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Original Research Communication |
1 From the Division of Nutritional Sciences, Cornell University, Ithaca, NY.
2 Supported by a grant from the Mead Johnson Research Fund and by NIH Training Grant 08-T32 DK07158.
3 Reprints not available. Address correspondence to JD Haas, Savage Hall, Cornell University, Ithaca, NY 14853. E-mail: jdh12{at}cornell.edu.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Objective: We investigated the effects of iron supplementation on adaptation to aerobic training among marginally iron-depleted women. We hypothesized that iron supplementation for 6 wk would significantly improve iron status and maximal oxygen uptake (
O2max) after 4 wk of concurrent aerobic training.
Design: Forty-one untrained, iron-depleted, nonanemic women were randomly assigned to receive either 50 mg FeSO4 or a placebo twice daily for 6 wk in a double-blind trial. All subjects trained on cycle ergometers 5 d/wk for 4 wk, beginning on week 3 of the study.
Results: Six weeks of iron supplementation significantly improved serum ferritin and serum transferrin receptor (sTfR) concentrations and transferrin saturation without affecting hemoglobin concentrations or hematocrit. Average O2max and maximal respiratory exchange ratio improved in both the placebo and iron groups after training; however, the iron group experienced significantly greater improvements in O2max. Both iron-status and fitness outcomes were analyzed after stratifying by baseline sTfR concentration (> and 
8.0 mg/L), which showed that the previously observed treatment effects were due to iron-status and fitness improvements among subjects with poor baseline iron status.
Conclusions: Our findings strongly suggest that iron deficiency without anemia but with elevated sTfR status impairs aerobic adaptation among previously untrained women and that this can be corrected with iron supplementation.
Key Words: Iron deficiency without anemia • iron depletion • women • aerobic training • O2max • maximal oxygen uptake • serum transferrin receptors • serum ferritin
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Deficiency is classified in 3 stages according to severity: depletion, marginal deficiency, and anemia (3). Depletion is characterized by depleted iron stores with normal iron-dependent protein production and normal hemoglobin concentrations. Marginal deficiency is characterized by depleted iron stores, reduced iron-dependent protein production (eg, oxidative enzymes), and normal hemoglobin concentrations. Anemia, the most severe form of deficiency, is characterized by depleted iron stores, reduced hemoglobin concentrations, and reduced iron-dependent oxidative enzyme concentrations.
The functional consequences of anemia are well documented and include reductions in maximal work capacity, endurance, and voluntary activity (4). However, the functional consequences of marginal deficiency and depletion are not fully understood, despite their prevalence in the United States and worldwide.
Evidence from both animal and human studies suggests that marginal deficiency reduces endurance capacity (5–8). Moreover, findings from animal studies also suggest that iron deficiency may impair training adaptation (9–11). Findings from human studies examining this relation are equivocal (7, 8, 12).
Rowland et al (7) found that iron supplementation significantly enhanced iron status and endurance capacity but not maximal oxygen uptake (O2max) after training among highly trained (
O2max: 
51 mL•min-1•kg-1) high school runners. Jensen et al (12) found that 12 wk of iron supplementation resulted in slightly more improvement in O2max after training (iron group: 13.5%; placebo group: 5.4%) among 13 moderately active college-aged women; however, the difference between groups was not significant. The conclusions that can be drawn from these studies are limited because of the small margin for improvement among subjects in the former study and the small sample size in the latter.
Clearly, more research is needed to assess the effect of iron deficiency without anemia on adaptation to aerobic training. The goal of the present study was to determine whether marginal iron deficiency impairs the ability of nonanemic, previously untrained women to increase their aerobic capacity in response to 4 wk of aerobic training on a cycle ergometer. We hypothesized that 6 wk of iron supplementation would prevent deterioration in iron status resulting from training and significantly improve O2max after 4 wk of aerobic training.
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SUBJECTS AND METHODS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Study design
This study was a randomized, double-blinded, placebo-controlled intervention trial. Subjects were randomly assigned to receive either an iron supplement (50 mg FeSO4, 8 mg elemental Fe) or an identical placebo capsule twice daily for 6 wk. All supplements were prepared in our laboratory with the use of gelatin capsules (Apothecary Products, Inc, Minneapolis). The iron supplements contained ferrous sulfate plus lactose filler, and the placebo supplements contained only lactose filler. The mean (±SD) iron content of the capsules was determined to be 49.4 ± 4.2 mg from a random sample of 20 capsules. The subjects were instructed to consume the capsules with citrus juice to enhance iron absorption and with meals to reduce possible side effects. They were also instructed to avoid consumption of any other multivitamin or mineral supplements during the study period. The subjects recorded capsule ingestion, consumption of medication, illness, menstrual status, gastrointestinal symptoms, physical activity, and musculoskeletal problems in a daily log. The subjects and investigators were blinded to the group assignment until completion of the data collection.
The sample size (minimum of 22 women per group) was determined at the outset to provide a 90% probability of detecting a difference of 200 mL/min in final O2max at the 5% significance level, allowing for a 10% dropout rate. These estimates were based on previous findings that used a similar training regimen in unsupplemented women, in which O2max increased by 0.24 L/min with an SD of 0.24 L/min (13).
Training
Subjects trained 5 d/wk for 4 wk beginning on week 3 of the study. To ensure that the subjects understood and complied with the training protocols, the first training session of each week was supervised. All other training sessions were self-reported. Training was performed in the research laboratory on a cycle ergometer (Ergociser E-3200; Cateye Co, Ltd, Osaka, Japan) equipped with a heart rate monitor and digital output of cadence (rpm) and work (W). Training sessions included a 4-min warm-up at no resistance, followed by a 25-min cycling session divided between workloads to target 75% and 85% of the subjects' maximum heart rate (HRmax), and a 1-min cooldown. Over the 4 wk, time spent training at 75% HRmax decreased weekly from 20 to 10 min, with a corresponding increase in the duration of cycling at 85% HRmax. During the first week of training, the subjects cycled for 20 min at 75% HRmax followed by 5 min at 85% HRmax. In week 2, they cycled for 18 min at 75% HRmax and 7 min at 85% HRmax. By week 4 they cycled for 10 min at 75% HRmax and 15 min at 85% HRmax. The subjects recorded heart rate, average cadence, and work for each training session in a training log.
Prestudy habitual physical activity levels were assessed by a frequency questionnaire, which was analyzed by using a method described previously to obtain a physical activity score for each subject (14). This was done to validate similar habitual physical activity between groups after randomization. Subjects were asked to maintain the same nontraining activity level during the entire study period to ensure that the prescribed training regimen was the only additional source of training.
For all subjects, body composition and physical performance were measured immediately before and after the 6-wk treatment period. In addition, dietary macro- and micronutrient intakes were assessed from a 4-d dietary record. All dietary records were analyzed with the use of NUTRITIONIST IV version 4.10 (Hearst, San Bruno, CA) to quantify dietary iron intake.
Physiologic measurements
Exercise tests were conducted on a mechanically braked, 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 and distance (km) pedaled. Concentrations of oxygen and carbon dioxide in expired air were analyzed with Ametek gas analyzers (Pittsburgh); respiratory volume was analyzed with a Fitco Micro Flow respiratory pneumotachograph (Fitness Instrument Technologies, Farmingdale, NY). A Hans Rudolph breathing valve (Kansas City, MO) was used for all tests. Data output from the instruments was directed to an IBM 386 computer for breath-by-breath calculation of O2, carbon dioxide production (CO2), respiratory exchange ratio (RER, CO2/ O2), and minute ventilation. Heart rate was monitored throughout the tests with an electrocardiograph (Burdick, Milton, WI). Electrocardiogram leads were connected at sites V1 and V6 and between intercostals 3 and 4 on the right side of the rib cage.
Subjects were asked not to perform any strenuous physical activities 2 d before the exercise tests. To control for the effects of dietary intake before exercise testing, subjects were asked to start recording food intake 3 d before the pretreatment exercise testing and to continue through the last day of pretreatment testing. They were instructed to consume the same diet for pretreatment and posttreatment exercise tests. Subjects were instructed not to consume food or caffeinated beverages for 3 h before exercise testing.
O2max was measured by following a modification of the protocol described by McArdle and Magel (15) 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 20 W/ 2 min until 2 of the following criteria were met: O2 did not increase by >150 mL over the previous workload, RER reached 
1.10, and heart rate was within 10 beats of the age-predicted maximum (220 beats/min - age). Tests not fulfilling 2 of 3 of these criteria were repeated after a 10-min rest and water break, starting at the workload below the highest workload previously achieved.
Body size and composition were measured in the Human Body Composition Laboratory at Cornell University. Anthropometry (weight, height) was assessed by using standard procedures described in Lohman et al (16). Percentage body fat and fat-free mass (FFM) were assessed by densitometry, with the use of the technique described by Akers and Buskirk (17). The Siri equation adapted for females was used, assuming the sex-specific density of FFM to be 1096 g/L.
Iron-status measurements
Iron status was assessed from nonfasting blood samples taken at screening, baseline, midpoint (3 wk), and completion of iron treatment (6 wk). Because serum iron-status indicators are not immediately influenced by food intake, subjects did not fast before having their blood drawn. As a result of time and scheduling constraints, neither time of day at which samples were drawn (1000–1400) nor menstrual phase was standardized. However, any possible confounding effect either of these factors may have had on iron status was controlled for through randomization.
Hemoglobin and hematocrit were assayed in whole blood immediately after sample collection. To control for potential variation in assay conditions, all plasma and serum samples were frozen at -20°C for no more than 3 mo. Each subject's complete set of samples was then analyzed concurrently at the completion of the study.
Hemoglobin concentration was determined with the cyanomethemoglobin method described by van Assendelft and England (18) (Sigma Diagnostics, St Louis). Hematocrit was determined by using the microhematocrit method. Serum soluble transferrin receptor (sTfR) and serum ferritin were assessed by enzyme-linked immunosorbent assay according to the methods of Flowers et al (19, 20) with commercial kits (Ramco Laboratories, Houston). Transferrin saturation (TS) was determined from the ratio of serum iron to total-iron-binding capacity by using the method described by Persijn et al (21) (Sigma Diagnostics).
Statistical analysis
Data were examined to verify normality of distribution. Serum ferritin and FFM had skewed distributions, and statistical analyses were performed on natural-log-transformed data. Results are reported as means ± SEs. Independent Student's t test was used to test group differences at baseline; characteristics differing at the P < 0.20 significance level were considered potential confounders and were included in subsequent regression models.
Repeated-measures analysis of variance (ANOVA) was used to test group and time effects as well as group-by-time interactions for both iron-status and fitness outcomes. The Wilk's lambda test statistic was used for all repeated-measures analyses. Interactions were considered significant at P < 0.15, and main effects were considered significant at P < 0.05.
Repeated-measures models of iron-status responses included baseline, week 3, and posttreatment values, unless otherwise stated. Because fitness outcomes were measured only twice, all models included only baseline and posttreatment values. For analytic purposes, O2max was expressed as both L O2 consumed/min (absolute O2max) and as mL O2 consumed•kg FFM-1•min-1 (relative O2max). When baseline and final HRmax during fitness testing differed by >3 beats/min, a prediction equation was generated for the subject by regressing O2 on heart rate. For the test with the lower HRmax, O2max was then extrapolated up to the higher heart rate.
Interactive effects between baseline characteristics and supplementation were tested by using analysis of covariance (ANCOVA), which included appropriate interaction terms and covariates. The effects of changes in iron status on fitness variables were analyzed by including baseline and change terms in the specified model. Pearson's correlation was used to examine the relation between change in iron-status and change in fitness outcomes. Statistical analyses were performed by using JMP version 3.1.5. (SAS Institute, Inc, Cary, NC).
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RESULTS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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O2max data. The final sample included 19 subjects in the placebo group and 22 subjects in the iron group. Those who dropped out or were excluded were not significantly different in baseline body composition, iron status, or physical performance from those who completed the study.
Diet analysis
Data from 4-d dietary records showed that neither macro- nor micronutrient intakes significantly differed between groups before the study, and intakes were highly variable (data not shown). Dietary iron intake ranged from 4.38 to 23.19 mg/d, with the placebo group consuming an average of 14.8 ± 2.0 mg/d and the iron group consuming an average of 14.7 ± 1.1 mg/d. Intake of both enhancers and inhibitors of iron absorption also showed wide variability: 13.9–593.3 mg vitamin C/d, 151.5–1577.5 mg Ca/d, and 5.3–29.4 g dietary fiber/d.
Twelve subjects (7 placebo group, 5 iron group) did not report consuming meat in their 4-d dietary records, suggesting possible vegetarian diets. Diet analyses showed that these subjects tended to consume more dietary iron per day than did those who reported eating meat (18.68 ± 2.4 compared with 12.88 ± 0.16 mg; P = 0.055); no other differences were observed in micronutrient intake. As expected, the vegetarians also consumed more carbohydrates as a percentage of energy (67.25 ± 1.9% compared with 57.35 ± 1.3%; P < 0.0001) and less fat as a percentage of energy (19.58 ± 2.0% compared with 28.00 ± 1.4%; P = 0.002). To identify possible confounding, baseline iron status, anthropometry, and fitness measures were compared between vegetarians and nonvegetarians; no significant differences were observed.
Training
The total number of training sessions (placebo group, 19.7 d; iron group, 19.9 d) and total work performed (placebo group, 59805 ± 2621 W; iron group, 54625 ± 2094 W) did not differ significantly between groups, nor were there significant group differences in habitual physical activity (data not shown). Training compliance was confirmed by weekly meetings between the subjects and research staff, along with a daily training log in which subjects recorded their average heart rate, cadence, and ergometer resistance settings required to achieve the target heart rates.
Supplementation compliance
Supplementation compliance was assessed from a personal log in which subjects recorded the number of capsules taken daily. These data indicated a high rate of compliance (placebo group, 88.6%; iron group, 91.4%), and that compliance did not differ significantly between groups (placebo group, 74.4 ± 3.0 capsules; iron group, 76.8 ± 1.6 capsules). The frequency and severity of reported side effects due to supplementation was very low and did not differ significantly between groups.
Anthropometry
Anthropometric measurments are presented in Table 1
. No significant group-by-time, group, or time effects were observed for weight, height, or FFM during the study. Conversely, a significant group-by-time interaction was observed for percentage body fat. Mean percentage body fat decreased by 1.2 ± 0.6% in the placebo group and increased by 0.6 ± 0.5% in the iron group.
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. Significant group-by-time and time effects were observed for serum ferritin, serum iron, and TS. A significant group effect was also observed for serum ferritin. Finally, a significant time effect was observed for hematocrit. Hemoglobin and sTfR concentrations and total-iron-binding capacity did not significantly change in the Fe or placebo group during the study.
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. Significant group-by-time and time effects were observed for both absolute O2max and relative O2max. Mean absolute O2max increased over baseline by 0.17 ± 0.09 L/min in the placebo group and by 0.37 ± 0.06 L/min in the iron group. Mean relative O2max increased over baseline by 3.40 ± 2.0 mL•kg FFM-1•min-1 in the placebo group and by 8.54 ± 1.5 mL•kg FFM-1•min-1 in the iron group. A significant time effect for RERmax was also observed. Mean RERmax decreased from baseline by 0.06 ± 0.03 in the placebo group and by 0.12 ± 0.03 in the iron group. HRmax did not significantly change in either group during the study.
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The analyses showed that indeed subjects with the most depleted tissue-iron status (highest sTfR concentrations) experienced the greatest improvements in both sTfR and O2max (Table 4, models 1 and 2). The predicted change in sTfR concentration across the observed range of baseline sTfR concentrations is depicted in Figure 1; the regression equation presented in model 1 was used for these data. The data show that there were no group differences in sTfR improvement among subjects who began the study with low sTfR concentrations, whereas large group differences occurred among subjects who began with high sTfR concentrations. The predicted change in relative O2max across baseline sTfR concentrations is shown in Figure 2; the regression equation presented in model 2 produced these data. The data show that subjects who began with higher sTfR concentrations and received iron supplements experienced the largest improvements in O2max. None of the other indicators of iron status yielded significant interactions with the supplementation group.
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O2max (Table 4
, models 3 and 4). Because the purpose of this study was to examine the relation between iron status and aerobic adaptation, we decided to further explore the relation between baseline sTfR status and responses to treatment by using stratified analyses. To maximize the likelihood that subjects in the upper stratum were truly tissue-iron deficient (normal range: 2.8–8.5 mg/L), and to maintain an adequate sample size within each stratum, we chose an sTfR cutoff value of 8.0 mg/L (22). The lower stratum comprised 12 subjects from the placebo group and 15 from the iron group. The upper stratum comprised 7 subjects from the placebo group and 7 from the iron group. Results from the stratified analyses follow.
Analyses stratified by baseline sTfR
Baseline subject characteristics
Baseline characteristics were compared across sTfR strata to ensure that only iron status differed among those who began the study with low or high sTfR concentrations; no significant differences were observed across strata for anthropometry, fitness, or training.
Anthropometry across sTfR strata
Stratifying the data by sTfR concentration showed significant group-by-time interactions for both weight (P = 0.02) and percentage body fat (P = 0.01) among subjects who began the study with low baseline sTfR concentrations. A significant time effect was observed for weight (P = 0.04) among subjects with high baseline sTfR concentrations. These findings suggest that the group-by-time interaction observed in the analysis of the complete sample was due to differences between the iron and placebo groups in the low baseline sTfR stratum. To control for potential confounding, changes in anthropometric measures were included in all subsequent regression analyses of the lower sTfR stratum.
Iron responses across sTfR strata
As expected, significant differences were observed in several iron-status indicators across sTfR strata. Subjects with high baseline sTfR concentrations (tissue-iron-deficient subjects) had significantly lower serum ferritin, serum iron, and TS values at baseline than did subjects with low baseline sTfR concentrations (tissue-iron-sufficient subjects). Hemoglobin concentration, hematocrit, and total-iron-binding capacity did not differ significantly across strata.
Iron-status results for subjects with high baseline sTfR concentrations are presented in Table 5. Among these subjects, significant group-by-time and time effects were observed for serum ferritin and TS. A significant group effect was also observed for serum ferritin, and a significant time effect was observed for serum iron. When only baseline and final values were included in the repeated-measures ANOVA model, a significant group-by-time interaction (P = 0.05) and time effect (P = 0.03) were observed for sTfR. No group-by-time or group effects were observed among subjects with low baseline sTfR concentrations; however, a significant time effect was observed for hematocrit, which explains the effect observed in the complete sample (data not shown).
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Fitness responses across sTfR strata
Stratified fitness responses are presented in Table 6. Significant group-by-time interactions were present for absolute and relative O2max and for RERmax among subjects in the upper sTfR stratum. These findings are similar to the iron-status results and suggest that the main effects observed in the complete sample were due to differential improvements between subjects in the placebo and iron groups with high baseline sTfR concentrations.
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O2max and for RERmax, suggesting that training did improve fitness among these subjects. Finally, there was also a significant group effect for relative O2max, showing that the O2max differences both at baseline and after treatment (placebo group > iron group) were significant.
Reassessment of interactions
Because significant interactions were observed for the complete sample (Table 4), we examined whether baseline characteristics altered responses to treatment within each of the sTfR strata. No significant interactions on either iron-status or fitness outcomes were observed between supplementation group and baseline iron status, fitness, or anthropometry.
Plausibility
To assess the plausibility of our findings that improvements in iron status mediated the greater improvements in fitness among subjects in the iron group, we examined correlations between changes in iron status and changes in fitness, stratified by baseline sTfR. Results from this analysis are presented in Table 7. These data show that changes in iron status were unrelated to changes in O2max (absolute or relative) or RERmax among subjects who began with low sTfR concentrations, whereas improvements in iron status were significantly related to improvements in fitness among subjects who began with high sTfR concentrations. sTfR and serum iron concentrations and TS were highly correlated with improvements in absolute O2max, and improvements in serum ferritin and iron concentrations and TS were highly correlated with improvements in relative O2max. Finally, improvements in serum iron concentrations and TS were also significantly correlated with improvements in RERmax. These findings suggest that indeed improvements in iron status may have partially mediated the observed improvements in fitness.
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O2max was found with the use of ANCOVA, as shown by model 1. As shown in model 2, accounting for improvements in TS partially accounted for the treatment effect on O2max, such that both the regression coefficient and the P value showed large changes. Before accounting for changes in TS (model 1), the least-squares mean for O2max improvement in the iron group was 6.93 mL•kg FFM-1•min-1, whereas after accounting for changes in TS (model 2), the least-squares mean for O2max improvement in the iron group was 3.23 mL•kg FFM-1•min-1, a 52.9% reduction. A significant group effect for RERmax when analyzed with the use of ANCOVA is illustrated in model 3. Accounting for improvements in TS partially accounted for the greater improvements in RERmax observed among subjects in the iron group, as shown by model 4. Before accounting for changes in TS, the least-squares-mean change in RERmax was –0.115, whereas after accounting for changes in TS, the least-squares-mean change in RERmax was –0.068, a 40.9% reduction.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Analysis of iron responses showed significant treatment effects for serum ferritin, serum iron, and TS. However, additional interaction analyses (Table 4) and subsequent stratified analyses (Table 5) showed that these treatment effects were driven by marked improvements among subjects with overt tissue-iron deficiency at baseline (ie, elevated sTfR concentrations). These findings confirm that subjects who began the study with higher sTfR concentrations were in fact more iron depleted, and as expected, they responded more to supplementation.
Significant treatment effects were also observed for O2max among the complete sample (Table 3), suggesting that iron supplementation can enhance aerobic adaptation among iron-depleted women. As with the treatment effects on iron status, additional analyses showed that these treatment effects on O2max were explained by improvements among subjects who were tissue-iron deficient at baseline. A significant effect was also observed for RERmax after stratifying the data by baseline sTfR, suggesting that the effect was masked when baseline tissue-iron status was not taken into account.
One possible explanation for the greater improvements in fitness among the more tissue-iron-depleted subjects is functional anemia, such that tissue depletion served as a proxy for impaired hemoglobin production. Although at baseline none of our subjects were anemic as defined by the conventional cutoff value (<120 g/L), hemoglobin production may have been impaired in the women who were more iron depleted, resulting in reduced oxygen-carrying capacity. However, if functional anemia were the underlying cause of this greater adaptive response, greater changes would be expected in both hemoglobin and fitness adaptation among those classified as more depleted at baseline and changes in hemoglobin would be correlated with changes in fitness. Our data do not support this explanation. Subjects with elevated sTfR concentrations at baseline did not experience greater improvements in hemoglobin during the study, nor were changes in hemoglobin correlated with improvements in fitness.
Alternatively, greater mitochondrial and myoglobin adaptations may explain why tissue-iron-deficient subjects experienced greater improvements in fitness. As previously discussed, training is known to increase iron-dependent mitochondrial constituents in the presence of sufficient cellular resources (24). Thus, those subjects who experienced the largest improvements in tissue-iron status were also more likely to experience the largest improvements in oxidative capacity.
A limitation of many of the previous studies examining the effect of iron deficiency on physical performance has been failure to conduct sufficient plausibility analyses. Although main-effect analyses indicate whether an experimental design was successfully implemented and had the intended effect, they cannot provide explanatory information. To show that the observed improvements in fitness were mediated by improvements in iron status, we examined the relation between changes in iron status and changes in fitness. First, we performed correlation analyses, followed by more rigorous regression analyses, which examined the effect of iron variables on treatment group regression coefficients and significance levels. All plausibility analyses were performed on stratified data because all the treatment effects were observed among subjects with elevated baseline sTfR concentrations.
As expected, assuming that our proposed mechanism is correct, changes in iron status (including serum ferritin, serum iron, and sTfR concentrations, and TS) were significantly associated with changes in both O2max and RERmax among subjects in the high sTfR stratum but not among subjects in the low sTfR stratum (Table 7). Although encouraging, these results are inherently limited because baseline status (ie, potential to benefit) was not accounted for in this analysis. The stronger evidence that improvements in iron status mediated improvements in fitness comes from the regression analyses presented in Table 8, which illustrate that accounting for improvements in TS explained the greater fitness adaptations observed in the iron group.
This study is the first to show that marginal iron deficiency without anemia, in the presence of overt tissue-iron deficiency, impairs aerobic adaptation among previously untrained women. These findings suggest that future research efforts would benefit from a more detailed characterization of the relation among iron-status indicators and from the development of a cutoff value for serum transferrin receptor that is sensitive to alterations in oxidative capacity.
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ACKNOWLEDGMENTS |
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REFERENCES |
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, iron group.
) in iron status and changes in maximal oxygen uptake (