Metabolic, catecholamine, and endurance responses to caffeine during intense exercise

Jackman, M., P. Wendling, D. Friars, and T. E. Graham.Metabolic, catecholamine, and endurance responses to caffeine during intense exercise. J. Appl.Physiol. 81(4): 1658-1663, 1996.This studyexamined the possible effects of caffeine ingestion on muscle metabolism and endurance during brief intense exercise. We tested 14 subjects after they ingested placebo or caffeine (6 mg/kg) with anexercise protocol in which they cycled for 2 min, rested 6 min, cycled2 min, rested 6 min, and then cycled to voluntary exhaustion. In eachexercise the intensity required the subject's maximalO₂ consumption. Eight subjects hadmuscle and venous blood samples taken before and after each exerciseperiod. The caffeine ingestion resulted in a significant increase inendurance (4.12 ± 0.36 and 4.93 ± 0.60 min for placebo andcaffeine, respectively) and resulted in a significant increase inplasma epinephrine concentration throughout the protocol but not innorepinephrine concentration. During the first two exercise bouts, thepower and work output were not different; blood lactate concentrationswere not affected significantly by caffeine ingestion, but during theexercise bouts muscle lactate concentration was significantly increasedby caffeine. The net decrease in muscle glycogen was not differentbetween treatments at any point in the protocol, and even at the time of fatigue there was at least 50% of the original glycogenconcentration remaining. The data demonstrated that caffeine ingestioncan be an effective ergogenic aid for exercise that is as brief as4-6 min. However, the mechanism is not associated with muscleglycogen sparing. It is possible that caffeine is exerting actionsdirectly on the active muscle and/or the neural processes thatare involved in the activity.

     

Effect of caffeine on metabolism, exercise endurance, and catecholamine responses after withdrawal

In this studythe effects of acute caffeine ingestion on exercise performance,hormonal (epinephrine, norepinephrine, insulin), and metabolic (freefatty acids, glycerol, glucose, lactate, expired gases) parametersduring short-term withdrawal from dietary caffeine were investigated.Recreational athletes who were habitual caffeine users(n = 6) (maximum oxygen uptake 54.5 ± 3.3 ml · kg¹ · min¹and daily caffeine intake 761.3 ± 11.8 mg/day) were tested under conditions of no withdrawal and 2-day and 4-day withdrawal from dietarycaffeine. There were seven trials in total with a minimum of 10 daysbetween trials. On the day of the exercise trial, subjects ingestedeither dextrose placebo or 6 mg/kg caffeine in capsule form 1 h beforecycle ergometry to exhaustion at 80-85% of maximum oxygen uptake.Test substances were assigned in a random, double-blind manner. A finalplacebo control trial completed the experiment. There was nosignificant difference in any measured parameters among days ofwithdrawal after ingestion of placebo. At exhaustion in the 2- and4-day withdrawal trials, there were significant increases in plasmanorepinephrine in response to caffeine ingestion. Caffeine-inducedincreases in serum free fatty acids occurred after 4 days and only atrest. Subjects responded to caffeine with increases in plasmaepinephrine (P < 0.05) atexhaustion and prolonged exercise time in all caffeine trials comparedwith placebo, regardless of withdrawal from caffeine. It is concluded that increased endurance is unrelated to hormonal or metabolic changesand that it is not related to prior caffeine habituation inrecreational athletes.

     

Metabolic responses to exercise after fasting

Fasting before exercise increases fat utilization and lowers the rate of muscle glycogen depletion. Since a 24-h fast also depletes liver glycogen, we were interested in blood glucose homeostasis during exercise after fasting. An experiment was conducted with human subjects to determine the effect of fasting on blood metabolite concentrations during exercise. Nine male subjects ran (70% maximum O2 consumption) two counterbalanced trials, once fed and once after a 23-h fast. Plasma glucose was elevated by exercise in the fasted trial but there was no difference between fed and fasted during exercise. Lactate was significantly higher (P less than 0.05) in fasted than fed throughout the exercise bout. Fat mobilization and utilization appeared to be greater in the fasted trial as evidenced by higher plasma concentrations of free fatty acids, glycerol, and beta-hydroxybutyrate as well as lower respiratory exchange ratio in the fasted trial during the first 30 min of exercise. These results demonstrate that in humans blood glucose concentration is maintained at normal levels during exercise after fasting despite the depletion of liver glycogen. Homeostasis is probably maintained as a result of increased gluconeogenesis and decreased utilization of glucose in the muscle as a result of lowered pyruvate dehydrogenase activity.     

Plasma free and sulfoconjugated catecholamine responses to varying exercise intensity

Plasma free catecholamines rise during exercise, but sulfoconjugated catecholamines reportedly fall. This study examined the relationship between exercise intensity and circulating levels of sulfoconjugated norepinephrine, epinephrine, and dopamine. Seven exercise-trained men biked at approximately 30, 60, and 90% of their individual maximal oxygen consumption (VO2max) for 8 min. The 90% VO2max period resulted in significantly increased plasma free norepinephrine (rest, 219 +/- 85; exercise, 2,738 +/- 1,149 pg/ml; P less than or equal to 0.01) and epinephrine (rest, 49 +/- 49; exercise, 555 +/- 516 pg/ml; P less than or equal to 0.05). These changes were accompanied by consistent increases in sulfoconjugated norepinephrine at both the 60% (rest, 852 +/- 292; exercise, 1,431 +/- 639; P less than or equal to 0.05) and 90% (rest, 859 +/- 311; exercise, 2,223 +/- 1,015; P less than or equal to 0.05) VO2max periods. Plasma sulfoconjugated epinephrine and dopamine displayed erratic changes at the three exercise intensities. These findings suggest that sulfoconjugated norepinephrine rises during high-intensity exercise.     

Metabolic and performance responses to constant-load vs. variable-intensity exercise in trained cyclists.

We studied glucose oxidation (Glu(ox)) and glycogen degradation during 140 min of constant-load [steady-state (SS)] and variable-intensity (VI) cycling of the same average power output, immediately followed by a 20-km performance ride [time trial (TT)]. Six trained cyclists each performed four trials: two experimental bouts (SS and VI) in which muscle biopsies were taken before and after 140 min of exercise for determination of glycogen and periodic acid-Schiff's staining; and two similar trials without biopsies but incorporating the TT. During two of the experimental rides, subjects ingested a 5 g/100 ml [U-(14)C]glucose solution to determine rates of Glu(ox). Values were similar between SS and VI trials: O(2) consumption (3.08 +/- 0.02 vs. 3.15 +/- 0.03 l/min), energy expenditure (901 +/- 40 vs. 904 +/- 58 J x kg(-1) x min(-1)), heart rate (156 +/- 1 vs. 160 +/- 1 beats/min), and rating of perceived exertion (12.6 +/- 0.6 vs. 12.7 +/- 0.7). However, the area under the curve for plasma lactate concentration vs. time was significantly greater during VI than SS (29.1 +/- 3.9 vs. 24.6 +/- 3. 7 mM/140 min; P = 0.03). VI resulted in a 49% reduction in total muscle glycogen utilization vs. 65% for SS, while total Glu(ox) was higher (99.2 +/- 5.3 vs. 83.9 +/- 5.2 g/140 min; P < 0.05). The number of glycogen-depleted type I muscle fibers at the end of 140 min was 98% after SS but only 59% after VI. Conversely, the number of type II fibers that showed reduced periodic acid-Schiff's staining was 1% after SS vs. 10% after VI. Despite these metabolic differences, subsequent TT performance was similar (29.14 +/- 0.9 vs. 30.5 +/- 0.9 min for SS vs. VI). These results indicate that whole body metabolic and cardiovascular responses to 140 min of either SS or VI exercise at the same average intensity are similar, despite differences in skeletal muscle carbohydrate metabolism and recruitment.     

Metabolic and performance responses during endurance exercise after high-fat and high-carbohydrate meals

We studied the effects of preexercise mealcomposition on metabolic and performance-related variables duringendurance exercise. Eight well-trained cyclists (maximal oxygen uptake65.0 to 83.5 ml · kg¹ · min¹)were studied on three occasions after an overnight fast. They weregiven isoenergetic meals containing carbohydrate (CHO), protein (P),and fat (F) in the following amounts (g/70 kg body wt):high-carbohydrate meal, 215 CHO, 26 P, 3 F; high-fat meal, 50 CHO, 14 P, 80 F. On the third occasion subjects were studied after an overnightfast. Four hours after consumption of the meal, subjects startedexercise for 90 min at 70% of their maximal oxygen uptake, followed by a 10-km time trial. The high-carbohydrate meal compared with the high-fat meal resulted in significant decreases(P < 0.05) in blood glucose, plasmanonesterified fatty acids, plasma glycerol, plasmachylomicron-triacylglycerol, and plasma 3-hydroxybutyrate concentrations during exercise. This was accompanied by anincrease in plasma insulin (P < 0.01 vs. no meal), plasma epinephrine, and plasma growth hormoneconcentrations (each P < 0.05 vs.either of the other conditions) during exercise. Despite these large differences in substrate and hormone concentrations in plasma, substrate oxidation during the 90-min exercise period was similar inthe three trials, and there were no differences in performance on thetime trial. These results suggest that, although the availability offatty acids and other substrates in plasma can be markedly altered bydietary means, the pattern of substrate oxidation during enduranceexercise is remarkably resistant to alteration.

     

Effect of caffeine on ventilatory responses to hypercapnia, hypoxia, and exercise in humans

The effect of oral caffeine on resting ventilation (VE), ventilatory responsiveness to progressive hyperoxic hypercapnia (HCVR), isocapnic hypoxia (HVR), and moderate exercise (EVR) below the anaerobic threshold (AT) was examined in seven healthy adults. Ventilatory responses were measured under three conditions: control (C) and after ingestion of either 650 mg caffeine (CF) or placebo (P) in a double-blind randomized manner. None of the physiological variables of interest differed significantly for C and P conditions (P greater than 0.05). Caffeine levels during HCVR, HVR, and EVR were 69.5 +/- 11.8, 67.8 +/- 10.8, and 67.8 +/- 10.9 (SD) mumol/l, respectively (P greater than 0.05). Metabolic rate at rest and during exercise was significantly elevated during CF compared with P. An increase in VE from 7.4 +/- 2.5 (P) to 10.5 +/- 2.1 l/min (CF) (P less than 0.05) was associated with a decrease in end-tidal PCO2 from 39.1 +/- 2.7 (P) to 35.1 +/- 1.3 Torr (CF) (P less than 0.05). Caffeine increased the HCVR, HVR, and EVR slopes (mean increase: 28 +/- 8, 135 +/- 28, 14 +/- 5%, respectively) compared with P; P less than 0.05 for each response. Increases in resting ventilation, HCVR, and HVR slopes were associated with increases in tidal volume (VT), whereas the increase in EVR slope was accompanied by increases in both VT and respiratory frequency. Our results indicate that caffeine increases VE and chemosensitivity to CO2 inhalation, hypoxia, and CO2 production during exercise below the AT.     

Metabolic and exercise endurance effects of coffee and caffeine ingestion

Caffeine (Caf) ingestion increases plasmaepinephrine (Epi) and exercise endurance; these results are frequentlytransferred to coffee (Cof) consumption. We examined theimpact of ingestion of the same dose of Caf in Cof or in water. Ninehealthy, fit, young adults performed five trials after ingesting(double blind) either a capsule (Caf or placebo) with water or Cof(decaffeinated Cof, decaffeinated with Caf added, or regularCof). In all three Caf trials, the Caf dose was 4.45 mg/kgbody wt and the volume of liquid was 7.15 ml/kg. After 1 h of rest, thesubject ran at 85% of maximal O₂consumption until voluntary exhaustion (~32 min in the placebo anddecaffeinated Cof tests). In the three Caf trials, the plasma Caf andparaxanthine concentrations were very similar. After 1 h of rest, theplasma Epi was increased (P < 0.05)by Caf ingestion, but the increase was greater(P < 0.05) with Caf capsules thanwith Cof. During the exercise there were no differences in Epi amongthe three Caf trials, and the Epi values were all greater(P < 0.05) than in the othertests. Endurance was only increased(P < 0.05) in the Caf capsule trial; there were no differences among the other four tests. One cannot extrapolate the effects of Caf to Cof; there must be a component(s) ofCof that moderates the actions of Caf.

     

Plasma catecholamine and nephrine responses to brief intermittent maximal intensity exercise

Catecholamines (noradrenaline, NA; adrenaline, AD; dopamine, DA) influence the metabolic and cardiovascular responses to exercise. However, changes in catecholamine metabolism during exercise are unclear. Plasma normetanephrine (NMET), metanephrine (MET) and catecholamine responses to a laboratory-based model of games-type exercise were examined. Twelve healthy men completed a resting control trial and a trial consisting of ten 6 s cycle ergometer sprints interspersed with 30 s recovery, in randomised order. Resting and post-sprint venous blood samples were taken. Plasma NA and AD increased after each sprint but DA was unaltered. Plasma nephrines increased significantly from sprint 4 onwards with peak NMET increasing 60% to 0.76 ± 0.19 nmol l⁻¹ and MET 230% to 0.37 ± 0.16 nmol l⁻¹ from resting values (P < 0.05). The results demonstrate increased catecholamine metabolism via elevated catechol-O-methyl transferase activity during intermittent sprinting. The results may aid regulation of the metabolic and cardiovascular responses to exercise by maintaining tissue adrenoceptor sensitivity to circulating catecholamines.     

Plasma Met-enkephalin and catecholamine responses to intense exercise in humans.

Native and cryptic Met-enkephalin and catecholamines are coreleased in response to stress. However, it is not known whether Met-enkephalin and catecholamines exhibit concurrent temporal relationships in response to exercise. The purpose of this investigation was to examine the corelease of catecholamines and Met-enkephalin in endurance-trained (n = 6) and untrained (n = 6) male subjects during a 6-min bout of exercise: 4 min at 70% of maximal O2 uptake (VO2max) followed by 2 min at 120% VO2max. Peak catecholamine levels were found at 1 min of recovery. In trained subjects, native Met-enkephalin peaked during exercise at 70% VO2max, declined during exercise at 120% VO2max, and returned to basal levels by 1 min of recovery. In the untrained subjects, native Met-enkephalin peaked at 120% VO2max (6 min) and returned to baseline by 5 min of recovery. In both groups, cryptic Met-enkephalin peaked at 70% VO2max and returned to basal levels during exercise at 120% VO2max. These data demonstrate that during exercise there is a temporal dissociation in plasma levels of Met-enkephalin and catecholamines.     

Plasma catecholamine responses to exercise after training with beta-adrenergic blockade

Exercise training has been shown to decrease plasma norepinephrine (NE) and epinephrine (EPI) levels during absolute levels of submaximal exercise, which may reflect alterations in sympathetic tone as a result of training. To determine if beta-adrenergic blockade altered these changes in the plasma concentration of catecholamines with exercise conditioning, we studied the effects of beta-adrenergic blockade on NE and EPI at rest and during exercise in 24 healthy, male subjects after a 6-wk exercise training program. The subjects were randomized to placebo (P), atenolol 50 mg twice daily (A), and nadolol 40 mg twice daily (N). There were no changes in resting NE and EPI compared with pretraining values in any subject group. During the same absolute level of submaximal exercise NE decreased in P and A but was unchanged in N, whereas EPI decreased only in P. At maximal exercise all three groups developed significant increases in NE after training that paralleled increases in systolic blood pressure. EPI at maximal exercise increased after training with N but was unchanged with P or A. These training-induced changes in plasma catecholamine levels were masked or blunted when the A and N groups were studied while still on medication after training. Thus beta-adrenergic blockade has important effects on adaptations of the sympathetic nervous system to training, especially during submaximal exercise.     

Acute and habitual caffeine ingestion and metabolic responses to steady-state exercise.

This study compared the exercise catecholamine and metabolic responses to a caffeine challenge in trained subjects before and after a 6-wk period of increased caffeine ingestion. Trained subjects (n = 6) were challenged with 500 mg of caffeine followed by prolonged exercise before and after 6 wk of increased caffeine ingestion (500 mg ingested before each daily run). A control group (n = 6) of trained subjects followed the same protocol except for caffeine ingestion. Acute caffeine ingestion resulted in increased plasma epinephrine and decreased respiratory exchange ratio (RER) during exercise. After 6 wk of caffeine supplementation, the epinephrine response to exercise or caffeine plus exercise was decreased, although the latter still resulted in a lower RER value compared with exercise without caffeine ingestion. Activity of key metabolic enzymes (hexokinase, citrate synthase, phosphorylase, and 3-hydroxyacyl-coenzyme A dehydrogenase) from biopsies of the gastrocnemius showed no response to 6 wk of this increased adrenergic receptor stimulation and, on the basis of the lower RER, enhanced fat metabolism. This study suggests that caffeine ingestion by trained subjects causes increases in plasma epinephrine and reduces the RER during exercise. However, habitual stimulation results in a general dampening of the epinephrine response to caffeine or exercise. There was no indication that increased adrenergic stimulation and fat oxidation caused any adaptation in the activity of metabolic enzymes.