Cytokine hypothesis of overtraining: a physiological adaptation to excessive stress?


Medicine & Science in Sports & Exercise:

SMITH, L. L. Cytokine hypothesis of overtraining: a physiological adaptation to excessive stress? Med. Sci. Sports Exerc., Vol. 32, No. 2, pp. 317–331, 2000. Overtraining syndrome (OTS) is a condition wherein an athlete is training excessively, yet performance deteriorates. This is usually accompanied by mood/behavior changes and a variety of biochemical and physiological alterations. Presently, there is no global hypothesis to account for OTS. The present paper will attempt to provide a unifying paradigm that will integrate previous research under the rubric of the cytokine hypothesis of overtraining. It is argued that high volume/intensity training, with insufficient rest, will produce muscle and/or skeletal and/or joint trauma. Circulating monocytes are then activated by injury-related cytokines, and in turn produce large quantities of proinflammatory IL-1β, and/or IL-6, and/or TNF-α, producing systemic inflammation. Elevated circulating cytokines then co-ordinate the whole-body response by: a) communicating with the CNS and inducing a set of behaviors referred to as “sickness” behavior, which involves mood and behavior changes that support resolution of systemic inflammation; b) adjusting liver function, to support the up-regulation of gluconeogenesis, as well as de novo synthesis of acute phase proteins, and a concomitant hypercatabolic state; and c) impacting on immune function. Theoretically, OTS is viewed as the third stage of Selye’s general adaptation syndrome, with the focus being on recovery/survival, and not adaptation, and is deemed to be “protective,” occurring in response to excessive physical/physiological stress. Recommendations are made for potential markers of OTS, based on a systemic inflammatory condition.

The purpose of this paper is to integrate available information pertaining to the overtraining syndrome (OTS) into one paradigm, which will be referred to as the cytokine hypothesis of overtraining. The following hypothesis is not presented as complete but is advanced in an attempt to focus future research efforts. For brevity, references are generally limited to review articles. The predominant focus of this paper will be on the systemic immune/inflammatory response. These terms are frequently used interchangeably due to their extensive overlap; for conciseness, the term systemic inflammation will be used.

Athletes train hard to optimize performance. Inherent in all training programs is the application of the progressive overload principle, which implies working beyond a comfortable level in order to maximize athletic ability (26,27,45,91). Unfortunately, there is a fine line between improved performance and deterioration. When deterioration in performance occurs in association with an arduous training schedule, it is referred to as overtraining, staleness, or burnout (66).

The universal criterion associated with overtraining is a decrease in performance. However, not all aspects of performance are affected simultaneously nor are they impacted to the same degree, making prediction and/or interpretation confusing (66). It is also probable that other signs/symptoms typically associated with overtraining are evident before a deterioration in performance. These might include generalized fatigue, depression, muscle and joint pain, and loss of appetite. However, it is the decline in performance frequently associated with an increased volume or load of training, that captures the attention of the athlete and coach. A large number of symptoms associated with overtraining, have been reported in the literature. Fry et. al. (27) have categorized these according to physiological performance, psychological/information processing, immunological, and biochemical parameters (see Table 1). However, there is no universally agreed upon cluster of symptoms, and no cluster that would conveniently describe overtraining associated with a particular sport, or a particular type of training (such as aerobic versus anaerobic). For the most part, multiple symptoms may be present in a variety of combinations, and it is this cluster that is referred to as OTS.

In contrast to overtraining, overreaching is a term used to imply a temporary deterioration in performance, reflecting the time period between the application of a exacting stimulus, and subsequent recovery and adaptation (26,27,45,48,91). In many training cycles, athletes experience this short-term overreaching as they increase intensity and/or volume but recover rapidly and improve or maintain performance. However, if the athlete continues to show a decrement in performance, even with an appropriate rest/regeneration period, this is most likely OTS.

Since there is a continual risk of imbalance between training, competition, and recovery, OTS is a common problem (48). Sixty percent of distance runners, 21% Australian swimmers, and more than 50% of soccer players, have been classified as overtrained. Presently the only known treatment is a decrease in training volume or in some instances complete rest. “Once the athlete has developed the full-blown overtraining syndrome, he or she must rest completely for anything between 6 to 12 weeks…” (64). OTS is most likely also prevalent amongst recreational athletes, but has not received the same attention, for obvious reasons.

Author Information

Department of Health, Leisure, and Exercise Science, Appalachian State University, Boone, NC 28608

Submitted for publication January 1999.

Accepted for publication November 1999.

Address for correspondence: Lucille Lakier Smith, Ph.D., Department of Exercise and Sport Science, 371 Ward Sports Medicine Building, East Carolina University, Greenville, NC 27858.

©2000The American College of Sports Medicine