Fuel metabolism in men and women during and after long-duration exercise

This study aimed to determine gender-based differences in fuel metabolism in response to long-duration exercise. Fuel oxidation and the metabolic response to exercise were compared in men (n = 14) and women (n = 13) during 2 h (40% of maximal O2 uptake) of cycling and 2 h of postexercise recovery. In addition, subjects completed a separate control day on which no exercise was performed. Fuel oxidation was measured using indirect calorimetry, and blood samples were drawn for the determination of circulating substrate and hormone levels. During exercise, women derived proportionally more of the total energy expended from fat oxidation (50.9 +/- 1.8 and 43. 7 +/- 2.1% for women and men, respectively, P < 0.02), whereas men derived proportionally more energy from carbohydrate oxidation (53.1 +/- 2.1 and 45.7 +/- 1.8% for men and women, respectively, P < 0.01). These gender-based differences were not observed before exercise, after exercise, or on the control day. Epinephrine (P < 0.007) and norepinephrine (P < 0.0009) levels were significantly greater during exercise in men than in women (peak epinephrine concentrations: 208 +/- 36 and 121 +/- 15 pg/ml in men and women, respectively; peak norepinephrine concentrations: 924 +/- 125 and 659 +/- 68 pg/ml in men and women, respectively). As circulating glycerol levels were not different between the two groups, this suggests that women may be more sensitive to the lipolytic action of the catecholamines. In conclusion, these data support the view that different priorities are placed on lipid and carbohydrate oxidation during exercise in men and women and that these gender-based differences extend to the catecholamine response to exercise.     

Effects of exercise on dietary protein requirements

This paper reviews the factors (exercise intensity, carbohydrate availability, exercise type, energy balance, gender, exercise training, age, and timing of nutrient intake or subsequent exercise sessions) thought to influence protein need. Although there remains some debate, recent evidence suggests that dietary protein need increases with rigorous physical exercise. Those involved in strength training might need to consume as much as 1.6 to 1.7 g protein x kg(-1) x day(-1) (approximately twice the current RDA) while those undergoing endurance training might need about 1.2 to 1.6 g x kg(-1) x day(-1) (approximately 1.5 times the current RDA). Future longitudinal studies are needed to confirm these recommendations and asses whether these protein intakes can enhance exercise performance. Despite the frequently expressed concern about adverse effects of high protein intake, there is no evidence that protein intakes in the range suggested will have adverse effects in healthy individuals.     

Caffeine, performance, and metabolism during repeated Wingate exercise tests

Investigations examining the ergogenic and metabolic influence of caffeine during short-term high-intensity exercise are few in number and have produced inconsistent results. This study examined the effects of caffeine on repeated bouts of high-intensity exercise in recreationally active men. Subjects (n = 9) completed four 30-s Wingate (WG) sprints with 4 min of rest between each exercise bout on two separate occasions. One hour before exercise, either placebo (P1; dextrose) or caffeine (Caf; 6 mg/kg) capsules were ingested. Caf ingestion did not have any effect on power output (peak or average) in the first two WG tests and had a negative effect in the latter two exercise bouts. Plasma epinephrine concentration was significantly increased 60 min after Caf ingestion compared with P1; however, this treatment effect disappeared once exercise began. Caf ingestion had no significant effect on blood lactate, O2 consumption, or aerobic contribution at any time during the protocol. After the second Wingate test, plasma NH3 concentration increased significantly from the previous WG test and was significantly higher in the Caf trial compared with P1. These data demonstrate no ergogenic effect of caffeine on power output during repeated bouts of short-term, intense exercise. Furthermore, there was no indication of increased anaerobic metabolism after Caf ingestion with the exception of an increase in NH3 concentration.     

Modulation of renal kallikrein production by dietary protein in streptozotocin-induced diabetic rats

Renal kallikrein levels and excretion rates are increased in insulin-treated diabetic rats with hyperfiltration, and inhibition of kallikrein or blockade of kinin receptors reduces GFR and RPF. In contrast, insulin-deprived severely (SD) diabetic rats that display renal vasoconstriction show reduced levels and excretion rates of renal kallikrein. In these two models, dietary protein manipulation was utilized to study further the relationships between renal kallikrein and renal hemodynamic regulation. Insulin-deprived SD and insulin-treated moderately diabetic (MD) rats were fed a low (9%), normal (25%), and a high (50%) protein diet. In SD rats fed the 50% protein diet, GFR, RPF, and kallikrein excretion rate were increased compared with SD rats fed the 25% protein diet (GFR, 2.66 +/- 0.16 versus 1.74 +/- 0.30 mL/min; RPF, 7.78 +/- 0.58 versus 5.14 +/- 1.03 mL/min; total kallikrein, 248 +/- 24 versus 120 +/- 30 micrograms/24 h, SD 50% versus SD 25%, respectively; P < 0.005). In MD rats fed the 9% protein diet, GFR, RPF, and kallikrein excretion rate were significantly reduced compared with MD 25% protein-fed rats (GFR, 1.54 +/- 0.07 versus 1.95 +/- 0.09 mL/min; RPF, 5.58 +/- 0.35 versus 7.81 +/- 0.35 mL/min; total kallikrein, 119 +/- 8.3 versus 219 +/- 15 micrograms/24 h, MD 9% versus MD 25%, respectively; P < 0.005). Protein restriction in normal nondiabetic rats resulted in a twofold decrease in kallikrein mRNA levels. These findings suggest that the renal hemodynamic response to dietary protein manipulation in diabetic rats could be mediated via changes in renal kallikrein-kinin system activity.     

Autonomic control of cardiovascular performance and whole body O2 delivery and utilization in swine during treadmill exercise

OBJECTIVE: The present study determined the role of the autonomic nervous system (ANS) in the regulation of systemic and pulmonary circulation and of O2 delivery and utilization in swine at rest and during graded treadmill exercise. METHODS: Instrumented swine (n = 12) were subjected to treadmill exercise (1-5 km/h) under control conditions and in the presence of single and combined beta-adrenergic, alpha-adrenergic and muscarinic (M) receptor blockade. RESULTS: Exercise produced a four-fold increase in body O2 consumption, due to a doubling of both cardiac output and the arterio-mixed-venous O2 content difference. The latter resulted from an increase in O2 extraction, from 45 +/- 1% at rest to 74 +/- 1% at 5 km/h, as the O2 carrying capacity [haemoglobin concentration (Hb)] increased by only approximately 10%. The increase in cardiac output resulted from a doubling of the heart rate and a small (< 10%) increase in stroke volume. The mean aortic pressure (MAP) was unchanged, implying a 50% decrease in systemic vascular resistance (P < or = 0.05). In contrast, exercise had no significant effect on pulmonary vascular resistance. The sympathetic division of the ANS controlled O2 delivery via beta-adrenoceptors (heart rate and contractility) and Hb concentration via alpha-adrenoceptor-mediated splenic contraction. In addition, the sympathetic division modulated systemic vascular tone via alpha- and beta-adrenoceptors, but also exerted a vasodilator influence on the pulmonary circulation via beta-adrenoceptors. The parasympathetic division controlled O2 delivery in part directly (heart rate) and in part indirectly via inhibition of beta-adrenoceptor activity (heart rate and contractility), even during heavy exercise. In addition, the parasympathetic division exerted a direct vasodilator influence on the pulmonary, but not on the systemic, circulation. CONCLUSIONS: Thus, in swine, in a manner similar to that in humans, both the sympathetic and parasympathetic division of the ANS contribute to cardiovascular homeostasis during exercise up to levels of high intensity.     

Modulation of vascular function by diet and exercise

Clinical research is conducted in free living individuals who are always subject to the influences on vascular function and the major cardiovascular regulators of their lifestyle. The purpose of this paper is to review some lifestyle influences on cardiovascular function, particularly the sympathetic nervous system and endothelially mediated vasodilatation. There are highly differentiated sympathetic responses to feeding, and to acute exercise. Over a longer period obesity has a typical pattern of sympathetic activity. Reduced dietary salt intake elicits profound localised increases in sympathetic activity to the kidney. Marine oil supplementation attenuates the sympathetic responses to psychological stress and improves endothelially mediated vasodilatation in hypercholesterolaemics. Exercise training reduced total noradrenaline spillover, the major beds affected being the renal and skeletal muscle. These examples illustrate the dynamic nature of vascular dilatation and that, like the sympathetic nervous system, it is modulated by short, medium and long term influences. In both cases there is regulation both at a local and systemic level. Habitual, and recent, lifestyle can exert important cardiovascular effects which must be taken into account in clinical and epidemiological research.     

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.     

Effect of theophylline on substrate metabolism during exercise

We tested the hypothesis that adenosine is involved in regulating substrate metabolism during exercise. Seven trained cyclists were studied during 30 minutes of exercise at approximately 75% maximal oxygen uptake (VO2max). Lipid metabolism was evaluated by infusing [2H5]glycerol and [1-13C]palmitate, and glucose kinetics were evaluated by infusing [6,6-2H]glucose. Fat and carbohydrate oxidation were also measured by indirect calorimetry. The same subjects performed two identical exercise tests, but in one trial theophylline, a potent adenosine receptor antagonist, was infused for 1 hour before and throughout exercise. Theophylline did not increase whole-body lipolysis (glycerol rate of appearance [Ra]) or free fatty acid (FFA) release during exercise, but fat oxidation was lower than control values (9.5 +/- 3.0 v 18.0 +/- 4.2 micromol x min(-1) x kg(-1), P < .01). Glucose Ra was not affected by theophylline infusion, but glucose uptake was lower (31.6 +/- 4.1 v 40.4 +/- 5.0 micromol x min(-1) x kg(-1), P < .05) and glucose concentration was higher (6.4 +/- 0.6 v 5.8 +/- 0.4 mmol/L, P < .05) than in the control trial. Total carbohydrate oxidation (302.3 +/- 26.2 v 265.5 +/- 11.7 micromol x min(-1) x kg(-1), P < .06), estimated muscle glycogenolysis (270.7 +/- 23.1 v 225.1 +/- 9.7 micromol x min(-1) x kg(-1), P < .05), and plasma lactate concentration (7.9 +/- 1.6 v 5.9 +/- 1.1 mmol/L, P < .001) were also higher during the theophylline trial. These data suggest that adenosine may play a role in stimulating glucose uptake and restraining glycogenolysis but not in limiting lipolysis during exercise.     

Gender and fat metabolism during exercise: a review

We examined the evidence for greater fat utilization by women during exercise and the potential gender differences in specific cellular processes. Results from well-controlled studies show that, compared to men, women oxidize more fat during submaximal exercise, resulting in the relative sparing of muscle glycogen. Mature female rats use less muscle glycogen during running and can run longer than male counterparts. Circulating estrogen is critical to these observations, as shown by studies where male rats were treated with estrogen. Estrogen-treated male rats use less muscle glycogen during exercise and can run longer than untreated males. The cellular mechanisms and factors underlying these findings are unknown and certainly multifactorial. We offer some information that, unfortunately, does not lead to any natural conclusion. However, this area is certainly ripe for research.     

Creatine supplementation and age influence muscle metabolism during exercise

Young [n = 5, 30 +/- 5 (SD) yr] and middle-aged (n = 4, 58 +/- 4 yr) men and women performed single-leg knee-extension exercise inside a whole body magnetic resonance system. Two trials were performed 7 days apart and consisted of two 2-min bouts and a third bout continued to exhaustion, all separated by 3 min of recovery. 31P spectra were used to determine pH and relative concentrations of Pi, phosphocreatine (PCr), and beta-ATP every 10 s. The subjects consumed 0.3 g . kg-1 . day-1 of a placebo (trial 1) or creatine (trial 2) for 5 days before each trial. During the placebo trial, the middle-aged group had a lower resting PCr compared with the young group (35.0 +/- 5.2 vs. 39.5 +/- 5.1 mmol/kg, P < 0.05) and a lower mean initial PCr resynthesis rate (18.1 +/- 3.5 vs. 23.2 +/- 6.0 mmol . kg-1 . min-1, P < 0.05). After creatine supplementation, resting PCr increased 15% (P < 0.05) in the young group and 30% (P < 0.05) in the middle-aged group to 45.7 +/- 7.5 vs. 45.7 +/- 5.5 mmol/kg, respectively. Mean initial PCr resynthesis rate also increased in the middle-aged group (P < 0.05) to a level not different from the young group (24.3 +/- 3.8 vs. 24.2 +/- 3.2 mmol . kg-1 . min-1). Time to exhaustion was increased in both groups combined after creatine supplementation (118 +/- 34 vs. 154 +/- 70 s, P < 0.05). In conclusion, creatine supplementation has a greater effect on PCr availability and resynthesis rate in middle-aged compared with younger persons.     

Tissue specific-distribution and metabolism of vitamin A are affected by dietary protein levels in rats

The prevalence of human immunodeficiency virus (HIV) in adolescents is difficult to assess as few adolescents consent to testing. This prospective study characterized urban youth requesting HIV testing at two types of health settings, inner-city school-based and hospital-based clinics. Data were obtained on 1652 inner-city youths aged 13 to 19 years who consented to individualized HIV counseling and testing from January 1993 to January 1994. Identified risks for HIV included sexual activity, sexually transmitted disease (STD) history, and substance use by self-report during a confidential structured interview. Data were analyzed using chi-squared analysis. Of the 1652 youth who were counseled, 1602 were from hospital-based clinics. A total of 827 (50%) requested HIV testing. Females accounted for the majority of youth who underwent counseling (79%) and requested HIV testing (75%). However, once counseled, males were more likely to be tested. Risk factors differed by gender; females were more likely to report STDs and marijuana use, and males more likely to report alcohol and cocaine use. These results indicate a need to identify developmentally appropriate methods to educate and counsel youth about HIV that will lead to more youth willing to be tested. School-based clinics may provide easier access than traditional health models for confidential HIV services.     

Modulation by dietary salt of verapamil disposition in humans

BACKGROUND: The intestine is an increasingly well-recognized site of first-pass drug metabolism. In this study, we determined the influence of dietary salt on the steady-state disposition of verapamil, a drug that undergoes extensive first-pass metabolism. METHODS AND RESULTS: Eight normal volunteers received 120 mg of racemic verapamil orally twice a day for 21 days. The disposition kinetics of verapamil enantiomers were determined after coadministration of intravenous deuterated verapamil with the morning oral dose on days 7, 14, and 21. Each study day was preceded by 7 days on a fixed-salt diet: in 5 subjects, the initial study was conducted during a low-salt (10 mEq/d) diet, the second study during a high-salt (400 mEq/d) diet, and the third during a low-salt diet, whereas in the other 3 subjects, the sequence of diets was reversed. Plasma concentrations of both unlabeled enantiomers (ie, from oral therapy) were significantly (P<0.05) lower during the high-salt phase (eg, mean area under the time-concentration curve [0 to 12 hours] for S-verapamil: 7765+/-2591 ng. min. mL-1 [high salt] versus 12 514+/-3527 ng. min. mL-1 [low salt], P<0.05). Peak plasma concentrations were significantly lower and the extent of PR interval prolongation significantly blunted with the high-salt diet. In contrast, data with labeled drug (ie, reflecting the intravenous route) were nearly identical for the 2 diets. CONCLUSIONS: These data indicate that a clinically important component of presystemic drug disposition occurs at the prehepatic (presumably intestinal) level and is sensitive to dietary salt.     

Training induced adaptation of skeletal muscle and metabolism during submaximal exercise

1. Six subjects were trained using a one-leg bicycle exercise for 2 months. The untrained leg served as control. After the training period, muscle oxidative capacity, determined as succinate dehydrogenase activity, was 27% higher in the trained (as opposed to the control) leg (P < 0.05).2. When the subjects in this situation performed a 1 h two-legged submaximal bicycle exercise bout (150-225 W), determinations of V(O2) of the single leg (leg blood flow x (A-V)(O2) difference) revealed that they appeared to choose to work harder with their trained than with their untrained leg, so as to make the relative loads for the two legs the same.3. Determinations of O(2) and CO(2) on femoral arterial and venous blood demonstrated that the R.Q. was lower in the trained as compared to the untrained leg, 0.91 cf. 0.96 (10 min) and 0.91 cf. 0.94 (50 min) (P < 0.05).4. That metabolism of fat was more pronounced in the trained leg was further supported by the finding of a significant net uptake of free fatty acids in this leg only. Moreover, a lower release of lactate from the trained leg was demonstrated.5. It is suggested that the shift towards a more pronounced metabolism of fat in the trained leg is a function of an increased muscle oxidative capacity.     

Influence of dietary protein and carbohydrate on antipyrine and theophylline metabolism in man

This study was undertaken to examine the influence of changes in dietary carbohydrate and protein content on the oxidation of antipyrine and theophylline in man. When the diets of 6 normal volunteers were changed from their usual home diets to low carbohydrate-high protein diets, the plasma half-life of antipyrine decreased from 16.2 hr to 9.5 hr, and the half-life of theophylline decreased from 8.1 hr to 5.2 hr. When the subjects' diets were changed from low carbohydrate-high protein diets to a high carbohydrate-low protein diets, the mean antipyrine half-life increased from 9.5 hr to 15.6 hr and the mean theophylline half-life increased from 5.2 hr to 7.6 hr. These changes in half-lives were accompanied by changes in metabolic clearance rates but not in the apparent volumes of distribution of the drugs tested. Qualitatively similar results were obtained when the subjects were placed on standard diets followed by the standard diets supplemented with carbohydrate or protein. Supplementing the standard diets with carbohydrate caused an increase in drug half-lives, whereas a protein supplement caused a decrease in the drug half-lives. These data demonstrate marked influences of nutritional factors on oxidative biotransformation of drugs in man.     

Acylcarnitine metabolism during fasting and after refeeding

Carnitine metabolism during starvation and just after refeeding was studied by the measurement of acylcarnitine (ACR) and total carnitine (TCR) concentration in the serum and liver of mice. Starvation caused marked increases in the concentration of serum ACR, and of acid-soluble ACR in the liver. The refeeding caused the quick decrement of serum ACR with a concomitant marked increase in the level of acid-soluble TCR in the liver. Through the use of positron emission tomography in a rhesus monkey, a marked increase in [2-11C]acetyl-L-carnitine uptake in the liver was observed after the administration of glucose accompanying the decrease of serum ACR. From this study, it is clear that the mammalian liver can salvage and conserve the unused ACR when the state of energy metabolism is improved.