained from
the seated subject in the fasted state from the antecubital vein into
two evacuated tubes: one contained EDTA, and the other was empty. Hb
and hematocrit were assayed in whole blood immediately after sample
collection. Coagulated blood was separated immediately by
centrifugation at 1,640 g for 10 min at room temperature.
Aliquots of serum samples were frozen at 20°C. To control
for potential variation in assay conditions, serum samples [serum
transferrin receptor (sTfR), sFer, and iron (sFe) and total
iron-binding capacity (TIBC)] for the same subject at all three
time points were analyzed concurrently at the completion of the study.
Statistical analysis. Data were examined to verify normality of distribution. The physical activity data showed a skewed distribution, and statistical analysis was performed on logarithmically transformed data. Independent Student's t-test was used to test group differences at baseline. Repeated-measures ANOVA was used to test group and time effects as well as group-by-time interactions for measures of iron status. Regression analysis with baseline measurements as covariates was used to analyze group differences in posttreatment iron status or physical performance. The effects of final iron status on final outcome variables were analyzed by multiple linear regression analysis (GLM), controlling for baseline outcome values and iron status as well as other potential confounding or mediating factors. Statistical significance was indicated at P < 0.05. Values are means ± SE. To test whether initial iron status modifies the effects of supplementation on outcome variables, appropriate interaction terms were included in the multiple linear regression model. An interaction was considered statistically significant at P < 0.2. All statistical analyses were performed using SAS version 6.0 (27) on a personal computer.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Subject characteristics.
The placebo and supplemented groups were of similar age (20.0 ± 0.4 and 21.0 ± 0.8 yr, respectively) and height (1.67 ± 0.02 and 1.66 ± 0.01 m, respectively). Body weight and composition did not
differ between the two groups before or after the study, nor were there
significant changes during the study (Table
1). Habitual physical activity did not
differ between groups, nor were there significant group differences in
the number of training sessions or total work performed during the
training (data not shown). There were no group differences in dietary
iron intake on the basis of the 4-day diet records (14.8 ± 1.9 and
14.7 ± 1.1 mg iron/day for placebo and supplemented groups,
respectively). Likewise, there were no group differences in reported
symptomology associated with iron treatment.
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Response to iron treatment.
Results of analysis of blood indexes of iron status measured at 0, 3, and 6 wk of the study are shown in Table 2.
There were no significant group differences in any measure of iron
status at baseline. After 3 wk of treatment, the iron-supplemented
group exhibited significant increases in sFer, sFe, and TS above
baseline values that persisted after 6 wk of treatment. In the
supplemented group the sTfR concentration decreased over the course of
the study and was significantly less than baseline after 6 wk of iron treatment. Response of sTfR to the iron supplement was dependent on
initial sTfR, such that women who began the study with higher sTfR
(i.e., lower tissue iron) exhibited a greater decrease in sTfR by the
end of the study (supplementation by initial sTfR interaction P = 0.019). In the placebo group, there were no significant changes in
any indicator of iron status throughout the course of the study. sFer,
sFe, and TS were significantly greater and sTfR was significantly lower
in the iron-supplemented group than in the placebo group after 6 wk of
treatment. There was a significant negative correlation between sTfR
and sFer at baseline (r = 0.56) and 6 wk (r = 0.70), whereas Hb was positively correlated with Hct (r = 0.74 and 0.88) and TS (r = 0.64 and 0.62) at both time points.
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Time trial.
Results of the physical performance measurements taken during the 15-km
time trial before and after iron treatment and exercise training are
presented in Table 3. There were no
significant differences between the supplemented and placebo groups at
baseline, although
O2 max tended to be
lower (Table 3),
%O2 max tended to be
higher, and more time was taken to complete the test (P < 0.1) in the supplemented group compared with placebo. Posttest O2 max, RER, work rate,
and time to complete the time trial were significantly improved in both
groups, suggesting a positive effect of the 4-wk training regimen.
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Time to finish the time trial.
There was a significant effect of iron supplementation on time to
complete the 15-km time trial. The supplemented group showed an
improvement in finishing time twice that of the placebo group (1.6 ± 0.5 and 3.4 ± 0.6 min for placebo and
supplemented groups, respectively), controlling for baseline time to
complete the time trial. The improved finishing time by the
supplemented group was primarily due to faster times in the second
(P = 0.082) and third (P = 0.027) 5-km segments of the
time trial (Fig. 1).
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O2 max, absolute work
rate, and training level. Only absolute work rate was correlated with
15-km time, and it was included as a covariate in all regression
models. Model 1 in Table 4 shows
that supplementation decreased time to finish by 1.61 ± 0.76 min
(P = 0.04), controlling for baseline time to finish and
posttest work rate during the time trial. After addition of either
initial and final sFer (Table 4, model 2) or Hb (Table 4,
model 4) to the model, the significance of supplementation as a
predictor of completion time was reduced, indicating that the effect of
supplementation was partially due to changes in iron status. Final sTfR
accounted for a greater proportion of the supplementation effect
compared with Hb (Table 4, models 2 and 4). Adding sTfR
to the model decreased the group coefficient ~70%
(
group decreased from 1.612 to 0.437),
whereas including Hb in the model decreased the group coefficient only
20% (group decreased from 1.612 to
1.267).
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Energy expenditure and absolute work rate.
The rate of energy expenditure during the time trial was calculated for
each subject on the basis of her average
O2 and average nonprotein RER
during the time trial (Table 5) after McArdle et al. (21). The total energy expended during the time trial
was similar in the pre- and posttests for both treatment groups. The
supplemented group was less efficient than the placebo group at
baseline on the basis of energy expenditure (in kcal) per unit of work
performed (in W). The iron-supplemented group significantly increased
the rate of energy expenditure 0.57 ± 0.23 kcal/min above baseline,
whereas the placebo group was unchanged. There were no significant
group differences in total energy expenditure or in the rate of energy
expenditure, controlling for baseline energy expenditure and absolute
work rate or %O2 max.
The results of multiple linear regression analysis to examine
relationships between energy expenditure, work rate, efficiency, and
iron status are shown in Table 6. Total
energy expended during the 15-km time trial was significantly and
negatively associated with the change in Hb concentration from 0 to 6 wk, after controlling for pretreatment energy expenditure. For every 1 g/l increase in Hb there was a 1.04-kcal decrease in energy expended.
Similarly, there was a significant positive relationship between
changes in Hb and absolute work rate during the time trial, after
controlling for initial work rate. As a result, changes in Hb were
positively associated (P = 0.09) with changes in efficiency
(i.e., the energy expended per watt of work performed).
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%O2 max and RER.
The iron-supplemented group significantly decreased
%O2 max, increased
average O2, and
tended to increase total O2 consumed during the time trial
(+4.2 ± 2.3 liters of O2, P = 0.08) compared with
baseline, whereas in the placebo group, these parameters remained
unchanged (Table 3). At 6 wk, both groups significantly decreased
average RER for the test and increased the absolute work rate. There
were no significant group differences in final %O2 max or final RER.
Multiple linear regression was used to further explore the
relationships between iron status and posttreatment %O2 max and RER,
controlling for pretreatment performance and potential confounders,
i.e., work rate and training. For
%O2 max, there was a
significant positive relationship with final sTfR ( = 1.14, P = 0.005) after controlling for training, pretreatment %O2 max, and initial
sTfR (equation not shown), indicating that for each 1 µg/l decrease
in sTfR, there was a 1.14% decrease in %O2 max during the
final time trial.
Physical performance during the final 5 km.
Because the effect of supplementation was greatest in the time to
complete the final 5-km segment of the time trial (Fig. 1), the
metabolic responses during this portion of the test were analyzed
separately (Table 7). This was done to test
for group differences that may not have been evident when the entire
15-km test was analyzed as a whole. However, the results for the final 5 km were similar to those for the entire test. Both groups
significantly decreased RER and energetic efficiency during the last 5 km in the posttest compared with baseline. The iron-supplemented group significantly increased average
O2, decreased
%O2 max, and increased
the rate of energy expenditure (i.e., kcal/min) in the posttest
compared with baseline.
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Initial iron status and adaptation to training.
Initial iron status modified the effect of iron supplementation on
adaptation to training. That is, there were significant interactive
effects between supplementation and initial sTfR concentrations on
changes in physical performance. The effect of supplementation to
decrease 15-km time (supplementation by initial sTfR interaction P = 0.18) and
%O2 max
(supplementation by initial sTfR interaction P = 0.03) and to
increase absolute work rate (supplementation by initial sTfR
interaction P = 0.17) was greater in women with lower initial
tissue iron stores. This result is similar to the interactive effect
between initial sTfR and supplementation on final sTfR described above.
Lactate.
Changes in serum lactate over the course of the 15-km time trial are
shown in Table 8. As expected, lactate
levels increased ~2.5-fold above the pretest value after the first 5 km of the time trial and remained elevated for the duration of the
test. Serum lactate was significantly reduced in the posttreatment time trial at four of the five time points in both groups (i.e., week 0 vs. week 6). There were no differences between the
treatment groups in pretreatment lactate levels (i.e., at week
0), nor were there significant differences during the posttreatment
trial after controlling for pretreatment and pretest lactate and work
rate during the final time trial test.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Improvements in endurance demonstrate that the training regimen employed in this study was adequate to induce physiological adaptation. Likewise, the supplementation regimen effectively improved iron status. After 3 wk of iron supplementation, sFer, sFe, and TS increased significantly from baseline in the iron-treated group and were significantly greater than in the placebo group. sTfR improved significantly after 6 wk of supplementation and was significantly reduced compared with placebo.
Iron supplementation enhanced the favorable adaptive response to training, as evidenced by a greater improvement in time to finish the 15-km time trial than with the placebo (Table 3). The greater improvement in the supplemented group was due to faster times in the second and third 5-km segments of the test, suggesting that these women were better able to sustain the workload at the end of the time trial and thus had increased their endurance capacity (Fig. 1). Furthermore, the plausibility that the supplementation effect on time to complete the time trial was due to changes in iron status was substantiated by linear regression analysis. This analysis demonstrated that the supplementation effect could be partially attributed to improvements in sFer and, to a lesser extent, in Hb (Table 4). This is consistent with the significant, positive association between change in endurance time and sFer in runners who maintained their usual training reported by Rowland et al. (25).
Although time to finish the 15-km time trial was significantly improved
with iron supplementation, there were no significant differences in
other measures of physical performance assessed during the time trial
test. The training regimen employed in this study produced significant
improvements in fitness that may have overridden any additional
benefits of iron supplementation. For example, LaManca and Haymes (16)
found a 3% decrease in
%O2 max during a
time-to-exhaustion endurance test after 8 wk of iron supplementation in
women with mild anemia; in the present study, %O2 max was decreased
~5% in the placebo group after 4 wk of training. Furthermore,
studies in rats have shown that iron deficiency does not obviate the
ability to respond to endurance exercise via non-iron-dependent
mechanisms (e.g., cardiovascular improvements) (31).
Multiple linear regression analysis showed that changes in iron status
were related to changes in physical performance independent of the
supplementation effect. Decreases in sTfR were positively associated
with improvements in
%O2 max, suggesting
increased efficiency of O2 utilization at the tissue level
with improved tissue iron status. This finding is consistent with
tissue iron, i.e., muscle oxidative capacity, being a limiting factor
in endurance capacity (8, 30, 31).
The women in this study were not anemic on the basis of a cutoff of Hb
>120 g/l. However, multiple regression analysis demonstrated that
energetic efficiency was improved with increases in Hb. Improvements in
Hb resulted in decreased energy expenditure, increased work rate, and
increased efficiency during the time trial (Table 6). Zhu and Haas (34)
found a similar functional anemia in untrained women with Hb >120
g/l, evidenced by negative associations between Hb and time,
%O2 max, and lactate
during the same 15-km time trial protocol used in this study. That is,
women with Hb >120 g/l may still be functionally anemic, having an Hb
concentration that is not sufficient for optimal physical performance
in stressful situations such as a 15-km time trial. The potential for
functional anemia is greater in the present study because of the 4-wk
aerobic training regimen, which may further increase the demand for
greater O2-carrying capacity (i.e., Hb) and tissue iron.
Studies by Magazanik et al. (20) and LaManca and Haymes (16)
demonstrating increases in Hb with iron supplementation and
significant, positive associations between changes in Hb and
O2 max in physically
active women who were not anemic (i.e., Hb >120 g/l) also support a
functional anemia associated with training.
Investigations of the effect of iron supplementation on blood lactate response during sustained submaximal exercise are equivocal and depend on the severity of the iron deficiency, level of exertion during the test, and fitness level of the subjects. LaManca and Haymes (16) reported a significant decrease in lactate in iron-supplemented women after an endurance test compared with placebo, whereas Klingshirn et al. (15) found no significant supplement effect on posttest lactate. The discrepancy may be attributed to differences in initial iron status between the two studies. The athletes in the study by LaManca and Haymes had lower initial Hb, which significantly improved with supplementation, whereas Hb was unchanged by supplementation in the study by Klingshirn et al. In the present study, no effect of iron supplementation on blood lactate was found during or after the time trial, nor was Hb changed due to supplementation. Another possible explanation for the lack of supplementation effect on lactate during the time trial is the large training effect (lactate decreased ~20% in the placebo group; Table 8) which may have obscured any additional supplementation effect.
In conclusion, we have demonstrated that iron supplementation enhances favorable physiological adaptation to endurance training and thus increases endurance capacity in iron-depleted, nonanemic women. Furthermore, associations between improved Hb, sFer, and sTfR status and physical performance during prolonged, submaximal exercise suggest that tissue iron stores and, to a lesser extent, O2-carrying capacity mediate the adaptation to aerobic training. These results are relevant for exercising young women whose dietary patterns and physical activity levels increase their risk of iron deficiency and suggest that repletion of iron stores may maximize the benefits of aerobic training.
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ACKNOWLEDGEMENTS |
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We gratefully acknowledge the assistance of Linda Bennett, Jackie Cohen, and Nazaneen Grant.
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FOOTNOTES |
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This work was supported in part by the Mead Johnson Research Fund and National Institute of Child Health and Human Development Training Grant HD-07331.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: J. D. Haas, Div. of Nutritional Sciences, 127 Savage Hall, Cornell University, Ithaca, NY 14853-6301 (E-mail: jdh12{at}cornell.edu).
Received 19 June 1999; accepted in final form 27 October 1999.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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1.
Aker, R.,
and
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P = 0.02.