Muscle metabolism during prolonged exercise in humans: influence of carbohydrate availability.

Eight endurance-trained men cycled to volitional exhaustion at 69 +/- 1% peak oxygen uptake on two occasions to examine the effect of carbohydrate supplementation during exercise on muscle energy metabolism. Subjects ingested an 8% carbohydrate solution (CHO trial) or a sweet placebo (Con trial) in a double-blind, randomized order, with vastus lateralis muscle biopsies (n = 7) obtained before and immediately after exercise. No differences in oxygen uptake, heart rate, or respiratory exchange ratio during exercise were observed between the trials. Exercise time to exhaustion was increased by approximately 30% when carbohydrate was ingested [199 +/- 21 vs. 152 +/- 9 (SE) min, P < 0.05]. Plasma glucose and insulin levels during exercise were higher and plasma free fatty acids lower in the CHO trial. No differences between trials were observed in the decreases in muscle glycogen and phosphocreatine or the increases in muscle lactate due to exercise. Muscle ATP levels were not altered by exercise in either trial. There was a small but significant increase in muscle inosine monophosphate levels at the point of exhaustion in both trials, and despite the subjects in CHO trial cycling 47 min longer, their muscle inosine monophosphate level was significantly lower than in the Con trial (CHO: 0.16 +/- 0.08, Con: 0.23 +/- 0.09 mmol/kg dry muscle). These data suggest that carbohydrate ingestion may increase endurance capacity, at least in part, by improving muscle energy balance.     

A threshold exists for the stimulatory effect of insulin on plasma L-carnitine clearance in humans

Maintaining hyperinsulinemia ( approximately 160 mU/l) during steady-state hypercarnitinemia ( approximately 550 mumol/l) increases skeletal muscle total carnitine (TC) content by approximately 15% within 5 h. The aim of the present study was to further examine the relationship between serum insulin concentration and skeletal muscle carnitine accumulation by attempting to identify the serum insulin concentration at which this stimulatory effect of insulin on carnitine retention becomes apparent. On four randomized experimental visits, eight healthy men (body mass index 23.8 +/- 0.9 kg/m(2)) underwent a 6-h euglycemic insulin clamp of 5, 30, 55, or 105 mU x m(-2) x min(-1) accompanied by a 5-h iv infusion of l-carnitine (15 mg/kg bolus followed by 10 mg x kg(-1) x h(-1)). The clamps produced steady-state serum insulin concentrations of 10.1 +/- 0.5, 48.8 +/- 1.0, 88.9 +/- 2.8, and 173.9 +/- 6.5 mU/l, respectively. During l-carnitine infusion, plasma TC concentration remained above 450 mumol/l during all four visits. However, there was a significant treatment effect of insulin (P < 0.001), such that by the end of infusion the plasma TC concentration in the 55- and 105-mU clamps was lower than that seen in the 5- (P < 0.05 and P < 0.01, respectively) and 30-mU (P < 0.01) clamps. The findings demonstrate that only high circulating serum insulin concentrations (> or =90 mU/l) are capable of stimulating skeletal muscle carnitine accumulation. This is of relevance to athletes, and the treatment of obesity and type 2 diabetes, where increasing skeletal muscle carnitine content may be used as tool to modify skeletal muscle energy metabolism.     

Effect of carbohydrate ingestion on glucose kinetics during exercise in the heat.

Six endurance-trained men [peak oxygen uptake (V(O(2))) = 4.58 +/- 0.50 (SE) l/min] completed 60 min of exercise at a workload requiring 68 +/- 2% peak V(O(2)) in an environmental chamber maintained at 35 degrees C (<50% relative humidity) on two occasions, separated by at least 1 wk. Subjects ingested either a 6% glucose solution containing 1 microCi [3-(3)H]glucose/g glucose (CHO trial) or a sweet placebo (Con trial) during the trials. Rates of hepatic glucose production [HGP = glucose rate of appearance (R(a)) in Con trial] and glucose disappearance (R(d)), were measured using a primed, continuous infusion of [6,6-(2)H]glucose, corrected for gut-derived glucose (gut R(a)) in the CHO trial. No differences in heart rate, V(O(2)), respiratory exchange ratio, or rectal temperature were observed between trials. Plasma glucose concentrations were similar at rest but increased (P < 0.05) to a greater extent in the CHO trial compared with the Con trial. This was due to the absorption of ingested glucose in the CHO trial, because gut R(a) after 30 and 50 min (16 +/- 5 micromol. kg(-1). min(-1)) was higher (P < 0.05) compared with rest, whereas HGP during exercise was not different between trials. Glucose R(d) was higher (P < 0.05) in the CHO trial after 30 and 50 min (48.0 +/- 6.3 vs 34.6 +/- 3.8 micromol. kg(-1). min(-1), CHO vs. Con, respectively). These results indicate that ingestion of carbohydrate, at a rate of approximately 1.0 g/min, increases glucose R(d) but does not blunt the rise in HGP during exercise in the heat.     

Oxidation rate of exogenous carbohydrate during exercise is higher in boys than in men.

To determine whether the relative utilization of exogenous carbohydrate (CHO(exo)) differs between children and adults, substrate utilization during 60 min of cycling at 70% peak O(2) uptake was studied in 12 pre- and early pubertal boys (9.8 +/- 0.1 yr) and 10 men (22.1 +/- 0.5 yr) on two occasions. Subjects consumed either a placebo or a (13)C-enriched 6% CHO(exo) beverage (total volume per trial: 24 ml/kg). Substrate utilization was calculated for the final 30 min of exercise. During both trials, total fat oxidation was higher (5.4 +/- 0.5 vs. 3.0 +/- 0.4 mg x kg(-1) x min(-1), P < 0.001) and total CHO oxidation lower (27.4 +/- 1.5 vs. 34.8 +/- 1.2 mg x kg(-1) x min(-1), P < 0.001) in boys than in men, respectively. During the CHO(exo) trial, CHO(exo) oxidation was higher (P < 0.001) in boys (8.8 +/- 0.5 mg x kg(-1) x min(-1)) than in men (6.2 +/- 0.5 mg x kg(-1) x min(-1)) and provided a greater (P < 0.001) relative proportion of total energy in boys (21.8 +/- 1.4%) than in men (14.6 +/- 0.9%). These results suggest that, although endogenous CHO utilization during exercise is lower, the relative oxidation of ingested CHO is considerably higher in boys than in men. The greater reliance on CHO(exo) in boys may be important in preserving endogenous fuels and may be related to pubertal status.     

Effect of carbohydrate ingestion on glucose kinetics and muscle metabolism during intense endurance exercise.

There has been recent interest in the potential performance and metabolic effects of carbohydrate ingestion during exercise lasting approximately 1 h. In this study, 13 well-trained men ingested in randomized order either a 6% glucose solution (CHO trial) or a placebo (Con trial) during exercise to exhaustion at 83+/-1% peak oxygen uptake. In six subjects, vastus lateralis muscle was sampled at rest, at 32 min, and at exhaustion, and in six subjects, glucose kinetics was determined by infusion of [6,6-(2)H]glucose in both trials and ingestion of [6-(3)H]glucose in the CHO trial. Of the 84 g of glucose ingested during exercise in the CHO trial, only 22 g appeared in the peripheral circulation. This resulted in a small (12 g) but significant (P<0.05) increase in glucose uptake without influencing carbohydrate oxidation, muscle glycogen use, or time to exhaustion (CHO: 68.1+/-4.1 min; Con: 69.6+/-5.5 min). Decreases in muscle phosphocreatine content and increases in muscle inosine monophosphate and lactate content during exercise were similar in the two trials. Although endogenous glucose production during exercise was partially suppressed in the CHO trial, it remained significantly above preexercise levels throughout exercise. In conclusion, only 26% of the ingested glucose appeared in the peripheral circulation. Glucose ingestion increased glucose uptake and partially reduced endogenous glucose production but had no effect on carbohydrate oxidation, muscle metabolism, or time to exhaustion during exercise at 83% peak oxygen uptake.     

Gastrointestinal permeability during exercise: effects of aspirin and energy-containing beverages.

The purpose of this study was to determine whether aspirin (A) ingestion combined with prolonged exercise increases gastrointestinal permeability and whether consumption of a carbohydrate-containing (CHO) or a CHO + glutamine-containing (CHO+G) beverage would reduce this effect. Seventeen subjects completed six experiments. They ingested A (1,300 mg) or placebo (P) pills the evening before and before running 60 min at 70% maximal oxygen uptake. Also, before running they ingested a solution containing 5 g lactulose (L), 5 g sucrose (S), and 2 g rhamnose (R). During each trial, either a 6% CHO beverage, a 6% CHO+G (0.6%; 41 mM) beverage, or a water placebo (WP) was consumed. For 4 h after a run, all urine was collected to measure urinary excretion of L, R, and S. S excretion (percentage of dose ingested; measure of gastroduodenal permeability) was significantly greater (P < 0.05) during the A trial while the subjects drank the WP compared with all other trials. Administration of A also significantly increased L/R (measure of intestinal permeability) for the CHO and WP trials compared with all P trials. Ingestion the CHO or CHO+G beverages significantly reduced S excretion and L excretion when A was administered, but it did not reduce L/R. These results indicate that gastroduodenal and intestinal permeability increase after A ingestion during prolonged running and that ingestion of a CHO beverage attenuates the gastroduodenal effect but not the intestinal effect. Furthermore, addition of G to the CHO beverage provided no additional benefit in reducing gastroduodenal or intestinal permeability.     

Energy substrate utilization during prolonged exercise with and without carbohydrate intake in preadolescent and adolescent girls.

Little information is available on energy metabolism during exercise in girls, particularly the contribution of exogenous carbohydrate (CHO(exo)). The purpose of this study was to determine substrate utilization during exercise with and without CHO(exo) intake in healthy girls. Twelve-yr-old preadolescent (YG; n = 12) and 14-yr-old adolescent (OG; n = 10) girls consumed flavored water (WT) or (13)C-enriched 6% CHO (CT) while cycling for 60 min at approximately 70% maximal aerobic power (Vo(2max)). Substrate utilization was calculated for the final 15 min of exercise. CHO(exo) decreased fat oxidation by approximately 50% in YG but not in OG (P < 0.001) and decreased endogenous CHO oxidation by approximately 15% in OG but not in YG (P = 0.006). Endogenous CHO oxidation was lower in YG than in OG regardless of trial (P < or = 0.01), whereas fat oxidation was higher in YG only during WT (P < 0.001). CHO(exo) oxidation rate was similar between YG and OG (7.1 +/- 0.5 and 6.8 +/- 0.4 mg.kg(-1).min(-1), respectively, P = 0.67), contributing approximately 19% to total energy expenditure. Serum estradiol levels in all girls correlated with fat (r = -0.50 to -0.59, P = 0.03 to 0.005) and endogenous CHO oxidation (r = 0.50 to 0.63, P = 0.03 to 0.005) but not with CHO(exo) oxidation (r = -0.09, P = 0.71). We conclude that CHO(exo) influences endogenous substrate utilization in an age-dependent manner in healthy girls but that total CHO(exo) oxidation during exercise is not different between YG and OG. Our results also point to potential sex-related differences in energy substrate utilization even during childhood.     

Differential excretion of xenobiotic acyl-esters of carnitine due to administration of pivampicillin and valproate

The fate of supplemental carnitine was studied in human subjects treated with drugs known to cause carnitine deficiency. Six children were treated with pivampicillin and equimolar L-carnitine for 7 days. On the last day of treatment, the plasma levels of total and free carnitine were decreased, but acylcarnitine levels were increased. A 12-fold increase in urinary excretion of acylcarnitines was found; it increased from 188.5 +/- 82.7 to 2218.4 +/- 484.1 mumole/day, and 84% was pivaloylcarnitine. Free carnitine excretion was reduced. Ten epileptic children on chronic valproate treatment received equimolar carnitine for a 2-week period. Plasma carnitine levels were elevated on the last day of treatment. A 3.4-fold increase in urinary acylcarnitines was found, but most of the excreted carnitines were free (64.5-fold increases). These data show that pivalate is readily converted to carnitine esters, in contrast to the limited conversion of valproate to acylcarnitines in humans.     

The influence of diet and carnitine supplementation on plasma carnitine, cholesterol and triglyceride in WHHL (Watanabe-heritable hyperlipidemic), Netherland dwarf and New Zealand rabbits (Oryctolagus cuniculus)

1. Plasma carnitine levels in the spontaneously (endogenously) hyperlipidemic Watanabe (WHHL) rabbit are approximately 2-fold higher (P less than 0.001) than in normal rabbits of the New Zealand (NZ) or Netherland Dwarf (NDw) breeds. 2. Plasma carnitine levels in WHHL (44 +/- 3 nmol/ml) can be approximated in NZ and NDw which are rendered exogenously hyperlipidemic by supplementation of the stock chow diet with cholesterol and peanut oil. 3. The induction of endogenous hyperlipidemia in NZ by feeding a sucrose casein rich diet results in a biphasic response of plasma carnitine (elevation followed by normalization). 4. Plasma carnitine in WHHL is readily elevated by supplemental L-carnitine and the elevation is associated with a reduction in plasma triglyceride which shows differences in individual response time; plasma cholesterol is unaffected by supplemental L-carnitine.     

High rates of exogenous carbohydrate oxidation from starch ingested during prolonged exercise.

This study compared the gastric emptying and oxidation of two 15% carbohydrate (CHO) solutions: a 22-chain-length glucose polymer (GP) and soluble starch (SS). Six endurance-trained subjects ingested 1,200 ml of either GP or SS while cycling for 90 min at 70% of maximal oxygen consumption (VO2max). Whereas the calculated total CHO oxidation (GP 266.8 +/- 41.9 g; SS 263.6 +/- 28.9 g) and the volume emptied from the stomach (GP 813 +/- 130 ml; SS 919 +/- 116 ml) were similar, the appearance of the 14C label in plasma occurred more rapidly from ingested SS than from GP (P less than 0.001). This resulted in a significantly greater rate of SS oxidation than that from GP (SS 105.9 +/- 21.9 g, GP 49.6 +/- 10.2 g; P less than 0.001). Exogenous CHO oxidation from GP accounted for 19% of total CHO oxidation, whereas the corresponding value for SS was 40%. This study suggests that the oxidation of SS and GP solutions ingested during exercise at 70% VO2max is not limited by gastric emptying. Rather, it appears to be either the rate of digestion or absorption of these solutions that determines their utilization.     

Metabolic response to carbohydrate ingestion during exercise in males and females

The present study investigated potential sex-related differences in the metabolic response to carbohydrate (CHO) ingestion during exercise. Moderately endurance-trained men and women (n = 8 for each sex) performed 2 h of cycling at approximately 67% Vo(2 max) with water (WAT) or CHO ingestion (1.5 g of glucose/min). Substrate oxidation and kinetics were quantified during exercise using indirect calorimetry and stable isotope techniques ([(13)C]glucose ingestion, [6,6-(2)H(2)]glucose, and [(2)H(5)]glycerol infusion). In both sexes, CHO ingestion significantly increased the rates of appearance (R(a)) and disappearance (R(d)) of glucose during exercise compared with WAT ingestion [males: WAT, approximately 28-29 micromol x kg lean body mass (LBM)(-1) x min(-1); CHO, approximately 53 micromol x kg LBM(-1) x min(-1); females: WAT, approximately 28-29 micromol x kg LBM(-1) x min(-1); CHO, approximately 61 micromol x kg LBM(-1) x min(-1); main effect of trial, P < 0.05]. The contribution of plasma glucose oxidation to the energy yield was significantly increased with CHO ingestion in both sexes (from approximately 10% to approximately 20% of energy expenditure; main effect of trial, P < 0.05). Liver-derived glucose oxidation was reduced, although the rate of muscle glycogen oxidation was unaffected with CHO ingestion (males: WAT, 108 +/- 12 micromol x kg LBM(-1) x min(-1); CHO, 108 +/- 11 micromol x kg LBM(-1) x min(-1); females: WAT, 89 +/- 10 micromol x kg LBM(-1) x min(-1); CHO, 93 +/- 11 micromol x kg LBM(-1) x min(-1)). CHO ingestion reduced fat oxidation and lipolytic rate (R(a) glycerol) to a similar extent in both sexes. Finally, ingested CHO was oxidized at similar rates in men and women during exercise (peak rates of 0.70 +/- 0.08 and 0.65 +/- 0.06 g/min, respectively). The present investigation suggests that the metabolic response to CHO ingestion during exercise is largely similar in men and women.     

Insulin-mediated H+ and NH+4 excretion in the urinary bladder of Bufo marinus

This study was done to determine if insulin mediates H+ and NH+4 excretion in the urinary bladder of Bufo marinus. Acidosis was induced by gavaging with 10 ml of 120 mM NH4Cl 3X daily for 2 days. Hemibladders were mounted between Lucite chambers. Insulin (porcine) was added to the serosal solution of the experimental bladder (10(2) mU/ml). After a 15-min equilibration the flux was measured for 2 hr. H+ excretion was measured from change in pH of the mucosal fluid and the NH+4 measured colorimetrically. The excretion was normalized for weight of bladder and reported in units of nanomoles (100 mg bladder)-1(min)-1. Plasma insulin was determined by radioimmunoassay and glucose by the glucose oxidase method. In 14 control bladders H+ excretion was 8.75 +/- 1.28 and experimental was 16.35 +/- 2.50 (P less than 0.025), while NH+4 excretion in control bladder was 3.29 +/- 0.95 and experimental was 6.58 +/- 1.89 (P less than 0.01). This response was absent when the insulin was heat inactivated (P greater than 0.2 and P greater than 0.3 respectively). Plasma insulin-like levels in 10 normal toads was 0.57 +/- 0.16 ngm/ml and in acidotic toads 1.25 +/- 0.16 ng/ml (P less than 0.025). Plasma glucose levels in 10 normal toads were 22.0 +/- 3.5 mg/dl and in 12 acidotic toads 17.8 +/- 0.75 mg/dl (P less than 0.025). We conclude that plasma insulin is increased in acidosis and that insulin stimulates excretion of H+ and NH+4 in the toad urinary bladder.     

Heat stress increases muscle glycogen use but reduces the oxidation of ingested carbohydrates during exercise.

The aim of the present study was to test the hypothesis that the oxidation rate of ingested carbohydrate (CHO) is impaired during exercise in the heat compared with a cool environment. Nine trained cyclists (maximal oxygen consumption 65 +/- 1 ml x kg body wt(-1) x min(-1)) exercised on two different occasions for 90 min at 55% maximum power ouptput at an ambient temperature of either 16.4 +/- 0.2 degrees C (cool trial) or 35.4 +/- 0.1 degrees C (heat trial). Subjects received 8% glucose solutions that were enriched with [U-13C]glucose for measurements of exogenous glucose, plasma glucose, liver-derived glucose and muscle glycogen oxidation. Exogenous glucose oxidation during the final 30 min of exercise was significantly (P < 0.05) lower in the heat compared with the cool trial (0.76 +/- 0.06 vs. 0.84 +/- 0.05 g/min). Muscle glycogen oxidation during the final 30 min of exercise was increased by 25% in the heat (2.07 +/- 0.16 vs. 1.66 +/- 0.09 g/min; P < 0.05), and liver-derived glucose oxidation was not different. There was a trend toward a higher total CHO oxidation and a lower plasma glucose oxidation in the heat although this did not reach statistical significance (P = 0.087 and P = 0.082, respectively). These results demonstrate that the oxidation rate of ingested CHO is reduced and muscle glycogen utilization is increased during exercise in the heat compared with a cool environment.     

High rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is coingested with caffeine.

We determined the effect of coingestion of caffeine (Caff) with carbohydrate (CHO) on rates of muscle glycogen resynthesis during recovery from exhaustive exercise in seven trained subjects who completed two experimental trials in a randomized, double-blind crossover design. The evening before an experiment subjects performed intermittent exhaustive cycling and then consumed a low-CHO meal. The next morning subjects rode until volitional fatigue. On completion of this ride subjects consumed either CHO [4 g/kg body mass (BM)] or the same amount of CHO + Caff (8 mg/kg BM) during 4 h of passive recovery. Muscle biopsies and blood samples were taken at regular intervals throughout recovery. Muscle glycogen levels were similar at exhaustion [ approximately 75 mmol/kg dry wt (dw)] and increased by a similar amount ( approximately 80%) after 1 h of recovery (133 +/- 37.8 vs. 149 +/- 48 mmol/kg dw for CHO and Caff, respectively). After 4 h of recovery Caff resulted in higher glycogen accumulation (313 +/- 69 vs. 234 +/- 50 mmol/kg dw, P < 0.001). Accordingly, the overall rate of resynthesis for the 4-h recovery period was 66% higher in Caff compared with CHO (57.7 +/- 18.5 vs. 38.0 +/- 7.7 mmol x kg dw(-1) x h(-1), P < 0.05). After 1 h of recovery plasma Caff levels had increased to 31 +/- 11 microM (P < 0.001) and at the end of the recovery reached 77 +/- 11 microM (P < 0.001) with Caff. Phosphorylation of CaMK(Thr286) was similar after exercise and after 1 h of recovery, but after 4 h CaMK(Thr286) phosphorylation was higher in Caff than CHO (P < 0.05). Phosphorylation of AMP-activated protein kinase (AMPK)(Thr172) and Akt(Ser473) was similar for both treatments at all time points. We provide the first evidence that in trained subjects coingestion of large amounts of Caff (8 mg/kg BM) with CHO has an additive effect on rates of postexercise muscle glycogen accumulation compared with consumption of CHO alone.     

Substrate utilization during exercise with glucose and glucose plus fructose ingestion in boys ages 10--14 yr.

We measured substrate utilization during exercise performed with water (W), exogenous glucose (G), and exogenous fructose plus glucose (FG) ingestion in boys age 10-14 yr. Subjects (n = 12) cycled for 90 min at 55% maximal O(2) uptake while ingesting either W (25 ml/kg), 6% G (1.5 g/kg), or 3% F plus 3% G (1.5 g/kg). Fat oxidation increased during exercise in all trials but was higher in the W (0.28 +/- 0.023 g/min) than in the G (0.24 +/- 0.023 g/min) and FG (0.25 +/- 0.029 g/min) trials (P = 0.04). Conversely, total carbohydrate (CHO) oxidation decreased in all trials and was lower in the W (0.63 +/- 0.05 g/min) than in the G (0.78 +/- 0.051 g/min) and FG (0.74 +/- 0.056 g/min) trials (P = 0.009). Exogenous CHO oxidation, as determined by expired (13)CO(2), reached a maximum of 0.36 +/- 0.032 and 0.31 +/- 0.030 g/min at 90 min in G and FG, respectively (P = 0.04). Plasma insulin levels decrease during exercise in all trials but were twofold higher in G than in W and FG (P < 0.001). Plasma glucose levels decreased transiently after the onset of exercise in all trials and then returned to preexercise values in the W and FG (approximately 4.5 mmol/l) trials but were elevated by approximately 1.0 mmol/l in the G trial (P < 0.001). Plasma lactate concentrations decreased after the onset of exercise in all trials but were lower by approximately 0.5 mmol/l in W than in G and FG (P = 0.02). Thus, in boys exercising at a moderate intensity, the oxidation rate of G plus F is slightly less than G alone, but both spare endogenous CHO and fat to a similar extent. In addition, compared with flavored W, the ingestion of G alone and of G plus F delays exhaustion at 90% peak power by approximately 25 and 40%, respectively, after 90 min of moderate-intensity exercise.     

Suppressing lipolysis increases interleukin-6 at rest and during prolonged moderate-intensity exercise in humans.

IL-6 induces lipolysis when administered to humans. Consequently, it has been hypothesized that IL-6 is released from skeletal muscle during exercise to act in a "hormonelike" manner and increase lipolysis from adipose tissue to supply the muscle with substrate. In the present study, we hypothesized that suppressing lipolysis, and subsequent free fatty acid (FFA) availability, would result in a compensatory elevation in IL-6 at rest and during exercise. First, we had five healthy men ingest nicotinic acid (NA) at 30-min intervals for 120 min at rest [10 mg/kg body mass (initial dose), 5 mg/kg body mass (subsequent doses)]. Plasma was collected and analyzed for FFA and IL-6. After 120 min, plasma FFA concentration was attenuated (0 min: 0.26 +/- 0.05 mmol/l; 120 min: 0.09 +/- 0.02 mmol/l; P < 0.01), whereas plasma IL-6 was concomitantly increased approximately eightfold (0 min: 0.75 +/- 0.18 pg/ml; 120 min: 6.05 +/- 0.89 pg/ml; P < 0.001). To assess the effect of lipolytic suppression on the exercise-induced IL-6 response, seven active, but not specifically trained, men performed two experimental exercise trials with (NA) or without [control (Con)] NA ingestion 60 min before (10 mg/kg body mass) and throughout (5 mg/kg body mass every 30 min) exercise. Blood samples were obtained before ingestion, 60 min after ingestion, and throughout 180 min of cycling exercise at 62 +/- 5% of maximal oxygen consumption. IL-6 gene expression, in muscle and adipose tissue sampled at 0, 90, and 180 min, was determined by using semiquantitative real-time PCR. IL-6 mRNA increased in Con (rest vs. 180 min; P < 0.01) approximately 13-fold in muscle and approximately 42-fold in fat with exercise. NA increased (rest vs. 180 min; P < 0.01) IL-6 mRNA 34-fold in muscle, but the treatment effect was not statistically significant (Con vs. NA, P = 0.1), and 235-fold in fat (Con vs. NA, P < 0.01). Consistent with the study at rest, NA completely suppressed plasma FFA (180 min: Con, 1.42 +/- 0.07 mmol/l; NA, 0.10 +/- 0.01 mmol/l; P < 0.001) and increased plasma IL-6 (180 min: Con, 9.81 +/- 0.98 pg/ml; NA, 19.23 +/- 2.50 pg/ml; P < 0.05) during exercise. In conclusion, these data demonstrate that circulating IL-6 is markedly elevated at rest and during prolonged moderate-intensity exercise when lipolysis is suppressed.     

Carbohydrate loading and supplementation in endurance-trained women runners.

The purpose of this study was to examine the effect of carbohydrate (CHO) augmentation on endurance performance and substrate utilization in aerobically trained women. Eight endurance-trained women completed a 24.2-km (15 mile) self-paced treadmill performance run under three conditions: CHO supplementation (S), CHO loading and supplementation (L+S), and placebo (P). Dietary CHO was approximately 75% of energy intake for L+S and approximately 50% for both S and P. A 6% CHO-electrolyte solution (S and L+S) or placebo (P) was ingested preexercise (6 ml/kg) and every 20 min during exercise (3 ml/kg). Blood glucose was significantly higher at 40, 60, and 100 min during L+S, and at 60, 80, and 100 min during S compared with P (P < 0.05). Blood lactate was significantly higher (P < 0.05) during L+S than S and P. Blood glycerol was significantly lower (P < 0.05) at 20, 80, and 100 min during L+S, and at 80 and 100 min during S than P. The proportion of CHO (%) utilized during exercise was significantly higher (P < 0.05) during L+S (71.3 +/- 3.8%) and S (67.3 +/- 4.3%) than P (59.2 +/- 4.6%). Performance times (P > 0.05) were 132.5 +/- 6.3 min (S), 134.4 +/- 6.3 min (L+S), and 136.6 +/- 7.9 min (P). In conclusion, it appears that when CHO availability in women is increased through CHO loading and/or CHO supplementation, there is a concomitant increase in CHO utilization. However, this may not necessarily result in significantly improved performance.     

Effect of carbohydrate ingestion on exercise metabolism

Five male cyclists were studied during 2 h of cycle ergometer exercise (70% VO2 max) on two occasions to examine the effect of carbohydrate ingestion on muscle glycogen utilization. In the experimental trial (CHO) subjects ingested 250 ml of a glucose polymer solution containing 30 g of carbohydrate at 0, 30, 60, and 90 min of exercise; in the control trial (CON) they received an equal volume of a sweet placebo. No differences between trials were seen in O2 uptake or heart rate during exercise. Venous blood glucose was similar before exercise in both trials, but, on average, was higher during exercise in CHO [5.2 +/- 0.2 (SE) mmol/l] compared with CON (4.8 +/- 0.1, P less than 0.05). Plasma insulin levels were similar in both trials. Muscle glycogen levels were also similar in CHO and CON both before and after exercise; accordingly, there was no difference between trials in the amount of glycogen used during the 2 h of exercise (CHO = 62.8 +/- 10.1 mmol/kg wet wt, CON = 56.9 +/- 10.1). The results of this study indicate that carbohydrate ingestion does not influence the utilization of muscle glycogen during prolonged strenuous exercise.     

Combined ingestion of protein and free leucine with carbohydrate increases postexercise muscle protein synthesis in vivo in male subjects

The present study was designed to determine postexercise muscle protein synthesis and whole body protein balance following the combined ingestion of carbohydrate with or without protein and/or free leucine. Eight male subjects were randomly assigned to three trials in which they consumed drinks containing either carbohydrate (CHO), carbohydrate and protein (CHO+PRO), or carbohydrate, protein, and free leucine (CHO+PRO+Leu) following 45 min of resistance exercise. A primed, continuous infusion of L-[ring-13C6]phenylalanine was applied, with blood samples and muscle biopsies collected to assess fractional synthetic rate (FSR) in the vastus lateralis muscle as well as whole body protein turnover during 6 h of postexercise recovery. Plasma insulin response was higher in the CHO+PRO+Leu compared with the CHO and CHO+PRO trials (+240 +/- 19% and +77 +/- 11%, respectively, P < 0.05). Whole body protein breakdown rates were lower, and whole body protein synthesis rates were higher, in the CHO+PRO and CHO+PRO+Leu trials compared with the CHO trial (P < 0.05). Addition of leucine in the CHO+PRO+Leu trial resulted in a lower protein oxidation rate compared with the CHO+PRO trial. Protein balance was negative during recovery in the CHO trial but positive in the CHO+PRO and CHO+PRO+Leu trials. In the CHO+PRO+Leu trial, whole body net protein balance was significantly greater compared with values observed in the CHO+PRO and CHO trials (P < 0.05). Mixed muscle FSR, measured over a 6-h period of postexercise recovery, was significantly greater in the CHO+PRO+Leu trial compared with the CHO trial (0.095 +/- 0.006 vs. 0.061 +/- 0.008%/h, respectively, P < 0.05), with intermediate values observed in the CHO+PRO trial (0.0820 +/- 0.0104%/h). We conclude that coingestion of protein and leucine stimulates muscle protein synthesis and optimizes whole body protein balance compared with the intake of carbohydrate only.     

Caffeine increases exogenous carbohydrate oxidation during exercise.

Both carbohydrate (CHO) and caffeine have been used as ergogenic aids during exercise. It has been suggested that caffeine increases intestinal glucose absorption, but there are also suggestions that it may decrease muscle glucose uptake. The purpose of the study was to investigate the effect of caffeine on exogenous CHO oxidation. In a randomized crossover design, eight male cyclists (age 27 +/- 2 yr, body mass 71.2 +/- 2.3 kg, maximal oxygen uptake 65.7 +/- 2.2 ml x kg(-1) x min(-1)) exercised at 64 +/- 3% of maximal oxygen uptake for 120 min on three occasions. During exercise subjects ingested either a 5.8% glucose solution (Glu; 48 g/h), glucose with caffeine (Glu+Caf, 48 g/h + 5 mg x kg(-1) x h(-1)), or plain water (Wat). The glucose solution contained trace amounts of [U-13C]glucose so that exogenous CHO oxidation could be calculated. CHO and fat oxidation were measured by indirect calorimetry, and 13C appearance in the expired gases was measured by continuous-flow IRMS. Average exogenous CHO oxidation over the 90- to 120-min period was 26% higher (P < 0.05) in Glu+Caf (0.72 +/- 0.04 g/min) compared with Glu (0.57 +/- 0.04 g/min). Total CHO oxidation rates were higher (P < 0.05) in the CHO ingestion trials compared with Wat, but they were highest when Glu+Caf was ingested (1.21 +/- 0.37, 1.84 +/- 0.14, and 2.47 +/- 0.23 g/min for Wat, Glu, and Glu+Caf, respectively; P < 0.05). There was also a trend (P = 0.082) toward an increased endogenous CHO oxidation with Glu+Caf (1.81 +/- 0.22 g/min vs. 1.27 +/- 0.13 g/min for Glu and 1.12 +/- 0.37 g/min for Wat). In conclusion, compared with glucose alone, 5 mg x kg(-1) x h(-1) of caffeine coingested with glucose increases exogenous CHO oxidation, possibly as a result of an enhanced intestinal absorption.