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DR. SMITH: * In keeping with our yearly tradition, was undertaken to provide background for these
this Medical Grand Rounds will be presented by emerging concepts, as well as to assist runners
our chief resident. Dr. Richard Locksley will dis- preparing for such an event.
cuss fuel utilization in marathons, and its impli- The energy expenditure of a marathon is
cations for performance. This is not just of aca- roughly 60 kcal per km (96 kcal per mile). Pace
demic interest to Dr. Locksley because he has has little effect on the caloric cost per mile."," The
run the marathon in less than 2 hours and 30 intensity of a competitive marathon is between
minutes himself. 70 percent and 80 percent of the maximal oxygen
uptake (Vo2 max). Vo2 max defines the point at
DR. LOCKSLEY:t Marathons have become increas- which oxygen consumption and combustion can
ingly popular races in the United States, with more no longer keep up with the breakdown of adeno-
than 50,000 men and women runners completing sine triphosphate (ATP) by contracting muscles;
such races in 1979. The high intensity and pro- that is, when oxidative (or aerobic) exercise can
longed duration of these grueling 42 km (26.2 no longer continue. Thus, a marathon is an aero-
mile) road races clearly illustrate the role of body bic event. This contrasts to the sprint events, in
fuels in sustained exercise. Furthermore, a study which ATP is supplied principally by anaerobic
of high-intensity prolonged aerobic exercise can glycolysis and consumption of the stored phos-
shed light on many facets of intermediary metabo- phagens ATP and creatine phosphate.
lism that are broadly applicable to other hyper- The fuel stores in an average man in the rest-
catabolic states, such as occur in trauma, starva- ing postabsorptive state are given in Table 1. At
tion or during surgical procedures. Recent data the pace of a competitive marathon, if only car-
increasingly suggest several metabolic benefits of bohydrate stores (glucose and glycogen) were
long-distance running." 2 The following review used, the blood glucose would be consumed in
*Lloyd H. Smith, Jr, MD, Professor and Chairman, Department less than half a mile, the hepatic glycogen by two
of Medicine.
tRichard Locksley, MD, Chief Medical Resident. miles, and the entire muscle glycogen supply in an
THE WESTERN JOURNAL OF MEDICINE 493
FUEL UTILIZATION IN MARATHONS
the glycogen is stored. The glucose-6-phosphate studies have documented positive correlations be-
units enter the Embden-Meyerhof pathway for tween Vo, max and percent of type I fibers, and
cellular combustion. Similarly, the reservoir for between time to fatigue and percent of type II
the plasma free fatty acids is the body adipose fibers.13'4 That elite athletes gravitate to events
tissue. Hormonal stimulation of adipose lipase at which they have genetic favorability is sub-
cleaves stored triglyceride into glycerol and three stantiated by biopsy data showing a high propor-
FFA, which are released into the blood. As is the tion of type I fibers (up to and over 90 percent)
case for muscle glycogen, muscle triglyceride is in successful long-distance runners versus the pre-
not exportable, as shown by the inability to show dominance of type II fibers in sprinters.'5
glycerol efflux from working muscle.7 Training does not change the inherited propor-
tion of fiber types,'6 although there are data that
Fiber Types show conversion of type Ilb fibers to their more
Human skeletal muscle is a mosaic of two fiber oxidative type Ila profile with endurance train-
types, designated type I and type II on the basis ing.'7 Training, however, is much more important
of myofibrillar ATPase activity measured at alka- than genetics in predicting success. Endurance
line pH.8 Type II fibers (high ATPase activity) training further increases oxidative capacity by
are further subdivided into types Ila and Ilb inducing mitochondrial proliferation in the type I
(Table 2). The proportion of fiber types is ge- fibers,'8 changing type II fibers to a more oxida-
netically inherited and independent of sex, al- tive profile,'7 enhancing the activity of enzymes
though variability is greater in males.9 The which mobilize and transport fatty acids to the
average composition of the human quadriceps muscle,19-24 and increasing sensitivity to the
muscle is 52 percent type I, 33 percent type Ila various hormones which orchestrate the metabolic
and 14 percent type lIb. response.2 This increased oxidative capacity is
As shown in Table 2, type I, or slow twitch reflected by the increased Vo., max in elite dis-
fibers, are characterized by higher oxidative en- tance runners. However, fuel utilization charac-
zyme activities, greater vascularization, higher teristics are applicable to all runners of all abili-
myoglobin content and higher lipid stores.10 These ties, and the following comments apply to all
fibers are ideally suited for activity of myofibrillar runners.
ATPase and glycolytic enzymes. Type II fibers Endogenous Fuels
develop peak tension more rapidly than type 1
fibers, but fatigue more rapidly, because of their Triglyceride
lesser oxidative capabilities. Type Ila fibers have Although muscle triglyceride can contribute up
greater oxidative capacity than type Ilb fibers.10 to between 50 percent and 70 percent of the total
Glycogen content is the same in both types of fatty substrate with exercise,6 the endogenous tri-
muscle fiber. By doing biopsies on muscle after glyceride levels in muscle seem not to affect per-
different types of exercise, the degree of glycogen formance. Depletion rates are related to the
depletion in each of the fiber types gives an indi- amount stored, and not to intensity or duration
cation of which type is used preferentially."1"12 As of exercise.26 In fact, elite runners have lower
expected, type I fibers are utilized for prolonged, endogenous muscle lipid levels. The lesser im-
aerobic work. Type II fibers are used for high portance of endogenous lipid supply to total fat
intensity work of short duration. In exercise at metabolism may be related to the fact that FFA
marathon intensity (70 percent to 80 percent uptake is not rate-limiting in muscle.27
Vo, max) type I fibers are used primarily. Type
II fibers are utilized at the initiation of exercise, Glycogen
before vasodilatation and substrate delivery to Repeat muscle biopsy specimens obtained dur-
type I fibers are maximal, and are recruited as ing the course of running at a steady intensity to
exercise is prolonged and type I fibers fatigue. exhaustion show a curvilinear decline in muscle
Thus, recruitment of type II fibers is dependent on glycogen as exercise is continued. The amount of
the intensity and duration of exercise. muscle glycogen decreases from a normal level of
As might be expected, an increased proportion 9 to 20 grams per kg of muscle to 0.6 to 1.0
of type I fibers would confer a metabolic advan- gram per kg (wet weight).28 With muscle gly-
tage in an event like the marathon, because of the cogen depletion, exhaustion occurs and the run-
increased aerobic capacity of the muscle. Several ning pace can no longer be sustained. Regardless
THE WESTERN JOURNAL OF MEDICINE 495
FUEL UTILIZATION IN MARATHONS
water formed by the metabolisni of 1 gram of At moderate work levels ingested glucose can
glycogen. Thus, each gram of glycogen stored in be utilized by working muscle, thus sparing
muscle yields just over 3 grams of water for re- muscle glycogen. But at marathon race pace,
pleting evaporative losses incurred with exercise.'; ingested glucose has little sparing effect on gly-
cogen.55 This may be due to the increased epi-
Exogenous Fuels nephrine levels at high work loads. In fact, large
Glucose doses of glucose preceding exercise will raise
The blood glucose represents a relatively small portal vein insulin levels and substantially lower
caloric source (20 grams) which must be pre- blood sugar by impairing hepatic glucose output.56
served for utilization by the brain, blood cells and
anaerobic tissues of the body. With exercise, pe- Fr-ee Faux Acids
ripheral uptake of glucose is greatly enhanced, Free fatty acids are the major exogenous sub-
despite the falling insulin levels, a feature ap- strate for working muscle. They are taken up and
preciated by diabetes specialists years ago. The oxidized almost to completion in direct relation-
exercise-induced glucose uptake does require ship to arterial concentration.7'57 The rate-limiting
small amounts of insulin, probably less than 10 to step in muscle FFA use is in mobilization from
12 mU per mi.4' As exercise is continued, glucose adipose stores. The latter occurs principally
turnover can increase 10-fold to 15-fold, and by through norepinephrine stimulation of adipose
three hours at moderate intensity can account for lipase, 5 which cleaves triglyceride, yielding glyc-
about a third of the total oxidative metabolism of erol and three FFA molecules, which are trans-
the let in human subjects."' In trained runners, ported in blood bound to albumin.
who display improved FFA mobilization and utili- At initiation of running, FFA levels decline
zation, less glucose is used, but it may still account owing to uptake by working muscle.5' Subsequent
for 10 percent to 20 percent of total metabolic FFA mobilization is rapid, mediated by sympa-
nceds. thetic outflow and falling insulin levels. After the
Hepatic glucose output increases progressively initial lag, mobilization outstrips uptake as docu-
up to fivefold as exercise continues, first through mented by rising levels of plasma FFA and glyc-
glycogenolysis, and later through enhanced glu- erol. After 40 to 60 minutes of running, FFA levels
concogenesis, as three-carbon substrates (prin- have risen to six times basal levels. Turnover of
cipally alanine, lactate, glycerol and pyruvate) FFA rises as well, reflecting increased muscle uti-
become available.4"; lization of fatty substrate as exercise continues,
All the major hormonal changes of exercise shown by the falling respiratory quotient in exer-
serve to preserve the blood glucose, and to mobi- cising subjects. Except for the initial lag period,
lize stored complex fuels to simpler forms that mobilization continues to supply FFA faster than
can be utilized by working muscle. Of major im- demand, and fractional extraction of FFA actually
portance are the rise in catecholamines and fall decreases as exercise is continued.60 When exer-
in insulin levels. Thus, epinephrine stimulates cise stops, mobilizing forces are unmasked as an
glycogenolysis, inhibits insulin release and inter- overshoot in the FFA level, which is responsible
feres with insulin action peripherally740 nor- for the ketosis after exercise.
epinephrine mobilizes FFA from adipose tissue; The relationship of FFA utilization to exercise
falling insulin levels minimize peripheral glucose intensity (percent Vo., max) is the reverse of
uptake while allowing lipolysis and glycogenolysis, that for glycogen.'' Therefore, at rest and with
and glucagon levels rise to stimulate splanchnic prolonged light exercise, fats can supply over 90
glucose output in concert with increased epineph- percent of the oxidative needs of the muscle. At
rine and falling insulin levels.' 52 moderate work intensities, free fatty acids become
If liver glycogen is depleted, either through the major blood-borne fuel, supplying up to 50
starvation or prolonged exercise, and the intensity percent of the needs of the muscle.60 However, as
of effort is such that the obligate carbohydrate intensity increases above 55 percent to 60 percent
requirement for the working muscle exceeds the Vo2 max, the amount of fat put to use declines in
glycogen content, blood glucose will be utilized. direct proportion to the amount of obligate carbo-
Gluconeogenesis alone cannot maintain the blood hydrate substrate required for reasons previously
glucose at high work intensities, and hypoglycemia discussed. This reciprocal relationship creates a
occurs, stopping exercise.5 3 continuum of fuel utilization from fats (principally
cise contributes a significant portion (approxi- can in no way approach the beneficial effects of
mately 20 percent) of total glycogen utilization. consistent training on performance.
* Dietary manipulation can double muscle gly-
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