PROMOTING ENDURANCE TRAINING ADAPTATIONS WITH NUTRITIONAL INTERVENTIONS: THE POTENTIAL BENEFITS OF ‘LOW CARBOHYDRATE’ TRAINING

etal muscle responds to endurance exercise via increased transcription of metabolic and stress-related genes ultimately to yield increased steady-state levels of specific proteins. These changes in transcriptional activity are highly dependent on the mode, duration, intensity and frequency of the contractile stimulus. One of the major challenges for exercise physiologists over the coming decades is to identify the exercise ‘signal(s)’ that are responsible for initiating the adaptive response and the precise signal transduction pathways which mediate the adaptive processes. In this regard, it is now becoming apparent that cellular energy status may have an important role to play in this process. For example, many stress-and metabolic-related genes are enhanced when the exercise is commenced under reduced pre-exercise muscle glycogen levels and attenuated when glucose is ingested during exercise. Taken together, such findings suggest that training under conditions of reduced carbohydrate availability from both endogenous and exogenous sources may provide an enhanced stimulus for inducing beneficial adaptations of skeletal muscle. This hypothesis is in marked contrast to the widely held belief that intense training periods should be supported by a high carbohydrate diet in order to maintain training intensity and replenish energy stores for future training sessions. This paper will outline the current thinking regarding the potential for carbohydrate availability to modulate the adaptations typically observed following periods of endurance training. Relevant data from the literature and our own laboratory is presented with a view to providing some potential advantages and disadvantages of training with reduced carbohydrate availability for both athletes and coaches. Key words: muscular endurance, endurance training, carbohydrate diet, cellular function, adaptive re- sponse, performance improvement Introduction Endurance training is a generic term for any repeated bouts of physical activity that aim at im- proving the ability of an individual to sustain ex- ercise performance for prolonged

advantages and disadvantages of training with reduced carbohydrate availability for both athletes and coaches. Key words: muscular endurance, endurance training, carbohydrate diet, cellular function, adaptive re- sponse, performance improvement Introduction Endurance training is a generic term for any repeated bouts of physical activity that aim at im- proving the ability of an individual to sustain ex- ercise performance for prolonged periods of time. This type of training is traditionally important in sports such as athletics and cycling as they predomi- nantly rely on the aerobic energy system for the re- generation of ATP. Such training is also important for invasive fi eld sports such as soccer, rugby and hockey as these intermittent activities, in which the exercise pattern includes frequent supra-maximal high-intensity efforts, also require a signifi cant con- tribution from aerobic metabolism to support their energy requirements. The acute bouts of exercise that are traditional- ly incorporated in endurance training programmes are prolonged and sub-maximal in nature. It is now clear from research undertaken over the last few decades that endurance training programmes should include a mixture of different exercise inten- sities (from sub-maximal to maximal) and different volumes. Such variation in training stimulus is the only way to ensure that exercise performance can be optimized for both the elite performer and the recreational athlete. This is a direct consequence of the relationship between the training stress and the body’s subsequent physiological, structural and biochemical adaptations (specifi city) in response to an exercise challenge. An appropriate exercise pre- scription over time therefore leads to a variety of changes that improve the delivery and utilization of oxygen and hence the potential for aerobic me- tabolism and performance. These changes include

Drust, B. and Morton, P. J.: PROMOTING ENDURANCE TRAINING ... Kinesiology 41(2009) 1:19-24 20 alterations in the structure and function of the car- diovascular, respiratory and musco-skeletal systems (Kubukeli, Noakes, & Dennis, 2002). Skeletal muscle is the largest organ in the hu- man body and possesses a tremendous capacity to adapt to the demands of endurance training via var- ious structural, functional and biochemical adap- tations (Booth & Baldwin, 1996). The adaptations that the muscle makes to endurance training include mitochondrial biogenesis (Holloszy & Coyle, 1984), fast to slow muscle-fi bre transformations (Taylor & Buchman, 1999), changes in substrate metabolism (Henrikssen, 1977) and an up-regulation of cellu- lar defence systems (Morton, et al., 2008). These adaptive responses lead to improvements in cellular function that serves to maintain balance between the demands placed on the system and the capac- ity to support these requirements (Basel-Duby & Olson, 2006), thereby leading to performance im- provements. Subtle alterations in the intensity and duration of exercise lead to variations in a range of primary and secondary messengers that are asso- ciated with exercise stress. These include (but are not limited to) increases in intracellular calcium (Chin, 2005), reactive oxygen species (Pattwell & Jackson, 2004), hypoxia (Fluck, 2003), mechanical stretch (Hornberger, Armstrong, Koh, Burkholder, & Esser, 2005) and substrate availability (Hawleay, Gibala, & Bermon, 2008). These ‘signals’ (acting alone or likely in combination with each other) can activate a multitude of signal transduction pathways (Wackerhage, 2006) and initiate the replication of a single gene or sets of genes that enable the tran- scription and translation of this genetic code into a series of amino acids to create new proteins (Cof- fey & Hawley, 2007). The cumulative effect of each acute exercise bout leads to a change in the steady- -state level of these specifi c proteins and hence a new functional threshold (Mahoney, Parise, Melov, Safdar, & Tarnopolsky, 2005). It is these repeat- ed and transient changes in gene expression which are thought to form the molecular basis for train- ing adaptation. Nutritional status as a mediator of the cellular and molecular adaptive responses to

change in the steady- -state level of these specifi c proteins and hence a new functional threshold (Mahoney, Parise, Melov, Safdar, & Tarnopolsky, 2005). It is these repeat- ed and transient changes in gene expression which are thought to form the molecular basis for train- ing adaptation. Nutritional status as a mediator of the cellular and molecular adaptive responses to ‘acute’ exercise The obvious way in which an individual’s nutri- tional intake could theoretically infl uence the adap- tive responses to training is by affecting the abil- ity of an athlete to complete the prescribed train- ing load. It has traditionally been accepted that a diet high in carbohydrate is benefi cial for endurance training as it is fundamental in supporting periods of highly intense activity (Karlsson & Saltin, 1971). High carbohydrate diets will support intense peri- ods of training by better maintaining both muscle and liver glycogen stores and ensuring high rates of carbohydrate oxidation during exercise (Hawley, Tipton, & Millard-Stafford, 2006). This will ensure that athletes are able to perform at the required in- tensity for the desired time, thereby maximizing their ability to maintain the ‘optimal’ physiological stimulus required for performance improvements. However, in recent years the role of glycogen has evolved beyond that of a simple energy store ad- vancing to a regulatory role which also recognizes glycogen as a mediator of cell signalling process- es that are associated with mediating the adap- tive responses to exercise and training (Hawley, et al., 2006). Altering substrate availability through changes in dietary intake will also alter the con- centration of blood-borne nutrients and hormonal responses to exercise (Hawley, et al., 2006). This will in-turn not only affect the storage profi le within muscle but more importantly the regulatory proc- esses underlying gene expression (Jump & Clarke, 1999). Several data sets demonstrate that conditions of reduced carbohydrate availability may provide an enhanced stimulus for exercise-induced adapta- tions of skeletal muscle. For example, genes encod- ing heat shock protein 72 (Febbraio, et al., 2002), IL-6 (Keller, et al., 2001), hexokinase and PDK4 (Pilegaard, et al., 2002) are expressed to a

proc- esses underlying gene expression (Jump & Clarke, 1999). Several data sets demonstrate that conditions of reduced carbohydrate availability may provide an enhanced stimulus for exercise-induced adapta- tions of skeletal muscle. For example, genes encod- ing heat shock protein 72 (Febbraio, et al., 2002), IL-6 (Keller, et al., 2001), hexokinase and PDK4 (Pilegaard, et al., 2002) are expressed to a greater extent when exercise is performed in a glycogen depleted state compared with normal muscle gly- cogen stores. The proposed ‘energy sensor’ of the cell, AMPK, also displays higher activity both at rest and following exercise when glycogen is low (Wojtaszewski, et al., 2003). Ingestion of glucose during exercise also blunts expression of meta- bolic genes such as PDK4, UCP3, PGC1α, CD36, CPT1 and AMPKα2 (Cluberton, McGee, Murphy, & Hargreaves, 2005), the exercise-induced increase in AMPKα2 activity (Akerstrom, et al., 2006) and the release of IL-6 from contracting skeletal muscle (Febbraio, et al., 2003). Taken together, these fi nd- ings indicate that substrate availability and utiliza- tion from both endogenous and exogenous sources, especially in relation to carbohydrate, are an im- portant factor in infl uencing the adaptive responses of skeletal muscle to exercise. Such data therefore suggest that carefully scheduled periods of training under conditions of low carbohydrate availability may be benefi cial for inducing skeletal muscle ad- aptations and improving subsequent performance (Baar & McGhee, 2008). Can ‘training’ with reduced carbohydrate availability enhance the training stimulus and improve performance? Despite the theoretical rationale provided from those ‘acute’ studies documented above, few re- searchers have attempted to manipulate ‘chroni- cally’ carbohydrate availability during training and examine the subsequent physiological, metabolic and performance adaptations that occur. Hansen,

Drust, B. and Morton, P. J.: PROMOTING ENDURANCE TRAINING ... Kinesiology 41(2009) 1:19-24 21 et al. (2005) provided the initial research in this area and showed that training under conditions of low muscle glycogen concentration enhances both biochemical and performance adaptations. These authors employed a one-legged training model in which one limb was trained twice every second day whereas the contra-lateral limb was trained once daily. In this way, both limbs performed the same amount of work throughout training, yet the limb that trained twice per day performed every second training session under conditions of low initial mus- cle glycogen levels. The limb that trained with re- duced muscle glycogen levels displayed signifi cantly greater increases in citrate synthase activity and also performed better on a “time to exhaustion” test. Whilst these data provide some useful insights into the potential for glycogen to modulate training ad- aptations, the specifi c nature of the training proto- col (i.e. one-legged knee extensor exercise) and the applicability of the fi ndings have been questioned in terms of their ecological validity (Hawley, et al., 2008). Furthermore, this study solely focused on the effects of low ‘muscle’ carbohydrate availabil- ity and did not examine any potential interactive effects between muscle and circulating substrate on adaptive responses. Based on this evidence, there seems to be a clear need to complete ‘whole-body’ externally valid training protocols that can simultaneously examine the role of both endogenous and exogenous carbo- hydrate availability on skeletal muscle adaptations to exercise training. Recent work in our laboratory has attempted to bridge this gap in the literature by completing an experimental study to examine the infl uence of both endogenous and exogenous car- bohydrate availability in modulating training-in- duced improvements in exercise performance and mitochondrial related adaptations of human skel- etal muscle. Three groups of subjects completed 6 weeks of high-intensity intermittent running oc- curring four times per week. Group 1 and 2 trained twice per day, two days per week (once in the morn- ing and once in the afternoon where training ses- sions were interspersed with a 3-4 h rest period)

and mitochondrial related adaptations of human skel- etal muscle. Three groups of subjects completed 6 weeks of high-intensity intermittent running oc- curring four times per week. Group 1 and 2 trained twice per day, two days per week (once in the morn- ing and once in the afternoon where training ses- sions were interspersed with a 3-4 h rest period) whereas Group 3 trained once per day four days per week. In this way, each group performed the same amount of work throughout the training pe- riod, yet groups 1 and 2 performed every second training session with reduced pre-exercise muscle glycogen levels. In order to allow us also to exam- ine the effects of exogenous glucose supplementa- tion on infl uencing training adaptations, the sub- jects in Group 1 (LOW+GLU) consumed a carbo- hydrate beverage (6.4%) immediately prior to and at designated intervals throughout every second (i.e. afternoon) training session, whereas the subjects in Group 2 (LOW+PLA) consumed an identical amount of a taste, consistency and odour matched placebo solution at identical times immediately pri- or to and throughout the exercise protocol. In con- trast, subjects in Group 3 (NORM) commenced every training session with normal glycogen stores and consumed no beverages during any of their training sessions. Resting muscle biopsies were ob- tained from the vastus lateralis and gastrocnemius muscles immediately before the fi rst training ses- sion and at 72 h after completion of the training programme. The subjects were also assessed for maximal oxygen uptake and intermittent running performance (Yo-Yo Intermittent Recovery test 2) before and after training interventions. Post-training biopsy samples from both muscles revealed signifi cantly greater increases in SDH ac- tivity in subjects training in the LOW+PLA condi- tion compared with the other two conditions. These data therefore confi rm and extend those fi ndings of Hansen and colleagues by also demonstrating that carbohydrate availability (from both endogenous and exogenous sources) appears to be an impor- tant modulator of the mitochondrial enzyme adap- tations induced during brief periods of endurance training. Interestingly, we also observed that the magnitude of the training-induced increase in

two conditions. These data therefore confi rm and extend those fi ndings of Hansen and colleagues by also demonstrating that carbohydrate availability (from both endogenous and exogenous sources) appears to be an impor- tant modulator of the mitochondrial enzyme adap- tations induced during brief periods of endurance training. Interestingly, we also observed that the magnitude of the training-induced increase in to- tal protein content of PGC1α was similar between groups, thus suggesting that the transcriptional co- -activator PGC1α protein (at least that of total pro- tein) did not provide a mechanistic explanation for our fi ndings. Finally, we also observed similar im- provements in performance between groups sug- gesting that although carbohydrate availability may have the potential to modulate subtle cellular altera- tions, they may not translate into whole body per- formance adaptations. Potential advantages and disadvantages associated with training with low carbohydrate training The data discussed in the present review may be of importance for athletic populations in that it provides initial evidence that carefully scheduled periods of ‘low-carbohydrate’ training may be ben- efi cial for inducing oxidative adaptations of skeletal muscle. Exercising in conditions of reduced car- bohydrate availability likely increases the poten- tial signalling pathways (although these remain to be elucidated precisely) associated with modulat- ing these adaptations, which may ultimately lead to improved metabolic control. However, the limited availability of supporting data in the literature, along with some uncertainty regarding the applicability of data to other popula- tions, currently prevents conclusive support for this training approach. For example, the participants dis- cussed in the preceding studies were recreationally active and thus it remains to be determined whether such observations are also apparent in other popu- lations such as highly trained individuals. Whilst it is possible that such nutritional interventions may

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This review discusses the effects of low carbohydrate training on endurance adaptations.