Andrew N. Bosch

Metabolic Consequences of Exercise-Induced Muscle Damage

Exercise-induced muscle damage (EIMD) is commonly experienced following either a bout of unaccustomed physical activity or following physical activity of greater than normal duration or intensity. The mechanistic factor responsible for the initiation of EIMD is not known; however, it is hypothesised to be either mechanical or metabolic in nature. The mechanical stress hypothesis states that EIMD is the result of physical stress upon the muscle fibre. In contrast, the metabolic stress model predicts that EIMD is the result of metabolic deficiencies, possibly through the decreased action of Ca2+-adenosine triphosphatase. Irrespective of the cause of the damage, EIMD has a number of profound metabolic effects. The most notable metabolic effects of EIMD are decreased insulin sensitivity, prolonged glycogen depletion and an increase in metabolic rate both at rest and during exercise. Based on current knowledge regarding the effects that various types of damaging exercise have on muscle metabolism, a new model for the initiation of EIMD is proposed. This model states that damage initiation may be either metabolic or mechanical, or a combination of both, depending on the mode, intensity and duration of exercise and the training status of the individual.

Physiological differences between black and white runners during a treadmill marathon

SummaryTo determine why black distance runners currently out-perform white distance runners in South Africa, we measured maximum oxygen consumption (VO2max), maximum workload during a VO2max test (Lmax), ventilation threshold (VThr), running economy, inspiratory ventilation (VI), tidal volume (VT), breathing frequency (f) and respiratory exchange ratio (RER) in sub-elite black and white runners matched for best standard 42.2 km marathon times. During maximal treadmill testing, the black runners achieved a significantly lower (P<0.05) Lmax (17 km h−1, 2% grade, vs 17 km h−1, 4% grade) and VI max (6.21 vs 6.821 kg−2/3 min−1), which was the result of a lower VT (101 vs 119 ml kg−2/3 breath−1) as fmax was the same in both groups. The lower VT in the black runners was probably due to their smaller body size. The VThr occurred at a higher percentage VO2max in black than in white runners (82.7%, SD 7.7% vs 75.6%, SD 6.2% respectively) but there were no differences in the VO2max. However, during a 42.2-km marathon run on a treadmill, the black athletes ran at the higher percentage VO2max (76%, SD 7.9% vs 68%, SD 5.3%), RER (0.96, SD 0.07 vs 0.91, SD 0.04) and f (56 breaths min−1, SD 11 vs 47 breaths min−1, SD 10), and at lower VT (78 ml kg−2/3 breath−1, SD 15 vs 85 ml kg−2/3 breath−1, SD 19). The combination of higher f and lower VT resulted in an identical VI. Blood lactate levels were lower in black than in white runners (1.3 mmol l−1, SD 0.6 vs 1.59 mmol l−1, SD 0.2 respectively). It appeared that the only physiological difference that may account for the superior performance of the black runners was their ability to run at a higher percentage VO2max max during competition than white runners.

Influence of muscle glycogen content on metabolic regulation

Euglycemia was maintained in 13 subjects with low muscle glycogen [low glycogen, euglycemic (LGE), n = 8; low glycogen, euglycemic, hyperinsulinemic (LGEI), n = 5] and 6 subjects with normal muscle glycogen (NGE), whereas hyperglycemia was maintained in 8 low muscle glycogen subjects (LGH). All subjects cycled for 145 min at 70% of maximal oxygen uptake during the infusions. Insulin was infused in LGEI at 0.2 mU.kg-1.min-1. During exercise, respiratory exchange ratio (RER) was lower and norepinephrine higher in LGE than in NGE. In LGEI and LGH, RER at the start of exercise was the same as in LGE but did not decrease as in LGE. Free fatty acids (FFA) were higher and plasma insulin concentrations lower in LGE than NGE, LGEI, or LGH over the first 45 min of exercise. Rate of glucose infusion (Ri) and rate of glucose oxidation (Rox) were higher in LGH and LGEI than in NGE or LGE, and Ri matched Rox in all groups except LGH, in which Ri was greater than Rox. Muscle glycogen disappearance was greater in NGE than LGE, LGEI, or LGH, but the latter three groups did not differ. In conclusion, this study showed that low muscle glycogen content results in a decrease in RER, an increase in FFA, fat oxidation, and norepinephrine both at rest and during exercise, and does not affect Rox when euglycemia is maintained by infusion of glucose alone. Rox was increased only during insulin and hyperglycemia.

The effect of the menstrual cycle on exercise metabolism: implications for exercise performance in eumenorrhoeic women.

The female hormones, oestrogen and progesterone, fluctuate predictably across the menstrual cycle in naturally cycling eumenorrhoeic women. Other than reproductive function, these hormones influence many other physiological systems, and their action during exercise may have implications for exercise performance. Although a number of studies have found exercise performance — and in particular, endurance performance — to vary between menstrual phases, there is an equal number of such studies reporting no differences. However, a comparison of the increase in the oestrogen concentration (E) relative to progesterone concentration (P) as the E/P ratio (pmol/ nmol) in the luteal phase in these studies reveals that endurance performance may only be improved in the mid-luteal phase compared with the early follicular phase when the E/P ratio is high in the mid-luteal phase. Furthermore, the late follicular phase, characterized by the pre-ovulatory surge in oestrogen and suppressed progesterone concentrations, tends to promote improved performance in a cycling time trial and future studies should include this menstrual phase. Menstrual phase variations in endurance performance may largely be a consequence of changes to exercise metabolism stimulated by the fluctuations in ovarian hormone concentrations. The literature suggests that oestrogen may promote endurance performance by altering carbohydrate, fat and protein metabolism, with progesterone often appearing to act antagonistically. Details of the ovarian hormone influences on the metabolism of these macronutrients are no longer only limited to evidence from animal research and indirect calorimetry but have been verified by substrate kinetics determined with stable tracer methodology in eumenorrhoeic women. This review thoroughly examines the metabolic perturbations induced by the ovarian hormones and, by detailed comparison, proposes reasons for many of the inconsistent reports in menstrual phase comparative research. Often the magnitude of increase in the ovarian hormones between menstrual phases and the E/P ratio appear to be important factors determining an effect on metabolism. However, energy demand and nutritional status may be confounding variables, particularly in carbohydrate metabolism. The review specifically considers how changes in metabolic responses due to the ovarian hormones may influence exercise performance. For example, oestrogen promotes glucose availability and uptake into type I muscle fibres providing the fuel of choice during short duration exercise; an action that can be inhibited by progesterone. A high oestrogen concentration in the luteal phase augments muscle glycogen storage capacity compared with the low oestrogen environment of the early follicular phase. However, following a carbo-loading diet will super-compensate muscle glycogen stores in the early follicular phase to values attained in the luteal phase. Oestrogen concentrations of the luteal phase reduce reliance on muscle glycogen during exercise and although not as yet supported by human tracer studies, oestrogen increases free fatty acid availability and oxidative capacity in exercise, favouring endurance performance. Evidence of oestrogen’s stimulation of 50-AMPactivated protein kinase may explain many of the metabolic actions of oestrogen. However, both oestrogen and progesterone suppress gluconeogenic output during exercise and this may compromise performance in the latter stages of ultra-long events if energy replacement supplements are inadequate. Moreover, supplementing energy intake during exercise with protein may be more relevant when progesterone concentration is elevated compared with menstrual phases favouring a higher relative oestrogen concentration, as progesterone promotes protein catabolism while oestrogen suppresses protein catabolism. Furthermore, prospective research ideas for furthering the understanding of the impact of the menstrual cycle on metabolism and exercise performance are highlighted.

Maintenance of plasma volume and serum sodium concentration despite body weight loss in ironman triathletes.

Objective:To examine the relationship between body weight, plasma volume, and serum sodium concentration ([Na+]) during prolonged endurance exercise. Design:Observational field study. Settings:2000 South African Ironman Triathlon. Participants:181 male triathletes competing in an Ironman triathlon. Main Outcome Measures:Body weight, plasma volume, and serum ([Na+]) change from pre- to postrace. Results:Significant body weight loss occurred (−4.9 ± 1.7%; P < 0.0001), while both plasma volume (1.0 ± 11.2%; P = 0.4: NS) and serum [Na+] (0.6 ± 2.4%; P < 0.001) increased from pre- to postrace. Blood volume (−0.6 ± 6.6%) and red cell volume (−2.6 ± 5.5%; P < 0.001) decreased in conjunction with the body weight loss. There was a strong correlation between blood and plasma volume change, both as a percentage, and absolute change in fluid volume (r = 0.9; P < 0.001). Body weight change was positively correlated with plasma volume change (r = −0.4; P < 0.001), but inversely correlated with serum [Na+] change (r = −0.4; P < 0.001). Plasma volume change was not significantly correlated with serum [Na+] change (r = 0.0; NS). Serum [Na+] change was inversely correlated with both percentage of red cell volume change (r = −0.2; P < 0.05) and percentage body weight change (r = −0.4; P < 0.001). Conclusion:Plasma volume and serum [Na+] were maintained in male Ironman triathletes, despite significant (5%) body weight loss during the course of the race. Body weight was not an accurate “absolute” surrogate of fluid balance homeostasis during prolonged endurance exercise. Clinicians should be warned against viewing these three regulatory parameters as interchangeable during an Ironman triathlon.

Glucose kinetics during prolonged exercise in euglycaemic and hyperglycaemic subjects.

To determine the limits to oxidation of exogenous glucose by skeletal muscle, the effects of euglycaemia (plasma glucose 5 mM, ET) and hyperglycaemia (plasma glucose 10 mM, HT) on fuel substrate kinetics were evaluated in 12 trained subjects cycling at 70% of maximal oxygen uptake (VO2, max) for 2 h. During exercise, subjects ingested water labelled with traces of U-14C-glucose so that the rates of plasma glucose oxidation (Rox) could be determined from plasma 14C-glucose and expired 14CO2 radioactivities, and respiratory gas exchange. Simultaneously, 2-3H-glucose was infused at a constant rate to estimate rates of endogenous glucose turnover (Ra), while unlabelled glucose (25% dextrose) was infused to maintain plasma glucose concentration at either 5 or 10 mM. During ET, endogenous liver glucose Ra (total Ra minus the rate of infusion) declined from 22.4±4.9 to 6.5±1.4 μmol/min per kg fat-free mass [FFM] (P<0.05) and during HT it was completely suppressed. In contrast, Rox increased to 152±21 and 61±10 μmol/min per kg FFM at the end of HT and ET respectively (P<0.05). HT (i. e., plasma glucose 10 mM) and hyperinsulinaemia (24.5±0.9 μU/ml) also increased total carbohydrate oxidation from 203±7 (ET) to 310±3 μmol/min per kg FFM (P<0.0001) and suppressed fat oxidation from 51±3 (ET) to 18±2 μmol/min per kg FFM (P<0.0001). As the rates of oxidation at more physiological euglycaemic concentrations of glucose were limited to 92±9 μmol/ min per kg FFM, and were similar to those reported when carbohydrate is ingested, the results of the current study suggest that the concentrations of glucose and insulin normally present during prolonged, intense exercise may limit the rate of muscle glucose uptake and oxidation.

The effect of a preexercise meal on time to fatigue during prolonged cycling exercise.

PURPOSE AND METHODS Seven subjects exercised to exhaustion on a bicycle ergometer at a workload corresponding to an intensity of 70% maximal oxygen uptake (VO2max). On one occasion (FED), subjects consumed a preexercise carbohydrate (CHO) containing breakfast (100 g CHO) 3 h before exercise. On the other occasion (FASTED), subjects exercised after an overnight fast. Exercise time to fatigue was significantly longer (P < 0.05) when subjects consumed the breakfast (136+/-14 min) compared with when they exercised in the fasted state (109+/-12 min). RESULTS Pre- and post-exercise muscle glycogen concentrations, respiratory exchange ratio, carbohydrate and fat oxidation, and lactate and insulin concentrations were not significantly different between the two trials. Insulin concentrations decreased significantly (P < 0.05) from 4.7+/-0.05 microIU.mL(-1) to 2.8+/-0.4 microIU.mL(-1) in FED and from 6.6+/-0.6 microIU.mL(-1) to 3.7+/-0.6 microIU.mL(-1) in FASTED subjects and free fatty acid concentrations (FFA) increased significantly (P < 0.05) from 0.09+/-0.02 mmol.L(-1) to 1.4+/-0.6 mmol.L(-1) in FED and from 0.17+/-0.02 mmol.L(-) to 0.74+/-0.27 mmol.L(-1) in FASTED subjects over the duration of the trials. CONCLUSIONS In conclusion, the important finding of this study is the increased time to fatigue when subjects ingested the CHO meal with no negative effects ascribed to increased insulin concentrations and decreased FFA concentrations after CHO ingestion.

Preexercise muscle glycogen content affects metabolism during exercise despite maintenance of hyperglycemia

Trained cyclists with low muscle glycogen (LGH; n = 8) or normal glycogen (NGH; n = 5) exercised for 145 min at 70% of maximal oxygen uptake during a hyperglycemic clamp. Respiratory exchange ratio was higher in NGH than LGH, and free fatty acid concentrations were lower in NGH than LGH. Areas under the curve for insulin and lactate were lower in LGH than NGH. Total glucose infusion and total glucose oxidation were not different between NGH and LGH, and total glucose oxidation amounted to 65 and 66% of total glucose infusion in NGH and LGH, respectively. Rates of glucose oxidation rose during exercise, reaching peaks of 9.2 ± 1.7 and 8.3 ± 1.1 mmol/min in NGH and LGH, respectively. Muscle glycogen disappearance was greater in NGH than LGH. Thus 1) low muscle glycogen content does not cause increased glucose oxidation, even during hyperglycemia; instead there is an increase in fat oxidation, 2) there is an upper limit to the rate of glucose oxidation during exercise with hyperglycemia irrespective of muscle glycogen status, and 3) net muscle glycogen utilization is determined by muscle glycogen content at the start of exercise, even during hyperglycemia.Trained cyclists with low muscle glycogen (LGH; n = 8) or normal glycogen (NGH; n = 5) exercised for 145 min at 70% of maximal oxygen uptake during a hyperglycemic clamp. Respiratory exchange ratio was higher in NGH than LGH, and free fatty acid concentrations were lower in NGH than LGH. Areas under the curve for insulin and lactate were lower in LGH than NGH. Total glucose infusion and total glucose oxidation were not different between NGH and LGH, and total glucose oxidation amounted to 65 and 66% of total glucose infusion in NGH and LGH, respectively. Rates of glucose oxidation rose during exercise, reaching peaks of 9.2 +/- 1.7 and 8.3 +/- 1.1 mmol/min in NGH and LGH, respectively. Muscle glycogen disappearance was greater in NGH than LGH. Thus 1) low muscle glycogen content does not cause increased glucose oxidation, even during hyperglycemia; instead there is an increase in fat oxidation, 2) there is an upper limit to the rate of glucose oxidation during exercise with hyperglycemia irrespective of muscle glycogen status, and 3) net muscle glycogen utilization is determined by muscle glycogen content at the start of exercise, even during hyperglycemia.

Oxidation of exogenous carbohydrate during prolonged exercise: the effects of the carbohydrate type and its concentration

SummaryWe studied rates of exogenous carbohydrate (CHO) oxidation during 90 min of cycling exercise in trained cyclists exercising at 70% of maximal oxygen consumption (VO2max) when they ingested glucose, sucrose, or glucose polymer solutions at concentrations of 7.5%, 10% or 15%. Drinks were labelled with [U-14C]glucose or sucrose and were ingested at a rate of 100 ml · 10 min−1. Rates of oxidation of the ingested CHO were calculated from the specific radio-activity of the labelled CHO, expired14CO2 and carbon dioxide output (VCO2). Total CHO oxidation, determined from oxygen consumption andVCO2 was not influenced by CHO type or concentration. Gastric emptying (P=0.01) and the rate of exogenous CHO oxidation (P=0.028) was greatest for the glucose polymer solutions, and least for glucose. Although gastric emptying (P=0.006) decreased with increasing CHO concentration, CHO delivery to the intestine and exogenous CHO oxidation increased linearly with increasing CHO concentration. The percentage of the CHO delivered to the intestine that was oxidized ranged from 30.0% for 7.5% CHO to 38.1% for 15% CHO. Our results indicated that the rate of gastric emptying for CHO was not controlled to provide a constant rate of energy delivery as is commonly believed and that factors subsequent to gastric emptying limit the rate of exogenous CHO oxidation from the ingested solution.

Fuel substrate turnover and oxidation and glycogen sparing with carbohydrate ingestion in non-carbohydrate-loaded cyclists

This study examined the effects of ingesting 500 ml/h of either a 10% carbohydrate (CHO) drink (CI) or placebo (PI) on splanchnic glucose appearance rate (endogenous + exogenous) (Ra), plasma glucose oxidation and muscle glycogen utilisation in 17, non-carbohydrate-loaded, male, endurance-trained cyclists who rode for 180 min at 70% of maximum oxygen uptake. Mean muscle glycogen content at the start of exercise was 130±6 mmol/kg ww; (mean ± SEM). Total CHO oxidation was similar in CI and PI subjects and declined during the trial. Ra increased significantly during the trial (P < 0.05) in both groups. Plasma glucose oxidation also increased significantly during the trial, reaching a plateau in the PI subjects, but was significantly (P < 0.05) higher in CI than PI subjects at the end of exercise [(98 ± 14 vs. 72 ± 10 μmol/min/kg fat-free mass) (FFM) (1.34 ± 0.19 vs. 0.93 ± 0.13 g/min)]. However, mean endogenous Ra was significantly (P < 0.05) lower in the CI than PI subjects throughout exercise (35 ± 7 vs. 54 ± 6 μmol/min/kg FFM), as was the oxidation of endogenous plasma glucose, which remained almost constant in CI subjects, and reached values at the end of exercise of 42 ± 13 and 72 ± 10 μmol/min/kg FFM in the CI and PI groups respectively. Of the 150 g CHO ingested during the trial, 50% was oxidised. Muscle glycogen disappearance was identical during the first 2 h of exercise in both groups and continued at the same rate in PI subjects, however no net muscle glycogen disappearance occurred during the final hour in CI subjects. We conclude that ingestion of 500 ml/h of a 10% CHO solution during prolonged exercise in non carbohydrate loaded subjects has a marked liver glycogen-sparing effect or causes a reduction in gluconeogenesis, or both, maintains plasma glucose concentration and has a muscle glycogen-sparing effect.