A signalling role for muscle glycogen in the regulation of pace during prolonged exercise

Introduction: In this study we examined the pacing strategy and the end muscle glycogen contents in eight cyclists, once when they were carbohydrate loaded and once when they were non-loaded.

Methods: Cyclists completed 2 hours of cycling at ~73% of maximum oxygen consumption, which included five sprints at 100% of peak sustained power output every 20 minutes, followed immediately by a 1 hour time trial. Muscle biopsies were performed before and immediately after exercise, while blood samples were taken during the 2 hour steady state rides and immediately after exercise.

Results: Carbohydrate loading improved mean power output during the 1 hour time trial (mean (SEM) 219 (17) v 233 (15) W; p<0.05) and enabled subjects to use significantly more muscle glycogen than during the trial following their normal diet. Significantly, the subjects, kept blind to all feedback except for time, started both time trials at similar workloads (~30 W), but after 1 minute of cycling, the workload average 14 W higher throughout the loaded compared with the non-loaded time trial. There were no differences in subjects' plasma glucose and lactate concentrations and heart rates in the carbohydrate loaded versus the non-loaded trial. Of the eight subjects, seven improved their time trial performance after carbohydrate loading. Finishing muscle glycogen concentrations in these seven subjects were remarkably similar in both trials (18 (3) v 20 (3) mmol/kg w/w), despite significantly different starting values and time trial performances (36.55 (1.47) v 38.14 (1.27) km/h; p<0.05). The intra-subject coefficient of variation (CV) for end glycogen content in these seven subjects was 10%, compared with an inter-subject CV of 43%.

Conclusions: As seven subjects completed the time trials with the same end exercise muscle glycogen concentrations, diet induced changes in pacing strategies during the time trials in these subjects may have resulted from integrated feedback from the periphery, perhaps from glycogen content in exercising muscles.

     

Effect of carbohydrate feeding during recovery from prolonged running on muscle glycogen metabolism during subsequent exercise

This study examined the effect of carbohydrate (CHO) intake during a 4 h recovery from prolonged running on muscle glycogen metabolism during subsequent exercise. On 2 occasions, 7 male subjects ran for 90 min at 70 % maximum oxygen uptake VO(2 max) on a motorized treadmill (R1) followed by a 4 h rest period (REC) and a 15 min run (R2) consisting of 5 min at 60 % and 10 min at 70 % VO(2 max) During REC, each subject ingested a total of 2.7 l of an isotonic solution containing either 50 g of CHO (LOW) or 175 g of CHO (HIGH). Biopsy samples were obtained from the vastus lateralis immediately after R1, REC and R2. During REC, a higher muscle glycogen resynthesis was observed in HIGH when compared with LOW trial (75 +/- 20 vs. 31 +/- 11 mmol x kg dry matter (dm) -1, respectively; p < 0.01). Muscle glycogen utilization during R2 was similar between the HIGH and LOW trials (39 +/- 10 vs. 46 +/- 11 mmol x kg dm -1, respectively). These results suggest that ingestion of a large amount of CHO at frequent intervals during recovery from exercise does not affect the rate of muscle glycogen utilization during subsequent exercise.     

Effect of fructose ingestion on muscle glycogen usage during exercise

Eight healthy males were studied to compare the effects of preexercise fructose and glucose ingestion on muscle glycogen usage during exercise. Subjects performed three randomly assigned trials, each involving 30 min of cycling exercise at 75% VO2max. Forty-five min prior to commencing each trial, subjects ingested either 50 g of glucose (G), 50 g of fructose (F), or sweet placebo (C). No differences in VO2 or respiratory exchange ratio were observed between the trials. Blood glucose was elevated (P less than 0.05) as a result of the glucose feeding. With the onset of exercise, blood glucose declined rapidly during G, reaching a nadir of 3.18 +/- 0.15 (SE) mmol X 1(-1) at 20 min of exercise. This value was lower (P less than 0.05) than the corresponding values in F (3.79 +/- 0.20) and C (3.99 +/- 0.18). No differences in exercise blood glucose levels were observed between F and C. Muscle glycogen utilization was greater (P less than 0.05) during G (55.4 +/- 3.3 mmol X kg-1 w.w.) than C (42.8 +/- 4.2). No difference was observed between F (45.6 +/- 4.3) and C. There was a trend (P = 0.07) for muscle glycogen usage to be lower during F than G. These results suggest that the adverse effects of preexercise glucose ingestion are, in general, not observed with either fructose or sweet placebo.     

Effects of exercise mode on muscle glycogen restorage during repeated days of exercise

The purpose of this study was to examine differences in muscle glycogen storage during three successive days of running or cycling. In a crossover design, seven male subjects performed two 3-d trials of either running (trial R) or cycling (trial C) for 60 min at 75% VO2max. Biopsy samples were obtained before and after each day's exercise from the gastrocnemius (trial R) or vastus lateralis (trial C) muscle. Diets in the 2 d preceding and during each trial contained 5 g carbohydrate.kg-1.d-1 and 14,475 +/- 402 kJ.d-1. Mean pre-exercise glycogen content (mmol.kg-1 wet wt.) was significantly reduced in both trials on day 3 (103.4 +/- 6.0) when compared to day 1 and day 2 (119.9 +/- 6.8 and 116.4 +/- 5.7, respectively). Day 1 glycogen reduction was significantly greater in trial C (P less than 0.03), and glycogen restorage was greater (P less than 0.02) only in trial C between the 1st and 2nd d. On day 3, spectrophotometric analysis of PAS strains showed that pre-exercise glycogen content in either muscle group was significantly (P less than 0.01) less in Type I as compared to Type II fibers. This difference in fiber glycogen storage did not appear to be attributable to muscle damage as negligible leukocyte infiltration and low blood CK levels were obtained. No difference between modes were observed for CK values throughout the trials. These data suggest that the depressed glycogen storage before the 3rd d of exercise was due to the moderate carbohydrate intake.     

Effects of different sodium concentrations in replacement fluids during prolonged exercise in women

OBJECTIVE: To investigate the effect of different sodium concentrations in replacement fluids on haematological variables and endurance performance during prolonged exercise. METHODS: Thirteen female endurance athletes completed three four hour runs on a 400 m track. Environmental conditions differed between the three trials: 5.3 degrees C and snow (trial 1), 19.0 degrees C and sunny weather (trial 2), 13.9 degrees C and precipitation (trial 3). They consumed 1 litre of fluid an hour during the trials with randomised intake of fluids: one trial (H) with high sodium concentration (680 mg/l), one trial (L) with low sodium concentration (410 mg/l), and one trial with only water (W). Before and after the trials, subjects were weighed and blood samples were taken for analysis of [Na(+)](plasma), packed cell volume, and mean corpuscular volume. RESULTS: The mean (SD) decrease in [Na(+)](plasma) over the whole trial was significantly (p<0.001) less in trial H (2.5 (2.5) mmol/l) than in trial W (6.2 (2.1) mmol/l). Mild hyponatraemia ([Na(+)](plasma) = 130-135 mmol/l) was observed in only six women (46%) in trial H compared with nine (69%) in trial L, and 12 (92%) in trial W. Two subjects (17%) in trial W developed severe hyponatraemia ([Na(+)](plasma)<130 mmol/l). No significant differences were found in performance or haematological variables with the three different fluids. There was no significant correlation between[Na(+)](plasma) after the run and performance. There was a significant correlation between changes in [Na(+)](plasma) and changes in body weight. CONCLUSIONS: Exercise induced hyponatraemia in women is likely to develop from fluid overload during prolonged exercise. This can be minimised by the use of replacement fluids of high sodium concentration. Sodium replacement of at least 680 mg/h is recommended for women in a state of fluid overload during endurance exercise of four hours. However, higher [Na(+)](plasma) after the run and smaller decreases in [Na(+)](plasma) during the trials were no indication of better performance over four hours.     

Effects of muscle CHO-loading manipulations on hormonal responses during prolonged exercise

This study examined the effects of a pre-experimental period of muscle carbohydrate (CHO)-loading manipulations followed by a 24-h CHO-poor diet, intended to increase muscle glycogen content and reduce hepatic glycogen levels, on substrate and endocrine responses during a period of prolonged exercise. Seven subjects pedaled a cycle ergometer for 70 min at 64% leg VO2max (1) after normal CHO intake (CHON) and (2) after leg muscle CHO loading (CHOL), both of these procedures being followed by a period of arm exercise (70 min; 70% arm VO2max) and 24 h CHO-poor intake. CHON, as compared to CHOL condition, resulted in greater blood concentrations of free fatty acids (1.8 vs 1.3 mmol X L-1), glycerol (0.41 vs 0.28 mmol X L-1), norepinephrine (2.2 vs 1.5 ng X ml-1), epinephrine (0.90 vs 0.27 ng X ml-1), and cortisol (47 vs 23 g X dl-1) at min 70 of exercise. Insulin concentrations during exercise showed a strong tendency to be lower in CHON than in CHOL condition, although the differences were not significant. There were no significant differences between the two conditions in blood glucose, lactate, and glucagon concentrations. These data indicate that muscle CHO-loading manipulations intended to specifically increase the muscle glycogen content are associated with the difference in metabolic adaptation and hormonal changes during exercise.     

Exogenous carbohydrate spares muscle glycogen in men and women during 10 h of exercise

PURPOSE: The purpose of the study was to evaluate the effects of carbohydrate (CHO) supplementation on whole-body and net muscle substrate use during 10 h of discontinuous exercise, simulating occupational settings in men and women. METHODOLOGY: Recreationally trained subjects (N = 7 males, N = 6 females) performed a graded exercise test on a treadmill (TM) and cycle ergometer (CE) to determine ventilatory threshold (VT) and V O2peak. In a double-blind, randomized crossover design, subjects received either CHO [20% maltodextrin (0.6 g.kg FFM.h)] or flavored placebo (PLA) drink each hour across 10 h of exercise. Exercise intensity was 71.3 +/- 3% and 72.4 +/- 4% VT for TM and CE, respectively. Hourly exercise included 9 min of upper-body ergometery, 19 min of cycling, and 20 min of treadmill walking, with a 1-min transition between modes, followed by a 10-min rest and feeding period. The protocol was selected to simulate arduous occupational settings. Vastus lateralis biopsies were obtained before and after exercise. Expired gases were collected every other hour to establish average rates of whole-body CHO and fat oxidation. Blood glucose (BG) was measured continuously. RESULTS: Whole-body CHO oxidation was maintained during CHO trial compared with the PLA trial. Net muscle glycogen use was 52% higher for the PLA trial (176.0 +/- 16.7, 117.0 +/- 20.9 and 164.5 +/- 11.0, 133.8 +/- 10.9 mmol.kg w.w. for PLA and CHO, respectively, P < 0.05). There were no significant sex-specific differences in glycogen use, whole-body substrate oxidation, or BG values. CONCLUSION: The ingestion of CHO during long-duration exercise decreases net muscle glycogen use while better maintaining whole-body carbohydrate oxidation, and potentially increasing performance in field settings. There are limited differences in sex-specific substrate oxidation.     

Novel aspects of skeletal muscle glycogen and its regulation during rest and exercise

Although it is often viewed as a homogenous substrate, glycogen is comprised of individual granules or 'glycosomes' that vary in their composition, subcellular localization, and metabolism. These differences result in additional levels of regulation allowing granules to be regulated individually or regionally within the cell during both rest and exercise.     

Effect of carbohydrate feeding frequencies and dosage on muscle glycogen use during exercise

Nine men were studied during three 4-h cycling bouts to determine the effect of frequency and dosage of solid carbohydrate (CHO) feedings (86 g) on muscle glycogen utilization and exercise performance. In the frequency trial (F), the subjects ingested 10.75 g of CHO along with 200 ml of water at 30-min intervals; in the dosage trial (D), the subjects ingested 21.5 g of CHO with 400 ml of water at 60-min intervals. During the control trial (C), the subjects ingested 400 ml of an artificially sweetened placebo at 60-min intervals. Respiratory exchange ratios were significantly elevated in both trials D and F (P less than 0.05). Blood glucose was significantly elevated in trial D 20 min post-feeding but had returned to control levels by 50 min. In trial F, blood glucose was maintained at a constant level throughout the entire 4 h. In trial C, blood glucose declined steadily during the entire 4 h. Despite the differences in blood glucose levels between the three trials, there were no significant differences in the rate of muscle glycogen utilization in any of the trials (D = 82.9 +/- 6.6 [SE] mmol X kg-1 vs C = 80.9 +/- 6.9 mmol X kg-1 vs F = 74.4 +/- 12.2 mmol X kg-1). In a sprint ride (100% VO2max) to exhaustion at the end of each trial, the subjects performed significantly longer in trial F compared to C (120.97 +/- 9.6 vs 81.0 +/- 7.1 s).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of caffeine, fructose, and glucose ingestion on muscle glycogen utilization during exercise

Five competitive cyclists were used to determine the effects of fluid intake (16 ml.kg-1) consisting of: (i) non-nutrient control (CON); (ii) fructose (1 g.kg-1) before exercise (FRU); (iii) caffeine (5 mg.kg-1) before exercise (CAF); (iv) glucose (1 g.kg-1) during exercise (GLU); and (v) fructose/caffeine before and glucose during exercise (CFG) on blood glucose, free fatty acids, muscle glycogen, and other parameters. Exercise consisted of 90 min of cycling at 65 to 70% VO2max. Following exercise, blood glucose was found to be significantly (P less than 0.05) higher for CFG and GLU (117 and 109 mg%) compared to CON, CAF, and FRU (92, 89, and 86 mg%). Blood free fatty acids rose (P less than 0.05) further for CON (1,336), CAF (1,126), and FRU (1,034) over CFG (737) and GLU (714 mumol.l-1). Muscle glycogen utilization was greater (P less than 0.05) for CON (91) vs CAF (63) and GLU (62 mumol/g-1 wet muscle weight). It was concluded that GLU and CAF decrease muscle glycogen utilization, FRU is likely to cause gastric upset, and ingestion of multiple substances produces the greatest variability in muscle glycogen utilization and may provide added endurance benefits in some individuals.     

Skeletal muscle water and electrolytes following prolonged dehydrating exercise

We studied if dehydrating exercise would reduce muscle water (H₂O_muscle) and affect muscle electrolyte concentrations. Vastus lateralis muscle biopsies were collected prior, immediately after, and 1 and 4 h after prolonged dehydrating exercise (150 min at 33 ± 1 °C, 25% ± 2% humidity) on nine endurance‐trained cyclists (VO_2max = 54.4 ± 1.05 mL/kg/min). Plasma volume (PV) changes and fluid shifts between compartments (Cl^? method) were measured. Exercise dehydrated subjects 4.7% ± 0.3% of body mass by losing 2.75 ± 0.15 L of water and reducing PV 18.4% ± 1% below pre‐exercise values (P < 0.05). Right after exercise H₂O_muscle remained at pre‐exercise values (i.e., 398 ± 6 mL/100 g dw muscle^?1) but declined 13% ± 2% (342 ± 12 mL/100 g dw muscle^?1; P < 0.05) after 1 h of supine rest. At that time, PV recovered toward pre‐exercise levels. The Cl^? method corroborated the shift of fluid between extracellular and intracellular compartments. After 4 h of recovery, PV returned to pre‐exercise values; however, H₂O_muscle remained reduced at the same level. Muscle Na⁺ and K⁺ increased (P < 0.05) in response to the H₂O_muscle reductions. Our findings suggest that active skeletal muscle does not show a net loss of H₂O during prolonged dehydrating exercise. However, during the first hour of recovery H₂O_muscle decreases seemly to restore PV and thus cardiovascular stability.     

The incidence of hyponatremia during prolonged ultraendurance exercise

Recent studies have shown that potentially fatal hyponatremia can develop during prolonged exercise. To determine the incidence of hyponatremia in athletes competing in ultradistance events, we measured serum sodium levels in 315 of 626 (50%) runners who were treated for collapse after two 90 km ultramarathon footraces (total starters 20,335; total finishers 18,031) and in 101 of 147 (69%) finishers in a 186 km ultratriathlon. In both races the athletes drank fluids with low sodium chloride content (less than 6.8 mmol.l-1). Hyponatremia (serum sodium level less than 130 mmol.l-1) was identified in 27 of 315 (9%) collapsed runners in the 90 km races and in none of the triathletes. In response to diuretic therapy, the runner with the most severe hyponatremia (serum sodium level = 112 mmol.l-1) excreted in excess of 7.5 l dilute urine during the first 17 h of hospitalization. These data suggest that, although symptomatic hyponatremia occurs in less than 0.3% of competitors during prolonged exercise even when they ingest little sodium chloride, it is found in a significant proportion (9%) of collapsed runners. A regulated contraction of the extracellular fluid volume would explain why the majority of athletes maintain normal serum sodium levels even though they develop a significant sodium chloride deficit during prolonged exercise. Alternatively, sodium chloride losses during prolonged exercise may be substantially less than are currently believed. Physicians treating collapsed ultradistance athletes need to be aware that as many as 10% or more of such patients may be hyponatremic.     

Effect of hypoxia on heart glycogen utilization during exercise

An investigation was made into the effects of physical exercise upon heart glycogen change in rats exposed to decreased barometric pressure in hypobaric chamber simulating the effects of 3,000 m and 5,000 m altitude. Blood and cardiac tissue samples were examined after 1 h and 5 h of treadmill running at sea level and at 3,000 m, and after 1 h at 5,000 m. At sea level, cardiac glycogen level showed a classic biphasic evolution which was not affected by running. At 3,000 m, 1 h of running promoted an initial increase of 16% from control values, while a secondary decrease of 15% was measured after 5 h of running. Running for 1 h at 5,000 m induced a total depletion in cardiac glycogen level, the latter being depressed by 90% from control values. Free fatty acid (FFA) plasma level was increased by physical exercise at all barometric pressures, but the response was gradually enhanced by hypoxia. These data indicate that heart glycogen utilization during prolonged physical exercise is stimulated by acute altitude exposure, which suppresses the sparing effect observed at sea level upon dependence of enhanced FFA availability. The great differences in cardiac glycogen utilization support the views that enhanced glycogenolysis during hypoxia is promoted by different parameters, thus affecting various pathways. The slight decrease at 3,000 m suggests a moderate increase in anaerobic metabolism while the exhaustion observed after 1 h of running at 5,000 m indicates a decrease in cellular respiration response and enhanced heart anaerobic metabolism.     

Sex difference in fluid balance responses during prolonged exercise

Maintaining a proper fluid balance is important during exercise as athletes are prone to develop dehydration during exercise. Although several factors may regulate the fluid balance, little is known about the role of sex during prolonged moderate‐intensity exercise. Therefore, we compared body mass changes and fluid balance parameters in men vs women in a large heterogeneous group of participants during prolonged exercise. Ninety‐eight volunteers walked 30–50 km at a self‐selected pace. Exercise duration (8 h, 32 min) and intensity (69% HR_max) were comparable between groups. Men demonstrated a significantly larger change in body mass than women (?1.6% vs ?0.9%, respectively, P < 0.001) and a higher incidence of dehydration (defined as ≥2% body mass loss) compared with women (34% vs 12%, respectively, odds ratio = 4.2, 95% CI = 1.1–16.7). Changes in blood sodium levels were significantly different between men (+1.5 mmol/L) and women (?0.4 mmol/L), while 27% of the men vs 0% of the women showed postexercise hypernatremia (sodium levels ≥ 145 mmol/L). Moreover, men demonstrated a significantly lower fluid intake (2.9 mL/kg/h) and higher fluid loss (5.0 mL/kg/h) compared with women (3.7 and 4.8 mL/kg/h, respectively). Taken together, our data suggest that men and women demonstrate different changes in fluid balance in response to a similar bout of exercise.     

Gastric emptying during prolonged cycling exercise in the heat

Eight trained male cyclists (age 20-33 yr) completed four 3-h bouts of cycling at 60% peak VO2 in the heat (33 degrees C) drinking either water (W), 5% glucose (G), 5% glucose polymer (GP), or 3.2% glucose polymer + 1.8% fructose (GP/F) at a rate of 350 ml every 20 min (3.15 l total volume). Similar changes in heart rate, sweat rate, rectal and mean skin temperatures, and plasma [Na+], [K+], and osmolality were observed during all trials. Mean changes in plasma volume, although not significantly different between trials, were lowest for the GP/F drink (-2.6%) and greatest for the G (-8.1%) drink. Plasma volume decreased (P less than 0.05) below pre-exercise control values during the W, G, and GP trails but was maintained at control values during the GP/F trials. In contrast to water ingestion, G, GP, and GP/F ingestion maintained plasma glucose and respiratory exchange ratios throughout the 3-h exercise bouts. Gastric residual volume (GRV) obtained at the end of exercise was similar for the W, GP, and GP/F trials. The G trials yielded greater (P less than 0.05) GRV than W trials. For all drinks ingested, over 90% of the 3.15 l consumed was emptied from the stomach during the 3-h exercise bouts. At a mean sweat rate of 1.2 l.h-1, cyclists replaced 73% of fluid lost and experienced only a 1.6% loss in body weight. This study demonstrates that, during prolonged (3-h) cycling exercise in the heat, large volumes of W and 5% carbohydrate can be emptied from the stomach to help minimize the effects of dehydration.     

Effect of carbohydrate feedings on muscle glycogen utilization and exercise performance

Ten men were studied during 4 h of cycling to determine the effect of solid carbohydrate (CHO) feedings on muscle glycogen utilization and exercise performance. In the experimental trial (E) the subjects ingested 43 g of sucrose in solid form along with 400 ml of water at 0, 1, 2 and 3 h of exercise. During the control trial (C) they received 400 ml of an artificially sweetened drink without solid CHO. No differences in VO2, heart rate, or total energy expenditure were observed between trials; however, respiratory exchange ratios were significantly (P less than 0.05) higher during E. Blood glucose was significantly (P less than 0.05) elevated 20 min post-feeding in E; however, by 50 min no differences were observed between trials until 230 min (E = 4.5 +/- 0.2 mmol X l-1 vs C = 3.9 +/- 0.2, means +/- SE; P less than 0.05). Muscle glycogen utilization was significantly (P less than 0.05) lower during E (100.7 +/- 10.2 mmol X kg-1 w.w.) than C (126.2 +/- 5.5). During a sprint (100% VO2max) ride to exhaustion at the end of each trial, subjects performed 45% longer when fed CHO (E = 126.8 +/- 24.7 s vs C = 87.2 +/- 17.5; P less than 0.05). It was concluded that repeated solid CHO feedings maintain blood glucose levels, reduce muscle glycogen depletion during prolonged exercise, and enhance sprint performance at the end of such activity.     

Effectiveness of carbohydrate feeding in delaying fatigue during prolonged exercise

Prolonged exercise in the fasted state frequently results in a lowering of blood glucose concentration, and when the intensity is moderate (i.e. 60-80% of VO2 max), muscle often becomes depleted of glycogen. The extent to which carbohydrate feedings contribute to energy production, and their effectiveness for improving endurance during prolonged exercise, are reviewed in this article. Prolonged exercise (i.e. greater than 2 hours) results in a failure of hepatic glucose output to keep pace with muscle glucose uptake. As a result, blood glucose concentration frequently declines below 2.5 mmol/L. Despite this hypoglycaemia, fewer than 25% of subjects display symptoms suggestive of central nervous system dysfunction. Since fatigue rarely results from hypoglycaemia alone, the effectiveness of carbohydrate feeding should be judged by its potential for muscle glycogen sparing. Carbohydrate feeding during moderate intensity exercise postpones the development of fatigue by approximately 15 to 30 minutes, yet it does not prevent fatigue. This observation agrees with data suggesting that carbohydrate supplementation reduces muscle glycogen depletion. It is not certain whether carbohydrate feeding increases muscle glucose uptake throughout moderate exercise or if glucose uptake is higher only during the latter stages of exercise. In contrast to moderate intensity exercise, carbohydrate feeding during low intensity exercise (i.e. less than 45% of VO2 max) results in hyperinsulinaemia. Consequently, muscle glucose uptake and total carbohydrate oxidation are increased by approximately the same amount. The amount of ingested glucose which is oxidised is greater than the increase in total carbohydrate oxidation and therefore endogenous carbohydrate is spared. The majority of sparing appears to occur in the liver, which is reasonable since muscle glycogen is not utilised to a large extent during mild exercise. Although carbohydrate feedings prevent hypoglycaemia and are readily used for energy during mild exercise, there is little data indicating that feedings improve endurance during low intensity exercise. When the reliance on carbohydrate for fuel is greater, as during moderate intensity exercise, carbohydrate feedings delay fatigue by apparently slowing the depletion of muscle glycogen.