Download Whey protein ingestion and muscle protein anabolism in elderly

Whey protein ingestion
and muscle protein anabolism
in elderly
CHRISTOS S. KATSANOS
Arizona State University
Centre for Metabolic Biology
PO Box 873704, Tempe, AZ, USA
AgroFood industry hi-tech - September/October 2009 - vol 20 n 5
Elderly nutrition
ABSTRACT: Decrease in muscle mass with age makes elderly susceptible to falls, loss of independence and disease.
Ingestion of whey protein exerts acute beneficial effects on muscle protein anabolism in elderly. This is probably due to the
specific amino acid profile of the whey protein (e.g. essential amino acids), together with its fast absorption and the rate of
appearance of its individual amino acids in blood. Further, ingestion of intact whey protein provides a greater anabolic
benefit than ingestion of its essential amino acids alone, suggesting that whey protein is more than just a simple source of
essential amino acids with respect to providing a stimulus for enhancing muscle protein anabolism in the elderly.
KEYWORDS: Dietary protein, whey protein, skeletal muscle,
lean body mass, aging.
introduction
Normal aging results in loss of muscle mass, a process that is
independent of any disease (1). Although the rates among
individuals may differ, the majority of people start
experiencing some loss of muscle mass around the fourth
decade of their life (2, 3). The etiology of this muscle loss is
probably multifactorial and the result of several intrinsic (e.g.
hormonal status) and extrinsic (e.g. nutritional and physical
activity patterns) factors. Whatever the cause may be, loss
of contractile proteins and associated skeletal muscle mass
can lead to frailty, increased risk of falls and an overall loss of
independence in elderly, ultimately making this population
more vulnerable to illness (4). Given that intrinsic factors
contributing to muscle protein loss as a result of normal aging
are likely less modifiable, extrinsic factors, such as nutrition
and physical activity, have gained special attention to
reverse or prevent muscle loss. Among nutritional
approaches, research has particularly focused on the
ingestion of high quality proteins, such as whey, casein as
well as soy protein. Absorption and appearance of amino
acids from ingested proteins into plasma serves to stimulate
and support the synthesis of new proteins in body tissues,
including the skeletal muscle. Whey and casein are the
major proteins found in milk.
Dietary protein intake and aging
Skeletal muscle contains more than half of all body’s
proteins. In the absence of adequate delivery of amino
acids in plasma via protein ingestion, skeletal muscle serves
as the primary pool of amino acids to support the synthesis of
proteins in other organs as well as metabolic processes such
as gluconeogenesis (5). Dietary protein intake, which has a
great impact on regulating normal skeletal muscle protein
turnover in humans, decreases in elderly (6, 7), and by itself
may be a contributing factor to skeletal muscle protein loss
with aging. The current recommendation for protein intake
for adults is 0.8 grams protein/kg/day. Whereas some
evidence points to the direction that this amount of dietary
protein intake, irrespective of age, is probably close to that
required by older adults (8), other evidence has argued that
20
this amount may not be adequate for elderly to meet their
daily protein requirements (9, 10). Larger amounts of daily
protein intake appear to result in increased whole body
protein turnover and amino acid oxidation, in parallel with
an increase in net nitrogen balance in elderly (11). Recent
evidence suggests that it may not be the overall daily
dietary protein intake, but rather other factors
related to the amount, type and timing of
protein ingestion that may be more critical in
regulating a favourable muscle protein
anabolism in elderly.
Protein Quality and Muscle Protein
Accumulation
In recent years, approaches to
enhance skeletal muscle protein
accumulation via nutritional means
have received particular attention.
Among these approaches,
ingestion of protein and various
amino acid mixtures have been
studied extensively in the elderly
and as such have largely improved
our knowledge with respect to the
role of protein/amino acids in
enhancing muscle protein
accumulation in this population.
Muscle protein accumulation can
theoretically be achieved by either
increasing the rate of protein synthesis,
decreasing the rate of protein
breakdown, or both. Increased muscle
protein accumulation by dietary protein
is achieved primarily via stimulation of
the muscle protein synthesis following the
absorption of the protein-associated
amino acids and as a result of the ensuing
plasma hyperaminoacidemia (12). Dietary
protein ingestion provides a practical
approach to increase the availability of
plasma amino acids. Such amino acids
serve not only as precursors for protein
synthesis but also act as signalling molecules
in the initiation process of muscle protein
synthesis (13). Essential amino acids (EAAs),
which are amino acids that the body cannot
Figure 1. Ingestion of 15 grams of whey protein results in greater
accumulation of bound phenylalanine, an index of accumulation of muscle
proteins, in the leg during the 3.5-hour postprandial period compared to the
ingestion of the whey protein’s essential amino acids. This evidence suggests
that whey protein is not a simple substrate of essential amino acids for the
stimulation of muscle protein anabolism (*, p < 0.05; based on data from
reference 20).
AgroFood industry hi-tech - September/October 2009 - vol 20 n 5
the exact same amounts of EAAs. Our data, shown in Figure
1, indicate that at that level of EAA ingestion (~ 7 grams),
ingestion of the intact whey protein (15 grams) results in
greater accrual of muscle proteins than ingestion of only the
EAAs found within the whey (20). Such evidence points to
the direction that the whey protein is not just a simple source
of EAAs with respect to its effects on muscle protein
accumulation. Combining this finding with the fact that
whey protein is more easily accessible and a more costeffective approach to stimulate muscle protein synthesis
relative to the EAAs ingestion, whey protein ingestion
provides a more practical approach than amino acids
ingestion to improve muscle protein anabolism through
dietary supplementation in elderly.
A number of studies have shown that older muscle is
associated with less than optimal stimulation of proteins
synthesis by the plasma amino acids, a response that can be
overcome by increasing the plasma availability of the
essential amino acid leucine (16, 21). The fact that,
compared to other high quality proteins (e.g. casein as well
as soy), whey protein has a relatively higher leucine content
(14, 22), makes whey a preferable source of dietary protein
to enhance muscle protein anabolism, in a circumstance
that sufficient amounts of protein are either not ingested or
not preferred by the elderly. Also, co-ingestion of whey
protein with a meal is known to increase the postprandial
plasma amino acid concentrations to a greater extent than
those observed after co-ingestion of casein with a meal (23).
Further, given other reported benefits of whey protein, such
as those in the immune function (24), which declines with
age, whey may provide a unique nutritional approach to
collectively address detrimental physiological and metabolic
consequences of aging.
Elderly nutrition
synthesize, such as the amino acid leucine, are the most
important stimuli of these molecular processes. High quality
proteins have a large EAAs content. In young individuals, a
slow absorbed protein, such as casein, is associated with
greater whole body protein accumulation compared to a
situation in which there is a rapid absorption and increase in
plasma amino acid concentration (14). Contrary to the
situation in the young, in the elderly there is greater utilization
of amino acids for whole body protein accumulation
following ingestion of whey protein, a rapidly digested
protein, when compared to the ingestion of casein (15).
Although the mechanisms for this greater protein
accumulation in elderly following whey versus casein
ingestion are not clear, greater whole body protein
accretion probably relates to the higher plasma
aminoacidemia following the whey ingestion as opposed to
the lower, albeit more prolonged, degree of plasma
aminoacidemia following the casein ingestion. Also, whey
protein appears to have a slightly greater content of the
amino acid leucine. It has now become evident that the
response of muscle protein synthesis to leucine is either
impaired with aging or there is an intrinsic resistance related
to protein synthesis in older muscle to the stimulatory effects
of plasma amino acids that can be overcome by specifically
increasing the plasma concentration of leucine (16).
An important aspect of a high quality protein is
that it provides all the EAAs in the amounts that
the body needs. EAAs provide the primary
stimulus for enhancing muscle protein
synthesis. For example, the response of
muscle protein synthesis to ingestion of 18
grams of EAAs in elderly is not further
enhanced by ingestion of a mixture that
contains the same EAAs together with 22
grams of non-essentials amino acids
(17), suggesting that non-essential
amino acids in whey protein may
not be necessary for the
stimulation of muscle anabolism
in elderly. Under the
circumstances of that study, it
is possible that a maximal
response was reached in
elderly as a result of the
increase in plasma EAAs
alone, and based on the
fact that the stimulation of
muscle protein synthesis
by plasma amino acids is
a saturable process (18).
We sought to determine
whether the benefit of whey
protein ingestion in elderly is
a direct result of the whey’s
EAAs content. To test our
hypothesis, elderly subjects
ingested EAAs at a dose
that we have previously
documented to result in
less than optimal muscle
protein accrual in these
individuals
when
compared to young
controls (19), and
compared this response
of muscle protein
accrual to that following
ingestion of whey
protein that contained
Amount of ingested whey protein to maximize muscle
protein accumulation
It should be indicated that only few studies (11, 25, 26) have
evaluated long-term effects of protein/amino acids
supplementation on muscle protein anabolism. Based on
these findings, the exact amount of either protein or amino
acids needed to achieve maximal stimulation of muscle
protein anabolism in elderly cannot be exactly determined.
However, it is known that when a given amount of dietary
protein is spread out over several meals during the day it
results in less than optimal whole body protein retention in
the elderly as opposed to when that same amount of
protein is provided in a single meal (27). This relates probably
to the fact that individual small increases in plasma amino
21
Elderly nutrition
AgroFood industry hi-tech - September/October 2009 - vol 20 n 5
22
acid concentrations are not sufficient to maximally stimulate
muscle protein synthesis in elderly (19). The exact amount of
ingested protein that results in maximal muscle protein
anabolism may differ among older individuals given the
wide continuum of the aging process and that the aging
process itself may differ among individuals. It is generally
known that muscle protein accumulation in elderly is similar
to that in young when 15 grams of EAAs are ingested (28).
This amount of EAAs could be extrapolated to ~30 grams of
whey protein because whey protein contains ~50 percent of
EAAs. According to a different line of evidence from studies
in elderly, it appears that muscle protein synthesis does not
increase further, and to a considerable degree, with the
ingestion of a bolus that contains more than 10 grams of
EAAs (29) . Further, and given the evidence (Figure 1) that
intact whey protein ingestion results in greater muscle protein
accrual than ingestion of its EAAs content, the ingested bolus
of whey needed to stimulate muscle protein accumulation in
elderly similar to that in young is probably less than 30 grams.
Overall, the evidence discussed in this paragraph suggests
that a bolus ingestion of approximately 20-30 grams of whey
protein (i.e. 10-15 grams of EAA) should be able to maximally
stimulate muscle protein anabolism during the postprandial
period in the elderly.
Timing of ingested whey protein to maximize muscle protein
accumulation
In view of the fact that the response of muscle protein
anabolism to protein ingestion generally diminishes
approximately 4-5 hours postprandially, it would be
reasonable to try to maintain this effect by spacing
adequate amounts of ingested protein over the course of the
day either with the major meals (e.g. morning, noon,
evening) or between meals when, for example, protein
ingestion is in the form of protein supplements. Such a
nutritional approach can retard or possibly reverse the loss of
muscle mass observed with aging. Relative to the latter, and
based on limited evidence from relevant studies showing
improved lean body mass in elderly via increased plasma
amino acid concentrations throughout the day by means of
amino acids supplements (25, 26), whey protein can provide
a similar, in addition to an inexpensive, way to enhance lean
body mass. It has been suggested that ingestion of a high
quality protein equal to 1.5 grams protein/kg over the course
of the day may be a more appropriate amount when
compared to current recommendations (i.e. 0.8 grams
protein/kg/day) to achieve optimal health outcomes in
elderly (30). Most importantly, given the evidence for a
ceiling effect in the stimulation of muscle protein anabolism
with large increases in plasma amino acid concentrations
over a certain period of time (18), and at the same time for a
less than optimal response with insufficient increases in
plasma amino acid concentrations in elderly (19), it appears
that the emphasis for adequate protein intake may need to
be placed not only on the overall amount of protein
consumed per day but also on the timing of the ingested
meal/supplement (e.g. ingestion of an adequate amount of
protein ~4-5 hours apart). Spreading the dietary protein out
over, for example, 3 times a day may confer the best benefit
in terms of muscle protein anabolism, assuming that the
amount of whey protein ingested each single time is in the
range of 20-30 grams of protein. Ingestion of smaller boluses
of protein may results in less than optimal stimulation of
muscle protein synthesis as has previously been found (27),
and discussed in the previous paragraph. On the other hand,
and given that the ingestion of large amounts of protein in
older people is still a matter of debate with respect to
undesirable physiological/metabolic effects (11, 30),
spreading out the amount of protein ingested during the
course of the day and at single amounts sufficient to optimize
muscle protein anabolism with each ingestion may be
important to avoid any potential undesirable effects while at
the same time improving muscle protein anabolism in elderly.
Conclusions
More evidence is needed from experimental and clinical
studies to quantify the long-term effects of whey protein
ingestion on improving muscle protein accumulation in
parallel with improved functional and health outcomes in
elderly. Given that the whey protein appears to be a faster
and probably a qualitatively better source of amino acids
(e.g. leucine) when compared to other proteins, whey may
be a preferable dietary source of protein for the
up-regulation of muscle protein anabolism in elderly. Overall,
current evidence suggests that a bolus ingestion of
approximately 20-30 grams of whey protein, when ingested
at regular intervals (e.g. between main meals), may provide
favourable benefits with respect to improving muscle protein
anabolism in elderly.
References and notes
R. Roubenoff, V.A. Hughes, J Gerontol A Biol Sci Med Sci., 55,
M716-724 (2000).
2. J. Dorrens, M.J. Rennie, Scand J Med Sci Sports, 13, pp. 26-33
(2003).
3. W.J. Evans, J Gerontol A Biol Sci Med Sci., 50 Spec No, pp. 5-8
(1995).
4. R. Roubenoff, Eur J Clin Nutr., 54(3), S40-47 (2000).
5. R.R. Wolfe, Am J Clin Nutr., 84, pp. 475-482 (2006).
6. P. Wakimoto, G. Block, J Gerontol A Biol Sci Med Sci., 56 Spec No
2, pp. 65-80 (2001).
7. S. Rousset, P. Patureau Mirand et al., Br J Nutr., 90, pp. 1107-1115
(2003).
8. W.W. Campbell, C.A. Johnson et al., Am J Clin Nutr., 88, pp. 13221329 (2008).
9. M.H. Morse, M.D. Haub et al., J Gerontol A Biol Sci Med Sci., 56,
M724-730 (2001).
10. W.W. Campbell, H.J. Leidy, J Am Coll Nutr., 26, 696S-703S (2007).
11. S. Walrand, K.R. Short et al., Am J Physiol Endocrinol Metab., 295,
E921-928 (2008).
12. R.R. Wolfe, J Nutr., 132, 3219S-3224S (2002).
13. S.R. Kimball, L.S. Jefferson, Curr Opin Clin Nutr Metab Care, 5, pp.
63-67 (2002).
14. M. Dangin, Y. Boirie et al., Am J Physiol Endocrinol Metab., 280,
E340-348 (2001).
15. M. Dangin, C. Guillet et al., J Physiol., 549, pp. 635-644 (2003).
16. C.S. Katsanos, H. Kobayashi et al., Am J Physiol Endocrinol
Metab., 291, E381-387 (2006).
17. E. Volpi, H. Kobayashi et al., Am J Clin Nutr., 78, pp. 250-258
(2003).
18. J. Bohe, A. Low et al., J Physiol., 552, pp. 315-324 (2003).
19. C.S. Katsanos, H. Kobayashi et al., Am J Clin Nutr., 82, pp. 10651073 (2005).
20. C.S. Katsanos, D.L. Chinkes et al., Nutr Res., 28, pp. 651-658 (2008).
21. I. Rieu, M. Balage et al., J Physiol., 575, pp. 305-315 (2006).
22. J.E. Tang, S.M. Phillips, Curr Opin Clin Nutr Metab Care, 12, pp.
66-71 (2009).
23. W.L. Hall, D.J. Millward et al., Br J Nutr., 89, pp. 239-248 (2003).
24. J. Beaulieu, R. Dubuc et al., J Med Food., 10, pp. 67-72 (2007).
25. E. Borsheim, Q.U. Bui et al., Clin Nutr., 27, pp. 189-195 (2008).
26. S.B. Solerte, C. Gazzaruso et al., Am J Cardiol., 101, 69E-77E
(2008).
27. M.A. Arnal, L. Mosoni et al., Am J Clin Nutr., 69, pp. 1202-1208
(1999).
28.D. Paddon-Jones, M. Sheffield-Moore et al., Am J Physiol
Endocrinol Metab., 286, E321-328 (2004).
29.D. Cuthbertson, K. Smith et al., Faseb J., 19, pp. 422-424 (2005).
30. R.R. Wolfe, S.L. Miller et al., Clin Nutr., 27, pp. 675-684 (2008).
1.