Creatine and low-dose lithium supplementation separately alter energy expenditure, body mass, and adipose metabolism for the promotion of thermogenesis.

Nutraceutical approaches to promote adipose tissue thermogenesis may help to prevent obesity onset. Creatine is a critical regulator of adipose metabolic function and low-dose lithium supplementation has been shown to promote adipose thermogenesis. In the present study, we sought to directly compare the two supplements for their effects on adipose metabolism and thermogenesis. We show that both supplements increase daily energy expenditure (EE) and reduce body mass in male Sprague-Dawley rats. Lithium increased brown adipose tissue (BAT) mitochondrial and lipolytic proteins that are associated with thermogenesis, while creatine increased BAT UCP1 and mitochondrial respiration. The BAT thermogenic findings were not observed in females. White adipose tissue and skeletal muscle markers of thermogenesis were unaltered with the supplements. Together, the data show that low-dose lithium and creatine have diverging effects on markers of BAT thermogenesis and that each increase daily EE and lower body mass in a sex-dependent manner.

Creatine monohydrate enhances strength and body composition in Duchenne muscular dystrophy.

OBJECTIVE: To determine whether creatine monohydrate (CrM) supplementation increases strength and fat-free mass (FFM) in boys with Duchenne muscular dystrophy (DD). METHODS: Thirty boys with DD (50% were taking corticosteroids) completed a double-blind, randomized, cross-over trial with 4 months of CrM (about 0.10 g/kg/day), 6-week wash-out, and 4 months of placebo. Measurements were completed of pulmonary function, compound manual muscle and handgrip strength, functional tasks, activity of daily living, body composition, serum creatine kinase and gamma-glutamyl transferase activity and creatinine, urinary markers of myofibrillar protein breakdown (3-methylhistidine), DNA oxidative stress (8-hydroxy-2-deoxyguanosine [8-OH-2-dG]), and bone degradation (N-telopeptides). RESULTS: During the CrM treatment phase, there was an increase in handgrip strength in the dominant hand and FFM (p < 0.05), with a trend toward a loss of global muscle strength (p = 0.056) only for the placebo phase, with no improvements in functional tasks or activities of daily living. Corticosteroid use, but not CrM treatment, was associated with a lower 8-OH-2-dG/creatinine (p < 0.05), and CrM treatment was associated with a reduction in N-telopeptides (p < 0.05). CONCLUSIONS: Four months of CrM supplementation led to increases in FFM and handgrip strength in the dominant hand and a reduction in a marker of bone breakdown and was well tolerated in children with DD.

Histological assessment of intermediate- and long-term creatine monohydrate supplementation in mice and rats.

Creatine monohydrate (CrM) supplementation appears to be relatively safe based on data from short-term and intermediate-term human studies and results from several therapeutic trials. The purpose of the current study was to characterize pathological changes after intermediate-term and long-term CrM supplementation in mice [healthy control and SOD1 (G93A) transgenic] and rats (prednisolone and nonprednisolone treated). Histological assessment (18-20 organs/tissues) was performed on G93A mice after 159 days, and in Sprague-Dawley rats after 365 days, of CrM supplementation (2% wt/wt) compared with control feed. Liver histology was also evaluated in CD-1 mice after 300 days of low-dose CrM supplementation (0.025 and 0.05 g x kg-1x day-1) and in Sprague-Dawley rats after 52 days of CrM supplementation (2% wt/wt) with and without prednisolone. Areas of hepatitis were observed in the livers of the CrM-supplemented G93A mice (P < 0.05), with no significant inflammatory lesions in any of the other 18-20 tissues/organs that were evaluated. The CD-1 mice also showed significant hepatic inflammatory lesions (P < 0.05), yet there was no negative effect of CrM on liver histology in the Sprague-Dawley rats after intermediate-term or long-term supplementation nor was inflammation seen in any other tissues/organs (P = not significant). Dietary CrM supplementation can induce inflammatory changes in the liver of mice, but not rats. The observed inflammatory changes in the murine liver must be considered in the evaluation of hepatic metabolism in CrM-supplemented mice. Species differences must be considered in the evaluation of toxicological and physiological studies.

Paradoxical effects of prior activity on human sarcoplasmic reticulum Ca2+-ATPase response to exercise.

To investigate the effects of intermittent heavy exercise (HE) on sarcoplasmic reticulum (SR) maximal Ca2+-ATPase activity (Vmax) and Ca2+ uptake, a continuous two-stage standardized cycling test was performed before and after HE by untrained men [peak aerobic power (Vo -->Vo2 peak) = 42.9 +/- 2.7 ml. kg-1 x min-1]. The HE consisted of 16 bouts of cycling performed for 6 min each hour at 90% Vo2 peak. Tissue was obtained from the vastus lateralis by needle biopsy before and during each cycle test. Before HE, reductions (P < 0.05 micromol. g protein-1x min-1) of 16 and 31% were observed in Vmax and Ca2+ uptake, respectively, after 40 min of the standardized test. Resting Vmax and Ca2+ uptake were depressed (P < 0.05) by 19 and 30%, respectively, when measured 36-48 h after HE. During the standardized test, after HE, Vmax increased (P < 0.05) by 20%, whereas no change was observed in Ca2+ uptake. The HE protocol resulted in small increases (P < 0.05) and decreases (P < 0.05) in sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) 2a and SERCA1 expression, respectively, as determined by Western blotting techniques. These results indicate that SR Ca2+-sequestering function in response to a prolonged exercise test depends on prior activity status, such that rested muscles exhibit a decrease and prior exercised muscles, an increase in Ca2+-ATPase activity. Moreover, it appears that changes in SERCA content can occur in response to a sustained session of intermittent exercise.

Resistance-training-induced adaptations in skeletal muscle protein turnover in the fed state.

Resistance training changes the balance of muscle protein turnover, leading to gains in muscle mass. A longitudinal design was employed to assess the effect that resistance training had on muscle protein turnover in the fed state. A secondary goal was investigation of the potential interactive effects of creatine (Cr) monohydrate supplementation on resistance-training-induced adaptations. Young (N = 19, 23.7 +/- 3.2 year), untrained (UT), healthy male subjects completed an 8-week resistance-training program (6 d/week). Supplementation with Cr had no impact on any of the variables studied; hence, all subsequent data were pooled. In the UT and trained (T) state, subjects performed an acute bout of resistance exercise with a single leg (exercised, EX), while their contralateral leg acted as a nonexercised (NE) control. Following exercise, subjects were fed while receiving a primed constant infusion of [d5]- and [15N]-phenylalanine to determine the fractional synthetic and breakdown rates (FSR and FBR), respectively, of skeletal muscle proteins. Acute exercise increased FSR (UT-NE, 0.065 +/- 0.025 %/h; UT-EX, 0.088 +/- 0.032 %/h; P < 0.01) and FBR (UT-NE, 0.047 +/- 0.023 %/h; UT-EX, 0.058 +/- 0.026 %/h; P < 0.05). Net balance (BAL = FSR - FBR) was positive in both legs (P < 0.05) but was significantly greater (+65%) in the EX versus the NE leg (P < 0.05). Muscle protein FSR and FBR were greater at rest following T (FSR for T-NE vs. UT-NE, +46%, P < 0.01; FBR for T-NE vs. UT-NE, +81%, P < 0.05). Resistance training attenuated the acute exercise-induced rise in FSR (T-NE vs. T-EX, +20%, P = 0.65). The present results demonstrate that resistance training resulted in an elevated resting muscle protein turnover but an attenuation of the acute response of muscle protein turnover to a single bout of resistance exercise.

Substrate turnover and oxidation during moderate-intensity exercise following acute plasma volume expansion.

In previous work using prolonged, light cycle exercise, we were unable to demonstrate an effect of acute plasma volume (PV) expansion on glucose kinetics or substrate oxidation, despite a decline in whole-body lipolysis (Phillips et al., 1997). However, PV is known to decrease arterial O2 content. The purpose of this study was to examine whether substrate turnover and oxidation would be altered with heavier exercise where the challenge to O2 delivery is increased. Eight untrained males (VO2max = 3.52 +/- 0.12 l/min) twice performed 90 min of cycle ergometry at 62 % VO2peak, both prior to (CON) and following induced plasma volume expansion (Dextran [6 %] or Pentaspan [10 %]) (6.7 ml/kg) (PVX). Glucose and glycerol kinetics were determined with primed constant infusions of [6.6-(2)H2] glucose and [(2)H5] glycerol, respectively. PVX resulted in a 15.8 +/- 2.2 % increase (p < 0.05) in PV. Glucose and glycerol appearance (Ra) and utilization (Rd), although increasing progressively (p < 0.05) with exercise, were not different between conditions. Similarly, no differences in substrate oxidation, either fat or carbohydrate, were observed between the two conditions. Prolonged exercise resulted in an increase (p < 0.05) in plasma glucagon and a decrease (p < 0.05) in plasma insulin during both conditions. With PVX, the exercise-induced increase in glucagon was diminished (p < 0.05). We conclude that impairment in O2 content mediated by an elevated PV does not alter glucose, and glycerol kinetics or substrate oxidation even at moderate exercise intensity.

Human neuromuscular fatigue is associated with altered Na+-K+-ATPase activity following isometric exercise.

The purpose of this study was to investigate the hypothesis that reductions in Na+-K+- ATPase activity are associated with neuromuscular fatigue following isometric exercise. In control (Con) and exercised (Ex) legs, force and electromyogram were measured in 14 volunteers [age, 23.4 +/- 0.7 (SE) yr] before and immediately after (PST0), 1 h after (PST1), and 4 h after (PST4) isometric, single-leg extension exercise at ~60% of maximal voluntary contraction for 30 min using a 0.5 duty cycle (5-s contraction, 5-s rest). Tissue was obtained from vastus lateralis muscle before exercise in Con and after exercise in both the Con (PST0) and Ex legs (PST0, PST1, PST4), for the measurements of Na+-K+-ATPase activity, as determined by the 3-O-methylfluorescein phosphatase (3-O-MFPase) assay. Voluntary (maximal voluntary contraction) and elicited (10, 20, 50, 100 Hz) force was reduced 30-55% (P < 0.05) at PST0 and did not recover by PST4. Muscle action potential (M-wave) amplitude and area (measured in the vastus medialis) and 3-O-MFPase activity at PST0-Ex were less than that at PST0-Con (P < 0.05) by 37, 25, and 38%, respectively. M-wave area at PST1-Ex was also less than that at PST1-Con (P < 0.05). Changes in 3-O-MFPase activity correlated to changes in M-wave area across all time points (r = 0.38, P < 0.05, n = 45). These results demonstrate that Na+-K+- ATPase activity is reduced by sustained isometric exercise in humans from that in a matched Con leg and that this reduction in Na+-K+-ATPase activity is associated with loss of excitability as indicated by M-wave alterations.

An acute oral dose of caffeine does not alter glucose kinetics during prolonged dynamic exercise in trained endurance athletes.

This study investigated the possible influence of oral caffeine administration on endogenous glucose production and energy substrate metabolism during prolonged endurance exercise. Twelve trained endurance athletes [seven male, five female; peak oxygen consumption (VO2peak) = 65.5 ml.kg-1.min-1] performed 60 min of cycle ergometry at 65% VO2peak twice, once after oral caffeine administration (6 mg.kg-1) (CAF) and once following consumption of a placebo (PLA). CAF and PLA were administered in a randomized double-blind manner 75 min prior to exercise. Plasma glucose kinetics were determined with a primed-continuous infusion of [6,6-2H]glucose. No differences in oxygen consumption (VO2), and carbon dioxide production (VCO2) were observed between CAF and PLA, at rest or during exercise. Blood glucose concentrations were similar between the two conditions at rest and also during exercise. Exercise did lead to an increase in serum free fatty acid (FFA) concentrations for both conditions; however, no differences were observed between CAF and PLA. Both the plasma glucose rate of appearance (Ra) and disappearance (Rd) increased at the onset of exercise (P < 0.05), but were not affected by CAF, as compared to PLA. CAF did lead to a higher plasma lactate concentration during exercise (P < 0.05). It was concluded that an acute oral dose of caffeine does not influence plasma glucose kinetics or energy substrate oxidation during prolonged exercise in trained endurance athletes. However, CAF did lead to elevated plasma lactate concentrations. The exact mechanism of the increase in plasma lactate concentrations remains to be determined.

Prolonged exercise following diuretic-induced hypohydration effects on fluid and electrolyte hormones.

To investigate the hypothesis that a reduction in plasma volume (PV) induced by diuretic administration would result in an increase in the fluid and electrolyte hormonal response to exercise, ten untrained males (VO(2) peak = 3.96 +/- 0.14 l/min) performed 60 min of cycle ergometry at 61 % VO(2) peak twice. The test was carried out once under control conditions (CON) (placebo) and once after 4 days of diuretic administration (DIU) (Novotriamazide; 100 mg triamterene and 50 mg hydrochlorothiazide). Calculated resting PV decreased by 14.6 +/- 3.3 % (p < 0.05) with DIU. No difference in plasma osmolality was observed between conditions. For the hormones measured, differences (p < 0.05) between conditions at rest were noted for plasma renin activity (PRA) (0.62 +/- 0.09 vs. 5.61 +/- 0.94 ng/ml/h), angiotensin I (ANG 1) (0.26 +/- 0.03 vs. 0.56 +/- 0.08 ng/ml), aldosterone (ALD) (143 +/- 14 vs. 1603 +/- 302 pg/ml), arginine vasopressin (AVP) (4.13 +/- 1.1 vs. 9.58 +/- 1.6 pg/ml) and atrial natriuretic peptide (alpha-ANP) (11.5 +/- 2.8 vs. 6.33 +/- 1.0 pg/ml). The exercise resulted in increases (p < 0.05) in PRA, ANG I, ALD, AVP, alpha-ANP. DIU led to higher levels of PRA, ANG I, and ALD (p < 0.05) and lower levels of alpha-ANP (p < 0.05) compared to CON. Arginine vasopressin was not affected by the loss of PV. For the catecholamines--norepinephrine (NE) and epinephrine (EPI)--only NE was higher during exercise with DIU compared to CON (p < 0.05). For PRA and ALD, the higher levels observed during exercise with DIU could be explained both by higher resting levels and a greater increase during exercise itself. For ANG I and NE, the effect of DIU only manifested itself during exercise. In contrast, the lower alpha-ANP observed during exercise with DIU was due to the lower resting levels. These results support the hypotheses that hypohydration leads to alterations in the secretion of all of the fluid and electrolyte hormones with the exception of AVP. The specific mechanisms of these alterations remain unclear, but appear to be related directly to the decrease in PV.

Acute plasma volume expansion in the untrained alters the hormonal response to prolonged moderate-intensity exercise.

To investigate the role of an increase in plasma volume (PV), characteristically observed with short-term endurance training, on the endocrine response to prolonged moderate intensity exercise, eight untrained males (VO2 peak = 3.52 +/- 0.12 l x min(-1)) performed 90 min of cycle ergometry at approximately 60% VO2peak both before (CON) and following (PVX) PV expansion. Acute PV expansion, which was accomplished using a solution of Dextran (6%) or Pentispan (10%) (6.7 ml kg(-1)), resulted in a calculated 15.8+/-2.2% increase (p<0.05) in PV. The prolonged exercise resulted in increases (p<0.05) in plasma vasopressin (AVP), plasma rennin activity (PRA), aldosterone (ALD), atrial naturetic peptide (alpha-ANP), and the catecholamines norepinephrine (NE) and epinephrine (EPI). PVX blunted the increases (p<0.05) in AVP, PRA, ALD, NE and EPI, during the exercise itself. The concentration of alpha-ANP was also lower (p<0.05) during exercise following PVX, an effect that could be attributed to the lower resting levels. No differences in osmolality was observed between conditions. These results demonstrate that PVX alters the fluid regulatory hormonal response in untrained subjects to moderate intensity dynamic exercise in a manner similar to that observed following short-term training induced alterations in PV. The specific mechanisms responsible for these alterations remain unclear, but appear to be related directly to the increase in PV.

Short-term 17-beta-estradiol administration does not affect metabolism in young males.

We have previously demonstrated that females oxidize more lipid and less protein and carbohydrate during endurance exercise [21]. Several studies in male rats have demonstrated similar metabolic changes after 4 d of 17-beta-estradiol (E2) administration. Our purpose was to study the effects of E2 administration upon substrate metabolism during 90min of cycle ergometry at 60% VO2peak in 11 healthy, young males. E2 was administered in a single-blind, cross-over, randomized fashion for 11 d (100 microg.d(-1) x 3.5d --> 200 microg.d(-1) x 3.5 d --> 300 microg.d(-1) x 4.0 d). Respiratory exchange ratio (RER), VO2, Ve, HR, lactate, and glucose were measured every 30 min during exercise and E2, testosterone TEST, glycerol and triglycerides were measured prior to exercise T = 0 min. Muscle biopsies were taken from the vastus lateralis before and after exercise for glycogen determination. Estradiol treatment resulted in lower plasma TEST (20.8-->7.8 nmol.L(-1), P<0.0001) and higher plasma E2 (168.1 327.3 pmol.L(-1), P < 0.002). Therewere no effects of E2 treatment upon any of the other measured variables including muscle glycogen: (E2 - PRE = 529.3 --> POST = 237.9; PL-PRE = 582.2 --> POST = 262.4 mmol.kg(-1) [dm]). We concluded that short-term E2 treatment increased plasma E2 to female follicular levels in males but had no effect upon lipid or carbohydrate metabolism.

Prolonged exercise after diuretic-induced hypohydration: effects on substrate turnover and oxidation.

To determine the influence of a diuretic-induced reduction in plasma volume (PV) on substrate turnover and oxidation, 10 healthy young males were studied during 60 min of cycling exercise at 61% peak oxygen uptake on two separate occasions > or =1 wk apart. Exercise was performed under control conditions (CON; placebo), and after 4 days of diuretic administration (DIU; Novotriamazide; 100 mg triamterene and 50 mg hydrochlorothiazide). DIU resulted in a calculated reduction of PV by 14.6 +/- 3.3% (P < 0.05). Rates of glucose appearance (R(a)) and disappearance (R(d)) and glycerol R(a) were determined by using primed constant infusions of [6,6-(2)H]glucose and [(2)H(5)]glycerol, respectively. No differences in oxygen uptake during exercise were observed between trials. Main effects for condition (P < 0.05) were observed for plasma glucose and glycerol, such that the values observed for DIU were higher than for CON. No differences were observed in plasma lactate and serum free fatty acid concentrations either at rest or during exercise. Hypohydration led to lower (P < 0.05) glucose R(a) and R(d) at rest and at 15 and 30 min of exercise, but by 60 min, the effects were reversed (P < 0. 05). Hypohydration had no effect on rates of whole body lipolysis or total carbohydrate or fat oxidation. A main effect for condition (P < 0.05) was observed for plasma glucagon concentrations such that larger values were observed for DIU than for CON. A similar decline in plasma insulin occurred with exercise in both conditions. These results indicate that diuretic-induced reductions in PV decreases glucose kinetics during moderate-intensity dynamic exercise in the absence of changes in total carbohydrate and fat oxidation. The specific effect on glucose kinetics depends on the duration of the exercise.

The effects of acute passive stretch on muscle protein synthesis in humans.

We examined the effect of an isolated bout of maximal tolerated passive stretch on fractional muscle protein synthetic rate in human soleus muscle. Eight healthy males performed two separate trials with the same leg: one session of passive stretch and one of intermittent active isometric contraction at a force equivalent to that which occurred during the passive stretch trial. This force was approximately 40% of maximum voluntary contraction force and produced volitional fatigue in approximately 27 min. Intermittent passive stretch, for the same duration, elicited a 6.1 degrees increase in joint angle (P<.0005) with silent electromyography. Fractional protein synthetic rate from experimental and control soleus in each trial was assessed from biopsy samples over the period 10-22 hr postexercise by the incorporation rate of L-[1-13C] leucine into muscle. Protein synthesis was elevated in the soleus of the exercised leg following the active contraction trial by 49% (P<.05) but not following the passive stretch trial. Results indicate that a single bout of maximal passive stretch does not significantly elevate fractional muscle protein synthetic rate in humans and thus suggests that muscle stretch per se is not the stimulus for the muscle hypertrophy that occurs with resistance training.

Macronutrient intake and whole body protein metabolism following resistance exercise.

UNLABELLED: The provision of carbohydrate (CHO) supplements following resistance exercise attenuated muscle protein (PRO) degradation (Roy et al. J. Appl. Physiol. 82:1882-1888, 1997). The addition of PRO may have a synergistic effect upon whole body protein balance by increasing synthesis (Biolo et al. Am. J. Physiol. 273:E122-E129, 1997). PURPOSE: To determine if the macronutrient composition of a postexercise beverage would alter muscle anabolism and/or catabolism following resistance exercise. METHODS: We provided isoenergetic CHO (1 g x kg(-1)) and CHO/PRO/FAT supplements and placebo (PL) immediately (t = 0 h) and 1 h (t = + 1 h) following resistance exercise (9 exercises/3 sets/80% 1 RM) to 10 young, healthy, resistance-trained males. Whole body leucine turnover was determined from L-[1-13C]leucine kinetics at approximately 4 h postexercise. RESULTS: No differences were observed for urinary 3-methylhistidine or urea nitrogen excretion between the trials. Leucine flux was significantly elevated at approximately 4 h postexercise for both CHO/PRO/FAT (177.59+/-12.68 micromol x kg(-1) x h(-1)) and CHO (156.18+/-7.77 micromol x kg(-1) x h(-1)) versus PL (126.32+/-10.51 micromol x kg(-1) x h(-1)) (P < 0.01). Whole body leucine oxidation was elevated at approximately 4 h for CHO/PRO/FAT (29.50+/-3.34 micromol x kg(-1) h(-1)) versus CHO (16.32+/-2.33 micromol x kg(-1) x h(-1)) (P < 0.01) and PL (21.29+/-2.54 micromol x kg(-1) x h(-1)) (P < 0.05). Nonoxidative leucine disposal (NOLD) was significantly elevated at approximately 4 h for both CHO/PRO/FAT (148.09+/-10.37 micromol x kg(-1) x h(-1)) and CHO (139.86+/-7.02 micromol x kg(-1) x h(-1)) versus PL (105.03+/-8.97 micromol x kg(-1) x h(-1)) (P < 0.01). CONCLUSIONS: These results suggest that consumption of either CHO or CHO/PRO/FAT immediately and 1 h following a resistance training bout increased NOLD as compared with a placebo.

Prolonged exercise following diuretic-induced hypohydration: effects on cardiovascular and thermal strain.

To examine the role of a reduction in plasma volume (PV) on the cardiovascular and thermoregulatory responses to submaximal exercise, ten untrained males (VO2 peak = 3.96 +/- 0.14 L x min(-1); mean +/- SE) performed 60 min of cycle exercise at -61% of VO2 peak while on a diuretic (DIU) and under control (CON) conditions. Participants consumed either Novotriamazide (100 mg triameterene + 50 mg hydrochlorothiazide, a diuretic) or a placebo, in random order, for 4 days prior to the exercise. Diuretic resulted in a calculated 14.6% reduction (P < 0.05) in resting PV. Heart rate was higher (P < 0.05) at rest and throughout exercise for DIU compared with CON. No differences were observed for cardiac output (Qc) and stroke volume (SV) at rest for the two conditions, but during exercise both Qc and SV were lower (P < 0.05) with DIU. Exercise VO2 (L x min(-1)) for CON and DIU at 30 min (2.39 +/- 0.09 vs 2.43 +/- 0.08) and 60 min (2.56 +/- 0.08 vs 2.53 +/- 0.12) were similar between conditions. Whole body a-vO2 difference was significantly greater (P < 0.05) for DIU both at rest and during exercise as compared with CON. Rectal temperature (Tre) was significantly higher (P < 0.05) during DIU from 15 min to the end of exercise. Blood concentrations of norepinephrine were higher (P < 0.05) with DIU compared to CON at 15 min of exercise and beyond. For blood epinephrine, no differences were observed between DIU and CON. These results suggest that reductions in PV led to greater circulating concentrations of norepinephrine which likely resulted from increased cardiac and thermoregulatory stresses. In addition, reductions in PV do not appear to increase cardiovascular instability during prolonged dynamic exercise.

Myofibrillar disruption following acute concentric and eccentric resistance exercise in strength-trained men.

We have previously quantified the extent of myofibrillar disruption which occurs following an acute bout of resistance exercise in untrained men, however the response of well-trained subjects is not known. We therefore recruited six strength-trained men, who ceased training for 5 days and then performed 8 sets of 8 uni-lateral repetitions, using a load equivalent to 80% of their concentric (Con) 1-repetition maximum. One arm performed only Con actions by lifting the weight and the other arm performed only eccentric actions (Ecc) by lowering it. Needle biopsy samples were obtained from biceps brachii of each arm approximately 21 h following exercise, and at baseline (i.e., after 5 days without training), and subsequently analyzed using electron microscopy to quantify myofibrillar disruption. A greater (P < or = 0.05) proportion of disrupted fibres was found in the Ecc arm (45 +/- 11%) compared with baseline values (4 +/- 2%), whereas fibre disruption in the Con arm (27 +/- 4%) was not different (P > 0.05) from baseline values. The proportion of disrupted fibres and the magnitude of disruption (quantified by sarcomere counting) was considerably less severe than previously observed in untrained subjects after an identical exercise bout. Mixed muscle protein synthesis, assessed from approximately 21-29 h post-exercise, was not different between the Con- and Ecc-exercised arms. We conclude that the Ecc phase of resistance exercise is most disruptive to skeletal muscle and that training attenuates the severity of this effect. Moreover, it appears that fibre disruption induced by habitual weightlifting exercise is essentially repaired after 5 days of inactivity in trained men.

Acute plasma volume expansion alters cardiovascular but not thermal function during moderate intensity prolonged exercise.

To investigate the hypothesis that the increase in plasma volume (PV) that typically occurs with training results in improved cardiovascular and thermal regulation during prolonged exercise, eight untrained males (V(O2)peak = 3.52 +/- 0.12 L x min(-1)) performed 90 min of cycle ergometry at 62% V(O2)peak before and after acute PV expansion. Subjects were infused with a PV-expanding solution (dextran (6%) or Pentaspan (10%)) equivalent to 6.7 mL x kg(-1) body mass (PVX) or acted as their own control (CON) in a randomized order. PVX resulted in a calculated 15.8% increase in resting PV, which relative to CON, was maintained throughout the exercise (P < 0.05). During PVX, heart rate was lower (P < 0.05) and stroke volume and cardiac output were higher (P < 0.05) during the exercise. Mean arterial pressure and total peripheral resistance, although altered by exercise (P < 0.05), were not different between the two conditions. Core temperature, which was progressively increased by the exercise (P < 0.01), was not affected by PVX. A similar decrease in body weight was observed between the conditions as a result of the exercise (P < 0.01). These results indicate that acute PVX alters cardiovascular performance without affecting the thermoregulatory response to prolonged cycle exercise.

Influence of differing macronutrient intakes on muscle glycogen resynthesis after resistance exercise.

The provision of additional protein (Pro) to a carbohydrate (CHO) supplement resulted in an enhanced rate of muscle glycogen resynthesis after endurance exercise (Zawadzki et al., J. Appl. Physiol. 72: 1854-1859, 1992). A comparison of isoenergetic CHO and CHO/Pro formula drinks on muscle glycogen resynthesis has not been examined after either endurance or resistance exercise. We studied the effect of isoenergetic CHO (1 g/kg) and CHO/Pro/fat (66% CHO, 23% Pro, 11% fat) defined formula drinks and placebo (Pl) given immediately (t = 0 h) and 1 h (t = +1 h) after resistance exercise in 10 healthy young men. They performed a whole body workout (9 exercises/3 sets at 80% 1 repetition maximum) with unilateral knee extension exercise [exercise (Ex) and control (Con) leg]. The CHO/Pro/fat and CHO trials resulted in significantly greater (P < 0. 05) plasma insulin and glucose concentration compared with Pl. Muscle glycogen was significantly lower (P < 0.05) for the Ex vs. Con leg immediately postexercise for all three conditions. The rate of glycogen resynthesis was significantly greater (P < 0.05) for both CHO/Pro/fat and CHO (23.0 +/- 4.5 and 19.3 +/- 6.1 mmol . kg dry muscle-1 . h-1, respectively) vs. Pl (Ex = 2.8 +/- 2.3 and Con = 1.4 +/- 3.6 mmol . kg dry muscle-1 . h-1). These results demonstrated that a bout of resistance exercise resulted in a significant decrease in muscle glycogen and that consumption of an isoenergetic CHO or CHO/Pro/fat formula drink resulted in similar rates of muscle glycogen resynthesis after resistance exercise. This suggests that total energy content and CHO content are important in the resynthesis of muscle glycogen.

A randomized, controlled trial of creatine monohydrate in patients with mitochondrial cytopathies.

Fatigue in patients with mitochondrial cytopathies is associated with decreased basal and postactivity muscle phosphocreatine (PCr). Creatine monohydrate supplementation has been shown to increase muscle PCr and high-intensity power output in healthy subjects. We studied the effects of creatine monohydrate administration (5 g PO b.i.d. x 14 days --> 2 g PO b.i.d. x 7 days) in 7 mitochondrial cytopathy patients using a randomized, crossover design. Measurements included: activities of daily living (visual analog scale); ischemic isometric handgrip strength (1 min); basal and postischemic exercise lactate; evoked and voluntary contraction strength of the dorsiflexors; nonischemic, isometric, dorsiflexion torque (NIDFT, 2 min); and aerobic cycle ergometry with pre- and post-lactate measurements. Creatine treatment resulted in significantly (P < 0.05) increased handgrip strength, NIDFT, and postexercise lactate, with no changes in the other measured variables. We concluded that creatine monohydrate increased the strength of high-intensity anaerobic and aerobic type activities in patients with mitochondrial cytopathies but had no apparent effects upon lower intensity aerobic activities.

Effect of glucose supplement timing on protein metabolism after resistance training.

We determined the effect of the timing of glucose supplementation on fractional muscle protein synthetic rate (FSR), urinary urea excretion, and whole body and myofibrillar protein degradation after resistance exercise. Eight healthy men performed unilateral knee extensor exercise (8 sets/approximately 10 repetitions/approximately 85% of 1 single maximal repetition). They received a carbohydrate (CHO) supplement (1 g/kg) or placebo (Pl) immediately (t = 0 h) and 1 h (t = +1 h) postexercise. FSR was determined for exercised (Ex) and control (Con) limbs by incremental L-[1-13C]leucine enrichment into the vastus lateralis over approximately 10 h postexercise. Insulin was greater (P < 0.01) at 0.5, 0.75, 1.25, 1.5, 1.75, and 2 h, and glucose was greater (P < 0.05) at 0.5 and 0.75 h for CHO compared with Pl condition. FSR was 36.1% greater in the CHO/Ex leg than in the CHO/Con leg (P = not significant) and 6.3% greater in the Pl/Ex leg than in the Pl/Con leg (P = not significant). 3-Methylhistidine excretion was lower in the CHO (110.43 +/- 3.62 mumol/g creatinine) than P1 condition (120.14 +/- 5.82, P < 0.05) as was urinary urea nitrogen (8.60 +/- 0.66 vs. 12.28 +/- 1.84 g/g creatinine, P < 0.05). This suggests that CHO supplementation (1 g/kg) immediately and 1 h after resistance exercise can decrease myofibrillar protein breakdown and urinary urea excretion, resulting in a more positive body protein balance.