Optimization of Glycogen Stores

Chapter 7
Optimization of Glycogen Stores
JOHN L. IVY
Introduction
The importance of carbohydrates as a fuel source
during physical activity has been recognized for
many years (Krogh & Lindhard 1920; Levine et al.
1924; Dill et al. 1932). Krogh and Lindhard (1920)
reported that subjects placed on a high fat diet
complained of feeling tired and had difficulty
performing a standardized 2-h exercise protocol
on a cycle ergometer. However, 3 days on a high
carbohydrate diet relieved their symptoms of
tiredness and the subjects were able to complete
the 2-h exercise task without undue stress. Similarly, Christensen and Hansen (1939a, 1939b)
found that the capacity for prolonged exercise
was three times greater after 3–7 days on a high
carbohydrate diet as opposed to a high fatprotein diet. They also reported that exhaustion
was accompanied by hypoglycaemia, and that
ingestion of a carbohydrate supplement during
recovery rapidly returned the blood glucose concentration back to normal and allowed considerable additional exercise to be performed. These
results were in agreement with the earlier observations of Levine et al. (1924), who found that
blood glucose levels of runners fell to very low
levels during a marathon. They also noted that in
conjunction with this hypoglycaemic state, the
participants were physically fatigued and displayed neuroglucopenia symptoms such as
muscular twitching and disorientation. Based on
these observations, it was generally accepted
that hypoglycaemia resulting from liver glycogen depletion was responsible for fatigue dur-
ing prolonged strenuous exercise. However, this
view would be modified as technical advances
allowed the direct investigation of muscle
metabolism during and following prolonged
strenuous exercise.
Based on the findings of several Scandinavian
research groups, it became apparent that there
is an increased reliance on muscle glycogen as a
fuel source as exercise intensity increases, and
that perception of fatigue during prolonged
strenuous exercise parallels the declining muscle
glycogen stores. It was also found that aerobic
endurance is directly related to the initial muscle
glycogen stores, and that strenuous exercise
could not be maintained once these stores are
depleted (Hermansen et al. 1965; Ahlborg et al.
1967a; Bergström et al. 1967; Hultman 1967).
The amount of glycogen stored in skeletal
muscle, however, is limited. If muscle glycogen
was the only fuel source available, it could be
completely depleted within 90 min of moderate
intensity exercise. Therefore, because of the
limited availability of muscle glycogen and its
importance during prolonged strenuous exercise, methods for increasing its concentration
above normal prior to exercise and for its rapid
restoration after exercise have been extensively
investigated. This chapter discusses our current
understanding of the regulation of muscle glycogen synthesis, the effect of diet and exercise on
the muscle glycogen concentration prior to exercise, and methods for muscle glycogen restoration immediately after exercise. The chapter
concludes with recommendations for increasing
97
98
nutrition and exercise
and maintaining muscle glycogen stores for competition and training.
Regulation of
muscle glycogen synthesis
Figure 7.1 illustrates the metabolic reactions
controlling glycogen synthesis. Upon crossing
the sarcolemma, glucose is rapidly converted to
glucose-6-phosphate (G6P) by the enzyme hexokinase. The G6P is then converted to glucose-1phosphate (G1P) by phosphoglucomutase. Next,
uridine triphosphate and G1P are combined to
form uridine diphosphate (UDP)-glucose, which
serves as a glycosyl carrier. The glucose attached
to the UDP-glucose is then transferred to the terminal glucose residue at the non-reducing end of
a glucan chain to form an a(1 Æ 4) glycosidic
linkage. This reaction is catalysed by the enzyme
glycogen synthase. The initial formation of
the glucan chain, however, is controlled by the
protein glycogenin, which is a UDP-glucoserequiring glucosyltransferase. The first step
involves the covalent attachment of glucose to a
single tyrosine residue on glycogenin. This reaction is brought about autocatalytically by glycogenin itself. The next step is the extension of the
glucan chain which involves the sequential addition of up to seven further glucosyl residues. The
glucan primer is elongated by glycogen synthase, but only when glycogenin and glycogen
synthase are complexed together. Finally, amylo
(1,4 Æ 1,6) transglycosylase catalyses the transfer
of a terminal oligosaccharide fragment of six or
seven glucosyl residues from the end of the
glucan 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 Æ 6) linkage
and thus create a compact molecular structure.
The synthesis of the glycogen molecule is terminated by the dissociation of glycogen synthase
from glycogenin (Smythe & Cohen 1991; Alonso
et al. 1995).
Following its depletion by exercise, muscle
glycogen synthesis occurs in a biphasic manner
(Bergström & Hultman 1967b; Piehl 1974; Ivy
1977; Maehlum et al. 1977; Price et al. 1994). Initially, there is a rapid synthesis of muscle glycogen that does not require the presence of insulin
(Ivy 1977; Maehlum et al. 1977; Price et al. 1994).
In normal humans, the rate of synthesis during
this insulin-independent phase has been found
to range between 12 and 30 mmol · g–1 wet
weight · h–1 and to last for about 45–60 min. The
second phase is insulin dependent (Ivy 1977;
Maehlum et al. 1977; Price et al. 1994) and in the
absence of carbohydrate supplementation occurs
at a rate that is approximately seven- to 10-fold
slower than that of the rapid phase (Price et al.
1994). If supplemented immediately after exercise with carbohydrates, however, the rate of
synthesis during the slow phase can be increased
several-fold, and if supplementation persists, the
muscle glycogen level can be increased above
–
Hexokinase
Glucose
Glucose-6-phosphate
Phosphoglucomutase
+
Glucose transporter
Glycogen synthase D
+ glycogenin
Glucose-1-phosphate
UDP-glucose
I
pyrophosphorylase
UDP-glucose
Glycogen
Fig. 7.1 The metabolic reactions
and the enzymes controlling the
reactions that are responsible for
the synthesis of muscle glycogen.
Enzymes are in italic. See text for
details.
optimization of glycogen stores
normal (Bergström et al. 1967). This elevation in
muscle glycogen above normal is referred to as
glycogen supercompensation. Interestingly, the
effectiveness of the carbohydrate supplement to
speed muscle glycogen recovery during the slow
phase is directly related to the plasma insulin
response to the supplement (Ivy 1991).
Rapid phase of glycogen synthesis
after exercise
After exercise that is of sufficient intensity and
duration to deplete the muscle glycogen stores,
the activity of glycogen synthase is increased.
Glycogen synthase is the rate-limiting enzyme in
the glycogen synthesis pathway. Its activity is
strongly influenced by the muscle glycogen
concentration (Danforth 1965; Bergström et al.
1972; Adolfsson 1973). Generally, the percentage
of glycogen synthase in its active I-form is
inversely related to the muscle glycogen concentration. That is, 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 its inactive D-form
increases.
An exercise-induced increase in glycogen synthase activity can catalyse the rapid restoration of
glycogen only if adequate substrate is available.
Thus, an additional factor that makes possible
the rapid increase in muscle glycogen after exercise is a protracted increase in the permeability of
the muscle cell membrane to glucose (Holloszy &
Narahara 1965; Ivy & Holloszy 1981; Richter et al.
1982). The increase in glucose transport induced
by muscle contractile activity, however, reverses
rapidly in the absence of insulin, with most of
the effect lost within several hours (Cartee et al.
1989). This rapid decline in muscle glucose transport appears to be inversely related to the muscle
glycogen concentration (Cartee et al. 1989;
Richter et al. 1984). Thus, the increase in membrane permeability to glucose, together with the
activation of glycogen synthase, allows for an
initial rapid insulin-independent resynthesis of
muscle glycogen following exercise.
99
Slow phase of muscle glycogen synthesis
after exercise
After the direct, insulin-independent effect of
exercise on glucose transport subsides, it is
rapidly replaced by a marked increase in the sensitivity of muscle glucose transport and glycogen
synthesis to insulin (Garetto et al. 1984; Richter
et al. 1984; Cartee et al. 1989). The magnitude of
the increased insulin sensitivity induced by exercise can be extremely high, and result in muscle
glucose uptake and glycogen synthesis with
insulin concentrations that normally have no
detectable effect on either process (Cartee et al.
1989; Price et al. 1994). Furthermore, this increase
in sensitivity can be sustained for a very long
period of time, and does not appear to reverse
completely until glycogen supercompensation
has occurred (Garetto et al. 1984; Cartee et al.
1989). These findings therefore suggest that an
increase in muscle insulin sensitivity is a primary component of the slow phase of glycogen
synthesis.
Although the percentage of glycogen synthase
in the I-form may be as high as 80% immediately
after exercise-induced glycogen depletion, as
glycogen levels are normalized the percentage of
glycogen synthase I decreases back to the preexercise level or lower in a negative feedback
manner (Danforth 1965; Bergström et al. 1972;
Adolfsson 1973; Terjung et al. 1974). However,
during the slow synthesis phase of glycogen,
glycogen synthase appears to be transformed
into an intermediate form which has a depressed
activity ratio, but enhanced sensitivity to activation by G6P (Kochan et al. 1981). Thus, a second
important component of the slow phase of glycogen synthase appears to be an increase in the sensitivity of glycogen synthase to G6P.
Another possible mechanism that might
contribute to an increase in glycogen synthesis during the slow insulin-dependent phase of
recovery is an increase in GLUT-4 concentration.
Recently, Ren et al. (1994) reported an increase in
GLUT-4 protein in skeletal muscle of rats after a
single prolonged exercise session. The increase in
GLUT-4 protein was accompanied by a propor-
100
nutrition and exercise
tional increase in insulin-stimulated glucose
transport and glycogen synthesis. Ren et al.
(1994) concluded that a rapid increase in GLUT-4
expression is an early adaptation of muscle to
exercise to enhance replenishment of muscle
glycogen stores.
Effect of carbohydrate supplementation
It is evident that the exercise-induced increase in
muscle permeability to glucose, insulin sensitivity, and glycogen synthase activity are, together,
not sufficient to result in the rapid repletion and
supercompensation of the glycogen stores, since
only a small increase in muscle glycogen occurs
following exercise in the absence of carbohydrate
feeding (Bergström et al. 1967; Bergström &
Hultman 1967b; Maehlum & Hermansen 1978;
Ivy et al. 1988b). Probable factors that prevent the
rapid repletion of muscle glycogen 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.
Carbohydrate feeding after exercise probably
stimulates glycogen synthesis by increasing arterial 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
elevated. It may also play a role in increasing
GLUT-4 expression which would facilitate
insulin-stimulated glucose transport (Ren et al.
1993; Hansen et al. 1995; Brozinick et al. 1996).
With increasing plasma glucose concentration,
glucose transport increases regardless of the
level of muscle permeability to glucose (Nesher
et al. 1985). Therefore, the increase in arterial
plasma glucose concentration functions to
increase the rate of glucose transport, further
increasing substrate availability, and providing sufficient G6P for activation of glycogen
synthase.
It has also been demonstrated that the insulin response to carbohydrate supplementation
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 normal glycogen repletion and
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.
Glycogen supercompensation
regimens
The discovery by Bergström and Hultman
(1967b) 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. Bergström et al. (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 three 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
optimization of glycogen stores
diet, the muscle glycogen concentration was
205.5 mmol · g–1 wet weight. This represented a
100% increase above the initial muscle glycogen
concentration. When the high carbohydrate diet
preceded the high fat–protein diet, the muscle
glycogen concentration was 183.9 mmol · g–1 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 al. 1967b; Bergström & Hultman
1967a), it was recommended that the best way to
glycogen supercompensate was, first, to deplete
the muscle glycogen stores with an exhaustive
exercise bout; second, to eat a carbohydrate-free
diet for 3 days; third, to deplete the glycogen
stores once more with an exhaustive exercise
bout; and fourth, to consume a high carbohydrate diet for 3 days.
Because of the strenuous nature of this
regimen, many athletes have found it impractical, even though it has been used successfully by
very elite performers. The 3 days of low carbohydrate diet may cause hypoglycaemia, irritability
and chronic fatigue. The two bouts of exhaustive
exercise prior to competition may result in injury,
soreness and fatigue, and prevents a proper taper
before competition. To address this problem,
Sherman et al. (1981) studied three types of
muscle glycogen supercompensation regimens
on six trained runners. Over a 6-day period,
.
the subjects ran at approximately 75% of Vo2max.
for 90 min, 40 min, 40 min, 20 min, 20 min, and
rested, respectively. During each taper, the subjects received one of three dietary treatments:
1 a mixed diet composed of 50% carbohydrate
(control diet),
2 a low carbohydrate diet (25% carbohydrate)
for the first 3 days and a high carbohydrate diet
(70% carbohydrate) for the last 3 days (classic
diet), and
3 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 4th and 7th days of each trial. During the
101
control treatment, muscle glycogen concentrations of the gastrocnemius were 135 and
163 mmol · g–1 wet weight on days 4 and 7, respectively. During the classic treatment, the corresponding muscle glycogen concentrations were
80 and 210 mmol · g–1 wet weight, and during
the modified treatment they were 135 and
204 mmol · g–1 wet weight (Fig. 7.2). These results
suggest that a normal training taper in conjunction with a moderate carbohydrate–high carbohydrate diet sequence is as effective as the classic
glycogen supercompensation regimen for highly
trained endurance athletes.
Enhancement of glycogen synthesis
after exercise
Long-term recovery
The amount of carbohydrate consumed has a significant effect on the rate of glycogen storage
after exercise. Unless sufficient carbohydrate
is ingested, muscle glycogen will not be normalized 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 150–650 g
carbohydrate · day–1 resulted in a proportionately greater muscle glycogen synthesis during
the initial 24 h after exercise, and that consumption of more than 600 g carbohydrate · day–1 was
of no additional benefit (Fig. 7.3). It has also been
demonstrated 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 (Costill et al.
1971; Sherman et al. 1993). For example, Sherman
et al. (1993) fed endurance athletes either 5 or 10 g
carbohydrate · kg–1 · day–1 over 7 days of controlled training. The lower carbohydrate diet
contained 42% of energy from carbohydrate and
the higher carbohydrate diet contained 84% of
energy from carbohydrate. Both diet and exercise
were controlled during the 7 days prior to the
102
nutrition and exercise
220
Glycogen
(µmol.g–1 wet wt)
Exercise
165
110
Exercise
Exercise
55
0
0
1
2
3
4
5
6
Regimen (days)
Fig. 7.2 A comparison of the classic Bergström et al. (1967) glycogen supercompensation method and a
modification of that method by Sherman et al. (1983). The classic method (—) consisted of depleting the glycogen
stores with an exhaustive exercise bout, followed by 3 days on a low carbohydrate diet. This was followed with
another glycogen-depleting exercise and 3 days on a high carbohydrate diet. The modifications by Sherman (- - - -)
included a hard exercise bout that was followed by 6 days of exercise tapering. During the first 3 days of the taper, a
mixed diet consisting of 50% carbohydrates was consumed. During the last 3 days, a high carbohydrate diet was
consumed. The two values for the classic regimen on day 3 represent before and after an exhaustive exercise bout.
䊐, low carbohydrate diet; 䉬, mixed diet; 䊉, high carbohydrate diet. From Sherman et al. (1983), with permission.
Glycogen storage
(µmol.g –1 wet wt.h –1)
80
60
40
20
0
–20
0
200
400
600
Consumed carbohydrate (g.day–1)
Fig. 7.3 The relationship between the amount of
carbohydrate consumed and the rate of muscle
glycogen storage during a 24-h period after glycogen
depletion by exercise. From Costill et al. (1981), with
permission.
experimental period to ensure that subjects
started with similar muscle glycogen levels. The
lower carbohydrate diet produced a significant
30% decline in muscle glycogen by day 5 of training, which was then maintained through day 7.
However, there was no decline in muscle glycogen during the 7 days of training when the athletes consumed the higher carbohydrate diet.
The type of carbohydrate consumed also
appears to have an effect on the rate of glycogen
resynthesis following exercise. Costill et al. (1971)
fed glycogen-depleted runners a starch or
glucose diet (650 g carbohydrate · day–1) during
the 2 days following depletion. During the first
24 h there was no difference in the synthesis of
muscle glycogen between the two diets, but after
the 2nd day, the starch diet resulted in a significantly greater glycogen synthesis than the
glucose diet. A difference in glycogen storage
between simple and complex carbohydrates,
however, was not demonstrated by Roberts et al.
(1988). Following glycogen-depleting exercise,
their subjects were fed diets consisting of either
88% simple and 12% complex carbohydrates or
15% simple and 85% complex carbohydrates.
After 3 days of recovery, it was found that the
two diets had produced equivalent increases in
muscle glycogen storage. The difference between
studies is not immediately clear, but may be due
to differences in the glycaemic indexes of the different carbohydrates provided.
The only study that appears to have investigated the impact of the glycaemic index of carbohydrate on muscle glycogen storage after
optimization of glycogen stores
Short-term recovery
While procedures for increasing muscle glycogen above normal levels in preparation for competition and maintaining normal glycogen levels
on a day-to-day basis have been defined, these
procedures do not address the problem of
athletic competitions that require the rapid
resynthesis of muscle glycogen within hours.
Although it is unlikely that muscle glycogen
stores could be completely resynthesized within
a few hours by nutritional supplementation
alone, it would be of benefit to the athlete if supplementation procedures which maximized the
rate of muscle glycogen storage after exercise
were defined. Factors that influence the rate of
muscle glycogen storage immediately following
exercise are the timing, amount and type of carbohydrate supplement consumed, the frequency
of feeding, and the type of exercise performed.
timing of carbohydrate
consumption after exercise
The time elapsed between competition or a prolonged exercise bout and the consumption of a
carbohydrate supplement will critically influence the rate of muscle glycogen resynthesis (Ivy
et al. 1988a). When carbohydrate supplements
are provided immediately after exercise, they
generally result in a rate of glycogen resynthesis
of between 5 and 6 mmol · g–1 wet weight · h–1
(Maehlum et al. 1977; Blom et al. 1987; Ivy et al.
1988a, 1988b). This rate is maintained for approximately 2 h and then declines by approximately
50% over the next 2 h as the blood glucose and
insulin levels decline to after-exercise levels (Ivy
et al. 1988a). If the supplement is delayed for 2 h,
the rate of glycogen resynthesis during the 2 h
immediately after consumption ranges between
3 and 4 mmol · g–1 wet weight · h–1, or about 50% as
fast as when the supplement is provided immediately after exercise (Fig. 7.4). This lower rate
of glycogen resynthesis occurs despite normal
increases in blood glucose and insulin levels. It
appears that when the carbohydrate supplement
is delayed for several hours after exercise, the
muscle becomes insulin resistant, reducing the
rate of muscle glucose uptake and glycogen
20
Glycogen synthesis (µmol.g–1 wet wt)
exercise was conducted by Burke et al. (1993).
Subjects were exercised to deplete the muscle
glycogen stores on two separate occasions and
provided a diet composed of carbohydrate with
a high glycaemic index on one occasion, and a
diet composed of carbohydrate with a low
glycaemic index on the other. Total carbohydrate intake over the 24-h recovery period
was 10 g · kg–1 body weight, evenly distributed
between meals eaten at 0, 4, 8 and 21 h after exercise. The increase in muscle glycogen averaged
106 mmol · g–1 wet weight for the high glycaemic
index carbohydrate and 71.5 mmol · g–1 wet
weight for the low glycaemic index. The difference in glycogen storage was significant. This
finding suggests that the increase in muscle
glycogen content during long-term recovery is
affected by the amount and glycaemic index of
the carbohydrate consumed.
103
15
10
5
0
0–120
120–240
Time after exercise (min)
Fig. 7.4 Muscle glycogen storage during the first 2 h
and second 2 h of recovery from exercise. The open bar
represents the glycogen storage when the
carbohydrate supplement was provided immediately
after exercise, and the black bar represents the
glycogen storage when the supplement was delayed
until 2 h into recovery. The carbohydrate supplement
consisted of a 23% solution of glucose polymers
(2 g · kg–1 body weight). From Ivy et al. (1988a), with
permission.
104
nutrition and exercise
resynthesis. Once developed, this state of insulin
resistance persists for several hours. Providing a
carbohydrate supplement soon after exercise
therefore appears to benefit the muscle glycogen
recovery process by preventing the development
of muscle insulin resistance. Furthermore,
during the time between the end of exercise and
the consumption of a carbohydrate supplement,
there is very little muscle glycogen resynthesis
(approximately 1–2 mmol · g–1 wet weight · h–1)
(Ivy et al. 1988a). Therefore, providing a carbohydrate supplement soon after exercise has the
added benefit of starting the muscle glycogen
recovery process immediately.
frequency and amount of
carbohydrate consumption
after exercise
The frequency of carbohydrate supplementation
as well as the amount of carbohydrate in each
supplement is also of importance in the regulation of muscle glycogen resynthesis. When an
adequate carbohydrate supplement is provided
immediately after exercise, its effect on muscle
glycogen recovery eventually declines as blood
glucose and insulin levels decline. However,
Blom et al. (1987) reported that providing a carbohydrate supplement immediately after exercise
and at 2-h intervals for the next 4 h maintained an
elevated blood glucose level and a rapid rate of
muscle glycogen resynthesis during a 6-h recovery period. Blom et al. (1987) also found that a
critical amount of carbohydrate must be consumed if the rate of muscle glycogen resynthesis
was to be maximized. When carbohydrate supplements of 0.7 or 1.4 g glucose · kg–1 body weight
were provided at 2-h intervals, the rate of glycogen storage did not differ between treatments
and averaged 5.7 mmol · g–1 wet weight · h–1.
However, when Blom et al. (1987) provided 0.35 g
glucose · kg–1 body weight at 2-h intervals, the
rate of muscle glycogen resynthesis was reduced
by 50%.
To better evaluate the critical level of carbohydrate supplementation required for maximal
glycogen resynthesis, we tested the effects of
supplements with different concentrations of
carbohydrate during 4 h of recovery from exercise (Fig. 7.5). Very little muscle glycogen resynthesis was found when carbohydrate
was withheld from the subjects (approximately
0.6 mmol · g–1 wet weight · h–1). With increasing
concentration of carbohydrate supplementation,
however, the rate of muscle glycogen resynthesis increased in a curvilinear pattern and
then plateaued at a rate of 5.5 mmol · g–1 wet
weight · h–1 as the carbohydrate concentration
Protein + CHO
7
Increase in muscle
glycogen concentration
(µmol. g–1. h–1)
6
5
4
3
2
1
0
0
0.5
1.0
1.5
2.0
Carbohydrate supplement
(g.kg–1 body wt)
2.5
3.0
Fig. 7.5 The average rate of
muscle glycogen resynthesis
during a 4-h exercise recovery
period after oral consumption of
different concentrations of
carbohydrate (CHO) from a liquid
supplement (ª 21% wt/vol).
Supplements were provided
immediately after exercise and 2 h
after exercise. Protein + CHO
represents the average muscle
glycogen resynthesis rate when
1.5 g CHO · kg–1 body weight plus
0.53 g protein · kg–1 body weight
(milk and whey protein isolate
mixture, 7.6% wt/vol) was
provided.
optimization of glycogen stores
approached 1–1.5 g · kg–1 body weight. These
results imply that when carbohydrate supplements are provided at 2-h intervals in amounts
below 1 g · kg–1 body weight, the rate of muscle
glycogen resynthesis will be submaximal. The
reduced rate of resynthesis is probably due to the
inability of a small carbohydrate supplement to
adequately increase and maintain blood glucose
and insulin levels for a 2-h interval, as smaller
supplements taken more frequently have been
found to be adequate (Doyle et al. 1993).
The reason for similar glycogen resynthesis
rates when carbohydrate supplements exceed
1 g · kg–1 body weight was not immediately clear.
Estimates of gastric emptying rates, based on the
research of Hunt et al. (1985), suggest that carbohydrate available to the muscle was far in excess
of the amount actually converted to glycogen.
This would indicate that under conditions of
high carbohydrate supplementation, the ratelimiting step in glycogen resynthesis is either
glucose transport or the processing of glucose
through the glycogen synthetic pathway. To test
this hypothesis, Reed et al. (1989) continuously
infused glycogen-depleted subjects with 3 g
glucose · kg–1 body weight during the first 3.75 h
of a 4-h exercise recovery period. The rate of
muscle glycogen resynthesis during infusion
was then compared with that which occurred
when a liquid supplement containing 1.5 g
glucose · kg–1 body weight was consumed immediately after and 2 h after exercise. During infusion, blood glucose increased to 10 mm, whereas
the blood glucose level only reached 6 mm when
the liquid glucose supplement was consumed
orally. Despite this large difference in blood
glucose, the rates of muscle glycogen resynthesis
were virtually identical at the end of the recovery
periods. The results of Reed et al. (1989) therefore
support the hypothesis that glycogen resynthesis
is not limited by glucose availability when adequate carbohydrate is consumed.
Prior research studies employing glucose infusion (Ahlborg et al. 1967b; Bergström & Hultman
1967c; Roch-Norlund et al. 1972), however, have
generally demonstrated greater rates of glycogen
synthesis than those reported by Reed et al.
105
(1989). Possibly accounting for the difference in
synthesis rates are the different rates of glucose
infusion. The rates of glucose infusion in the
earlier studies were much faster and plasma
glucose concentrations two to three times higher
than those reported by Reed et al. (1989). It is
likely that plasma insulin concentrations in the
earlier studies were greater as well, although
these results were not reported.
It was of interest to note that in the study by
Reed et al. (1989) the plasma insulin response
during the infusion treatment was similar to that
produced by the liquid supplement, and therefore could account for the similar rates of glycogen storage for these two treatments. The blood
insulin concentration plays a major role in determining the rate of muscle glycogen storage.
Insulin stimulates both muscle glucose transport
and activation of glycogen synthase. The results
raised the possibility that increasing the insulin
response to a carbohydrate supplement could
increase the rate of muscle glucose uptake and
glycogen storage.
protein plus carbohydrate
Certain amino acids are effective secretagogues
of insulin and have been found to synergistically
increase the blood insulin response to a carbohydrate load when administered in combination
(Floyd et al. 1966; Fajans et al. 1967). Of the 20
amino acids normally found in protein, the most
effective insulin secretagogue is arginine (Fajans
et al. 1967). When infused with carbohydrate,
arginine has been found to increase the insulin
response fivefold above that produced by the
carbohydrate or arginine alone. However, we
have found the use of amino acids to be impractical when added to a carbohydrate supplement
because they produce many unwanted sideeffects such as mild borborygmus and diarrhoea.
Protein meals and supplements also have been
found to enhance the insulin response to a carbohydrate load and do not produce the unwanted
side-effects of the amino acids (Rabinowitz et al.
1966; Pallota & Kennedy 1968; Spiller et al. 1987).
For example, Spiller et al. (1987) demonstrated an
106
nutrition and exercise
Increase in muscle
glycogen concentration
(µmol.kg–1 wet wt)
increased blood insulin response and decreased
blood glucose response with the addition of
protein to a 58 g carbohydrate supplement. The
insulin response was found to be directly proportional and the glucose response inversely
proportional to the protein content of the
carbohydrate–protein supplement. No adverse
side-effects were reported.
We therefore investigated the effects of a carbohydrate–protein supplement on muscle glycogen resynthesis after exercise (Zawadzki et al.
1992). The supplements tested consisted of 112 g
carbohydrate or 112 g carbohydrate plus 40.7 g
protein (21% wt/vol mixture). The supplements
were administered immediately after exercise
and 2 h after exercise. It was found that the combination of carbohydrate plus protein resulted in
a synergistic insulin response. In conjunction
with the greater insulin response was a significantly lower blood glucose response and a 38%
faster rate of muscle glycogen storage compared with carbohydrate supplementation
alone. Rates of muscle glycogen resynthesis averaged 7.1 mmol · g–1 wet weight · h–1 for the carbohydrate–protein treatment and 5.0 mmol · g–1 wet
weight · h–1 for the carbohydrate treatment
during the 4-h recovery period (see Fig. 7.5). It
was also found that carbohydrate oxidation rates
and blood lactate concentrations for the carbohy-
drate–protein and carbohydrate treatments
were similar. These results suggested that the
increased rate of muscle glycogen resynthesis
during the carbohydrate–protein treatment was
the result of an increased clearance of glucose by
the muscle due to the increased blood insulin
response. Since the carbohydrate–protein supplement was palatable and there were no
unwanted side-effects, it would appear to be a
viable supplement for postexercise glycogen
recovery.
differences in
simple carbohydrates
The effect of supplements composed of predominately glucose, fructose and sucrose have also
been investigated (Blom et al. 1987). Glucose and
fructose are metabolized differently. They have
different gastric emptying rates and are absorbed
into the blood at different rates. Furthermore, the
insulin response to a glucose supplement is generally much greater than that of a fructose supplement. Blom et al. (1987) found that ingestion
of glucose or sucrose was twice as effective as
fructose for restoration of muscle glycogen (Fig.
7.6). They suggested that the differences between
the glucose and fructose supplementations were
the result of the way the body metabolized these
40
Glucose
Sucrose
20
Fructose
0
0
1
2
3
Time (h)
4
5
6
Fig. 7.6 Increases in muscle
glycogen concentration when
glucose, fructose and sucrose are
provided in amounts of 0.7 g · kg–1
body weight immediately after
exercise and at 2-h intervals.
From Blom et al. (1987), with
permission.
optimization of glycogen stores
sugars. Fructose metabolism takes place predominantly in the liver (Zakin et al. 1969),
whereas the majority of glucose appears to
bypass the liver and be stored or oxidized by the
muscle (Maehlum et al. 1978). When infused,
fructose has been found to result in a four 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 (Bergström &
Hultman 1967c).
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 al. (1987) was that fructose, by virtue
of its rapid metabolism in the liver, compared
with that of glucose, inhibits the postexercise
hepatic glucose uptake, thereby rendering a large
proportion of absorbed glucose available for
muscle glycogen resynthesis.
solid vs. liquid supplements
The form in which the carbohydrate is provided
has also been investigated. Keizer et al. (1986)
found that providing approximately 300 g of
carbohydrate in either liquid or solid form
after exercise resulted in a glycogen storage rate
of approximately 5 mmol · g–1 wet weight · h–1 over
the first 5 h of recovery. However, these solid
feedings contained a substantial amount of fat
and protein that is typically not found in liquid
supplements. Therefore, Reed et al. (1989) compared the postexercise glycogen storage rates
following liquid and solid carbohydrate supplements of similar compositions. Again there were
no differences noted between the two treatments.
The average glycogen storage rates for the liquid
and solid supplements were 5.1 and 5.5 mmol · g–1
wet weight · h–1, respectively.
107
influence of type of exercise
As previously indicated, during prolonged bouts
of exercise in which muscle and liver glycogen
concentrations are reduced and hypoglycaemia
results, muscle glycogen synthesis is typically
5–6 mmol · g–1 wet weight · h–1, provided an adequate carbohydrate supplement is consumed.
However, if the exercise rapidly reduces the
muscle glycogen concentration, resulting in
elevated blood and muscle lactate, synthesis of
glycogen can be very rapid even in the absence of
a carbohydrate supplement. Hermansen and
Vaage (1977) depleted the muscle glycogen levels
of their subjects by multiple 1-min maximal exercise bouts on a cycle ergometer. During the first
30 min of recovery, the rate of muscle glycogen
synthesis averaged 33.6 mmol · g–1 wet weight ·
h–1. The increase in muscle glycogen was found
to parallel the decline in muscle lactate, which
had increased to 26.4 mmol · g–1 wet weight after
the last exercise bout. MacDougall et al. (1977)
also found a relatively rapid rate of storage after
muscle glycogen depletion when subjects per.
formed 1-min cycling sprints at 150% of Vo2max.
to exhaustion. The difference in storage rates following prolonged exercise, as opposed to highintensity exercise, can probably be explained by
the availability of substrate for muscle glycogen
synthesis. With multiple high-intensity sprints,
glycogen depletion is accompanied by hyperglycaemia and elevated blood and muscle lactate
concentrations, which can be used immediately
as substrate for glycogen synthesis. By contrast,
prolonged sustained exercise severely reduces
the endogenous precursors of muscle glycogen,
thereby requiring an exogenous carbohydrate
source for rapid muscle glycogen synthesis.
Exercise that results in muscle damage also
affects muscle glycogen synthesis. Sherman et al.
(1983) found that after a marathon, restoration of
muscle glycogen was delayed and that this delay
was related to muscle damage caused by the run
(Hikida et al. 1983; Sherman et al. 1983). Eccentric
exercise which involves the forced lengthening
of active muscles and the transfer of external
power from the environment to the muscle
108
nutrition and exercise
causes severe muscle damage. O’Reilly et al.
(1987) reported that muscle glycogen stores
reduced by eccentric exercise were still significantly below normal levels after 10 days of recovery. Costill et al. (1990) also found that the rate of
muscle glycogen resynthesis was significantly
reduced following glycogen depletion by exercise that incorporated a substantial eccentric
component, and that the reduced rate of resynthesis was associated with muscle damage. More
recently, Asp et al. (1995) demonstrated that
muscle damage induced by eccentric exercise
resulted in a down regulation of GLUT-4 protein
that lasted for several days. In addition, it was
not until the GLUT-4 protein returned to the preexercise concentration that normal muscle glycogen levels were restored. These results suggest
that muscle damage following exercise can limit
glucose uptake due to a reduced GLUT-4 protein
concentration, and that this limits the restoration
of muscle glycogen.
Recommendations
From a dietary position, the first concern of the
endurance athlete is that energy consumption
and energy expenditure be in balance (Sherman
1995). The endurance athlete may expend 15–
30 MJ · day–1 when training. If consumption is
inadequate and not balanced with 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. It was suggested by
Sherman and Lamb (1988) that the endurance
athelete’s diet consists of approximately 65% carbohydrate during strenuous training. However,
this percentage can be modified according to
actual energy consumption. What is important is
the amount of carbohydrate consumed. Costill
et al. (1981) recommended that endurance
trained athletes consume approximately 8 g carbohydrate · kg–1 body weight · day–1 to maintain a
normal muscle glycogen concentration during
training. Similarly, a recommendation of 7 g
carbohydrate · kg–1 body weight · day–1 was provided by Sherman (1995).
Prior to competition, the muscle and liver
glycogen stores should be maximized. For the
best results with the least amount of stress, it is
recommended 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 45–50% carbohydrate consumed.
During the next 3 days, 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 that
normally produced by the classic 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 1 g · kg–1 body weight
immediately after competition or after a training
bout. Continuation of supplementation every 2 h
will maintain a maximal rate of storage up to
6 h after exercise; smaller supplements taken
more frequently are also effective. Increasing
the amount of carbohydrate consumption
above 1.0–1.5 g · kg–1 body weight · supplement–1
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. It might also be of benefit to include
some protein with the carbohydrate supplement
as this will enhance the rate of glycogen resynthesis. Finally, carbohydrates in solid or liquid
form can be consumed immediately after exercise with similar results. However, a liquid
supplement immediately after exercise is recommended because it is easier to digest and less
filling, and therefore will not tend to adversely
affect one’s normal appetite. A liquid supplement also provides a source of fluid for rapid
rehydration.
optimization of glycogen stores
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