Protein prior to rest/recovery/sleep and what about BCAA's (Medical Study included)

Eating for recovery before bed..Facts vs Myths

I just wanted to put this out there, because to many bro's advocate-
"Long as you hit your required protein macros before bed then there is no need to take it before bed.""

- Not entirely true, but there's some truth to that, but other benefits also exist with slow absorption proteins while resting/recovering/sleep

There is some absolute truth with consuming slow/fast acting proteins.
The speed of absorption of dietary amino acids varies according to the type of ingested dietary protein... Learn just how important slow and fast proteins, taken at the appropriate time, can affect your ability to put on lean mass.Many people avoid eating right before bed as they fear that the calories are more likely to be stored as fat. This is not the case though. Your body doesn't have an on-off switch and you still burn calories while you sleep. According to the American Dietetic Association, it's excess calories that determine whether you gain weight, not when you eat them. Too many calories at breakfast or lunch will be just as detrimental as too many calories right before bed.

Premise
As much as we may think of bodybuilding as a cloistered subculture, we are forever bombarded with training and nutritional tips from sources far removed from squat racks and posing daises. So it is with this axiom, which is such a ubiquitous feature of the sort of diets Oprah hypes that many beginning bodybuilders dare not breach it, and it breeds confusion about what and when to eat to gain only muscle and not fat

Science
When you sleep, you?re on a fast. During that fast, your body is forced to turn to your own muscle protein for fuel, converting those amino acids into glucose. In other words, while you?re in dreamland, you?re experiencing the nightmare of cannibalizing your own muscles. The longer you go before sleep without eating, the more your muscle will be eaten away. That?s why we always recommend that you end your day with a slow-digesting protein, such as a casein protein shake or cottage cheese.
(Research from Groups located in Texas, and even the Netherlands discovered that trained bodybuilders drinking a casein protein shake right before bed for eight weeks gained significantly more muscle than those who consumed the same casein shake in the middle of the day.)

Verdict
We started with the easiest myth to shoot down, for not only is it OK to chow down long after sundown, it?s crucial to eat a protein meal immediately before going to bed in order to feed your muscles the nutrients they need to recover and grow while you sleep. Go with 20-40 grams of slow-digesting protein, such as a casein shake or cottage cheese. If you?re trying to pack on mass and don?t store fat easily, take your protein with about 20-40 g of slow-digesting carbs, such as oatmeal, sweet potatoes or whole-wheat bread.

Now with this being said:
Read the study and see the charts in regards to why a slow releasing protein has a full advantage (pre-sleep)

Slow and fast dietary proteins differently modulate postprandial protein accretion. Boirie Y, et al. Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14930-5.Full text at:
Proc. Natl. Acad. Sci. USA
Vol. 94, pp. 14930?14935, December 1997
Physiology
Slow and fast dietary proteins differently modulate postprandial
protein accretion
(amino acid turnoverypostprandial protein anabolismymilk proteinystable isotopes)
YVES BOIRIE*, MARTIAL DANGIN*?, PIERRE GACHON*, MARIE-PAULE VASSON?, JEAN-LOUIS MAUBOIS?,
AND BERNARD BEAUFRE`RE*?
*Laboratoire de Nutrition Humaine, Universite? Clermont Auvergne, Centre de Recherche en Nutrition Humaine, BP 321, 63009 Clermont-Ferrand Cedex 1,
France; ?Nestec, Ltd., Nestle? Research Center, P.O. Box 44, CH 1000 Lausanne 26, Switzerland; ?Laboratoire de Biochimie, Biologie Mole?culaire et Nutrition,
Universite? Clermont Auvergne, BP 38, 63001 Clermont-Ferrand Cedex 1, France; and ?Laboratoire de Technologie Laitie`re, Institut National de la Recherche
Agronomique, 35042 Rennes Cedex, France
Communicated by John Waterlow, University of London, London, United Kingdom, October 7, 1997 (received for review April 20, 1997)

In relation to the 1997 Boirie study, Lyle summarized that the researchers found the following: whey spiked blood amino acid levels faster than casein, but blood amino acid levels dropped more quickly as well. Casein, in contrast, took much longer to digest, actually providing amino acids for around 8 hours to the body ... Both casein and whey hit the bloodstream at about the same time (about an hour in), that is, whey didn?t actually get into the system faster. However, whey spiked blood amino acid levels higher at that one hour point.

ABSTRACT The speed of absorption of dietary amino
acids by the gut varies according to the type of ingested dietary
protein. This could affect postprandial protein synthesis,
breakdown, and deposition. To test this hypothesis, two intrinsically
13C-leucine-labeled milk proteins, casein (CAS)
and whey protein (WP), of different physicochemical properties
were ingested as one single meal by healthy adults.
Postprandial whole body leucine kinetics were assessed by
using a dual tracer methodology. WP induced a dramatic but
short increase of plasma amino acids. CAS induced a prolonged
plateau of moderate hyperaminoacidemia, probably
because of a slow gastric emptying. Whole body protein
breakdown was inhibited by 34% after CAS ingestion but not
after WP ingestion. Postprandial protein synthesis was stimulated
by 68% with the WP meal and to a lesser extent (131%)
with the CAS meal. Postprandial whole body leucine oxidation
over 7 h was lower with CAS (272 6 91 mmolzkg21) than with
WP (373 6 56 mmolzkg21). Leucine intake was identical in
both meals (380 mmolzkg21). Therefore, net leucine balance
over the 7 h after the meal was more positive with CAS than
with WP (P < 0.05, WP vs. CAS). In conclusion, the speed of
protein digestion and amino acid absorption from the gut has
a major effect on whole body protein anabolism after one
single meal. By analogy with carbohydrate metabolism, slow
and fast proteins modulate the postprandial metabolic response,
a concept to be applied to wasting situations.
Dietary carbohydrates are commonly classified as slow and fast
because it now is well recognized that their structure affects
their speed of absorption, which in turn has a major impact on
the metabolic and hormonal response to a meal (1). On the
other hand, little is known about whether postprandial protein
kinetics are affected by the speed of absorption of dietary
amino acids; the latter is very variable, depending on gastric
and intestinal motility, luminal digestion, and finally mucosal
absorption. This lack of data is due to the fact that postprandial
amino acid kinetics have been studied almost exclusively
during continuous feeding, obtained either by a nasogastric
infusion or by small repeated meals (2?7). Measurements are
done 2?4 h after initiation of feeding, once isotopic and
substrate steady-state is achieved. Under these conditions, any
difference related to the speed of dietary amino acid absorption
is blunted.
There is, however, indirect evidence that this parameter
might be of importance. Indeed, the postprandial amino acid
levels differ a lot depending on the mode of administration of


a dietary protein; a single protein meal results in an acute but
transient peak of amino acids (9?11) whereas the same amount
of the same protein given in a continuous manner, which
mimics a slow absorption, induces a smaller but prolonged
increase (12). Amino acids are potent modulators of protein
synthesis, breakdown, and oxidation, so such different patterns
of postprandial amino acidemia might well result in different
postprandial protein kinetics and gain. Of interest, whole body
leucine balance, an index of protein deposition, was shown
recently to differ under these two circumstances (13).
Therefore, our hypothesis was that the speed of absorption
by the gut of amino acids derived from dietary proteins might
affect whole body protein synthesis, breakdown, and oxidation,
which in turn control protein deposition. To test this hypothesis,
we compared those parameters, assessed by leucine
kinetics, after ingestion of a single meal containing either whey
protein (WP) or casein (CAS), taken as paradigms for ??fast??
and ??slow?? proteins, respectively. Indeed, WP is a soluble
protein whereas CAS clots into the stomach, which delays its
gastric emptying and thus probably results in a slower release
of amino acids (14). Speed of amino acid absorption was
directly assessed by using a newly developed tracer, i.e., milk
protein fractions intrinsically labeled with L-[1-13C]leucine
(15). Leucine kinetics were modelized by using non-steadystate
equations as recently described (16). Our results demonstrate
that amino acids derived from CAS are indeed slowly
released from the gut and that slow and fast proteins differently
modulate postprandial changes of whole body protein
synthesis, breakdown, oxidation, and deposition.


I just wanted to post some of the study.. I will include the hyper link below that provides full detail,in regards to fast/slow proteins/and aminos..

(Slow and fast dietary proteins differently modulate postprandial protein)

Now with this being said more reads in regards-

ne)levels peak during sleep. 75 percent of daily hGH output is produced nse to get all the nutrients you'll need, then let the GH do
tNow what protein is the best to
consume prior to sleeping?
"Casein "

Keep reading

What is casein protein?
Casein (pronounced kay-seen) is the predominant protein found in milk. It is made by separating the casein from the whey in dairy (milk protein is 80 percent casein and 20 percent whey). There are three main types of casein protein: micellar casein, milk protein isolate and calcium caseinate. On average, one scoop (30 grams) of casein protein powder has approximately 100-120 calories and 25 grams of protein.

Besides its slow-digesting benefits, casein is invaluable for its high glutamine content. Of all the protein powders available, casein has the highest concentration of this amino acid. Glutamine provides a multitude of functions, which include increasing levels of the branched chain amino acid leucine in muscle fibers, enhancing protein synthesis and therefore, muscle growth. Because the immune system requires glutamine to function, consuming extra glutamine prevents the immune system from stealing it from muscle fibers, further averting catabolism. Glutamine also boosts growth hormone levels and can even aid fat loss by increasing the amount of calories and body fat burned both at rest and during exercise.

Do blended proteins such as whey offer the same effect as straight casein?
Either protein supplements are straight whey, soy, egg or casein; or they are a combination of any or all of these kinds of proteins, making them blends. What can a blend of proteins offer that a straight protein cannot? Basically, different rates of digestion. This means you can take a blended protein any time to get quick, medium, and prolonged absorption of protein.

But, I really like my ?whey? protein supplement.
Turn your favorite whey protein shake into a slow digesting one by simply mixing with milk, preferably low fat or skimmed. While casein protein is ?optimal? before bed, don?t forget that milk is 80 percent casein, adding it to any whey protein will slow down its absorption. Adding a fat such as natural peanut butter, flax or other healthy fat can further slow digestion, thus ?mimicking? casein protein.


To close the read and get to the conclusion here..
Don't deprive yourself, and fall for the hoopla that if you consume your proper intake of macro's that you don't need protein prior to rest/recovery(sleep)..
It most certainly won't hinder your gains on a large scale,but it surely is more beneficial than going without!

Regards,
Vision

____________________________

More info

BCAA's before bed is it necessary?

Truth is BCAA's need to be avail for use along with protein many researches
have stated that low to no protein before bed yields a low protein synthesis rate while sleeping,
you do burn cals when sleeping, you ever wake up lighter in the AM???

Its been proven that it will yield an add advantage with keeping plasma BCAA's levels higher throughout the state of rest/sleep/night

Pre-Sleep Protein Ingestion to Improve the Skeletal Muscle Adaptive Response to Exercise Training

Jorn Trommelen and Luc J. C. van Loon*

Author information ► Article notes ► Copyright and License information ► Disclaimer

This article has been cited by other articles in PMC.


Abstract

Protein ingestion following resistance-type exercise stimulates muscle protein synthesis rates, and enhances the skeletal muscle adaptive response to prolonged resistance-type exercise training. As the adaptive response to a single bout of resistance exercise extends well beyond the first couple of hours of post-exercise recovery, recent studies have begun to investigate the impact of the timing and distribution of protein ingestion during more prolonged recovery periods. Recent work has shown that overnight muscle protein synthesis rates are restricted by the level of amino acid availability. Protein ingested prior to sleep is effectively digested and absorbed, and thereby stimulates muscle protein synthesis rates during overnight recovery. When applied during a prolonged period of resistance-type exercise training, protein supplementation prior to sleep can further augment gains in muscle mass and strength. Recent studies investigating the impact of pre-sleep protein ingestion suggest that at least 40 g of protein is required to display a robust increase in muscle protein synthesis rates throughout overnight sleep. Furthermore, prior exercise allows more of the pre-sleep protein-derived amino acids to be utilized for de novo muscle protein synthesis during sleep. In short, pre-sleep protein ingestion represents an effective dietary strategy to improve overnight muscle protein synthesis, thereby improving the skeletal muscle adaptive response to exercise training.

Keywords: sleep, recovery, exercise, hypertrophy, casein


1. Introduction

A single session of exercise stimulates muscle protein synthesis rates, and to a lesser extent, muscle protein breakdown rates [1,2]. However, the muscle protein net balance will remain negative in the absence of food intake [2]. Protein ingestion stimulates muscle protein synthesis and inhibits muscle protein breakdown rates, resulting in net muscle protein accretion during the acute stages of post-exercise recovery [3]. Therefore, post-exercise protein ingestion is widely applied as a strategy to augment post-exercise muscle protein synthesis rates and, as such, to facilitate the skeletal muscle adaptive response to exercise training. Various factors have been identified which can modulate the post-exercise muscle protein synthetic response to exercise including the amount [4,5], type [6,7], timing [8], and distribution [9] of protein ingestion.
Only few studies have investigated the dose-response relationship between protein ingestion and post-exercise muscle protein synthesis rates in young [4,5] and older adults [10,11,12]. Ingestion of 20 g egg or whey protein has been shown sufficient to maximize muscle protein synthesis rates during recovery from lower-body resistance-type exercise in young males [4,5]. More recent evidence indicates that this dose-response relationship may depend on the amount of muscle tissue that was recruited during exercise, with the ingestion of 40 g protein further increasing muscle protein synthesis rates during recovery from whole-body resistance-type exercise [13].
A large variety of dietary protein sources have been shown to stimulate post-exercise muscle protein synthesis rates, including egg protein [4], whey and casein protein [14], milk and beef protein [15], and soy protein [6]. However, dietary protein sources can differ in their capacity to stimulate muscle protein synthesis rates, which appears to be largely dependent on differences in protein digestion and absorption kinetics [14,16] and amino acid composition [6,17], with the leucine content being of particular relevance [18,19].
Besides the amount and type of ingested protein, the timing and distribution of protein ingestion throughout the day can modulate post-exercise muscle protein synthesis rates. An even distribution of total protein intake over the three main meals stimulates 24 h muscle protein synthesis rates more effectively than an unbalanced distribution in which the majority (>60%) of total daily protein intake is consumed at the evening meal [20]. During 12 h of post-exercise recovery, an intermediate pattern of protein ingestion (20 g every 3 h) seems to increase muscle protein synthesis rates to a greater extent than the same amount of protein provided in less frequent but larger amounts (40 g every 6 h), or in more frequent, smaller amounts (10 g every 6 h) [9]. Therefore, an effective pattern of daily protein intake distribution to support muscle protein synthesis is to provide at least 20 g of protein with each main meal with no more than 4–5 h between meals.
As overnight sleep is typically the longest post-absorptive period during the day, we have recently introduced the concept of protein ingestion prior to sleep as a means to augment post-exercise overnight muscle protein synthesis. The aim of this review is to discuss the current state of evidence regarding the efficacy of pre-sleep protein ingestion to stimulate overnight muscle reconditioning.


2. Overnight Protein Metabolism

In general, most studies assess the effects of food intake on the muscle protein synthetic response to exercise performed in an overnight fasted state. Such post-absorptive conditions differ from normal everyday practice in which recreational sports activities are often performed in the late afternoon or evening after a full day of habitual physical activity and food intake. Therefore, we evaluated the impact of exercise performed in a fed state in the evening and the efficacy of protein ingestion immediately after exercise on muscle protein synthesis during prolonged overnight recovery [21]. The ingestion of 20–25 g of protein during exercise increased muscle protein synthesis rates during exercise, but we observed no increase in muscle protein synthesis rates during the prolonged overnight recovery period. Muscle protein synthesis rates during overnight sleep were unexpectedly low, with values being even lower than those typically observed in the in the morning following an overnight fast. Thus, a day of habitual food intake and the ingestion of 20–25 g of protein during and/or immediately after an exercise bout performed in the evening does not suffice to augment overnight muscle protein reconditioning.


3. Does the Gut Function at Night?

As overnight muscle protein synthesis rates are surprisingly low [21], we questioned whether they are limited by overnight plasma amino acid availability. Therefore, we hypothesized that protein provision during sleep increases overnight plasma amino acid availability and stimulates overnight muscle protein synthesis rates. As human intestinal motility follows a circadian rhythm with reduced activity during the night [22], we first assessed whether dietary protein provision during sleep leads to proper dietary protein digestion and amino acid absorption. In a proof-of-principle study, we first administrated specifically produced intrinsically l-[1-13C]-phenylalanine-labeled casein protein via a nasogastric tube while subjects were asleep and assessed the subsequent protein digestion and absorption kinetics [23]. We observed that administration of 40 g casein via a nasogastric tube during overnight sleep is followed by proper dietary protein digestion and absorption kinetics, thereby increasing overnight plasma amino acid availability and increasing muscle protein synthesis rates. Clearly, these data demonstrated that the gut functions properly at night and that protein provided during sleep strongly increases overnight muscle protein synthesis rates.


4. Pre-Sleep Protein Feeding as a Strategy to Increase Overnight Muscle Protein Synthesis

Our observation that protein administered during sleep is effectively digested and absorbed provided proof-of-principle that the gut functions properly during sleep [23]. However, nasogastric tube feeding does not represent a feasible feeding strategy for athletes. Therefore, our next step was to assess if protein ingestion prior to sleep would represent an effective dietary strategy to increase muscle protein synthesis rates during overnight post-exercise recovery [24]. Therefore, we studied recreational athletes during overnight recovery from a single bout of resistance-type exercise performed in the evening after a full day of dietary standardization. Immediately after exercise, all athletes ingested a recovery drink containing 20 g protein to maximize muscle protein synthesis rates during the acute stages of post-exercise recovery [4,24]. As explained above, this prescribed recovery strategy does not suffice to maintain elevated muscle protein synthesis rates during more prolonged overnight sleep [21]. Therefore, we provided subjects with either 40 g casein protein or a placebo drink immediately prior to sleep. In line with intragastric protein administration during sleep [23], the bolus of protein ingested prior to sleep was properly digested and absorbed throughout overnight sleep. The greater plasma amino acid availability following pre-sleep protein ingestion improved the overnight whole-body protein balance, allowing the net protein balance to become positive. In line, muscle protein synthesis rates were approximately 22% higher during overnight recovery when protein was ingested prior to sleep when compared to the placebo treatment. From these data we concluded that pre-sleep protein ingestion represents an effective dietary strategy to further augment the skeletal muscle adaptive response to resistance-type exercise training (Figure 1).
Figure 1
Schematic representation of the process of muscle protein synthesis (MPS) and muscle protein breakdown (MPB) throughout the day. Protein ingestion stimulates MPS rates and allows for net muscle protein accretion (green areas). During post-absorptive conditions, MPB rates exceed MPS rates, resulting in a net loss of muscle protein (red areas). Overnight sleep is the longest post-absorptive period of the day (A). Pre-sleep protein ingestion stimulates overnight muscle protein synthesis rates (B), thereby improving muscle reconditioning during overnight sleep.



To test this hypothesis, we assessed the impact of pre-sleep protein feeding to facilitate the skeletal muscle adaptive response to prolonged resistance-type exercise training [25]. Specifically, we selected healthy young men to participate in a 12-week resistance-type exercise training program (three exercise sessions per week) during which they ingested either 27.5 g of protein prior to sleep, or a non-caloric placebo. Muscle mass and strength increased to a greater extent in the group that ingested protein prior to sleep. These results indicate that protein supplementation prior to sleep represents an effective dietary strategy to augment the gains in muscle mass and strength during resistance-type exercise training. It remains to be established what dose and type of pre-sleep protein should be used to further optimize overnight muscle protein synthesis rates and, as such, can support greater gains in muscle mass and strength.
It should be noted that the ingestion of the pre-sleep protein supplement in both our acute and long-term studies was compared with a non-protein placebo, and not compared with protein supplementation provided at other time points. Therefore, we can only speculate on the surplus benefits of pre-sleep protein provision when compared to other time points. It can be speculated that the greater gains in muscle mass and strength are, at least partly, attributed to the pre-sleep timing of the protein supplement, as the vast majority of studies in which protein has been supplemented immediately before and/or after exercise do not show an increase in muscle mass gains when compared to a placebo [26]. However, it has been suggested that protein supplementation increases muscle mass gains mainly as a function of increased total protein intake, rather than the specific timing of a protein supplement [27,28]. As a meta-analysis was required to demonstrate that additional protein intake augments training-induced muscle hypertrophy [26], it seems unlikely that a possible positive effect of protein timing (i.e., protein supplementation at a time point compared to protein supplementation at different time point) on muscle mass gains can be detected in a longitudinal study. While it is currently unclear whether pre-sleep protein ingestion is superior to protein ingestion at a different time point, we propose that a more relevant question is whether pre-sleep protein ingestion is additive to protein intake earlier in the day. We suggest that athletes should aim to ingest sufficient protein intake at every meal to maximize muscle protein synthesis until the next meal. We have recently shown that the ingestion of large amounts of protein in the early post-exercise recovery phase does not compromise the muscle protein synthetic response to protein ingestion at a later stage [29]. This suggests that every meal moment represents a unique opportunity to stimulate muscle protein synthesis and that the muscle protein synthetic response to each meal may be additive. In addition, we have recently shown that athletes typically consume well above 1.2 g protein/kg/day, with the majority of protein consumed during the three main meals, and only a small amount of protein eaten as an evening snack (~7 g) [30]. As such, additional pre-sleep protein ingestion represents a practical strategy to increase the total daily protein intake, add another meal moment, and increase the overnight muscle protein synthesis rates; this effect is likely additive to muscle protein synthesis rates observed throughout the day.


5. Pre-Sleep Protein Feeding Characteristics

While we have identified the overnight sleeping period as a new window of opportunity to augment post-exercise training adaptations, it remains to be established how we can maximize the impact of pre-sleep protein feeding on overnight muscle protein synthesis rates. Previously we have shown that the ingestion of 40 g protein prior to sleep stimulates overnight muscle protein rates [24], which is considerably more than the 20 g of protein that is supposed to maximize muscle protein synthesis rates during the first few hours of post-exercise recovery [4,5]. Therefore, we questioned if a more moderate amount of protein would suffice to augment overnight muscle protein synthesis rates. To address this issue, we performed a follow-up study similar in design to our previous pre-sleep protein work, with the main difference that we provided 30 g of highly enriched intrinsically labeled protein prior to sleep, with or without an additional 2 g of free leucine. In contrast to our previous findings with 40 g protein, the ingestion of 30 g protein prior to sleep did not significantly increase overnight muscle protein synthesis rates (preliminary observations). This suggests that a pre-sleep protein dose-response relationship exists, which differs from the immediate post-exercise recovery period during which the ingestion of merely 20 g protein seems to maximize post-exercise muscle protein synthesis rates in young adults.
The ingestion of highly enriched, intrinsically l-[1-13C]-phenylalanine-labeled protein allowed us to also directly assess the metabolic fate of the pre-sleep dietary protein-derived amino acids. Pre-sleep protein-derived l-[1-13C]-phenylalanine was incorporated in de novo muscle protein as evidenced by the increase in muscle protein–bound l-[1-13C]-phenylalanine following overnight recovery, demonstrating that the pre-sleep protein provided amino acids as precursors for de novo myofibrillar protein accretion during overnight sleep. This provides mechanistic evidence to support our observation that the ingestion of 30 g protein prior to sleep augments muscle mass during three months of resistance-type exercise training [25]. However, our data suggest that at least 40 g of pre-sleep protein is required to induce a more substantial, detectable increase in muscle protein synthesis rates when assessed acutely over a 7.5 h overnight period.
As we anticipated that 30 g of pre-sleep protein might not be sufficient to adequately increase overnight muscle protein synthesis rates, we included a third treatment in which 2 g crystalline leucine was added to the 30 g bolus of protein. The addition of supplemental free leucine to a suboptimal amount of protein has been shown to enhance post-exercise muscle protein synthesis rates [18,19,31,32]. Despite these previous observations, co-ingesting free leucine with 30 g of casein prior to sleep did not augment the overnight muscle protein synthetic response. Given the extended duration of overnight sleep compared to a typical postprandial period (8 vs. 4–5 h), it is tempting to speculate that larger amounts of protein (≥40 g) are required to maximize muscle protein synthesis rates during overnight sleep.


6. Prior Exercise

It has been well established that the muscle protein synthetic response to protein ingestion is enhanced following exercise when exercise is performed in the morning following an overnight fast [12,33]. Recently, we evaluated the effect of resistance-type exercise performed in the evening on the muscle protein synthetic response to pre-sleep protein ingestion [34]. Postprandial overnight muscle protein synthesis rates were higher when exercise had been performed earlier that evening and more of the ingested protein-derived amino acids were directed towards de novo myofibrillar protein synthesis during overnight sleep. Therefore, protein ingestion prior to sleep represents an effective strategy to enhance overnight muscle reconditioning and is likely of even more relevance on exercise training days. In line, we have shown that physical activity performed in the evening increases the overnight muscle protein synthetic response to pre-sleep protein ingestion in older adults [35]. Clearly, combing pre-sleep protein ingestion with resistance-type exercise represents a more effective strategy to further enhance overnight skeletal muscle protein synthesis rates and increases the efficiency by which dietary protein is used for muscle protein accretion (Figure 2).
Figure 2
Conceptual framework of the overnight muscle protein synthetic response to 40 g of pre-sleep protein feeding at rest or following prior exercise.





7. Type of Pre-Sleep Protein

As protein sources differ in their capacity to stimulate muscle protein synthesis, the type of protein ingested prior to sleep may modulate the overnight muscle protein synthetic response. So far, all studies assessing the efficacy of pre-sleep protein ingestion on exercise reconditioning have provided casein protein. Casein is a more slowly digestible protein source, allowing a more moderate but prolonged rise in plasma amino acid concentrations [17]. Given the extended nature of overnight sleep, it could be speculated that such a more sustained postprandial aminoacidemia during overnight sleep is preferred as it will provide precursors to support muscle protein synthesis rates throughout the entire night. In contrast, whey protein is a more rapidly digestible protein, resulting in a pronounced but transient rise in plasma amino acid concentrations [17]. Ingestion of a single bolus of whey protein has been shown to stimulate muscle protein synthesis rates to a greater degree than casein protein when assessed over periods up to 6 h [6,17,36]. This has been attributed to the more rapid protein digestion and amino acid absorption kinetics as well as the higher leucine content in whey versus casein protein, resulting in a more rapid rise in postprandial plasma leucine concentrations [37]. It remains to be established if whey is superior to casein protein when ingested prior to sleep and muscle protein synthesis rates are assessed over a more prolonged overnight period of 7.5 h. The plasma levels of leucine do not seem to be the only factor in this regard, as we recently did not observe any differences in overnight muscle protein synthesis rates following the ingestion of 30 g casein with or without 2 g crystalline leucine (preliminary observations). Snijders et al. [25] provided a casein protein supplement that consisted of 50% micellar casein and 50% casein hydrolysate. When casein protein is hydrolyzed, its digestion and absorption properties resemble a more rapid digestible protein [38]. Therefore, pre-sleep ingestion of a mixture of a slow and more rapidly digestible protein source appears to be effective to augment muscle mass and strength gains during a prolonged resistance-type exercise program. We speculate that a variety of high-quality animal-based protein sources can augment overnight muscle protein synthesis rates when provided in sufficient amounts (≥40 g; Table 1), with relatively minor differences in efficacy between sources.
Table 1

Quantity of protein sources to provide 40 g pre-sleep protein.





8. Applications

Overnight sleep has emerged as a novel window of opportunity to modulate muscle protein metabolism. Pre-sleep protein ingestion represents an effective dietary strategy to stimulate both the acute and long-term skeletal muscle adaptive response to resistance-type exercise training [24,25]. There are numerous other potential applications of protein ingestion prior to sleep. Protein ingestion prior to sleep may also enhance exercise training adaptations to other exercise modalities. However, research on the impact of protein supplementation on other modes of exercise such as concurrent training [39] or endurance-type exercise training [40] is surprisingly scarce. While protein ingested immediately after endurance-type exercise does not appear to further augment mitochondrial protein synthesis rates [40], amino acid administration at rest stimulates mitochondrial protein synthesis rates [41]. It remains to be established if pre-sleep protein can augment the adaptive response to endurance-type exercise training with greater increases in skeletal muscle oxidative capacity, vascular density and/or endurance performance capacity.
Protein administration during sleep has been shown to stimulate overnight muscle protein synthesis rates in older adults [23]. Consequently, pre-sleep protein feeding may also represent an effective interventional strategy to support muscle mass maintenance in the older population or possibly even in patients in more clinically compromised conditions characterized by accelerated muscle loss such as acute sickness, systematic inflammation, and muscle disuse [42,43].


9. Conclusions

Muscle protein synthesis rates are particularly low during sleep, even when 20 g protein is ingested immediately after exercise performed in the evening. Protein ingested immediately prior to sleep is effectively digested and absorbed, thereby increasing amino acid availability during overnight sleep. Greater amino acid availability during sleep stimulates muscle protein synthesis rates and improves whole-body protein net balance during overnight recovery. At least 40 g of dietary protein should be ingested prior to sleep to elicit a robust stimulation of muscle protein synthesis rates throughout the night. Resistance-type exercise performed during the day augments the overnight muscle protein synthetic response to pre-sleep protein ingestion and allows more of the protein-derived amino acids to be used as precursors for de novo muscle protein synthesis. When applied during prolonged resistance-type exercise, pre-sleep protein supplementation can be used effectively to further increase gains in muscle mass and strength.

thanks for Sharing

I've done both.
No difference for me.
I just can't see the benefit.

I figured out this one long ago. I take in 50 grams of casein in 12 oz 1% milk. I may even have a little fruit. This happens about 5 hours after training, so all calories are shuttled towards recovery. Yes, I am on gear and GH, but I would do so even if natural as long as I was training hard. I fast for another few hours after waking and I am sub 7% fat. Your body needs macros to repair while sleeping.

Procard said:

I figured out this one long ago. I take in 50 grams of casein in 12 oz 1% milk. I may even have a little fruit. This happens about 5 hours after training, so all calories are shuttled towards recovery. Yes, I am on gear and GH, but I would do so even if natural as long as I was training hard. I fast for another few hours after waking and I am sub 7% fat. Your body needs macros to repair while sleeping.

Click to expand...

I agree with this a hundred percent even if someone is not a competitive bodybuilder but just a athlete or someone that is in Fitness.. people completely underestimate and do not know the true fundamentals behind recovery and nutrients when you're sleeping.. this doesn't mean a full-course meal and much like you're saying basically just 50 grams and a little bit of milk, because all of that is being shuttled right into your muscles for recovery.. when people hear this Theory they expect they're going to be the Incredible Hulk when that's not the case you're just basically assisting with your Macros it may or may not make a significant difference in your appearance but the quality of your muscle and the health and the chances of getting injury is even reduced.. the truth of the matter is it does build healthy tissue

I had a former client who was not having luck with Intermittent Fasting. He would train, have a whey shake and no other nutrients before going to bed because he thought eating before bedtime was a big no no.

Procard said:

I figured out this one long ago. I take in 50 grams of casein in 12 oz 1% milk. I may even have a little fruit. This happens about 5 hours after training, so all calories are shuttled towards recovery. Yes, I am on gear and GH, but I would do so even if natural as long as I was training hard. I fast for another few hours after waking and I am sub 7% fat. Your body needs macros to repair while sleeping.

Click to expand...

All calories are not shuttled towards recovery after training. First there is a conversion process that energy goes through before it can be used by the body and other functions such as brain function, catalyst formation, etc happen before muscle tissue repair begins.

Anyone have anything to share or add to this?

The topic came up about BCAA's, so what's everyone's thought on this, as it seems there's always a study that can contradict one an other?


Branched-chain amino acids and muscle protein synthesis in humans: myth or reality?

Robert R. Wolfe
University of Arkansas for Medical Sciences, 4301 West Markham street, slot 806, Little Rock, AR 72205-7199 USA

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568273/

Abstract

The branched chain amino acids (BCAAs) are leucine, valine and isoleucine. A multi-million dollar industry of nutritional supplements has grown around the concept that dietary supplements of BCAAs alone produce an anabolic response in humans driven by a stimulation of muscle protein synthesis. In this brief review the theoretical and empirical bases for that claim are discussed. Theoretically, the maximal stimulation of muscle protein synthesis in the post-absorptive state in response to BCAAs alone is the difference between muscle protein breakdown and muscle protein synthesis (about 30% greater than synthesis), because the other EAAs required for synthesis of new protein can only be derived from muscle protein breakdown. Realistically, a maximal increase in muscle protein synthesis of 30% is an over-estimate because the obligatory oxidation of EAAs can never be completely suppressed. An extensive search of the literature has revealed no studies in human subjects in which the response of muscle protein synthesis to orally-ingested BCAAs alone was quantified, and only two studies in which the effect of intravenously infused BCAAs alone was assessed. Both of these intravenous infusion studies found that BCAAs decreased muscle protein synthesis as well as protein breakdown, meaning a decrease in muscle protein turnover. The catabolic state in which the rate of muscle protein breakdown exceeded the rate of muscle protein synthesis persisted during BCAA infusion. We conclude that the claim that consumption of dietary BCAAs stimulates muscle protein synthesis or produces an anabolic response in human subjects is unwarranted.


Background

There are a total of twenty amino acids that comprise muscle protein. Nine of the twenty are considered essential amino acids (EAAs), meaning they cannot be produced by the body in physiologically significant amounts, and therefore are crucial components of a balanced diet. Muscle protein is in a constant state of turnover, meaning that protein synthesis is occurring continuously to replace protein lost as a consequence of protein breakdown. For synthesis of new muscle protein, all the EAAs, along with the eleven non-essential amino acids (NEAAs) that can be produced in the body, must be present in adequate amounts. The branched-chain amino acids leucine, isoleucine and valine are three of the nine EAAs. Leucine is not only a precursor for muscle protein synthesis, but also may play a role as a regulator of intracellular signaling pathways that are involved in the process of protein synthesis (e.g., [1]).
The concept that the BCAAs may have a unique capacity to stimulate muscle protein synthesis has been put forward for more than 35 years. Data supporting this hypothesis have been obtained from studies of the responses of rats. In 1981 Buse [2] reported that in rats the BCAAs may be rate limiting for muscle protein synthesis. Additional studies supported the concept of a unique effect of BCAAs on muscle protein synthesis in rats, although few have studied the response to oral consumption of only BCAAs. Garlick and Grant showed that infusion of a mixture of BCAAs into rats increased the rate of muscle protein synthesis in response to insulin [3], but they did not measure the effects of BCAAs alone. The infusion of BCAAs alone into rats by Kobayashi et al. [4] was shown to induce an increase in muscle protein synthesis, but the response was only transient. Presumably the rate of synthesis quickly became limited by the availability of the other EAAs.
Studies of muscle protein synthesis in rats have limited relevance to human responses. Skeletal muscle comprises a much smaller percentage of the total body mass in rats as compared to humans and regulation of muscle protein synthesis differs in many respects. Thus, in their landmark book on protein metabolism Waterlow and associates concluded from available data that dietary amino acids do not stimulate muscle protein synthesis in rats [5]. While recent work challenges this assertion, the limited stimulatory effect of dietary amino acids on protein synthesis in the rat reflects the fact that under normal post-absorptive conditions there are excess endogenous amino acids available to enable an increase in protein synthesis if the activity of intracellular factors involved in the initiation of protein synthesis is stimulated. Expressed differently, muscle protein synthesis in the rat is apparently limited by the initiation process rather than the translation process. In contrast, as will be discussed below, that does not appear to be the case in humans. Another important distinction between studies investigating the effects of amino acids on muscle protein synthesis in humans and rats relates to the methodologies commonly used. The “flooding dose” technique [6] has usually been used in rat studies. This procedure involves measurement of the incorporation of an amino acid tracer into muscle protein over a very short time window, often as short as 10 min. This approach does not distinguish between a transient and a sustained stimulation of protein synthesis. Only a sustained stimulation of synthesis is relevant physiologically. Consumption of an imbalanced mixture of amino acids, such as the BCAAs, may transiently stimulate protein synthesis by utilizing endogenous stores of the other precursors of protein synthesis. However, endogenous stores of amino acids, such as those in plasma and free intracellular pools, are quite limited and may quickly become depleted. If the stimulation of protein synthesis cannot be sustained, there is little physiological significance. Consequently, the flooding dose technique commonly used to measure muscle protein synthesis in the rat produces results with uncertain relevance to human nutrition. Since BCAA dietary supplements are intended for human consumption, the focus of this short review will be research in human subjects.
The sale of BCAAs as nutritional supplements has become a multi-million dollar business. At the center of the marketing for these products is the widely-believed claim that consumption of BCAAs stimulates muscle protein synthesis, and as a result elicits an anabolic response. BCAAs may also be consumed for the purpose of improving “mental focus”, but we will not consider that application. The primary purpose in this paper to evaluate the assertion that BCAAs alone are anabolic is adequately supported either theoretically or empirically by studies in human subjects. Implicit in our assessment will be the examination of whether or not the phosphorylation state of the eukaryotic initiation factors plays a rate-controlling role in the regulation of muscle protein synthesis in humans.

Muscle protein turnover and dietary protein intake
Muscle protein is in a constant state of turnover, meaning that new protein is continuously being produced while older proteins are being degraded. The anabolic state has no specific definition, but generally refers to the circumstance in which the rate of muscle protein synthesis exceeds the rate of muscle protein breakdown. The results in a gain of muscle mass. Conventionally the anabolic state is considered to be driven by a stimulation of muscle protein synthesis, but theoretically could also result from an inhibition of muscle protein breakdown.
The overriding metabolic goal of consuming BCAA supplements is to maximize the anabolic state. It is widely asserted that BCAAs induce an anabolic state by stimulating muscle protein synthesis. An abundant availability of all EAAs is a requisite for a significant stimulation of muscle protein synthesis [7]. Muscle protein synthesis will be limited by the lack of availability of any of the EAAs, whereas a shortage of NEAAs can be compensated for by increased de novo production of the deficient NEAAs [7]. In the post-prandial state following a meal containing protein, all of the EAA precursors required for new muscle protein synthesis can be derived from either the elevated plasma concentrations resulting from digestion of the consumed protein or from recycling from protein breakdown. In this circumstance of abundant availability of EAAs the rate of muscle protein synthesis exceeds the rate of breakdown, thereby producing an anabolic state. In the post-absorptive state the plasma EAA levels fall below the post-prandial values because amino acids are no longer being absorbed. As a result, EAAs are no longer taken up by muscle, but rather released by muscle into plasma [8]. This catabolic state of muscle protein in the post-absorptive state enables continued availability of EAAs for other tissues to maintain the rate of protein synthesis at the expense of muscle protein, which can be considered to play a role as the reservoir of EAAs for the rest of the body to draw upon.
Since EAAs cannot be produced in the body and there is a net release of EAAs from muscle, in the post-absorptive state the only source of EAA precursors for muscle protein synthesis is intracellular EAAs derived from muscle protein breakdown [8]. In addition to being reincorporated into muscle protein via synthesis, some EAAs released from muscle protein breakdown may be partially oxidized within muscle, thereby making them unavailable for reincorporation into muscle protein. EAAs released from muscle protein breakdown that are not reincorporated into muscle protein or oxidized within muscle tissue are released into plasma, whereupon they can either be taken up by other tissues as precursors for protein synthesis or irreversibly oxidized [9]. Thus, the rate of muscle protein synthesis will always be lower than the rate of muscle protein breakdown in the post-absorptive state, owing to the net flux of EAAs from protein breakdown into plasma and to oxidative pathways. Expressed differently, it is impossible for muscle protein synthesis to exceed the rate of muscle protein breakdown when the precursors are derived entirely from protein breakdown, and thus an anabolic state cannot occur in the absence of exogenous amino acid intake.

Are BCAAs anabolic in the post-absorptive state?

Theoretical considerations

All EAA precursors for muscle protein synthesis in the post-absorptive state are derived from muscle protein breakdown. It has been consistently reported that in normal post-absorptive humans the rate of muscle protein breakdown exceeds the rate of muscle protein synthesis by approximately 30% [10]. Consumption of BCAAs alone (i.e., without the other EAAs) can only increase muscle protein synthesis in the post-absorptive state by increasing the efficiency of recycling of EAAs from protein breakdown back into protein synthesis, as opposed to either being released in to plasma or oxidized. This is because all 9 EAAs (as well as 11 NEAAs) are required to produce muscle protein, and EAAs cannot be produced in the body. If only 3 EAAs are consumed, as is the case with consumption of BCAAs, then protein breakdown is the only source of the remaining EAAs required as precursors for muscle protein synthesis. It is therefore theoretically impossible for consumption of only BCAAs to create an anabolic state in which muscle protein synthesis exceeds muscle protein breakdown. If the generous assumption is made that BCAA consumption improves the efficiency of recycling of EAAs from muscle protein breakdown to muscle protein synthesis by 50%, then this would translate to a 15% increase in the rate of muscle protein synthesis(30% recycled in basal state X 50% improvement in recycling = 15% increase in synthesis). Further, a 50% reduction in the release of EAAs into plasma from muscle would also reduce the plasma and intracellular pools of free EAAs. Figure Fig. 1 schematically illustrates these principles. Since a 50% improvement in recycling efficiency would be about the reasonable maximal limit, this means that the maximal stimulation of muscle protein synthesis could not exceed 15%. This would correspond to an increase in the fractional synthetic rate of muscle from a basal value of about 0.050%/h in the basal state to 0.057%/h, and this difference in the fractional synthetic rate (FSR) of protein would be difficult to accurately measure [11].

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Fig. 1
Schematic representation of the recycling of essential amino acids (EAAs) from muscle protein breakdown into muscle protein synthesis in the post-absorptive state. Arbitrary units are used for simplicity and are based on measured rates of each pathway in post-absorptive human subjects [10]. a Normal circumstance in the post-absorptive state. Approximately 70% of EAAs from muscle protein breakdown are recycled into protein synthesis [10]. There is a net efflux of approximately 85% of EAAs released from protein breakdown, which can either be taken up and incorporated into protein in other tissues or oxidize. About 15% of EAAs from protein breakdown are partially oxidized in muscle and unavailable for protein synthesis. The figures for outward flux and intracellular oxidation of EAAs are averages, since some EAAs, such as phenylalanine, are not oxidized at all in muscle. b Representation of a 50% increase in efficiency of recycling of EAAs from muscle protein breakdown into protein synthesis. In this example there would be an increase in synthesis from 70 to 80 units, or 20%. Protein synthesis can never exceed protein breakdown in the post-absorptive state, since protein breakdown is the only source of EAAs




Empirical results

BCAAs have been administered intravenously in the only studies determining the response of muscle protein metabolism in human subjects to BCAAs alone. While the infusion of BCAAs is not the conventional manner in which a dietary supplement would be consumed, intravenously infused and orally-ingested amino acids have been shown to elicit comparable effects on muscle protein synthesis in other circumstances [12]. Consequently, it is reasonable to evaluate the papers in which the response of muscle protein synthesis to the intravenous infusion of BCAAs in human subjects.
Louard et al. [13] used the forearm balance method to quantify the response to the intravenous infusion of a mixture of BCAAs for 3 h in 10 post-absorptive subjects. The forearm balance method involves the measurement of the uptake and release of individual EAAs (leucine and phenylalanine in this case) and their isotopically-labelled counterparts. Rates of disappearance (Rd) and appearance (Ra) of phenylalanine and leucine are calculated. With the assumption that the balance across the muscle of leucine and phenylalanine is representative of all EAAs, Rd. of phenylalanine is taken to be a reflection of muscle protein synthesis, since protein synthesis is the only fate of phenylalanine taken up by muscle from plasma. The Rd. of leucine cannot be interpreted with regard to protein synthesis, as leucine taken up by muscle can be oxidized as well as incorporated into protein. The 3 h infusion of BCAAs increased plasma concentrations of all 3 BCAAs four-fold, while the concentrations of other EAAs decreased [13]. Rather than being stimulated by the BCAA infusion, muscle protein synthesis decreased from 37+/− 3 to 21 +/− 2 nmol/min/100 ml leg (statistically significant, p < 0.05) [13]. There was no significant change in net phenylalanine balance, indicating that muscle protein breakdown was also reduced an amount similar to the reduction in muscle protein synthesis. The balance between muscle protein synthesis and breakdown remained negative, meaning that the catabolic state persisted and an anabolic state was not produced. The simultaneous decreases in muscle protein synthesis and breakdown during BCAA infusion can be described as decreased muscle protein turnover.
Similar results were obtained by the same investigators when they extended the infusion of BCAA to 16 h in 8 normal volunteers and determined if chronic elevation of BCAAs stimulated muscle protein synthesis [14]. The same forearm balance methodology was used as in the previous study to calculate muscle protein synthesis and breakdown. The 16 h infusion increase BCAA concentrations from 5 to 8 fold [14], which is as much as double the levels achieved with a normal dose of BCAAs ingested orally [15]. As in the previous study, muscle protein synthesis (as reflected by phenylalanine Rd) was reduced in the subjects receiving BCAAs as compared to saline infusion from 36 +/− 5 to 27 +/−2 nmol/min/100 ml.Muscle protein breakdown was also reduced, meaning that muscle protein turnover was reduced as well, and a catabolic state persisted.
We can conclude from these two studies that BCAA infusion not only fails to increase the rate of muscle protein synthesis in human subjects, but actually reduces the rate of muscle protein synthesis and the rate of muscle protein turnover. The catabolic state was not reversed to an anabolic state in either study. Further, a sustained reduction in the rate of muscle protein turnover would be expected to have a detrimental effect on muscle strength, even if muscle mass is maintained. Muscle protein turnover renews the muscle fibers and results in increased efficiency of contraction at the single fiber level [16], which is reflected in increased strength in vivo, independent of muscle mass [17, 18].
The failure of muscle protein synthesis to increase significantly in response to the infusion of BCAAs alone is as expected according to the theoretical considerations discussed above and illustrated in Fig. Fig. 1 with regard to the requirement for all EAAs to sustain an increase. Instead, since muscle protein breakdown decreased, the availability of EAAs also fell, which in turn actually reduced the rate of muscle protein synthesis.

Are the anabolic signaling factors rate-limiting in the post-absorptive state?

The claim that muscle protein synthesis is stimulated by the BCAAs stems at least in part from the observation that intracellular anabolic signaling is increased, including the activation state of key factors involved in the initiation of protein synthesis [1]. The theory that activation of intracellular anabolic signaling factors causes an increased rate of muscle protein synthesis has become entrenched in modern concepts of the regulation of muscle protein synthesis. Increased anabolic signaling in response to BCAAs has been cited as evidence of a stimulation of muscle protein synthesis, even in the absence of the measurement of muscle protein synthesis (e.g., [1]). However, activation of the anabolic signaling pathways can only coincide with increased muscle protein synthesis if there are ample EAAs to provide the necessary precursors to produce complete protein.
Dissociation of the phosphorylation state of the signaling factors and muscle protein synthesis in humans has been shown in a variety of circumstances when the availability of all of the EAAs is limited. For example, an increase in insulin concentration (for example, as a result of glucose intake) is a potent activator of the anabolic signaling pathways, but this fails to increase muscle FSR because of a deficiency of EAAs [19]. Conversely, consumption of a small amount (3 g) of EAAs stimulates muscle protein synthesis without affecting initiation factor activity e.g., Akt, S6 kinase, and 4E–BP1 [20]. A small increase in plasma concentrations of EAAs would have no effect if protein synthesis was limited by the activation state of the initiation factors. In the studies cited above in which BCAAs were infused intravenously, it is reasonable to presume that such a large increase in BCAA concentrations would have activated the signaling factors, yet muscle protein synthesis actually decreased due to lack of availability of EAAs resulting from a decrease in protein breakdown. Thus, in human subjects provision of EAAs can increase muscle protein synthesis in the absence of any change in the activation of initiation factors, and activation of the initiation factors in the absence of consumption of all of the EAAs has no effect on muscle protein synthesis. These results can only be interpreted as demonstrating that the rate-limiting control of basal muscle protein synthesis in humans is availability of all of the EAAs as opposed to anabolic signaling factor activity. This conclusion casts further doubt on the role of dietary supplement of BCAAs alone as stimulators of muscle protein synthesis.
When all evidence and theory is considered together, it is reasonable to conclude that there is no credible evidence that ingestion of a dietary supplement of BCAAs alone results in a physiologically-significant stimulation of muscle protein. In fact, available evidence indicates that BCAAs actually decrease muscle protein synthesis. All EAAs must be available in abundance for increased anabolic signaling to translate to accelerated muscle protein synthesis.


BCAA co-ingestion with other nutrients

The focus of this review has been the response to BCAAs alone, as this is the logical intent of BCAA nutritional supplements. As in the case of consumption of BCAAs alone, there are limited studies of the co–ingestion of BCAAs with other nutrients. When BCAAs or an isonitrogenous mixture of threonine, methionine and histidine were administered to human subjects along with carbohydrate, the rate of muscle protein synthesis decreased equally in both groups, indicating no unique role of the BCAAs [21]. Similarly, consumption of a mixture of BCAAs to carbohydrate after resistance exercise did not increase the anabolic signaling factors to any greater extent than carbohydrate alone [22]. Thus, available evidence does not support the notion of a special anabolic effect of the BCAAs when given with carbohydrate.
In contrast to the lack of an interactive effect between BCAAs and carbohydrate, BCAAs may enhance the anabolic effect of a protein meal. For example, the addition of 5 g of BCAAs to a beverage containing 6.25 g whey protein increased muscle protein synthesis to a level comparable to that induced by 25 g of whey protein [23]. This result suggests that one or more of the BCAAs might be rate limiting for the stimulation of muscle protein synthesis by whey protein, or that the extra BCAAs induced a greater potential for an anabolic response of muscle to whey protein by activating the initiation factors. In either case, the response of BCAAs in conjunction with intact protein is a different issue that the effect of BCAAs alone, since the intact protein provides all of the EAAs necessary to produce an intact protein.

Individual effects of leucine, valine and isoleucine

In this paper we have considered only the response to mixtures of BCAAs. The responses to individual BCAAs (i.e., leucine, valine or isoleucine) might differ from the combination of the three for several reasons. Evidence indicates that leucine alone may exert and anabolic response (e.g., [24]), while no such data exists for isoleucine or valine. Thus, it might be expected that leucine alone would be more effective than the combination of all of the BCAAs. However, there are two significant limitations of a dietary supplement of leucine alone. First, the same issues that limit the extent of stimulation of muscle protein synthesis by BCAAs alone regarding the availability of the other EAAs necessary for the production of intact muscle protein also limit the response to leucine alone. Second, elevation of the plasma concentration of leucine activates the metabolic pathway that oxidizes all of the BCAAs. As a result, ingestion of leucine alone results in a decrease in the plasma concentrations of both valine and isoleucine. The availability of valine and isoleucine may therefore become rate limiting for muscle protein synthesis when leucine alone is consumed. This may be why long-term outcome studies with dietary leucine supplementation have failed to yield positive results [25]. The principal rationale for a dietary supplement containing all of the BCAAs as opposed to leucine alone is to overcome the decreases in plasma concentrations of valine and isoleucine that would occur when leucine is given alone.
While a dietary supplement with all of the BCAAs will overcome the decreases in concentration resulting from consumption of leucine alone, the addition of valine and isoleucine may nonetheless limit the effectiveness of leucine alone due to competition for transport into muscle cells. The BCAAs are all actively transported into cells, including muscle cells, by the same transport system. Therefore, when provided together the BCAAs compete with each other for transport into the cells. If one of the BCAAs (e.g., leucine) is rate limiting for protein synthesis, addition of the other two BCAAs might limit the stimulation of protein synthesis because of reduced entry of leucine into the cell. The BCAAs also compete with other amino acids for transport, including phenylalanine, and this competition could affect the intramuscular availability of other EAAs. As a result of competition for transporters, it is possible that leucine alone, for example, could have a transitory stimulatory effect on muscle protein synthesis (e.g., [21]) where the BCAAs fail to elicit such response [13, 14].


Conclusion

A physiologically-significant increase in the rate of muscle protein synthesis requires adequate availability of all amino acid precursors. The source of EAAs for muscle protein synthesis in the post-absorptive state is the free intracellular pool. Intracellular free EAAs that are available for incorporation into protein are derived from muscle protein breakdown. Under normal conditions about 70% of EAAs released by muscle protein breakdown are reincorporated into muscle protein. The efficiency of reincorporation of EAAs from protein breakdown back into muscle protein can only be increased to a limited extent. For this fundamental reason, a dietary supplement of BCAAs alone cannot support an increased rate of muscle protein synthesis. The availability of the other EAAs will rapidly become rate limiting for accelerated protein synthesis. Consistent with this perspective, the few studies in human subjects have reported decreases, rather than increases, in muscle protein synthesis after intake of BCAAs. We conclude that dietary BCAA supplements alone do not promote muscle anabolism.