Proceedings of the Nutrition Society (2011), 70, 100103

g The Author 2010 First published online 22 November 2010

doi:10.1017/S002966511000399X

The Summer Meeting of the Nutrition Society hosted by the Scottish Section was held at Heriot-Watt University, Edinburgh on
28 June1 July 2010

Conference on Nutrition and health: cell to community

Symposium 2: Exercise and protein nutrition

The science of muscle hypertrophy: making dietary protein count
Stuart M. Phillips

Proceedings of the Nutrition Society

Exercise Metabolism Research Group, Department of Kinesiology, McMaster University, 1280 Main St West, Hamilton,
ON L8S 4K1, Canada

Growing evidence supports the conclusion that consumption of protein in close temporal
proximity to the performance of resistance exercise promotes greater muscular hypertrophy.
We can also state with good certainty that merely consuming energy, as carbohydrate for
example, is also not sufficient to maximise muscle protein synthesis leading to anabolism and
net new muscle protein accretion. Recent work also indicates that certain types of proteins,
particular those that are rapidly digested and high in leucine content (i.e. whey protein), appear
to be more efficient at stimulating muscle protein synthesis. Continued practice of consumption
of these types or proteins after exercise should lead to greater hypertrophy. Reviews of
numerous training studies indicate that studies in which milk proteins and principally whey
protein show an advantage of these proteins over and above isoenergetic carbohydrate and soya
protein in promoting hypertrophy. Thus, the combined evidence suggests a strategic advantage
of practising early post-exercise consumption of whey protein or dairy-based protein to promote muscle protein synthesis, net muscle protein accretion and ultimately hypertrophy.
Whey: Skeletal muscle: Lean body mass: Human muscle

Human skeletal muscle protein turnover comprises the

processes of both muscle protein synthesis (MPS) and
muscle protein breakdown. These two processes are
ongoing and simultaneous and provide for a mechanism to
trim protein components and modify protein composition
within muscle fibres. In fact, remodelling of the muscle
proteome is the underlying mechanism of skeletal muscle
plasticity in response to different loading patterns such as
would occur during weightlifting, which leads to hypertrophy(13). Thus, imbalances between MPS and muscle
protein breakdown in adults dictate a net gain (i.e. hypertrophy) or loss (i.e. atrophy) of muscle fibre protein. For
most adults in their third, fourth and even their fifth decade
of life their muscle mass is constant and thus MPS =
muscle protein breakdown. However, beyond the fifth
decade of life, sarcopenic muscle loss begins to occur and
muscle mass slowly declines(4,5). What has been repeatedly
shown, however, is that resistance exercise can promote
increases in MPS(68). A number of reviews have pointed
to the fact that repeated elevations in MPS create periods

of positive net protein balance that sum up to create

hypertrophy(2,3). The main questions examined in this review are how the timing of protein consumption in concert
with exercise affects rises in MPS, how the source of
dietary protein ingested can affect rises in MPS and ultimately hypertrophy.

Protein enhances exercise-induced rises in muscle

protein synthesis: timing effects
When protein is consumed after resistance exercise, the
effects of resistance and the accompanying hyperaminoacidemia on MPS are synergistic and an even greater
stimulation of MPS occurs(911). The resultant net accumulation of muscle protein is thought to sum over time to
yield muscle hypertrophy(2,3). Empirical support for this
thesis has been observed. For example, Wilkinson et al.(12)
showed a greater acute post-exercise accumulation of
muscle protein with milk v. matched soya protein

Abbreviations: EAA, essential amino acids; MPS, muscle protein synthesis.

Corresponding author: Professor S. M. Phillips, fax + 1-905-523-6011, email phillis@[Link]

Proceedings of the Nutrition Society

Protein and muscle mass

MILK

300

SOYA

AUC Leucine

20 000

*
b

15 000
10 000
5000
0

Milk

250

[Leu] (M)

consumption. This acute finding when practised chronically

during a 12-week training study resulted in net greater gains
in muscle fibre hypertrophy and whole-body lean mass(13).
In the opposite direction, that is, induction of muscle
atrophy, declines in acute fasted-(14,15) and fed-state(15)
rates of MPS were quantitatively predictive of changes in
muscle cross-sectional area(16). Thus, acute changes in
MPS, but not changes in muscle protein breakdown which
are 35 times less than MPS during a given day, are
qualitatively predictive of long-term phenotypic changes.
The studies of post-exercise protein consumption are
unequivocal in their finding of an enhanced rate of MPS
after exercise(6,9,10,17). In contrast, only a few studies of
pre-exercise protein(18,19) and amino acid(20) consumption
have been conducted with equivocal results in terms of
benefits of pre-exercise feeding on MPS. This is perhaps
not overly surprising, since it appears that during exercise
a low cellular energy charge(21) or increased Ca concentration(22) appear to suppress protein synthesis. Thus,
the provision of protein prior to exercise would result in a
hyperaminoacidemia during exercise when the muscle
would be unable to mount an anabolic response. Provision
of protein during a workout would in theory be no more
beneficial than pre-workout protein consumption since
amino acids would, depending on the length of the workout, be appearing in the circulation when muscle is not
able to make good use of them. One study has examined
peri-exercise protein consumption and the subsequent
response of MPS(23) and has shown benefits in terms of
elevating post-exercise MPS. This was a rather prolonged
(2 h) exercise bout and it was impossible to tell from the
timing of biopsies whether the rise in MPS actually
occurred during the bout or whether it occurred sometime
afterward and may in fact have occurred during both periods. Nonetheless, consumption of protein and carbohydrate during the exercise bout did result in a 50 % greater
rise in MPS post-exercise implying that some benefit may
be gained by peri-workout protein consumption.
A consistent finding has been that post-workout protein
consumption promotes increments and MPS(9,11,12), which
ultimately sum up to yield muscle hypertrophy. The rise in
MPS occurs rapidly following a maximally stimulatory
bolus dose of protein(24) being apparent within the first
hour after resistance exercise and peaking at 3 h postexercise(9). Interestingly, the dose of protein in younger
men that maximally stimulated MPS was found to be
approximately 20 g(24), which corresponds to approximately 8.5 g essential amino acids (EAA) or 1.5 g leucine.
The EAA and leucine content of the protein are mentioned
because it appears that only the EAA are required to stimulate MPS(25) and leucine is a key metabolic regulator of
MPS through the activation of the mammalian target of
rapamycin pathway(26,27). The addition of carbohydrate to
this dose of protein does not appear to enhance MPS further than the protein itself (AW Staples and SM Phillips,
unpublished results), consistent with the concept that
insulin is a permissive hormone for protein synthesis and
not stimulatory(28). Thus, a prescription for optimal stimulation of MPS post-exercise would appear to encompass the
following: at least 25 g high-quality protein containing at
least 810 g EAA, higher leucine content would appear

101

Soya

200

a,b

150
a,b

a,b

100

a
a

50
Exercise

0
Pre

Post

30

60

90

120

180

Time (min)
Fig. 1. Whole blood leucine concentration (mM) following resistance
exercise from subjects who consumed 500 ml fluid skim (low fat)
milk and an isonitrogenous and isoenergetic quantity of a soya drink
(drawn with data from Wilkinson et al.(12)). AUC, area under the
curve. Means with different letters are significantly different from
each other (P < 0.05). *Indicates a significant difference from the
soya condition at the same time point or from each other in total
(P < 0.05). Values are means with their standard errors.

to be advantageous, delivered as soon as possible post

exercise.
Different dietary source proteins elicit different
responses in muscle protein synthesis
A number of studies have now shown that different proteins elicit different anabolic responses when consumed at
both a whole-body(2931) and skeletal muscle(12,32) level.
What is clear is that rates of digestion of proteins, in
addition to the amino acid content of the protein, will
dictate the amplitude and duration of the rise of EAA and
leucine, which will affect the degree of stimulation of
MPS. The concept of a leucine trigger or threshold for the
activation of MPS has been advanced by a number of
groups based on different observations(1,3335). A notable,
albeit in vitro, observation is that C2C12 myotubes in
culture show activation of portions of the mammalian target of rapamycin signalling pathway in response to a
number of amino acids, but only leucine triggers an
increase in signalling of mammalian target of rapamycin,
eucaryotic initiation factor 4E binding protein and p70S6
kinase(36). It appears that leucine has a controlling influence over the activation but not the duration of MPS(35),
but differing doses of leucine elicit a graded response in
MPS in terms of feeding at rest(37) and post exercise(24).
The role of EAA therefore in the activation of MPS is
questionable and one wonders whether EAA are simply
substrate and not also signalling molecules. Clearly, more
work remains to be performed to ascertain the interrelated
nature of leucine and EAA in activating and maintaining
a robust MPS response. However, for the importance of
this discussion, it would seem that high-quality proteins
(i.e. protein digestibility corrected amino acid score
(PDCAAS) of > 1.0) that have a high leucine content

Proceedings of the Nutrition Society

102

S. M. Phillips

would be beneficial for the stimulation of MPS. One caveat

to these guidelines would be that the digestion of the protein would have to be rapid providing a peak in leucine
concentration to result in leucinemia of sufficient magnitude to reach the leucine threshold and activate MPS. This
is likely critically important for older subjects who show a
relative resistance to hyperaminoacidemia in terms of stimulation of MPS(37). In older subjects, it appears that leucinemia needs to be higher to trigger rises in MPS(34,38,39),
which emphasises the role of higher quality, and specifically higher leucine content, proteins in the prevention of
an age-related decline in muscle mass.
Work from our lab indicated that dairy proteins specifically those found in fluid milk were superior in eliciting
acute rises in MPS than isonitrogenous and isoenergetic
quantities of soya protein(12). The observation reported in
that published paper was that total aminoacidemia was
slower in milk than the soya-based drink(12). This reflects
the fact that milk is by composition 80% casein and 20 %
whey and that casein is digested slowly, whereas whey is
rapidly digested(40). However, the appearance of leucine in
the systemic circulation was markedly different and actually more rapid in the milk condition (Fig. 1). Thus, while
the total aminoacidemia is slower with milk consumption
the leucinemia is greater and more prolonged with milk
consumption than soya presumably reflecting the contribution of the digestion of whey proteins within milk,
which are higher in leucine than both casein and soya(12).
When comparing the digestion of individual proteins
contained within milk, we observed that whey, as a
hydrolysed protein, resulted in a pronounced and rapid
hyperaminoacidemia and leucinemia compared to both
isonitrogenous quantities of soya and casein. While all of
these proteins have excellent PDCAAS scores
(whey = 1.15, casein = 1.23 and soya = 1.04), and are thus
considered complete, the pattern of aminoacidemia and, in
particular, leucinemia affected the rise in resting and postprandial MPS. Specifically, whey and soya promoted
increases in resting MPS that were greater than soya, but
increments in post-resistance exercise MPS were greater in
whey than both soya and casein(32). These findings are
different than those seen with whole-body measurements(40,41), but it needs to be realised that only 25 % of the
whole-body response is due to muscle protein and acute
changes in whole-body protein turnover with feeding will
reflect the much more rapidly turning over proteins of the
gut(42) and not those in muscle. This is an important point
and one that underpins why some have concluded that
whey protein cannot sustain an anabolic response compared to more slowly digested proteins(29) (casein or milk
proteins). Recently, we reviewed the evidence for the
efficacy of whey as exercise supplement in supporting
resistance training-induced gains in lean mass and found
that milk proteins and particularly whey were more effective than carbohydrate or soya supplements(43).

Conclusions
Post-exercise consumption of protein is the most effective
strategy to induce increments in MPS and promote muscle

mass gains. The increment in MPS is maximally stimulated

at a dose of protein of approximately 25 g or 10 g EAA.
This rise is based solely on protein consumption and is not
augmented by carbohydrate, at least when protein is adequate. Leucine plays a key role in the stimulation of MPS
and appears to be a key activator in switching on MPS,
which appears important in the elderly and also following
resistance exercise. Thus, high-quality, rapidly digested,
leucine-rich proteins such as whey protein would appear to
be ideal candidates for stimulating MPS and promotion of
hypertrophy.
Acknowledgements
S. M. P. is the recipient for grants from the Canadian Natural Science and Engineering Research Council (NSERC),
the US National Dairy Council and the Canadian Institutes
for Health Research (CIHR) and is grateful for those
agencies for funding portions of the work presented here.
The author declares no conflict of interest.
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