Recovery from Exercise Taking into Consideration Circadian, Diurnal, and Ultradian Cycles and Subsequent Results on Tissue Induced Growth and Regeneration

By Mike Croskery

June 1994

Abstract

Diurnal, ultradian, and circadian rhythms tend to govern the secretion patterns of hormones. Since few hormonal responses are truly circadian (regulated by no external stimulus) in nature, several factors such as sleep-wake cycles, nutrition, meal timing, exercise, other hormones, and stress can alter diurnal (daily) rhythm patterns. It is precisely for this reason that competitive and recreational athletes and their coaches should be aware of these cycles and related hormonal interactions as well as the individual hormonal effects of exercise. The athlete should strive to establish a set daily pattern in order to ensure regulated and optimal levels of anabolic hormones and growth factors.

Sleep is very important to recovery and tissue growth as it is during the third and fourth stages of sleep that growth hormone (GH) peaks are highest. GH release positively affects testosterone secretion which both interact with necessary growth factors that have powerful effects on tissue growth and recovery. Alterations in the sleep-wake cycle can negatively affect testosterone levels and GH secretion.

Concerning meals, nutrient abundance is necessary for an anabolic state while nutrient deficiency will result in a catabolic state. The majority of meals should be eaten from morning to early evening throughout the day, at regular intervals in order to maximize the effect of lower blood glucose levels (resulting from circadian cycles of insulin) and its positive effect on allowing full expression of GH pulse amplitude during the day and sleep. The pre-exercise meal should be low in fat in order not to suppress GH release by inhibiting somatostatin release from the pancreas. A meal high in glucose should also be avoided as this can inhibit GH.

Exercise is the main external factor that causes tissue growth and subsequent adaption to the stimulus. Intense, resistance exercise emphasizing volume tends to be the greatest stimulus for tissue growth through increases in pulses and amplitude of GH, growth factors, and testosterone. Increasing frequency of brief and intense training sessions may bring about increased growth through increased number of pulses of GH and growth factors. GH appears to regulate mobilization of energy stores when it comes to endurance training more so than causing musculoskeletal hypertrophy. Testosterone does not seem to be a factor in improving endurance performance as testosterone typically decreases with long term endurance training. It also important to consider the ratio between catabolic and anabolic hormones in response to exercise when determining over all anabolic status.

Introduction

Hormones and neurohumors are the most powerful chemicals produced by the body that help govern exercise recovery and tissue growth. It is the relationships between hormones and their specific secretion patterns that cause certain effects on the target tissue or tissues.

Many hormones are governed by circadian, ultradian, and diurnal patterns. Entrainment of circadian and ultradian patterns of hormones can be modified by internal and external behaviours such as changes in the sleep-wake cycle, meal-timing, light-dark cycles, hypothalamic pacemaker effects, environmental temperature, and social cues (Vander et al. 1990, Van Couter 1990). This paper will focus primarily on the first three behaviours.

Exercise effects can stimulate acute changes in the number and amplitude of pulses and overall release levels of certain hormones such as growth hormone, testosterone and cortisol, during the previously established circadian rhythms (Fox et al. 1988, Kraemer et al. 1991, Borer 1994, Cooper 1994, Van Cauter 1990)

Recovery from exercise taking into consideration circadian, diurnal, and ultradian cycles and subsequent results on tissue-induced growth and regeneration is the primary topic of this paper. The main focus will be placed on the body's reaction to anabolic hormones (testosterone, growth hormone and insulin) from normal and exercise induced release, established biological rhythms of these hormones, as well as released neurohumors (growth factors) and their role in the process of exercise recovery and tissue growth.

Catabolic hormones and other hormones that regulate the three anabolic hormones and their established biological rhythms will also be mentioned in regard to their role in the anabolic process of tissue growth and recovery.

In order to keep this paper concise and simple, diseases that affect secretory patterns of the previously mentioned hormones and the endocrine system in general will not be considered. However, it is important to remember that such diseases can have an enormous impact on this topic and on the regulation of the endocrine system in general.

Testosterone

Testosterone is an anabolic hormone that is produced in the testes in the male, the ovaries in the female, and the adrenal cortex of both sexes. It is governed by the gonadotropic system (Vander et al. 1990). Males have a higher testosterone free-index rating (a rating related to the amount of testosterone in circulation not binded to beta-globulin thus facilitating its entry into the cells to exert its anabolic-androgenic effect (Clark et al. 1975)) than females which can account for their greater masculine physical traits and general increase in upper body muscle mass (Kraemer et al. 1991).

Testosterone directly increases protein synthesis with in the cell by modifying DNA and RNA transcription. Another potential way testosterone can stimulate muscle hypertrophy and overall growth is by influencing growth hormone and somatomedins or neurohumors, particularly insulin-like growth factor I (IGF-1) (Borer 1994). Both of these can have positive effects on protein synthesis. In addition, some research has suggested that testosterone can promote conversion of muscle fibers from slow oxidative to fast glycolytic fibers (Borer 1994).

Circadian rhythms and sleep patterns governing testosterone secretion are not fully understood (Van Cauter 1990). Typically in a normal, male individual testosterone acrophase peak levels tended to occur between the morning hours of 5 AM to 9 AM and showed evidence of a circadian rhythm (Van Cauter 1990, Juneja et al. 1991, Yagamuchi et al. 1991). However, an article by Touitou et al. in 1990 on the effects of shift work on night time secretory patterns of testosterone showed unpredictable acrophase and nadir times as well as an overall decrease in serum levels. This tends to support the theory that testosterone levels are not truly circadic in nature, but can be strongly influenced by external shifts in daily life patterns. Furthermore, luteinizing hormone (LH), responsible for testosterone secretion in males, does not follow a consistent diurnal pattern similar to testosterone, thus complicating the matter (Van Cauter 1990).

High intensity training and resistance training can increase blood testosterone levels above resting basal levels during the training period (Fox et al. 1988, Kraemer et al. 1991). Typically the greater volume protocol in resistance training used in the research performed by Kramer et al. showed slightly higher testosterone levels. Chronic use of this type of training may or may not cause elevated testosterone levels during normal circadian rhythm patterns when not exercising.

Higher testosterone levels may also contribute to increased strength performance in males (Alen and Hakkinen 1987). However, females tend to exhibit similar gains in strength performance as males which might indicate that other hormonal factors such as growth hormone also play key roles (Kraemer et al.)

Endurance exercise has shown to decrease exercising testosterone levels (Keizer et al. 1989) and free testosterone levels in athletes compared to sedentary controls (Komorowski 1994). It is important to note that significant decreases in free testosterone levels occurred only in endurance athletes who have practiced this type of training for years, thus suggesting a long term adaptation by the endocrine system (Komorowski 1994). Short term studies of only a few months have indicated the reverse - actual rises in resting free testosterone levels during training and exercise in untrained males (Keizer et al. 1989, Fox et al. 1988).

Growth Hormone

Growth hormone (GH) secretion is regulated by the hypothalamus and anterior pituitary. It functions to increase protein synthesis, lipolysis, gluconeogenesis, and inhibits glucose uptake (Vander et al. 1990). Although GH can have catabolic properties when release is by a high stress stimulus, GH's direct and indirect effects on anabolism will be discussed for the purpose of this paper.

Factors that govern tissue growth and recovery in regards to GH include: direct effects on cell protein synthesis and mRNA resulting in tissue growth by mediating growth factors such as IGF-1 and fibroblast growth factor (to be discussed later); indirect effects by synthesis and secretion of growth factors; interaction with secretory patterns of testosterone; and decreased levels of somatostatin (a GH-inhibiting hormone) (Vander et al. 1990, Tannenbaum et al. 1990, Borer 1994, Cooper 1994, Kraemer et al. 1991).

GH exhibits a diurnal and weak circadian rhythm consisting of several ultradian pulses primarily during sleep (Vander et al. 1990, Van Cauter 1990). These strong secretory pulses generally occur after the onset of sleep and are manifested during the third and fourth stages of sleep. However, GH pulses associated with sleep could occur during waking hours when sleep times were advanced by 5 hours (Van Cauter 1990). The GH pulse that had followed the established diurnal rhythm occurred when sleep was anticipated to occur, in this case during waking hours, due to the shift in sleep times. This gives additional support to the idea that GH does indeed follow at least a weak circadian rhythm. Incidently, this would also indicate that somatostatin would follow a complimentary rhythm as well (Tannenbaum et al. 1990).

Meal timing and choice may also contribute to the diurnal pulse amplitudes of GH. GH is stimulated during low blood glucose levels (this often corresponds to periods of negative energy balance or nutrient deficiency) in order to maintain relative homeostasis. This notion, along with information presented by Cooper in 1994 suggest that the amplitude of GH response from high intensity exercise was significantly inhibited by high fat and high glucose pre-exercise meals. When this idea is applied to daily life, the different types of meals chosen could affect the pulse amplitude of GH during normal diurnal and circadian rhythms.

Other than sleep, exercise is the next most potent natural external condition that elicits an increase in GH pulses and amplitude during the diurnal rhythm (Fox et al. 1988, Cooper 1994, Kraemer et al. 1991, Borer 1994). High intensity and high workload exercise creates a large increase in acute plasma levels of GH (Fox et al 1988). High resistance training focusing on higher volume loads and thus challenging the anaerobic energy system seems to also increase plasma levels of GH in comparison to pure strength training (Kraemer et al. 1991). Endurance exercise for long durations can also raise GH levels, and when exercise is performed routinely for years, can result in larger resting basal levels (Borer 1994). However, it is important to note that proportional increases in levels of intensity of exercise or duration do not result in a proportionally higher anabolic status. This is due to the fact that these higher intensities and longer durations result in an increased stress response from the endocrine system resulting in increased levels of cortisol, epinephrine and other strong catabolic hormones (Borer 1994). This would counteract the anabolic effect of GH.

By increasing GH pulses and amplitude, potential for increased tissue growth and recovery is increased. This is partly due to the fact that increased pulses in GH lead to corresponding increases in growth (Borer 1994). One explanation for this may be the corresponding frequent release of growth factors that are secreted in response to GH.

A final note about GH: there can be differences in basal GH levels between males and females. During the follicular phase of the menstrual cycle, GH levels are generally higher than during other periods of the menstrual cycle. This increase is significant and may be part of the reason, along with increased estrogen levels, why women tend to have higher growth hormone levels than men (Ho et al. 1990, Kraemer et al. 1991).

Insulin

During pre-pubertal and pubertal growth, insulin can exert an anabolic effect on tissue growth. However, once the epiphyseal plates close, insulin serves an indirect effect on protein synthesis by facilitating amino acids to enter the target cell and stimulating secretion of growth factors (Borer 1994). During adulthood, insulin has a much greater direct anabolic effect on glycogen stores and fat stores for fuel storage than protein synthesis (Borer 1994).

Insulin seems to exhibit a circadian effect through rhythms associated with blood sugar levels (Van Cauter 1990). Research shows that normal non-obese subjects exhibit a circadian pattern where the acrophase for blood glucose is highest during the evening and the nadir occurs during the afternoon (Van Cauter 1990). This cycle represents the body's varying tolerances to blood glucose during certain times of the day. A true circadian rhythm would continue irrespective of external stimulus. However, in this case sleep seems to be a critical factor (Van Cauter 1990). Additionally, this fluctuation in blood glucose failed to occur in fasting subjects (Van Cauter 1990).

Neurohumors (Growth Factors)

Neurohumors or growth factors (GF) are some of the most important chemicals responsible for tissue growth and consequently, tissue recovery. Although there are many growth factors in the human body, for the sake of simplicity and brevity, this section will deal with two groups: Insulin-like Growth Factor I and II (IGF-I, IGF-II) and Fibroblast Growth Factor (FGF).

IGF I and II are primarily stored in the liver and pancreas and are synthesized by GH (Vander et al. 1990, Borer 1994). These GF's are stimulated by increases in plasma levels of insulin (or nutrient abundance), testosterone, but mainly by GH. IGF I and II can act on all tissues to stimulate growth. However, they can also modulate carbohydrate and lipid metabolism (Borer 1994). For example, somatomedin (IGF I) levels can rise one to two hours after exercise, resulting in increased lipolysis (Borer 1994) or tissue regeneration (Kraemer et al. 1991). They can also demonstrate autocrine and paracrine function in terms of self-regulation.

FGFs are GF's that act solely on the muscle protein matrix. FGFs stimulate protein synthesis by triggering the DNA within the cell to stimulate the mRNA to increase structural protein resulting in muscle hypertrophy. IGF I and II work in a similar way. FGFs have a localized effect on the muscle and are primarily regulated on an autocrine and paracrine mediation resulting in tissue growth (Cooper 1994, Borer 1994). It appears that the main stimulus to enact FGF is mechanical force or, in other words, exercise (Borer 1994).

According to Borer (1994), there are circadian rhythms of IGF-I which are most likely due to the circadian variation of insulin. Since growth factors are usually reliant on other hormones such as testosterone and GH, it would be reasonable to assume the GF's would follow similar patterns.

High resistance exercise is the most effective exercise method for stimulating increases in levels of growth factors throughout the body. The resulting anabolic action of high resistance exercise manifested usually by specific muscle hypertrophy is a result of GF's being released into the blood normally at least two to nine hours after exercise (Borer 1994, Kraemer et al. 1991). IGF-I, FGF, nerve growth factor, epidermal growth factor, and several others all help to increase tissue growth by being made available to the target tissue (Borer 1994).

Part of the reason for this release of growth factors may be the accompanying increase in pulse amplitude of GH and testosterone during high resistance exercise (Kraemer et al. 1991, Borer 1994).  Endurance exercise also has a similar rise in GFs, although in this case the anabolic action elicited by these chemicals comes in the form of increased carbohydrate metabolism and increased lipolysis (Borer 1994).

Cortisol

Cortisol is a catabolic hormone primarily responsible for mobilization of energy stores in response to a stress stimulus. The greater the stressor, the greater the cortisol catabolic effect. In order to achieve an anabolic effect, cortisol must be minimized in relation to the anabolic hormone. Therefore a measure such as comparing cortisol levels to testosterone levels (free testosterone: cortisol ratio (FTCR)) may give an accurate level of the anabolic status concerning the interaction of those two hormones (Vervoon 1992). It is important to note that cortisol tends to have proportional acrophase diurnal secretation levels proportional to testosterone (Van Cauter 1990). Another example for determining anabolic status may be determining the GH or GF's to cortisol ratio after exercise. Anabolic status is more important after exercise than during exercise since it is after exercise that tissue recovery and growth take place.

In other words, it is important to consider the effects of cortisol when considering the anabolic "portrait" or "profile" of an individual. For example, a situation in which testosterone levels may be high and GH pulses are large and frequent may suggest an anabolic condition. However, in this case cortisol may also be consistently high which would negate the effect of the two anabolic hormones and might suggest that GH is high due to a large stress response.

Application of the Discussed Hormones, Growth Factors, and Biological Rhythms on Exercise Recovery and Tissue Growth

In general, a situation which encourages tissue growth and protein synthesis within the body is beneficial to exercise recovery. Therefore these two situations (recovery and tissue growth) will be used synonymously throughout this section.

Perhaps the most important factor in governing recovery and tissue growth is to establish a set daily pattern of meals, exercise, and sleep and follow this pattern as closely as possible. This will ensure regulated and optimal levels of anabolic hormones and growth factors as well as a decrease in stress, subsequently decreasing cortisol. Each factor pertinent to the diurnal and ultradian cycles will be discussed in more detail in the following paragraphs.

(1) Sleep - Since GH is an anabolic hormone, length and quality of sleep is essential for maximal tissue regeneration, and tissue growth. As previously, discussed GH levels peak during the stages of deep sleep (stages 3 and 4) and seem to follow an ultradian pattern throughout the night, generally decreasing in amplitude throughout sleep (Van Cauter 1990). Additionally, GH release positively affects testosterone secretion which both interact with necessary growth factors that also have a powerful effect on tissue growth and recovery. Alterations in the sleep-wake cycle can negatively affect testosterone levels. Therefore, an established daily pattern of sleep times is important.

(2) Daily meals - Nutrient abundance is necessary for an anabolic state while nutrient deficiency will result in a catabolic state concerning tissue growth. Meals should be eaten throughout the day at regular intervals. The pre-exercise meal should be low in fat in order not to suppress GH release by inhibiting somatostatin release from the pancreas. A meal high in glucose should also be avoided as this can inhibit GH.

The evening meal should be eaten well ahead of sleep times and be low in fat, in order that the amplitude of ultradian patterns of GH are not suppressed. It appears that a lower blood glucose level stimulates GH release as well therefore it is important to allow enough time to allow insulin to bring blood glucose down and stabilize it.

Regarding the circadian effect of insulin, the majority of meals should be eaten during the day and early evening in order to maximize the effect of lower blood glucose levels and its positive effect on allowing full expression of GH amplitude.

As mentioned above, high growth hormone levels stimulate necessary growth factors for recovery and tissue growth. This is why optimally high levels of GH during recovery are important for tissue growth.

(3) Exercise - Exercise is the main external factor that causes tissue growth and subsequent adaption to the stimulus. Resistance exercise emphasizing volume tends to be the greatest stimulus for tissue growth through increases in pulses and amplitude of GH, growth factors, and testosterone. Increasing frequency of brief and intense training sessions may bring about increased growth through increased number of pulses of GH.

Intensity must be given adequate attention as too much will increase cortisol levels and destroy the anabolic condition. Too little intensity will not bring about necessary rises in GH pulse frequency and amplitude, testosterone levels, and other necessary metabolic changes.

When endurance is the goal of the athlete, attention must be paid concerning the duration of exercise. Too long a duration will increase cortisol ratios and negatively affect recovery; too short a duration will not provide adequate stimulus to the energy systems to improve performance. GH appears to regulate mobilization of energy stores when it comes to endurance training more so than causing musculoskeletal hypertrophy. Testosterone does not seem to be a factor in improving endurance performance as testosterone typically decreases with long term endurance training.

Conclusion

As previously discussed, diurnal, ultradian, and circadian rhythms tend to govern the secretion patterns of hormones. Since few hormonal responses are truly circadian in nature, several factors such as sleep-wake cycles, nutrition, meal timing, exercise, other hormones, and stress can alter diurnal rhythm patterns. It is precisely for this reason that competitive and recreational athletes and their coaches should be aware of these cycles and related hormonal interactions as well as the individual hormonal effects of exercise.

 

References

Alen M., Hakkinen K. (1987) Androgenic Steroid Effects on Serum Hormones and on Maximal Force Development in Strength Athletes. Journal of Sports Medecine and Physical Fitness. 27 (1):38-46.

Borer K. (1994) Neurohumoral Mediation of Exercise-Induced Growth. Medecine and Science in Sports and Exercise. 26(6): 741-754.

Clark A., Marcellus S., deLory B., Bird C. (1975) Plasma Testosterone Free Index: A Better Indicator of Plasma Androgen Activity? Fertility and Sterility. 26(10):1001-1005.

Cooper D. (1994) Evidence for and Mechanisms of Exercise Modulation of Growth - An Overview. Medecine and Science in Sports and Exercise. 26(6): 733-740.

Ho K., Weissberger A. (1990) Secretory Patterns of Growth Hormone According to Sex and Age. Hormone Research. 33(suppl 4):7-11.

Juneja H., Karanth S., Dutt A., Parte P., Meherjee P., (1991) Diurnal Variations and Temporal Coupling of Bioactive and Immunoactive Luteinizing Hormone, Prolactin, Testosterone, and 17-Beta-Estradiol in Adult Men. Hormone Research. 35: 3-4.

Keizer H., Janssen G., Menheere P., Kranenburg G. (1989) Changes in Basal Plasma Testosterone, Cortisol, and Dehydroepiandrosterone Sulfate in Previously Untrained Males and Females Preparing for a marathon. International Journal of Sports Medecine. 10 (Suppl. 3): s139-s145.

Komorowski J. (1994) Notes from an exercise physiology course taken at University of Ottawa APA 3413. Human Kinetics Faculty.

Kraemer W., Gordon S., Fleck S., Marchitelli L., Mello R., Dziados J., Friedl K., Harman E., Maresh C., Fry A. (1991) Endogenous Anabolic Hormonal and Growth Factor Responses to Heavy Resistance Exercise in Males and Females. International Journal of Sports Medecine. 12: 228-235.

Touitou Y., Motohashi Y., Reinberg A., Touitou C., Bourdeleau P., Bogdan A., Auzeby A. (1990) Effect of Shift Work on the Night-time Secretory Patterns of Melatonin, Prolactin, Cortisol, and Testosterone. European Journal of Applied Physiology and Occupational Physiology. 60(4): 288-292

Van Cauter E. (1990) Diurnal and Ultradian Rhythms in Human Endocrine Function: A Minireview. Hormone Research. 34: 45-53.

Vervoon C., Vermulst L., Boelens-Quist A., Koppeschaar H., Erich W., Thijssen J., de-Vries W. (1992) Seasonal Changes in Performance and Free Testosterone: Cortisol Ratio of Elite Female Rowers. European Journal of Applied Physiology and Occupational Physiology. 64(1):14-21.

Yagamuchi M., Mizunuma H., Miyamoto K., Wasegawa Y., Ibuki Y., Igarishi M. (1991) Immunoreactive Inhibin Concentrations in Men: Presence of a Circadian Rhythm. Journal of Clinical Endocrinology and Metabolism. 72(3): 554-559.


For more information please send us mail at myomax@irtech.com or call us directly at 613-832-1360.