Oxidative stress biomarkers responses to physical overtraining: Implications for diagnosis

Abstract

Overtraining syndrome is characterized by declining performance and transient inflammation following periods of severe training with major health implications for the athletes. Currently, there is no single diagnostic marker for overtraining. The present investigation examined the responses of oxidative stress biomarkers to a resistance training protocol of progressively increased and decreased volume/intensity. Twelve males (21.3 ± 2.3 years) participated in a 12-week resistance training consisting of five 3-week periods (T1, 2 tones/week; T2, 8 tones/week; T3, 14 tones/week; T4, 2 tones/week), followed by a 3-week period of complete rest. Blood/urine samples were collected at baseline and 96 h following the last training session of each period. Performance (strength, power, jumping ability) increased after T2 and declined thereafter, indicating an overtraining response. Overtraining (T3) induced sustained leukocytosis, an increase of urinary isoprostanes (7-fold), TBARS (56%), protein carbonyls (73%), catalase (96%), glutathione peroxidase, and oxidized glutathione (GSSG) (25%) and a decline of reduced glutathione (GSH) (31%), GSH/GSSG (56%), and total antioxidant capacity. Isoprostanes and GSH/GSSG were highly (r = 0.764–0.911) correlated with performance drop and training volume increase. In conclusion, overtraining induces a marked response of oxidative stress biomarkers which, in some cases, was proportional to training load, suggesting that they may serve as a tool for overtraining diagnosis.

Introduction

Regular physical training is associated with a mild tissue trauma followed by recovery [1]. When adequate recovery is allowed, there is an adaptation and athletic performance improves, a process often called “adaptive microtrauma” [1]. However, when exercise volume and/or intensity are increased, usually abruptly, and the athlete is not sufficiently recovered, a mild trauma could develop into a more chronic, severe form of tissue trauma. Athletes often develop a transient inflammation-like reaction following very intense acute exercise [2] or a prolonged period of severe training which is often called “overtraining syndrome” (OTS) and is characterized by declining performance despite an extended rest period, accompanied by physiological, biochemical, immunological, and psychological symptoms [3], [4]. Interestingly, < 0.1% of the general population [5] and 37% of a group of elite athletes from various sport disciplines have been reported to experience OTS at least once in their athletic career [6].

An overtrained athlete usually sustains a more diffuse, widespread, low-grade trauma that cannot be identified as an acute injury and resembles an overuse injury or a repetitive-motion injury resulting from high-volume training [3] and is accompanied by soreness, edema, performance deterioration, and protein release into plasma [7], [8]. Recent work from our laboratory [8] demonstrates that overtraining induces a significant rise in inflammatory and apoptotic markers. Muscle microtrauma induces reductions in strength [8] and range of motion [9] due to swelling in the injured area as well as a local inflammatory response with activated circulating monocytes and systemic inflammation and possibly immunosuppression [10].

Overtraining-induced muscle damage is associated with an inflammatory response characterized by increased susceptibility to infections attributable to changes in the functional status of immune cells [2]. Intense physical exercise has been reported to generate reactive oxygen species (ROS), resulting in oxidative stress [11]. Furthermore, ROS have been linked to mechanisms related to postexercise inflammatory response and possibly with propagation of muscle damage [12]. An inflammatory response during the repair of overtraining-induced muscle damage promotes neutrophil and macrophage infiltration of muscles, most likely initiated by ROS [13], [14]. Following exercise, neutrophil and macrophage counts are increased in muscle for several days [14], [15]. Neutrophils and macrophages generate superoxide, which may be converted to hydrogen peroxide, which then reacts with superoxide in the presence of a transition metal to form hydroxyl radical [12]. However, information regarding ROS generation in OTS is scarce. Overtraining effects on oxidative stress markers have been examined by only one animal study [16] and currently there are no available data from human studies. Ogonovszky et al. [16] reported that although aerobic exercise overtraining induced an oxidative damage to nuclear DNA in rats, there were no signs of lipid peroxidation. However, the authors questioned whether an overtraining response was induced in that study. Moreover, no single reliable diagnostic marker of OTS is currently available apart from a declined performance. Oxidative stress biomarkers could be significant and complementary with other biochemical indices since several links exist between oxidative stress and OTS. This is the first human study that investigated the possible role of oxidative stress in overtraining response. We tested the hypothesis that exercise of progressively increased and decreased training volume and intensity, which potentially could lead to overtraining, may induce oxidative damage to lipids and proteins as evidenced by changes in indirect blood markers of oxidative stress.