Periodical Exercise Therapeutics Update & Commentary: Exercise and Cortisol

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Resistance exercise overtraining and overreaching: neuroendocrine responses

Sports Med 823(2): 106, 1997.

Summary: Physiological effects of weight training are not nearly as well studied as those of aerobic exercise. This lengthy article reviews the neuroendocrine responses to weight training and overtraining. Only the section of the article dealing with cortisol will be summarized. For the purpose of this article the authors will be defining overtraining as an increase in number of repetitions or number of circuits or amount of weight lifted, leading to strength decrements. Often this decrease in performance is accompanied by generalized fatigue.

The direct stimulus for release of cortisol from the adrenal gland is ACTH (adrenocorticotropic hormone) from the anterior pituitary. ACTH is released due to CRH (corticotropin releasing hormone) from the hypothalamus. CRH is released regardless of the type of stress, i.e. physical, emotional. traumatic, etc. This cascade of hormonal responses to stress is known as the HPA axis (hypothalamic, pituitary, adrenal). Overtraining of any sort may lead to dysfunction of the HPA axis.

The release of cortisol in response to an exercise bout (moderate to high intensity for aerobic exercise and for all types of weight training bouts) is seen as beneficial. Cortisol is needed to help maintain blood glucose, while facilitating the metabolic shift towards greater fat oxidation.

Typically, the greater the amount of weight being lifted (i.e. greater stress), the higher the rise in cortisol during training. Moving to greater training volumes (more repetitions per exercise) or higher intensities (lifting greater weights) too quickly, may lead to higher resting cortisol levels. Yet when weight lifting is undertaken, cortisol levels may actually decline during the exercise bout.

Commentary: Cortisol is the classic "stress" hormone. Dr. Hans Selye, a pioneering stress physiologist, clearly established the essentiality of cortisol in allowing the body to withstand all types of stresses.(1) Selye found that if the adrenal glands were removed from animals they would quickly die, unable to deal with normal life stresses.

It would appear that some amount of cortisol is beneficial during a stress (e.g. weight training bout), while too much cortisol can become detrimental. When the volume of weight training is too great, it appears that even during rest, cortisol blood levels remain high. Cortisol can cause muscle tissue to break down thereby explaining why strength might actually start to decrease with higher levels of training (i.e. overtraining).

(1.) Selye H. The Stress of Life. New York: McGraw-Hill, 1956.

Effects of exercise on neuroendocrine secretions and glucose regulation at different times of day

Am J Physiol 274 (Endocrinol Metab 37):E1040, 1998.

Summary: A number of hormones exhibit diurnal variations, including cortisol. Typically, cortisol levels are highest in the early morning and lowest in the evening. These authors wanted to know if cortisol responses to exercise were dependent on the time of day in which exercise was undertaken. Twenty-two young men, in good physical condition, were recruited for the study. The men were divided into morning exercise group, late afternoon exercise group, and around midnight exercise group. Each exercise group underwent a 3-hr exercise session (at the designated time) which included moderate intensity, low intensity exercise and rest cycles on an arm/leg ergometer. Cortisol levels were measured at different time points throughout the three hour exercise session.

Only the group exercising during the late afternoon had a significant exercise-induced rise of cortisol. This is normally the time of day when cortisol levels would be decreasing.

Commentary: The most interesting aspect of this study is that the authors clearly demonstrated a different hormonal response to exercise which is influenced by the time of day in which exercise is undertaken. Most exercise studies tend to ignore diurnal variations and conduct their tests during the early morning hours. Interestingly, optimal sports performance tends to occur in the afternoon and early evening. This timing nicely corresponds to the greatest exercise-induced cortisol response as reported by these researchers.

Corticotrophic axis sensitivity after exercise in endurance-trained athletes

Clin Endocrinol 48:493, 1998.

Summary: Negative feedback from cortisol to the hypothalamus and pituitary is the normal way HPA axis regulation occurs. In animal studies repeated stress reduces the sensitivity of the HPA axis to negative feedback control. These authors used endurance-trained athletes as a model of repeated stress to test whether the HPA axis of humans also exhibits reduced feedback control.

Eight male marathon runners were asked to run for 2 hours after which a catheter was inserted into the arm vein. Blood could be collected for sampling and ACTH or CRH could be injected to assess the sensitivity of the runner's HPA axis. Saliva samples were also obtained to compare blood and salivary cortisol levels.

Cortisol levels remained elevated at least two hours after an intense and prolonged exercise bout. The results from the ACTH and CRH stimulation tests suggest that endurance athletes do have reduced pituitary feedback to hypercortisolism. This altered sensitivity may represent a beneficial adaptation in the HPA axis to endurance training.

Commentary: High levels of cortisol following an especially stressful exercise bout might facilitate recovery from that exercise bout. High cortisol can lead to feelings of euphoria and diminish pain sensations. It also has anti-inflammatory effects and may be helpful to blunt inflammatory responses following microtrauma to muscle and connective tissue.

These authors also clearly demonstrated that saliva cortisol changes correlate well with blood cortisol changes. This is an important confirmation of other studies which also found a good correlation. Furthermore, these authors actually found that salivary cortisol was a more accurate measure of cortisol during stimulation tests, when very high levels of cortisol occur. Salivary cortisol is an especially useful tool in the assessment of HPA axis function since saliva sampling is non-invasive and numerous samples can be easily obtained in an effort to account for the normal diurnal variation of saliva. The cortisol found in saliva actually represents the biologically active, unbound fraction of cortisol. This in fact may make salivary cortisol a more clinically relevant measure of HPA axis activity.

Metabolic effects of low cortisol during exercise in humans

J Appl Physiol 84(3): 939, 1998.

Summary: The metabolic effects of cortisol under resting conditions have been well established, as already mentioned in the first article's summary. The importance of cortisol during exercise has not been fully elucidated, although speculations abound. These authors wanted to determine some of the metabolic effects of exercise-induced cortisol in humans by blocking cortisol synthesis during an exercise bout.

Nine healthy college students were recruited for the study. All students underwent two bicycle ergometry tests. One was conducted the morning following an evening dose of placebo and the other was conducted following a dose of a cortisol blocking drug (metyrapone). Blood samples were taken throughout each exercise bout and analyzed for substrates; glucose, lactate, glycerol, amino acids and hormones; cortisol, glucagon, epinephrine, norepinephrine.

Before exercise, cortisol levels were 70% lower on the day after the use of metyrapone. Cortisol levels remained low during the two hours of exercise. Blood glucose and lactate levels were the same under both cortisol conditions. Blood glycerol increased more slowly during exercise under low cortisol conditions. Plasma amino acids were lower under low cortisol conditions, however their response to exercise was similar for both cortisol conditions. Plasma insulin levels will decline during an exercise bout, during an exercise bout under low cortisol levels, plasma insulin declines were even greater. Plasma glucagon was no different between the two conditions, however greater levels of epinephrine and norepinephrine were found in the low cortisol condition.

Higher blood glycerol levels are usually considered indicative of greater rates of lipolysis (i.e. fat mobilization from adipose tissue). Despite differences in blood glycerol during the normal and low cortisol conditions, there was no difference in substrate utilization (as assessed by respiratory quotient). In essence, regardless of whether blood cortisol increased or not during exercise, the amount of carbohydrates compared to the amount of fat that was being oxidized did not differ. The differences in plasma insulin, epinephrine and norepinephrine under low cortisol conditions suggests that redundant hormonal mechanisms kick in to maintain blood glucose, despite the lack of cortisol.

Commentary: The overall metabolic effects of cortisol during an exercise bout appear to be rather minor. Cortisol may even be considered a permissive hormone. That means that its direct effects are not as important as having a low level of the hormone around to ensure that other hormones have their effects. Regarding the switch in substrate utilization which occurs with exercise, from dependence of the muscles on glucose (carbohydrate) oxidation to more fat oxidation, cortisol appears to enhance the effects of epinephrine and norepinephrine. This metabolic switch is considered important for endurance activities and utilizing exercise as a therapeutic tool in weight management.

Although this was a small, but elegant study to try to clarify the physiological effects of cortisol on energy metabolism during exercise, perhaps other effects of cortisol are more important. As mentioned earlier the central nervous system effects (euphoria) and immune regulating effects may make cortisol elevations during exercise most helpful in appropriate recovery from the stress of exercise.

Impaired pituitary hormonal response to exhaustive exercise in overtrained endurance athletes

Med Sci Sports Exerc 30(3): 407, 1998.

Summary: Our understanding of overtraining is still immature. Hormonal responses to acute exercise bouts in endurance overtrained athletes over a period of time as not been previously studied. Seventeen male endurance-trained athletes (cyclists and triathletes) were recruited. At different times during a 19 month period the athletes were asked to increase their training frequency for several weeks. Once they felt they were overtrained they were asked to come to the laboratory for testing. A 30 minute bicycle ergometry test was performed in which periodic blood samples were taken. The blood samples were analyzed for cortisol and other hormones.

At rest the level of ACTH and cortisol was lower during overtraining compared with normal training, however this difference was not statistically significant. At the end of the exercise bout ACTH and cortisol were lower during overtraining compared to normal training. Exercise induced responses of epinephrine and norepinephrine were not different between the normal and over training condition.

Commentary: The results of this study suggest that overtrained endurance athletes have a blunted ACTH and cortisol response to an acute stress. Whether this can help account for the symptoms of fatigue, heavy feeling in legs during exercise or a decreased exercise endurance are unclear, but would seem likely. Clearly, overtraining negatively impacts the HPA axis. In particular it would seem that excessive, repeated stress has led to a relative weakened HPA axis response to stress. It would appear that even though physical stress has led to the weakened response, that the overtrained individual will be less able to deal with other stressors, physical or emotional. This may explain an increased susceptibility to upper respiratory tracts infections, since physiological levels of cortisol are known to help prevent infectious illness.

Perhaps the study of overtraining, used as a model for studying the physiological effects of excessive stress, can finally convince the orthodox medical community that there is such a syndrome as adrenal "burnout." That the symptoms of adrenal burnout are those now associated with overtraining. Fatigue, depression, insomnia, mood swings, weakness, etc. can be understood in physiological terms, not just psychological. The first treatment for HPA axis dysfunction is to delineate the stressors and remove them. Attending a seminar on coping skills is another way to improve one's ability to deal with life stresses. Perhaps if stresses can be dealt with "psychologically" then the physiological (HPA axis) response will not have to be as intense.

Column summary: Cortisol is the classic stress hormone. We would die without the ability to release cortisol in times of stress. Understanding the normal physiological effects and how the HPA axis is regulated is paramount to understanding how to better deal with life in the 20th century. Exercise represents a wonderful model by which to study the normal responses of the HPA axis to stress as well as the adaptations of the axis to repeated physiological stress.

It may be that moderate levels of regular exercise leads to a beneficial adaptive response of the HPA axis, so that other life stresses don't induce such a large HPA response. While excessive levels of exercise, i.e. overtraining, can lead to dysfunction of the axis leaving the athlete vulnerable to the effects of long term low cortisol.

Townsend Letter for Doctors & Patients.

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By Anna MacIntosh

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