The effects of creatine and glycerol hyperhydration on running economy in well trained endurance runners

Running economy (RE), which is defined as the sub-maximal oxygen consumption $\left(\dot{\mathsf{\text{V}}}{\mathsf{\text{O}}}_{\mathsf{\text{2}}}\right)$ at a given running velocity, is an important physiological parameter as superior RE is essential for successful endurance running performance [1, 2]. In general, runners with good RE use less oxygen than runners with poor RE at the same absolute exercise intensity. RE appears to be influenced by many physiological factors [1] including hydration status. Coyle (2003) proposed that a -4 to -8% body mass (BM) deficit due to dehydration (i.e., the process of reducing body water) may lower the oxygen cost of movement [3], given that athletes who lose the most BM during a race are usually the most successful [4]. Nevertheless, this theoretical paradigm contradicts the prevailing view of a body water deficit in excess of 2-3% BM constituting the level of dehydration that can adversely affect performance [5].

During exercise, skeletal muscle produces a significant amount of heat. When this metabolic heat production exceeds total heat loss, core body temperature (T_core) rises. Consequently, endurance exercise performance in hot and dry environments can be limited by the increase in T_core[6]. An increase in T_core during can be attenuated via the secretion and evaporation of sweat through the skin with inevitable body water loss. This decrease in body water is hypothesized to decrease plasma volume (PV) and consequently reduce the sweating response and therefore thermoregulation capacity, increase heart rate (HR) and reduce skin blood flow [7]. Improved maintenance of PV is the overriding rationale for fluid ingestion during exercise by those supportive of the "cardiovascular model of dehydration" [5]. However, proposed guidelines [5] are not always practical (e.g., difficulties providing adequate drinks during a race, athletes difficulties in drinking while running) and athletes typically refrain from consuming recommended amounts of fluids. Other means to expand PV can be by infusion of isotonic saline [8] with somewhat conflicting success [8, 9]. More recent approaches aimed at expanding body water compartments using hydrating agents such as creatine (Cr) and glycerol (Gly) have successfully attenuated the rise in T_core and HR during exercise in heat [10, 11].

Cr has been shown to have hydrating effects [12, 13], although the exact process has yet to be established. Ingestion of 20 g·d^-1 of Cr dissolved in 500 mL of water for 7 days have proved successful in attenuating the rise in HR and T_core during exercise in the heat [13]. These effects have been attributed to an increase in intracellular water (ICW), resulting in an increased specific heat capacity of the body [12, 13]. Moreover, whole body Cr retention is 60% higher when consumed with carbohydrate (CHO) compared to when Cr was consumed alone [14]. Although the mechanism by which CHO enhances Cr uptake is not completely understood, consumption of 100 g per 5 g of Cr has been recommended for the effective improvement of Cr uptake [15]. Like Cr, Gly has been found to be an effective agent in expanding the water compartments within the human body [11, 16]. Gly, seems to expand the ICW as well as the extracellular water (ECW) [17]. In general, doses of 1.0-1.5 g Gly·kg^-1 BM dissolved in 1.4 - 2.0 L of fluid 2.5 - 4 h before exercise [18] increase total body water (TBW) compartments and reduce thermal and cardiovascular strain during exercise in the heat.

Supplementation with combined hydrating agents such as Gly or Cr has consistently produced modest fluid retention of 400 - 800 mL [10–12]. Easton et al. (2007) were the first to add Gly to a Cr containing solution and demonstrate that a combination of the two hyperhydrating agents has an additive effect, as the addition of Gly to Cr significantly increased TBW more than Cr alone. Although the combination of the aforementioned hyperhydrating agents results in an increase in TBW and a reduction in certain cardiovascular and thermoregulatory responses [19], the BM increase due to enhanced hydration status could potentially reduce RE. The reduction of the energy cost of movement at a sub-maximal velocity by way of reducing BM to improve running performance is well known [20]. For instance, it is noted that some marathon runners perform well despite dehydration of 4-8% BM [21]. Coyle [3] proposed that this may occur because fluid loss (i.e., reduced body mass) lowers the oxygen cost of movement. On the other hand, the acute influences of hyperhydration on RE has not been investigation to date. Hence, the aim of the present study was to investigate the effects of hyperhydration induced by a combined Cr and Gly supplementation on thermoregulatory and cardiovascular responses and RE during 30 min of running at a running speed corresponding to 60% $\dot{\mathsf{\text{V}}}{\mathsf{\text{O}}}_{\mathsf{\text{2}}}max$ in cool (10°C with a relative humidity of 70%) and hot conditions (35°C with a relative humidity of 70%) in well trained male athletes. In cool ambient conditions were intended to minimize heat stress during exercise this enabling a focus on the effects of the altered BM induced by hyperhydration on RE at 60% $\dot{\mathsf{\text{V}}}{\mathsf{\text{O}}}_{\mathsf{\text{2}}}max$. However, effects of hyperhydration on thermoregulatory and cardiovascular responses are also expected during exercise in hot and humid conditions; conditions typical of major sporting events (e.g., Olympic Summer Games). As such, it was hypothesized that an increase in BM and TBW induced by hydrating agents such as Gly or Cr would improve thermoregulatory and cardiovascular responses in line with previous findings but potentially negatively influence RE during running in the heat.

The novel finding of this study is that a previously established pre-exercise water loading strategy using a combination of hydrating agents such as Cr and Gly that significantly increased body water compartments and reduced cardiovascular (Figure 5) and thermoregulatory (Figure 6) responses during running at 35°C, had no effect on the oxygen cost of running at 60% of $\dot{\mathsf{\text{V}}}{\mathsf{\text{O}}}_{\mathsf{\text{2}}}max$. The magnitude of change in BM following hyperhydration was similar to that previously reported in our laboratory [19] and by Kern et al. (2001). Somewhat smaller differences in body water compartments were observed in the present study compared to the previous investigation by Easton et al. (2007). For example, Easton et al [19] reported an increase of 0.9 L in TBW and 0.5 L in ICW after 7 days of supplementation. In the present study TBW and ICW were elevated by 0.7 and 0.3 L respectively after 7 days of supplementation. These differences could only be attributed to individual responses (i.e., level of "responders" to Cr supplementation as previously demonstrated) [13, 34] as similar protocols were utilised. In the present study, the retained water was dispersed in both the ICW and ECW. Despite the significant increase in BM and body water compartments and consequently improved thermoregulatory responses during exercise, no significant differences in any of the respiratory variables were found between the pre- and post-supplementation exercise trials. Therefore, the finding that a significant increase in BM did not negatively impact on RE of trained runners supports the use of hyperhydration during endurance running when running in hot and humid conditions although confirmatory results are required during faster running speeds typical of sporting competition (i.e., > 85% $\dot{\mathsf{\text{V}}}{\mathsf{\text{O}}}_{\mathsf{\text{2}}}max$).

Temperature and cardiovascular regulation during exercise in the heat do appear to be critically dependent on hydration status [35, 36]. In the present study, combined Cr and Gly supplementation induced significant hyperhydration and substantially attenuated the increase in HR at the end of the 30 min run at 35°C (Figure 5). This attenuation of HR during exercise was of similar magnitude to that previous reported by Easton et al. (2007). As free water in the form of sweat is primarily lost from plasma and since no differences were found in PV changes pre- and post-supplementation despite the increase in TBW, ICW and ECW, it can be suggested that the increase in other water compartments resulted in water moving towards the plasma due to an osmotic gradient. This in turn leaves the PV unaffected. It should be also noted that in order for blood volume to be maintained in conditions of significant thermal stain and therefore sweating, fluid loss is obtained in varying proportions from ECW as well as ICW body water compartments [37]. Furthermore, as loss of body water increases during exercise in the heat as a result of sweating, T_core also increases [37]. Therefore, increasing body water could potentially result in better maintenance of T_core during exercise in the heat. Nose et al. [38] reported a strong association between the loss of water in sweat and urine and the decrease in ICW after prolonged exercise in the heat. In the present study, Cr and Gly induced an increase in ICW and consequently, there was a significant attenuation in the rise of T_core during exercise in the heat (Figure 6). It is possible that this Cr- and Gly-induced increase in ICW resulted in an increase of the specific heat capacity of the body [13].

Published studies to date appear to confirm the reduction of T_core during exercise in the heat following Cr supplementation [12, 13, 19]. Conversely, when Gly was used alone, ICW was increased without significantly attenuating the rise in T_core during the exercise period [19]. The effects of Gly ingestion on T_core and thermoregulation in general during exercise in the heat is equivocal, with several studies reporting a reduction in T_core during exercise [39] and numerous other studies finding no such effect [16, 40]. In addition, several studies concluded that PV expansion has no effect on thermoregulatory responses or exercise performance during exercise in the heat [9, 41]. These conflicting results and assertions provide strong support that the thermoregulatory benefits exhibited with Gly ingestion in the present study did not arise from any PV expansion but most likely from an increase heat capacity of the body. Nevertheless, it should also be noted that these thermoregulatory benefits were exerted when Gly was co-ingested with Cr.

Despite the significant increase in TBW and consequently improvement in cardiovascular and thermoregulatory responses during exercise, no differences in $\dot{\mathsf{\text{V}}}{\mathsf{\text{O}}}_{\mathsf{\text{2}}}$ were observed during running at 60% $\dot{\mathsf{\text{V}}}{\mathsf{\text{O}}}_{\mathsf{\text{2}}}max$. Coyle proposed that a reduction in BM induced by dehydration would impact on RE during marathon running by reducing the oxygen cost of running [3]. In contrast, hyperhydration should theoretically increase the oxygen cost of running and therefore RE. However, no such effect was found in the present study. Furthermore, there was no increase in $\dot{\mathsf{\text{V}}}{\mathsf{\text{O}}}_{\mathsf{\text{2}}}$ over time during the trial at 10°C. The latter finding indicates that the subjects were working steadily at the calculated individual running speed corresponding 60% of $\dot{\mathsf{\text{V}}}{\mathsf{\text{O}}}_{\mathsf{\text{2}}}max$. It should be noted that this relatively low intensity was chosen in order to ensure that the present data would be comparable with previous studies conducted under similar conditions [12]. Furthermore, the relatively low intensity was chosen as to secure that all subjects could complete the experiment in the heat while it was high enough to observe possible adaptations in cardiopulmonary or thermoregulatory parameters encountered with supplementation. However, $\dot{\mathsf{\text{V}}}{\mathsf{\text{O}}}_{\mathsf{\text{2}}}$ was increased during the trial in the heat. This was an expected effect as when exercising in hot environmental conditions, T_core rises accordingly. It has been shown that with an increase in T_core, $\dot{\mathsf{\text{V}}}{\mathsf{\text{O}}}_{\mathsf{\text{2}}}$ (and therefore RE) also increases [42]. Despite this observation, no discernable difference in $\dot{\mathsf{\text{V}}}{\mathsf{\text{O}}}_{\mathsf{\text{2}}}$ between pre- and post-supplementation trials was reported. No other changes in any of the respiratory variables could be observed in the pre- and post-supplementation trials. Similar results have been reported in several other studies using Cr as the hyperhydrating agent [13] as well as during constant load exercise in the study by Easton et al. (2007) where hyperhydration was induced by Cr and Gly [19]. The data from the present study suggest that an increase in BM of approximately 1.4% (average increase in BM in the present study) has no significant effect on $\dot{\mathsf{\text{V}}}{\mathsf{\text{O}}}_{\mathsf{\text{2}}}$. Whether such an increase in BM would influence running performance remains to be determined. Furthermore, as HR responses reflect those of $\dot{\mathsf{\text{V}}}{\mathsf{\text{O}}}_{\mathsf{\text{2}}}$[43], the finding that HR during exercise was not significantly different between pre- and post-supplementation trials conducted at 10°C is further evidence against any detrimental metabolic effect of the added BM induced by hyperhydration on RE.

A hyperhydration strategy that combines Cr and Gly supplementation for 7 days increased BM and TBW and consequently reduced cardiovascular and thermal strain but did not significantly affect the oxygen cost of running at 60% of $\dot{\mathsf{\text{V}}}{\mathsf{\text{O}}}_{\mathsf{\text{2}}}max$ at 35°C in trained runners. The finding that a significant increase in BM did not negatively impact on RE of trained runners, supports the use of effective hyperhydration strategies during endurance running when conditions so dictate (i.e., running in hot and humid conditions). Further studies are necessary however to confirm these findings during faster running speeds reflective of true performance.