Sports Med (2014) 44 (Suppl 2):S185S194

DOI 10.1007/s40279-014-0258-7

REVIEW ARTICLE

Dietary Protein Considerations to Support Active Aging

Benjamin T. Wall Naomi M. Cermak
Luc J. C. van Loon

The Author(s) 2014. This article is published with open access at Springerlink.com

Abstract Given our rapidly aging world-wide population, the loss of skeletal muscle mass with healthy aging
(sarcopenia) represents an important societal and public
health concern. Maintaining or adopting an active lifestyle
alleviates age-related muscle loss to a certain extent. Over
time, even small losses of muscle tissue can hinder the
ability to maintain an active lifestyle and, as such, contribute to the development of frailty and metabolic disease.
Considerable research focus has addressed the application
of dietary protein supplementation to support exerciseinduced gains in muscle mass in younger individuals. In
contrast, the role of dietary protein in supporting the
maintenance (or gain) of skeletal muscle mass in active
older persons has received less attention. Older individuals
display a blunted muscle protein synthetic response to
dietary protein ingestion. However, this reduced anabolic
response can largely be overcome when physical activity is
performed in close temporal proximity to protein consumption. Moreover, recent evidence has helped elucidate
the optimal type and amount of dietary protein that should
be ingested by the older adult throughout the day in order
to maximize the skeletal muscle adaptive response to
physical activity. Evidence demonstrates that when these
principles are adhered to, muscle maintenance or hypertrophy over prolonged periods can be further augmented in
active older persons. The present review outlines the current understanding of the role that dietary protein occupies
B. T. Wall
N. M. Cermak
L. J. C. van Loon
NUTRIM School for Nutrition, Toxicology and Metabolism,
Maastricht University, Maastricht 6200 MD, The Netherlands
L. J. C. van Loon (&)
Department of Human Movement Sciences, Maastricht
University, Maastricht 6200 MD, The Netherlands
e-mail: [email protected]

in the lifestyle of active older adults as a means to increase

skeletal muscle mass, strength and function, and thus
support healthier aging.

1 Progressive Muscle Loss in the Older Adult

Global demographics indicate that the number of individuals aged 60 years and over is set to triple by the year
2050, with the fastest growing sub-population being those
aged over 85 years [1]. A key hallmark of aging is a progressive loss of muscle mass, which occurs independently
of health status [2]. The association between muscle loss
and increased incidence of falls, fractures, metabolic disease and other health complications, indicates that the
burden of our aging society on healthcare systems will
increase dramatically over the upcoming decades [1, 2].
The physiological mechanisms underpinning the age-related loss of muscle mass and strength are complex and
multifactorial, and remain to be fully elucidated. It has
been established that reduced levels of physical activity,
prevalence of disease, periods of hospitalization, and an
inadequate diet all play a role in this process [2]. However,
it should be noted that muscle tissue of adults of all ages
and health statuses retains the ability to recondition in
response to regular exercise, either with respect to muscle
hypertrophy or an increase in oxidative capacity [39].
Moreover, it is clear that those older adults who maintain
high physical activity levels throughout their lifespan
experience significantly less muscle loss compared with
their more sedentary peers [39]. Importantly, data generated thus far indicates that resistance-type exercise training
yields the clearest benefits with respect to maintaining (or
increasing) muscle mass as we age [39]. In accordance
with the positive effects of active aging, reports of the

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magnitude of age-related muscle loss vary greatly from

*0.5 to 2 % of total muscle mass loss per year from the
age of *50 years onwards [1012]. A large proportion of
this variance can indeed be explained by the habitual
physical activity levels and/or training status of the individuals studied [9]. As such, the importance of retaining an
active lifestyle to support healthy aging is unequivocal.
However, even the active older adult still experiences some
muscle loss with advancing age. Even modest losses of
muscle mass over the advancing years will compromise
strength, oxidative capacity and overall exercise performance [2, 9, 1315], and may hinder the ability to remain
active, thus instigating a vicious circle of declining health.
As such, muscle loss with aging should not only be viewed
as a clinical challenge to the most frail, sarcopenic elderly
[16], but also as a concern for those elderly wishing to stay
(or become more) physically active in an effort to improve
their quality of life.
Optimal nutrition has long been considered a key consideration for maintaining a healthy lifestyle, and the
benefits of correctly applied nutritional support for young
individuals involved in regular training have been studied
extensively [1719]. Of particular relevance, the amount,
type and timing of dietary protein consumed during prolonged resistance-type exercise training has been shown to
modulate gains in muscle mass and strength in young men
[17, 18, 2024]. In contrast, however, less research has
been directed at how nutrition can be used to maximize the
skeletal muscle adaptive response to a more physically
active lifestyle in the older population. The present review
will discuss muscle protein metabolism in elderly individuals and address the key considerations relating to
dietary protein intake to support healthy aging in the active
older adult.

2 Nutritional Regulation of Muscle Protein Metabolism

in the Elderly
From a physiological standpoint, skeletal muscle mass is in
a constant state of turnover, with muscle proteins being
synthesized and broken down simultaneously throughout
the day. Accordingly, relevant gains or losses of skeletal
muscle mass must be attributed to a persistent alteration in
muscle protein synthesis rates, breakdown rates, or a
combination of the two. Daily muscle protein turnover
(*12 %) is regulated in large part by nutrition [25].
Specifically, protein and/or amino acid intake increases
muscle protein synthesis rates (and also inhibits muscle
protein breakdown rates to a lesser extent), thereby
allowing net muscle protein accretion. The post-prandial
elevation in muscle protein synthesis rates are driven by the
rise in plasma concentration of the essential amino acids

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[26], and leucine in particular [27, 28], whereas the inhibition of protein breakdown is mainly attributed to hyperinsulinemia [29, 30]. These post-prandial periods offset the
net loss of muscle protein which occurs during fasting
periods. Consequently, both post-absorptive muscle protein
turnover rates as well as the magnitude of post-prandial
stimulation of muscle protein synthesis rates are viewed as
key factors for skeletal muscle mass maintenance.
Attempts to elucidate the impairments in muscle protein
metabolism that may underpin age-related muscle loss
initially focused on assessing basal (post-absorptive)
muscle protein synthesis and/or breakdown rates in young
and elderly subjects. Early studies observed no age-related
differences in basal muscle protein breakdown rates [9],
but found considerably lower mixed, myofibrilar, and/or
mitochondrial muscle protein synthesis rates in older
compared with younger men [3135]. However, more
recent studies have been unable to reproduce these findings, with no measurable differences being reported
between older and younger men [28, 3642]. The apparent
discrepancy may be attributed to differences in study
design and health status, habitual physical activity level
and/or dietary habits between the recruited cohorts of
subjects [36, 43]. Due to this uncertainty, research focus
has since shifted to the assessment of the impact of aging
on potential impairments in the muscle protein synthetic
response to the main anabolic stimuli: food intake and
physical activity.
Much data has accumulated in recent years demonstrating that elderly individuals have a blunted muscle
protein synthetic response to either intravenous [41, 44] or
oral [38, 39] administration of essential amino acids. An
interesting additional consideration is that some data also
suggest that the normal post-prandial inhibition of muscle
protein breakdown (primarily due to the rise in circulating
insulin) may be blunted in elderly men [45]. Collectively,
this reduced responsiveness to meal ingestion in older
adults has been termed anabolic resistance and is now
commonly thought to be a key factor in the etiology of
sarcopenia [4649]. However, the mechanisms underlying
anabolic resistance remain to be established. It is logical
that impairments may reside at the level of protein digestion [5052], amino acid absorption [5052], the postprandial hormonal response and subsequent microvascular
perfusion [53, 54], amino acid uptake in skeletal muscle
tissue [55], intramuscular signaling [38, 56], and/or myofibrillar muscle protein accretion [38]. Impaired dietary
protein digestion and subsequent amino acid absorption
rates and/or a greater retention of ingested amino acids
within the splanchnic area have been observed in older
compared with younger men [42, 57], although not all
studies confirm this [58]. Such findings imply that fewer
amino acids may become available for post-prandial

Dietary Protein and Aging

muscle protein synthesis. Evidence also exists suggesting

that insulin resistance at the level of capillary recruitmentmediated muscle perfusion following meal ingestion is a
key factor underlying anabolic resistance [53, 54, 59].
Some data demonstrate a reduced gene and/or protein
expression of key muscle amino acid transporter proteins in
older men following meal ingestion [60]. However,
dynamic measurements of intracellular amino acid transport in young and older men following meal ingestion are
necessary to confirm whether this is a potential site of
regulation for age-related anabolic resistance. The intracellular signaling pathways responsible for regulating
muscle protein synthesis are highly dependent upon the
activation of the mammalian target of rapamycin (mTOR)
[61, 62]. Indeed, mTOR signaling is highly responsive to
an increase in plasma and/or intracellular essential amino
acid concentrations, with leucine being of particular relevance [63]. It has been shown that the activation (in
response to amino acids and/or insulin) of mTOR and its
key downstream targets controlling translation initiation
(e.g., P70S6K) is impaired with aging [38, 44]. Though a
reduced ability of the senescent muscle cell to sense and/or
transduce a nutrient signal may be a mechanistic basis for
anabolic resistance, this could also simply be a consequence of reduced amino acid delivery by any of the previously mentioned potential sites of (dys)regulation.
Overall, it is clear that anabolic resistance may be
explained by impairments at various levels of physiology.
However, of specific interest is the observation that physical activity performed prior to the ingestion of a meal-like
amount of dietary protein can compensate for anabolic
resistance in the older adult, resulting in muscle protein
synthesis rates not different from those observed in the
young [52]. Physical activity sensitizes skeletal muscle
tissue to the anabolic properties of amino acids for at least
24 hours [64]. This enhanced sensitivity is of great relevance, suggesting that, as opposed to aging per se, anabolic
resistance to protein intake may be more related to the level
of physical activity of the specific individual. In keeping
with this idea, we [65] and others [66] have demonstrated
that 2 weeks of inactivity (muscle disuse via limb immobilization), or even simply decreased physical activity
(reduced step count) [67], can also induce anabolic resistance to amino acid administration or protein ingestion.
This opens up the attractive possibility that an active older
person can successfully overcome anabolic resistance on a
daily basis and therefore attenuate age-related muscle loss.
Moreover, given the relatively long-lasting effects of
physical activity upon muscle protein metabolism [64], it is
important to consider the interaction between nutrition and
exercise and address their synergistic effects on muscle
protein turnover within the context of active elderly individuals. Such information will help to define the optimal

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protein requirements for healthy, active elderly persons to

support the maintenance or increase in muscle mass,
strength and physical performance.

3 Dietary Protein to Support Post-Exercise Muscle

Protein Accretion
Aside from food intake, muscle contraction represents the
main physiological stimulus controlling muscle protein
turnover. Following a single bout of exercise, muscle
protein synthesis rates are increased within 24 hours, an
effect which persists for up to 16 hours in trained [68] and
2448 hours in untrained [6870] individuals. A single
bout of exercise also increases muscle protein breakdown
rates [70, 71], albeit to a lesser extent than the increase in
protein synthesis rates. As such, exercise improves the net
muscle protein balance; an effect that is likely maintained
for up to 48 hours [70]. However, in the absence of nutrient
intake, muscle protein balance will still remain negative
[70]. For these reasons, it has often been suggested that the
timing of protein or amino acid provision with respect to
physical activity and exercise is instrumental in modulating
the overall anabolic response [72, 73].
The ingestion of dietary protein in close temporal
proximity to physical activity and/or exercise has a synergistic impact on muscle protein synthesis rates, such that
greater muscle protein synthesis rates are observed when
compared with settings where a single stimulus is provided
[52, 7476]. Furthermore, the modest post-prandial
hyperinsulinemia that occurs following dietary protein
ingestion may be of sufficient magnitude to maximally
inhibit post-exercise muscle protein breakdown rates [29,
77, 78]. The resultant improvement in muscle protein
balance following the combined effects of exercise and
nutrition allows net muscle protein accretion during
recovery from exercise. It has generally been accepted that
muscle protein breakdown rates are less responsive to
exercise and/or nutritional stimuli when compared with
muscle protein synthesis rates, and therefore changes in
muscle protein synthesis rates are presumed to have a
greater influence over long-term changes in muscle mass
[70, 79]. It is apparent that dietary protein ingestion prior to
[73, 80], during [81, 82], immediately after [52, 76, 83, 84]
or 4 hours [84] after exercise all elicit comparable
increases in post-exercise muscle protein synthesis rates.
Consequently, a specific and narrow window of opportunity may not be as vital as often suggested, but protein
consumption in close temporal proximity to physical
activity clearly forms an important recommendation to
maximize the skeletal muscle adaptive response. It is also
true, as mentioned above, that a single bout of exercise can
elevate muscle protein synthesis rates for up to 48 hours

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[6870] and it is known that skeletal muscle retains its

exercise-induced enhanced sensitivity to the anabolic
properties of amino acids for at least 24 hours following
physical activity [64]. This suggests that the older individual may gain an additional benefit (from a muscle
protein synthetic perspective) from all meals consumed
within 12 days following a single bout of exercise (rather
than solely the post-exercise meal). It is important to
acknowledge, however, that at present no data are available
concerning how post-exercise meals may influence the
anabolic response to consecutive meals consumed thereafter. Nevertheless, this information brings to light the
importance of carefully considering nutrition over the
course of the day and not exclusively within the immediate
temporal proximity of a single bout of exercise.
In general, ingestion of a protein-rich meal results in net
muscle protein accretion for a period of *4 hours [74],
with peak stimulation of post-prandial muscle protein
synthesis rates occurring at *2 hours following meal
ingestion [74]. Based on this, current guidelines for young
athletes wishing to maximize gains in muscle mass and
strength during resistance-type exercise training programmes generally advise the consumption of 46 smaller,
high protein meals per day [83]. The same rationale can be
applied to the active older adult, particularly in the
2448 hours following physical activity where the benefits
from each meal would likely be enhanced. An emerging
strategy to increase meal frequency and promote improved
24-hour muscle protein synthesis rates is to consider the
overnight period. We have shown that the low muscle
protein synthesis rates observed nocturnally [85] can be
robustly stimulated by protein ingestion prior to sleep [86]
or by intra-gastric protein administration during sleep [85]
in young or elderly men. In keeping with the concept that
frequent meals may optimize post-exercise reconditioning,
recent evidence reports that, following a bout of physical
activity, four smaller protein meals (20 g) spread across the
day resulted in greater 12-hour muscle protein synthesis
rates compared with larger (40 g) protein meals consumed
on two occasions [87]. Moreover, the same study also
demonstrated that the same amount of protein consumed in
10 g doses on eight occasions was less effective at
increasing post-exercise muscle protein synthesis rates
compared with four boluses of 20 g [87]. These data
underline the importance of also considering optimal protein sources and amounts to maximize the benefits of each
meal during the post-exercise phase.

4 Type and Amount of Dietary Protein

Aside from considerations of the specific timing of nutrition in relation to physical activity, research has also

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investigated the individual properties of a meal that can

maximize the anabolic response to food intake. As discussed, protein is the fundamentally anabolic macronutrient, hence studies have attempted to define the optimal
amount [83, 8890] and type [9194] of dietary protein to
maximize muscle protein synthesis rates. Other studies
have looked at the impact of co-ingesting other macronutrients with protein [9597] or specific supplementation
with other compounds [98100]. The muscle protein synthetic response to dietary protein ingestion increases in a
dose-response fashion [83, 8890], with maximal postexercise muscle protein synthesis rates being achieved in
young men following the ingestion of *20 g of a high
quality dietary protein [83, 88, 90]. However, in elderly
individuals, more protein may be required to maximize
post-prandial muscle protein synthesis rates. In support,
ingestion of 35 g whey protein increases resting muscle
protein synthesis rates to a greater extent than 20 g [89]. It
has also been shown that ingestion of 40 g whey protein
results in greater post-exercise muscle protein synthesis
rates when compared with the ingestion of 20 g whey
protein in older men [88]. Highlighting the importance of
paying close attention to protein dose, a recent study
reported that when ample protein is consumed across all
meals (*30 g per meal), a favourable 24-hour muscle
protein synthetic rate is achieved when compared with the
consumption of the same amount of protein unevenly distributed over the various meals (1060 g per meal) [101].
Interestingly, when extreme skewed diets are employed
(*80 % of daily protein intake [*8085 g] consumed in a
single meal with the rest spread across the remaining
meals), favourable effects on nitrogen retention, whole
body protein balance and/or lean mass have been reported
compared with a more spread feeding approach [102, 103].
However, in these studies, the spread feeding condition
provided protein amounts per meal generally below the
likely requirement for optimal stimulation of muscle protein synthesis rates in elderly individuals. Moreover, to
date, such studies have not investigated the impact of these
severe modifications of protein amounts consumed
throughout the day on muscle protein turnover. Therefore,
taken together, available data illustrate the importance of
consuming ample protein with each main meal, avoiding
unnecessarily high protein meals (as they seem to infer
little to no additional benefit and result in a waste of daily
protein intake) and avoiding the typically low protein
breakfast often reported in older populations [104]. It is
worthy to note, however, that it is currently unknown
whether 40 g of protein represents an upper limit in terms
of what can be utilized by an elderly individual for muscle
protein synthesis, especially in the post-exercise phase
[105]. Likewise, how the type, duration and intensity of
exercise performed by the individual may affect a dose

Dietary Protein and Aging

currently available [109], particularly obtained within a

nutritionally relevant context [110]. Nonetheless, at this
stage we can state that frequent meals consumed by older
adults in close proximity to exercise do not need to be of a
high energy density; rather, attention should be focussed on
the amount and type of dietary protein contained within
each meal.
The current understanding of nutritional/physical activity manipulations capable of manipulating the post-prandial muscle protein synthetic response in elderly
individuals is summarized graphically in Fig. 1.

5 Dietary Protein to Support Muscle Reconditioning

During Exercise Training
Insight into the processes that underlie the regulation of
skeletal muscle mass is paramount if we are to understand
how healthy, active older adults can maintain or gain
skeletal muscle mass. However, ultimately, the impact of
nutritional and/or exercise interventions to stimulate
muscle protein accretion must be translated to studies
250

Postprandial MPS (%)

200
150
100
50

20 g casein + 60-80 g CHO

Physical activity + 20 g casein

Disuse + 20 g casein

10 g whey

35 g whey

20 g whey

20 g casein (+2.5 g leucine)

20 g hydrolyzed casein

0
20 g casein

response relationship in the rates of synthesis of different

fractions of skeletal muscle proteins also remains to be
investigated. As such, available information thus far suggests that the ingestion of 3040 g of a high quality dietary
protein immediately following physical activity and at
regular intervals thereafter may best support reconditioning
in the active older adult.
Theoretically, when ample protein is provided following
exercise, it is likely that the type and composition of the
protein is less relevant since the sensitivity of the skeletal
muscle tissue to the anabolic properties of amino acids is
elevated during recovery from exercise [106]. However, for
the active older adult wishing to maximize muscle protein
anabolism, consuming large and frequent protein-rich
meals can be arduous. Accordingly, scientific attention has
also turned to the specific type of dietary protein capable of
best promoting post-prandial anabolism to a given dose
[27, 51, 91, 92, 107]. The key properties determining the
anabolic potential of a dietary protein appear to be its
digestion and absorption kinetics, and its amino acid
composition. A dietary protein exhibiting rapid digestion
and subsequent absorption kinetics, such as whey protein,
has been shown to elicit a greater muscle protein synthetic
response compared with slower proteins such as soy [92,
108] or casein [51, 92] in young and older men. Moreover,
even if a slow protein such as casein is artificially predigested (hydrolyzed) to ensure digestion and absorption
kinetics similar to whey, the post-prandial muscle protein
synthetic response of casein is still less pronounced compared with whey [51]. The latter may be attributed to the
greater leucine content in whey compared with casein
protein [27, 51]. Indeed, it has been shown that fortifying a
single bolus of dietary protein with only 23 g of crystalline leucine can amplify the post-prandial anabolic
response in elderly men [27, 28]. Consequently, it appears
that selecting a rapidly digestible protein source, with a
high leucine content (or fortifying other dietary protein
sources with leucine) represents a feasible strategy to
reduce the protein dose required for optimal post-prandial
muscle protein synthesis rates. However, more work is
necessary to assess the relevance of such a strategy in a
post-exercise recovery setting in older adults.
Recent work has started to address whether co-ingestion
of other macronutrients with protein modulates the postprandial muscle protein synthetic response. For instance,
carbohydrate co-ingestion could increase post-prandial
muscle protein synthesis rates by increasing circulating
insulin in the older (less insulin-sensitive) population.
However, we [96, 97] and others [95] have been unable to
observe any benefits of carbohydrate co-ingestion with
protein in either young or older men at rest or following
exercise. The potential impact of dietary fat on the anabolic
response to meal ingestion is less clear, as few data are

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Fig. 1 Schematic representation of the relative muscle protein

synthetic (MPS) response to the ingestion of a single protein bolus
in elderly individuals. A 20 g dose of casein protein is taken as a
control/normal response due to its resemblance to the protein content
found in a normal meal (in terms of protein quantity, digestion and
absorption kinetics, and amino acid profile) and is given an arbitrary
100 % value. Thereafter, bars refer to the relative modulations
(either increase or decrease) from normal (i.e., 100 %) by different
interventions, details of which are reported on the x axis. Data were
extrapolated from numerous studies performed within our laboratory
[27, 51, 52, 65, 89, 96, 97]. Note: wherever possible, the 100 %
control response for each intervention is obtained from the values
obtained within that specific study. CHO carbohydrate

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assessing clinically relevant end-points, such as changes in

skeletal muscle mass, body composition, muscle strength,
and functional capacity. Habitual protein consumption
generally declines with advancing age [111]. Importantly,
a higher ([1.0 g per kg body mass per day) dietary protein intake has been associated with an attenuated decline
in muscle mass and functional performance in older adults
in both epidemiological and intervention-based studies
[112114]. Moreover, prolonged resistance-type exercise
training has been shown to represent the most effective
strategy to increase muscle mass and strength, as well as
functional capacity in the elderly. Various long-term
intervention studies have confirmed the paradigm that
protein feeding in close temporal proximity to each bout
of exercise augments training-induced gains in muscle
mass and strength [2024, 115120]. However, many
other studies have been unable to confirm these surplus
benefits of protein supplementation above and beyond
those afforded by exercise training only [121129]. We
previously argued that small cohorts and differences in
study design may explain this apparent discrepancy in the
literature [17]. In order to resolve this issue, we recently
conducted a meta-analysis to more thoroughly examine
the proposed benefits of protein supplementation to further
augment the adaptive response during prolonged resistance-type exercise training in young and older men [17].
This approach revealed that protein supplementation
augmented training-induced gains in muscle mass and
strength in adults of all ages. Older individuals who
ingested dietary protein around the time of each exercise
bout exhibited a 38 and 33 % greater gain in fat-free mass
and strength, respectively, compared with those not consuming additional protein with training [17]. Interestingly,
we have recently shown that additional dietary protein
supplementation was required to actually gain additional
muscle mass at all during prolonged resistance-type
exercise training in frail, elderly subjects [130]. During
the 6-month intervention, the frail elders were unable to
gain measurable increases in skeletal muscle when no
additional protein was provided. Taken together, these
data illustrate the importance of dietary protein to support
muscle reconditioning for the active older adult. However,
given the variance in findings from smaller cohort studies,
we feel that the surplus benefits of dietary protein supplementation largely depend on the type, dose and timing
of the protein supplements that are being consumed.

B. T. Wall et al.

help to enhance the muscle adaptive response in the active

older adult. Oral supplementation with creatine has been a
long-standing, evidenced-based strategy employed by recreational and competitive athletes as an ergogenic aid for
high-intensity exercise performance, and to augment
training adaptations in young athletes [131133]. Creatine
is generally consumed in relatively large doses (*20 g per
day) for 57 days in order to load the muscle [134], with
a maintenance dose of 25 g per day thereafter to maintain
elevated muscle creatine levels for several weeks [131
133]. Ergogenic benefits are attributed to an increased
muscle store of phosphocreatine, allowing improved
adenosine triphosphate delivery from phosphocreatine
hydrolysis during high-intensity exercise, allowing for a
greater training stimulus and, ultimately, an augmented
training adaptation. Although most studies have been
conducted in young athletes, a recent meta-analysis concluded that the addition of oral creatine supplementation to
regular exercise training in older adults also allows for
greater gains in muscle mass and strength [100]. It seems
evident that this would be of more relevance to the more
experienced older athletes, who may have reached limits in
the exercise-induced gains in muscle mass and strength,
compared with that of the novice healthy adult starting out
on an exercise intervention program.
Another nutritional approach that has received much
recent attention is the fish oil-derived omega-3 fatty acids
(eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA)
[98, 99, 135138]. It has been reported that 8 weeks of
omega-3 supplementation (4 g per day) results in a greater
muscle protein synthetic response to amino acid administration in adults of all ages [98, 99]. Importantly, this
appears to translate into functional benefits. Long-term
(6 months) fish oil supplementation has been reported to
improve physical performance indices such as walking
speed [138]. Moreover, during a 90-day resistance-type
exercise training program in older women, the consumption of fish oil supplements (2 g per day) resulted in greater
gains in muscle strength and functional capacity when
compared with a placebo [137]. More data are required to
determine whether fish oil supplementation represents an
effective adjunct strategy to augment the exercise-induced
gains in muscle mass, strength and functional performance
in the older population.

7 Conclusions
6 Nutritional Compounds to Support Active Aging
Although a healthy, well balanced diet forms the foundation of any nutritional plan to support muscle reconditioning, there may be nutritional compounds that could

123

Developing nutritional strategies to support skeletal muscle

reconditioning in active older adults is of great clinical
relevance given our rapidly aging population. Prior work
investigating the mechanisms of age-related muscle loss
has highlighted a reduced muscle protein synthetic

Dietary Protein and Aging

response to dietary protein ingestion in older individuals as

a key responsible factor. However, performing physical
activity and consuming dietary protein in close temporal
proximity can compensate for anabolic resistance by
increasing the muscle protein synthetic response to food
intake. Evidence suggests that 3040 g of protein represents an optimal dose to best promote (post-exercise)
muscle protein synthesis rates in older adults. Moreover,
sub-optimal doses of dietary protein can be optimized by
selecting proteins with rapid digestion and absorption
kinetics that are also rich in leucine (e.g., whey), and/or
specifically enriched protein with leucine. Long-term
intervention studies have been able to demonstrate the
surplus benefits of dietary protein supplementation to further augment the gains in muscle mass and strength during
prolonged resistance-type exercise training. Emerging
evidence also suggests that oral creatine and/or fish oilderived fatty acid supplementation may be effective as a
means to enhance training adaptations in the older population. Future work will translate the mechanistic insight of
how the timing, amount and type of dietary protein impacts
the muscle protein synthetic response to more effective
interventional strategies to maximize gains in muscle mass,
strength and function during exercise training in the older
population. Such studies will allow a further refinement of
dietary protein recommendations to support active aging.
Acknowledgments This article was published in a supplement
supported by Gatorade Sports Science Institute. The supplement was
guest edited by Lawrence L. Spriet who attended a meeting of the
Gatorade Sports Science Institute (GSSI) expert panel in February
2013 and received honoraria from the GSSI, a division of PepsiCo,
Inc., for his meeting participation and the writing of his manuscript.
He has not received any honoraria for guest editing the supplement.
L.L.S. selected peer reviewers for each paper (except his own) and
managed the process. Luc van Loon, PhD attended a meeting of the
GSSI Expert Panel in February 2013 and received honoraria from the
GSSI, a division of PepsiCo, Inc., for his meeting participation and
the writing of this manuscript. The views expressed in this manuscript
are those of the author and do not necessarily reflect the position or
policy of PepsiCo, Inc.
Open Access This article is distributed under the terms of the
Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original
author(s) and the source are credited.

References
1. WHO. http://www.who.int/topics/ageing. website. 2008.
2. Evans W. What is sarcopenia? J Gerontol A Biol Sci Med Sci.
1995;50:58.
3. Klitgaard H, Mantoni M, Schiaffino S, et al. Function, morphology and protein expression of ageing skeletal muscle: a
cross-sectional study of elderly men with different training
backgrounds. Acta Physiol Scand. 1990;140:4154.

S191
4. Peterson M, Sen A, Gordon P. Influence of resistance exercise
on lean body mass in aging adults: a meta-analysis. Med Sci
Sports Exerc. 2011;43:24958.
5. Peterson M, Rhea M, Sen A, et al. Resistance exercise for
muscular strength in older adults: a meta-analysis. Ageing Res
Rev. 2010;9:22637.
6. Yarasheski K, Pak-Loduca J, Hasten D, et al. Resistance exercise training increases mixed muscle protein synthesis rate in
frail women and men [76 yr old. Am J Physiol. 1999;277:
11825.
7. Sillanpaa E, Hakkinen A, Laaksonen D, et al. Serum basal
hormone concentrations, nutrition and physical fitness during
strength and/or endurance training in 3964-year-old women.
Int J Sports Med. 2010;31:1107.
8. Booth F, Zwetsloot K. Basic concepts about genes, inactivity
and aging. Scand J Med Sci Sports. 2010;20:14.
9. Cherin P, Voronska E, Fraoucene N, et al. Prevalence of sarcopenia among healthy ambulatory subjects: the sarcopenia
begins from 45 years. Aging Clin Exp Res. 2014;26:13746.
10. Buford T, Anton S, Judge A, et al. Models of accelerated sarcopenia: critical pieces for solving the puzzle of age-related
muscle atrophy. Ageing Res Rev. 2010;9:36983.
11. Nair K. Aging muscle. Am J Clin Nutr. 2005;81:95363.
12. Mitchell W, Williams J, Atherton P, et al. Sarcopenia, dynapenia, and the impact of advancing age on human skeletal muscle
size and strength; a quantitative review. Front Physiol. 2012;3:
260.
13. Dirks M, Wall B, Nilwik R, et al. Skeletal muscle disuse atrophy
is not attenuated by dietary protein supplementation in healthy,
older men. J Nutr. 2014 (in press).
14. Suetta C, Frandsen U, Jensen L, et al. Aging affects the transcriptional regulation of human skeletal muscle disuse atrophy.
PLoS One. 2012;7:51238.
15. Verdijk L, Koopman R, Schaart G, et al. Satellite cell content is
specifically reduced in type II skeletal muscle fibers in the
elderly. Am J Physiol Endocrinol Metab. 2007;292:1517.
16. Gill T, Baker D, Gottschalk M, et al. A program to prevent
functional decline in physically frail, elderly persons who live at
home. N Engl J Med. 2002;347:106874.
17. Cermak N, Res P, de Groot L, et al. Protein supplementation
augments the adaptive response of skeletal muscle to resistancetype exercise training: a meta-analysis. Am J Clin Nutr.
2012;96:145464.
18. Volek J, Volk B, Gomez A, et al. Whey protein supplementation
during resistance training augments lean body mass. J Am Coll
Nutr. 2013;32:12235.
19. Cermak N, van Loon L. The use of carbohydrates during exercise as an ergogenic aid. Sports Med. 2013;43:113955.
20. Hartman J, Tang J, Wilkinson S, et al. Consumption of fat-free
fluid milk after resistance exercise promotes greater lean mass
accretion than does consumption of soy or carbohydrate in young,
novice, male weightlifters. Am J Clin Nutr. 2007;86:37381.
21. Josse A, Tang J, Tarnopolsky M, et al. Body composition and
strength changes in women with milk and resistance exercise.
Med Sci Sports Exerc. 2010;42:112230.
22. Kerksick C, Rasmussen C, Lancaster S, et al. The effects of
protein and amino acid supplementation on performance and
training adaptations during ten weeks of resistance training.
J Strength Cond Res. 2006;20:64353.
23. Walker T, Smith J, Herrera M, et al. The influence of 8 weeks of
whey-protein and leucine supplementation on physical and cognitive performance. Int J Sport Nutr Exerc Metab. 2010;20:
40917.
24. Willoughby D, Stout J, Wilborn C. Effects of resistance training
and protein plus amino acid supplementation on muscle anabolism, mass, and strength. Amino Acids. 2007;32:46777.

123

S192
25. Rennie M, Edwards R, Halliday D, et al. Muscle protein synthesis measured by stable isotope techniques in man: the effects
of feeding and fasting. Clin Sci. 1982;63:51923.
26. Tipton K, Gurkin B, Matin S, et al. Nonessential amino acids are
not necessary to stimulate net muscle protein synthesis in
healthy volunteers. J Nutr Biochem. 1999;10:8995.
27. Wall B, Hamer H, de Lange A, et al. Leucine co-ingestion
improves post-prandial muscle protein accretion in elderly men.
Clin Nutr. 2013;32:4129.
28. Katsanos C, Kobayashi H, Sheffield-Moore M, et al. A high
proportion of leucine is required for optimal stimulation of the
rate of muscle protein synthesis by essential amino acids in the
elderly. Am J Physiol Endocrinol Metab. 2006;291:3817.
29. Greenhaff P, Karagounis L, Peirce N, et al. Disassociation
between the effects of amino acids and insulin on signaling,
ubiquitin ligases, and protein turnover in human muscle. Am J
Physiol Endocrinol Metab. 2008;295:595604.
30. Gelfand R, Barrett E. Effect of physiologic hyperinsulinemia on
skeletal muscle protein synthesis and breakdown in man. J Clin
Invest. 1987;80:16.
31. Hasten D, Pak-Loduca J, Obert K, et al. Resistance exercise
acutely increases MHC and mixed muscle protein synthesis rates
in 7884 and 2332 yr olds. Am J Physiol Endocrinol Metab.
2000;278:6206.
32. Balagopal P, Rooyackers O, Adey D, et al. Effects of aging on
in vivo synthesis of skeletal muscle myosin heavy-chain and sarcoplasmic protein in humans. Am J Physiol. 1997;273:790800.
33. Welle S, Thornton C, Jozefowicz R, et al. Myofibrillar protein
synthesis in young and old men. Am J Physiol. 1993;264:6938.
34. Welle S, Thornton C, Statt M. Myofibrillar protein synthesis in
young and old human subjects after three months of resistance
training. Am J Physiol. 1995;268:4227.
35. Yarasheski K, Zachwieja J, Bier D. Acute effects of resistance
exercise on muscle protein synthesis rate in young and elderly
men and women. Am J Physiol. 1993;265:2104.
36. Volpi E, Sheffield-Moore M, Rasmussen B, et al. Basal muscle
amino acid kinetics and protein synthesis in healthy young and
older men. JAMA. 2001;286:120612.
37. Rooyackers O, Adey D, Ades P, et al. Effect of age on in vivo
rates of mitochondrial protein synthesis in human skeletal
muscle. Proc Natl Acad Sci USA. 1996;93:153649.
38. Cuthbertson D, Smith K, Babraj J, et al. Anabolic signaling
deficits underlie amino acid resistance of wasting, aging muscle.
FASEB J. 2005;19:4224.
39. Katsanos C, Kobayashi H, Sheffield-Moore M, et al. Aging is
associated with diminished accretion of muscle proteins after the
ingestion of a small bolus of essential amino acids. Am J Clin
Nutr. 2005;82:106573.
40. Paddon-Jones D, Sheffield-Moore M, Zhang X, et al. Amino
acid ingestion improves muscle protein synthesis in the young
and elderly. Am J Physiol Endocrinol Metab. 2004;286:E3218.
41. Volpi E, Mittendorfer B, Rasmussen B, et al. The response of
muscle protein anabolism to combined hyperaminoacidemia and
glucose-induced hyperinsulinemia is impaired in the elderly.
J Clin Endocrinol Metab. 2000;85:448190.
42. Volpi E, Mittendorfer B, Wolf S, et al. Oral amino acids stimulate muscle protein anabolism in the elderly despite higher
first-pass splanchnic extraction. Am J Physiol. 1999;277:
51320.
43. Rennie M, Selby A, Atherton P, et al. Facts, noise and wishful
thinking: muscle protein turnover in aging and human disuse
atrophy. Scand J Med Sci Sports. 2010;20:59.
44. Guillet C, Prodhomme M, Balage M, et al. Impaired anabolic
response of muscle protein synthesis is associated with S6K1
dysregulation in elderly humans. FASEB J. 2004;18:15867.

123

B. T. Wall et al.
45. Wilkes E, Selby A, Atherton P, et al. Blunting of insulin inhibition of proteolysis in legs of older subjects may contribute to
age-related sarcopenia. Am J Clin Nutr. 2009;90:134350.
46. Rennie M, Wilkes E. Maintenance of the musculoskeletal mass
by control of protein turnover: the concept of anabolic resistance
and its relevance to the transplant recipient. Ann Transplant.
2005;10:314.
47. Breen L, Phillips S. Skeletal muscle protein metabolism in the
elderly: interventions to counteract the anabolic resistance of
ageing. Nutr Metab. 2011;8:68.
48. Burd N, Gorissen S, van Loon L. Anabolic resistance of muscle
protein synthesis with aging. Exerc Sport Sci Rev. 2013;41:16973.
49. Burd N, Wall B, van Loon L. The curious case of anabolic
resistance: old wives tales or new fables? J Appl Physiol.
2011;112:12335.
50. Ferrando A, Lane H, Stuart C, et al. Prolonged bed rest
decreases skeletal muscle and whole body protein synthesis. Am
J Physiol Endocrinol Metab. 1996;270(4):62733.
51. Pennings B, Boirie Y, Senden J, et al. Whey protein stimulates
postprandial muscle protein accretion more effectively than do
casein and casein hydrolysate in older men. Am J Clin Nutr.
2011;93:9971005.
52. Pennings B, Koopman R, Beelen M, et al. Exercising before
protein intake allows for greater use of dietary protein-derived
amino acids for de novo muscle protein synthesis in both young
and elderly men. Am J Clin Nutr. 2011;93:32231.
53. Rasmussen B, Fujita S, Wolfe R, et al. Insulin resistance of
muscle protein metabolism in aging. FASEB J. 2006;20:
7689.
54. Timmerman K, Lee J, Dreyer H, et al. Insulin stimulates human
skeletal muscle protein synthesis via an indirect mechanism
involving endothelial-dependent vasodilation and mammalian
target of rapamycin complex 1 signaling. J Clin Endocrinol
Metab. 2010;95:384857.
55. Drummond M, Glynn E, Fry C, et al. An increase in essential
amino acid availability upregulates amino acid transporter
expression in human skeletal muscle. Am J Physiol Endocrinol
Metab. 2010;298:10118.
56. Fry C, Drummond M, Glynn E, et al. Aging impairs contractioninduced human skeletal muscle mTORC1 signaling and protein
synthesis. Skelet Muscle. 2011;1:11.
57. Boirie Y, Gachon P, Beaufre`re B. Splanchnic and whole-body
leucine kinetics in young and elderly men. Am J Clin Nutr.
1997;65:48995.
58. Koopman R, Walrand S, Beelen M, et al. Dietary protein
digestion and absorption rates and the subsequent postprandial
muscle protein synthetic response do not differ between young
and elderly men. J Nutr. 2009;139:170713.
59. Timmerman K, Lee J, Fujita S, et al. Pharmacological vasodilation
improves insulin-stimulated muscle protein anabolism but not
glucose utilization in older adults. Diabetes. 2010;59:276471.
60. Dickinson J, Drummond M, Coben J, et al. Aging differentially
affects human skeletal muscle amino acid transporter expression
when essential amino acids are ingested after exercise. Clin
Nutr. 2013;32:27380.
61. Drummond M, Fry C, Glynn E, et al. Rapamycin administration
in humans blocks the contraction-induced increase in skeletal
muscle protein synthesis. J Physiol. 2009;587:153546.
62. Dickinson J, Fry C, Drummond M, et al. Mammalian target of
rapamycin complex 1 activation is required for the stimulation
of human skeletal muscle protein synthesis by essential amino
acids. J Nutr. 2011;141:85662.
63. Bohe J, Low A, Wolfe R, et al. Human muscle protein synthesis
is modulated by extracellular, not intramuscular amino acid
availability: a dose-response study. J Physiol. 2003;552:31524.

Dietary Protein and Aging

64. Burd N, West D, Moore D, et al. Enhanced amino acid sensitivity
of myofibrillar protein synthesis persists for up to 24 h after
resistance exercise in young men. J Nutr. 2011;141:56873.
65. Wall B, Snijders T, Senden J, et al. Disuse impairs the muscle
protein synthetic response to protein ingestion in healthy men.
J Clin Endocrinol Metab. 2013;98:48728.
66. Glover E, Phillips S, Oates B, et al. Immobilization induces
anabolic resistance in human myofibrillar protein synthesis with
low and high dose amino acid infusion. J Physiol. 2008;586:
604961.
67. Breen L, Stokes K, Churchward-Venne T, et al. Two weeks of
reduced activity decreases leg lean mass and induces anabolic
resistance of myofibrillar protein synthesis in healthy elderly.
J Clin Endocrinol Metab. 2013;98:260412.
68. Tang J, Perco J, Moore D, et al. Resistance training alters the
response of fed state mixed muscle protein synthesis in young
men. Am J Physiol Regul Integr Comp Physiol. 2008;294:
1728.
69. Chesley A, MacDougall J, Tarnopolsky M, et al. Changes in
human muscle protein synthesis after resistance exercise. J Appl
Physiol. 1992;73:13838.
70. Phillips S, Tipton K, Aarsland A, et al. Mixed muscle protein
synthesis and breakdown after resistance exercise in humans.
Am J Physiol. 1997;273:99107.
71. Biolo G, Maggi S, Williams B, et al. Increased rates of muscle
protein turnover and amino acid transport after resistance
exercise in humans. Am J Physiol. 1995;268:51420.
72. Esmarck B, Andersen J, Olsen S, et al. Timing of postexercise
protein intake is important for muscle hypertrophy with resistance training in elderly humans. J Physiol. 2001;15:30111.
73. Tipton K, Rasmussen B, Miller S, et al. Timing of amino acidcarbohydrate ingestion alters anabolic response of muscle to
resistance exercise. Am J Physiol Endocrinol Metab. 2001;281:
197206.
74. Moore D, Tang J, Burd N, et al. Differential stimulation of
myofibrillar and sarcoplasmic protein synthesis with protein
ingestion at rest and after resistance exercise. J Physiol.
2009;587:897904.
75. Moore D, Phillips S, Babraj J, et al. Myofibrillar and collagen
protein synthesis in human skeletal muscle in young men after
maximal shortening and lengthening contractions. Am J Physiol
Endocrinol Metab. 2005;288:11539.
76. Biolo G, Tipton K, Klein S, et al. An abundant supply of amino
acids enhances the metabolic effect of exercise on muscle protein. Am J Physiol. 1997;273:1229.
77. Roy B, Tarnopolsky M, MacDougall J, et al. Effect of glucose
supplement timing on protein metabolism after resistance
training. J Appl Physiol. 1997;82:18828.
78. Brsheim E, Cree M, Tipton K, et al. Effect of carbohydrate
intake on net muscle protein synthesis during recovery from
resistance exercise. J Appl Physiol. 2004;96:6748.
79. Phillips S. The science of muscle hypertrophy: making dietary
protein count. Proc Nutr Soc. 2011;70:1003.
80. Tipton K, Elliott T, Cree M, et al. Stimulation of net muscle
protein synthesis by whey protein ingestion before and after
exercise. Am J Physiol Endocrinol Metab. 2007;292:716.
81. Koopman R, Pannemans D, Jeukendrup A, et al. Combined
ingestion of protein and carbohydrate improves protein balance
during ultra-endurance exercise. Am J Physiol Endocrinol
Metab. 2004;287:71220.
82. Beelen M, Koopman R, Gijsen A, et al. Protein coingestion
stimulates muscle protein synthesis during resistance-type
exercise. Am J Physiol Endocrinol Metab. 2008;295:707.
83. Moore D, Robinson M, Fry J, et al. Ingested protein dose
response of muscle and albumin protein synthesis after resistance exercise in young men. Am J Clin Nutr. 2009;89:1618.

S193
84. Rasmussen B, Tipton K, Miller S, et al. An oral essential amino
acid-carbohydrate supplement enhances muscle protein anabolism after resistance exercise. J Appl Physiol. 2000;88:38692.
85. Groen B, Res P, Pennings B, et al. Intragastric protein administration stimulates overnight muscle protein synthesis in elderly
men. Am J Physiol Endocrinol Metab. 2012;302:5260.
86. Res P, Groen B, Pennings B, et al. Protein ingestion prior to
sleep improves post-exercise overnight recovery. Med Sci
Sports Exerc. 2012;44:15609.
87. Areta J, Burke L, Ross M, et al. Timing and distribution of
protein ingestion during prolonged recovery from resistance
exercise alters myofibrillar protein synthesis. J Physiol.
2013;591:231931.
88. Yang Y, Breen L, Burd N, et al. Resistance exercise enhances
myofibrillar protein synthesis with graded intakes of whey
protein in older men. Br J Nutr. 2012;7:19.
89. Pennings B, Groen B, de Lange A, et al. Amino acid absorption
and subsequent muscle protein accretion following graded
intakes of whey protein in elderly men. Am J Physiol Endocrinol
Metab. 2012;302:E9929.
90. Witard O, Jackman S, Breen L, et al. Myofibrillar muscle protein synthesis rates subsequent to a meal in response to
increasing doses of whey protein at rest and after resistance
exercise. Am J Clin Nutr. 2014;99:8695.
91. Boirie Y, Dangin M, Gachon P, et al. Slow and fast dietary
proteins differently modulate postprandial protein accretion.
Proc Natl Acad Sci USA. 1997;94:149305.
92. Tang J, Moore D, Kujbida G, et al. Ingestion of whey hydrolysate, casein, or soy protein isolate: effects on mixed muscle
protein synthesis at rest and following resistance exercise in
young men. J Appl Physiol. 2009;107:98792.
93. West D, Burd N, Coffey V, et al. Rapid aminoacidemia
enhances myofibrillar protein synthesis and anabolic intramuscular signaling responses after resistance exercise. Am J Clin
Nutr. 2011;94:795803.
94. Pennings B, Groen B, van Dijk J, et al. Minced beef is more
rapidly digested and absorbed than beef steak, resulting in
greater postprandial protein retention in older men. Am J Clin
Nutr. 2013;98:1218.
95. Staples A, Burd N, West D, et al. Carbohydrate does not augment exercise-induced protein accretion versus protein alone.
Med Sci Sports Exerc. 2011;43:115461.
96. Hamer H, Wall B, Kiskini A, et al. Carbohydrate co-ingestion
with protein does not further augment post-prandial muscle
protein accretion in older men. Nutr Metab. 2013;10:105.
97. Gorissen S, Burd N, Hamer HM, et al. Carbohydrate co-ingestion delays dietary protein digestion and absorption but does not
modulate postprandial muscle protein accretion. J Clin Endocrinol Metab. 2014;99:22508.
98. Smith G, Atherton P, Reeds D, et al. Dietary omega-3 fatty acid
supplementation increases the rate of muscle protein synthesis in
older adults: a randomized controlled trial. Am J Clin Nutr.
2011;93:40212.
99. Smith G, Atherton P, Reeds D, et al. Omega-3 polyunsaturated
fatty acids augment the muscle protein anabolic response to
hyperinsulinaemia-hyperaminoacidaemia in healthy young and
middle-aged men and women. Clin Sci. 2011;121:26778.
100. Devries M, Phillips S. Creatine supplementation during resistance training in older adults-a meta-analysis. Med Sci Sports
Exerc. 2014;46:1194203.
101. Mamerow M, Mettler J, English K, et al. Dietary protein distribution positively influences 24-h muscle protein synthesis in
healthy adults. J Nutr. 2014;144:87680.
102. Arnal M, Mosoni L, Boirie Y, et al. Protein pulse feeding
improves protein retention in elderly women. Am J Clin Nutr.
1999;69:12028.

123

S194
103. Bouillanne O, Curis E, Hamon-Vilcot B, et al. Impact of protein
pulse feeding on lean mass in malnourished and at-risk hospitalized elderly patients: a randomized controlled trial. Clin Nutr.
2013;32:18692.
104. Tieland M, Borgonjen-Van den Berg K, van Loon L, et al.
Dietary protein intake in community-dwelling, frail, and institutionalized elderly people: scope for improvement. Eur J Nutr.
2011;51:1739.
105. Deutz N, Wolfe R. Is there a maximal anabolic response to
protein intake with a meal? Clin Nutr. 2013;32:30913.
106. Koopman R, Verdijk L, Beelen M, et al. Co-ingestion of leucine
with protein does not further augment post-exercise muscle
protein synthesis rates in elderly men. Br J Nutr. 2008;99:
57180.
107. Robinson M, Burd N, Breen L, et al. Dose-dependent responses
of myofibrillar protein synthesis with beef ingestion are
enhanced with resistance exercise in middle-aged men. Appl
Physiol Nutr Metab. 2013;38:1205.
108. Yang Y, Churchward-Venne T, Burd N, et al. Myofibrillar
protein synthesis following ingestion of soy protein isolate at
rest and after resistance exercise in elderly men. Nutr Metab.
2012;9:57.
109. Elliot T, Cree M, Sanford A, et al. Milk ingestion stimulates net
muscle protein synthesis following resistance exercise. Med Sci
Sports Exerc. 2006;38:66774.
110. Svanberg E, Moller-Loswick A, Matthews D, et al. The role of
glucose, long-chain triglycerides and amino acids for promotion
of amino acid balance across peripheral tissues in man. Clin
Physiol. 1999;19:31120.
111. Zhu K, Devine A, Suleska A, et al. Adequacy and change in
nutrient and food intakes with aging in a seven-year cohort study
in elderly women. J Nutr Health Aging. 2010;14:7239.
112. Tieland M, van de Rest O, Dirks M, et al. Protein supplementation improves physical performance in frail elderly people: a
randomized, double-blind, placebo-controlled trial. J Am Med
Dir Assoc. 2012;13:7206.
113. Houston D, Nicklas B, Ding J, et al. Dietary protein intake is
associated with lean mass change in older, community-dwelling
adults: the Health, Aging, and Body Composition (Health ABC)
Study. Am J Clin Nutr. 2008;87:1505.
114. Beasley J, Wertheim B, LaCroix A, et al. Biomarker-calibrated
protein intake and physical function in the Womens Health
Initiative. J Am Geriatr Soc. 2013;61:186371.
115. Candow D, Burke N, Smith-Palmer T, et al. Effect of whey and
soy protein supplementation combined with resistance training
in young adults. Int J Sport Nutr Exerc Metab. 2006;16:23344.
116. Burke D, Chilibeck P, Davidson K, et al. The effect of whey
protein supplementation with and without creatine monohydrate
combined with resistance training on lean tissue mass and
muscle strength. Int J Sport Nutr Exerc Metab. 2001;11:34964.
117. Coburn J, Housh D, Housh T, et al. Effects of leucine and whey
protein supplementation during eight weeks of unilateral resistance training. J Strength Cond Res. 2006;20:28491.
118. Cribb P, Williams A, Hayes A. A creatine-protein-carbohydrate
supplement enhances responses to resistance training. Med Sci
Sports Exerc. 2007;39:19608.
119. Andersen L, Tufekovic G, Zebis M, et al. The effect of resistance training combined with timed ingestion of protein on
muscle fiber size and muscle strength. Metabolism. 2005;54:
1516.
120. Vieillevoye S, Poortmans J, Duchateau J, et al. Effects of a
combined essential amino acids/carbohydrate supplementation
on muscle mass, architecture and maximal strength following
heavy-load training. Eur J Appl Physiol. 2010;110:47988.

123

B. T. Wall et al.
121. Hulmi J, Tannerstedt J, Selanne H, et al. Resistance exercise
with whey protein ingestion affects mTOR signaling pathway
and myostatin in men. J Appl Physiol. 2009;106:17209.
122. Herda A, Herda T, Costa P, et al. Muscle performance, size, and
safety responses after eight weeks of resistance training and
protein supplementation: a randomized, double-blinded, placebocontrolled clinical trial. J Strength Cond Res. 2013;27:3091100.
123. Rankin J, Goldman L, Puglisi M, et al. Effect of post-exercise
supplement consumption on adaptations to resistance training.
J Am Coll Nutr. 2004;23:32230.
124. Rozenek R, Ward P, Long S, et al. Effects of high-calorie supplements on body composition and muscular strength following
resistance training. J Sports Med Phys Fit. 2002;42:3407.
125. White K, Bauer S, Hartz K, et al. Changes in body composition
with yogurt consumption during resistance training in women.
Int J Sport Nutr Exerc Metab. 2009;19:1833.
126. Beck T, Housh T, Johnson G, et al. Effects of a drink containing
creatine, amino acids, and protein combined with ten weeks of
resistance training on body composition, strength, and anaerobic
performance. J Strength Cond Res. 2007;21:1004.
127. Chromiak J, Smedley B, Carpenter W, et al. Effect of a 10-week
strength training program and recovery drink on body composition, muscular strength and endurance, and anaerobic power
and capacity. Nutrition. 2004;20:4207.
128. Lemon P, Tarnopolsky M, MacDougall J, et al. Protein requirements and muscle mass/strength changes during intensive training
in novice bodybuilders. J Appl Physiol. 1992;73:76775.
129. Verdijk L, Jonkers R, Gleeson B, et al. Protein supplementation
before and after exercise does not further augment skeletal
muscle hypertrophy after resistance training in elderly men. Am
J Clin Nutr. 2009;89:60816.
130. Tieland M, Dirks M, van der Zwaluw N, et al. Protein supplementation increases muscle mass gain during prolonged resistance-type exercise training in frail elderly people: a
randomized, double-blind, placebo-controlled trial. J Am Med
Dir Assoc. 2012;13:7139.
131. Greenhaff P, Casey A, Short A, et al. Influence of oral creatine
supplementation of muscle torque during repeated bouts of
maximal voluntary exercise in man. Clin Sci. 1993;84:56571.
132. van Loon L, Oosterlaar A, Hartgens F, et al. Effects of creatine
loading and prolonged creatine supplementation on body composition, fuel selection, sprint and endurance performance in
humans. Clin Sci. 2003;104:15362.
133. Casey A, Greenhaff P. Does dietary creatine supplementation
play a role in skeletal muscle metabolism and performance? Am
J Clin Nutr. 2000;72:60717.
134. Harris R, Soderlund K, Hultman E. Elevation of creatine in
resting and exercised muscle of normal subjects by creatine
supplementation. Clin Sci. 1992;83(3):36774.
135. Di Girolamo F, Situlin R, Mazzucco S, et al. Omega-3 fatty
acids and protein metabolism: enhancement of anabolic interventions for sarcopenia. Curr Opin Clin Nutr Metab Care.
2014;17:14550.
136. Stephens F, Mendis B, Shannon C, et al. Fish oil omega-3 fatty
acids partially prevent lipid induced insulin resistance in human
skeletal muscle without limiting acylcarnitine accumulation.
Clin Sci. 2014; (in press).
137. Rodacki C, Rodacki A, Pereira G, et al. Fish-oil supplementation enhances the effects of strength training in elderly women.
Am J Clin Nutr. 2012;95:42836.
138. Hutchins-Wiese H, Kleppinger A, Annis K, et al. The impact of
supplemental n-3 long chain polyunsaturated fatty acids and
dietary antioxidants on physical performance in postmenopausal
women. J Nutr Health Aging. 2013;17:7680.