Biomedical subjects

T E Graham

Publications and source records attributed to T E Graham.

At least 19 recordsLinked to original sources

PubMed2000

Physiology of common map turtles (Graptemys geographica) hibernating in the Lamoille river, Vermont.

Common map turtles (Graptemys geographica) were collected from a natural underwater hibernaculum in Vermont at monthly intervals during the winter of 1997-1998. Blood was sampled by cardiac puncture and analyzed for pH, PCO(2), PO(2), and hematocrit; separated plasma was tested for Na(+), K(+), Cl(-), total [Ca], total [Mg], [lactate], and osmolality (mOsm kg(-1) H(2)O). Control (eupneic; 1 degrees C) values for pH, PO(2), PCO(2), [HCO(3)(-)], and [lactate] were 7.98 +/- 0.03, 47.4 +/- 18.7, 10.1 +/- 0.7 (mm Hg), 36.1 +/- 0.2 (mmol liter(-1)), and 2.1 +/- 0.1 (mmol liter(-1)), respectively. Between November 1997 and March 1998, ice covered the river and the turtles rested on the substratum, fully exposed to the water, and were apneic. Blood PO(2) was maintained at less than 3 mm Hg (range 0.9 +/- 0.2 to 2.1 +/- 0.7 mm Hg), PCO(2) decreased slightly, plasma [lactate] was <5 mmol liter(-1), and plasma [HCO(3)(-)] decreased significantly. In March [lactate] rose to 7.5 +/- 1.5 mmol liter(-l), but there was no acidemia. Map turtles meet most of their metabolic demand for O(2) via aquatic respiration and tolerate prolonged submergence at 1 degrees C with little change in acid-base or ionic status. The adaptive significance of remaining essentially aerobic during winter is to avoid the life-threatening progressive acidosis that results from anaerobic metabolism. J. Exp. Zool. 286:143-148, 2000.

Animals↗

PubMed2000

Glycogenin activity in human skeletal muscle is proportional to muscle glycogen concentration.

The de novo biosynthesis of glycogen is catalyzed by glycogenin, a self-glucosylating protein primer. To date, the role of glycogenin in regulating glycogen metabolism and the attainment of maximal glycogen levels in skeletal muscle are unknown. We measured glycogenin activity after enzymatic removal of glucose by alpha-amylase, an indirect measure of glycogenin amount. Seven male subjects performed an exercise and dietary protocol that resulted in one high-carbohydrate leg (HL) and one low-carbohydrate leg (LL) before testing. Resting muscle biopsies were obtained and analyzed for total glycogen, proglycogen (PG), macroglycogen (MG), and glycogenin activity. Results showed differences (P < 0.05) between HL and LL for total glycogen (438.0 +/- 69.5 vs. 305.7 +/- 57.4 mmol glucosyl units/kg dry wt) and PG (311.4 +/- 38.1 vs. 227.3 +/- 33.1 mmol glucosyl units/kg dry wt). A positive correlation between total muscle glycogen content and glycogenin activity (r = 0.84, P < 0.001) was observed. Similar positive correlations (P < 0.05) were also evident between both PG and MG concentration and glycogenin activity (PG, r = 0.82; MG, r = 0.84). It can be concluded that glycogenin does display activity in human skeletal muscle and is proportional to glycogen concentration. Thus it must be considered as a potential regulator of glycogen synthesis in human skeletal muscle.

Adult↗

PubMed2000

Glutamate ingestion: the plasma and muscle free amino acid pools of resting humans.

Monosodium glutamate (MSG) ingestion is known to increase plasma glutamate concentration, and MSG infusion stimulates insulin secretion. We investigated the impact of MSG ingestion on both the plasma and intramuscular amino acid pools. Nine postprandial adults ingested MSG (150 mg/kg) and rested for 105 min. Venous blood was sampled preingestion and then every 15 min; vastus lateralis muscle biopsies were taken preingestion and at 45, 75, and 105 min postingestion. Venous plasma glutamate and aspartate concentrations increased (P </= 0.05) approximately 700-800 and 300-400%, respectively, after 30-45 min. Although several other plasma amino acids increased modestly, the rise in glutamate accounted for approximately 80% of the increase in total plasma amino acids. In addition, plasma insulin increased threefold after 15 min; this occurred before a significant increase in plasma glutamate, indicating a feed-forward stimulation from the gastrointestinal tract. The intramuscular amino acid pool was remarkably constant, with only glutamate increasing (P </= 0.05) by 3.56 mmol/kg dry wt. By 105 min, the plasma and muscle amino acids had returned to resting concentrations. This increase in muscle glutamate concentration could account for approximately 40% of the MSG ingested; we propose that resting skeletal muscle is a major sink for the glutamate and metabolizes it to aspartate.

Administration, Oral↗

PubMed2000

Plasma leptin in moderately obese men: independent effects of weight loss and aerobic exercise.

The independent effects of weight loss and exercise on plasma leptin and total (AT), subcutaneous (SAT), and visceral (VAT) adipose tissue were investigated in 52 obese men. Subjects were randomly assigned to four 12-wk protocols: 1) control (C, n = 8), 2) diet-induced weight loss (DWL, n = 14), 3) exercise-induced weight loss (EWL, n = 14), and 4) exercise with weight maintenance (EWS, n = 16). Plasma leptin was unchanged in C (from 7.8 +/- 1.3 to 7.7 +/- 1.0 ng/ml). Equivalent weight loss (7.5 kg) decreased leptin significantly but similarly (DWL, from 8.5 +/- 1.0 to 4.8 +/- 0.6 ng/ml; EWL, from 10.1 +/- 1.0 to 5.0 +/- 0.6 ng/ml). Exercise in the absence of weight loss did not alter leptin levels (from 10.1 +/- 1. 3 to 9.2 +/- 1.2 ng/ml). Changes in leptin correlated with changes in AT and SAT (both P < 0.05) but not in VAT. We conclude that reduction in adipose tissue after weight loss results in a collateral decrease in circulating leptin, and exercise, independent of its effects on weight loss, has no profound influence on leptin secretion.

Adipose Tissue↗

PubMed2000

Plasma leptin in female athletes: relationship with body fat, reproductive, nutritional, and endocrine factors.

The relationship of leptin to thyroid and sex hormones, insulin, energy intake, exercise energy expenditure, and reproductive function was assessed in 39 female athletes. They comprised elite athletes who were either amenorrheic (EAA; n = 5) or cyclic (ECA; n = 8) and recreationally active women who were either cyclic (RCA; n = 13) or taking oral contraceptives (ROC; n = 13). Leptin was significantly lower in EAA (1.7 +/- 0.2 ng/ml) than in ECA (2.9 +/- 0.3 ng/ml), RCA (5.8 +/- 0.9 ng/ml), and ROC (7.4 +/- 1.3 ng/ml). Hypoleptinemia in EAA was paralleled by reductions (P < 0.05) in caloric intake, insulin, estradiol, and thyroid hormones. Leptin increased by 40-46% (P < 0.05) in the luteal phase of the menstrual cycle in RCA and ECA. Plasma leptin was similar in the placebo and active pill phases in ROC despite a significant increase in ethinylestradiol. Leptin correlated (P < 0.05) with triiodothyronine and insulin but not with estrogen, energy intake, or exercise energy expenditure. These data suggest that in female athletes 1) leptin may be a metabolic signal that provides a link between adipose tissue, energy availability, and the reproductive axis and 2) sex hormones do not directly regulate leptin secretion.

Adipose Tissue↗

PubMed2000

Comparison of caffeine and theophylline ingestion: exercise metabolism and endurance.

This two-part investigation compared the ergogenic and metabolic effects of theophylline and caffeine. Initially (part A), the ergogenic potential of theophylline on endurance exercise was investigated. Eight men cycled at 80% maximum O(2) consumption to exhaustion 90 min after ingesting either placebo (dextrose), caffeine (6 mg/kg; Caff), or theophylline (4.5 mg/kg Theolair; Theo). There was a significant increase in time to exhaustion in both the Caff (41.2+/-4.8 min) and Theo (37.4+/-5.0 min) trials compared with placebo (32.6+/-3.4 min) (P<0.05). In part B, the effects of Theo on muscle metabolism were investigated and compared with Caff. Seven men cycled for 45 min at 70% maximum O(2) consumption (identical treatment protocol as in part A). Neither methylxanthines (MX) affected muscle glycogen utilization (P>0.05). Only Caff increased plasma epinephrine (P<0.05), but both MX increased blood glycerol levels (P<0.05). Muscle cAMP was increased (P<0.05) by both MX at 15 min and remained elevated at 45 min with Theo. This demonstrates that both MX are ergogenic and that this can be independent of muscle glycogen.

Acetyl Coenzyme A↗

PubMed1999

Leptin and reproduction: is it a critical link between adipose tissue, nutrition, and reproduction?

Exercise-associated reproductive disorders are frequently reported among recreationally active and elite female athletes. Although an association between exercise and menstrual disorders has been established, the mechanism by which exercise disrupts reproductive function remains unknown. Recent findings suggest that low energy availability rather than inadequate body fatness or exercise stress is likely the mechanism by which exercise impinges negatively on the hypothalamic-pituitary-ovarian axis in female athletes. The peripheral signal that informs the neural network of energy availability remains unknown. The identification of the adipocyte-derived ob gene product, leptin, and subsequent findings of its association with reproduction in both rodents and humans, led to speculations that it may be involved in the interactions between nutrition and reproduction. This review article focuses on leptin's role in modulating reproduction, and in particular, as a peripheral signal of nutritional status that integrates adipose tissue, nutrition, and reproduction in female athletes.

Adipose Tissue↗

PubMed1999

Dietary carbohydrate and its effects on metabolism and substrate stores in sedentary and active individuals.

This review of carbohydrate (CHO) ingestion and exercise addresses three major issues: (a) how CHO ingestion influences CHO and fat stores, (b) how exercise, by changing CHO stores, alters the responses to CHO or fat ingestion, and (c) the roles of CHO in exercise performance and metabolism. Dietary manipulation is not a simple issue; increasing the dietary content of any specific nutrient alters the entire diet composition. High CHO diets are often low fat diets, hence changing the metabolism and storage of both fat and CHO. Acute CHO ingestion increases CHO oxidation and the "spared" fats are deposited as fat. Chronic high CHO ingestion (without an active lifestyle) leads to muscle becoming insulin-insensitive, adipose tissue processing CHO to fatty acids, and the liver increasing production of VLDL triglycerides. CHO ingestion prior to and during prolonged exercise can increase endurance. It has been suggested that moderate or low glycemic index forms be used prior to and during the exercise, but there is no consensus as to whether it should be a recommendation. The physiological nature of the regulation of CHO stores is poorly understood, but the recent identification of a key enzyme, glycogenin, and two forms of glycogen (pro- and macroglycogen) show promise of a deeper understanding.

Body Composition↗

PubMed1999

Low glycogen and branched-chain amino acid ingestion do not impair anaplerosis during exercise in humans.

We examined the hypothesis that increasing the rate of branched-chain amino acid (BCAA) oxidation, during conditions of low glycogen availability, reduces the level of muscle tricarboxylic acid cycle intermediates (TCAI) by placing a carbon "drain" on the cycle at the level of 2-oxoglutarate. Six men cycled at approximately 70% of maximal oxygen uptake for 15 min under two conditions: 1) low preexercise muscle glycogen (placebo) and 2) low glycogen combined with BCAA ingestion. We have previously shown that BCAA ingestion increased the activity of branched-chain oxoacid dehydrogenase, the rate-limiting enzyme for BCAA oxidation in muscle, compared with low glycogen alone [M. L. Jackman, M. J. Gibala, E. Hultman, and T. E. Graham. Am. J. Physiol. 272 (Endocrinol. Metab. 35): E233-E238, 1997]. Muscle glycogen concentration was 185 +/- 22 and 206 +/- 22 mmol/kg dry wt at rest for the placebo and BCAA-supplemented trials, respectively, and decreased to 109 +/- 18 and 96 +/- 10 mmol/kg dry wt after exercise. The net increase in the total concentration of six measured TCAI ( approximately 95% of TCAI pool) during exercise was not different between trials (3.97 +/- 0. 34 vs. 3.88 +/- 0.34 mmol/kg dry wt for the placebo and BCAA trials, respectively). Muscle 2-oxoglutarate concentration decreased from approximately 0.05 at rest to approximately 0.03 mmol/kg dry wt after exercise in both trials. The magnitude of TCAI pool expansion in both trials was similar to that seen previously in subjects who performed an identical exercise bout after a normal mixed diet [M. J. Gibala, M. A. Tarnopolsky, and T. E. Graham. Am. J. Physiol. 272 (Endocrinol. Metab. 35): E239-E244, 1997]. These data suggest that increasing the rate of BCAA oxidation has no measurable effect on muscle TCAI during exercise with low glycogen in humans. Moreover, it appears that low resting glycogen per se does not impair the increase in TCAI during moderate exercise.

Adult↗

PubMed1998

MEK and ERK activation in ras-disabled RBL-2H3 mast cells and novel roles for geranylgeranylated and farnesylated proteins in Fc epsilonRI-mediated signaling.

Cross-linking the high affinity IgE receptor Fc epsilonRI of basophils and mast cells activates receptor-associated protein-tyrosine kinases and stimulates a signaling cascade leading to secretion, ruffling, spreading, and cytokine production. Previous evidence that the pan-prenylation inhibitor lovastatin blocks Ag-stimulated Ca2+ influx, secretion, and membrane/cytoskeletal responses implicated isoprenylated proteins in the Fc epsilonRI-coupled signaling cascade but could not distinguish between contributions of C15 (farnesylated) and C20 (geranylgeranylated) species. Here we establish concentrations of lovastatin and the farnesyl-specific inhibitor BZA-5B that inhibit the farnesylation and Ag-induced activation of Ras species in RBL-2H3 cells (H-Ras, K-RasA, and K-RasB). These inhibitors have little effect on tyrosine kinase activation, which initiates Fc epsilonRI signaling. Although Ras is disabled, only lovastatin substantially blocks Raf-1 activation, and neither inhibitor affects mitogen-activated protein kinase kinase/extracellular signal regulated kinase kinase (MEK) or ERK1/ERK2 activation. Thus, the pathway to Fc epsilonRI-mediated MEK/ERK and ERK activation can apparently bypass Ras and Raf-1. Predictably, only lovastatin inhibits Ag-induced ruffling, spreading, and secretion, previously linked to geranylgeranylated Rho and Rab family members. Additionally, only lovastatin inhibits phospholipase Cgamma-mediated inositol (1,4,5) trisphosphate production, sustained Ca2+ influx, and Ca2+-dependent IL-4 production, suggesting novel roles for geranylgeranylated (lovastatin-sensitive, BZA-5B-insensitive) proteins in Fc epsilonRI signal propagation. Remarkably, BZA-5B concentrations too low to inactivate Ras reduce the lag time to Ag-induced Ca2+ stores release and enhance secretion. These results link a non-Ras farnesylated protein(s) to the negative regulation of Ca2+ release from intracellular stores and secretion. We identified no clear role for Ras in Fc epsilonRI-coupled signaling but suggest its involvement in mast cell growth regulation based on the inhibition of cell proliferation by both BZA-5B and lovastatin.

Alkyl and Aryl Transferases↗

PubMed1998

Anaplerosis of the tricarboxylic acid cycle in human skeletal muscle during exercise. Magnitude, sources, and potential physiological significance.

In comparison to cardiac tissue, relatively few data are available regarding the concentrations of tricarboxylic acid cycle intermediates (TCAI) and the potential influence of TCAI pool size on the regulation of cycle flux in mammalian skeletal muscle. However, recent human exercise studies have confirmed the fundamental observation made in electrically-stimulated rodent muscle that moderate to intense contraction results in a net accumulation of TCAI. The increase in TCAI pool size, termed "anaplerosis," appears exponentially related to work intensity, although the relative changes in the individual cycle intermediates differ markedly. While a number of mechanisms could potentially contribute to the increase in TCAI, the reaction catalyzed by alanine aminotransferase appears primarily responsible for anaplerosis at the onset of exercise in humans. The expansion of the TCAI pool has been suggested to be important for aerobic energy provision, and various theories have been proposed which link the total concentration of TCAI with the capacity for TCA cycle flux during exercise. However, despite the recent advances which have been made with regard to the magnitude and potential source of TCAI expansion in humans, our understanding of the physiological significance of anaplerosis is limited. Indeed, it remains speculative whether the increase in TCAI pool size represents an important regulatory signal or is simply a consequence of the huge increase in metabolic flux which occurs during exercise.

Exercise↗

PubMed1998

Ammonia and amino acid metabolism in skeletal muscle: human, rodent and canine models.

This review considers four experimental models for studying the dynamics of ammonia and amino acid metabolism in skeletal muscle: the rat hindlimb, the isolated dog gastrocnemius, the leg extensor for humans, and the traditional approach of humans performing two-legged exercise. The rat hindlimb is well suited for studying intense exercise with fast-twitch white fibers, but it is poorly suited for studying prolonged exercise because of rapid fatigue of major portions of the muscle and the restrictions of taking multiple blood samples. The traditional human model is limited because of the inability to quantify accurately the active muscle mass and to determine the true blood flow to the entire active tissue. Despite species differences and the various limitations of the paradigms, there are numerous consistencies in the literature. For example, human muscle and the canine gastrocnemius demonstrate similar magnitudes of efflux of ammonia, glutamine, and alanine (when indexed for the active mass) during prolonged exercise. Muscle has a large ammonia producing capacity during either intense or prolonged exercise. In prolonged exercise this is accompanied by similar productions of alanine and glutamine as well as a large uptake of glutamate. Despite the latter, the intramuscular glutamate concentration rapidly declines by more than 50% and remains constant throughout the exercise period. The leg extensor model and the canine gastrocnemius offer the greatest opportunities to quantify these responses during prolonged exercise.

Amino Acids↗

PubMed1998

Dietary carbohydrate and postexercise synthesis of proglycogen and macroglycogen in human skeletal muscle.

This study examined the role of carbohydrate (CHO) ingestion on the resynthesis of two pools of glycogen, proglycogen (PG) and macroglycogen (MG), in human skeletal muscle. Nine males completed an exhaustive glycogen depletion exercise bout at 70% maximal O2 consumption on two occasions. Subsequent 48-h dietary interventions consisted of either high (HC, 75% of energy intake) or low (LC, 32% of energy intake) CHO diets. Muscle biopsies were taken at exhaustion (EXH) and 4, 24, and 48 h later. The total muscle glycogen (Gt) at EXH for the HC and LC conditions was not significantly different, and the MG represented approximately 12% of the Gt. From EXH to 4 h, there was an increase in the PG only for HC and no change in MG in either diet (P < 0.05). From 4 to 24 h, the concentration of PG increased in both conditions (P < 0.05). Between 24 and 48 h, in HC the majority of the increase in Gt was due to the MG pool (P < 0.05). The MG and PG concentrations for HC were significantly greater than for LC at 24 and 48 h (P < 0.05). At 48 h the MG represented 40% of the Gt for the HC diet and only 21% for the LC diet. There was no change in the net rates of synthesis of PG or MG over 48 h for LC (P < 0.05). The net rate of PG synthesis from 0 to 4 h for HC was 16 +/- 1.68 mmol glucosyl units . kg dry wt-1 . h-1, which was threefold greater than for LC (P < 0. 05). The net rate of PG synthesis decreased significantly from 4 to 24 h for HC, whereas the net rate of MG synthesis was not different over 48 h but was significantly greater than in LC (P < 0.05). The two pools are synthesized at very different rates; both are sensitive to CHO, and the supercompensation associated with HC is due to a greater synthesis in the MG pool.

Adult↗

PubMed1998

Tricarboxylic acid cycle intermediate pool size and estimated cycle flux in human muscle during exercise.

We examined the relationship between tricarboxylic acid (TCA) cycle intermediate (TCAI) pool size, TCA cycle flux (calculated from leg O2 uptake), and pyruvate dehydrogenase activity (PDHa) in human skeletal muscle. Six males performed moderate leg extensor exercise for 10 min, followed immediately by intense exercise until exhaustion (3.8 +/- 0.5 min). The sum of seven measured TCAI (SigmaTCAI) increased (P </= 0.05) from 1.39 +/- 0.11 at rest to 2. 88 +/- 0.31 after 10 min and to 5.38 +/- 0.31 mmol/kg dry wt at exhaustion. TCA cycle flux increased approximately 70-fold during submaximal exercise and was approximately 100-fold higher than rest at exhaustion. PDHa corresponded to 77 and 90% of TCA cycle flux during submaximal and maximal exercise, respectively. The present data demonstrate that a tremendous increase in TCA cycle flux can occur in skeletal muscle despite a relatively small change in TCAI pool size. It is suggested that the increase in SigmaTCAI during exercise may primarily reflect an imbalance between the rate of pyruvate production and its rate of oxidation in the TCA cycle.

Adult↗

PubMed1998

Comparison of traditional measurements with macroglycogen and proglycogen analysis of muscle glycogen.

Traditionally, there have been two methods for measuring total muscle glycogen (Glytot), either by acid hydrolysis (AC) or by enzymatic hydrolysis (EZ). As well, it has been determined that rodent muscle contains two pools of glycogen, macroglycogen (MG) and proglycogen (PG). This MG/PG determination of Glytot has never been compared with AC or EZ methods, nor has it been determined whether the two pools exist in human skeletal muscle. A detailed comparison of the three methods was performed by using both rodent and human muscle. It was found that repeated analysis of independent portions of muscle generally gave coefficients of variation of <10%. The PG fraction was always in excess of MG, which was 6-10% of Glytot in rodent muscle and in human samples when Glytot was low but increased to approximately 40% when Glytot was high. It was found that AC and EZ Glytot were not statistically different (P < 0.05), nor was there a difference between the MG+PG Glytot and that determined by AC or EZ. The Glytot from MG+PG extraction had a strong correlation with the values obtained by either AC (r = 1.0) or EZ (r = 0.96). These data suggest that MG+PG do exist in human skeletal muscle and can be measured reliably in biopsy-sized samples. All three methods give an accurate representation of human Glytot and are comparable in their precision.

Animals↗

PubMed1998

Metabolic and exercise endurance effects of coffee and caffeine ingestion.

Caffeine (Caf) ingestion increases plasma epinephrine (Epi) and exercise endurance; these results are frequently transferred to coffee (Cof) consumption. We examined the impact of ingestion of the same dose of Caf in Cof or in water. Nine healthy, 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 regular Cof). In all three Caf trials, the Caf dose was 4.45 mg/kg body wt and the volume of liquid was 7.15 ml/kg. After 1 h of rest, the subject ran at 85% of maximal O2 consumption until voluntary exhaustion (approximately 32 min in the placebo and decaffeinated Cof tests). In the three Caf trials, the plasma Caf and paraxanthine concentrations were very similar. After 1 h of rest, the plasma Epi was increased (P < 0.05) by Caf ingestion, but the increase was greater (P < 0.05) with Caf capsules than with Cof. During the exercise there were no differences in Epi among the three Caf trials, and the Epi values were all greater (P < 0.05) than in the other tests. 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) of Cof that moderates the actions of Caf.

Adult↗

PubMed1998

Caffeine ingestion and metabolic responses of tetraplegic humans during electrical cycling.

Normally, caffeine ingestion results in a wide spectrum of neural and hormonal responses, making it difficult to evaluate which are critical regulatory factors. We examined the responses to caffeine (6 mg/kg) ingestion in a group of spinal cord-injured subjects [7 tetraplegic (C5-7) and 2 paraplegic (T4) subjects] at rest and during functional electrical stimulation of their paralyzed limbs to the point of fatigue. Plasma insulin did not change, caffeine had no effect on plasma epinephrine, and there was a slight increase (P < 0. 05) in norepinephrine after 15 min of exercise. Nevertheless, serum free fatty acids were increased (P < 0.05) after caffeine ingestion after 60 min of rest and throughout the first 15 min of exercise, but the respiratory exchange ratio was not affected. The exercise time was increased (P < 0.05) by 6% or 1.26 +/- 0.57 min. These data suggest that caffeine had direct effects on both the adipose tissue and the active muscle. It is proposed that the ergogenic action of caffeine is occurring, at least in part, by a direct action of the drug on muscle.

Adult↗

PubMed1998

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

In this study the effects of acute caffeine ingestion on exercise performance, hormonal (epinephrine, norepinephrine, insulin), and metabolic (free fatty acids, glycerol, glucose, lactate, expired gases) parameters during 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 x kg-1 x min-1 and daily caffeine intake 761.3 +/- 11.8 mg/day) were tested under conditions of no withdrawal and 2-day and 4-day withdrawal from dietary caffeine. There were seven trials in total with a minimum of 10 days between trials. On the day of the exercise trial, subjects ingested either dextrose placebo or 6 mg/kg caffeine in capsule form 1 h before cycle ergometry to exhaustion at 80-85% of maximum oxygen uptake. Test substances were assigned in a random, double-blind manner. A final placebo control trial completed the experiment. There was no significant difference in any measured parameters among days of withdrawal after ingestion of placebo. At exhaustion in the 2- and 4-day withdrawal trials, there were significant increases in plasma norepinephrine in response to caffeine ingestion. Caffeine-induced increases in serum free fatty acids occurred after 4 days and only at rest. Subjects responded to caffeine with increases in plasma epinephrine (P < 0.05) at exhaustion and prolonged exercise time in all caffeine trials compared with placebo, regardless of withdrawal from caffeine. It is concluded that increased endurance is unrelated to hormonal or metabolic changes and that it is not related to prior caffeine habituation in recreational athletes.

Administration, Oral↗