Nutritional modulation of training-induced skeletal

muscle adaptations
John A. Hawley, Louise M. Burke, Stuart M. Phillips and Lawrence L. Spriet
J Appl Physiol 110:834-845, 2011. First published 28 October 2010;
doi:10.1152/japplphysiol.00949.2010

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 J Appl Physiol 110: 834–845, 2011.
Review First published October 28, 2010; doi:10.1152/japplphysiol.00949.2010.

HIGHLIGHTED TOPIC Signals Mediating Skeletal Muscle Remodeling by Activity

Nutritional modulation of training-induced skeletal muscle adaptations

John A. Hawley,1 Louise M. Burke,2 Stuart M. Phillips,3 and Lawrence L. Spriet4
1
Health Innovations Research Institute, School of Medical Sciences, RMIT University, Bundoora, Australia; 2Department of
Sports Nutrition, Australian Institute of Sport, Belconnen, Australia; 3Department of Kinesiology, McMaster University,
Hamilton; and 4Department of Human Health and Nutritional Sciences, College of Biological Sciences, University of Guelph,
Guelph, Ontario, Canada
Submitted 17 August 2010; accepted in final form 25 October 2010

Hawley JA, Burke LM, Phillips SM, Spriet LL. Nutritional modulation of
training-induced skeletal muscle adaptations. J Appl Physiol 110: 834–845, 2011. First
published October 28, 2010; doi:10.1152/japplphysiol.00949.2010.—Skeletal muscle dis-
plays remarkable plasticity, enabling substantial adaptive modifications in its
metabolic potential and functional characteristics in response to external stimuli

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such as mechanical loading and nutrient availability. Contraction-induced adapta-
tions are determined largely by the mode of exercise and the volume, intensity, and
frequency of the training stimulus. However, evidence is accumulating that nutrient
availability serves as a potent modulator of many acute responses and chronic
adaptations to both endurance and resistance exercise. Changes in macronutrient
intake rapidly alter the concentration of blood-borne substrates and hormones,
causing marked perturbations in the storage profile of skeletal muscle and other
insulin-sensitive tissues. In turn, muscle energy status exerts profound effects on
resting fuel metabolism and patterns of fuel utilization during exercise as well as
acute regulatory processes underlying gene expression and cell signaling. As such,
these nutrient-exercise interactions have the potential to activate or inhibit many
biochemical pathways with putative roles in training adaptation. This review
provides a contemporary perspective of our understanding of the molecular and
cellular events that take place in skeletal muscle in response to both endurance and
resistance exercise commenced after acute and/or chronic alterations in nutrient
availability (carbohydrate, fat, protein, and several antioxidants). Emphasis is on
the results of human studies and how nutrient provision (or lack thereof) interacts
with specific contractile stimulus to modulate many of the acute responses to
exercise, thereby potentially promoting or inhibiting subsequent training adapta-
tion.
amino acids; adenosine 5=-monophosphate-activated protein kinase; antioxidants;
carbohydrate; fatty acid translocase; endurance training; fat; leucine; mitochondrial
biogenesis; mrna; protein; mitogen-activated protein kinase; pyruvate dehydroge-
nase; resistance training; training adaptation; train-low

SKELETAL MUSCLE IS A MALLEABLE TISSUE with the capacity to alter
its phenotype in response to external stimuli such as contractile
activity and nutrient availability (22). The process of exercise-
induced adaptation in muscle can be simplistically viewed as
the consequence of the accumulation of the type and amount of
specific proteins, with the gene expression promoting an in-
crease in protein concentration pivotal to the training-induced
response (42). Although the responsiveness of individual mes-
senger RNA (mRNA) species to contractile activity is variable
(59), ultimately any increase in steady-state mRNA levels is
the result of synthesis (transcription) and degradation (mRNA
Address for reprint requests and other correspondence: J. A. Hawley, Health
Innovations Research Institute, School of Medical Sciences, RMIT University,
P. O. Box 71, Bundoora, Victoria 3083 Australia (e-mail: john.hawley
@rmit.edu.au).
834 8750-7587/11 Copyright © 2011 the American Physiological Society
stability), with the relative contribution of these processes
playing an important role in phenotypic adaptation (22). The
functional consequences of contraction-induced adaptations
are determined largely by the mode of training (i.e., endurance
vs. resistance based) and the volume, intensity, and frequency
of this stimulus (44). Ultimately, however, the ability of a
given muscle cell to alter the type and quantity of protein is a
function of its half-life; proteins that turn over rapidly and have
high rates of synthesis are capable of attaining a new steady-
state level faster than those that turn over slowly during
adaptation to contractile and other stimuli.
The interaction between exercise training-induced responses
and nutrient availability has long been recognized. Indeed, the
extent to which acutely altering substrate supply can modify
the “training impulse” has been a key research area among
exercise scientists for several decades (5, 46 – 49). Skeletal
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TRAINING-NUTRIENT INTERACTIONS IN SKELETAL MUSCLE
muscle energy status exerts profound effects on resting metab-
olism and fuel use during exercise (2), exercise capacity (5),
acute regulatory events underlying cell signaling (24, 100) and
gene expression (3, 17, 20), and many processes involved in
training adaptation (42, 68, 104).
The major disruptions to cellular homeostasis occur during
exercise, being largely dependent on the relative exercise
intensity and prevailing substrate availability within the active
muscles. The metabolic signals that are believed to play major
roles in activating the various energy-producing pathways can
be broadly classified into three categories: calcium release,
metabolites related to the cytoplasmic phosphorylation poten-
tial ([ATP]/[ADP] [Pi]), and the mitochondrial reduction/oxi-
dation (redox) state of nicotinamide adenine dinucleotide
(NAD/NADH). In addition, the prevailing hormonal milieu,
elevated production of O2 free radicals, electrolyte imbalances
across cell membranes, and disturbances in pH all help “fine-
tune” the metabolic pathways that match the rate of ATP
synthesis with ATP demand (Fig. 1). In response to these
Review
835
ments of muscle-signaling proteins and substrate fluxes during
several hours of postexercise recovery). This review provides a
contemporary perspective of our understanding of the molec-
ular and cellular events that occur in skeletal muscle in re-
sponse to endurance and resistance exercise undertaken after
acute and chronic manipulations of substrate availability. Em-
phasis is on the results of human studies and how nutrient
provision (or lack thereof) interacts with specific contractile
stimuli to modulate many of the acute responses to exercise,
thereby potentially promoting or inhibiting subsequent training
adaptation.
Carbohydrate Availability and the Training
Response/Adaptation
Skeletal muscle glycogen concentration exerts a regulatory
effect on many cellular processes. For example, contraction-
induced as well as insulin-stimulated glucose transport and
glucose transporter 4 (GLUT4) translocation are inhibited by
high muscle glycogen levels (84). Carbohydrate availability

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perturbations, the postexercise period is characterized by a
“general homeostatic recovery phase” that includes the resyn-
thesis of fuel stores, free radical quenching, repair of free
radical-mediated damage, and the restoration of intracellular
electrolyte concentrations and pH (60). This phase is facilitated
through the activation of multiple stress-activated protein ki-
nases and upregulation of gene expression (50, 60) and may
ultimately be the stimulus for the chronic intracellular adapta-
tions that occur over months and years of repeated contractile
activity (97). This premise is attractive and currently forms the
rationale on which the majority of exercise/nutrient studies are
based (i.e., acute interventions coupled with serial measure-
also modulates the expression of many exercise-induced genes;
the rate of translation of postexercise skeletal muscle interleu-
kin-6 (IL-6) mRNA is reduced by glucose feeding during
exercise, whereas lowering glycogen content prior to exercise
amplifies the induction of IL-6 transcription and mRNA in
skeletal muscle. Commencing endurance exercise with low
muscle glycogen stores also results in a greater transcriptional
activation of enzymes involved in carbohydrate metabolism,
including the adenosine 5=-monophosphate-activated protein
kinase (AMPK), GLUT4, hexokinase, and the pyruvate dehy-
drogenase (PDH) complex, compared with when glycogen

Fig. 1. Some of the contraction-induced signals elicited during and after an acute bout of exercise that are likely to be responsible for many of the long-term
(chronic) adaptations as a result of training. These include 1) systemic factors such as an increased blood flow, leading to greater delivery of substrates to muscle
and the concomitant alterations in the hormonal milieu to activate receptor-mediated signaling, 2) the release of cytokines and growth factors from muscle that
would act to stimulate cell surface receptors and activate intracellular signaling cascades, and 3) muscle contraction (resistance or endurance based) per se. In
addition to these, many interdependent factors (both local and systemic) elicit signal transduction in skeletal muscle, including substrate depletion (i.e., glycogen),
hypoxia, impaired oxygen flux, leading to increased muscle lactate accumulation and decreased muscle (and blood) pH, and increased muscle temperature. It
is likely that any contraction-induced response is an integrated summation of several of these factors and does not depend on one single signaling pathway and/or
mechanism. Although the major disruptions to cellular homeostasis occur during an exercise bout, the time course responses of several signaling pathways during
recovery from exercise are likely to be of major significance for the activation of many of the stress-activated protein kinases and upregulation of gene
transcription. AdipoR1, adiponectin receptor 1; AMPK, AMP-activated protein kinase; AS160, Akt substrate of 160 kDa; GLUT4, glucose transporter 4; IMTG,
intramyocellular triglyceride; IRS, insulin receptor substrate; LAT1, L-type amino acid transporter; mTOR, mammalian target of rapamycin; ROS, reactive
oxygen species; SIRT1, sirtuin 1; PGC-1, peroxisome proliferator-activated receptor-␥ coactivator-1; PPAR, peroxisome proliferator-activated receptor.

J Appl Physiol • VOL 110 • MARCH 2011 • www.jap.org

Review
836 TRAINING-NUTRIENT INTERACTIONS IN SKELETAL MUSCLE
content is normal (for review, see Ref. 46). Because the time
course of transcriptional activation for many exercise-induced
genes occurs during the first few hours of recovery (60),
returning to basal values within 24 h (101), such events may be
linked by common signaling and/or regulatory mechanisms,
such as the restoration of muscle energy stores, predominantly
glycogen (84).
Against this “molecular background,” Hansen et al. (42)
proposed that training commenced with low muscle glycogen
availability would promote adaptation to a greater extent than
when the same sessions were commenced with normal glyco-
gen concentration. To test this hypothesis, these workers used
a 10-wk training block and a study design in which the right
and left legs of the same (untrained) subject performed the
same amount of total work during the intervention period with
different preexercise muscle glycogen content. Resting muscle
glycogen content, the maximal activity of citrate synthase, and
exercise time to exhaustion were all enhanced to a greater
extent in the leg that commenced training sessions with low
compared with normal muscle glycogen content. The term
“train-low, compete-high” was promulgated to describe this
novel training approach (42). Subsequently, we investigated
the train-low paradigm during a 3-wk intervention in well-
trained individuals (104). We reasoned that athletes would
have maximized their training adaptation and that further gains
would be negligible, irrespective of whether they trained with
low or normal levels of muscle glycogen. Training frequency
and intensity was manipulated so that intense interval training
sessions were commenced at a time when glycogen stores were
lowered by ⬃50% through prior exercise or were replete (104).
Maximal self-selected power output was lower when athletes
commenced intervals with low compared with normal glyco-
gen availability. Yet despite a lower training impulse resting
muscle glycogen concentration, the maximal activities of ci-
trate synthase and ␤-hydroxyacyl-CoA-dehydrogenase and the
total protein content of cytochrome c oxidase subunit IV were
higher (compared to pretraining values) only in subjects who
commenced interval training with low muscle glycogen con-
tent. Hulston et al. (53) also reported that self-selected power
output was compromised when trained cyclists started high-
intensity interval training sessions with low glycogen stores
and that tracer-derived measures of fat oxidation during sub-
maximal cycling were increased after train-low. Specifically,
muscle-derived triacylglycerol oxidation increased after train-
ing with low glycogen availability (53).
In addition to altering endogenous carbohydrate stores, other
exercise/diet protocols have been utilized to manipulate exog-
enous glucose availability, including training after an overnight
fast, prolonged training with or without an overnight fast, and
withholding carbohydrate intake during the session and/or
withholding carbohydrate during the first hours of recovery
(reviewed in Ref. 46). In contrast to the robust effects of
commencing endurance training sessions with low muscle
glycogen stores, the results of studies that have manipulated
glucose availability before, during, and/or after endurance
exercise on selected muscle adaptations are equivocal. Several
investigations report that, after 6- to 10-wk intervention peri-
ods, a range of training-responsive metabolic markers (includ-
ing succinate dehydrogenase activity, GLUT4, and hexokinase
II content) are increased by a similar extent with or without
carbohydrate supplementation (1, 32). However, others have
J Appl Physiol • VOL
reported subtle differences in muscle adaptation after reducing
carbohydrate availability during training (23, 73). To date, only
one study has examined the interactive effects of endogenous
muscle glycogen and exogenous glucose availability on train-
ing adaptation. Morton et al. (68) employed a variety of
training protocols (twice/day, 2 days/wk, or once/day, 4 days/
wk) and dietary manipulations (with or without carbohydrate
support before and during exercise) in recreational subjects for
6 wk. All protocols were associated with an increase in the
protein concentrations of cytochrome c oxidase IV and the
peroxisome proliferator-activated receptor-␥ coactivator-1␣
(PGC-1␣), with no differences in the magnitude of change
between groups who trained with low vs. high carbohydrate
availability. Only the maximal activity of succinate dehydro-
genase was greater in subjects who commenced training with
lowered muscle glycogen stores and who did not receive
carbohydrate support during/after training.
Taken collectively, the results of these studies (1, 23, 32, 42,
53, 73, 104) demonstrate that, independent of prior training
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status, short-term (3–10 wk) training programs in which a
portion of workouts are commenced with either low muscle
glycogen and/or low exogenous glucose availability augment
training adaptation (i.e., they increase the maximal activities of
selected enzymes involved in carbohydrate and/or lipid metab-
olism and promote mitochondrial biogenesis) to a greater
extent than when all workouts are undertaken with normal or
elevated glycogen stores. However, carbohydrate availability is
not the only variable manipulated in these investigations. The
studies employed different modes of training and a range in the
number of training sessions (both in total number and those
undertaken under conditions of low carbohydrate availability),
along with variable intervention periods. It is quite possible
that some of the results are not directly attributable to differ-
ences in carbohydrate availability per se but rather to the
effects of the exercise training protocol itself (i.e., differences
in recovery time between workouts, training once/day vs. twice
every 2nd day). Notwithstanding this possibility, there is no
evidence of impaired adaptation (or a decrement to perfor-
mance outcomes) after short-term training with low carbohy-
drate availability. Although the potential mechanisms underly-
ing these training-nutrient interactions have not been eluci-
dated, they may involve roles for two exercise-sensitive
signaling molecules that promote many of the contractile-
induced adaptations in skeletal muscle, the AMPK and the
mitogen-activated protein kinase (MAPK). Recent studies (dis-
cussed below) demonstrate that the activation of these two
proteins is certainly modified by nutrient availability (or lack
thereof), but at present it is not clear how altering AMPK
and/or p38 activity might lead to an improved training adap-
tation.
One molecule with a central role in monitoring cellular
energy status is the AMPK. In humans, seven genes encode
AMPK subunits (␣1, ␣2, ␤1, ␤2, ␥1, ␥2, and ␥3), giving the
possibility of at least 12 ␣,␤,␥ heterotrimers. The recent
discovery of glycogen-binding sites on the AMPK ␤-subunits
(61) has led to the hypothesis that this regulatory domain may
also allow AMPK to act as a sensor of endogenous glycogen
stores (62). In this scenario, the glycogen-binding domains act
as sensors enabling AMPK to gauge the state of cellular
glycogen, increasing AMPK activity when stores are low and
decreasing the signal when stores are replete or elevated.
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TRAINING-NUTRIENT INTERACTIONS IN SKELETAL MUSCLE
Experimental evidence from human studies provides indirect
support for this hypothesis. Wojtaszewski et al. (100) first
demonstrated that lowering muscle glycogen stores in trained
individuals increased ␣1 and ␣2 activity and acetyl-CoA car-
boxylase Ser221 phosphorylation at rest and during subsequent
exercise to a greater extent than when exercise was com-
menced with elevated glycogen levels. We also found that the
magnitude of increase in AMPK phosphorylation in well-
trained individuals who performed a bout of high-intensity
interval training was greater when the session was commenced
with low compared with normal glycogen stores (103). The
AMPK has been reported to phosphorylate and inactivate
histone deactylase 5 (HDAC5), leading to the removal of
HDAC5 from the nucleus and allowing the myocyte enhancer
factor 2 to bind and activate PGC-1␣. PGC-1␣ has a cAMP
response element in its promoter region, whereas cAMP re-
sponse element-binding protein (CREB) has also been identi-
fied as a downstream target of AMPK. To determine whether
the increase in AMPK activation after an acute bout of intense
training commenced with low glycogen availability might
explain our previously observed training-induced differences
in muscle adaptation (104), we analyzed several downstream
protein targets of AMPK with putative roles in mitochondrial
biogenesis. We found no differences in the localization of
HDAC5 and the phosphorylation state of CREB when subjects
commenced intense exercise with either low or normal muscle
glycogen content (103), suggesting that the exercise/nutrient-
induced increase in AMPK phosphorylation was insufficient to
specifically increase its activity toward HDAC5 and CREB or
that there are other mechanisms by which chronic activation of
AMPK increases mitochondrial enzyme activity.
MAPK pathways have also been implicated as possible
signaling mechanisms involved in the regulation of exercise/
nutrient adaptations (97). Signal transduction through one of
these kinases, the p38 MAPK, is mediated by four isoforms (␣,
␤, ␦, and ␥), with the existence of these isoforms giving
specificity in mediating downstream biological responses in-
duced by exercise and/or nutrient availability (97). Chan et al.
(19) first showed that alterations in macronutrient intake that
reduced muscle glycogen content lead to an increased phos-
phorylation of nuclear p38 MAPK in human skeletal muscle in
response to moderate exercise. However, we recently found
little change in either the phosphorylation state of this kinase or
one of its downstream targets (activating transcription factor 2)
after a bout of intense cycling commenced with either low or
normal muscle glycogen content (103). Cochran et al. (21)
investigated the effects of altering glucose availability during
recovery from exercise on metabolic and signaling responses to
a subsequent bout of exercise undertaken several hours later
(i.e., twice/day training). Two identical sessions of high-inten-
sity interval exercise separated by a 3-h recovery period,
during which subjects consumed carbohydrate (HI-HI) or pla-
cebo (HI-LO), were performed. There was a fourfold increase
in phosphorylated p38 MAPK after the first session that had
returned to baseline levels prior to the second session regard-
less of carbohydrate availability. However, after the second
session, p38 MAPK phosphorylation was ⬃50% higher in
HI-LO vs. HI-HI. Since resting glycogen content and glycogen
utilization during exercise were similar between treatments,
these workers (21) concluded that “carbohydrate ingestion, and
not necessarily changes in muscle glycogen content per se,
J Appl Physiol • VOL
Review
837
alters the metabolic response to repeated sessions of high-
intensity interval exercise.” Although it is tempting to presume
that there is an amplified training adaptation when training
sessions are commenced with low muscle stores and/or altered
glucose availability before, during, and/or after endurance-
based exercise, it is important to note that carbohydrate restric-
tion has reciprocal and pronounced effects on lipid availability.
The responses to altering fat availability on training adaptation
are now discussed.
Fat Availability and the Training Response/Adaptation
The oxidation of fat makes an important contribution to
energy production during exercise at low to moderate intensi-
ties, with the absolute amount of fat oxidized being largely a
function of the mitochondrial volume of the contracting mus-
culature. Although muscle and liver glycogen stores are para-
mount to the successful performance of intense aerobic exer-
cise, the oxidation of fat plays an important role in “sparing” or
providing an alternate substrate to carbohydrate at exercise
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intensities of up to ⬃60 – 65 of maximal O2 uptake (V̇O2max) in
untrained and 75– 85% of V̇O2max in trained individuals (89).
Accordingly, consuming a high-fat diet while undertaking
daily training could augment the normal training-induced in-
creases in fat oxidation, reduce carbohydrate utilization, and
delay the onset of fatigue during prolonged exercise. Helge et
al. (49) were the first modern-day researchers to study the
interaction of training and a high-fat diet on metabolism and
training capacity. They studied 20 untrained males who in-
gested either a high-fat (n ⫽ 10) or high-carbohydrate (n ⫽ 10)
diet while performing endurance training 3– 4 times/wk for 7
wk. During the 8th wk, both groups ingested a high-carbohy-
drate diet. Endurance performance undertaken at the comple-
tion of the 7th wk of the training program revealed a signifi-
cantly greater improvement after a carbohydrate-rich diet had
been consumed during training compared with a fat-rich diet
(56%). Even when the high-fat diet was replaced by a high-
carbohydrate diet for the 8th wk of training, endurance perfor-
mance was still significantly lower than in subjects who had
trained for the complete duration on a high-carbohydrate diet.
Helge et al. (49) concluded that “ingesting a fat-rich diet during
an endurance training programme is detrimental to endurance
performance . . . due to suboptimal adaptations that are not rem-
edied by the short-term increase in carbohydrate availability.”
Given that the greatest stimulus to any exercise-induced
skeletal muscle adaptation is repeated training bouts, diet
alterations must be tolerable and robust enough to ultimately
cause an augmented adaptation that serves some functional
purpose. With these issues in mind, a more practical training
diet approach was formulated in which already well-trained
athletes were exposed to a short-term (4 –7 days) high-fat diet
(“fat adaptation”) while they maintained their normal strenuous
training regimens (15–17, 88, 89). This period of fat adaptation
is immediately followed by a “carbohydrate restoration” phase,
during which a high-carbohydrate diet is consumed for 24 –72
h. Compared with an isoenergetic carbohydrate diet, such
“dietary periodization” increases rates of whole body fat oxi-
dation and attenuates the rate of muscle glycogenolysis during
submaximal exercise (15) without concomitant changes in
mitochondrial content. Remarkably, these metabolic pertur-
bations favoring the oxidation of fat persist even in the face
110 • MARCH 2011 • www.jap.org
Review
838 TRAINING-NUTRIENT INTERACTIONS IN SKELETAL MUSCLE
of increased carbohydrate availability, namely replenished
muscle and liver glycogen stores and exogenous glucose
ingestion (16).
Although consumption of high-fat diets in individuals who
maintain their normal training regimen elicits higher rates of
fat oxidation during submaximal exercise compared with high-
carbohydrate diets (45), such efforts require greater physiolog-
ical and mental effort (89). Indeed, it seems unlikely that fat
oxidation can sustain the demands of high-intensity training
typically undertaken by competitive endurance athletes. To test
this hypothesis, Stepto et al. (89) determined the effect of
consuming a high-fat diet for 4 days on the training responses
of competitive ultraendurance cyclists/triathletes. During the
intervention period, subjects performed two high-intensity cy-
cle interval training sessions consisting of a 20-min warm up at
65% of V̇O2max followed by 8 ⫻ 5-min work bouts at 86% of
V̇O2max with 1-min recovery. Rates of fat oxidation during the
20-min warmup were 69 ⫾ 25 ␮mol·kg⫺1·min⫺1, and despite
an increase in both the relative and absolute power output
(from 232 to 323 W), rates of fat oxidation were not signifi-
cantly different (89). This indicates that after 4 days of a
high-fat diet, well-trained athletes were better able to oxidise
fat during high-intensity exercise to compensate for their low
muscle glycogen stores. Although the subjects in that study
(89) could complete a short-term diet-training regimen, it
seems likely that consumption of a fat-rich diet for longer
periods would limit the ability of well-trained athletes to
undertake strenuous training.
What mechanisms explain how fat adaptation strategies
increase fat oxidation during exercise and reduce the reliance
on carbohydrate in the absence of mitochondrial volume
changes in athletes who already have the capacity for high
absolute rates of fat oxidation? Potential signals for upregulat-
ing the proteins that metabolize fat (while also possibly down-
regulating proteins that metabolize carbohydrate) are the
chronic decreases in insulin concentration and reciprocal in-
creases in plasma fatty acid (FA) levels that occur during the
fat adaptation phase of the intervention. For example, FAs are
ligands for the family of peroxisome proliferator-activated
receptors (PPARs), transcription factors that upregulate fat-
metabolizing proteins (36). To date, however, few cellular
studies have been undertaken in an attempt to unravel the
mechanisms underpinning the carbohydrate sparing reported
after fat adaptation.
The movement of long-chain FAs into contracting skeletal
muscle cells is mainly via the FA transporters fatty acid
translocase (FAT)/CD36 and plasma membrane fatty acid-
binding protein (FABPpm) (40, 70). FAs also require transport
into mitochondria, where they are ultimately oxidized, a pro-
cess involving the carnitine palmitoyl transferase complex
(52). Five days of fat adaptation did not alter the total muscle
protein abundance of carnitine palmitoyl transferase I or FAB-
Ppm but did increase total FAT/CD36 protein content in
skeletal muscle (17). Carbohydrate restoration restores FAT/
CD36 protein content to those levels measured prior to fat
adaptation (102), suggesting that FAT/CD36 is the transport
protein most sensitive to alterations in dietary fat intake.
However, FA transport proteins are present in the cytoplasm
and on both the sarcolemmal and mitochondrial membranes.
Previous studies have been limited to measurements of changes
in total muscle protein and therefore provide no information
J Appl Physiol • VOL
regarding the location where such perturbations occurred. Re-
cent human experiments reveal that, although exercise training
increases total muscle FABPpm and FAT/CD36 content, the
changes at the sarcolemma were confined to FABPpm, with the
increase in FAT/CD36 occurring on the mitochondrial mem-
branes (90). In addition, exercise (2 h of moderate-intensity
cycling) resulted in a translocation of FAT/CD36 to the muscle
membrane (Bradley NS, Snook LA, Jain SS, Heigenhauser
GJF, Bonen A, and Spriet LL, unpublished observations) and
the mitochondrial membranes (51). Future work is required to
determine whether fat adaptation and carbohydrate restoration
alters the presence of FA transporters on the muscle and
mitochondrial membranes both at rest and during subsequent
exercise.
Fat adaptation increases intramyocellular triglyceride (IMTG) lev-
els (102) and also increases the activity of hormone-sensitive
lipase (HSL) (88), suggesting that IMTGs contribute more fuel
to exercise following fat adaptation. However, such a hypoth-
esis has not been verified experimentally. The overall triglyc-
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eride (TG) content within muscle following a training session
or prior to the next session is dependent on the balance between
the rates of FA uptake, oxidation, and storage and TG hydro-
lysis. The esterification of TG requires acylation by acyl-CoA
synthetase and the sequential addition of FAs to a glycerol
backbone in a series of reactions with the activities of glycerol-
3-phosphate acyltransferase (GPAT) and diacylglycerol acyl-
transferase (DGAT) believed to be regulatory. On the break-
down side, adipose triacylglycerol lipase (ATGL) and HSL
appear to work hierarchically to regulate complete TG hydro-
lysis. ATGL initiates lipolysis by removing the first FA from
TG to produce diacylglycerol, which is then hydrolyzed by
HSL to generate a second FA and monoglycerol (MG), which
is converted to FA and glycerol by MG lipase (96). Although
all the key enzymes may be upregulated after fat adaptation,
the activities of DGAT and GPAT may be dominant at rest
(resulting in higher IMTG levels), whereas ATGL and HSL
may be more active during exercise (resulting in greater IMTG
utilization), but this hypothesis has not been tested.
Fat adaptation also has profound effects on the regulation of
PDH, the key enzyme regulating muscle carbohydrate oxida-
tion. High-fat diets rapidly downregulate the active form of
PDH protein at rest (74), accomplished by rapid upregulation
of PDH kinase (PDK) activity, mainly through an increased
content of the diet-sensitive PDK4 isozyme. Increased PDK
activity moves most of the PDH to the inactive form and
decreases carbohydrate oxidation. It is likely that the high-fat
diet-induced reduction in circulating insulin concentration and
the increased FA levels rapidly affect these changes (75).
Following fat adaptation (81) and carbohydrate restoration
(88), PDH activation is reduced at rest and over a range of
exercise intensities. Accordingly, carbohydrate oxidation is
reduced and contributes to a sparing of muscle glycogen (81,
88). Refeeding with carbohydrate following a high-fat diet
quickly decreases PDK activity, but the suppression of PDH
activation and impaired carbohydrate oxidation remain for
several hours at rest (9). Carbohydrate restoration for 24 h
partially restores rates of carbohydrate oxidation to normal, but
PDH activation remains blunted during moderate and all-out
exercise (88). These studies are consistent with a persistent
effect of fat adaptation on muscle fuel choice, but clearly,
110 • MARCH 2011 • www.jap.org

TRAINING-NUTRIENT INTERACTIONS IN SKELETAL MUSCLE
additional work is needed to examine the cellular regulation of
these changes following this dietary protocol.
Protein Availability and the Training Response/Adaptation
Protein synthesis is the end point in the complex process of
contraction-induced adaptation that promotes phenotype-spe-
cific characteristics in skeletal muscle. From this perspective, it
is clear that both resistance exercise and the feeding of protein
or amino acids (AAs) have a marked stimulatory effect on rates
of muscle protein synthesis (MPS) (6, 12, 78). AA feeding is
synergistically stimulatory with resistance-type exercise for
MPS, and when combined the resultant increase in net protein
balance [defined as MPS minus muscle protein breakdown
(MPB)] is greater than either alone (7, 77). Although the time
course of stimulation of MPS with feeding is rather transient,
being in the range of hours at most (66), contractile activity can
stimulate MPS for 48 –72 h (64, 79). Although the duration for
which MPS is elevated postexercise is reduced in trained
individuals (92), the stimulation of MPS is still much longer
than after feeding alone. Undertaking chronic resistance exer-
cise also elevates basal rates of MPS (77, 79) and results in a
latent stimulatory effect on the feeding-induced rise in MPS as
long as 24 h postexercise (13). In contrast, it is not currently
known whether protein supplementation has similar benefits
for athletes undertaking repeated endurance training sessions.
However, mitochondrial protein synthesis is stimulated follow-
ing acute and chronic endurance exercise (98), and one might
speculate that this capacity would be amplified with increased
exogenous protein availability. Our current view of the adap-
tive response to exercise is that acute changes in net protein
balance are relevant and meaningful since they have been
shown to be, at least qualitatively, predictive of a long-term
phenotypic change (93). In this model, protein is more than
merely substrate; it is an input into the system that affects
phenotype due to the influence it exerts over the regulation of
rates of MPS.
There are three easily defined time periods for increasing
nutrient (i.e., protein/AA) availability to augment the acute
contraction-induced adaptive response in skeletal muscle: pre-
exercise (within 1 h before the start of a bout of exercise),
during the exercise bout itself, and postexercise (⬍3 h after the
completion of the exercise bout). Tipton et al. (95) investigated
whether consumption of an oral essential AA-carbohydrate
supplement before a bout of resistance exercise results in a
greater anabolic response than supplementation after exercise.
Blood and muscle phenylalanine concentrations were increased
by ⬃130% after drink consumption in both trials. However,
delivery of AA ([AA] ⫻ blood flow) was greater with pre- vs.
postexercise feeding during the exercise bout and in the 1st
hour after exercise (95). These results show that the response
of net muscle protein synthesis to consumption of protein
immediately before resistance exercise is greater than when the
solution is consumed after exercise and suggest a preexercise
feeding enhancement of blood flow and subsequent amino acid
delivery as being primary determining factors in protein accre-
tion. However, the results from that study (95) could not be
reproduced subsequently by the same group (94) or others (38).
Thus, preexercise protein feeding is unlikely to confer benefit
for promotion of increases in MPS and long-term gains in
muscle mass.
J Appl Physiol • VOL
Review
839
The provision of protein during exercise appears to be an
effective strategy for promoting MPS since the AA substrate
may allow earlier rises in the blood AA profile and “kick-start”
MPS and/or trigger local or systemic signaling responses that
promote increased MPS. However, during exercise, MPS is
blunted (18, 33). Although the precise mechanisms underlying
this phenomenon are not well understood, Rose et al. (86) have
demonstrated that Ca2⫹-mediated signaling is involved in
suppressing MPS during contraction, at least in fast-twitch
muscles of rats undergoing in situ stimulation. Using the
phosphorylation of eukaryotic elongation factor-2 as a proxy
marker for MPS, Rose et al. (87) also showed that endurance
exercise induced a rapid increase in the phosphorylation state
of this protein, suggesting that the elongation phase of MPS is
suppressed. However, it is unlikely that the same situation
occurs in humans during resistance exercise since the continual
rest-recovery cycles that are an integral part of resistance-based
training bouts are likely to permit a degree of recovery in
muscle energetic and/or calcium ion homeostasis not observed
Downloaded from jap.physiology.org on March 23, 2011
in animal models. In fact, when protein is consumed during
resistance exercise, a rise in MPS does occur (4), indicating
either that the perturbations in energy status and/or to Ca2⫹
signaling were not sufficient to suppress synthesis or that
protein feeding overcomes any suppression of MPS. Thus,
exercise has already started to activate signaling mechanisms
during resistance exercise, and AA delivery to the muscle
begins to stimulate a significant rise in MPS.
Postexercise nutrient provision has a significant, positive
impact on MPS, being markedly greater than exercise alone (7,
77). Nutrient provision (i.e., increased AA availability) or the
associated rise in insulin (8) also suppresses the resistance
exercise-induced MPB that occurs in the absence of nutrition
(6, 78). The resultant positive net protein balance has been
postulated to be additive and result in protein accumulation and
skeletal muscle hypertrophy over time. A number of training
studies have utilized immediate postexercise protein provision
vs. delayed nutrition or provision of energy alone (usually as
carbohydrate) and have reported that early postexercise protein
provision is more beneficial in promoting hypertrophy (25, 43).
In summary, there is robust evidence to support the hypothesis
that postexercise protein consumption promotes a pronounced
rise in the rate of MPS while concomitantly suppressing rates
of MPB, leading to increases in net muscle protein balance and
protein accretion. Long-term studies that have manipulated the
timing of protein provision report enhanced gains in the ana-
bolic profile with early postexercise ingestion, although this is
not always the case. A number of factors may explain the
variable results between training studies, including the protein
dose (66), the type (i.e., source) of protein (43, 91, 99), and the
age and training status of the participants. Finally, several
training studies have used a combination of pre- and postex-
ercise feeding to augment gains in muscle mass (14, 26),
preventing a clear conclusion regarding protein timing being
made.
Recent work has provided insight into the identity of the
molecular pathways involved in the nutrition- and resistance
training-induced increase in MPS. A comprehensive evaluation
of this topic is beyond the scope of the present article, and
readers are referred to recent reviews of this area (34, 55).
Many groups have identified a central role for the mammalian
target of rapamycin cascade in anabolic processes following
110 • MARCH 2011 • www.jap.org
Review
840 TRAINING-NUTRIENT INTERACTIONS IN SKELETAL MUSCLE
acute and chronic resistance exercise in humans and also the
proteins implicated in translational control, such as ribosomal
protein S6 kinase (S6K1) and eukaryotic initiation factor 4E-
binding protein. There is evidence for an important role of
S6K1 in skeletal muscle hypertrophy. For example, increases
in S6K1 phosphorylation after a bout of resistance exercise
display a similar time course to that of myofibrillar protein
synthesis (57) and strongly correlate with the chronic increase
in muscle mass and strength after a 14-wk resistance training
program in humans (93). These results show that the acute
responses to exercise/nutrient protocols that have measured
either dynamic changes in muscle protein turnover or early
activation of muscle signaling proteins such as S6K1 are
qualitatively predictive of long-term phenotypic changes.
If, as proposed, both exercise and feeding elicit independent
and synergistic effects on MPS, then what are the factors that
influence these responses? Clearly, different contraction pro-
tocols will affect the adaptation responses of MPS that may be
specific to mitochondrial or myofibrillar protein pools (11, 13,
65, 67). In addition, only recently have we begun to appreciate
how different proteins and AAs can affect MPS. Leucine has
emerged as a key nutritional regulator of MPS, and a number
of studies in humans have reported greater stimulation of MPS
with leucine-enriched AA mixtures (34) and naturally leucine-
enriched proteins (91) than casein-rich AAs. These observa-
tions lead us to hypothesize that there exists a “leucine trigger”
or “leucine threshold” concentration for a maximal rate of
MPS, which is the concentration of blood leucine at which
MPS is maximally stimulated. Based on the data of Moore et
al. (66), an oral dose of leucine of ⬃2 g is sufficient to elicit a
blood leucine concentration that maximally stimulates protein
synthesis. However, it is important to realize that these data are
taken from young men, and the situation is likely quite differ-
ent in persons with lower body masses or in the elderly.
Nonetheless, although many questions remain unanswered
within the complex molecular processes that determine the
specificity of training adaptation and nutrient-training interac-
tions in skeletal muscle, the equation for protein is simple;
contraction followed by protein or AA ingestion yields en-
hanced protein synthesis and favorable phenotype-specific ad-
aptations.
Antioxidants and Phytochemicals
Recent recognition that vitamins and other food chemicals
interact with the signaling events that underpin training adap-
Fig. 2. Suggested representation of homesis applied to
oxidative stress and antioxidant supplementation. Some
oxidative stress is needed to induce endogenous antioxidant
defenses and activate select signaling pathways underpin-
ning mitochondrial biogenesis. Large amounts of oxidative
stress cause cellular damage and impair cellular function.
RNOS, reactive nitrogen and oxygen species.
J Appl Physiol • VOL
tation has stimulated several new areas of research. Such
interest has been driven largely by the discovery of a broad
range of bioactive but nonnutritive substances in plant sources,
including fruits, vegetables, grains, herbs, and spices. Collec-
tively, these compounds are known as phytochemicals, and
although many are well recognized for their antioxidant prop-
erties, their bioactivity may be promoted via a multitude of
mechanisms.
An acute bout of exercise results in an increased generation
of reactive nitrogen and oxygen species (known collectively as
RNOS) within skeletal muscle and other tissues (28). Increased
levels of RNOS are associated with acute impairment of
muscle force production as well as excessive inflammation and
damage to the cell (56). Although increasing cellular antioxi-
dant capacity via supplementary intake of antioxidants seems a
logical approach to counteract the negative effects of RNOS on
muscle force capability, studies of supplementation with anti-
oxidant vitamins in association with acute or chronic exercise
models have produced equivocal outcomes with respect to
Downloaded from jap.physiology.org on March 23, 2011
restoration of performance capacity and attenuation of muscle
damage (37). The theory of “hormesis,” which states that
biological systems respond to some stresses in a bell-shaped,
curve-like manner, has been applied to RNOS to explain such
findings (82). In this model (Fig. 2), large changes in oxidative
stress impair cellular function, whereas small and confined
changes confer positive benefits. For example, small redox
changes play a role in signal transduction of key events
underlying mitochondrial biogenesis, with RNOS recently be-
ing shown to induce PGC-1␣ promoter activity and mRNA
expression via the activation of AMPK (54). In addition, small
amounts of oxidative stress promote upregulation of the en-
dogenous oxidative defense system, which consists of complex
interactions of enzymatic and nonenzymatic antioxidants com-
partmentalized throughout the cytoplasm and within various
structures such as the mitochondria (80).
The hormetic curve predicts several potential interactions
between exercise, RNOS, and dietary compounds with antiox-
idant properties that warrant further investigation. For instance,
since “antioxidants” are redox agents that can act as antioxi-
dants in some circumstances and pro-oxidants in others, de-
pending on the dosage and site of activity, as such, can
antioxidant supplementation mimic the oxidative stimulus
achieved by contractile stimuli? Does provision of antioxidants
confer an additive stimulus when combined with exercise or
suppress the signaling activities underpinning the acute re-
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TRAINING-NUTRIENT INTERACTIONS IN SKELETAL MUSCLE
sponses to exercise, leading to subsequent training adaptation?
Adding complexity to these issues is the type and dosage of
antioxidant compounds, the training status of individuals, and
the other bioactive properties of these compounds. In review-
ing the evidence for these interactions, it would be ideal to
consider only human data; however, because of the recent
nature of this work, we are forced to rely on investigations with
in vitro or animal models. We note that particular caution
should be taken in extrapolating these data to trained humans
because of the potential for differences in the bioavailability or
bioactivity of vitamins and phytochemicals.
The results of investigations that have determined the effect
of antioxidant vitamin supplementation on mitochondrial bio-
genesis and the training response are mixed. Ristow et al. (85)
studied the effects of 4 wk of aerobic training and antioxidant
supplementation (1,000 mg/day vitamin C and 400 IU/day
vitamin E) in groups of trained and previously untrained males.
Matched groups treated with placebos exhibited an increase in
oxidative stress as a result of exercise (increased thiobarbituric
Review
841
have failed to find evidence of an impaired response to training
while exposed to antioxidant supplements. Yfanti et al. (105)
studied healthy but previously sedentary men who trained
strenuously for 12 wk and were supplemented with a daily
intake of 500 mg of vitamin C and 400 IU of vitamin E or a
placebo treatment. Independent of treatment condition, all
subjects had improved exercise capacity and increased muscle
superoxide dismutase, glycogen concentration, and maximal
enzyme activities of citrate synthase and ␤-hydroxyacyl-CoA-
dehydrogenase (105). It is important to undertake further
investigation of the effect of supplementation with antioxidant
vitamins on training adaptations because of the prevalence of
vitamin supplementation among athletes and the potential for
negative outcomes.
The literature pertaining to the interaction of exercise and
supplementation with phytochemicals is also equivocal. Many
of the polyphenolic compounds exert a variety of biological
activities, making it hard to determine direct cause-effect
relationships. For example, quercetin is known to be an anti-

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acid-reactive substances) as well as increased expression of
PPAR␥ and its coactivators PGC-1␣ and PGC-1␤. These
outcomes were not observed in antioxidant-treated groups,
regardless of background training status. Molecular mediators
of endogenous antioxidant defense (superoxide dismutases 1
and 2; glutathione peroxidase) and an increase in insulin
sensitivity were also induced by exercise but blocked by
antioxidant supplementation (85).
A similar blunting of exercise benefits was noted when
previously untrained men undertook 8 wk of aerobic training
supplemented by a daily dose of 1 g of vitamin C; a placebo-
matched group improved their V̇O2max by 22%, whereas the
supplemented group experienced only an 11% increase (41). A
parallel set of experiments detailed in the same study reported
impaired aerobic capacity and endurance in exercised rats
supplemented with vitamin C compared with a placebo-treated
group. Nonsupplemented rats displayed an increase in mito-
chondrial cytochrome c concentrations and the transcription
factors PGC-1, nuclear respiratory factor-1, and mitochondrial
transcription factor A, whereas these measurements were in-
hibited in animals supplemented with vitamin C. A blunting of
the increase in antioxidant enzymes superoxide dismutase and
glutathione peroxidise was also observed. In contrast, others
oxidant, an anti-inflammatory and adenosine receptor antago-
nist (30). In vitro and rodent models show that some phyto-
chemicals can also act as so-called “exercise mimetics,” pro-
moting a direct enhancement of mitochondrial biogenesis.
Table 1 summarizes studies involving sedentary models and
supplementation with compounds such as resveratrol, querce-
tin, nootkatone, and epigallocatechin-3-gallate (EGCG), agents
that induce metabolic responses that mimic the effects of
aerobic training in the absence of an exercise stimulus through
the activation of PGC-1␣, sirtuin 1, and other exercise-induc-
ible pathways (30, 58, 69). Human studies involving short-term
supplementation in sedentary subjects have focused on func-
tional outcomes such as enhancement of insulin sensitivity and
exercise capacity, with mixed findings (27, 29, 39, 83). The
lack of direct measurements of muscle responses in human
studies makes it difficult to ascertain whether the divergent
findings of the various studies reflect differences in the efficacy
of supplemental compounds in different circumstances (i.e.,
background fitness level of subjects, type and dosing regimen
of phytochemicals, etc.) or differences in the sensitivity of
various research protocols to detect changes in the functional
outcome variables. Whether dietary sources of phytochemicals
can attain the optimal dose of any products found to be

Table 1. Examples of phytochemicals with exercise mimetic effects in sedentary models (supplementation in the absence of
exercise or training stimulus)
Compound Sources Evidence of Effects

EGCG Green tea Forty-eight hours of EGCG supplementation (3 ⫻ 135 mg/day) increased V̇O2max in healthy subjects (83).
Nootkatone Grapefruit Mice fed with nootkatone showed increases in muscle AMPK activity and ␤-oxidation, protection against
weight gain with a high-fat diet, and enhanced swimming endurance (64). Cell culture studies showed
increased activity of PGC-1␣ with nootkatone (69).
Quercetin Apples, onions, berries Seven days supplementation with quercetin (1 g/day) increased V̇O2max and cycling endurance in sedentary
men; although no mechanisms were measured, authors proposed an increase in mitochondrial biogenesis
(29). Fourteen days of supplementation (1 g/day) increased cycling performance and was associated
with a trend toward increased mRNA content for SIRT1, PGC-1␣, cytochrome c oxidase, and citrate
synthase (72). In contrast, other studies of untrained subjects have failed to find improvements in
exercise capacity or metabolism with 1 g/day quercetin supplementation for 7–16 (27) or 5 days (39).
Resveratrol Grapes Mice fed with resveratrol were protected against weight gain with high-fat diet and showed increases in
muscle mitochondrial size and density, oxidative enzymes, and endurance capacity. Effects were
achieved via activation of SIRT1 and PGC-1␣ (58).
EGCG, epigallocatechine-3-gallate; V̇O2max, maximal oxygen uptake; AMPK, AMP-activated protein kinase; PGC-1␣, peroxisome proliferator-activated
receptor-␥ coactivator-1␣; SIRT1, sirtuin 1.

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Review
842 TRAINING-NUTRIENT INTERACTIONS IN SKELETAL MUSCLE
beneficial will be important to determine. In the case of
substances like quercetin, this seems unlikely, since human
studies have typically provided doses of ⬃1 g/day (see Table
1), whereas dietary intakes are typically ⬍40 mg/day (27).
The additive effect of phytochemical intake and exercise
training is also of interest, but again, the present literature is not
sufficiently robust to allow firm guidelines and recommenda-
tions to be made. Among human studies of trained individuals,
supplementation with quercetin (1 g/day) for 3 wk did not alter
O2 consumption or patterns of substrate utilization (35),
whereas EGCG intake (270 mg/day) for 6 days had little effect
on cycling performance or fuel oxidation (31). Two weeks of
supplementation with quercetin (1 g/day) with or without the
addition of EGCG (120 mg/day), isoquercetin, and ␻-3 fatty
acids had no effect on muscle mRNA expression for PGC-1␣,
cytochrome c oxidase, and citrate synthase; there was also no
effect on cycling performance during a 3-day period of inten-
sified training, although the combined supplement appeared to
achieve a reduction in the inflammatory response to the in-
creased training stimulus (71). However, 6 wk of supplemen-
tation with quercetin (600 mg/day) added to a multicomponent
antioxidant supplement enhanced cycling performance over
baseline measurements and the effect of the antioxidant sup-
plement alone (63).
Summary and Directions for Future Research
Acute alterations in substrate availability modify the imme-
diate exercise response and, when repeated over days and
weeks, modulate many adaptive processes in skeletal muscle
that ultimately underpin the phenotype-specific characteristics
observed in trained individuals. Investigations that have ma-
nipulated carbohydrate availability demonstrate that, indepen-
dent of prior training status, short-term training programs in
which some workouts are commenced with either low muscle
glycogen levels and/or low exogenous carbohydrate availabil-
ity augment training adaptation to the same or to a greater
extent than when similar workouts are undertaken with normal
glycogen stores. From a molecular/cellular perspective, unrav-
eling the precise mechanism(s) underlying the benefit to train-
ing adaptation with reduced carbohydrate availability is diffi-
cult because carbohydrate restriction has reciprocal and
marked effects on lipid availability and utilization. Indeed,
future work involving alterations in carbohydrate and fat avail-
ability should determine whether such exercise-diet interven-
tions alter the localization (i.e., sarcolemmal and/or mitochon-
drial) and activity of putative carbohydrate and fat transporters
both at rest and during exercise; this may help explain the
persistent effects of low-carbohydrate and/or high-fat diets on
muscle fuel choice. From a practical perspective, low-carbo-
hydrate, high-fat diets have been associated with the develop-
ment of insulin resistance and associated health risks, so
studies are urgently needed to identify the minimal dietary
intervention period required to “trigger” the cascade of positive
adaptive responses as well as the optimal volume and/or
intensity of training required to augment training adaptation.
Both resistance exercise and the feeding of protein and AAs
have a marked stimulatory effect on rates of MPS. Although
MPS is blunted during contractile activity, the provision of
protein after a resistance-based exercise bout is an effective
strategy for promoting MPS, since the AA substrate may allow
J Appl Physiol • VOL
earlier rises in the blood AA profile and kick-start MPS and/or
trigger local or systemic signaling responses that promote
increased MPS. It is clear that the increase in MPS in response
to resistance exercise is critically dependent on the timing and
pattern of protein intake. As such, investigations to define the
time course of the signaling events and MPS responses during
prolonged (12–24 h) recovery from resistance exercise with
different protein feeding protocols are needed. Such evidence
will provide the framework to design effective and practical
population-specific interventions to increase muscle mass in
athletes and prevent sarcopenia in the elderly.
At present there would appear to be merit in further inves-
tigating the effects of antioxidants and phytochemicals on
mitochondrial biogenesis and adaptations to exercise. Cur-
rently, much of the evidence linking RNOS signaling to muscle
adaptation is based on changes in mRNA in muscle cells;
future studies should determine the role that RNOS signaling
plays in the rates of translation and in posttranslational modi-
fications of proteins. Work utilizing a variety of in vitro and in
Downloaded from jap.physiology.org on March 23, 2011
vivo techniques and models will be needed to isolate the
characteristics under which any benefits of antioxidants and
phytochemicals can be measured in trained humans along with
the mechanism(s) underpinning such an enhancement. Clearly,
many future studies are required to enhance our understanding
of how nutrient availability acts at a cellular level to modulate
training-induced adaptation in skeletal muscle.
ACKNOWLEDGMENTS
We thank Dr. Vernon G. Coffey for constructive comments during the
preparation of this review.
GRANTS
The writing of this review was, in part, supported by an Australian Research
Council Grant to J. A. Hawley, L. M. Burke, and S. M. Phillips (ARC
LP1000100010).
DISCLOSURES
No conflicts of interest, financial or otherwise, are declared by the authors.
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