Vol. 85, Issue 3, 1175-1186, September 1998
Training-induced alterations of carbohydrate metabolism in
women: women respond differently from men
Anne L.
Friedlander,
Gretchen A.
Casazza,
Michael A.
Horning,
Melvin J.
Huie,
Maria Francesca
Piacentini,
Jeffrey K.
Trimmer, and
George A.
Brooks
Exercise Physiology Laboratory, Department of Integrative
Biology, University of California, Berkeley, California 94720-3140
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ABSTRACT |
We examined the hypothesis that glucose flux was
directly related to relative exercise intensity both before
and after a 12-wk cycle ergometer training program [5
days/wk, 1-h duration, 75% peak
O2 consumption
(
O2 peak)] in
healthy female subjects (n = 17; age
23.8 ± 2.0 yr). Two pretraining trials (45 and 65% of
O2 peak)
and two posttraining trials [same absolute workload (65% of old
O2 peak)
and same relative workload (65% of new
O2 peak)] were
performed on nine subjects by using a primed-continuous infusion of
[1-13C]- and
[6,6-2H]glucose.
Eight additional subjects were studied by using
[6,6-2H]glucose.
Subjects were studied postabsorption for 90 min of rest and 1 h of
cycling exercise. After training, subjects increased
O2 peak by 25.2 ± 2.4%. Pretraining, the intensity effect on glucose kinetics was
evident between 45 and 65% of
O2 peak with rates of
appearance (Ra: 4.52 ± 0.25 vs. 5.53 ± 0.33 mg · kg
1 · min
1),
disappearance (Rd: 4.46 ± 0.25 vs. 5.54 ± 0.33 mg · kg
1 · min
1),
and oxidation (Rox: 2.45 ± 0.16 vs. 4.35 ± 0.26 mg · kg
1 · min
1)
of glucose being significantly greater
(P
0.05) in the 65% than
in the 45% trial. Training reduced
Ra (4.7 ± 0.30 mg · kg
1 · min
1),
Rd (4.69 ± 0.20 mg · kg
1 · min
1),
and Rox (3.54 ± 0.50 mg · kg
1 · min
1)
at the same absolute workload (P
0.05). When subjects were tested at the same relative workload,
Ra,
Rd, and
Rox were not significantly
different after training. However, at both workloads after training,
there was a significant decrease in total carbohydrate oxidation as
determined by the respiratory exchange ratio. These results show the
following in young women: 1)
glucose use is directly related to exercise intensity;
2) training decreases
glucose flux for a given power output;
3) when expressed as
relative exercise intensity, training does not affect the magnitude of
blood glucose flux during exercise; but
4) training does reduce total
carbohydrate oxidation.
stable isotopes; substrate utilization; exercise; glucose
metabolism; menstrual cycle; crossover concept; glycogen; lactate
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INTRODUCTION |
ALTHOUGH THE USE OF STABLE ISOTOPES has emerged as an
important methodology for studying substrate utilization in humans, few
studies have used tracers to investigate the effects of exercise intensity and endurance training on substrate flux rates in women. With
use of labeled palmitate, Poelhman et al. (41) demonstrated that free
fatty acid (FFA) flux and norepinephrine (NE) turnover increase at rest
in response to training in postmenopausal women. In addition, Rudy et
al. (43) used labeled glucose to demonstrate that glucose rate of
appearance (Ra) was reduced in
response to short-term estrogen treatment in amenorrheic
females. However, to our knowledge, there are currently no
published reports that used stable isotopes to measure the influence of
training on glucose flux in women during exercise. Because metabolite
concentration does not provide information about turnover rate and the
respiratory exchange ratio (RER) alone cannot be used to distinguish
between oxidation of blood borne and intracellular substrate sources, tracer studies can add valuable information on the use of specific substrates as energy sources.
Available data on gender differences in substrate utilization suggest
that, at rest or for given relative submaximal exercise intensities,
women oxidize a smaller proportion of carbohydrate (CHO) relative to
lipid than do men, as indicated by lower RER values (24, 46, 47).
Furthermore, decreased net glycogen utilization and lower blood lactate
concentrations have been observed in women compared with men while both
were exercising at similar relative intensities (39, 46). Whereas some
studies have shown gender differences at submaximal exercise, others
have shown that differences in RER between men and women disappear
during higher intensity exercise (16) or when the individuals are
highly trained (10, 15).
Some of the discrepancies in data comparing men and women may be
attributed to the difficulties involved with accurately matching subjects or with the timing of measurements relative to the menstrual cycle. The ovarian hormones (estrogen and progesterone) are potential effectors of substrate utilization (7, 22, 25, 26), and lower
circulating FFA, changed RER, and decreased ability to maintain blood
glucose during exercise in women who are in the luteal rather than the
follicular phase of the menstrual cycle have been reported (2, 20,
30). However, not all investigators have been able to
demonstrate differences related to cycle phase, and there is still
debate on whether there are menstrual variations in athletic performance (13, 31, 37).
Because of the limited information available on glucose kinetics in
women, the purpose of the present study was to examine the effects of
exercise intensity and training on glucose kinetics in female subjects
to evaluate the hypothesis that, as was demonstrated in men (14),
during hard exercise, blood glucose flux is not affected by training if
relative exercise intensity is considered. In addition, to determine
whether there are gender differences in the metabolic response to
exercise and endurance training, the present investigation provides
data for comparison with those from a similar study that used male
subjects.
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METHODS |
Subjects.
Eighteen healthy, nonsmoking, sedentary female subjects between the
ages of 18 and 35 yr were recruited from the University of California
campus community by flyers and mailings. Subjects were recruited in two
groups of nine. One subject withdrew from the study before posttraining
testing for reasons unrelated to the study protocol, leaving only eight
subjects in the second group. Each group followed the same protocol
except that different tracers were infused (see Tracer
protocol). Subjects were considered sedentary if they
had participated in <2 h of regular strenuous activity per week for
at least the last year and if they had a peak oxygen consumption
(
O2 peak) between 30 and 42 ml · kg
1 · min
1
as determined by a continuous-progressive maximal stress test on the
cycle ergometer. To qualify for participation in the study, subjects
were required to be diet and weight stable; to have a body fat percent
of <30%; to have a regular (28- to 35-day) menstrual cycle; to
not be pregnant, lactating, or taking oral contraceptives; and to be
disease and injury free as determined by medical questionnaire and
physical examination. All subjects provided informed consent, and the
study protocol was approved by the University of California Committee
for the Protection of Human Subjects (approval no. 93-12-45).
General experimental design.
After an initial screening interview and screening tests, two stable
isotope infusion trials were performed while the subjects pedaled on a
cycle ergometer for 1 h at 45 and 65% of
O2 peak (45UT and
65UT, respectively). All isotope trials were performed on
the women in the midfollicular phase of the menstrual cycle (between
days 5 and
10 from the first day of menses) and
after 36-48 h without exercise training. Isotope trials were
performed ~1 mo apart (1 cycle length), and the order of the trials
was randomized. Subjects began training 2 days after their second isotope trial and continued for 12 wk. The screening tests were repeated at 4, 8, and 12 wk of training. At ~8 and 12 wk of training, two more isotope trials were performed, one was at the same absolute workload that elicited 65% of pretraining
O2 peak (ABT), and the second was at a workload that elicited 65% of the new,
posttraining
O2 peak
or the same relative workload (RLT). The two posttraining trials were
also ~1 mo apart (again matched to the midfollicular phase of the
menstrual cycle) and randomized, and training was continued between the
two trials. In two cases, because of illness at 8 wk, the women
performed both isotope trials during the same cycle (12 wk). In
addition, two subjects performed both of their trials during second
cycle because the approach of the holiday season and the end of the
school term would have prevented completion of the final test at
12-15 wk (the timing problem was due to an increase in cycle
duration for 1 subject and a delay in recruitment for the other).
However, all subjects had at least 8 wk of training before the
posttraining trials began. The trials completed within the same cycle
were randomized and performed a minimum of 2 days apart but were still
conducted within the 5- to 10-day postmenses window of testing. The
exact duration of training varied slightly between subjects depending
on the length of each women's menstrual cycle. The timing of the
isotope trials was determined by the menstrual cycle phase, not the
duration of training. Throughout the training intervention, the
subjects were weighed daily and instructed to increase their energy
intake to compensate for increased energy expenditure and to ensure
weight and body fat stability. Because of the extensive work by Schutz
and associates (44), it was deemed necessary to prevent large changes
in total body or fat mass because changes in tissue mass are likely to
affect insulin action and the balance of substrate utilization,
independent of training.
Screening tests.
Body composition was determined both by skin-fold measurement and
underwater weighing.
O2 peak was
determined on an electronically braked cycle ergometer (Monark
Ergometric 829E) during a continuous, progressive protocol that
increased 25 or 50 W every 3 min until voluntary cessation. Respiratory
gases were analyzed (Ametek S-3A1 O2 and Beckman LB-2
CO2 analyzers) and recorded by an
online, real-time personal computer-based system every minute. Each
subject underwent two
O2 peak tests before
commencement of the study, and the tests were evaluated on maximal
heart rate, RER values (>1.15) and
O2 consumption
(
O2) uniformity to ensure a
true maximum effort both before and after training. Three-day dietary records were kept at the beginning, 4 wk into training, and before each
posttraining isotope trial to monitor the dietary composition and
quantity of intake for each subject. Dietary analysis of these records
was performed by using the Nutritionist III program
(N-Squared Computing, Salem, OR).
Tracer protocol.
All subjects were studied in a postabsorptive state in the morning, and
dietary intake was monitored for the 24 h immediately preceding each of
the four isotope trials. Dinner the night before each trial (12 h) was
selected by the individual subject and repeated before each trial. Each
subject was given a standardized snack (535 kcal: 17% protein, 53%
CHO, 30% fat) to consume before bed, 8-10 h before the trial, and
a standardized breakfast (320 kcal: 18% protein, 82% CHO; skim milk
and cereal) to consume 1-2 h before reporting to the laboratory.
In the first group of nine subjects, on the morning of the trial, a
catheter was placed in the radial artery for sampling, and an
antecubital venous catheter was placed in the opposite arm for primed
continuous infusion of the tracers for 90 min of rest and 1 h of
exercise. In the second group of nine subjects, "arterialized"
blood samples were obtained by using the "heated-hand vein"
technique. Because there was no significant difference in the data
obtained in the two groups of subjects, the glucose-flux data were
pooled for analysis. The first group of subjects received
[1-13C]glucose,
[6,6-2H]glucose
(D2-glucose),
and
[1,1,2,3,3,-2H]glycerol
(D5-glycerol)
while the second group received
[1-13C]palmitate,
[6,6-2H]glucose, and
[1,1,2,3,3,-2H]glycerol.
The glycerol and palmitate kinetics data will be reported separately.
After the collection of background blood and expired-air samples, a
priming bolus was given and the subjects rested semisupine for 90 min.
For both glucose isotopes, the priming doses were 125 times the resting
minute infusion rate. By using a Harvard Apparatus syringe pump (model
2400-01, Natick, MA), the resting infusion rate was set at 15 ml/h and
the continuous infusion cocktail contained 6.4 mg/ml each of
[1-13C]glucose and
[6,6-2H]glucose. Thus,
the resulting infusion rate was 1.6 mg/min for both isotopes. On
initiation of exercise, the infusion rate was increased to 45 ml/h (4.8 mg/min) for the two pretraining isotope trials and for the 65% of the
old
O2 peak
posttraining trial (same ABT). Because of the increased
metabolic flux anticipated for the 65% of the new
O2 peak posttraining,
the exercise infusion rate was increased to 60 ml/h (6.4 mg/min). We
chose our infusion rates based on the "steady-state" model that
emphasizes constant concentrations and isotopic enrichments to
facilitate the calculation of substrate kinetics. On the
basis of previous experiments, we selected infusion rates to yield
steady and comparable isotopic enrichments for all testing workloads.
Because of the smaller mean body size in the female subjects relative
to the previously used male subjects, the absolute infusion rates were
reduced for the women, but the relative relationship of infusion rates
between the trials was identical to that of the men (14). Arterial
samples were taken at 0, 75, and 90 min of rest and at 5, 15, 30, 45, and 60 min of exercise. All isotopes were obtained from Cambridge Isotope Laboratories (Woburn, MA), diluted in 0.9% sterile saline, pharmaceutically tested for sterility and pyrogenicity (Univerity of
California San Francisco School of Pharmacy, San Francisco, CA), and,
on the day of the experiment, passed through a 0.2-µm Millipore
filter (Nalgen, Rochester, NY).
At each of the blood-sampling time points, respiratory gas exchange was
determined by using the same system described above, and a sample of
expired air was collected in a 10-ml vacuum container to determine
13CO2
isotopic enrichment. The expired-air samples were stored
at room temperature until they were analyzed by using isotope ratio mass spectrometry (IRMS) by Metabolic Solutions (Merrimack, NH). Heart
rate was recorded throughout rest and exercise by using a Quinton Q750
electrocardiogram (Seattle, WA). Hematocrit was determined during the
last 15 min of rest and exercise to ensure that the measurements of
metabolite and hormone concentrations were not influenced by changes in
plasma volume.
Blood-sample collection and analysis.
Blood samples for the analysis of glucose and lactate concentration and
glucose isotopic enrichment were collected in 8% perchloric acid.
Plasma glucose concentration was determined by using a hexokinase enzymatic kit (Sigma Chemical, St. Louis, MO), and plasma lactate concentration was determined by using the method of Gutmann and Wahlefeld (19). Glucose isotopic enrichment was measured by using gas
chromatography-mass spectrometry (GCMS) (GC model 5890 series II and MS
model 5989A, Hewlett-Packard) of the pentaacetate derivative. Plasma
catecholamine concentrations were determined by using HPLC with
electrochemical detection (35). The details of the GCMS and
catecholamine analysis have been described extensively elsewhere (14).
Training protocol.
Subjects were required to exercise with a personal trainer in our
facility 5 days/wk for 1 h each day on the cycle ergometer. The
personal trainers were current undergraduate students in, or recent
graduates of, the Department of Human Biodynamics and, for the most
part, were competitive or recreational athletes themselves. During
the first 3 wk of training, exercise intensity was gradually increased from 50% of each participant's
O2 peak to 75% of
their
O2 peak.
Subjects were asked to warm up for 5 min and stretch before their hour
of exercise. The personal trainers used heart rate monitors and data
from periodic
O2 peak
tests to adjust workloads as the subjects improved. In addition to the
supervised training, subjects were required to exercise an additional 1 h on the weekend in any manner they desired. Subjects were weighed daily to ensure that they remained weight stable and were asked to
increase their caloric intake without altering their normal dietary
composition to match their increased energy expenditure.
Calculations and statistics.
The Ra, glucose rate of
disappearance (Rd), and glucose
metabolic clearance rate (MCR) were calculated by using equations defined by Steele and modified for use with stable isotopes (48); data
and calculations on men have been previously reported in detail
(14). Glucose rate of oxidation was calculated by using the IRMS analysis of the expired air samples (14). Energy derived from
glucose, total CHO, and lipid oxidation was calculated by using the
following equations
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(1)
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(2)
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(3)
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(4)
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where
O2 is in liters per minute,
glucose oxidation rate (Rox) is in
milligrams per kilogram per minute, and BW represents body weight in
kilograms. Numbers for kilocalories per liter oxygen and kilocalories
per gram CHO are standard values used in the field (6).
Data are represented as means ± SE. Calculations of steady-state
glucose kinetics were made by using the last two (75 and 90 min) and
three (30, 45, and 60 min) isotopic enrichment measurements obtained
during rest and exercise, respectively. Because the study was designed
with two groups of subjects receiving slightly different isotopes, the
number of subjects available for particular analyses differs throughout
this report. Calculations done by using the 13C glucose isotope (e.g.,
Rox, recycling rate) had nine
subjects, whereas all other data such as
Ra,
Rd, and metabolite concentrations were calculated with 17 subjects. To assess differences between the
four isotope trials, an analysis of variance with repeated measures was
used, and, where appropriate, the Fisher least significant difference
test was used for post hoc analysis. Comparisons between genders were
performed by using an unpaired two-tailed
t-test. Statistical significance was
set at
= 0.05.
 |
RESULTS |
Subject characteristics.
Pre- and posttraining characteristics of the 17 women who completed the
study are listed in Table 1. Subjects were
weight stable throughout the study period and did not lose a
significant amount of body fat whether measured by skinfolds or
underwater weighing.
O2 peak improved by
25.17 ± 2.43% over the training period. The workload
characteristics for the four isotope trials are presented in Table
2. Because the training-induced increase in
aerobic capacity, the posttraining trial at the same absolute workload
was equivalent to 50% of the subject's new
O2 peak. There was a
significant exercise intensity and training effect on average
exercising heart rate. Training resulted in a significantly reduced
heart rate during exercise at the same ABT but not RLT (Table 2).
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Table 2.
Ergometric parameters and physiological characteristics of female
subjects during rest and exercise, before and after training
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Plasma glucose concentration and glucose kinetics.
Blood glucose concentrations fell significantly
(P < 0.05) during the first 15 min
of exercise; however, there was no significant difference in blood
glucose concentration among the four trials during steady-state
exercise, and the concentration remained steady at ~4.6 mM throughout
exercise (Table 2). Glucose isotopic enrichments are shown in Fig.
1, A and
B, for
[6,6-2H]- and
[1-13C]glucose,
respectively. Ra increased
significantly between rest and exercise for all four of the exercise
conditions (Fig. 2). Furthermore, glucose
Ra was 22% higher during the last
30 min of exercise in the 65UT trial compared with the 45UT trial,
demonstrating a significant intensity effect pretraining. In addition,
there was an intensity effect posttraining, with
Ra 27% higher in RLT than ABT.
Also, when measured at the same ABT pre- and posttraining, Ra was significantly lower (17%)
after training. However, when measured at the same relative intensity,
there was no difference in the values pre- and posttraining.

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Fig. 1.
A: isotopic enrichments (IE) of
[6,6-2H]glucose over
time for the 4 isotope trials. Values are means ± SE for = 17 women. B: IE of
[1-13C]glucose over
time for the 4 isotope trials. Values are means ± SE for 9 women.
45UT, 45% pretraining trial; 65UT, 65% pretraining trial; ABT, same
absolute workload as 65UT; RLT, same relative workload (65% of
postraining peak O2
consumption).
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Fig. 2.
Rate of glucose appearance (Ra)
calculated from
[6,6-2H]glucose
over time for the 4 isotope trials. Time points are set as midpoint
between blood-collection times.
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Responses of Rd to exercise and
training were similar to those of
Ra and are presented as the
average of the last 15 min of rest and 30 min of exercise for the four
trials in Fig.
3A.
There was a significant intensity effect pre- and posttraining, as well as a training effect at the same ABT but not the same RLT. In addition,
because blood glucose concentration was not significantly different
between exercise trials, the relationship between MCR and exercise
intensity among the four trials tracked responses in
Rd (Fig.
3B). When
Rd was calculated as a percent of
total energy expenditure (RdE),
values were significantly lower during exercise vs. rest and lower at
65UT than at 45UT. After training, RdE tended to decrease at both the
same ABT and RLT, but the decrease did not reach significance (Fig.
3C).

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Fig. 3.
A: effect of exercise intensity and
training on the plasma glucose rate of disappearance (Rd).
Values are means ± SE of last 15 and 30 min for rest and exercise,
respectively, for 17 women.
Significantly different
from rest, P < 0.05. * Significantly different from 45UT,
P < 0.05. + Significantly different
from 65UT, P < 0.05. # Significantly different
from ABT, P < 0.05. B: effect of exercise intensity and
training on glucose metabolic clearance rate (MCR). Values are means ± SE of last 15 and 30 min for rest and exercise, respectively, for
17 women. Significantly different from rest,
P < 0.05. * Significantly different from 45UT,
P < 0.05. + Significantly different
from 65UT, P < 0.05. # Significantly different
from ABT, P < 0.05. C: effect of exercise intensity and
training on the plasma glucose rate of disappearance as a percentage of
total energy expenditure (RdE). Values are means ± SE
of last 15 and 30 min for rest and exercise, respectively, for 17 women. Significantly
different from rest, P < 0.05. * Significantly different from 45UT,
P < 0.05. D: effect of exercise intensity and
training on rate of glucose oxidation (Rox). Values are
means ± SE of last 15 and 30 min for rest and exercise,
respectively, for 9 women.
Significantly different
from rest, P < 0.05. * Significantly different from 45UT,
P < 0.05. + Significantly different
from 65UT, P < 0.05. E: effect of exercise intensity and
training on rate of glucose recycling. Values are means ± SE of
last 15 and 30 min for rest and exercise, respectively, for 9 women.
Significantly different
from rest, P < 0.05. F: effect of exercise intensity and
training on arterial lactate concentration ([Lactate]). Values are
means ± SE of last 15 and 30 min for rest and exercise,
respectively, for 17 women.
Significantly different
from rest, P < 0.05. * Significantly different
from 45UT, P < 0.05. + Significantly different
from 65UT, P < 0.05. # Significantly different
from ABT, P < 0.05.
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Rox and RER.
Rox was significantly higher
during all four exercise intensities compared with resting values.
Also, Rox demonstrated an intensity effect pretraining and a significant training effect at the
same ABT. Rox tended to be lower
at the same RLT after training, but the difference was not significant
(Fig. 3D).
RER values increased significantly in the transition between rest and
exercise. Values for RER during steady-state exercise were
significantly higher for the 65UT trial compared with the 45UT trial.
After training, RER was significantly lower during rest. RER was also
lower during steady-state exercise at both the same ABT and RLT
compared with the 65UT (Table 2). However, there were no differences
between the two posttraining workloads (ABT vs. RLT).
Glucose recycling rate and lactate concentrations.
Glucose recycling rate, calculated as the difference between the
Ra values as determined from
[1-13C]- and
[6,6-2H]-labeled
tracers, estimates the carbon recycling through gluconeogenesis from
three carbon precursors, predominantly lactate. The
recycling rate in the women tended to follow a pattern similar to
Ra; however, because of the high
SEs and low calculated values for recycling, none of the values were
significantly different between trials (Fig.
3E). Blood lactate concentrations
were significantly elevated at higher intensities both pre- and
posttraining and were significantly lower after training at both the
same ABT and RLT (Fig. 3F).
Ovarian hormone responses.
All of the isotopic measurements were performed between
days 5 and
10 of the menstrual cycle, with a mean
day of menses of ~6 for each trial (Table
3). During the early to midfollicular phase
of the menstrual cycle, both estrogen
(E2) and progesterone (P4) concentrations and
variability are lowest (17). We did not measure hormonal variations
throughout the cycle, but the resting values of
P4 and
E2 in our subjects were in the
normal range for the midfollicular phase (17). There was no training effect at rest on either P4 or
E2 levels.
P4 increased significantly between
rest and exercise for all but the 45UT trial, and, during exercise, a
pattern similar to that seen in the glucose flux data was observed
between trials; e.g., concentrations were higher during steady-state
exercise at 65UT vs. 45UT, and values for ABT, but not RLT, were lower
after training (Table 3). During exercise,
E2 increased significantly for all
exercise trials. In the first group of nine women,
E2 demonstrated a significant intensity and training effect (Table 3). However, the second group of
eight women did not show the same effect. The reason for this apparent
discrepancy between groups in E2,
but not P4, is unclear at this
time.
Catecholamine responses.
Concentrations of epinephrine (Epi) were significantly higher during
all four exercise trials than at rest, but they were not different
between any of the exercise intensities (Fig.
4A). NE
also was higher during exercise than rest, but, unlike Epi, NE
demonstrated both an increase with intensity pretraining, and a
decrease during both workloads after training (Fig.
4B).

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Fig. 4.
Comparison between epinephrine (A;
Epi) and norepinephrine (B)
concentrations in males and females before and after endurance
training. Values are means ± SE for each isotope trial for 9 men
and 15 women.
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Contributions from different fuel sources.
On the basis of the RER and average
O2 during rest and exercise
for the four isotope trials, the percent contributions of total CHO and
lipid were calculated. At rest, >50% of the energy was derived from
lipid sources. During exercise in all conditions, there was a shift to
a greater reliance on CHO with >50% of the energy coming from CHO
sources. A maximum of 73% of energy from CHO sources was obtained in
the 65UT trial and a minimum of 53% during the ABT trial (Table 2).
The caloric equivalents from the oxidation of blood glucose, other CHO,
and lipid fuel sources are presented for rest and the four isotope
trials in Fig. 5. Total energy expenditure
during exercise was 4.67, 6.63, 6.53, and 8.47 kcal/min for 45UT, 65UT,
ABT, and RLT, respectively.

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Fig. 5.
Contributions of energy from different substrate sources during rest
and exercise before and after training. SE and statistical symbols are
for total energy expenditure only. Values are for 9 subjects. CHO,
carbohydrate.
Significantly different
from rest, P < 0.05. * Significantly different from 45UT,
P < 0.05;
+ Significantly different
from 65UT, P < 0.05. # Significantly different
from ABT, P < 0.05.
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DISCUSSION |
Results of the present investigation on women corroborate earlier
studies demonstrating a direct relationship between exercise intensity
and blood glucose flux (27, 42). Furthermore, our results are
consistent with the hypothesis that
Ra and Rd are exponentially related to relative effort as given by percent
O2 peak in both
men and women (Fig.
6A).
Results of our study on the effects of training on glucose flux are
consistent with investigations that show training reduces glucose flux
for exercise of a given power output (5, 8). However, when expressed at
similar relative power outputs, our results obtained with use of a
longitudinal design differed from those obtained in men that used a
cross-sectional design (9). The pattern of glucose flux in response to
exercise intensity and training in women paralleled the pattern that we observed in men following a similar protocol (Fig.
6B) (14).

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Fig. 6.
Relationship of glucose rate of disappearance
(Rd) with relative
(A) and absolute
(B) exercise intensity for men and
women. Values are means ± SE for each isotope trial for 19 men and
17 women. O2 max,
maximal O2 consumption;
O2,
O2 consumption.
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We tested our subjects both at the same ABT and RLT after training.
Numerous studies have demonstrated that at given ABT, both short- and
long-term exercise training change the balance of substrate utilization
away from CHO toward lipid. In men, support for such a training effect
comes from observations that training decreases RER (8), increases
total fat oxidation (33), decreases glucose flux (14), and reduces the
rate of muscle glycogenolysis (23) during exercise at defined power
outputs. Although there are fewer data on women, observations of
decreased resting RER (41), decreased lactate concentrations during
exercise (15), and increased in vitro catecholamine stimulated adipose
cell lipolytic rate (34) after training can be interpreted to suggest a
similar CHO-sparing adaptation in women as well. However, to our
knowledge, no long-term endurance training studies using RER or stable
isotopes to investigate substrate utilization during exercise have been completed in women.
Few studies have tested subjects at the same RLT after training.
Inclusion of the measurements performed at the same RLT may provide
data that is more applicable to active adults as well as athletes in a
nonlaboratory setting. As athletes and others train and improve, they
are capable of performing at higher absolute as well as relative power
outputs. Several studies have indicated that highly trained men work at
high intensity levels and, therefore, rely predominantly on CHO
regardless of their muscle oxidative capacity (40). In one study by
Kjær et al. (27), who used male subjects, the glucose kinetics of
trained and untrained subjects were compared at maximal workloads. No
differences were observed in Rd
between groups, although elevated glucose concentrations in the trained
group resulted in lower MCRs. Another study by Coggan et al. (9)
compared male endurance athletes and untrained individuals for 30 min
of exercise at 80%
O2 peak and
showed no difference in Ra but a
lower Rd in the trained subjects.
The present data, obtained from a longitudinal study of women,
demonstrated that glucose flux was similar when measured at the same
relative intensity (65% of
O2 peak) before and
after endurance training.
Importance of menstrual cycle phase.
We tested all of our female subjects in the midfollicular phase of
their menstrual cycles to ensure lower and more consistent levels of
E2 and
P4 and thus to reduce the
variability of ovarian hormone impact on substrate utilization.
Estrogen can alter glucose metabolism directly by decreasing
gluconeogenesis and insulin-binding capacity (7), whereas
P4 has been shown to decrease
glucose uptake and oxidation in adipose tissue, decrease hepatic
gluconeogenesis, increase hepatic glycogen storage, decrease peripheral
insulin sensitivity, and increase insulin production by directly
affecting the pancreas (25). Alternatively, the ovarian hormones may
impact CHO utilization indirectly by biasing lipid metabolism toward FFA mobilization and oxidation by
E2 or FFA storage by
P4 (7, 25). Hackney et al. (20)
demonstrated elevated levels of lipid oxidation in women who were in
the midluteal phase of their menstrual cycles. The differences were
observed at rest and 35 and 65% of
O2 peak, but
at 75% of
O2 peak the
differences disappeared. Similarly, Graham et al. (18) showed
differences in FFA and lactate levels between amenorrheic and
eumenorrheic women during rest and exercise at 30% of maximum capacity
but not at 60 and 90% of maximum capacity (18). At higher intensities,
it is likely that glycolytic flux governs substrate selection and the
impact of mitigating factors such as menses, training, and nutritional status is reduced. Several investigators have shown that women in the
follicular phase of their menstrual cycle are more capable of
maintaining blood glucose levels during prolonged exercise (15, 46) or
after CHO-deficient diet (30) than are men. Ovarian hormones (and
androgens) may have a suppressive effect on hepatic gluconeogenesis
(30, 46); therefore, in terms of glucose metabolism, women may be more
similar to men during the luteal phase of the menstrual cycle. Because
we only measured our female subjects during the follicular phase of the
menstrual cycle, gender differences observed in this investigation may
not be as apparent in women studied throughout all phases of the
menstrual cycle.
Gender differences in substrate utilization.
Because there are inherent problems in matching subjects of different
genders, especially when using a cross-sectional design (e.g., problems
accounting for body composition, training status, maximal
O2, and relative vs. absolute
exercise intensity), it is difficult to obtain directly comparable data
on men and women. However, the longitudinal study design,
training intervention, and methodologies used in the present
investigation on women were identical to an earlier published training
study on glucose flux in men (14) and thus provide parallel information
for comparison. Although the glucose-flux data were similar (both in
magnitude and direction) to the data we obtained on men (Table
4), the magnitudes of total CHO and lipid
oxidation differed between genders. During rest and each
of the parallel workloads matched as percentage of
O2 peak, female
subjects tended to have lower RER values than did the men and the
values were significantly lower in all cases after training (Table 4).
Lower RER values in women compared with men during exercise at similar
relative intensities have been reported previously in cross-sectional
studies that used well-matched subjects (46, 47). Additionally, when
women and men are compared, the lower RER values for a given relative
workload in women, despite the similar magnitude of glucose flux values between genders in our data, suggest that a higher percentage of total
CHO oxidation could be obtained from blood glucose in women. Also, because the women were working at
substantially lower ABTs than were the men, the women had higher
glucose-flux values per unit energy expenditure than did the men (Table
4). Observations of decreased RER with similar or relatively greater
glucose flux in women are consistent with findings of decreased
glycogen utilization and decreased lactate levels in women exercising
at the same relative workloads as men (39, 46). We too observed lactate
levels that were lower in our female subjects than in the male subjects for a given relative exercise intensity (Table 4).
The mechanism for lower total CHO oxidation in women relative to men
has not yet been determined. Some investigators who have analyzed
biopsies of the vastus lateralus of training-matched men and women have
demonstrated that the women have a higher percentage of type I
(slow-oxidative) fibers and a higher ratio of oxidative to glycolytic
enzymes than do the men (29, 32, 38). These results may suggest that
women have greater capacity for muscle lipid oxidation than do men.
However, a more likely explanation comes from previous data showing men
to have higher circulating levels of Epi than do women at similar
relative intensities (46). Higher circulating Epi in men could increase
the rate of muscle glycogenolysis without increasing glucose uptake
(3). In addition, higher initial muscle glycogen concentration in men
could promote increased glycogenolysis and lactate production during
exercise (21). Our data demonstrated no gender difference in
catecholamines at rest or before training, but our male subjects did
have significantly higher concentrations of both Epi and NE during
exercise after training (see Gender differences in
training response). Thus the observed differences in
RER may have been influenced by differences in lactate production and
oxidation. Gender differences in receptor availability and affinity may
also be important in determining substrate utilization in response to
circulating hormone levels. For example, insulin-receptor binding was
shown to be greater and more similar to observations of binding in men
when women were in their follicular rather than luteal phase of the
menstrual cycle (1, 12). It is likely that even low levels of ovarian hormones may interact with other circulating hormones to modulate the
substrate response in a way that reduces glycogen utilization in women.
The rate of glucose recycling was significantly lower in women than in
men at rest and during exercise at all four workloads. A combination of
lower circulating lactate and catecholamine levels likely impacted the
differences in glucose recycling.
Gender differences in training response.
The major difference in training response between our male and female
subject was that, at the same RLT after training, women demonstrated a
significant reduction in RER, whereas the men did not. Because glucose
flux values were unchanged in both men and women at the same relative
intensity, the implication is that, in women, training had a greater
glycogen-sparing effect than in men for a given RLT. The reason for
such a gender difference is unclear, although it could result from
differences in the training-induced response of the sympathetic nervous
system. The endurance-training protocol that we used resulted in a
trend of elevated Epi levels in the men at both the same ABT and RLT
after training. In contrast, our female subjects showed no difference
in Epi levels and significantly reduced NE levels during exercise at
both workloads after training (Fig. 5). Others have shown
training-induced hypertrophy of the adrenal medulla in rats (45) and
increased capacity for Epi secretion in highly trained male athletes
(28). Why the sympathetic nervous system adapts differently to training
in women and men has yet to be determined.
Our female subjects improved their
O2 peak by 25.2%
overall, which is substantially greater than the increase of 9.4%
observed in our male subjects. It is possible that the larger
CHO-sparing effect after training in women (vs. men) was a result of
the greater training effect rather than differences in type of
adaptations between genders. The capacity to increase
O2 peak is dependent on
both the initial starting value and genetic disposition (4). The women
that were recruited for our study might have been more untrained
relative to the male subjects, who tended to be generally more active,
and thus the women may have been able to increase their maximum
capacity to a larger extent than their male counterparts. However,
O2 peak is more closely
related to central cardiovascular capacity and is not necessarily the
best indicator of endurance-training adaptations. Changes that impact
endurance capacity usually relate more to peripheral adaptations such
as increases in mitochondrial content (11). Because substrate
utilization is also closely related to peripheral adaptations, one
could argue that the endurance-training component was actually more
effective in the male subjects, because our male subjects exhibited a
larger decrease in glucose flux at a defined power output in response
to training (21%) than did our female subjects (17%). In addition,
short-term training studies that recorded a reduction in
Ra and an increase in whole body fat oxidation with no concomitant changes in
O2 peak provide evidence that large changes in maximum aerobic capacity are not critical to alter substrate selection (36).
Methodological considerations.
When measured at the same relative workload, both men and women
demonstrated a decline in Rox
(significant in men, trend in women), despite the similar flux values
pre- and posttraining. The discrepancy between
Rd and
Rox at the same relative workload in both men and women suggests increased nonoxidative disposal of
glucose after training that may be a result of increased cycling of
glycogen in nonworking muscles (J. Azevedo, J. K. Linderman, S. L. Lehman, and G. A. Brooks; unpublished observations).
However, an alternative explanation might be found in the equation used to calculate Rox. A correction
factor is used to account for retention of labeled
CO2 in the bicarbonate buffering
system. On the basis of previous research in our laboratory, a
correction factor (k) of 0.65 at
rest and 0.9 during exercise was used for the retention of CO2 in body pools. However,
differences in acid-base status related to gender or training-induced
changes in lactate concentration or the capacity of the bicarbonate
system are not accounted for in our calculations. Only a small
reduction in k after training (from
0.9 to 0.8 in women or from 0.9 to 0.75 in men) would have resulted in
the same values for pre- and posttraining
Rox values at the same RLT (Table
5). An increased retention of
label after training is consistent with the physiology of training (5), but further research is needed to determine the magnitude of the adjustment.
View this table:
[in this window]
[in a new window]
|
Table 5.
Glucose oxidation rates in men and women pre- and posttraining at same
relative workload calculated using different correction factors
|
|
In addition to changes with training, our overall values for blood
Rox were lower than anticipated
during rest (~0.56
mg · kg
1 · min
1),
given the glucose-flux values in the range of 2.8-3.0
mg · kg
1 · min
1.
Therefore, at rest only ~20% of
Rd was oxidized. Although we primed the glucose pool before commencing the resting infusion, we did
not specifically prime the bicarbonate pool. Such a low oxidation rate
could be explained by additional metabolically generated labeled
CO2, not accounted for by the
correction factor, being trapped as bicarbonate. During exercise the
percentage of Rd oxidized ranged
from 56 to 80% for the women and from 72 to 93% for the men. Although
there is less label retention during exercise, the values could still
be impacted by overall label retention or by gender-based differences
in retention.
Whole body vs. working muscle substrate use.
The present study presents some of the first isotopic data available on
glucose flux in women. However, the data can only provide insights into
whole body adaptations to training. It is possible that the reduction
in glucose flux at the same absolute workload after training is not a
response that is localized in the working muscle. Data that are
currently emerging from our laboratory (by means of measurements of
arteriovenous differences for O2, CO2, and
metabolites across the working limbs of male subjects) suggest that, in
men, the respiratory quotient of working muscle is close to 1.0 and
does not change with training, despite a significant reduction in whole
body RER (B. C. Bergman, G. E. Butterfield, E. E. Wolfel, G. A. Casazza, G. D. Lopaschuk, and G. A. Brooks, unpublished
observations). The implication is that the working muscle
oxidizes CHO regardless of intensity or training and that whole body
tracer studies measure adaptations from active as well as nonactive
tissues. Such adaptations are important in that they assist with the
ability of the body to provide working muscle with a readily available
CHO supply, but caution should be used when attributing changes in
whole body measurements to adaptations in working muscle.
Summary and conclusions.
The results of this study support the hypothesis that glucose flux in
women is related to relative exercise intensity both before and after
training. After training, we observed a significant decrease in glucose
flux and oxidation (Ra,
Rd, MCR,
Rox) at the same ABT but not at
the same RLT. Although the results of the glucose-flux data were
consistent with those we observed in men (14), the response of total
CHO oxidation to endurance training differed between men and women when
measured at the same relative intensity. Women had a more exaggerated
substrate shift toward lipid use than did the men in response to
similar training protocols. Therefore, caution should be used when
combining substrate utilization data obtained from both genders.
Furthermore, because Rd is as high
but pulmonary RER is lower in women than men during exercise at similar
relative intensities, it appears that women rely less on muscle
glycogen and lactate during exercise than do men. The glucose flux data
in this investigation are interpreted to mean the following in women:
1) glucose use is directly related
to exercise intensity; 2) training
decreases glucose flux for a given power output; and
3) when expressed as
relative exercise intensity, training does not affect blood glucose
flux. Our results are consistent with those of others showing decreased
CHO oxidation in exercising women compared with men.
 |
ACKNOWLEDGEMENTS |
We thank Gail Butterfield for consultation on all aspects
of the study. We also thank Katie Milano, Robin Rynbrandt, Tam Ho, Tani
Brown, Matt Inlay, Catherine Chen, and Chung Lu, who provided much of
the laboratory support throughout the study. We are also grateful to
all of the student trainers who assisted with the subject training and
testing.
 |
FOOTNOTES |
This work was supported by National Institute of Arthritis and
Musculoskeletal and Skin Diseases Grant AR-42906.
Present address of A. L. Friedlander: General Research, Education, and
Clinical Center, 182B, Palo Alto Veterans Affairs Health Care System,
3801 Miranda Ave., Palo Alto, CA 94304 (E-mail:
friedlan{at}leland.stanford.edu).
Address for reprint requests: G. A. Brooks, Dept. of Integrative
Biology, 3060 Valley Life Science Bldg., Univ. of California, Berkeley,
Berkeley, CA 94720-4480.
Received 17 December 1997; accepted in final form 24 April 1998.
 |
REFERENCES |
1.
Bertoli, A.,
R. De Pirro,
A. Fusco,
A. V. Greco,
and
R. Magnatta.
Differences in insulin receptors between men and menstruating women and influence of sex hormones in insulin binding during menstrual cycle.
J. Clin. Endocrinol.
50:
246-250,
1980[Abstract].
2.
Bonen, A.,
F. J. Haynes,
W. Watson-Wright,
M. M. Sopper,
G. N. Pierce,
M. P. Low,
and
T. E. Graham.
Effects of menstrual cycle on metabolic responses to exercise.
J. Appl. Physiol.
55:
1506-1513,
1983[Abstract/Free Full Text].
3.
Bonen, A.,
L. A. Megeney,
S. C. McCarthy,
J. C. McDermott,
and
M. H. Tan.
Epinephrine administration stimulates GLUT 4 translocation but reduces glucose transport in muscle.
Biochem. Biophys. Res. Commun.
187:
685-691,
1992[Medline].
4.
Bouchard, C.,
and
L. Perusse.
Heredity, activity level, fitness, and health.
In: Physical Activity, Fitness, and Health, edited by C. Bouchard,
R. J. Shepard,
and T. Stevens. Champaign, IL: Human Kinetics, 1994, p. 106-118.
5.
Brooks, G. A.,
and
C. M. Donovan.
Effect of endurance training on glucose kinetics during exercise.
Am. J. Physiol.
244 (Endocrinol. Metab. 7):
E505-E512,
1983[Abstract/Free Full Text].
6.
Brooks, G. A.,
T. D. Fahey,
and
T. P. White.
Exercise Physiology: Human Bioenergetics and Its Applications. Mountain View, CA: Mayfield, 1996.
7.
Bunt, J.
Metabolic actions of estradiol: significance for acute and chronic exercise responses.
Med. Sci. Sports Exerc.
22:
286-290,
1990[Medline].
8.
Coggan, A. R.,
W. M. Kohrt,
R. J. Spina,
D. M. Bier,
and
J. O. Holloszy.
Endurance training decreases plasma glucose turnover and oxidation during moderate-intensity exercise in men.
J. Appl. Physiol.
68:
990-996,
1990[Abstract/Free Full Text].
9.
Coggan, A. R.,
C. A. Raguso,
B. D. Williams,
L. S. Sidossis,
and
A. Gastaldelli.
Glucose kinetics during high-intensity exercise in endurance-trained and untrained humans.
J. Appl. Physiol.
78:
1203-1207,
1995[Abstract/Free Full Text].
10.
Costill, D. L.,
W. J. Fink,
L. H. Getchell,
and
J. L. Ivy.
Lipid metabolism in skeletal muscle of endurance-trained males and females.
J. Appl. Physiol.
47:
787-791,
1979[Abstract/Free Full Text].
11.
Davies, K. J. A.,
L. Packer,
and
G. A. Brooks.
Biochemical adaptation of mitochondria, muscle, and whole-animal respiration to endurance training.
Arch. Biochem. Biophys.
209:
539-554,
1981[Medline].
12.
De Pirro, R.,
A. Fusco,
A. Bertoli,
A. V. Greco,
and
R. Lauro.
Insulin receptors during menstrual cycle in normal women.
J. Clin. Endocrinol. Metab.
47:
1387-1389,
1978[Abstract].
13.
Dibrezzo, R.,
I. Fort,
and
B. Brown.
Relationships among strength, endurance, weight and body fat during three phases of the menstrual cycle.
J. Sports Med. Phys. Fitness
31:
89-94,
1991[Medline].
14.
Friedlander, A. L.,
G. A. Casazza,
M. A. Horning,
M. J. Huie,
and
G. A. Brooks.
Training-induced alterations of glucose flux in men.
J. Appl. Physiol.
82:
1360-1369,
1997[Abstract/Free Full Text].
15.
Friedmann, B.,
and
W. Kindermann.
Energy metabolism and regulatory hormones in women and men during endurance exercise.
Eur. J. Appl. Physiol.
59:
1-9,
1989.
16.
Froberg, K.,
and
P. K. Pedersen.
Sex differences in endurance capacity and metabolic response to prolonged, heavy exercise.
Eur. J. Appl. Physiol.
52:
446-450,
1984.
17.
Goldfien, A.,
and
S. E. Monroe.
Ovaries.
In: Endocrinology (3rd ed.), edited by F. S. Greenspan. Norwalk, CT: Appleton & Lange, 1991, p. 442-490.
18.
Graham, T. E.,
J. P. Van Dijk,
M. Viswanathan,
K. A. Giles,
A. Bonen,
and
J. C. George.
Exercise metabolic responses in men and eumenorrheic and amenorrheic women.
In: Biochemistry of Exercise VI, edited by B. Saltin. Champaign, IL: Human Kinetics, 1986, p. 2227-2228.
19.
Gutmann, I.,
and
A. W. Wahlefeld.
L-(+)-Lactate determination with lactate dehydrogenase and NAD.
In: Methods of Enzymatic Analysis (2nd ed.), edited by H. Bergmeyer. New York: Academic, 1974, p. 1464-1468.
20.
Hackney, A. C.,
M. A. McCracken-Compton,
and
B. Ainsworth.
Substrate responses to submaximal exercise in the midfollicular and midluteal phase of the menstrual cycle.
Int. J. Sport Nutr.
4:
299-308,
1994[Medline].
21.
Hargreaves, M.,
G. McConell,
and
J. Proietto.
Influence of muscle glycogen on glycogenolysis and glucose uptake during exercise in humans.
J. Appl. Physiol.
78:
288-292,
1985[Abstract/Free Full Text].
22.
Hatta, H.,
Y. Atomi,
S. Shinohara,
Y. Yamamoto,
and
S. Yamada.
The effects of ovarian hormones on glucose and fatty acid oxidation during exercise in female ovariectomized rats.
Horm. Metab. Res.
20:
609-611,
1988[Medline].
23.
Hurley, B. F.,
P. M. Nemeth,
W. H. Martin,
J. M. Hagberg,
G. P. Dalsky,
and
J. O. Holloszy.
Muscle triglyceride utilization during exercise: effect of training.
J. Appl. Physiol.
60:
562-567,
1986[Abstract/Free Full Text].
24.
Jansson, E.
Sex differences in metabolic response to exercise.
In: Biochemistry of Exercise VI, edited by B. Saltin. Champaign, IL: Human Kinetics, 1986, p. 228-229.
25.
Kalkhoff, R. K.
Metabolic effects of progesterone.
Am. J. Obstet. Gynecol.
142:
735-738,
1982[Medline].
26.
Kendrick, Z. V.,
C. A. Steffen,
W. L. Rumsey,
and
D. I. Goldberg.
Effect of estradiol on tissue glycogen metabolism in exercised oopherectomized rats.
J. Appl. Physiol.
63:
492-496,
1987[Abstract/Free Full Text].
27.
Kjær, M.,
P. A. Farrell,
N. J. Christensen,
and
H. Galbo.
Increased epinephrine response and inaccurate glucoregulation in exercising athletes.
J. Appl. Physiol.
61:
1693-1700,
1986[Abstract/Free Full Text].
28.
Kjær, M.,
and
H. Galbo.
Effect of physical training on the capacity to secrete epinephrine.
J. Appl. Physiol.
64:
11-16,
1988[Abstract/Free Full Text].
29.
Komi, P.,
and
J. Karlsson.
Skeletal muscle fibre types, enzyme activities and physical performance in young men and women.
Acta Physiol. Scand.
103:
210-218,
1978[Medline].
30.
Lavoie, J. M.
Sex differences in epinephrine and blood glucose response to exercise.
In: Biochemistry of Exercise VI, edited by B. Saltin. Champaign, IL: Human Kinetics, 1986, p. 229-230.
31.
Lebrun, C. M.,
D. C. McKenzie,
J. C. Prior,
and
J. E. Taunton.
Effects of menstrual cycle phase on athletic performance.
Med. Sci. Sports Exerc.
27:
437-444,
1995[Medline].
32.
Lundberg, B.,
M. Esbjornsson,
G. Hedberg,
and
E. Jansson.
Skeletal muscle fiber types and physical performance. A 10 year follow up study.
Clin. Physiol.
5:
167,
1985.
33.
Martin, W. H.,
G. P. Dalsky,
B. F. Hurley,
D. E. Mathews,
D. M. Bier,
J. M. Hagberg,
M. A. Rogers,
K. D. S,
and
J. O. Holloszy.
Effect of endurance training on plasma free fatty acid turnover and oxidation during exercise.
Am. J. Physiol.
265 (Endocrinol. Metab. 28):
E708-E714,
1993[Abstract/Free Full Text].
34.
Mauriege, P.,
D. Prud'Homme,
M. Marcotte,
M. Yoshioka,
A. Tremblay,
and
J. P. Despres.
Regional differences in adipose tissue metabolism between sedentary and endurance-trained women.
Am. J. Physiol.
273 (Endocrinol. Metab. 36):
E497-E506,
1997[Abstract/Free Full Text].
35.
Mazzeo, R. S.,
and
P. Marshall.
Influence of plasma catacholamines on the lactate threshold during graded exercise.
J. Appl. Physiol.
67:
1319-1322,
1989[Abstract/Free Full Text].
36.
Mendenhall, L. A.,
S. C. Swanson,
D. L. Habash,
and
A. R. Coggan.
Ten days of exercise training reduces glucose production and utilization during moderate-intensity exercise.
Am. J. Physiol.
266 (Endocrinol. Metab. 29):
E136-E143,
1994[Abstract/Free Full Text].
37.
Nicklas, B. J.,
A. C. Hackney,
and
R. L. Sharp.
The menstrual cycle and exercise: performance, muscle glycogen, and substrate responses.
Int. J. Sports Med.
10:
264-269,
1989[Medline].
38.
Nygaard, E.
Skeletal muscle fibre characteristics in young women.
Acta Physiol. Scand.
112:
299-304,
1981[Medline].
39.
Nygaard, P. K.
Sex differences in adaptation to exercise.
In: Biochemistry of Exercise VI, edited by B. Saltin. Champaign, IL: Human Kinetics, 1986, p. 230-231.
40.
O'Brien, M. J.,
C. A. Viguie,
R. S. Mazzeo,
and
G. A. Brooks.
Carbohydrate dependence during marathon running.
Med. Sci. Sports Exerc.
25:
1009-1017,
1993[Medline].
41.
Poehlman, E. T.,
A. W. Gardner,
P. J. Arciero,
M. I. Goran,
and
J. Calles-Escandon.
Effects of endurance training on total fat oxidation in elderly persons.
J. Appl. Physiol.
76:
2281-2287,
1994[Abstract/Free Full Text].
42.
Romijn, J. A.,
E. F. Coyle,
L. S. Sidossis,
A. Gastaldelli,
J. F. Horowitz,
E. Endert,
and
R. R. Wolfe.
Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration.
Am. J. Physiol.
265 (Endocrinol. Metab. 28):
E380-E391,
1993[Abstract/Free Full Text].
43.
Rudy, B. C.,
R. A. Robergs,
D. L. Waters,
M. Burge,
C. Mermier,
and
L. Stolarczyk.
Effects of estradiol on substrate turnover during exercise in amenorrheic females.
Med. Sci. Sports Exerc.
29:
1160-1169,
1997[Medline].
44.
Schutz, Y.,
A. Tremblay,
R. L. Weinier,
and
K. M. Nelson.
Role of fat oxidation in long-term stabilization of body weight in obese women.
Am. J. Clin. Nutr.