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.     

Human muscle glycogen metabolism during exercise. Effect of carbohydrate supplementation

Carbohydrate (CHO) ingestion during exercise, in the form of CHO-electrolyte beverages, leads to performance benefits during prolonged submaximal and variable intensity exercise. However, the mechanism underlying this ergogenic effect is less clear. Euglycaemia and oxidation of blood glucose at high rates late in exercise and a decreased rate of muscle glycogen utilisation (i.e. glycogen 'sparing') have been proposed as possible mechanisms underlying the ergogenic effect of CHO ingestion. The prevalence of one or the other mechanism depends on factors such as the type and intensity of exercise, amount, type and timing of CHO ingestion, and pre-exercise nutritional and training status of study participants. The type and intensity of exercise and the effect of these on blood glucose, plasma insulin and catecholamine levels, may play a major role in determining the rate of muscle glycogen utilisation when CHO is ingested during exercise. The ingestion of CHO (except fructose) at a rate of > 45 g/h, accompanied by a significant increase in plasma insulin levels, could lead to decreased muscle glycogen utilisation (particularly in type I fibres) during exercise. Endurance training and alterations in pre-exercise muscle glycogen levels do not seem to affect exogenous glucose oxidation during submaximal exercise. Thus, at least during low intensity or intermittent exercise, CHO ingestion could result in reduced muscle glycogen utilisation in well trained individuals with high resting muscle glycogen levels. Further research needs to concentrate on factors that regulate glucose uptake and energy metabolism in different types of muscle fibres during exercise with and without CHO ingestion.     

Factors which alter the relationship between ventilation and carbon dioxide production during exercise in normal subjects

The slope of the linear relationship between ventilation (V(E)) and carbon dioxide production (VC0(2)) has been thought to indicate that VC0(2) is one of the major stimuli to V(E). A group of 15 normal subjects undertook different incremental treadmill exercise protocols to explore the relationship between V(E) and VCO(2). An incremental protocol using 1 instead of 3-min stages of exercise resulted in an increase in the V E to VCO(2) ratio [26.84 (SEM 1.23) vs 31.08 (SEM 1.36) (P <0.008) for the first stage, 25.24 (SEM 0.86) vs 27.83 (SEM 0.91) (P <0.005) for the second stage and 23.90 (SEM 0.86) vs 26.34 (SEM 0.81) (P = 0.001) for the third stage]. Voluntary hyperventilation to double the control level of V(E) during exercise resulted in an increase in the V(E) to VCO(2) slope [from 21.3 (SEM 0.71) for the control run to 35.1 (SEM 1.2) for the hyperventilation run (P <0.001)]. Prolonged hyperventilation (5 min) during exercise at stage 2 of the Bruce protocol resulted in a continued elevation of VCO(2) and the V(E)/VCO(2) slope. A steady state of V(E) and metabolic gas exchange can only be said to have been present after at least 3 min of exercise. Voluntary hyperventilation increased the slope of the relationship between V(E) and VCO(2). End-tidal carbon dioxide fell, but remained within the normal range. These results would suggest that a non-carbon dioxide factor may have been responsible for the increase we found in V(E) during exercise, and that factors other than increased dead space ventilation can cause an increased ventilation to VCO(2) slope, such as that seen in some pathophysiological conditions, such as chronic heart failure.     

Free radicals, exercise, and antioxidant supplementation

Free radicals have been implicated in the development of diverse diseases such as cancer, diabetes, and cataracts, and recent epidemiological data suggest an inverse relationship between antioxidant intake and cardiovascular disease risk. Data also suggest that antioxidants may delay aging. Research has indicated that free radical production and subsequent lipid peroxidation are normal sequelae to the rise in oxygen consumption with exercise. Consequently, antioxidant supplementation may detoxify the peroxides produced during exercise and diminish muscle damage and soreness. Vitamin E, beta carotene, and vitamin C have shown promise as protective antioxidants. Other ingestible products with antioxidant properties include selenium and coenzyme Q10. The role (if any) that free radicals play in the development of exercise-induced tissue damage, or the protective role that antioxidants may play, remains to be elucidated. Current methods used to assess exercise-induced lipid peroxidation are not extremely specific or sensitive; research that utilizes more sophisticated methodologies should help to answer many questions regarding dietary antioxidants.     

Oxyhemoglobin desaturation and aberrant carbon dioxide homeostasis during electrically stimulated exercise in a ventilator-dependent tetraplegic patient

This single-subject case examined oxyhemoglobin saturation and alveolar end-tidal carbon dioxide levels in a ventilator-dependent tetraplegic patient undergoing electrical stimulation cycle ergometry. When exercising with a closed tracheostomy cuff under resting ventilator settings (resting intermittent mandatory ventilation; frequency = 6breaths/min, tidal volume = 83.3mL, minute ventilation =5L/min), his oxyhemoglobin saturation decreased from 100% to 92%, while alveolar endtidal carbon dioxide increased linearly to 47mmHg. These undesirable changes were corrected under adjusted intermittent mandatory ventilation conditions (frequency = 12breaths/min, tidal volume = 83.3mL, minute ventilation = 10L/min), during which oxyhemoglobin saturation remained above 98% and the alveolar end-tidal carbon dioxide trend resembled that of ventilator-independent tetraplegic individuals undergoing the same exercise. Because the subject's heart rate was higher under adjusted ventilation conditions, these responses may have been caused by augmented venous return resulting from greater abdominothoracic pumping at the higher breathing frequency. These findings support the need to modify ventilator settings in ventilator-dependent tetraplegic persons while undergoing exercise to maintain oxyhemoglobin saturation and carbon dioxide homeostasis.     

Creatine supplementation and exercise performance: an update

Creatine, a natural nutrient found in animal foods, is alleged to be an effective nutritional ergogenic aid to enhance sport or exercise performance. Research suggests that oral creatine monohydrate supplementation may increase total muscle creatine [TCr], including both free creatine [FCr] and phosphocreatine [PCr]. Some, but not all, studies suggest that creatine supplementation may enhance performance in high-intensity, short-term exercise tasks that are dependent primarily on PCr (i.e., < 30 seconds), particularly laboratory tests involving repeated exercise bouts with limited recovery time between repetitions; additional corroborative research is needed regarding its ergogenic potential in actual field exercise performance tasks dependent on PCr. Creatine supplementation has not consistently been shown to enhance performance in exercise tasks dependent on anaerobic glycolysis, but additional laboratory and field research is merited. Additionally, creatine supplementation has not been shown to enhance performance in exercise tasks dependent on aerobic glycolysis, but additional research is warranted, particularly on the effect of chronic supplementation as an aid to training for improvement in competitive performance. Short-term creatine supplementation appears to increase body mass in males, although the initial increase is most likely water. Chronic creatine supplementation, in conjunction with physical training involving resistance exercise, may increase lean body mass. However, confirmatory research data are needed. Creatine supplementation up to 8 weeks has not been associated with major health risks, but the safety of more prolonged creatine supplementation has not been established. Creatine is currently legal and its use by athletes is not construed as doping.     

Effect of creatine supplementation on sprint exercise performance and muscle metabolism

The aim of the present study was to examine the effect of creatine supplementation (CrS) on sprint exercise performance and skeletal muscle anaerobic metabolism during and after sprint exercise. Eight active, untrained men performed a 20-s maximal sprint on an air-braked cycle ergometer after 5 days of CrS [30 g creatine (Cr) + 30 g dextrose per day] or placebo (30 g dextrose per day). The trials were separated by 4 wk, and a double-blind crossover design was used. Muscle and blood samples were obtained at rest, immediately after exercise, and after 2 min of passive recovery. CrS increased the muscle total Cr content (9.5 +/- 2.0%, P < 0.05, mean +/- SE); however, 20-s sprint performance was not improved by CrS. Similarly, the magnitude of the degradation or accumulation of muscle (e.g., adenine nucleotides, phosphocreatine, inosine 5'-monophosphate, lactate, and glycogen) and plasma metabolites (e.g. , lactate, hypoxanthine, and ammonia/ammonium) were also unaffected by CrS during exercise or recovery. These data demonstrated that CrS increased muscle total Cr content, but the increase did not induce an improved sprint exercise performance or alterations in anaerobic muscle metabolism.     

Role of the liver in interorgan homeostasis of glutathione and cyst(e)ine

There are many pathological changes in patients with cystic fibrosis (CF) which can lead to alterations in drug disposition. Although, in patients with CF, the extent of drug absorption varies widely and the rate of absorption is slower, bioavailability is not altered. Plasma protein binding for the majority of drugs studied did not differ in patients with CF compared with control groups. The difference in volume of distribution of most drugs between patients with CF and healthy individuals vanished when corrected for lean body mass. Despite hepatic dysfunction, patients with CF have enhanced clearance of many, but not all, drugs. Phase I mixed-function oxidases are selectively affected: cytochrome P450 (CYP) 1A2 and CYP2C8 have enhanced activity, while other CYP isoforms such as CYP2C9 and CYP3A4 are unaffected. Increased phase II activities are also demonstrated: glucuronyl transferase, acetyl transferase (NAT1) and sulfotransferase. The increased hepatic clearance of drugs in the presence of CF may be the consequence of disease-specific changes in both enzyme activity and/or drug transport within the liver. The renal clearance (CLR) of many drugs in patients with CF is enhanced although there has been no pathological abnormality identified which could explain this finding: glomerular filtration rate and tubular secretion appear normal in patients with CF. The precise mechanisms for enhanced drug clearance in patients with CF remain to be elucidated. The optimisation of antibiotic therapy in patients with CF includes increasing the dose of beta-lactams by 20 to 30% and monitoring plasma concentrations of aminoglycosides. The appropriate dosage of quinolones has not been definitively established.     

Change in glutathione S-transferase and glyceraldehyde-3-phosphate dehydrogenase activities in the organs of mice treated with 2-chloroethyl ethyl sulfide or its oxidation products

We have analyzed the immediate and mid-term (1 and 2 years) results of percutaneous mitral valvuloplasty (PMV) by Inoue's catheter in 97 patients < 60 years (Group A) compared with 34 patients > 60 years (Group B). In 61% Group A the patients were in NYHA functional class II, 36% in III, and 3% in I; in Group B, 56% of the patients were in NYHA functional class III, 38% in II, and 6% in IV. Mean mitral valve area was 1.1 cm2 before dilatation in both groups, and a significant (p < 0.0001) increase was obtained in both Group A (0.9 +/- 0.3 cm2) and Group B (0.8 +/- 0.3 cm2). No significant differences were observed between the two groups. Mean transvalvular gradient decreased significantly (p < 0.0001) from 13.6 +/- 5.7 to 7.2 +/- 3.1 mmHg in Group A, and from 9.9 +/- 4 to 6.5 +/- 2.3 mmHg in Group B (A vs B: p < 0.02). Optimal result was obtained in 94% and 88% of Group A and Group B patients, respectively. Suboptimal result was obtained in 2% and 6% of Group A and Group B patients, respectively. These differences were not significant. Failure of PMV occurred in 4% and 6%, respectively. At 1-year follow-up Group A 7 patients and 5 Group B patients showed restenosis; at 2-year follow-up one more restenosis was present in Group A (A vs B at 1 and 2 years: NS). We conclude that PMV is a safe and effective technique in young patients and in patients > 60 years.     

Effect of estrogen supplementation on exercise thermoregulation in premenopausal women

This study examined the effects of 3 days of estrogen supplementation (ES) on thermoregulation during exercise in premenopausal (20-39 yr) adult women during the follicular phase of the menstrual cycle. Subjects (11 control, 10 experimental) performed upright cycle ergometer exercise at 60% of maximal O2 consumption in a neutral environment (25 degreesC, 30% relative humidity) for 20 min. Subjects were given placebo (P) or beta-estradiol (2 mg/tablet, 3 tablets/day for 3 days). All experiments were conducted between 6:30 and 9:00 AM after ingestion of the last tablet. Heart rate, forearm blood flow (FBF), mean skin temperature, esophageal temperature (Tes), and forearm sweat rate were measured. Blood analysis for estrogen and progesterone reflected the follicular phase of the menstrual cycle. Maximal O2 consumption (37.1 +/- 6.2 in P vs. 38.4 +/- 6.3 ml. kg-1. min-1 in ES) and body weight-to-surface area ratio (35.58 +/- 2.85 in P vs. 37.3 +/- 2.7 in ES) were similar between groups. Synthesis of 70-kDa heat shock protein was not induced by 3 days of ES. Neither the threshold for sweating (36.97 +/- 0.15 in P vs. 36.90 +/- 0.22 degreesC in ES), the threshold for an increase in FBF (37.09 +/- 0. 22 in P vs. 37.17 +/- 0.26 degreesC in ES), the slope of sweat rate-Tes relationship (0.42 +/- 0.16 in P vs. 0.41 +/- 0.17 in ES), nor the FBF-Tes relationship (10.04 +/- 4.4 in P vs. 9.61 +/- 3.46 in ES) was affected (P > 0.05) by 3 days of ES. We conclude that 3 days of ES by young adult women in the follicular phase of their menstrual cycle have no effect on heat transfer to the skin, heat dissipation by evaporative cooling, or leukocyte synthesis of 70-kDa heat shock protein.     

Serum levels of 5-hydroxyindole derivates after administration of L-5-hydroxytryptophan ethyl ester

Serum levels of 5-hydroxytryptophan ethyl ester, 5-hydroxytryptophan, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid (5-HTPE, 5-HTP, 5-HT and 5-HIAA, respectively), were measured after intravenous administration of L-5-HTPE in humans, premedicated with a peripheral decarboxylase inhibitor. Semi-automated methods for the estimation of the 5-hydroxyindole derivatives are described. Only serum levels of 5-HTP and 5-HIAA were found to be increased, indicating that the ethyl ester is rapidly hydrolyzed and that the decarboxylation of 5-HTP is in part inhibited. The levels of 5-HTP increased during the infusion, but dropped rapidly when the intravenous administration was terminated. Serum levels of 5-HIAA remained constant for at least 6 hours, although during the same period the levels of 5-HTP do change markedly. The persistently increased serum levels of 5-HIAA suggests, that this metabolite is formed from the 5-HT stored in peripheral or central tissue. Serum levels of 5-HIAA may therefore be indicative of changes of 5-HT metabolism during drug treatment. Levels of 5-HTP may be used for the estimation of the availability of the ethylester of 5-HTP.     

Zinc supplementation aggravates body fat accumulation in genetically obese mice and dietary-obese mice

Human colostrum, the first product of lactation, has antioxidant properties and inhibits selected enzyme and bactericidal activities of human neutrophils. We examined the subsequent product of lactation, mature human milk, with respect to its antioxidant activities, its effects on neutrophil enzyme activities (myeloperoxidase, beta-glucuronidase, and lysozyme), and its effects on neutrophil bactericidal and phagocytic activities. Mature human milk displayed antioxidant characteristics similar to those of human colostrum, reducing cytochrome c and consuming H2O2. Mature milk also displayed colostrum-like characteristics in depressing neutrophil myeloperoxidase and beta-glucuronidase activities, but not in altering lysozyme activity. Neutrophil bactericidal activity against Staphylococcus aureus was depressed by both mature milk and colostrum, without dramatic effects on phagocytic activity. These data show that mature milk shares characteristics with human colostrum that may result in anti-inflammatory effects, but the magnitude of these effects is generally smaller.     

Mechanisms of homeostasis establishment during prolonged microgravity

Investigations performed during prolonged microgravity were aimed at determination of phenomenology of the microgravity effects, and collection of data that would permit analysis of the micro-g specific homeostasis. As was stated, long-term microgravity alters the level of functioning of the main body systems, and a number of parameters of human metabolism and internal medium. It also instigates restructuring of some tissues and organs (primarily the musculoskeletal apparatus), brings along another level of energy and plastic (protein) metabolism, enhances the catabolic processes, and modifies the neuroendocrine regulation. In microgravity, the balance of functional loads on various body systems changes affecting rearrangement of the homeostasis regulation. The paper details the functional and morphological changes arising during long stay in microgravity and mechanisms culminating in a novel homeostasis in microgravity.     

Effects of ozone and airway inflammation on glutathione status and iron homeostasis in the lungs of horses

OBJECTIVE: To investigate the effects of ozone and airway inflammation on indices of oxidant injury in horses. ANIMALS: 5 clinically normal horses and 25 horses referred for poor performance. PROCEDURE: Blood, tracheal wash, and bronchoalveolar lavage fluid samples were collected before and after ozone exposure (n = 5) or from clinical cases (n = 25), and were analyzed for reduced glutathione (GSH), glutathione disulfide (GSSG), and free and total iron (Fe) values. A scoring system (0 to 5) was used to assess airway inflammation on the basis of clinical signs and cytologic analysis of the tracheal wash and bronchoalveolar lavage fluid samples. RESULTS: Ozone induced significant (P < 0.05) increases in GSH (195.4 +/- 68.5 microM), GSSG (19.4 +/- 6.4 microM), and free (25.5 +/- 16.1 microM) and total (93.1 +/- 13.4 microM) Fe values in the pulmonary epithelial lining fluid, compared with preozone samples (49.2 +/- 18.6, 2.4 +/- 1.2, 0.0, and 33.1 +/- 5.9 microM, respectively). The presence of airway inflammation (19/25) was associated with high GSSG and free and total Fe, but not GSH, values in epithelial lining fluid, compared with values for clinically normal horses (6/25). There were no differences in the systemic values of GSH, GSSG, and free and total Fe between any of the groups. A strong correlation (r = 0.84; P < 0.001) existed between inflammation score and the glutathione redox ratio (GSSG/[GSH + GSSG]) in the 25 horses admitted for clinical examination. CONCLUSIONS: Oxidant injury in the lung will induce changes in the glutathione status and Fe homeostasis that could affect pathogenesis of the disease. CLINICAL RELEVANCE: Measurement of indices of oxidant injury may be useful in the diagnosis of airway inflammation and the response to inhaled oxidants.     

Influence of carbohydrate supplementation early in exercise on endurance running capacity

The aim of this study is to examine the effect of carbohydrate (CHO) ingestion during the first hour of treadmill running on endurance capacity. Eleven male subjects ran at 70% VO2max to exhaustion on three occasions one week apart. On two occasions two CHO-electrolyte solutions (a 5.5% (E) and a 6.9% (L) were ingested for the first hour of exercise; water was ingested until exhaustion. On the third occasion water (W) was ingested throughout the run. The order testing was randomly assigned. Exhaustion times for the W, E, and L trials were 109.6 +/- 9.6 min, 124.5 +/- 8.4 min, and 121.4 +/- 9.4 min, respectively. There was no difference between the two CHO trials, but time to exhaustion was longer only for the E trial (P < 0.05), compared with the W trial. Nevertheless the average performance times for the combined results of the two CHO trials were longer than the water trial. Carbohydrate ingestion resulted in higher blood glucose concentration (P < 0.01) at 20 min in the E trail only and lower (P < 0.05) serum growth hormone and plasma FFA and glycerol concentrations at 60 min but not at exhaustion in both E and L trials compared with the W trial. Blood lactate, plasma ammonia, electrolytes, catecholamines, and serum insulin and cortisol concentrations were not different in the three trials. In conclusion, CHO ingestion during the first hour of exercise improves endurance capacity go a greater extent compared with water alone.     

Glutathione peroxidase activity and glutathione concentration in genetically dystrophic mice

The case of a 6-year-old boy is reported who was delivered out of a frontal position by application of the vacuum cup to the left part of the forehead. His left eye exhibits a pronounced somewhat irregular astigmatism. There are some vertical descemet tears. Because of the application of the vacuum pump close to the left bulbus, an increase of the tissue tension and consequently a deformation of the bulbus occurred by the vacuum in the bulbar region. The described lesions parallel the vertical descement tears which occur in forceps-delivery. Owing to the greater horizontal corneal diameter, a more pronounced extension of the cornea in the horizontal meridian occurs, which would explain the vertical course of the descemet tears. The obstetric contraindication for the application of the vacuum extraction in case of a frontal or facial position of the fetus is justified also from the ophthalmological point of view because of the risk of occurrence of irreversible corneal lesions.     

Erythrocyte glutathione balance and membrane stability during preeclampsia

OBJECTIVE: To assess the risk of borderline ovarian cancer among infertile women treated with fertility drugs. DESIGN: Case-control study. SETTING: Nationwide data obtained from public registers and postal questionnaires. PATIENT(S): All Danish women <60 years old with borderline ovarian cancer during the period 1989-1994 and randomly selected population controls. The analysis included 231 cases and 1,721 controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Influence of parity, infertility, and fertility drugs on the risk of borderline ovarian cancer after multivariate confounder control. RESULT(S): The odds ratio (OR) for borderline ovarian cancer among infertile untreated nulliparous women compared with fertile nulliparous women was 1.9. The OR for borderline ovarian cancer among treated nulliparous women compared with untreated infertile nulliparous women was 1.5, and the OR among treated parous women compared with untreated infertile parous women was 1.5. CONCLUSION(S): Among fertile women, the difference in the risk of borderline ovarian cancer between nulliparous women and parous women was not statistically significant. Nulliparous women who were infertile and who did not receive medical treatment had a twofold higher risk of borderline ovarian cancer than fertile nulliparous women. There was no statistically significant increase in the risk of borderline ovarian cancer among nulliparous women who were treated with fertility drugs compared with nulliparous untreated infertile women or among parous women who were treated with fertility drugs compared with parous untreated infertile women.     

Induction of glutathione S-transferase activity by curcumin in mice

Curcumin, a natural constituent of Curcuma longa (turmeric, CAS 458-37-7), has been studied for its induction of glutathione S-transferase activity in mice. At a dose of 250 mg/kg orally for 15 days, the enzyme activity in liver was increased by 1.8 fold. Its effect on other tissues like stomach, small intestine, lungs, kidney was not significant. Curcumin also depleted sulfhydryl levels in tissues, especially in stomach where 45% depletion was observed.     

Effects of dietary supplementation with n-3 fatty acid ethyl esters on coccidiosis in chickens

The ethyl esters of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids were added to a broiler starter diet singly or in combination [as bulk purified ethyl ester concentrate from menhaden oil (n3FAC)] in quantities similar to those found in a diet supplemented with 5% menhaden oil (MO). Diets were fed to chickens from 1 d of age through 3 wk of age. At 2 wk of age, the chickens were infected with Eimeria tenella, Eimeria acervulina, or Eimeria maxima. At 6 d postinfection (PI), the effects of the diets were assessed on weight gains, plasma carotenoids, gross lesion scores, and histological parasite scores in gut cross sections, or oocyst output. Significant ameliorating effects of diet on lesion scores and parasite scores were only seen in E. tenella infections and were only produced by the n3FAC and MO supplements. These two supplements, which contained higher molar concentrations of double bonds than the other supplements, also significantly reduced plasma carotenoids in uninfected chickens, indicating that they promoted a state of oxidative stress. These results are consistent with previous reports on the interaction of coccidiosis with dietary n-3 fatty acids and strengthen the hypotheses that dietary-induced oxidative stress is an effective deterrent against cecal coccidiosis in chickens.