The neuroendocrine response is quite an interesting phenomena because it has been vastly overlooked by the weightlifting and sports industries. Its existence is verified by high intensity protocols, which show greater fat loss than traditional cardiovascular steady state work. For example, an experiment performed by Tremblay et al. on high intensity intermittent training (HIIT) against endurance training (ET) resulted in the HIIT group losing 3 times the amount of subcutaneous fat (13.9 mm vs 4.5 mm) with half of the caloric expenditure during the workout (120.4 ± 31.0 vs. 57.9 ± 14.4) [1]. This represents a 9 fold increase in fat loss per caloric expenditure in favor of HIIT over ET.

Through thorough investigation of the evidence beyond HIIT vs. ET there should be a neuroendocrine response universal to all forms of exercise which is primarily determined by the application of such exercise. Specifically, an increase in intensity of the exercise should generate a stronger acute hormonal response which is essential for changes in body composition and increased performance.

The failure of EPOC

Excess post-exercise oxygen consumption (EPOC) has generally been the explaining for the phenomena superior fat loss for HIIT versus ET. This theory is incorrect. A closer look at various studies detailing EPOC indicates that it may be negligible in total calories expended versus steady state work which confirms that it cannot be the cause of the large increases in fat loss experienced through HIIT. For instance, in a review in 2004 by Meirelles et al [2], they come to the conclusion that “based on current knowledge and considering all variables related to resistance training, it is still not possible to determine the best exercise protocol in order to substantially increase energy expenditure in comparison of various studies on HIIT and ET.” The results of the multiple studies in the review cannot find a conclusive advantage of HIIT versus ET solely in energy expenditure.

Similarly, in 2006 Laforgia et al. comes to the same conclusion as their data indicates that “EPOC comprises only 6 - 15% of the net total oxygen cost of the exercise [3].” This data agrees with an earlier study in 1997 by Laforgia et al., contrasting 60 minutes of HIIT comprised of 1 minute at 105% VO2max running with 2 minutes active recovery, and 30 minutes of ET was composed of 70% VO2max running where they determined that there was <100 kcal burned in EPOC [4]. These values were 7.1% and 13.8% of net oxygen cost for ET and HIIT respectively. A study by Romijn et al. in 1995 basically confirms this data – they conclude that a 65% VO2max pace sustained for 60 minutes will generate a similar EPOC to that of HIIT [5]. Additionally, since a submaximal VO2max pace starts to consume lipids very quickly through B-oxidation, as opposed to high intensity which depletes glycogen, there is apparently more than just simple energy consumption that needs to be addressed. Thus, there is no significant difference in HIIT and ET by EPOC.

Resistance exercise tends to have the same effect on fatty acid metabolism as HIIT, according to a 2007 study by Ormsbee et al [6]. Since humans are physiologically the same and the constant is exercise, there is a disconnect between proposed EPOC and resistance exercise. Likewise, HIIT metabolism in resistance exercise was elevated after exercise for a short duration although it was only increased approximately 100 kcal/hr which indicates that it is not a significant factor in fat metabolism. Results that mirror HIIT were also found in an experiment by Chatzinikolaou et al [7]. In obese and lean individuals, there was an increased utilization of fatty acids immediately after exercise (within 5-10 mins) with a delayed response in the obese as well as increased energy expenditure. These results indicate that HIIT exercise is very similar to resistance training in the nature of lipolysis.

In conclusion, another plausible explanation must exist for the increased abilities of HIIT versus ET in the metabolism of significant lipid mass considering the difference in calories burned is insignificant between the two methods. The fact that HIIT and resistance exercise tend to produce the same physiological markers in lipolysis and elevated energy expenditure after exercise indicates that there needs to be a different reason for increased fat metabolism than EPOC. EPOC fails to produce the necessary energy expenditure and exclusivity.

The observations

There are a few important things that are known about training, and the observations that can be made from them are very important. From these observations a hypothesis can be made. But first, the data must be collected and analyzed for a pattern.

HIIT is superior to ET in terms of fat loss or fat metabolism for more or less the same amount of time or caloric expenditure put into each [1]. The same may be true of tabata protocol as it is a type of interval. Similarly, high intensity resistance exercise such as heavy lifting is decent for fat metabolism (not to mention hypertrophy) [11]. Likewise, other high intensity exercise such as metabolic conditioning and/or circuit training are all fairly effective for burning fat [6,12]. Extremely long endurance ET burns a significant amount of fat, but such activities support very little hypertrophy (e.g. marathon runners) [3,4].

When analyzing this data for a pattern, the common theme besides extremely long endurance training seems to be mediated by intensity of repetitions (limit strength or power) or for the whole workout (such as maximizing total workload or workload per time). The most important effect of high intensity workouts seem to be a general overall depletion of muscular energy stores. There also seems to be some correlation of high cardiovascular output which is consistent with a strong stress response although such a cardiovascular response is slightly blunted in resistance training compared to HIIT [52]. Thus, varying intensity in exercise should elicit a hormonal response consistent with these physiological effects.

The physiology

In response to exercise, the sympathetic nervous system is activated [8][9]. Sympathetic nervous system activation can be caused by merely thinking about exercise [8]. In response to sympathetic nervous system activation, the hypothalamus-pituitary-adrenal axis (HPA axis) is stimulated so that the hypothalamus releases corticotropin releasing hormone (CRH). CRH travels to the anterior pituitary where it causes the secretion of adrenocorticotropic hormone (ACTH). ACTH travels to the adrenal glands and provokes catecholamine production such as epinephrine and norepinephrine as well as glucocorticoid production such as cortisol. In conjunction with this response, the preganglionic sympathetic nerves also stimulate the adrenal glands aiding in epinephrine and norepinephrine release [9]. The effects of such hormone production on the body are well know as the 'fight or flight' response due to increases in heart rate, dilation of pupils, depression of the digestive tract, stimulation and increase nutrient uptake by the muscles, and other such effects [10].

Sympathetic nervous system output of catecholamines and glucocorticoids seem to be the most important because they are secreted in greater magnitude as the stress increases. The glucocorticoid cortisol and the catecholamines epinephrine and norepinephrine in particular are strongly secreted in response to elevated stress levels. Cortisol helps induce the breakdown of glycogen and fatty acids to be released into the bloodstream, and it improves the performance of catecholamines [53]. The modulation of the HPA axis by a high intensity stress such as HIIT at maximal levels compared to a lower intensity stress of ET at a steady VO2max shows a higher catecholamine output for HIIT versus ET [9]. Epinephrine inhibits the anabolic hormone insulin [13,14]—insulin is responsible for the storage of carbohydrates into adipose and muscle tissue [15] and also for inhibition of lipolysis [15]. Concurrently, epinephrine also strongly enhances glycolysis [16] and release of glucose into the blood stream [16] as well as lipolysis by mobilizing enzymes that catabolize lipids to be released into the blood as free fatty acids (FFAs) [16,18]. The elevated ACTH levels also stimulate the increased activity of hormone sensitive lipase, which is one of the main enzymes responsible for increases in FFA concentration in the blood [19]. Norepinephrine secretion coincides with increased blood flow and heart rate as well as greater levels of glucose oxidation suggesting that it may play a significant role in this process during exercise [21]. Increased production of FFAs are important because like glucose they are used by skeletal and cardiac muscle [54] as sources of fuel.

Since high intensity exercise consumes the glycogen content of muscles almost completely while lower intensity exercise does not [17,20], there are multiple pathways functioning to resupply the muscles with energy. Rapid glycogen depletion occurs during high intensity exercise such as resistance training or intervals [20,22]. Glucose uptake by muscles after high intensity exercise is high and although lipolysis in adipose tissue is depressed in a recovery period after high intensity exercise, FFA content in the blood is increased suggesting an increased uptake of FFAs into the muscle [17]. This suggests that both glucose and FFAs are used extensively to provide energy for muscles depleted of their glycogen energy reserves. Similarly, following maximal intensity exercise (sprints), Trapp et al. [24] found significant catecholamine output that corresponded with high blood glycerol levels which indicates a high degree of FFA output into the bloodstream. One specific pathway mediated by high intensity exercise shows that muscle fatty acid content is only metabolized with increasing intensity (high muscle triglyceride content is partially responsible for insulin receptor downregulation, which can lead to diabetes) [20]. On the other hand, lower intensity exercise (under the lactate/anaerobic threshold) tends to leave glycogen and muscle triglyceride stores within muscles and tends to directly utilize FFA content for continued energy output [23]. The maximal fat oxidation during exercise occurs somewhere between 59-64% of VO2max [25].

During any exercise, the cytokine interleukin-6 (IL-6) is strongly secreted by muscle tissue [26,27,28,29,31,32,33]. There is evidence that high secretion of catecholamine output is responsible for at least part of IL-6 output [26,27], but the rest occurs because muscular contractions activate the genes for IL-6 production [31,33]. In endurance training the concentrations of IL-6 increase exponentially with duration, peaking quickly after exercise is completed [31]. The highest levels were found after extended running efforts such as marathon running. On the other hand, moderate increases in IL-6 concentration have also been found due to increases in the intensity of exercise [31,33] although not as strongly as long duration ET. Interestingly, it has been shown that even though IL-6 has a half life of 1-2 hours, its production is markedly elevated above basal rate hours and days after exercise as been completed [30,31,33]. Nonetheless, IL-6 expression is conserved which means that its levels are not regulated by either training status or starting intramuscular glycogen levels, which supports that muscle is still sensitive to IL-6 [34]. This will mean an unhindered IL-6 response, which suggests it is strongly involved in regulating an acute response to exercise at all levels of training experience.

In the body, IL-6 is responsible for a number of effects, especially mobilization of energy stores such as glucose from the liver, fatty acids from adipose tissue, and the increase in the body temperature during exercise [28,31,33]. IL-6 is also responsible for increasing glucose uptake from the digestive system as well as absorption of energy substrates into muscle tissue [31]. If glycogen levels are low during exercise then there is a strong activation of IL-6 gene to help increase the glucose and fatty acid uptake into muscles [33]. IL-6 secretion is also involved with myoblast and satellite cell proliferation, suggesting that it is involved with hypertrophy, although overproduction of IL-6 is related to muscle atrophy due to increases in a class of lysosomal proteases [31]. These effects are due to both direct and indirect responses such as a balance between stimulation of anabolic processes like the myoblast proliferation and hormones such as vascular endothelial growth factor (capillary vascularization) juxtaposed against catabolic processes like the aforementioned lysosomal proteases. No threshold of the limitation to maximize the benefits of IL-6 production has been proposed yet although it will be discussed later. Thus, IL-6 is very important in modulation of the response to exercise induced training because of its hormone-like effects.

Growth hormone (GH) levels are also increased during exercise and occur in a pulse-like manner corresponding to the body's circadian rhythm (24 hour cycle). During exercise, an increase in GH secretion corresponds to increases in body temperature [35]. Increase in GH levels in response to exercise is fast and consistent between genders but decreases with age [37]. In resistance training, serum human growth hormone tends to increase with intensity of exercise with the highest amounts being secreted with high workloads and low rest times [36]. Indeed, most types of acute stress raise GH levels, but if prolonged they lead to an increase in cortisol which inhibits not only GH but also luteinizing hormone and testosterone [38,40]. Anaerobic exercise also tends to lead to the production of more GH compared to aerobic training and is related to the intensity of the exercise [38]. Specifically, GH tends to increase linearly with exercise intensity as there is more GH secreted per pulse [44].

Growth hormone is responsible for multiple effects in the body. In particular, GH is a multipurpose hormone that affects catabolic processes such as lipolysis and anabolic processes such as protein synthesis and insulin-like growth factor-1 (IGF-1) production, which helps modulate muscle hypertrophy [39]. During exercise the body is in a catabolic state due to sympathetic nervous system activation; thus, the main role of GH is to encourage lipolytic activity to provide enough energy for the body due to increased FFA turnover [35]. GH secretion is responsible for some of the lipolysis during exercise and in post exercise recovery as it peaks 2.5 hours after exercise and corresponds with an increase in blood FFA concentrations to help restore the body to homeostasis [41]. In addition, there is one interesting effect in untrained men and women in which their GH and testosterone levels were elevated and cortisol levels decreased at rest from pre-exercise levels after the implementation of an 8-week resistance exercise program [42]. This indicates that training has an important hormonal regulatory effect on the body.

Post exercise the release of growth hormone occurs in the pulse-like manner with the largest secretion occurring during the period of sleep right before rapid eye movement called slow wave sleep (SWS) [39]. The body enters through many periods of SWS during a normal night. Exercise may be one of the most potent stimulants of slow wave sleep [45,46,47]. It has been shown that total sleep time and increases in lengths of slow wave sleep occur in response to exercise on the same day [46,47]; there is an increase in amplitude but not frequency of the pulses of growth hormone emitted [45,47]. On similar note, decrease in SWS and thus decrease in GH secretion with rise in cortisol levels during said sleep has been implicated to be one of the major causes of senescence (aging) [45,49]. Unlike exercise, senescence is marked with the decrease in amplitude of GH pulses but not frequency of pulses [49]. This very important, as 60-70% of GH production occurs during sleep [47].

Analysis

Exercise is very important as previously shown because of the huge amount of neuroendocrine variation that arises from different modalities. When looking through the physiology, it becomes a bit clearer how the observations are related.

The physiology of endurance training shows a low-moderate increase in catecholamines, small increases in IL-6, which grow according to duration of exercise, and low-moderate amounts of GH secretion. Of these, IL-6 is the most important as its levels have the potential to be the highest for lipolytic activity. Because IL-6 tends to increase logarithmically with duration of ET, fat metabolism is more heavily relied as the primary energy source. This is consistent with the model that ET tends to burn large amounts of fat during exercise. However, since extremely high IL-6 concentrations are related to muscular atrophy, there is very little hypertrophy due to long duration ET. Similarly, since ET tends to use fatty acids, long duration ET runners (marathoners) will tend to be on the very thin side of body composition—only enough muscle mass to perform well and very little body fat because of high use of fat metabolism to supply energy.

HIIT, as well as resistance training with high volume and low rest (metabolic conditioning if ever a term was needed), tend to show a large increase in catecholamines, moderate to high levels of IL-6 and moderate to high increases in GH secretion. Across the board, these hormones modulate a large amount of lipolysis. During the exercise, the large release of hormones is due to the depleted glycogen state in muscles. Indeed, it is in the rest periods of the intermittent exercise that the levels of FFAs are increased as well as in the post exercise recovery period. Although EPOC is insignificant, the main culprit may be that increases in muscular damage due to high intensity exercise and subsequent repair of the tissues is most likely the cause of increased energy expenditure. In particular, the disruption of muscle structures such as the sarcolemma, extracellular matrix, basal lamina as well as damage to contractile and cytoskeleton proteins (releasing myoglobin and creatine kinase) is particularly elevated in response to high intensity exercise as opposed to endurance training [55]. Thus, the excess energy needed for reconstruction as well as potential hypertrophy because of any high intensity exercise is related to the degree of muscular damage accrued. However, too much muscular damage can lead to crippling soreness that hinders training and/or induces rhabdomyolysis. Since it is well know that most recovery from training occurs during the sleep period (which is also a prolonged 'fasting' state), the energy to fuel muscular repair and growth may come from the lipolysis from increased output of IL-6 and GH specifically. Comparatively, prolonged ET may have the same effect because there should be much accumulated muscular damage, but the limited muscular damage from low-moderate ET training along with the atrophy effect from IL-6 results in less need for energy for repair and muscular growth.

Resistance training stimulates high amounts of catecholamines, moderate amounts of IL-6, and moderate increases in GH. Although the hormones secreted are less overall than during HIIT or resistance training with high volume low rest, there is a fair to large amount of muscular damage as well as stimulation of more significant levels of strength and hypertrophy than said exercise protocols. That will increase the need for additional energy for muscular repair and hypertrophy and therefore lead to similar amounts of lipolysis as HIIT. As increases in amount of muscle mass require more energy metabolically, this may also contribute some to help metabolize excess fat.

Diet, of course, plays an important role in mass loss or mass gain. Another hormone, ghrelin, which stimulates appetite, modulates growth hormone release by stimulating the anterior pituitary. However, increasing the intensity of exercise does not affect ghrelin induced growth hormone secretion [35,40,43]. The digestive system is inhibited by the sympathetic nervous system during intense physical exercise as blood is shunted away from the gastrointestinal tract. Since ghrelin is secreted by the P/D1 cells of the stomach and epsilon cells of the pancreas, there is no ghrelin available to stimulate hunger [56]. This means that the extra energy needed for muscular repair and hypertrophy does not come from additional ingested food. This is most likely the main driving force of why exercise tends to help to metabolize fat from adipose tissue in people with non-regulated diets. On the other hand, a diet overabundant in calories will definitely lead to increased weight gain as well as fat gain if it exceeds basal metabolic rate and energy needed for muscular repair and hypertrophy. A good diet, therefore, should be a key in modulation of body composition changes.

As stated before, sleep is a time for the body to rebuild and repair itself and resupply a lot of its intracellular metabolites. Since serum testosterone levels tend to increase during sleep, and the majority of GH secretion occurs during sleep with no food intake, this is with strong certainty where body composition changes are occurring. This correlates strongly with the observation that sleep deprivation with accumulated training fatigue is a quick way to overtraining/underrecovery. It has been shown that recovery sleep after a period of exercise and sleep deprivation induces stronger GH production than normal [51], much like progressive training beyond the body's recovery limits may be able to induce a stronger supercompensation phase due to increased hormonal output. In post sleep deprived sleep, GH is even secreted even during non-SWS sleep. Since it is known that decreases in SWS and GH are related to senescence, this strongly suggests that exercise is a strong anti-aging tool. Thus, sleep is extremely important for recovery from exercise, body composition changes and anti-aging.

Based on the analysis, resistance exercise or high intensity protocols like HIIT, metabolic conditioning, or Tabata intervals in combination with a regulated diet and sleep are superior to ET for post exercise fat metabolism. Interval training seems to evoke a stronger neuroendocrine response than resistance exercise and ET, although total fat metabolism depends on the many factors such as duration, muscle damage and hypertrophy stress. While intervals may be the most time efficient way to metabolize excess fat due to a stronger neuroendocrine response per amount of time put into exercise, a stronger neuroendocrine response may not necessarily lead to any other such results like better increases in muscle mass or cardiovascular ability, although that is beyond the scope of this article.

Conclusions

The neuroendocrine response is particularly complex because it involves many hormones in the endocrine system and various pathways by which they function. Catecholamines, interleukin-6 and growth hormone are some of the major hormonal influences that determine which modalities of exercise stimulate various metabolic process that lead to potential body composition changes.

In all, it seems very unlikely that ONLY these three hormones are involved with the processes that modulate such body composition changes. For example, testosterone plays an obvious role as it is a potent anabolic hormone responsible for the increased muscle mass in men over women. It also plays a role in many of the above processes such as increased fat metabolism, which is why men tend to be able to lose fat much easier than women. Likewise, other important hormonal processes such as the modulation of IGF-1 by GH or vascular endothelial growth factor by IL-6 have not been covered.

Other non-hormonal effects like the compound adenosine may modulate fatigue in humans as well. It turns out that caffeine binds to adenosine receptors in the brain, which stave off fatigue [49]. Some recent research in rats shows that accumulated adenosine in the brain after high intensity exercise may help induce a homeostatic sleep response [50]. The rats in the study had an increased level of SWS, which, as previously mentioned, helps lead to increased GH secretion. Unfortunately, all hormonal and exercise induced metabolites are not discussed as detailing them, their effects, and interrelations due to exercise would take books.

This is just a very basic look at the how different neuroendocrine responses arise due to different training modalities. The unfortunate part is that most studies have looked only at parts of the system or only a few hormones. This is flawed as the body works as a unit and any variable that has input on the body such as training, sleep, and diet all have different systemic effects that must be take into account in concert with each other. Hopefully in the future, studies will focus more on this larger picture.


References:

1. Tremblay A, Simoneau JA, Bouchard C. Impact of Exercise Intensity on Body Fatness and Skeletal Muscle Metablism. Metabolism. 1994 43(7): 814-818.

2. Meirelles CM, Gomes, PSC. Acute effects of resistance exercise on energy expenditure: revisiting the impact of the training variables. Revista Brasileira de Medicina do Esporte, 2004; Vol. 10, No. 2: 122-130

3.Laforgia J, Withers RT, Gore, CJ. Effects of exercise intensity and duration on the excess post-exercise oxygen consumption. J Sports Sci. 2006 Dec ;24 (12):1247-64

4. Laforgia J, Withers RT, Shipp NJ, Gore CJ. Comparison of energy expenditure elevations after submaximal and supramaximal running. J Appl Physiol. 1997 Feb ;82 (2):661-6

5. Romijn JA, Coyle EF, Sidossis LS, Zhang XJ, Wolfe RR. Relationship between fatty acid delivery and fatty acid oxidation during strenuous exercise. J Appl Physiol. 1995 Dec;79(6):1939-45.

6. Ormsbee MJ, Thyfault JP, Johnson EA, Kraus RM, Choi MD, Hickner RC. Fat metabolism and acute resistance exercise in trained men. J Appl Physiol. 2007 May;102(5):1767-72.

7. Chatzinikolaou A, Fatouros I, Petridou A, Jamourtas A, Avloniti A, Douroudos I, Mastorakos G, Lazaropoulou C, Papassotiriou I, Tournis S, Mitrakou A, Mougios V. Adipose Tissue Lipolysis is Upregulated in Lean and Obese Men During Acute Resistance Exercise. Diabetes Care. 2008 Mar 28.

8. Mougios, V. Exercise Biochemistry. Human Kinetics; 2006.

9. Viru, Atko. Hormones in Muscular Activity: Volume I Hormonal Ensemble in Exercise. CRC Press; 1985.

10. Wikipedia contributors. Fight-or-flight response. Wikipedia, The Free Encyclopedia. April 15, 2008, 00:18 UTC. Available at: http://en.wikipedia.org/w/index.php?title=Fight-or-flight_response&oldid=205678989.

11. Abernethy PJ, Jürimäe J, Logan PA, Taylor AW, Thayer RE. Acute and chronic response of skeletal muscle to resistance exercise. Sports Med. 1994 Jan;17(1):22-38.

12. Essén-Gustavsson B, Tesch PA. Glycogen and triglyceride utilization in relation to muscle metabolic characteristics in men performing heavy-resistance exercise. Eur J Appl Physiol Occup Physiol. 1990;61(1-2):5-10.

13. Raz I, Katz A, Spencer MK. Epinephrine inhibits insulin-mediated glycogenesis but enhances glycolysis in human skeletal muscle. Am J Physiol Endocrinol Metab 1991; 260: E430-E435

14. Ullrich S, Wollheim CB. GTP-dependent inhibition of insulin secretion by epinephrine in permeabilized RINm5F cells. Lack of correlation between insulin secretion and cyclic AMP levels. J. Biol. Chem., 1988 Jun; Vol. 263, Issue 18, 8615-8620

15. Wikipedia contributors. Insulin. Wikipedia, The Free Encyclopedia. April 24, 2008, 20:16 UTC. Available at: http://en.wikipedia.org/w/index.php?title=Insulin&oldid=207945111. Accessed April 26, 2008.

16. Wikipedia contributors. Epinephrine. Wikipedia, The Free Encyclopedia. April 26, 2008, 02:01 UTC. Available at: http://en.wikipedia.org/w/index.php?title=Epinephrine&oldid=208242998.

17. Arkinstall MJ, Bruce CR, Clark SA, Rickards CA, Burke LM, Hawley JA. Regulation of fuel metabolism by preexercise muscle glycogen content and exercise intensity. J Appl Physiol 2004; 97: 2275-2283.

18. Mora-Rodriguez R, Coyle EF. Effects of plasma epinephrine on fat metabolism during exercise: interactions with exercise intensity. Am J Physiol Endocrinol Metab 2000; 278: E669-E676

19. Kraemer FB, Shen WJ. Hormone-Sensitive Lipase Knockouts. Nutrition & Metabolism 2006; 3:12

20. Romijn JA, Cyle EF, Sidossis LS, Gastaldelli A, Horowitz JF, Endert E, Wolfe RR. Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration. Am J Physiol Endocrinol Metab 1993; 265: E380-E391,

21. Wojtaszewski JFP, MacDonald C, Nielsen JN, Hellsten Y, Hardie DG, Kemp BE, Kiens B, and Richter EA. Regulation of 5'AMP-activated.protein kinase activity and substrate utilization in exercising human skeletal muscle. Am J Physiol Endocrinol Metab 2003; 284: E813–E822.

22. Hoffman SJ, Earle RW, Harris JC, Drews CM. Essentials of Strength Training and Conditioning. Human Kinetics; 2000.

23. Venables MC, Jeukendrup AE. Endurance training and obesity: effect on substrate metabolism and insulin sensitivity. Med Sci Sports Exerc. 2008 Mar;40(3):495-502.

24. Trapp EG, Chisholm DJ, Boutcher SH. Metabolic response of trained and untrained women during high-intensity intermittent cycle exercise. Am J Physiol Regul Integr Comp Physiol 2007; 293: R2370-R2375.

25. Achten J, Jeukendrup AE. Optimizing fat oxidation through exercise and diet. Nutrition. 2004 Jul-Aug;20(7-8):716-27.

26. Paspanicolaou DA, Petrides JS, Tsigos C, Bina S. Exercise stimulates interleukin-6 secretion: inhibition by glucocorticoids and correlation with catecholamines. Am J Physiol Endocrinol Metab. 1996; 271: E601-E605.

27. Frost RA, Nystrom GJ, Lang CH. Epinephrine stimulates IL-6 expression in skeletal muscle and C2C12 myoblasts: role of c-Jun NH2-terminal kinase and histone deacetylase activity. Am J Physiol Endocrinol Metab 2004; 286: E809-E817.

28. Wikipedia contributors. Interleukin 6. Wikipedia, The Free Encyclopedia. April 4, 2008, 18:06 UTC. Available at: http://en.wikipedia.org/w/index.php?title=Interleukin_6&oldid=203335613.

29. Pedersen BK. Exercise and cytokines. Immunology and Cell Biology. 2000; 78, 532–535

30. Holmes AG, Watt MJ, Febbraio. Suppressing lipolysis increases interleukin-6 at rest and during prolonged moderate-intensity exercise in humans. J Appl Physiol 2004; 97: 689-696.

31. Pedersen BK, Steensberg A, Schjerling P. Muscle-derived interleukin-6: possible biological effects. J Appl Physiol 2007; 103: 1093-1098.

32. Pedersen BK, Akerstrom TCA, Nielsen AR, Fischer CP. Role of myokines in exercise and metabolism. J Appl Physiol 2007; 103: 1093-1098.

33. Pedersen BK, Steensberg A. Fischer C. Keller C, Keller P, Plomgaard P, Wolsk-Peterson E, Febbraio M. The metabolic role of IL-6 produced during exercise: is IL-6 an exercise factor? Proceedings of the Nutrition Society 2004;, 63:263-267.

34. Keller C, Steensberg A, Hansen AK, Fischer CP, Plomgaard P, Pedersen BK. Effect of exercise, training, and glycogen availability on IL-6 receptor expression in human skeletal muscle. J Appl Physiol 2005; 99: 2075-2079.

35. Jørgensen JO, Krag M, Kanaley J, Møller J, Hansen TK, Møller N, Christiansen JS, Orskov H. Exercise, hormones, and body temperature. regulation and action of GH during exercise. J Endocrinol Invest. 2003; Sep;26(9):838-42.

36. Kraemer WJ, Marchitelli L, Gordon SE, Harman E, Dziados JE, Mello R, Frykman P, McCurry D, Fleck SJ. Hormonal and growth factor responses to heavy resistance exercise protocols. J Appl Physiol 1990; 69: 1442-1450.

37. Pyka G, Wiswell RA, Marcus R. Age-dependent effect of resistance exercise on growth hormone secretion in people. Journal of Clinical Endocrinology & Metabolism, 1992; Vol 75, 404-407.

38. Jacques B. IHO Urinary Growth Hormone – Clininal Value Applicatiions. International Health Organization. April 27, 2008. Available at: http://www.ihealthorg.com/iho_data.html.

39. Wikipedia contributors. Growth hormone. Wikipedia, The Free Encyclopedia. April 27, 2008, 12:38 UTC. Available at: http://en.wikipedia.org/w/index.php?title=Growth_hormone&oldid=208512988.

40. Kraemer RR, Durand RJ, Acevedo EO, Johnson LG, Kraemer GR, Hebert EP, Castracane VD. Rigorous Running Increases Growth Hormone and Insulin-Like Growth Factor-I Without Altering Ghrelin. Experimental Biology and Medicine 2004; 229:240-246.

41. Wee J, Charlton C, Simpson H, Jackson NC, Shojaee-Moradie F, Stolinski M, Pentecost C, Umpleby AM. GH secretion in acute exercise may result in post-exercise lipolysis. Growth Hormone & IGF Research. 2005 Dec; Vol 15, 6:397-404

42. Kraemer WJ, Staron RS, Hagerman FC, Hikida RS, Fry AC, Gordon SE, Nindl BC, Gothshalk LA, Volek JS, Marx JO, Newton RU, Häkkinen K. The effects of short-term resistance training on endocrine function in men and women. Eur J Appl Physiol Occup Physiol. 1998 Jun;78(1):69-76.

43. King NA, Lluch A, Stubbs RJ, Blundell JE. High dose exercise does not increase hunger or energy intake in free living males. Eur J Clin Nutr. 1997 Jul;51(7):478-83.

44. Pritzlaff CJ, Wideman Laurie, Weltman JY. Impact of acute exercise intensity on pulsatile growth hormone release in men. J Appl Physiol 1999; 87: 498-504.

45. Appenzeller O, Oribe E. The Autonomic Nervous System: An Introduction to Basic and Clinical Concepts. Elsevier Health Services; 1997.

46. Shapiro CM, Bortz R, Mitchell D, Bartel P, Jooste P. Slow-wave sleep: a recovery period after exercise. Science. 1981 Dec; Vol. 214 4526:1253-1254

47. Cauter EV, Leproult R, Plat L. Age-Related Changes in Slow Wave Sleep and REM Sleep and Relationship With Growth Hormone and Cortisol Levels in Healthy Men. JAMA. 2000;284:861-868.

48. van Coevorden A, Mockel J, Laurent E, Kerkhofs M, L'Hermite-Balériaux M, Decoster C, Nève P, Van Cauter E. Neuroendocrine rhythms and sleep in aging men. Am J Physiol. 1991 Apr;260(4 Pt 1):E651-61.

49. Davis JM, Zhao Z, Stock HS, Mehl KA, Buggy J, Hand GA. Central nervous system effects of caffeine and adenosine on fatigue. Am J Physiol Regul Integr Comp Physiol 2003; 284: R399-R404.

50. Dworak M, Diel P, Voss S, Hollmann W, Struder HK. Intense exercise increases adenosine concentrations in rat brain: Implications for a homeostatic sleep drive. Neuroscience. 2007 Oct 5; 150(4):789-95.

51. Davidson JR, Moldofsky H, Lue FA. Growth hormone and cortisol secretion in relation to sleep and wakefulness. J Psychiatry Neurosci. 1991 July; 16(2): 96–102.

52. Alcaraz PE, Sánchez-Lorente J, Blazevich AJ. Physical Performance and Cardiovascular Responses to an Acute Bout of Heavy Resistance Circuit Training versus Traditional Strength Training. J Strength Cond Res. 2008 Apr 15

53. Wikipedia contributors. Cortisol. Wikipedia, The Free Encyclopedia. May 2, 2008, 22:20 UTC. Available at: http://en.wikipedia.org/w/index.php?title=Cortisol&oldid=209790693.

54. Tuunanen H, Engblom E, Naum A, Någren K, Hesse B, Airaksinen KE, Nuutila P, Iozzo P, Ukkonen H, Opie LH, Knuuti J. Free fatty acid depletion acutely decreases cardiac work and efficiency in cardiomyopathic heart failure. Circulation. 2006 Nov 14;114(20):2130-7.

55. Hawke TJ. Muscle stem cells and exercise training. Exerc Sport Sci Rev. 2005 Apr;33(2):63-8.

56. Wikipedia contributors. Ghrelin. Wikipedia, The Free Encyclopedia. May 3, 2008, 17:25 UTC. Available at: http://en.wikipedia.org/w/index.php?title=Ghrelin&oldid=209936015.

Note: Any wikipedia sourced information (mainly hormone effects) is fairly common knowledge and cited well. Anymore information on these hormones can be found in physiology textbooks if there is any skepticism of wikipedia.