Share this article on:

Dose-Response Effects of Ingested Carbohydrate on Exercise Metabolism in Women


Medicine & Science in Sports & Exercise: January 2007 - Volume 39 - Issue 1 - p 131-138
doi: 10.1249/01.mss.0000241645.28467.d3
BASIC SCIENCES: Original Investigations

Purpose: The effect of different quantities of carbohydrate (CHO) intake on CHO metabolism during prolonged exercise was examined in endurance-trained females.

Method: On four occasions, eight females performed 2 h of cycling at approximately 60% V˙O2max with ingestion of beverages containing low (LOW, 0.5 g·min−1), moderate (MOD, 1.0 g·min−1), or high (HIGH, 1.5 g·min−1) amounts of CHO, or water only (WAT). Test solutions contained trace amounts of [U-13C] glucose. Indirect calorimetry combined with measurement of expired 13CO2 and plasma 13C enrichment enabled calculation of exogenous CHO, liver-derived glucose, and muscle glycogen oxidation during the last 30 min of exercise.

Results: The highest rates of exogenous CHO oxidation were observed in MOD, with no further increases in HIGH (peak rates of 0.33 ± 0.02, 0.50 ± 0.03, and 0.48 ± 0.05 g·min−1 for LOW, MOD, and HIGH, respectively; P < 0.05 for LOW vs MOD and HIGH). Endogenous CHO oxidation was lowest in MOD (0.99 ± 0.06, 0.82 ± 0.08, 0.70 ± 0.07, and 0.89 ± 0.09 g·min−1; P < 0.05 for MOD vs all other trials). Compared with WAT, CHO ingestion reduced liver glucose oxidation during exercise by approximately 30% (P < 0.05 for WAT vs all CHO). Differential rates of muscle glycogen oxidation were observed with different CHO doses (0.57 ± 0.07, 0.53 ± 0.08, 0.41 ± 0.07, and 0.60 ± 0.09 g·min−1 for WAT, LOW, MOD, and HIGH respectively; P < 0.05 for MOD vs HIGH).

Conclusion: In endurance-trained women, the highest rates of exogenous CHO oxidation and greatest endogenous CHO sparing was observed when CHO was ingested at moderate rates (1.0 g·min−1, 60 g·h−1) during exercise.

School of Sport and Exercise Sciences, University of Birmingham, Birmingham, UNITED KINGDOM

Address for correspondence: Asker E. Jeukendrup, Ph.D., School of Sport and Exercise Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom; E-mail:

Submitted for publication April 2006.

Accepted for publication August 2006.

During the last 30 yr, a large number of studies have investigated the metabolic and performance responses to carbohydrate (CHO) ingested during endurance exercise (13). The majority of these studies were carried out using healthy or endurance-trained men as the subject population. However, sex-related differences in the metabolic response to endurance exercise have been identified, with women relying more on lipid and less on CHO oxidation (26). Therefore, some aspects of the metabolic response to CHO ingestion during exercise may be different in women, although our understanding of these relationships remains limited (1,4,18,24,29).

The studies that have been performed in women demonstrate that ingested CHO is readily oxidized and can contribute significantly to the energy yield during cycling exercise (18,24,29). Furthermore, CHO ingestion has been shown to attenuate endogenous CHO oxidation during exercise by reducing hepatic glucose production/oxidation (4,29) and, possibly, muscle glycogen oxidation (4), although this latter observation was not confirmed in a recent study from our laboratory (29). Metabolic responses in these studies were evaluated by comparing water/placebo ingestion with CHO ingested at a single rate during exercise. In men, the oxidation of ingested CHO (13) and the suppression of hepatic glucose production (3,16,20) have been shown to be dependent on the rate of CHO intake during cycling exercise, whereas muscle glycogen oxidation is generally unaffected regardless of the CHO dose ingested (6,11,14,16). The extent to which the rate of CHO ingestion influences metabolic responses during exercise in women has not been systematically investigated.

Therefore, the purpose of the present study was to investigate the oxidation of the respective CHO sources (exogenous CHO, liver-derived glucose, and muscle glycogen) in response to CHO ingestion at a range of doses during prolonged moderate-intensity cycling exercise in endurance-trained women.

Back to Top | Article Outline



Eight females (age, 33 ± 2 yr; body mass, 63 ± 3 kg) volunteered to participate in this study. All had an endurance-training background that included cycling (road cycling, mountain biking, duathlon, or triathlon). On average, subjects had been training for 6 ± 1 yr, and, in the 3-month period before the study, they had been training 4 ± 1 d·wk−1 and 8 ± 1 h·wk−1. The subjects' maximal oxygen uptake (V˙O2max) and maximum power output (Wmax) achieved during an incremental test (see below) were 53 ± 1 mL·kg−1·min−1 and 279 ± 7 W, respectively. Subjects were eumenorrheic, had normal and regular menstrual cycle length (25-32 d), and had not taken hormonal contraceptive agents for at least 6 months before the onset of the study. All subjects were informed of the purpose, practical details, and risks associated with the procedures before giving their written informed consent to participate. All subjects were healthy as assessed by a general health questionnaire. The study was approved by the local ethics committee.

Back to Top | Article Outline

Preliminary Testing.

Participants were asked to provide details of their menstrual cycle history through a written questionnaire to predict the start date of their next two consecutive menstrual cycles (day 1 being first sign of menstruation). On the basis of their history, subjects attended the laboratory for a preliminary exercise testing session between 7 and 14 d before the first main experimental trial.

During this preliminary session, volunteers completed an incremental cycle test performed to volitional exhaustion on an electromagnetically braked cycle ergometer (Lode Excalibur Sport, Groningen, Netherlands) to determine maximal power output (Wmax) and V˙O2max as previously described (29). Gas-exchange measurements during this test were made using the Douglas bag method, with V˙O2 and carbon dioxide production (V˙CO2) calculated using conventional equations. Wmax values were used to determine 45% Wmax, which was the workload later employed in the experimental trials.

Back to Top | Article Outline

Experimental design.

Each subject performed four exercise trials consisting of 120 min of cycling at 45% Wmax while ingesting water (WAT), low-carbohydrate (LOW, ingestion rate; 0.5 g glucose per minute, 3.2% solution), moderate-carbohydrate (MOD, 1.0 g·min−1, 6.4% solution), or high-carbohydrate (HIGH, 1.5 g·min−1, 9.6% solution) solutions. To quantify exogenous CHO oxidation, corn-derived glucose (Meritose 200, Amylum Europe N.V., Belgium) was used, which has a high natural abundance of 13C (−10.77 δ‰ vs Pee Dee Bellemnitella (PDB)). In addition, approximately 0.04 g·L−1 of [U-13C] glucose (> 99% 13C/12C, Cambridge Isotope Laboratories, MA) was added to the ingested solutions (including the WAT), to reach a final enrichment of 106.41 ± 1.90, 55.73 ± 0.75, and 36.96 ± 0.38 δ‰ versus PDB for LOW, MOD, and HIGH, respectively. The 13C enrichment of the ingested glucose was determined by elemental analyzer isotope ratio mass spectrometry (EA-IRMS; Europa Scientific GEO 20-20, Crewe, UK).

Trials were performed over the course of two or three consecutive menstrual cycles, with two trials performed in the follicular phase (days 3-12) of each cycle. The order of the trials was randomly assigned and separated by 4-7 d. On average, the WAT trial was performed on day 8 ± 1 of the menstrual cycle, with LOW, MOD, and HIGH performed on days 8 ± 2, 6 ± 1, and 7 ± 1, respectively.

Back to Top | Article Outline

Diet and activity before testing.

The test solutions to be ingested contained [U-13C] glucose to quantify exogenous CHO and plasma glucose oxidation. Therefore, subjects followed a specific exercise/diet regime in the 4-7 d leading up to the experimental trials to reduce the background shift (change in 13C) from endogenous substrate stores during exercise, as described previously (29). Subjects were also asked to record their food intake and activity pattern 2 d before the first exercise trial and were then instructed to follow the same diet and activities before the next three trials. In addition, subjects were instructed to refrain from strenuous exercise and to not drink any alcohol in the 24 h before the exercise trials.

Back to Top | Article Outline

Experimental protocol.

Participants arrived at the laboratory in the morning after an overnight fast (~10 h). All experimental trials were performed at the same time of day to avoid circadian variance. On arrival, subjects were weighed, and then a 20-gauge Teflon catheter (Venflon, BD, Plymouth, UK) was inserted into an antecubital vein of one arm and attached to a three-way stopcock (Sims Portex, Kingsmead, UK) to allow for repeated blood sampling during exercise. The cannula was kept patent by flushing with 1.0-1.5 mL of isotonic saline (0.9%, BD, Plymouth, UK) after each blood sample collection.

The subjects then mounted the cycle ergometer, and a resting breath sample was collected into 10-mL Exetainer tubes (Labco Ltd., Brow Works, High Wycombe, UK), which were filled directly from a 2-L mixing chamber to determine the 13C/12C ratio in the expired air. A resting blood sample (10 mL) was collected and stored on ice until centrifugation. Subjects then started a 120-min exercise bout at a work rate equivalent to 45% Wmax (~60% V˙O2max). Additional blood samples were drawn at 15-min intervals until cessation of exercise. Expiratory breath samples were collected every 15 min until the end of exercise for 3-min periods. During the first 2 min, V˙O2, V˙CO2, and respiratory exchange ratio (RER) were measured using the Douglas bag technique as described above. With the subject continuing to breathe through the breathing apparatus, the respiratory tubing attached to the closed Douglas bags was connected to the mixing chamber, and after a 40-s equilibration period, duplicate Exetainer tubes were filled directly from the chamber as described above.

During the first 2-3 min of exercise, subjects ingested an initial bolus (600 mL) of one of the four experimental drinks. Thereafter, smaller equal doses of the test beverage were provided every 15 min during exercise. The total fluid intake during the exercise bout was 1.875 L. All exercise tests were performed at 18-22°C and 50-60% relative humidity. During the exercise trials subjects were cooled with standing floor fans to minimize thermal stress.

Back to Top | Article Outline

Gastrointestinal disturbances.

Every 30 min during the exercise bout, subjects were requested to verbally answer a short questionnaire containing questions regarding the presence (or absence) of gastrointestinal (GI) problems at that moment. GI symptoms were scored on a 10-point scale (1 = not at all and 10 = very, very much). The severity of the GI symptoms was divided into two categories; severe and nonsevere symptoms, as previously described (15). Severe complaints included nausea, stomach problems, bloated feeling, diarrhea, urge to vomit, and stomach and intestinal cramps because these are symptoms that commonly impair performance and that may cause health risks. The above symptoms were only registered as severe symptoms when a score of 5 or higher out of 10 was reported. When a score below 5 was given, they were registered as nonsevere. All other symptoms were registered as nonsevere regardless of the score reported.

Back to Top | Article Outline


All blood samples were collected into prechilled vacutainers containing EDTA and were centrifuged at 3000 rpm for 10 min at 4°C. Aliquots of the plasma were frozen in liquid nitrogen and stored at −70°C until further analysis. Plasma samples were analyzed for glucose, lactate, and free fatty acid concentration on a semiautomatic analyzer (Cobas Mira S-Plus, ABX, UK) using commercially available assays (Glucose HK and Lactic Acid, both ABX Diagnostics, UK; free fatty acids, NEFA-C Kit, Alpha Laboratories, UK). Plasma insulin concentrations were determined using enzyme immunoassay (Ultra Sensitive Insulin ELISA, IDS, UK).

Plasma 13C glucose enrichment was determined using the method of Pickert et al. (22), modified for use with gas chromatography-combustion-IRMS (GC-C-IRMS). Briefly, plasma samples were extracted with methanol-chloroform (2.3:1, v/v) and then chloroform-water (pH 2.0) (2:1, v/v). After drying under nitrogen gas, samples were derivatized using the butlyboronic acid-acetyl derivative made according to standard procedures. The glucose derivative (1 μL) was injected into the GC (split ratio 1:15) and analyzed by GC-C-IRMS (GC, Trace GC Ultra; C, GC Combustion III; IRMS, Delta Plus XP; all Thermo Finnigan, Herts, UK). The measured 13C enrichment was corrected by a factor of 16/6 to account for isotopic carbon dilution from the butlyboronic acid-acetyl derivative. Breath samples were analyzed for 13C/12C ratio by continuous-flow IRMS (GC, Trace GC Ultra; IRMS, Delta Plus XP; both Thermo Finnigan, Herts, UK).

Back to Top | Article Outline


Total CHO and fat oxidation (g·min−1) were calculated from stochiometric equations (17), and protein oxidation was assumed to be negligible.

The isotopic enrichment in the expired breath samples and plasma samples was expressed as δ per milliliter difference between the 13C/12C ratio of the sample and a known laboratory reference standard using the following formula (8):

The δ 13C was then related to an international standard (PDB).

The rate of exogenous CHO oxidation was calculated using the following formula (23):

in which δExp is the 13C enrichment of expired air during exercise at different time points, δIng is the 13C enrichment of the ingested glucose solution, δExpbkg is the 13C enrichment of expired air in a trial with the ingestion of water (background) at different time points, and k is the amount of CO2 (in liters) produced by the oxidation of 1 g of glucose (k = 0.7467 L of CO2 per gram of glucose). In the present experiment, changes in δExpbkg with water ingestion could not be measured because of the trace amount of [U-13C] glucose added, but these changes were estimated from the average consistent values observed in a similar experiment involving endurance-trained females in our laboratory (mean increase = 0.58 ± 0.30 δ‰ vs PDB; range, 0.13-1.64 δ‰ vs PDB) (29).

From plasma glucose 13C/12C measurements, plasma glucose oxidation was calculated using the following formula (10):

in which PG is the plasma glucose 13C enrichment, PGbkg, is the plasma glucose 13C enrichment before exercise (background), and the constant k is the same as above.

Plasma glucose oxidation represents the glucose oxidized from ingested CHO, liver glycogenolysis, and gluconeogenesis. Muscle glycogen oxidation and liver-derived glucose oxidation were calculated using the following formulas:

These values should be regarded as estimates because they are calculated indirectly from tracer and whole-body indirect calorimetry measurements.

Recovery of 13CO2 from oxidation will approach 100% after 60 min of exercise when the dilution in the bicarbonate pool becomes negligible (21,25). Furthermore, steady-state values for plasma glucose enrichment for all trials were only attained during 90-120 min of exercise. Therefore, to enable comparison between all trials, whole-body substrate oxidation and the oxidation of the respective CHO sources were averaged for the last 30 min of exercise.

Back to Top | Article Outline


All data are expressed as mean ± standard error of the mean (mean ± SE). One-way analysis of variance (ANOVA) for repeated measures was performed to study differences in exercise intensity (average over complete exercise bout) and substrate oxidation rates (average over the final 30 min) between trials. Significant effects were followed by pairwise comparisons using the false discovery rate procedure (9). Two-way ANOVA for repeated measures was performed to study differences over time between the trials for plasma metabolites and glucose enrichments. In this case, a Tukey post hoc test was applied where a significant interaction was detected. Analyses were adjusted using the Greenhouse-Geisser correction where necessary. For all statistical analyses, significance was accepted at P < 0.05.

Back to Top | Article Outline


Workload and exercise intensities.

The workload of 45% Wmax (129 ± 3 W) employed during the 2-h trials elicited at an average absolute V˙O2 of 1.96 ± 0.05, 1.96 ± 0.05, 1.92 ± 0.04, and 1.93 ± 0.05 L·min−1 for WAT, LOW, MOD, and HIGH respectively. Accordingly, the average relative exercise intensity and energy expended during exercise was similar between trials (59-60% V˙O2max and 40-41 kJ·min−1, respectively). Average heart rate during the 2-h exercise bouts were similar between WAT, LOW, and MOD (132 ± 5, 133 ± 5, and 133 ± 5 respectively) but was approximately 6 bpm higher during HIGH (139 ± 5, P < 0.05 vs other three trials). Average RPE (from 6 to 20) was 12 ± 0 for all trials.

Back to Top | Article Outline

RER, CHO, and fat oxidation.

As shown in Table 1, RER and CHO oxidation were lower and fat oxidation was higher when water was ingested compared with when CHO was ingested during exercise (main effect of trial, P < 0.05). Furthermore, RER and CHO oxidation was lower and fat oxidation was higher (P < 0.05) in LOW and MOD compared with HIGH; LOW and MOD did not differ significantly in these variables (Table 1). Compared with the first 30 min of exercise, total CHO oxidation had declined by 13 ± 4% by the last 30 min of exercise in the WAT trial (P < 0.05) but was not reduced significantly over time when CHO was ingested.



The relative contribution of substrates to energy is depicted in Figure 1. Total CHO oxidation contributed 42 ± 3, 48 ± 4, 51 ± 5, and 59 ± 4% for WAT, LOW, MOD, and HIGH, respectively. Compared with WAT, relative CHO oxidation was significantly higher when CHO was ingested during exercise (main effect of trial, P < 0.05). Relative CHO oxidation did not differ between LOW and MOD but was significantly higher in HIGH (P < 0.05 vs LOW and MOD) Conversely, fat contributed 58 ± 3, 52 ± 4, 49 ± 5, and 41 ± 4% for WAT, LOW, MOD, and HIGH, respectively.

Back to Top | Article Outline

Exogenous CHO and plasma glucose oxidation.

The average exogenous CHO oxidation over the last 30 min of exercise was significantly lower in LOW than MOD and HIGH, but no difference was observed between MOD and HIGH (Table 1). Peak oxidation rates achieved at the final collection point were 0.33 ± 0.02, 0.50 ± 0.03, and 0.48 ± 0.05 g·min−1 for LOW, MOD, and HIGH, respectively (P < 0.05 LOW vs MOD and HIGH). Exogenous CHO oxidation contributed significantly less to energy expenditure in LOW (13 ± 1%, P < 0.05 vs MOD and HIGH) compared with MOD and HIGH (19 ± 2 and 18 ± 2%, respectively) (Fig. 1).



As shown in Table 1, plasma glucose oxidation was significantly lower in the WAT trial compared with the CHO trials (main effect of trial, P < 0.05). Furthermore, plasma glucose oxidation was significantly lower in the LOW trial compared with MOD and HIGH (P < 0.05) but was similar in MOD and HIGH. This pattern held when plasma glucose oxidation was expressed as a function of total energy expenditure, contributing 16 ± 1, 24 ± 2, 30 ± 2, and 30 ± 2% in WAT, LOW, MOD, and HIGH, respectively.

Back to Top | Article Outline

Endogenous CHO oxidation.

Total endogenous CHO oxidation and the oxidation of the respective endogenous CHO sources during the last 30 min of exercise are shown in Table 1. Compared with WAT, endogenous CHO oxidation was significantly lower in LOW and MOD (P < 0.05) but not compared with HIGH. Endogenous CHO oxidation was lowest in MOD (P < 0.05 vs all other trials). Liver-derived glucose oxidation expressed as grams per minute (Table 1) or relative to energy expenditure (Fig. 1) was higher when WAT was ingested during exercise compared with CHO (main effect of trial, P < 0.05) but was not different between the CHO trials. Estimated muscle glycogen oxidation was not statistically different between trials when expressed as oxidation rates (Table 1) or as a relative contribution to energy expenditure (25 ± 4, 23 ± 3, 18 ± 3, and 27 ± 5% in WAT, LOW, MOD, and HIGH, respectively, Fig. 1). However, compared with the WAT trial, average muscle glycogen oxidation was 0.16 g·min−1 (~28%) lower in MOD. Furthermore, muscle glycogen use was significantly lower in MOD compared with HIGH (P < 0.05, Table 1).

Back to Top | Article Outline

Plasma metabolites and insulin.

Plasma glucose concentrations remained stable (between 4.0 and 4.3 mM) when water was ingested during the exercise period (Fig. 2A). In the WAT trial, glucose concentrations were significantly lower (P < 0.05) than those in the CHO trials from 15 min onwards. Also, glucose concentrations were significantly lower in LOW compared with MOD and HIGH toward the end of exercise (105- to 120-min period, P < 0.05) but not significantly different between MOD and HIGH. Plasma lactate concentrations increased significantly above resting values in all trials after 15 min of exercise (main effect of time, P < 0.05) and remained elevated for the duration of the exercise period (Fig. 2B). Plasma free fatty acid concentrations increased over time in the WAT, and this was statistically significant (from resting values) from 75 to 120 min (Fig. 2C). When CHO was ingested, plasma free fatty acid concentrations did not change significantly from resting values and were lower than those observed in WAT from approximately 30 to 45 min onwards (P < 0.05) but were not different between specific CHO trials.



Plasma insulin concentrations did not change significantly from baseline values over time in the WAT trial (Fig. 2D). Compared with WAT, the ingestion of CHO increased plasma insulin concentrations during exercise with significant differences observed with MOD and HIGH (P < 0.05, between 30-60 min and 30-90 min for MOD and HIGH, respectively, vs WAT). The total insulin area under the curve was 307 ± 39, 477 ± 69, 712 ± 100, and 774 ± 79 mU·mL−1 for WAT, LOW, MOD, and HIGH, respectively. This was lower when WAT was ingested compared with CHO (P < 0.05, WAT vs CHO) and also when LOW was ingested compared with MOD and HIGH (P < 0.05) but did not differ statistically between MOD and HIGH.

Back to Top | Article Outline

GI discomfort.

GI and related complaints are displayed in Table 2. These data will be discussed as descriptive data only; because of insufficient sample size, it is not possible to perform nonparametric statistical procedures on these nominal data. Participants reported fewer nonsevere GI complaints during WAT and LOW (12 and 10, respectively) compared with MOD and HIGH (23 and 22, respectively). In addition, participants reported more occurrences of severe GI complaints during HIGH (8) compared with the other three trials (~1-2).



Back to Top | Article Outline


In this study, the influence of the rate of CHO ingestion (0.5, 1.0, and 1.5 g·min−1) on carbohydrate use during exercise in endurance-trained women was investigated. The findings from this study demonstrate that 1) the highest rates of exogenous CHO oxidation were attained when the women ingested CHO at rates of 1.0 g·min−1 or above; 2) CHO ingestion during exercise reduced estimated liver-derived glucose oxidation; 3) endogenous CHO oxidation was lowest when CHO was ingested at 1.0 g·min−1, possibly as a result of muscle glycogen sparing; and 4) estimated muscle glycogen oxidation was significantly higher when CHO was ingested at 1.5 g·min−1 compared with 1.0 g·min−1. These findings are discussed sequentially.

Although well studied in investigations using only male participants (13), this is the first study to examine dose-response relationships between CHO intake and exogenous CHO oxidation during exercise in trained women. Increasing the CHO-ingestion rate from 0.5 to 1.0 g·min−1 (LOW and MOD respectively) increased exogenous CHO oxidation by approximately 42% (Table 1). However, exogenous CHO oxidation did not further increase when larger amounts of CHO (1.5 g·min−1, HIGH) were ingested during exercise. Additionally, the peak exogenous CHO oxidation rates observed in the present study (~0.5 g·min−1) are consistent with previous studies that have measured exogenous CHO oxidation during exercise in women (0.5-0.7 g·min−1) (18,24,29). These data complement the results from a similar previous study in trained men (28) and support previous conclusions that oxidation rates from ingested CHO during exercise do not increase once ingestion rates of 1.0-1.2 g·min−1 have been reached (13).

Although the peak oxidation rates observed for the women in the present study do seem to be slightly lower than the highest rates observed in studies performed on men (0.5 vs up to 1.1 g·min−1) (13), it is unlikely that this represents a true sex-related difference in peak exogenous CHO oxidation. In support of this, we recently reported similar peak oxidation rates (~0.7 g·min−1) in a well-matched group of men and women when 1.5 g·min−1 (HIGH) was ingested during prolonged cycling at approximately 67% V˙O2max (29). Rather, in the present study, the relatively low absolute workload (and thus the total requirement for CHO oxidation) may explain the lower oxidation rates observed (19).

Of note, the similar peak oxidation rates observed in MOD and HIGH were markedly lower than the rate of CHO ingestion (30-50% of the ingestion rate). This has been reported previously (28) and leads us to question both the fate of the nonoxidized ingested CHO and the limitation to the use of large amounts of ingested CHO as a source of blood glucose oxidation during exercise. Although it has not been directly determined, most evidence suggests that the limitation lies at the level of intestinal CHO absorption and/or CHO release from the splanchnic region (13). Glucose kinetics (rate of appearance of glucose from the gut and the liver) could not be determined from the methods used in the present study, and therefore, firm conclusions on this issue cannot be made. However, from the large number of gastrointestinal complaints reported in MOD (mainly nonsevere symptoms) and HIGH (nonsevere and severe symptoms) trials compared with LOW and WAT (Table 2), it could be speculated that a significant portion of the nonoxidized CHO is retained/accumulating in the gastrointestinal tract with the remainder directed towards other endogenous pools (such as the liver), as previously suggested (13,28).

CHO ingestion in the present study resulted in an approximately 30% reduction in estimated liver-derived glucose oxidation compared with when water was ingested (Table 1), indicating a sparing of this endogenous CHO source. A reduction in endogenous glucose production and/or oxidation has been reported in previous studies in men (3,16,20) and women (4,29) when CHO was fed during exercise. In men, it has been demonstrated that ingestion of small amounts of CHO during low-intensity exercise (35 g·h−1) can partially reduce hepatic glucose production (~65% reduction), whereas large amounts of CHO (175 g·h−1) can completely suppress hepatic glucose production (16). In contrast, the provision of small (30 g·h−1), moderate (60 g·h−1), or high (90 g·h−1) CHO doses in the present study exerted similar reductions in liver-derived glucose oxidation (Table 1). The present data are, however, not dissimilar (although slightly lower) to previous studies reporting that ingestion of CHO at moderate to large doses (50-100 g·h−1) reduced hepatic glucose production during moderate- to high-intensity exercise by 50-70% (3,4,20).

In the present study, the lowest rates of endogenous CHO oxidation were observed in MOD (Table 1). In addition to reduced liver-derived glucose oxidation with CHO feeding, compared with WAT, muscle glycogen use was approximately 28% lower in MOD (not statistically significant). Interestingly, this dose (~1 g·min−1) has previously been reported to spare muscle glycogen during exercise in trained women (4). However, CHO ingestion in general (6) or at a range of doses (14,16) does not affect muscle glycogen use during constant-load cycling exercise in men, suggesting that this response may be specific to women. The reason(s) for this apparent sparing of glycogen at this ingestion rate for the women studied presently cannot be determined from the present data. However, it could be that in these women, the elevated glucose and insulin concentrations in MOD, compared with WAT increased muscle glucose uptake to a magnitude sufficient to reduce muscle glycogenolysis. Such a mechanism has been proposed to explain the observation that CHO ingestion attenuates muscle glycogen use during constant-intensity running exercise (27). Verification of these observations with direct measurement of glycogen use in skeletal muscle could be of considerable practical importance for prescribing optimal CHO feeding strategies for women endurance athletes.

Interestingly, endogenous CHO and estimated muscle glycogen oxidation were not different between WAT and HIGH (Table 1). The latter confirms our previous report demonstrating that CHO ingestion at 90 g·h−1 does not affect muscle glycogen use in trained females (29). Therefore, unlike in MOD, the elevated glucose and insulin response in HIGH did not seem sufficient to attenuate estimated muscle glycogen use, and, in fact, glycogen use was significantly increased relative to MOD. The discrepancies between the observed muscle glycogen use in MOD and HIGH cannot be readily explained. However, heart rate was elevated in HIGH (by approximately 6 bpm), which may reflect a greater sympathetic nervous system response. Although catecholamine concentrations were not determined, an increased catecholamine response associated with increased sympathetic drive could explain the augmented muscle glycogenolysis (30). It might be speculated that the high incidence of severe gastrointestinal distress reported by participants in the HIGH trial (Table 2) contributed to the higher overall physiological stress in this condition. Alternatively, a reduction in the use of fat as a substrate in HIGH (Table 1) may actually have resulted in a compensatory augmentation of muscle glycogen use (2). Unfortunately, it is not possible to determine from the present data whether increased glycolytic flux (from increased muscle glycogen use) acted to suppress fat oxidation (7) or whether muscle glycogen oxidation was augmented secondary to action of insulin to reduce fat availability and oxidation during exercise (7,12).

In summary, the highest exogenous CHO oxidation rates and greatest sparing of endogenous CHO was observed when a moderate amount of CHO (1 g·min−1, 60 g·h−1) was ingested during exercise. These data extend previous recommendations based on studies using male participants to endurance-trained females. Thus, when a single CHO form is to be ingested, it seems that for men and women, optimal benefits in terms of exogenous energy delivery and endogenous CHO use are attained from ingesting approximately 60 g·h−1 (5,13). Future studies should be directed towards substantiating the effects of CHO feeding on muscle metabolism in endurance-trained women, and investigating if these optimal benefits in terms of whole-body carbohydrate metabolism translate into optimal endurance performance improvements.

This study was funded by a research grant from GlaxoSmithKline Consumer Healthcare (UK). The results of the present study do not constitute endorsement of the product by the authors or ACSM.

Back to Top | Article Outline


1. Bailey, S. P., C. M. Zacher, and K. D. Mittleman. Effect of menstrual cycle phase on carbohydrate supplementation during prolonged exercise to fatigue. J. Appl. Physiol. 88:690-697, 2000.
2. Bergstrom, J., E. Hultman, L. Jorfeldt, B. Pernow, and J.Wahren. Effect of nicotinic acid on physical working capacity and on metabolism of muscle glycogen in man. J. Appl. Physiol. 26:170-176, 1969.
3. Bosch, A. N., S. C. Dennis, and T. D. Noakes. Influence of carbohydrate ingestion on fuel substrate turnover and oxidation during prolonged exercise. J. Appl. Physiol. 76:2364-2372, 1994.
4. Campbell, S. E., D. J. Angus, and M. A. Febbraio. Glucose kinetics and exercise performance during phases of the menstrual cycle: effect of glucose ingestion. Am. J. Physiol. Endocrinol. Metab. 281:E817-E825, 2001.
5. Coyle, E. F. Fluid and fuel intake during exercise. J. Sports Sci. 22:39-55, 2004.
6. Coyle, E. F., A. R. Coggan, M. K. Hemmert, and J. L. Ivy. Muscle glycogen utilization during prolonged strenuous exercise when fed carbohydrate. J. Appl. Physiol. 61:165-172, 1986.
7. Coyle, E. F., A. E. Jeukendrup, A. J. Wagenmakers, and W. H. Saris. Fatty acid oxidation is directly regulated by carbohydrate metabolism during exercise. Am. J. Physiol. Endocrinol. Metab. 273:E268-E275, 1997.
8. Craig, H. W. Isotopic standards for carbon and oxygen correction factors. Geochim. Cosmochim. Acta. 12:133-149, 1957.
9. Curran-Everett, D., and D. J. Benos. Guidelines for reporting statistics in journals published by the American Physiological Society. Am. J. Physiol. Endocrinol. Metab. 287:E189-E191, 2004.
10. Derman, K. D., J. A. Hawley, T. D. Noakes, and S. C. Dennis. Fuel kinetics during intense running and cycling when fed carbohydrate. Eur. J. Appl. Physiol. Occup. Physiol. 74:36-43, 1996.
11. Flynn, M. G., D. L. Costill, J. A. Hawley, et al. Influence of selected carbohydrate drinks on cycling performance and glycogen use. Med. Sci. Sports Exerc. 19:37-40, 1987.
12. Horowitz, J. F., R. Mora-Rodriguez, L. O. Byerley, and E. F. Coyle. Substrate metabolism when subjects are fed carbohydrate during exercise. Am. J. Physiol. 276:E828-E835, 1999.
13. Jeukendrup, A. E. Carbohydrate intake during exercise and performance. Nutrition 20:669-677, 2004.
14. Jeukendrup, A. E., A. Raben, A. Gijsen, et al. Glucose kinetics during prolonged exercise in highly trained human subjects: effect of glucose ingestion. J. Physiol. 515:579-589, 1999.
15. Jeukendrup, A. E., K. Vet-Joop, A. Sturk, et al. Relationship between gastro-intestinal complaints and endotoxaemia, cytokine release and the acute-phase reaction during and after a long-distance triathlon in highly trained men. Clin. Sci. (Lond.) 98:47-55, 2000.
16. Jeukendrup, A. E., A. J. Wagenmakers, J. H. Stegen, A. P. Gijsen, F. Brouns, and W. H. Saris. Carbohydrate ingestion can completely suppress endogenous glucose production during exercise. Am. J. Physiol. 276:E672-E683, 1999.
17. Jeukendrup, A. E., and G. A. Wallis. Measurement of substrate oxidation during exercise by means of gas exchange measurements. Int. J. Sports Med. 26(Suppl 1):S28-S37, 2005.
18. M'Kaouar, H., F. Peronnet, D. Massicotte, and C. Lavoie. Gender difference in the metabolic response to prolonged exercise with [13C]glucose ingestion. Eur. J. Appl. Physiol. 92:462-469, 2004.
19. Massicotte, D., F. Peronnet, E. Adopo, G. R. Brisson, and C.Hillaire-Marcel. Effect of metabolic rate on the oxidation of ingested glucose and fructose during exercise. Int. J. Sports Med. 15:177-180, 1994.
20. McConell, G., S. Fabris, J. Proietto, and M. Hargreaves. Effect of carbohydrate ingestion on glucose kinetics during exercise. J. Appl. Physiol. 77:1537-1541, 1994.
21. Pallikarakis, N., N. Sphiris, and P. Lefebvre. Influence of the bicarbonate pool and on the occurrence of 13CO2 in exhaled air. Eur. J. Appl. Physiol. Occup. Physiol. 63:179-183, 1991.
22. Pickert, A., D. Overkamp, W. Renn, H. Liebich, and M. Eggstein. Selected ion monitoring gas chromatography/mass spectrometry using uniformly labelled (13C)glucose for determination of glucose turnover in man. Biol. Mass Spectrom. 20:203-209, 1991.
23. Pirnay, F., M. Lacroix, F. Mosora, A. Luyckx, and P. Lefebvre. Effect of glucose ingestion on energy substrate utilization during prolonged muscular exercise. Eur. J. Appl. Physiol. Occup. Physiol. 36:247-254, 1977.
24. Riddell, M. C., S. L. Partington, N. Stupka, D. Armstrong, C. Rennie, and M. A. Tarnopolsky. Substrate utilization during exercise performed with and without glucose ingestion in female and male endurance trained athletes. Int. J. Sport Nutr. Exerc. Metab. 13:407-421, 2003.
25. Robert, J. J., J. Koziet, D. Chauvet, D. Darmaun, J. F. Desjeux, and V. R. Young. Use of 13C-labeled glucose for estimating glucose oxidation: some design considerations. J. Appl. Physiol. 63:1725-1732, 1987.
26. Tarnopolsky, M. A. Gender differences in substrate metabolism during endurance exercise. Can. J. Appl. Physiol. 25:312-327, 2000.
27. Tsintzas, O. K., C. Williams, L. Boobis, and P. Greenhaff. Carbohydrate ingestion and glycogen utilization in different muscle fibre types in man. J. Physiol. (Lond.) 489:243-250, 1995.
28. Wagenmakers, A. J., F. Brouns, W. H. Saris, and D. Halliday. Oxidation rates of orally ingested carbohydrates during prolonged exercise in men. J. Appl. Physiol. 75:2774-2780, 1993.
29. Wallis, G. A., R. Dawson, J. Achten, J. Webber, and A. E. Jeukendrup. Metabolic response to carbohydrate ingestion during exercise in males and females. Am. J. Physiol. Endocrinol. Metab. 290:E708-E715, 2006.
30. Watt, M. J., K. F. Howlett, M. A. Febbraio, L. L. Spriet, and M.Hargreaves. Adrenaline increases skeletal muscle glycogenolysis, pyruvate dehydrogenase activation and carbohydrate oxidation during moderate exercise in humans. J. Physiol. (Lond.) 534:269-278, 2001.


©2007The American College of Sports Medicine