SEEMEDJ 2023, Vol 7, No 1 Thermoregulation and exercise 13 Southeastern European Medical Journal, 2023; 7(1) Review article The Physiology of Thermoregulation in Exercise: A Brief Review 1 Helena Lenasi* 1, Janez Šijanec 2 1 Institute of Physiology, Faculty of Medicine, University of Ljubljana, Slovenia 2 Bežigrad High School, Ljubljana, Slovenia *Corresponding author: Helena Lenasi, helena.lenasi.ml@mf.uni-lj.si Received: Mar 20, 2023; revised version accepted: Apr 6, 2023; published: Apr 30, 2023 KEYWORDS: exercise, thermoregulation, skin microcirculation, vasodilation, sweating Abstract During physical exercise, the production of heat in the working skeletal muscles increases, imposing heat stress on the body. Thermoregulatory mechanisms induce adjustments of cutaneous vascular conductance and thus skin blood flow (SkBF), sweating rate, and increased cardiac output to achieve thermal homeostasis. The response depends on the intensity, type, duration of exercise, and environmental temperature: during extreme exercise in a hot environment SkBF can attain up to 7 L/min compared to 300 mL/min at rest whereas the sweating rate can reach as high as 4 L/h. Due to opposing non-thermal reflexes, the thermoregulatory response of SkBF during exercise differs from that at rest: the threshold to induce vasodilation in the skin is shifted to higher body core temperature and the sensitivity of the “SkBF to-core temperature” slope is altered. Regular training induces better adaptations to physical stress which enable sportsmen to eliminate additional heat more optimally. The review emphasizes physiological mechanisms involved in thermoregulation during exercise and exposes some thoughts regarding the estimation t of the core temperature in humans, as well as some new approaches for an up-to-date assessment of parameters important for appropriate heat dissipation thereby maintaining core temperature. (Lenasi H*, Šijanec J. The Physiology of Thermoregulation in Exercise: A Brief Review. SEEMEDJ 2023; 7(1); 13-27) SEEMEDJ 2023, Vol 7, No 1 Thermoregulation and exercise 14 Southeastern European Medical Journal, 2023; 7(1) Introduction Humans as homeothermic organisms need to maintain their body temperature irrespective of relatively high fluctuations in their external or internal environment. During resting conditions, it is mainly external temperature that is fluctuating, whereas, during exercise, the most profound temperature perturbation occurs in the internal environment (1, 2). Though, when exercising in extreme environmental temperature conditions, this additionally impacts the human thermoregulatory system (3, 4). Thermoregulation encompasses reflex mechanisms enabling that heat elimination from the body equals heat production thus maintaining a constant body core temperature. Core temperature is regulated by a classical negative feedback loop including sensors (central and peripheral thermoreceptors), thermoregulatory center and effectors (2, 5). The information on temperature perturbation is relayed by thermoreceptors to the thermoregulatory center located in the central nervous system which compares the sensed value with the more or less flexible reference temperature value (“set-point”) and accordingly switches on and off effector mechanisms to eliminate the perturbation and return the core temperature to the “set-point” value (2, 5). The main effectors include skin arterioles and sweat glands, brown adipose tissue and skeletal muscles. In addition, behavioral changes contribute to thermoregulation (2, 5). Heat is eliminated from the body by four distinct physical principles, namely radiation, conduction, convection and evaporation (passive and active). The physiological thermoregulatory mechanisms in response to core temperature perturbation adjust the fractions of the four physical principles according to the body’s needs: during rest, the majority of heat is eliminated by radiation (60%) and only 20% by passive perspiration, while during exercise the majority of heat elimination is achieved by active evaporation and convection (2, 6). Physiological principles of thermoregulation during exercise While skeletal muscles consume approximately 1.5 mL oxygen/min/kg body weight in resting conditions, their oxygen consumption might reach up to 150 mL/min/kg during intensive exercise (4, 5, 7), implying additional heat burden that during exercise may exceed 1,000 Watt (W) as compared to only 70 W at rest. A thermal load of this magnitude would raise the core temperature by 1oC every 10 minutes if there were no thermoregulatory mechanisms (4). Accordingly, thermoregulatory reflexes are activated to eliminate this additional heat from the body to the environment, respectively preserving thermal homeostasis. Thermoregulatory center Situated in the preoptic area of the anterior hypothalamus, the thermoregulatory center is believed to comprise a “cold-sensitive” and “hot- sensitive” area activated by a corresponding temperature perturbation (8–11). Yet, the exact anatomic location, the neurotransmitters involved, and the effector pathways are not precisely known in humans as most of the information has been obtained from animal model experiments (8). The center is regarded as an integrator, integrating thermal information from the periphery and core (2): in response to the mismatch between the perturbation and the reference signal, an autonomic involuntary thermoregulation response is mediated by descending projections from the preoptic area, leading to activation of different thermo- effectors, mainly through the sympathetic pathways (9, 12, 13). An important contribution of oxytocin, modulating autonomic and behavioral mechanisms underlying thermoregulation at both central and peripheral levels has been implicated (14). Thermoreceptors The thermoregulatory center receives and integrates information on temperature perturbation from the central and peripheral thermoreceptors, respectively (2). Central thermoreceptors are located mainly in the SEEMEDJ 2023, Vol 7, No 1 Thermoregulation and exercise 15 Southeastern European Medical Journal, 2023; 7(1) central nervous system (brain, the spinal cord), although other parts, such as blood vessels and skeletal muscles have been implicated (2). However, the most important ones are part of the thermoregulatory center in the preoptic area and anterior hypothalamus (2, 8, 9). The peripheral thermoreceptors are scattered in the skin throughout the body. Similarly, as for the central ones, there are two types of anatomically distinct peripheral thermoreceptors: warmth receptors and cold receptors, whose distribution and density differ regarding skin site (2, 5, 9). Central thermoreceptors During exercise, the central thermoreceptors receive the information of increased core temperature (in the range of 2ºC to 4ºC) (2, 5) When a certain temperature threshold, usually denoted as a “set-point” value, has been reached, effector mechanisms are activated for heat elimination which subsequently establishes thermal homeostasis (2, 5, 9). The exact physiological background of the set-point has not been known; the role of various “transient- receptor potential” (TRP) membrane channels, similarly as for the cold sensing, have been implicated in the activation of these “hot- sensitive” neurons (9, 13, 15). It is worth mentioning that the “set-point” has a rather variable value, as for example during fever it is shifted to higher values (2). Similarly, the value of the “set-point” changes during exercise, i. e. the system is operating at a higher temperature steady state during exercise as compared to resting conditions (2, 5, 7). Moreover, additional factors importantly affect the value of the “set- point”, such as the circadian rhythm (6, 16), and sex as well as the phase of the menstrual cycle in premenopausal women (17–19), consequently also impacting exercise performance. Apart from these reflexes of the negative feedback mechanisms, some of the effector mechanisms are activated before an increase in core temperature, at the very beginning of exercise, denoting a “central command” and assumingly reflecting the anticipatory, feed- forward impulses from the prefrontal, supplementary and premotor cortex (5, 11, 20). Peripheral thermoreceptors In addition, the hypothalamus also receives information on the temperature changes over the skin surface relayed by peripheral thermoreceptors, specialized free nerve endings embedded in the skin dermis all over the skin surface (1, 2, 5). Changes in surface skin temperature are sensed before the core temperature is altered and, in this respect, peripheral thermoreceptors represent a protection mechanism that diminishes too extensive fluctuations of core temperature during resting conditions, (5), and might be regarded as an additional feed-forward thermoregulatory mechanism (2, 5, 9). During exercise, the response differs: peripheral thermoreceptors are thought to modulate the response of the thermoregulatory center during exercise (2, 6, 15, 21). As explained later, at the beginning of exercise, vasoconstriction in the skin is sufficient to cause temporal storage of excessive heat produced by the working muscles inducing an increase in core temperature which is then sensed by the central thermoreceptors, and reflexes for heat dissipation are activated (2, 4, 6). In fact, during exercise when a new steady-state core temperature is established, mean skin temperature decreases during exercise because of the increased evaporative cooling of the skin caused by sweating (2), increasing the temperature gradient between the body surface and the environment, thus making conductive- convective heat elimination more efficient (2, 5). In a warm environment and when skin temperature is high, the mechanisms of heat elimination are activated at lower core temperature, i.e. the threshold for heat elimination is lowered (3, 4, 11, 22–24), while the threshold is increased in a cool environment when skin temperature is low (25, 26). Peripheral thermoreceptors have been shown to have a great potential for adaptability, especially when exercising in a hot environment; nevertheless, the mechanisms of these adaptations have not been fully understood (15, 24, 27). SEEMEDJ 2023, Vol 7, No 1 Thermoregulation and exercise 16 Southeastern European Medical Journal, 2023; 7(1) Increased core temperature induces fatigue and might lead to hyperthermia The increased core temperature has been linked to “central fatigue”, which is speculated to represent a protection mechanism from potential brain injury (10, 28, 29). Fatigue and exhaustion are warning signs that exercise should be stopped or adjusted to reduce brain temperature increase. Brain temperature is determined by its metabolic activity and its perfusion, reflecting the temperature of blood (2, 15, 30). Many studies are being conducted on how to reduce brain heating during exercise, accordingly, improving thermoregulatory mechanisms, prolonging exercise duration and improving sports performance. The application of central pre-cooling or whole-body cooling has been advocated, being achieved by drinking cold drinks, applying cooled gel sacks, or whole- body cooling using special cool water-recycling suits (31–33); yet the best regime needs to be defined. As evaporative-heat loss is imminently connected with water loss, the role of an appropriate replacement of fluid and electrolyte could not be overemphasized (1, 15, 34). Hyperthermia exaggerates fluid loss, inducing a self-perpetuating, vicious cycle of both hyperthermia and hypovolemia, potentially leading to heat stroke and hypovolemic shock (1, 2, 5, 35). Cutaneous circulation is the main effector of thermoregulation during physical exercise In response to increased heat stress during exercise, the thermoregulatory center activates reflexes to transfer additional heat to the body surface from where heat is dissipated into the surroundings, accordingly, establishing a new steady state. Besides an increase in cardiac output during exercise, skin perfusion is increased due to profound vasodilation of skin arterioles, reducing cutaneous vascular conductance (CVC) and increasing skin blood flow (SkBF). These mechanisms enable an efficient heat transfer to the skin from where it is eliminated and significantly increase the surface area for heat exchange between the body and the environment. The vasodilation of skin micro- vessels can induce an immense increase of SkBF compared to resting conditions, i.e. from 300 mL/min in thermoneutral conditions (while in a cold environment as low as 100 mL/min) up to 7 L/min during exercise in a hot climate (4, 7, 24). The regulation of vascular tone in skin microcirculation is very complex, including neural and local mechanisms (21, 36–39). A decrease in vascular tone is mainly achieved by the withdrawal of the sympathetic tone regulating CVC as the skin arterioles throughout the body are innervated by sympathetic vasoconstrictor nerve fibers (11, 21, 36, 39–41). In addition, non-glabrous non-acral parts of the skin also receive vasodilatory sympathetic fibers which mediate active vasodilation (21, 36, 39). It is speculated that during exercise, these fibers contribute to active vasodilation in non-acral parts of the skin, such as the trunk, skin of the forehead and face, and non-acral parts of extremities (11, 21, 36). While vasoconstrictor fibers mainly mediate their action via noradrenaline acting on α-adrenergic receptors, the exact neurotransmitter of the sympathetic vasodilatory fibers remains questionable: proposed potential (co)transmitters include acetylcholine (ACh), substance P, calcitonin-gene-related polypeptide (CGRP) and nitric oxide (NO) (21, 36, 38). Respectively, the active role of endothelium seems to importantly contribute to active vasodilation in the skin (38, 39, 42). Special anatomical features present in skin microcirculation of glabrous acral parts, such as fingers, toes, palms, feet, ear lobes and nose, are arteriovenous anastomoses, direct connections between arterioles and venules (43, 44) which when open significantly increase the rate of heat elimination (24, 36, 43, 45). SEEMEDJ 2023, Vol 7, No 1 Thermoregulation and exercise 17 Southeastern European Medical Journal, 2023; 7(1) Figure 1. Thermoregulatory mechanisms during exercise. The thermoregulatory center integrates thermal (from central thermoreceptors sensing changes in core temperature, and peripheral thermoreceptors sensing changes in skin temperature (T)) and non-thermal input, compares the temperature perturbation with the “set-point” value, and activates appropriate reflexes to dissipate excessive heat from the body surface by adjusting the response of cutaneous vascular conductance and sweating, respectively. Temperature gradient determines the quantitative heat transfer from the core to the surface, where heat is dissipated by four physical principles, whose percentages are variable ( %) and modified by physiological response according to the quantity of the produced heat and ambient conditions, respectively. SEEMEDJ 2023, Vol 7, No 1 Thermoregulation and exercise 18 Southeastern European Medical Journal, 2023; 7(1) Evaporation-related heat loss during exercise is increased by sweating Another very efficient mechanism of heat elimination is active sweating which is tightly linked to changes in CVC. Each gram of water evaporated from the skin surface removes about 2.5 kJ of heat from the body (1, 5). Sweat glands are innervated by the sympathetic nerve fibers with ACh being a putative transmitter acting concomitantly with other cotransmitters (11, 46); an important role of various aquaporins in the skin has recently been reviewed (47). When fully active, sweat glands can increase their sweating rate up to 30 g sweat/min in response to the body’s needs which could account for up to 2-4 L/h during high-intensity exercise in a hot environment (1, 11, 15, 24). Indeed, in a hot environment when the ambient temperature exceeds the core temperature, there is no or even a negative temperature gradient for conductive-convective heat transfer, making evaporation the only way to dissipate heat (1, 2, 4, 24). Yet, besides physiologic adjustments in the sweating rate and composition of sweat (46, 48–50), the efficiency of sweating also depends on environmental factors, predominantly on the humidity (3, 15, 50, 51). Increased humidity can make sweating ineffective when there is no water vapor gradient between the environment and the surface of the body, predisposing to the development of hyperthermia which can be fatal (1, 2). Increased SkBF and sweating rate persist also far in the recovery period after exercise cessation, depending on the duration and intensity of exercise and the production of heat, until all additional heat is eliminated and the resting temperature steady state is achieved (16, 45, 52–54). A schematic representation of the mechanisms governing thermoregulation during exercise is depicted in Figure 1. How could skin blood flow and sweating be assessed The dynamics of skin microcirculation and skin temperature changes during exercise could be traced by using laser Doppler fluxmetry (LDF) (39, 45) and the corresponding skin temperature measurement (Fig. 2), various laser Doppler imaging techniques (55, 56) or ultrasound Doppler flowmetry (UDF) (57), and have been considered to be a more reliable measure of SkBF than plethysmography (58, 59). To obtain a better insight into the particular physiological mechanism behind it, different approaches and algorithms are being developed for the spectral decomposition of the LDF signal (60). Interestingly, glabrous and non-glabrous parts of the skin behave differently during exercise and its recovery (45, 57, 61) (Fig. 2). A strong cross-coupling between glabrous SkBF and core temperature in thermoregulatory function has recently been established based on experimental and modeling data (62). A promising device for tracing sweat rate during exercise as accurately as possible and providing a low-cost device platform to detect other health-relevant biomarkers in the sweat (vapor) as the next-generation sweat sensor for smart healthcare and personalized medicine has been introduced (63). SEEMEDJ 2023, Vol 7, No 1 Thermoregulation and exercise 19 Southeastern European Medical Journal, 2023; 7(1) Figure 2. The responses of skin blood flow and the corresponding skin temperature to exercise and its recovery differ between glabrous and non-glabrous areas. A representative tracing of the laser Doppler flux (LDF), expressed in arbitrary perfusion units (AU) and the corresponding skin temperature (T) in skin microcirculation on the volar forearm (glabrous site) and the finger pulp (non-glabrous site) during graded dynamic exercise and its recovery is shown. Exercise load is expressed in Watts (W). Adapted from (45). The main differences between thermoregulation during rest and exercise: a summary Apart from thermoreflexes, many opposing non- thermoregulatory reflexes (mechano-, metabo- and baroreflex to list some) are activated during exercise and its recovery to ensure sufficient perfusion of skeletal muscles and the preservation of blood pressure (7, 15, 20, 54, 64– 66). Therefore, thermoregulation during exercise importantly differs from that at rest. The most manifest differences are depicted in Fig. 3, representing the relation between the body core temperature and the SkBF. To assess the characteristics of this relation, i.e. the slope of the curve, the body core temperature and the SkBF, potentially with the corresponding skin temperature, should be traced. Core temperature is usually determined by an esophageal thermo-sensor, although other methodological aspects have been addressed (5, 20, 22, 62). Nevertheless, the data should be interpreted cautiously, especially when measuring peripheral skin T to estimate core temperature, which is rather questionable (67). On the other hand, there are much more options for assessing skin temperature; besides the above mentioned, infrared thermography has gained increasing importance; yet, similarly to other methods, it has not been standardized (68, 69). At the beginning of exercise, an increase of the sympathetic tone throughout the body, presumably due to a central command, enables redistribution of blood flow, increasing CVC and reducing SkBF and thus shifting the starting point toward lower SkBF at unchanged core temperature (Fig. 3) (2, 5, 7, 20, 24). Another distinctive difference is a shift in the threshold to induce active vasodilation and sweating in the skin, toward higher core temperatures (Fig. 3); interestingly, the threshold shift depends on SEEMEDJ 2023, Vol 7, No 1 Thermoregulation and exercise 20 Southeastern European Medical Journal, 2023; 7(1) exercise intensity and is even more pronounced in high-intensity exercise (11, 20, 36). The dependence of the thermoregulatory threshold on the intensity of exercise might partly explain rapid fatigue and exhaustion during intense exercise due to a higher increase in core temperature, which might even lead to hyperthermia (15, 22, 29). The third pronounced difference is the responsiveness of the effectors in the skin: the maximal vasodilation in the skin during exercise comprises only 60% of the maximal vasodilation attained in resting conditions (Fig. 3) (7, 20, 24). Pooling of additional blood in the periphery impedes venous return to the heart, and activates baroreflex, leading to “cardiovascular drift” and heart rate increase that is disproportional to the needs of the skeletal muscles (5, 52, 70). Figure 3. The main differences between thermoregulation during rest and dynamic exercise. Skin blood flow (SkBF) in relation to body core temperature is shown. The “starting point” is shifted toward lower SkBF at the onset of exercise due to vasoconstriction in the skin (A). The temperature threshold to induce vasodilation is shifted toward a higher core temperature during exercise (B). Maximal vasodilation in the skin is reduced compared to resting conditions (C). Adapted from (4). In addition, it has been proposed that skin temperature, independently of the core temperature, affects sports performance: maximal oxygen uptake (VO2max) at the same core temperature was shown to be lower at higher skin temperatures than at lower ones (23, 70). Increased skin temperature during exercise reduces the temperature gradient for heat elimination, impeding heat exchange. To overcome the decreased temperature gradient, SkBF is increased on account of diminished blood flow through skeletal muscles. From the above observations on opposing thermo- and non-thermoregulatory reflexes during exercise and its recovery, it is obvious that hyperthermia is more often an issue when exercising than when resting. Interestingly, simplified thermoregulation models of the human body exercising in warm conditions have been proposed considering all the above-mentioned players (62, 71). Exercise and thermoregulation in extreme environmental conditions Hot environment Exercising in a hot environment undoubtedly compromises thermoregulation. Pooling of additional blood in the periphery increases cardiovascular drift in a hot climate. It has been shown that a heart rate increase of 20 beats/min could not compensate for the decreased stroke volume due to the pooling of blood in the skin: cardiac output was about 1.5 L/min lower during heavy exercise in the heat than during comparable exercise in a cool environment (1, 5, 15). Due to insufficient muscle perfusion, the amount of anaerobic metabolism increases, decreasing plasma pH and additionally compromising performance (15, 72). In addition to the pooling of blood, another problem during prolonged exercise is the loss of water and electrolytes, additionally compromising venous return, and consequently jeopardizing the maintenance of blood pressure. To overcome the threatening hypotension, relative cutaneous vasoconstriction issues, rendering the person more susceptible to developing hyperthermia (1, 5, 24). In addition, the reflex of sweating is reset toward higher core temperatures as water preservation due to SEEMEDJ 2023, Vol 7, No 1 Thermoregulation and exercise 21 Southeastern European Medical Journal, 2023; 7(1) reduced osmolarity surpasses the need to eliminate heat by sweating (20, 73–75). Respectively, a vicious cycle could ensue leading to hyperthermia and/or shock (35). In this respect, sufficient fluid and electrolytes substitution is a prerequisite for sustaining exercise (24, 34, 76). It has been shown that even 1% of body mass reduction due to dehydration strongly impacts sports performance and VO2max (77). Figure 4. The effect of regular training and acclimatization on thermoregulation Training and staying in a warm environment for a longer period induce a shift in the temperature threshold for heat elimination (presented as sweating rate) as well as the sensitivity of thermoreflex. Adapted from (81). When regularly exercising in a warm environment, acclimatization processes take place which improve sports performance: the sensitivity of thermoreflex is reset toward a lower core temperature threshold (Fig. 4), the maximal sweat rate increases and sweat composition changes, becoming more diluted thus helping to preserve body electrolytes (24, 50, 51, 78, 79). In addition, an increase in plasma volume in a longer-term improves circulation and heat exchange (24, 77). All these adaptations improve VO2max and sports performance. Interestingly, similar adaptations have also been shown in endurance elite sportsmen exercising in a thermoneutral environment (Fig. 4) (48, 73, 78–81). Cold environment On the other hand, exercising in a cold environment is not problematic from the thermoregulatory point of view provided it is not of too long duration or performed in cold water which has a 25-fold higher heat conductivity compared to air (5, 25–27, 82). As long as the body core temperature is maintained in a physiological range, the low ambient temperature does not impact sports performance and VO2max. Yet, cooling of the muscles impacts their functional abilities in terms of decreasing their strength, maximal force, velocity and reaction time (83, 84). Due to vasoconstriction in the skin, the release of free fatty acids from subcutaneous adipose tissue is reduced, limiting the oxidation of fat as fuel for muscle contraction and accordingly increasing the oxidation of carbohydrates. Potential hypothermia results from a drop in core temperature when exercising for a longer time, or insufficiently dressed or performing water sports (26). Acclimatization to cold induces adaptive mechanisms which enable better preservation of heat on one side and increased production on the other, including shivering and brown fat adipose tissue thermogenesis (2, 25–27). Effect of sex and age on thermoregulation during exercise An interesting issue to be discussed is the effect of sex on thermoregulation. On one side, centrally mediated mechanisms might affect the response regarding sex, and on the other, sex hormones are known to exert direct peripheral effects on the vascular tone (11, 18, 19, 36, 85). Yet, studies reported controversial results. Most often, the main differences are attributed to the sweating response: the slope of the curve representing sweating rate dependency on the body core temperature was reduced in women compared to men (86, 87) even though women exhibited a greater number of sweat glands (51). The differences in the sweat rate were more pronounced when exercising at higher intensities (86). It seems that the temperature threshold to induce vasodilation in the skin is SEEMEDJ 2023, Vol 7, No 1 Thermoregulation and exercise 22 Southeastern European Medical Journal, 2023; 7(1) higher in women (85). However, a recent meta- analysis has shown that despite increased core T in women in the luteal phase of the menstrual cycle this does not significantly impact thermoregulatory response, at least in terms of sweat rate and skin temperature (19, 88). Finally, it is worth emphasizing that aging also affects the thermoregulatory response to exercise (1). Effect of endurance training on thermoregulation during exercise Regular training in both men and women induces significant adaptations of the thermoregulatory system, including cutaneous vascular reactivity as well as sweating. The threshold to activate effectors for heat elimination is lower in trained compared to sedentary (64, 77, 81, 89) (Fig. 4). Sweat rate and composition are altered in terms of increased sweat rate at the same exercise intensity (expressed as % VO2max) and more diluted sweat, respectively enabling more efficient electrolytes preservation in sportsmen (51, 78, 80). In addition, sportsmen have been shown to better acclimatize to the heat, which rather than reflecting structural changes has been attributed to functional vessel alterations (79, 90). A part of altered vascular responsiveness might be attributed to increased endothelium- dependent vasodilation (91, 92) which might additionally contribute to beneficial thermoregulatory adaptations. All these adaptations enable sportsmen better adjustments to physical and thermal stress, reaching higher VO2max values and performing exercise for longer periods, in thermoneutral, as well as in extreme environmental conditions. Conclusion Thermoregulation during exercise differs from that in resting conditions since, during exercise, thermoregulatory reflexes oppose the non- thermoregulatory ones. The opposing reflexes integrate at the level of skin microcirculation which is the main organ for heat elimination. An important issue when exercising is a sufficient substitution of water and electrolytes, especially in a warm and humid environment. Regular physical activity induces several beneficial changes, including better thermoregulatory mechanisms. Yet, exact mechanisms, as well as the most optimal training regime, remain to be determined, and above others, appropriate methods to measure the many players involved in thermoregulation in humans in vivo need to be established. Acknowledgement. None. Disclosure Funding. No specific funding was received for this study. Competing interests. None to declare. References 1. McArdle WD, Katch FI, Katch VL. Essentials of Exercise Physiology. 3rd ed. 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