Sports Med 2003; 33 (2): 117-144

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 1. Regulation of Muscle Glycogen Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 1.1 Glucose Transport . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 1.2 Conversion of Glucose to Glycogen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 2. The Rapid and Slow Phases of Glycogen Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 2.1 The Rapid Phase of Muscle Glycogen Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 2.2 The Slow Phase of Muscle Glycogen Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 3. Timing of Carbohydrate (CHO) Intake . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 4. Amount of CHO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 5. Presence of Other Nutrients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130 6. Type of CHO Ingested . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132 7. Form of CHO Intake . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133 8. Factors Related to Post-Exercise Glycogen Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133 8.1 Training Status . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133 8.2 Feeding Schedule . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134 8.3 Magnitude of Muscle Glycogen Depletion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 8.4 Muscle Fibre Types . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136 8.5 Mode of Exercise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137 9. Limitations of Muscle Glycogen Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138 10. Directions for Future Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 11. Practical Implications, Guidelines and Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 The pattern of muscle glycogen synthesis following glycogen-depleting exerAbstract cise occurs in two phases. Initially, there is a period of rapid synthesis of muscle glycogen that does not require the presence of insulin and lasts about 30–60 minutes. This rapid phase of muscle glycogen synthesis is characterised by an exercise-induced translocation of glucose transporter carrier protein-4 to the cell surface, leading to an increased permeability of the muscle membrane to glucose. Following this rapid phase of glycogen synthesis, muscle glycogen synthesis occurs at a much slower rate and this phase can last for several hours. Both muscle contraction and insulin have been shown to increase the activity of glycogen synthase, the rate-limiting enzyme in glycogen synthesis. Furthermore, it has been shown that muscle glycogen concentration is a potent regulator of glycogen 118 Jentjens & Jeukendrup synthase. Low muscle glycogen concentrations following exercise are associated with an increased rate of glucose transport and an increased capacity to convert glucose into glycogen. The highest muscle glycogen synthesis rates have been reported when large amounts of carbohydrate (1.0–1.85 g/kg/h) are consumed immediately post-exercise and at 15–60 minute intervals thereafter, for up to 5 hours post-exercise. When carbohydrate ingestion is delayed by several hours, this may lead to ~50% lower rates of muscle glycogen synthesis. The addition of certain amino acids and/ or proteins to a carbohydrate supplement can increase muscle glycogen synthesis rates, most probably because of an enhanced insulin response. However, when carbohydrate intake is high (≥1.2 g/kg/h) and provided at regular intervals, a further increase in insulin concentrations by additional supplementation of protein and/or amino acids does not further increase the rate of muscle glycogen synthesis. Thus, when carbohydrate intake is insufficient (<1.2 g/kg/h), the addition of certain amino acids and/or proteins may be beneficial for muscle glycogen synthesis. Furthermore, ingestion of insulinotropic protein and/or amino acid mixtures might stimulate post-exercise net muscle protein anabolism. Suggestions have been made that carbohydrate availability is the main limiting factor for glycogen synthesis. A large part of the ingested glucose that enters the bloodstream appears to be extracted by tissues other than the exercise muscle (i.e. liver, other muscle groups or fat tissue) and may therefore limit the amount of glucose available to maximise muscle glycogen synthesis rates. Furthermore, intestinal glucose absorption may also be a rate-limiting factor for muscle glycogen synthesis when large quantities (>1 g/min) of glucose are ingested following exercise. Muscle glycogen is the primary fuel source durcentrations can increase to above ‘normal’ levels in the previously exercised muscle, a process often ing prolonged moderate-to-high intensity exerreferred to as glycogen supercompensation.[12] cise.[1] Fatigue during prolonged exercise is often associated with muscle glycogen depletion[2,3] and While dietary interventions to achieve supercomtherefore high pre-exercise muscle glycogen levels pensated muscle glycogen concentrations in prepaare believed to be essential for optimal performration for competition have been well defined,[13-16] these procedures do not address the problem of ance.[4-7] The restoration of muscle glycogen stores athletic events that require rapid synthesis of muscle following exhaustive exercise is probably the most glycogen within a short period of time (<8 hours). important factor determining the time needed to Athletes may train or compete more than once per recover. It appears that muscle glycogen synthesis in day, and some events require qualification <8 hours the post-exercise recovery period has such high metbefore the actual event. Although it is unlikely that abolic priority that intramuscular triglycerides are muscle glycogen stores can be completely broken down at an increased rate to supply lipid fuel resynthesised within hours, it would be of benefit to for oxidative muscle metabolism.[8] Depending on the athlete to define nutrition guidelines that would the extent of glycogen depletion and provided that maximise the rate of glycogen storage in the early sufficient carbohydrate (CHO) is consumed, the hours post-exercise. complete restoration of muscle glycogen can occur within 24 hours.[2,9-11] Furthermore, it has been In this review a detailed summary of the literature shown that when a high-CHO diet is consumed for on post-exercise muscle glycogen synthesis during at least 3 days after exercise, muscle glycogen conshort-term recovery (<8 hours) will be presented.  Adis Data Information BV 2003. All rights reserved. Sports Med 2003; 33 (2) Muscle Glycogen Synthesis Post-Exercise 119 The main questions that will be addressed are: what in very low abundance in skeletal muscle and is are the best nutritional strategies to obtain maximal suggested to play a role in basal glucose uptake by muscle glycogen synthesis rates following exercise the muscle.[20] In the unstimulated state, the and which factors limit the ability of skeletal muscle GLUT-4 isoform is located intracellularly and is to synthesise glycogen. The purpose of this review is translocated to the plasma membrane when insulin to give a comprehensive overview and critical disbinds to its receptor. Muscle contractions stimulate cussion of the research that has addressed the factors glucose transport directly, independent of insulin affecting post-exercise muscle glycogen synthesis. action, by inducing the GLUT-4 transporter to the This review will conclude with guidelines for CHO cell surface (figure 1).[21,22] The observation that ingestion post-exercise to achieve high rates of musmaximal insulin stimulation and contraction have cle glycogen synthesis and to maintain high muscle additive effects on translocation of GLUT-4 in musglycogen concentrations for daily training or comcle may suggest the presence of two different pools petition. It should be noted that results of different of glucose transporters.[18,21] However, the exact instudies are sometimes difficult to compare because tracellular locations of the putative exerciseand of differences in experimental designs, such as variinsulin-stimulated GLUT-4 pools (pools A and B, ations in biopsy methods, site of biopsy taking, respectively in figure 1) have not yet been elucidattiming of biopsy taking, preand post-exercise mused. The maximal rate of muscle glucose transport is cle glycogen concentrations and training status of determined by both the total GLUT-4 concentration participants. The reader should keep this in mind and the proportion that is translocated to the cell when interpreting the results of various studies. In membrane in response to insulin and/or muscle conorder to facilitate comparison of data between studtraction.[23] Furthermore, the intracellular signalling ies, muscle glycogen synthesis rates in this review pathways that lead to insulinand exercise-stimulatare all expressed as mmol/kg dry weight (dw)/h, ed GLUT-4 translocation are also different. Insulin unless otherwise stated. Therefore, muscle glycogen activates a phosphatidylinositol-3-kinase-dependent concentrations reported in the literature as mmol/kg mechanism, whereas the contraction signal may be wet weight (ww), were multiplied by 4.28 to acinitiated by calcium (Ca2+) release from the count for water weight.[17] sarcoplasmic reticulum, leading to the activation of other signalling intermediaries (e.g. protein kinase 1. Regulation of Muscle C). Other possible signals that trigger exercise-inGlycogen Synthesis duced GLUT-4 translocation are: increased concentrations of nitric oxide and adenosine, increased activity of AMPK and low muscle glycogen concen1.1 Glucose Transport trations. The importance of the GLUT-4 transporters Replenishment of muscle or liver glycogen stores for muscle glycogen synthesis will be further disrequires glucose derived from the diet or glucose cussed in section 2.1. In addition, for more detailed resulting from gluconeogenesis. In the postabsorbinformation on this topic the reader is referred to tive state, the majority of glucose for glycogen synreviews by Ivy and Kuo[24] and by Richter et al.[25] thesis comes from orally ingested CHO. The first step in the pathway of muscle glycogen synthesis is 1.2 Conversion of Glucose to Glycogen the transport of glucose across the muscle cell membrane (figure 1). Glucose transport in the skeletal Upon entering the muscle cell, glucose is rapidly muscle occurs primarily by facilitated diffusion, phosphorylated to glucose-6-phosphate (G6P) by utilising glucose transporter carrier proteins the enzyme hexokinase (figure 1).[26] G6P is then (GLUT).[18] Two isoforms of the facilitative glucose converted to glucose-1-phospate (G1P) by the actransporter family, GLUT-4 and GLUT-1, are extion of phosphoglucomutase. Thereafter, uridine pressed in the skeletal muscle.[19] GLUT-1 is present diphosphate glucose (UDP-glucose) is synthesised  Adis Data Information BV 2003. All rights reserved. Sports Med 2003; 33 (2) 120 Jentjens & Jeukendrup GLUT-4 Pool (B) IRS-1 PI-3-kinase GLUT-4 translocation Glycogen particles Insulin Proglycogen Macroglycogen (Phosphorylase + debranching enzyme) UDP