Leucine Supplementation

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  The loss of skeletal muscle mass with advancing age (termed sarcopaenia), impairs physical function, thereby reducing independent living in older adults and causing growing concern to the public healthcare sector. The precise mechanisms underpinning sarcopaenia are not fully elucidated, but almost certainly involve alterations in muscle protein metabolism culminating in protein loss (i.e. when therate of muscle protein breakdown chronically exceeds synthesis). There is likely tobe some programme in sarcopaenia that is truly a consequence of ageing per se, but it is undoubtedly exacerbated through periods of muscle unloading and disuse. Periods of disuse, for example during hospitaliation (i.e. leg casting or bed rest), can reduce postabsorptive and, more dramatically, postprandial rates of muscle protein synthesis, outcomes even healthy young muscles cannot escape when inactive (!lover et al. ##$)% &lunting of the normally robust muscle protein synthetic response to amino acids with disuse'inactivity has been termed anabolic � resistance. t is intuitive to expect that as we age the times spent physically � inactive due to illness will become more frequent. uring such times, dramatic lossof muscle mass and impairments in the ability of older muscles to recover anabolic sensitivity upon resuming normal activities of daily living are thought to be the underlying basis for sarcopaenia (&reen * Phillips, #++).s an example of how frequent periods of physical inactivity may induce anabolic resistance in older muscles, we recently showed that healthy older adults require agreater dose of protein to acutely increase muscle protein synthesis above fasting rates compared with the young (-ang et al. #+ ). ith this in mind, dietary strategies to assist in muscle maintenance and hypertrophy during ill health and subsequent recovery are critical for older adults. n this issue of The /ournal of Physiology, 0agne et al. ( #+ ) elegantly examine the effectiveness of different dietary protein interventions for assisting in the recovery of muscle mass in old rodents following dramatic disuse1induced atrophy. 2pecifically, rats were fed a standard casein or casein plus free leucine diet over 3# days of recovery from a period of hindlimb immobiliation. The branched chain amino acid leucine occupies aposition of prominence in that it alone can act as a stimulatory signal for muscle protein synthesis (therton et al. #+#). 4urthermore, peak leucinaemia appears, atleast in part, to dictate the amplitude of the muscle anabolic response to protein ingestion (5orton et al. ##67 &reen * Phillips, #++). t has been demonstrated that long1term free leucine supplementation does not promote muscle hypertrophy in healthy older adults (8erhoeven et al. ##6). 9owever, little is known of how leucine supplementation during and after immobiliation might affect muscle mass.0agne et al. ( #+ ) demonstrate that immobiliation atrophied the gastrocnemius by : #;. n addition, isotopic tracer techniques allowed the authors to show that the atrophied muscles were no longer able to mount a normal muscle protein � � synthetic or intramuscular signalling response to food intake, congruent with disuse1induced anabolic resistance observed in humans (!lover et al. ##$). hat was most intriguing was the finding that consumption of additional free leucine on top of a normal casein diet during recovery did not promote any gains in muscle mass, despite the fact that the anabolic sensitivity of muscles returned to pre1immobiliation levels. n explanation of this paradoxical finding, the authors hypothesied that leucine merely acts as a trigger for muscle protein synthetic � � machinery, and that despite transiently elevating rates of synthesis the response was not sustained long enough to result in net protein accretion and hypertrophy. t is known that free leucine is rapidly digested and, thus, the lag between the anabolic actions of leucine and the availability of other amino acid substrates required to prolong the muscle protein synthetic response (5orton et al. ##6) may explain the absence of any hypertrophic response.To verify the importance of synchroniation between the leucine signal and amino � � acid availability, the authors conducted a pilot experiment in which they provided two additional groups of rodents with (i) a whey protein diet or (ii) a whey plus casein protein diet (high protein) during recovery from immobiliation. hey  protein has been well defined as a rapidly digested, leucine rich intact protein source providing all other essential amino acids, whereas casein is slowly digestedresulting in prolonged aminoacidaemia compared with whey (&oirie et al. +66<). s hypothesied, the authors were able to show that consumption of whey protein duringrecovery, alone or in addition to a normal casein diet, induced a gain of :=#; of the muscle lost. 0echanistically, the benefits of whey and whey plus casein proteindiets on the recovery of muscle mass may be explained by the sustained aminoacidaemia that was observed, which may have prolonged the muscle protein synthetic response.n conclusion, 0agne et al. ( #+ ) have affirmed that impairments in the recovery of muscle mass following disuse are due to a blunted response to normally robust anabolic stimuli (i.e. amino acids). 4urthermore, they have presented us with intriguing evidence that despite the potent anabolic properties of leucine supplementation, a full complement of essential amino acids, in a rapidly digestible form of whey, is required to facilitate the anabolic actions of leucine leading to muscle protein accretion and hypertrophy. 4inally, as human physiologists, we acknowledge it is difficult to draw parallels between rodents andhumans due to complex differences in the biology of wasting between species. 4rom anutritional standpoint, however, the work of 0agne et al. ( #+ ) allows us to gain valuable insight into the efficacy of amino acid and protein supplementation for muscle remodelling following disuse. 9opefully, we might be able to apply this knowledge to older humans in the very near future.
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