Review Article

Sports Medicine 11 (1): 6-19, 1991 0112-1642/91/0001-0006/$07.00/0 © Adis International Limited All rights reserved. SPORT2343

Muscle Glycogen Synthesis Before and After Exercise John L. Ivy Exercise Physiology and Metabolism Laboratory, Department of Kinesiology, University of Texas at Austin, Austin, Texas, USA

Contents

Summary .................. .. .. .............. ............................................................................. ................... ... 6 I. Regulation of Muscle Glycogen Synthesis ................... .......... ..... ..... .............. .... ..... ............... 8 2. Muscle Glycogen Stores Following Exercise ................................. ....... ........... ...................... 9 2.1 Mechanisms Responsible for the Rapid Phase of Muscle Glycogen Storage After Exercise .. ...... ................. .. ............ ............................................................................. .. 9 2.2 Mechanisms Responsible for the Slow Phase of Muscle Glycogen Storage After Exercise ..................................................................... ................... ............................ 10 3. Effect of Diet on Glycogen Resynthesis ................................... ..... ............. ..... .. .. .... ..... ....... II 3.1 Glycogen Supercompensation Regimens ........................................ ............................. .. 12 4. Muscle Glycogen Storage Immediately After Exercise .............. ........................... .. .......... .. 13 4.1 Glycogen Storage Upon Completion of Exercise .......... ....... ............. ......... .. ................ 13 4.2 Timing of Carbohydrate Consumption After Exercise ................. ................ ............... 13 4.3 The Effect of Multiple Supplements and Different Amounts of Carbohydrate ........ 14 4.4 The Effect of Glucose Infusion ...................................................................................... 16 5. Recommendations for the Endurance Athlete ..................... .... ............ .......... ..................... 17

Summary

The importance of carbohydrates as a fuel source during endurance exercise has been known for 60 years. With the advent of the muscle biopsy needle in the 1960s, it was determined that the major source of carbohydrate during exercise was the muscle glycogen stores. It was demonstrated that the capacity to exercise at intensities between 65 to 75% V02max was related to the pre-exercise level of muscle glycogen, i.e. the greater the muscle glycogen stores, the longer the exercise time to exhaustion. Because of the paramount importance of muscle glycogen during prolonged, intense exercise, a considerable amount of research has been conducted in an attempt to design the best regimen to elevate the muscle's glycogen stOres prior to competition and to determine the most effective means of rapidly replenishing the muscle glycogen stores ·after exercise. The rate-limiting step in glycogen synthesis is the transfer of glucose from uridine diphosphate-glucose to an amylose chain. This reaction is catalysed by the enzyme glycogen synthase which can exist in a glucose-6-phosphate-dependent, inactive form (D-form) and a glucose-6-phosphate-independent, active form (I-form). The conversion of glycogen synthase from one form to the other is controlled by phosphorylation-dephosphorylation reactions. The muscle glycogen concentration can vary greatly depending on training status, exercise routines and diet. The pattern of muscle glycogen resynthesis following exerciseinduced depletion is biphasic. Following the cessation of exercise and with adequate

7

Muscle Glycogen Synthesis

carbohydrate consumption, muscle glycogen is rapidly resynthesised to near pre-exercise levels within 24 hours. Muscle glycogen then increases very gradually to above-normal levels over the next few days. Contributing to the rapid phase of glycogen resynthesis is an increase in the percentage of glycogen synthase I, an increase in the muscle cell membrane permeability to glucose, and an increase in the muscle's sensitivity to insulin. The slow phase of glycogen synthesis appears to be under the control of an intermediate form of glycogen synthase that is highly sensitive to glucose-6-phosphate activation. Conversion of the enzyme to this intermediate form may be due to the muscle tissue being constantly exposed to an elevated plasma insulin concentration subsequent to several days of high carbohydrate consumption. For optimal training performance, muscle glycogen stores must be replenished on a daily basis. For the average endurance athlete, a daily carbohydrate consumption of 500 to 600g is required. This results in a maximum glycogen storage of 80 to 100 ~molfg wet weight. To glycogen supercompensate in preparation for competition, the muscle glycogen stores must first be exercise-depleted. This should then be followed with a natural training taper. During the first 3 days of tapering, a mixed diet composed of 40 to 50% carbohydate should be consumed. During the last 3 days of tapering, a diet consisting of 70 to 80% carbohydrate is consumed. This procedure results in muscle glycogen concentrations that are comparable to those produced by more rigorous regimens that can result in chronic fatigue and injury. For rapid resynthesis of muscle glycogen stores, a carbohydrate supplement in excess of I g/kg bodyweight should be consumed immediately after competition or after a training bout. Continuation of supplementation every 2 hours will maintain a maximal rate of storage up to 6 hours after exercise. Supplements composed of glucose or glucose polymers are more effective for the replenishment of muscle glycogen stores after exercise than supplements composed ofpredominantiy fructose. However, some fructose is recommended because it is more effective than glucose in the replenishment of liver glycogen.

The importance of carbohydrates as a fuel source during prolonged, endurance exercise has been recognised for more than 60 years. Levine and associates (1924) found that blood glucose levels of runners fell from approximately 90 ml/dl to 45 ml/ dl during a 25-mile (40km) race. It was noted that the participants were physically fatigued and somewhat disoriented. Christensen and Hansen (1939a,b), reported that a high-carbohydrate diet would significantly enhance endurance during prolonged exercise. They found that time to exhaustion was accompanied by hypoglycaemia and that ingestion of a carbohydrate supplement at the time of exhaustion rapidly returned the blood glucose concentration back to normal and allowed considerable additional exercise to be performed. From these observations, it was generally believed that fatigue during prolonged aerobic exercise resulted from a reduced blood glucose concentration which was due to the depletion of the liver glycogen stores.

It was not until the 1950s that the importance of muscle glycogen as a fuel source during prolonged aerobic exercise was recognised. One of the first to realise the relationship between muscle glycogen and fatigue was Grollman (1955). He found that the aerobic endurance and muscle glycogen concentration of trained rats were significantly greater than those of untrained rats. With the development of the biopsy needle in the early 1960s it became practical to investigate the relationship between muscle glycogen and aerobic endurance in humans. The major work in this area was conducted by several Scandinavian research groups (Ahlborg et al. I 967b; Bergstrom et al. 1967; Bergstrom & Hultman 1967a; Hermansen et al. 1965; Hultman 1967). In general, these investigators demonstrated that with increasing intensity of exercise there was an increased reliance on muscle glycogen, and that one's perception of fatigue during moderately intense exercise paralleled the de-

Sports Medicine 11 (1) 1991

8

clining muscle glycogen stores. It was also found that the capacity to exercise at work rates between 70 to 85% of V02max was related to the initial muscle glycogen stores, and that the increase in endurance capacity following training or diets high in carbohydrates was partially due to increased muscle glycogen stores (Ahlborg et al. 1967b; Bergstrom et al. 1967; Bergstrom & Hultman I 967a; Hermansen et al. 1965; Hultman 1967). Because of the paramount importance of muscle glycogen during intense prolonged exercise, methods for increasing its concentration above normal, and for its rapid restoration following exercise have been extensively investigated. This review summarises our current understanding of: (a) the regulation of muscle glycogen synthesis; (b) the effect of diet on muscle glycogen synthesis; and (c) methods for rapid muscle glycogen replenishment immediately after exercise. The review concludes with recommendations on how to increase and maintain muscle glycogen stores for competition and training.

1. Regulation 0/ Muscle Glycogen Synthesis Upon entering the cell, glucose is rapidly converted to glucose-6-phosphate (G6P) by the enzyme hexokinase. The G6P is then converted to glucose-I-phosphate (G 1P) by phosphoglucomutase. Next, uridine triphosphate and GIP are combined to form uridine diphosphate-glucose (UDPglucose) which serves as a glycosyl carrier. The glucose attached to the UDP-glucose is then transferred to the terminal glucose residue at the nonreducing end of an amylose chain to form an a(l .....4) glycosidic linkage. This reaction is catalysed by the enzyme glycogen synthase. Amylo (1,4-+1,6) transglycosylase catalyses the transfer of a terminal oligosaccharide fragment of 6 or 7 glucosyl residues from the end of the amylose chain to the 6-hydroxyl group of a glucose residue of the same or another chain. This occurs in such a manner as to form an a( 1-+6) linkage and thus create a branch point and glycogen. It is believed that the rate-limiting reaction for

the formation of glycogen is the transfer of glucose from UDP-glucose to an amylose chain. This reaction is controlled by the enzyme glycogen synthase. Glycogen synthase is known to exist in 2 interconvertible forms, the I-form and the D-form (Danforth 1965; Lamer et al. 1963). The I-form, which is considered the active form, is independent of G6P for its activation. The D-form, which is considered the inactive form, is dependent on G6P for its activation. The conversion of glycogen synthase from one form to the other is controlled by phosphorylation-dephosphorylation reactions. Glycogen synthase can be phosphorylated at 3 to 6 sites, and is phosphorylated by several kinases, including cAMP-dependent protein kinase, glycogen synthase kinase, casein kinase and calmodulindependent multiprotein kinase (Huang & Huang 1980; Roach & Lamer 1977). When 3 or more sites are phosphorylated on glycogen synthase, the enzyme is converted to the less active D-form. When dephosphorylated by the action of glycogen synthase phosphatase, its activity progressively increases with decreasing phosphate content until it is completely active in the absence of G6P (Roach & Lamer 1976; Roach & Lamer 1977). Typically, the activity of glycogen synthase is expressed as the ratio of enzyme in the I form to total enzyme activity (I/I+D). This is referred to as the activity ratio. However, it has been demonstrated that the enzyme can exist in intermediate forms which have a depressed activity ratio but enhanced sensitivity to G6P (Guinovart et al. 1979; Kochan et al. 1979; Kochan et al. 1981).

2. Muscle Glycogen Stores Following Exercise Muscle glycogen stores are quite variable depending on training status, exercise patterns and previous diet. In untrained, sedentary individuals, muscle glycogen stores range between 80 to 100 "mol/g wet weight (Bergstrom & Hultman 1967a; Hultman 1967). Trained individuals who are exercising daily and consuming a normal diet (45 to 50% carbohydrate) typically have muscle glycogen stores of about 130 to 135 "mol/g wet weight

Muscle Glycogen Synthesis

(Sherman 1981). If trained individuals cease training for several days, their muscle glycogen stores will rise to approximately 170 to 180 I'mol/g wet weight (Bergstrom et al. 1967), and if during this rest period they consume a high carbohydrate diet (70% carbohydrate), their muscle glycogen concentration may exceed 210 I'mol/g wet weight (Bergstrom et aI. 1967; Sherman et aI. 1983). Rapid synthesis of muscle glycogen occurs in response to carbohydrate feeding following an exercise bout that significantly lowers the muscle glycogen stores. This was exquisitely demonstrated by Bergstrom and Hultman (1 976b). Two subjects performed I-legged cycling activity at 75% V02max until the exercising leg was exhausted. They then rested for 3 days while consuming a high carbohydrate diet. Muscle biopsies were taken from the vastus lateralis at exhaustion and at 24-hour intervals for 3 days. It was found that the depletion of muscle glycogen was localised to the exercised muscle and that the subsequent glycogen synthesis resulted in muscle glycogen stores above the preexercise level. After 3 days, the exercised leg had increased its glycogen stores by more than 2-fold above the pre-exercise level, while the nonexercised leg's glycogen content remained relatively unchanged. From this experiment it was concluded that glycogen synthesis following exercise glycogen synthesis was localised to muscle recruited during the exercise and depleted of its glycogen stores, and that to raise the muscle glycogen concentration above normal (supercompensation) some form of depleting exercise must first be employed. Subsequent studies have demonstrated that the pattern of resynthesis of muscle glycogen stores following exercise-induced depletion is a biphasic response (Bergstrom et aI. 1967; Kochan et aI. 1979; Yakovlev 1968). Following the cessation of exercise and with adequate carbohydrate consumption, muscle glycogen is rapidly resynthesised to near preexercise levels within 24 hours, provided there has not been prior muscle glycogen supercompensation. Muscle glycogen then increases very gradually to above-normal levels over the next few days. This suggests that 2 phases of glycogen synthesis exist following exercise: (a) a rapid phase of resynthesis

9

to the pre-exercise level which is related to the acute depletion of the muscle's glycogen stores; and (b) a slow phase of synthesis above the pre-exercise level which is dependent on carbohydrate consumption and physical activity pattern. 2.1 Mechanisms Responsible for the Rapid Phase of Muscle Glycogen Storage After Exercise It is well documented that glycogen plays an important role in regulating the activity of glycogen synthase (Adolfsson 1973; Bergstrom et aI. 1972; Danforth 1965). Generally, the percentage of glycogen synthase in the I-form is inversely related to the muscle glycogen concentration, i.e. as the muscle glycogen concentration declines the percentage of glycogen synthase in the I-form increases. Conversely, as the glycogen concentration increases the percentage of glycogen synthase in the D-form increases. The reason for the inverse relationship between muscle glycogen content and glycogen synthase I activity may relate to the binding of both glycogen synthase and glycogen phosphatase to glycogen as part of a glycogen protein complex that also includes glycogen phosphorylase (Fischer et aI. 1971). When the glycogen concentration decreases, both glycogen synthase and glycogen phosphatase are released, enabling the active phosphatase to catalyse dephosphorylation of glycogen synthase thus converting it to its I-form. An exercise-induced increase in glycogen synthase activity can catalyse the rapid restoration of glycogen only if adequate substrate is available. Thus, the second factor that makes possible the rapid increase in muscle glycogen is an increase in the permeability of the muscle cell membrane to glucose. In this respect muscle contractions have a strong and protracted insulin-like effect on the permeability of muscle to glucose (Fell et aI. 1982; Holloszy & Narahara 1965; Ivy 1987; Ivy & Holloszy 1981; Richter et aI. 1982). This affect can last for a long time and appears to be inversely related to the muscle glycogen concentration (Fell et aI. 1982; Richter et aI. 1984). Muscle contraction also increases the muscle's sensitivity to insulin (Ri-

Sports Medicine 11 (J) 1991

10

2.2 Mechanisms Responsible for the Slow Phase of Muscle Glycogen Storage After Exercise

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Fig. 1. The activity of muscle glycogen synthase in the absence (-) and presence (--) of insulin of different concentrations of glycogen. Note that insulin alters the .position, but not the general shape, of the curve relating glycogen to synthase I activity [after Danforth (1965) with permission].

chter et al. 1982; Richter et al. 1984). Thus, the increase in membrane permeability to glucose and muscle insulin sensitivity, together with the activation of glycogen synthase, allows for the rapid resynthesis of glycogen following exercise. Carbohydrate feeding accentuates these effects by increasing plasma insulin and glucose concentrations. The increase in circulating insulin not only functions to increase muscle glucose uptake, but also functions to keep glycogen synthase activity high (Danforth 1965; Lamer et al. 1963). In the presence of insulin the percentage of glycogen synthase I is increased for a given glycogen concentration (fig. 1) which indicates that insulin's effect on glycogen synthase is independent of the glycogen concentration (Danforth 1965). With an increase in the plasma glucose concentration, the glucose uptake rate increases regardless of the level of muscle permeability to glucose (Nesher et al. 1985). Therefore, the increase in glucose concentration functions to increase the rate of glucose uptake, further increasing substrate availability.

The regulatory mechanisms responsible for the slow rise in muscle glycogen above normal levels (glycogen supercompensation) are not as well understood as those that control the rapid phase of glycogen synthesis. It is evident that the exercise-induced increase in muscle permeability to glucose and the depletion of muscle glycogen are, together, not sufficient to result in glycogen supercompensation, since only a small increase in muscle glycogen occurs following exercise in the absence of carbohydrate feeding (Bergstrom et al. 1967; Bergstrom & Hultman 1967b; Ivy et al. 1988b; Maehlum & Hermansen 1978). Probable factors that prevent muscle glycogen supercompensation in the fasted state are a depressed circulating insulin concentration, and an increase in plasma free fatty acids and fatty acid oxidation by muscle (Ivy et al. 1988a). These conditions are actually advantageous during fasting as they serve to slow muscle glucose uptake and conserve blood glucose for use by the nervous system until sufficient carbohydrate is available. The finding that glycogen supercompensation occurs only in muscle that has been exercise-depleted of its glycogen stores suggests that the high level of insulin and glucose that result from carbohydrate loading are also insufficient to induce glycogen supercompensation (Bergstrom & Hultman 1967b; Hultman 1967). However, it has been demonstrated that elevated plasma insulin is a prerequisite. This is evidenced by the finding that alloxan diabetic rats are incapable of increasing their muscle glycogen stores above pre-exercise levels following a glycogen supercompensation regimen (Ivy 1977). A persistent increase in the percentage of glycogen synthase I is also an unlikely mechanism to account for glycogen supercompensation. Although the percentage of glycogen synthase in the I form may be as high as 80% following exercise-induced glycogen depletion, as glycogen levels are normalised the percentage of glycogen synthase I decreases back to the pre-exercise level or lower in a

11

Muscle Glycogen Synthesis

negative feedback manner (Adolfsson 1973; Bergstrom et al. 1972; Danforth 1965; Terjung et al. 1974). This paradox of glycogen synthesis occurring in spite of an extremely low activity ratio was examined by Kochan et al. (1981). They found that during the slow synthesis phase of a glycogen supercompensation regimen glycogen synthase was in an intermediate form which had a depressed activity ratio but had enhanced sensitivity to activation by G6P. They suggested that this intermediate form of the enzyme was responsible for glycogen synthesis during the supercompensation phase. It has also been demonstrated that the insulin response to carbohydrate loading increases over subsequent days while glucose tolerance remains the same or actually improves (Ivy et al. 1985). This increase in insulin response to carbohydrate loading is thought to be the result of an increase in the pancreatic response to glucose (Szanto & Yudkin 1969). Since insulin is required for glycogen supercompensation, it is possible that the hyperinsulinaemic response following several days of high carbohydrate consumption is responsible for the increased sensitivity of glycogen synthase to G6P. The elevated plasma insulin may also serve to increase the rate of muscle glucose transport, thus increasing the availability of glucose to glycogen synthase, as well as possibly increasing the intracellular concentration of G6P. Hexokinase activity in muscle is also increased during subsequent days of carbohydrate loading (Ivy et al. 1983). This too could be of functional significance since an increase in hexokinase activity would prevent the rate limiting step in glucose uptake from shifting from transport to glucose phosphorylation as the G6P concentration increased. In summary, the slow rise in muscle glycogen during the supercompensation phase of synthesis appears to be under the control of an intermediate form of glycogen synthase with increased sensitivity to activation of G6P. This alteration by glycogen synthase may result from an elevated plasma insulin concentration exerting its effect on the enzyme secondary to high carbohydrate ingestion.

3. Effect of Diet on Glycogen Resynthesis The rate of muscle glycogen storage following exercise is dependent on the amount of carbohydrate consumed. Unless sufficient carbohydrate is ingested, muscle glycogen will not be normalised on a day-to-day basis between training bouts, nor will efforts to supercompensate muscle glycogen stores be successful. In general, with an increase in carbohydrate ingestion there is an increase in muscle glycogen storage. Costill et al. (1981) reported that consuming 150 to 650g of carbohydrate per day resulted in a proportionately greater muscle glycogen synthesis during the initial 24-hours after exercise, and that consumption of more than 600g of carbohydrate per day was of no additional benefit (fig. 2). It was also demonstrated by Costill et al. (1971) that when the carbohydrate concentration of the diet was inadequate, successive days of intense, prolonged exercise resulted in a gradual reduction in the muscle glycogen stores and a deterioration in performance. The type of carbohydrate consumed also appears to have an effect on the rate of glycogen resynthesis following exercise (Costill et al. 1971). Subjects that had depleted their muscle glycogen stores by running were fed either a starch or glucose diet (650g CHO/day) during the 2 days fol-

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12

lowing depletion. During the first 24 hours there was no difference in the synthesis of muscle glycogen between the 2 diets. However, aftt;r the second day, the starch diet resulted in a significantly greater glycogen synthesis than the glucose diet. It was suggested that the difference in treatments may have been due to different effects on insulin secretion. Generally starches, as compared to glucose, are better able to maintain elevated plasma insulin levels (Hodges & Krehl 1965). Therefore, consuming starch-based diets in the time period following the initial 24 hours after exercise may result in relatively larger amounts of muscle glycogen storage than equivalent glucose-based diets. The effect of simple dietary carbohydrates on glycogen storage has also been evaluated. Blom et aI. (1987) found that ingestion of glucose and sucrose was twice as effective as fructose for restoration of muscle glycogen. They suggested that the differences between the glucose and fructose supplementations were the result of the way the body handles these sugars. Fructose metabolism takes place predominantly in the liver (Zakin et aI. 1969), whereas the majority of glucose appears to bypass the liver and be stored or oxidised by the muscle (Maehlum et aI. 1978). When infused, fructose has been found to result in a 4 times greater liver glycogen storage than glucose (Nilsson & Hultman 1974). On the other hand, a considerably higher glycogen storage rate has been demonstrated in skeletal muscle after glucose than after fructose infusion (Bergstrom & Hultman I 967c). The similar rates of glycogen storage for the sucrose and glucose supplements could not be accounted for by Blom et al. (1987). Sucrose contains equimolar amounts of glucose and fructose. If muscle glycogen storage was chiefly dependent on the glucose moiety of the disaccharide, one should expect a lower rate of glycogen storage from sucrose than from a similar amount of glucose. One possible explanation provided by Blom et aI. (1987) was that fructose, by virtue of its rapid metabolism in the liver, compared with that of glucose, inhibits postexercise hepatic glucose uptake, thereby rendering a large proportion of absorbed glucose available for muscle glycogen synthesis.

Sports Medicine 11 (1) 1991

3.1 Glycogen Supercompensation Regimens The discovery by Bergstrom and Hultman (l967b) that a high carbohydrate diet following the depletion of muscle glycogen by exercise would result in an above normal muscle glycogen concentration led to a series of studies to identify the regimen of exercise and diet that would best supercompensate the muscle glycogen stores. Bergstrom et aI. (1967) had subjects exercise to exhaustion to deplete their muscle glycogen stores. Six of the subjects then received a high fat-protein diet for 3 days. This was followed by another exhaustive exercise bout and 3 days of a high carbohydrate diet. The remaining 3 subjects followed the same protocol as above except the order of administration of the diets was reversed. When the high carbohydrate diet followed the high-fat protein diet, the muscle glycogen concentration was 205.5 #lmol/g wet weight following the high carbohydrate diet. This concentration was 100% above the initial muscle glycogen concentration. When the high carbohydrate diet preceded the high fat-protein diet, the muscle glycogen concentration was 183.9 #lmol/g wet weight following the high carbohydrate diet. It was suggested that a period of carbohydrate-free diet further stimulated glycogen synthesis when carbohydrates were given following exercise. Based on this study and several similar studies (Ahlborg et a1. 1967a; Bergstrom & Hultman 1967a), it was recommended that the best way to glycogen supercompensate was to: (a) deplete the muscle glycogen stores with an exhaustive exercise bout; (b) eat a carbohydrate-free diet for 3 days; (c) deplete the glycogen stores once more with an exhaustive exercise bout; and (d) consume a high carbohydrate diet for 3 days. Because of the strenuous nature of this regimen many athletes have found it impractical. The 3 days of low carbohydrate diet may cause hypoglycaemia, irritability and chronic fatigue. The 2 bouts of exhaustive exercise prior to competition may result in injury, soreness and fatigue, and may prevent a proper taper before competition. To address this problem, Sherman et a1. (1981) studied 3 types of muscle glycogen supercompensation regimens

Muscle Glycogen Synthesis

13

4. Muscle Glycogen Storage Immediately After Exercise

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Fig. 3. A comparison of the classical (Bergstrom et al. 1967) [3 days low (25%) carbohydrate, 3 days high carbohydrate] and modified (Sherman et al. 1981) [3 days mixed (50% car-

bohydrate) diet, 3 days high carbohydrate] glycogen supercompensation regimens during 6 days of exercise tapering after exhaustive exercise on day O. The 2 values for the classical regimen on day 3 represent before and after a high intensity exercise bout [after Sherman (1983) with permission].

Although methods of increasing muscle glycogen to above normal levels in preparation for competition and maintaining normal glycogen levels on a day-to-day basis have been defined, there has been little research on how to maximise glycogen storage during the hours immediately following exercise. It should also be pointed out that the maximum amount of muscle glycogen stored when fed a high carbohydrate diet during the 24 hours immediately after exercise is approximately 80 I'mol/ g (Costill et al. 1981). Thus, it is likely that daily intensive exercise training could result in deficient muscle glycogen stores even when consuming a high carbohydrate diet. 4.1 Glycogen Storage Upon Completion of Exercise

on 6 trained runners. On 6 consecutive days, the subjects ran at 73% of ~02max for 90, 40, 40, 20 and 20 minutes and rested, respectively. During each taper the subjects received one of 3 diets: (a) a mixed diet composed of 50% carbohydrate (control diet); (b) a low carbohydrate diet (25% carbohydrate) for the first 3 days and a high carbohydrate (70% carbohydrate) for the last 3 days (classical diet); and (c) a mixed diet (50% carbohydrate) for the first 3 days and a high carbohydrate diet (70% carbohydrate) the last 3 days (modified diet). Muscle biopsies were obtained on the morning of the fourth and seventh days of each trial. During the control treatment, muscle glycogen concentrations of the gastrocnemius were 135 and 163 I'mol/g wet weight on days 4 and 7, respectively. During the classical treatment, the corresponding muscle glycogen concentrations were 80 and 210 I'mol/g wet weight respectively, and during the modified treatment they were 135 and 204 I'mol/g wet weight, respectively (fig. 3). These results suggest that a normal training taper in conjunction with a moderate carbohydrate-high carbohydrate diet sequence is as effective as the classical glycogen supercompensation regimen.

When a carbohydrate supplement is provided immediately after exercise, the rate of glycogen storage has generally been reported to be between 5 to 8 I'mol/g wet weight/h (Ivy et al. 1988a; Keizer et aI. 1986; Maehlum et aI. 1977; Maehlum et aI. 1978). Maehlum et al. (1978) found that ingestion of loog (1.44 g/kg of bodyweight) of glucose 15 minutes after an exhaustive bicycle exercise resulted in a glycogen storage rate of 7.1 I'mol/g wet weight/h in the quadriceps during the subsequent 135 minutes. Maehlum et al. (1977) aIso found a similar rate of glycogen storage following exercise when a carbohydrate-rich diet was consumed. Keizer et al. (1986) reported that providing approximately 300g of carbohydrate in either liquid or solid form after exercise resulted in a glycogen storage rate of approximately 5 I'mol/g wet weight! h over the first 5 hours of recovery. 4.2 Timing of Carbohydrate Consumption After Exercise In agreement with previous research findings, we have observed rates of glycogen storage between 5 to 8 I'mol/g wet weight!h during the hours

Sports Medicine 11 (1) 1991

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immediately after exercise when a carbohydrate supplement was provided (Ivy et al. 1988a,b; Reed et al. 1989). In the first of 3 studies, we investigated the effect that the time of administering the carbohydrate supplement had on muscle glycogen recovery postexercise. Two grams of glucose polymers/kg of bodyweight were administered in a 23% solution either immediately following exercise (PEX) or 2 hours after exercise (2P-EX) [Ivy et al. 1988a). During the first 2 hours postexercise, the rate of muscle glycogen storage was 7.7 /oLmol/g wet weight/ h for the P-EX treatment, but only 2.5 /oLmol/g wet weight/h for the 2P-EX treatment. During the second 2 hours of recovery, the rate of glycogen storage slowed to 4.3 /oLmol/g wet weight/h during treatment P-EX, but increased to 4.1 /oLmol/g wet weight/ h during treatment 2P-EX (fig. 4). However, even with the increase, the rate of storage during the 2PEX treatment was still 45% slower than that for the P-EX treatment during the first 2 hours of recovery. These results suggest that delaying the

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Fig. 4. Muscle glycogen storage during the first 2 hours and second 2 hours of recovery for the P-EX treatment (Ii) and the 2P-EX treatment (_). * Significantly different than the basal rate of storage, represented by the glycogen storage rate during the first 2 hours postexercise of treatment 2P-EX, and significantly different from treatment 2P-EX during the second 2 hours of recovery (p < 0.05); P-EX ingestion of the supplement immediately postexercise [after Ivy et al. (\988a) with permission).

ingestion of a postexercise carbohydrate supplement will result in a reduced rate of muscle glycogen storage. It was also noted that the fall in the glycogen storage rate during the P-EX treatment was accompanied by a decline in the blood glucose and insulin levels. We therefore investigated the possibility that the initial rate of glycogen storage following a postexercise carbohydrate supplement could be sustained by maintaining elevated blood glucose and insulin concentrations with multiple supplements. We also investigated whether the rate of muscle glycogen storage could be enhanced during the initial 4-hour postexercise period by substantially increasing the amount of the carbohydrate consumed (Ivy et al. I 988a). 4.3 The Effect of Multiple Supplements and Different Amounts of Carbohydrate Riders cycled for 2 hours on 3 separate occasions to deplete their muscle glycogen stores. Immediately postexercise and 2 hours postexercise, they consumed either 0 (P), 1.5 (L) or 3.0g (H) glucose polymers/kg of bodyweight from a glucose polymer solution. Blood glucose and insulin declined significantly during exercise in each of the three treatments. They remained below the pre-exercise concentrations during recovery in the P treatment, but increased significantly above the preexercise concentrations during the Land H treatments. By the end of the 4-hour recovery period, blood glucose and insulin were still significantly above the pre-exercise concentrations in both treatments. Consequently, the rate of muscle glycogen storage over the second 2 hours of recovery remained similar to that of the first 2 hours of recovery (Ivy et al. 1988b). This is in agreement with the finding of Blom et al. (1987) that providing a carbohydrate supplement at 2-hour intervals resulted in a consistent rate of muscle glycogen storage during the first 6 hours after exercise. Although there was a substantial difference in the amount of glucose consumed in the L (225g) and H (450g) treatments, there were no differences in the rates

15

Muscle Glycogen Synthesis

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Fig. 5. Muscle glycogen storage during the first 2 hours and second 2 hours of recovery for placebo (_), low carbohydrate (Iii!) and high carbohydrate (II) treatments. * Significantly different from placebo [after Ivy et al. (l988b) with permission].

of muscle glycogen storage for these treatments (fig. 5). These results are supported by previous studies demonstrating that a consistent rate of muscle glycogen storage occurs the first few hours following prolonged exhaustive exercise if the amount of carbohydrate consumed is above a threshold level (Keizer et al. 1986; Maehlum et al. 1977; Maehlum et al. 1978; Blom et al. 1987). For example, Blom et al. (1987) found that during the 6 hours immediately following exhaustive exercise the average glycogen storage rate was 5.7 Jlmol/g wet weight! h whether 0.7 or l.4g glucose/kg ofbodyweight was consumed at 2-hour intervals. When the carbohydrate supplement was reduced to 0_35 g/kg of bodyweight, however, the rate of storage was reduced by approximately 50%. The reasons for the similar glycogen storage rates when different amounts of glucose were consumed was not immediately clear. Hunt et al. (1985) reported that the mean rate of glucose emptying from the stomach is approximately 0.5 g/min, but that the rate of emptying is subject to the volume of the glucose solution ingested and its concentration. An increase in the amount or concentration of the glucose solution increases the rate of glucose emptying. Based on the results of Hunt et al. (1985), the

amount of glucose emptied during the Hand L treatments would have been approximately 180g and 132g, respectively. Thus, gastric emptying alone would have reduced the difference in glucose availability between the Hand L treatments by 78% (from 225g to 48g). The difference in the availability of glucose to the muscle, however, is also subject to the amount of glucose escaping the liver and the metabolic requirements of the nervous system. Based on the results of Maehlum et al. (1978), and assuming a gastric emptying rate of 0.5 g/min for an oral glucose load, it can be estimated that approximately 85% of the glucose emptied escapes the liver and is available to the muscle following exercise. The nervous system requires about 5g glucose per hour (Shreeve et al. 1956), thus reducing the availability of glucose to the muscle by 20g during the 4-hour recovery period. When all these factors are considered, it is estimated that the amount of glucose available to the active muscles was 137g during the H treatment and 97g during the L treatment. It is therefore possible that the gastric emptying rate and distribution of glucose have a significant bearing on the amount of glucose available for glycogen restoration following exercise, and that these factors may have had a significant role in limiting the difference in glycogen storage between the 2 treatments. It was also observed, however, that only a small percentage of the estimated glucose available to the muscle was converted to glycogen (Ivy et al. 1988b). Assuming an active muscle mass of 10kg, it was calculated that the amount of glycogen stored in the active muscles averaged 37g for the H treatment and 33g for the L treatment. Therefore, during the H treatment only 27% and during the L treatment only 34% of the glucose theoretically available to the active muscle was stored as glycogen. These results suggest that either muscle glucose uptake or the conversion of glucose to glycogen was rate limiting. The findings that the glucose oxidation rate was significantly higher during the H treatment, and that the activity of glycogen synthase was the same for the 2 treatments

Sports Medicine 11 (I) 1991

16

suggests that the processing of glucose through the glycogen synthetic pathway was limiting.

20

1:

0>

'iii

;:

1il ;:

4.4 The Effect of Glucose Infusion

15

~

To determine the role of gastric emptying in muscle glycogen restoration after exercise, we compared the rates of glycogen storage after administering an oral glucose supplement and after bypassing gastric emptying by intravenous infusion of glucose (Reed et al. 1989). Following exercise bouts that resulted in depleted muscle glycogen stores, subjects received 3g of glucose/kg of bodyweight in a liquid (glucose polymers) form or intravenously (25% sterile glucose). The liquid supplement was divided into 2 equal doses and administered immediately and 120 minutes after exercise. During the infusion treatment, glucose was administered continuously during the first 235 minutes of the 240-minute recovery period. Providing the glucose by infusion, as opposed to providing it orally, resulted in a significantly greater rise in blood glucose, suggesting that gastric emptying had restricted the amount of glucose available to the muscle for storage (fig. 6). However, the rates of glycogen storage were not significantly different between the liquid and infusion treatments (fig. 7).

o~~~--~~~~~~~~~

40

80

0

40

80 120 160 200 240

1-0- Exercise-t11it-.---Recovery

-I

Time (min)

Fig. 6. Blood glucose concentrations during exercise and recovery in subjects receiving solid (.), liquid (0) and intravenous (.&) glucose supplements. Values are means ± SEM in mg,! I 00 ml at each time point. * Significant differences (p < 0.05) between treatments [after Reed et al. (1989) with permission).

"0

E

.3 10 Q)

C1>

'" 2 en c:

Q)

5

C1> 0 .

C3

Time after exercise (min)

Fig. 7. Glycogen storage rates during recovery in subjects receiving liquid (1riI), solid (.) and intravenous (II) glucose supplements. Values are means ± SEM in I'mol/g during each 120-minute period [after Reed et al. (1989) with permission).

Previous studies employing glucose infusion have generally observed greater rates of glycogen synthesis than those seen in the above mentioned study. Ahlborg (l967b) infused 2 subjects continuously during exercise and observed their postexercise storage rates. One subject, who received 2.9g glucose/kg of bodyweight during 60 minutes of exercise, had a glycogen storage rate of 12.1 ~molfg wet weight/h in the first hour after exercise. The other subject, who received 5.1g glucose/kg of bodyweight during 160 minutes of exercise, showed a glycogen storage rate of 24.9 ~molfg wet weight/ h during the first hour after exercise. Bergstrom and Hultman (l967c), while infusing 4g glucosejkg of bodyweight for 4 hours after exercise, observed a glycogen storage rate of 25 ~mol/g wet weight/h. Finally, Roch-Norlund et al. (1972), when infusing 8g glucosejkg ofbodyweight over 4 hours following exercise, reported a glycogen storage rate of 33.3 ~molfg wet weightjh for the second 2 hours after exercise. An important difference between these earlier studies and the present study is that in the earlier studies the glucose was infused at a much higher rate, resulting in blood glucose values that were generally 2 to 3 times greater than in the present

17

Muscle Glycogen Synthesis

study. It is also likely that plasma insulin values were greater as well, although these data were not reported. Insulin is an activator of both muscle glucose transport and glycogen synthase and these possible differences may explain the different rates of muscle glycogen storage between studies. This could also explain the similar glycogen storage rates during our liquid and infusion treatments since the plasma insulin responses were similar for the 2 treatments. The recent findings of Young et al. (1988) support the idea that the blood insulin concentration plays a major role in determining the rate of muscle glycogen storage. They reported that the total glucose disposal during an euglycaemic clamp increased with increasing insulin infusion. However, during the low insulin infusions (plasma insulin concentrations of 16 to 50 mUlL) disposal occurred because of an increase in glucose oxidation. At plasma insulin concentrations from 150 to 500 mUlL, the major site of glucose disposal shifted from oxidation to storage with a concomitant increase in the activity of glycogen synthase.

5. Recommendations for the Endurance A.thlete From a dietary position, the first concern of the endurance athlete is that caloric consumption and caloric expenditure be in balance. The endurance athlete may expend 3500 to 7000 kcal/day when training. If caloric consumption is inadequate and not balanced with caloric expenditure, the athlete's training and competitive abilities will eventually be adversely affected. It is also important that a substantial percentage of the diet consist of carbohydrate. Costill et al. (1981) found that a diet consisting of approximately 8g carbohydrate/kg bodyweight/day was required to maintain a normal muscle glycogen concentration on a daily basis. It was suggested by Sherman and Lamb (1988) that the endurance athlete's diet consist of 65 to 70% carbohydrate during strenuous training. Prior to competition, the muscle and liver glycogen stores should be maximised. For the best results with the least amounts of stress, it is rec-

ommended that a hard training bout be performed 7 days prior to competition to reduce the muscle glycogen stores. During the next 3 days training should be of moderate intensity and duration and a well-balanced mixed diet composed of about 45 to 50% carbohydrate consumed. During the 3 days after that training should be gradually tapered and the carbohydrate content of the diet should be increased to 70%. This should result in muscle glycogen stores similar to those normally produced by the classical glycogen supercompensation regimen, but with much less stress and fatigue. For the rapid replenishment of muscle glycogen stores, one should consume a carbohydrate supplement in excess of I g/kg bodyweight immediately after competition or after a training bout. Continuation of supplementation every 2 hours will maintain a maximal rate of storage up to 6 hours after exercise. Increasing the amount of carbohydrate consumption above 1.0 g/kg bodyweight per supplement appears to provide no additional benefit, and may have the adverse effects of causing nausea and diarrhoea. Supplements composed of glucose or glucose polymers are more effective for the replenishment of muscle glycogen stores after exercise than supplements composed of predominantly fructose. However, some fructose is recommended because it is more effective than glucose in the replenishment of liver glycogen. Finally, carbohydrates in solid or liquid form can be consumed immediately after exercise with similar results. However, liquid supplements are recommended because they are easy to digest and less filling, and therefore do not tend to adversely affect one's normal appetite. They also provide a source of fluid for rapid rehydration.

A.cknowledgements I wish to thank Carol Torgah and Miriam Cortez for their critical review of the manuscript, and Mina Rathbun for the typing of the manuscript.

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medicine: prolonged exercise, pp. 213-277, Benchmark Press, Indianapolis, IN, 1988 Shreeve WW, Baker N, Miller M, et al. 14(: studies in carbohydrate metabolism: oxidation of glucose in diabetic human subjects. Metabolism 5: 22-29, 1956 Szanto S, Yudkin J. The effect of dietary sucrose on blood lipids, serum insulin, platelet adhesiveness and body weight in human volunteers. Postgraduate Medical Journal 45: 602-607 1%9 ' Terjung RL, Baldwin KM, Winder WW, Holloszy JO. Glycogen in different types of muscle and in liver after exhausting exercise. American Journal of Physiology 226: 1387-1391, 1974 Yakovlev NN. The effect of regular muscular activity on enzymes of glycogen, and g1ucose-6-phosphate in muscles and liver. Biochemistry 33: 602-607, 1968 Young AA, Bogardus C, Stone K, Mott OM. Insulin response of components of whole-body and muscle carbohydrate metabolism in humans. American Journal of Physiology 254; E231E236, 1988 Zakin 0, Herfman RH, Gordon We. The conversion of glucose and fructose to fatty acids in the human liver. Biochemical Medicine 2: 427-437, 1969

Correspondence and reprints: Dr John L Ivy. Department of Kinesiology, Bellmont Hall 222, University of Texas at Austin, Austin, TX 78712, USA.