Antioxidant supplementation and endurance training: Win or loss?

Typically, free radicals are thought of as perpetrators of cell damage, ageing, even cancer, whereas antioxidants are seen as the defence against these threats. Accordingly, antioxidants are among the most common sports supplements used by amateur and professional athletes. However, the sensibility of this practice has recently been challenged in the scientific literature. This article briefly summarizes both positive and negative physiological effects of free radicals and antioxidants, culminating with emphasis on the signalling roles played by free radicals during training adaptations and the ability of superfluous antioxidants to weaken these desired signals, as revealed in several recent publications. The aim of this article is not to explicitly condemn antioxidant supplementation by athletes, but to underscore complexity of the situation and to champion efforts to achieve a deeper understanding of circumstances (e.g. dosage, timing, and setting) that might deem antioxidant supplementation as either largely beneficial or largely detrimental for endurance athletes in training.

Atrial remodeling, autonomic tone, and lifetime training hours in nonelite athletes

Endurance athletes have an increased risk of developing atrial fibrillation (AF) at 40 to 50 years of age. Signal-averaged P-wave analysis has been used for identifying patients at risk for AF. We evaluated the impact of lifetime training hours on signal-averaged P-wave duration and modifying factors. Nonelite men athletes scheduled to participate in the 2010 Grand Prix of Bern, a 10-mile race, were invited. Four hundred ninety-two marathon and nonmarathon runners applied for participation, 70 were randomly selected, and 60 entered the final analysis. Subjects were stratified according to their lifetime training hours (average endurance and strength training hours per week × 52 × training years) in low (<1,500 hours), medium (1,500 to 4,500 hours), and high (>4,500 hours) training groups. Mean age was 42 ± 7 years. From low to high training groups signal-averaged P-wave duration increased from 131 ± 6 to 142 ± 13 ms (p = 0.026), and left atrial volume increased from 24.8 ± 4.6 to 33.1 ± 6.2 ml/m(2) (p = 0.001). Parasympathetic tone expressed as root of the mean squared differences of successive normal-to-normal intervals increased from 34 ± 13 to 47 ± 16 ms (p = 0.002), and premature atrial contractions increased from 6.1 ± 7.4 to 10.8 ± 7.7 per 24 hours (p = 0.026). Left ventricular mass increased from 100.7 ± 9.0 to 117.1 ± 18.2 g/m(2) (p = 0.002). Left ventricular systolic and diastolic function and blood pressure at rest were normal in all athletes and showed no differences among training groups. Four athletes (6.7%) had a history of paroxysmal AF, as did 1 athlete in the medium training group and 3 athletes in the high training group (p = 0.252). In conclusion, in nonelite men athletes lifetime training hours are associated with prolongation of signal-averaged P-wave duration and an increase in left atrial volume. The altered left atrial substrate may facilitate occurrence of AF. Increased vagal tone and atrial ectopy may serve as modifying and triggering factors.

Gene expression in skeletal muscle of coronary artery disease patients after concentric and eccentric endurance training

Low-intensity concentric (CET) and eccentric (EET) endurance-type training induce specific structural adaptations in skeletal muscle. We evaluated to which extent steady-state adaptations in transcript levels are involved in the compensatory alterations of muscle mitochondria and myofibrils with CET versus EET at a matched metabolic exercise intensity of medicated, stable coronary patients (CAD). Biopsies were obtained from vastus lateralis muscle before and after 8 weeks of CET (n=6) or EET (n=6). Transcript levels for factors involved in mitochondrial biogenesis (PGC-1alpha, Tfam), mitochondrial function (COX-1, COX-4), control of contractile phenotype (MyHC I, IIa, IIx) as well as mechanical stress marker (IGF-I) were quantified using an reverse-transcriptase polymerase chain reaction approach. After 8 weeks of EET, a reduction of the COX-4 mRNA level by 41% and a tendency for a drop in Tfam transcript concentration (-33%, P=0.06) was noted. This down-regulation corresponded to a drop in total mitochondrial volume density. MyHC-IIa transcript levels were specifically decreased after EET, and MyHC-I mRNA showed a trend towards a reduction (P=0.08). Total fiber cross-sectional area was not altered. After CET and EET, the IGF-I mRNA level was significantly increased. The PGC-1alpha significantly correlated with Tfam, and both PGC-1alpha and Tfam significantly correlated with COX-1 and COX-4 mRNAs. Post-hoc analysis identified significant interactions between the concurrent medication and muscular transcript levels as well as fiber size. Our findings support the concept that specific transcriptional adaptations mediate the divergent mitochondrial response of muscle cells to endurance training under different load condition and indicate a mismatch of processes related to muscle hypertrophy in medicated CAD patients.

Eccentric endurance training in subjects with coronary artery disease: a novel exercise paradigm in cardiac rehabilitation?

This study evaluated the effects of 8 weeks of eccentric endurance training (EET) in male subjects (age range 42-66 years) with coronary artery disease (CAD). EET was compared to concentric endurance training (CET) carried out at the same metabolic exercise intensity, three times per week for half an hour. CET ( n=6) was done on a conventional cycle ergometer and EET ( n=6) on a custom-built motor-driven ergometer. During the first 5 weeks of the training program the metabolic load was progressively increased to 60% of peak oxygen uptake in both groups. At this metabolic load, mechanical work rate achieved was 97 (8) W [mean (SE)] for CET and 338 (34) W for EET, respectively. Leg muscle mass was determined by dual-energy X-ray absorptiometry, quadriceps strength with an isokinetic dynamometer and muscle fibre composition of the vastus lateralis muscle with morphometry. The leg muscle mass increased significantly in both groups by some 3%. Strength parameters of knee extensors improved in EET only. Significant changes of +11 (4.9)%, +15 (3.2)% and +9 (2.5)% were reached for peak isometric torque and peak concentric torques at 60 degrees s(-1) and 120 degrees s(-1), respectively. Fibre size increased significantly by 19% in CET only. In conclusion, the present investigation showed that EET is feasible in middle-aged CAD patients and has functional advantages over CET by increasing muscle strength. Muscle mass increased similarly in both groups whereas muscle structural composition was differently affected by the respective training protocols. Potential limitations of this study are the cautiously chosen conditioning protocol and the restricted number of subjects.

Effect of lifetime endurance training on left atrial mechanical function and on the risk of atrial fibrillation

Background Left atrium (LA) dilation and P-wave duration are linked to the amount of endurance training and are risk factors for atrial fibrillation (AF). The aim of this study was to evaluate the impact of LA anatomical and electrical remodeling on its conduit and pump function measured by two-dimensional speckle tracking echocardiography (STE). Method Amateur male runners > 30 years were recruited. Study participants (n = 95) were stratified in 3 groups according to lifetime training hours: low (< 1500 h, n = 33), intermediate (1500 to 4500 h, n = 32) and high training group (> 4500 h, n = 30). Results No differences were found, between the groups, in terms of age, blood pressure, and diastolic function. LA maximal volume (30 ± 5, 33 ± 5 vs. 37 ± 6 ml/m2, p < 0.001), and conduit volume index (9 ± 3, 11 ± 3 vs. 12 ± 3 ml/m2, p < 0.001) increased significantly from the low to the high training group, unlike the STE parameters: pump strain − 15.0 ± 2.8, − 14.7 ± 2.7 vs. − 14.9 ± 2.6%, p = 0.927; conduit strain 23.3 ± 3.9, 22.1 ± 5.3 vs. 23.7 ± 5.7%, p = 0.455. Independent predictors of LA strain conduit function were age, maximal early diastolic velocity of the mitral annulus, heart rate and peak early diastolic filling velocity. The signal-averaged P-wave (135 ± 11, 139 ± 10 vs. 148 ± 14 ms, p < 0.001) increased from the low to the high training group. Four episodes of non-sustained AF were recorded in one runner of the high training group. Conclusion The LA anatomical and electrical remodeling does not have a negative impact on atrial mechanical function. Hence, a possible link between these risk factors for AF and its actual, rare occurrence in this athlete population, could not be uncovered in the present study.

Training-related modulations of the autonomic nervous system in endurance athletes: is female gender cardioprotective?

The risk of sudden death is increased in athletes with a male predominance. Regular physical activity increases vagal tone, and may protect against exercise-induced ventricular arrhythmias. We investigated training-related modulations of the autonomic nervous system in female and male endurance athletes. Runners of a 10-mile race were invited. Of 873 applicants, 68 female and 70 male athletes were randomly selected and stratified according to their average weekly training hours in a low (≤4 h) and high (>4 h) volume training group. Analysis of heart rate variability was performed over 24 h. Spectral components (high frequency [HF] and low frequency [LF] power in normalized units) were analyzed for hourly 5 min segments and averaged for day- and nighttime. One hundred and fourteen athletes (50 % female, mean age 42 ± 7 years) were included. No significant gender difference was observed for training volume and 10-mile race time. Over the 24-h period, female athletes exhibited a higher HF and lower LF power for each hourly time-point. Female gender and endurance training hours were independent predictors of a higher HF and lower LF power. In female athletes, higher training hours were associated with a higher HF and lower LF power during nighttime. In male athletes, the same was true during daytime. In conclusion, female and male athletes showed a different circadian pattern of the training-related increase in markers of vagal tone. For a comparable amount of training volume, female athletes maintained their higher markers of vagal tone, possibly indicating a superior protection against exercise-induced ventricular arrhythmias.

Endurance training modulates the muscular transcriptome response to acute exercise

We hypothesized that in untrained individuals (n=6) a single bout of ergometer endurance exercise provokes a concerted response of muscle transcripts towards a slow-oxidative muscle phenotype over a 24-h period. We further hypothesized this response during recovery to be attenuated after six weeks of endurance training. We monitored the expression profile of 220 selected transcripts in muscle biopsies before as well as 1, 8, and 24 h after a 30-min near-maximal bout of exercise. The generalized gene response of untrained vastus lateralis muscle peaked after 8 h of recovery (P=0.001). It involved multiple transcripts of oxidative metabolism and glycolysis. Angiogenic and cell regulatory transcripts were transiently reduced after 1 h independent of the training state. In the trained state, the induction of most transcripts 8 h after exercise was less pronounced despite a moderately higher relative exercise intensity, partially because of increased steady-state mRNA concentration, and the level of metabolic and extracellular RNAs was reduced during recovery from exercise. Our data suggest that the general response of the transcriptome for regulatory and metabolic processes is different in the trained state. Thus, the response is specifically modified with repeated bouts of endurance exercise during which muscle adjustments are established.

Different response to eccentric and concentric training in older men and women

Sarcopenia is the age-related loss of muscle mass and strength and has been associated with an increased risk of falling and the development of metabolic diseases. Various training protocols, nutritional and hormonal interventions have been proposed to prevent sarcopenia. This study explores the potential of continuous eccentric exercise to retard age-related loss of muscle mass and function. Elderly men and women (80.6 +/- 3.5 years) were randomized to one of three training interventions demanding a training effort of two sessions weekly for 12 weeks: cognitive training (CT; n = 16), conventional resistance training (RET; n = 23) and eccentric ergometer training (EET; n = 23). Subjects were tested for functional parameters and body composition. Biopsies were collected from M. vastus lateralis before and after the intervention for the assessment of fiber size and composition. Maximal isometric leg extension strength (MEL: +8.4 +/- 1.7%) and eccentric muscle coordination (COORD: -43 +/- 4%) were significantly improved with EET but not with RET (MEL: +2.3 +/- 2.0%; COORD: -13 +/- 3%) and CT (MEL: -2.3 +/- 2.5%; COORD: -12 +/- 5%), respectively. We observed a loss of body fat (-5.0 +/- 1.1%) and thigh fat (-6.9 +/- 1.5%) in EET subjects only. Relative thigh lean mass increased with EET (+2.5 +/- 0.6%) and RET (+2.0 +/- 0.3%) and correlated negatively with type IIX/type II muscle fiber ratios. It was concluded that both RET and EET are beneficial for the elderly with regard to muscle functional and structural improvements but differ in their spectrum of effects. A training frequency of only two sessions per week seems to be the lower limit for a training stimulus to reveal measurable benefits.

Skeletal muscle mitochondria in the elderly: effects of physical fitness and exercise training.

Context: Sarcopenia is thought to be associated with mitochondrial (M) loss. It is unclear whether the decrease in M content is consequent to aging per se or to decreased physical activity. Objectives: To examine the influence of fitness on M content and function, and to assess whether exercise could improve M function in older adults. Design and subjects: Three distinct studies were conducted: 1) a cross-sectional observation comparing M content and fitness in a large heterogeneous cohort of older adults; 2) a case-control study comparing chronically endurance-trained older adults (A) and sedentary (S) subjects matched for age and gender; 3) a 4-month exercise intervention in S. Setting: University-based clinical research center Outcomes: M volume density (Mv) was assessed by electron microscopy from vastus lateralis biopsies, electron transport chain proteins (ETC) by western blotting, mRNAs for transcription factors involved in M biogenesis by qRT-PCR and in-vivo oxidative capacity (ATPmax) by (31)P-MR spectroscopy. Peak oxygen uptake (VO2peak) was measured by GXT. Results: VO2peak was strongly correlated with Mv in eighty 60-80 yo adults. Comparison of A vs. S revealed differences in Mv, ATPmax and some ETC complexes. Finally, exercise intervention confirmed that S are able to recover Mv, ATPmax and specific transcription factors. Conclusions: These data suggest that 1) aging per se is not the primary culprit leading to M dysfunction, 2) an aerobic exercise program, even at an older age, can ameliorate the loss in skeletal muscle M content and may prevent aging muscle comorbidities and 3) the improvement of M function is all about content.

The impact of antioxidant supplements and endurance exercise on genes of the carbohydrate and lipid metabolism in skeletal muscle of mice

To ascertain whether reactive oxygen species (ROS) contribute to training-induced adaptation of skeletal muscle, we administered ROS-scavenging antioxidants (AOX; 140 mg/l of ascorbic acid, 12 mg/l of coenzyme Q10 and 1% N-acetyl-cysteine) via drinking water to 16 C57BL/6 mice. Sixteen other mice received unadulterated tap water (CON). One cohort of both groups (CON(EXE) and AOX(EXE) ) was subjected to treadmill exercise for 4 weeks (16-26 m/min, incline of 5°-10°). The other two cohorts (CON(SED) and AOX(SED) ) remained sedentary. In skeletal muscles of the AOX(EXE) mice, GSSG and the expression levels of SOD-1 and PRDX-6 were significantly lower than those in the CON(EXE) mice after training, suggesting disturbance of ROS levels. The peak power related to the body weight and citrate synthase activity was not significantly influenced in mice receiving AOX. Supplementation with AOX significantly altered the mRNA levels of the exercise-sensitive genes HK-II, GLUT-4 and SREBF-1c and the regulator gene PGC-1alpha but not G6PDH, glycogenin, FABP-3, MCAD and CD36 in skeletal muscle. Although the administration of AOX during endurance exercise alters the expression of particular genes of the ROS metabolism, it does not influence peak power or generally shift the metabolism, but it modulates the expression of specific genes of the carbohydrate and lipid metabolism and PGC-1alpha within murine skeletal muscle.

REGULATION OF WHOLE-BODY ENERGY HOMEOSTASIS WITH GROWTH HORMONE REPLACEMENT THERAPY AND ENDURANCE EXERCISE

We hypothesized that network analysis is useful to expose coordination between whole body and myocellular levels of energy metabolism and can identify entities that underlie skeletal muscle's contribution to growth hormone-stimulated lipid handling and metabolic fitness. We assessed 112 metabolic parameters characterizing metabolic rate and substrate handling in tibialis anterior muscle and vascular compartment at rest, after a meal and exercise with growth hormone replacement therapy (GH-RT) of hypopituitary patients (n = 11). The topology of linear relationships (| r | ≥ 0.7, P ≤ 0.01) and mutual dependencies exposed the organization of metabolic relationships in three entities reflecting basal and exercise-induced metabolic rate, triglyceride handling, and substrate utilization in the pre- and postprandial state, respectively. GH-RT improved aerobic performance (+5%), lean-to-fat mass (+19%), and muscle area of tibialis anterior (+2%) but did not alter its mitochondrial and capillary content. Concomitantly, connectivity was established between myocellular parameters of mitochondrial lipid metabolism and meal-induced triglyceride handling in serum. This was mediated via the recruitment of transcripts of muscle lipid mobilization (LIPE, FABP3, and FABP4) and fatty acid-sensitive transcription factors (PPARA, PPARG) to the metabolic network. The interdependence of gene regulatory elements of muscle lipid metabolism reflected the norm in healthy subjects (n = 12) and distinguished the regulation of the mitochondrial respiration factor COX1 by GH and endurance exercise. Our observations validate the use of network analysis for systems medicine and highlight the notion that an improved stochiometry between muscle and whole body lipid metabolism, rather than alterations of single bottlenecks, contributes to GH-driven elevations in metabolic fitness.

Secondary prevention through cardiac rehabilitation: physical activity counselling and exercise training: key components of the position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation

Cardiac patients after an acute event and/or with chronic heart disease deserve special attention to restore their quality of life and to maintain or improve functional capacity. They require counselling to avoid recurrence through a combination of adherence to a medication plan and adoption of a healthy lifestyle. These secondary prevention targets are included in the overall goal of cardiac rehabilitation (CR). Cardiac rehabilitation can be viewed as the clinical application of preventive care by means of a professional multi-disciplinary integrated approach for comprehensive risk reduction and global long-term care of cardiac patients. The CR approach is delivered in tandem with a flexible follow-up strategy and easy access to a specialized team. To promote implementation of cardiac prevention and rehabilitation, the CR Section of the EACPR (European Association of Cardiovascular Prevention and Rehabilitation) has recently completed a Position Paper, entitled 'Secondary prevention through cardiac rehabilitation: A condition-oriented approach'. Components of multidisciplinary CR for seven clinical presentations have been addressed. Components include patient assessment, physical activity counselling, exercise training, diet/nutritional counselling, weight control management, lipid management, blood pressure monitoring, smoking cessation, and psychosocial management. Cardiac rehabilitation services are by definition multi-factorial and comprehensive, with physical activity counselling and exercise training as central components in all rehabilitation and preventive interventions. Many of the risk factor improvements occurring in CR can be mediated through exercise training programmes. This call-for-action paper presents the key components of a CR programme: physical activity counselling and exercise training. It summarizes current evidence-based best practice for the wide range of patient presentations of interest to the general cardiology community.

ZeroG: overground gait and balance training system

A new overground body-weight support system called ZeroG has been developed that allows patients with severe gait impairments to practice gait and balance activities in a safe, controlled manner. The unloading system is capable of providing up to 300 lb of static support and 150 lb of dynamic (or constant force) support using a custom-series elastic actuator. The unloading system is mounted to a driven trolley, which rides along an overhead rail. We evaluated the performance of ZeroG's unloading system, as well as the trolley tracking system, using benchtop and human-subject testing. Average root-mean-square and peak errors in unloading were 2.2 and 7.2 percent, respectively, over the range of forces tested while trolley tracking errors were less than 3 degrees, indicating the system was able to maintain its position above the subject. We believe training with ZeroG will allow patients to practice activities that are critical to achieving functional independence at home and in the community.