Fuel for the Work Required: A Theoretical Framework for Carbohydrate Periodization and the Glycogen Threshold Hypothesis

Abstract

Deliberately training with reduced carbohydrate (CHO) availability to enhance endurance-training-induced metabolic adaptations of skeletal muscle (i.e. the 'train low, compete high' paradigm) is a hot topic within sport nutrition. Train-low studies involve periodically training (e.g., 30-50% of training sessions) with reduced CHO availability, where train-low models include twice per day training, fasted training, post-exercise CHO restriction and 'sleep low, train low'. When compared with high CHO availability, data suggest that augmented cell signalling (73% of 11 studies), gene expression (75% of 12 studies) and training-induced increases in oxidative enzyme activity/protein content (78% of 9 studies) associated with 'train low' are especially apparent when training sessions are commenced within a specific range of muscle glycogen concentrations. Nonetheless, such muscle adaptations do not always translate to improved exercise performance (e.g. 37 and 63% of 11 studies show improvements or no change, respectively). Herein, we present our rationale for the glycogen threshold hypothesis, a window of muscle glycogen concentrations that simultaneously permits completion of required training workloads and activation of the molecular machinery regulating training adaptations. We also present the 'fuel for the work required' paradigm (representative of an amalgamation of train-low models) whereby CHO availability is adjusted in accordance with the demands of the upcoming training session(s). In order to strategically implement train-low sessions, our challenge now is to quantify the glycogen cost of habitual training sessions (so as to inform the attainment of any potential threshold) and ensure absolute training intensity is not compromised, while also creating a metabolic milieu conducive to facilitating the endurance phenotype.

Conflict of interest statement

Conflict of Interest

Samuel Impey, Mark Hearris, Kelly Hammond, Jonathan Bartlett, Julien Louis, Graeme Close and James Morton declare that they have no conflicts of interest.

Funding

No sources of funding were used to assist in the preparation of this manuscript.

Figures

Fig. 1

Schematic overview of the potential exercise-nutrient-sensitive cell signalling pathways regulating the enhanced mitochondrial adaptations associated with training with low CHO availability. (1) Reduced muscle glycogen enhances both AMPK and p38MAPK phosphorylation that results in (2) activation and translocation of PGC-1α and p53 to the mitochondria and nucleus. (3) Upon entry into the nucleus, PGC-1α co-activates additional transcription factors (i.e. NRF1/2) to increase the expression of COX subunits and Tfam, as well as autoregulating its own expression. In the mitochondria, PGC-1α co-activates Tfam to coordinate regulation of mtDNA, and induces expression of key mitochondrial proteins of the electron transport chain, e.g. COX subunits. Similar to PGC-1α, p53 also translocates to the mitochondria to modulate Tfam activity and mtDNA expression, and to the nucleus where it functions to increase expression of proteins involved in mitochondrial fission and fusion (DRP-1 and MFN-2) and electron transport chain proteins. (4) Exercising in conditions of reduced CHO availability increases adipose tissue and intramuscular lipolysis via increased circulating adrenaline concentrations. (5) The resulting elevation in FFA activates the nuclear transcription factor, PPARδ, to increase expression of proteins involved in lipid metabolism, such as CPT1, PDK4, CD36 and HSL. (6) However, consuming pre-exercise meals rich in CHO and/or CHO during exercise can downregulate lipolysis (thereby negating FFA-mediated signalling), as well as reducing both AMPK and p38MAPK activity, thus having negative implications for downstream regulators. (7) High-fat feeding can also modulate PPARδ signalling and upregulate genes with regulatory roles in lipid metabolism (and downregulate CHO metabolism), although high-fat diets may also reduce muscle protein synthesis via impaired mTOR-p70S6K signalling, despite feeding leucine-rich protein. 4EBP1 eukaryotic translation initiation factor 4E-binding protein 1, AMPK AMP-activated protein kinase, CHO carbohydrate, CD36 cluster of differentiation 36, COX cytochrome c oxidase, CPT1 carnitine palmitoyltransferase 1, Drp1 dynamin-related protein 1, FA fatty acid, FABP fatty acid binding protein, GLU glucose, GLUT4 glucose transporter type 4, HSL hormone-sensitive lipase, IMTG intramuscular triglycerides, LAT1 large neutral amino acid transporter, LEU leucine, Mfn2 mitofusion-2, mTORC1 mammalian target of rapamycin complex 1, p38MAPK p38 mitogen-activated protein kinase, p53 tumor protein 53,  p70S6K ribosomal protein S6 kinase, PDK4 pyruvate dehydrogenase kinase 4, PGC-1α peroxisome proliferator-activated receptor gamma coactivator 1-α, PPARδ peroxisome proliferator-activated receptor, Tfam mitochondrial transcription factor A

Fig. 2

Overview of studies supporting the glycogen threshold hypothesis. Studies are categorized into those examining a cell signalling, b gene expression and c muscle contractile capacity and post-exercise signalling. In a and b, the green bars represent the trial within the specific study that has been completed with high muscle glycogen, and the red bars represent the trial completed with low muscle glycogen. The length of the bar in both instances corresponds to the pre- and post-exercise muscle glycogen concentration. Additionally, in studies from the authors’ laboratory (Bartlett et al. [38] and Impey et al. [48]), black and white circles represent individual subjects’ pre- and post-exercise muscle glycogen concentrations, respectively. In c, a variety of CHO manipulation protocols have been adopted to examine the effect of high (green bars) and low (red bars) muscle glycogen concentration on contractile properties and post-exercise cell signalling. The shaded area represents a potential muscle glycogen threshold in which exercise should be commenced (albeit specific to the training status of the participants studied in these investigations). AMPK AMP-activated protein kinase, ACC acetyl-CoA carboxylase, Ca2+ calcium, COX cytochrome c oxidase, p38MAPK p38 mitogen-activated protein kinase, p70S6K ribosomal protein S6 kinase, PDK4 pyruvate dehydrogenase kinase 4, PGC-1α peroxisome proliferator-activated receptor gamma coactivator 1-α, Tfam mitochondrial transcription factor A

Fig. 3

Muscle glycogen utilization according to studies incorporating varied exercise intensity, duration, and pre-exercise muscle glycogen concentration. Such data illustrate how the pattern of glycogen use can vary (according to the interactive effects of the aforementioned parameters) and how this should be considered in relation to the proposed glycogen threshold (shaded area). Data represent a sampling from studies compiled from cycling exercise protocols only and represent glycogen use in the vastus lateralis muscle