For those who try to maximise muscle protein synthesis

[Mrpb]

Disclaimer: for most hitting their daily protein requirement is the most important thing. This thread is about spreading your protein over the day in order to achieve optimal protein synthesis. These ideas have not been proven (yet) to make a meaningful difference for real world muscle gains.

Layne norton suggest that to reach the leucine threshold one should consume for example at least 140 gram chicken for a ~160 pound man. This gives 43 gram protein and 3.2 gram leucine.
http://spotmebro.com/layne-norton-ph...and-how-often/

Stuart Phillips puts the bar a lot lower: "We know for sure that ingestion of ~0.25g/kg of protein (or more. see above) will maximally stimulate muscle protein synthesis and that should work across the day." That's only ~20 gram protein for a 160 pound man.
http://www.leanbodiesconsulting.com/...uart-phillips/

If a 160 pound man would consume 25 gram of protein it would be enough according to Stuart, while according to Layne it wouldn't reach the leucine threshold.

Has anyone investigated these ideas in more depth? Who makes the more credible case?

[snorkelman]

Over the last couple of years Layne Norton has posted regarding his position on the topic of leucine. At the 5th Annual ISSN Conference he presented that 3-4 grams (0.045 grams – 0.6 grams/kg) of leucine that will maximally stimulate MPS. See http://www.slideshare.net/biolayne/o...nd-muscle-mass

You may have seen the youtube video of Layne Norton presenting a poster presentation of some recent research,
.

Essentially his conclusion appears to be that distributing protein is important for rodents’ effective use of protein for muscle anabolism. His recommendation of eating three evenly spaced meals with protein of about 30-40 grams would have you ingesting an average of about 2-3 grams leucine. That seems to be a lowering of his earlier recommendations of 3-4 grams (from the 5th Annual ISSN Conference).

[Mrpb]

Essentially his conclusion appears to be that distributing protein is important for rodents’ effective use of protein for muscle anabolism. His recommendation of eating three evenly spaced meals with protein of about 30-40 grams would have you ingesting an average of about 2-3 grams leucine. That seems to be a lowering of his earlier recommendations of 3-4 grams (from the 5th Annual ISSN Conference).

Thanks that's helpful. I'll try to find some recent interviews to get more info.

[WonderPug]

I think the generic nature of your question reduces answers to, at best, averages with little practical impact to the individual.

I say this because the human protein synthetic machinery has high plasticity, based on myriad factors including contractile load. Total skeletal muscle, age, metabolic function, etc. also factor into the equation.

[Mrpb]

I was listening again to the radio show (2013) here, episode 2. It actually covers my questions. As Snorkelman said, his recommendation is to get at least 2-3 grams leucine. He also gives few reasons why it might be good to eat a bit more. (after 19 -20 minutes)
http://www.rxmuscle.com/2013-01-11-0...e-college.html

I think the generic nature of your question reduces answers to, at best, averages with little practical impact to the individual.

I say this because the human protein synthetic machinery has high plasticity, based on myriad factors including contractile load. Total skeletal muscle, age, metabolic function, etc. also factor into the equation.

That's a good reminder thanks.

[cumminslifter]

I think the generic nature of your question reduces answers to, at best, averages with little practical impact to the individual.

I say this because the human protein synthetic machinery has high plasticity, based on myriad factors including contractile load. Total skeletal muscle, age, metabolic function, etc. also factor into the equation.

this^ its going to vary depending on many factors such as age, race, LBM, training experience. etc.

[Mrpb]

I found a presentation of Stuart Phillips from 2014. Here are a couple of relevant slides. The whole presentation was very interesting.







Being 41 I might want to aim for >30 grams I guess.

Complete pdf: http://www.senr.org.uk/wp-content/up...an-31-2014.pdf

PS. the elder men in that study were ~71 years old.

[MichielN]

Subbed.

[adpayne]

So, will the optimal protein synthesis balance out the added cortisol from stressing about meal timing?

To each their own, but I've had better success since giving up focusing on the minor things, and putting my effort into getting the proper macros and correct training.

I'm worried that posts like this will get newbies over thinking things that should only concern competitive athletes.

[Mrpb]

So, will the optimal protein synthesis balance out the added cortisol from stressing about meal timing?

To each their own, but I've had better success since giving up focusing on the minor things, and putting my effort into getting the proper macros and correct training.

I'm worried that posts like this will get newbies over thinking things that should only concern competitive athletes.

The disclaimer I put in bold letters should be a good guidance.

However, if they're going to worry I'd rather see them worry about optimal protein intake than about making a 16 hour fast in order to achieve lean gains

[snorkelman]

I know your disclaimer is about achieving optimal protein synthesis, but you should keep in mind that both MPS and FSR are not necessarily guarantees of hypertrophy.

[Mrpb]

I know your disclaimer is about achieving optimal protein synthesis, but you should keep in mind that both MPS and FSR are not necessarily guarantees of hypertrophy.

I'm aware, that's why said it hasn't been proven to make a meaningful difference for real world muscle gain (yet).

[ThunderBee]

too much "kg" does not compute. other than that very interesting!

[RedSox1990]

I usually get about 200-240g @ 215lbs. Majority of it comes in my postworkout meal which contains ~70-100g of protein. Then I usually have two more meals to finish off w.e macro needs I have left. I guess I somewhat use Norton's theory, works well for me.

[adpayne]

The disclaimer I put in bold letters should be a good guidance.

However, if they're going to worry I'd rather see them worry about optimal protein intake than about making a 16 hour fast in order to achieve lean gains

The difference being, I have never suggested that someone follow my eating pattern. Just that it has worked well for me. I certainly wouldn't suggest someone go out their way to meeting a 16 fast in the hopes of it offering any more than convenience, etc.

[Mrpb]

I certainly wouldn't suggest someone go out their way to meeting a 16 fast in the hopes of it offering any more than convenience, etc.

Good to know.

[DannPM]

Subbed. This is the best thread I've seen since I have gotten back on here. Love the info and the discussion!

[Mrpb]

Any ideas about optimal meal spacing for those who want to maximise muscle protein synthesis?

Norton recommends 4-5 hours. While Phillips recommends equally spaced meals, which could be 3 hours for example. Listening to Norton he seems to believe 3 hours is too early for another meals because of certain things (forgot which) that are still elevated. According to him after four hours the body is more sensitive again to protein.

Ps. I realize this is probably only interesting for people who are interested in minute details.

[Gxp23]

Any ideas about optimal meal spacing for those who want to maximise muscle protein synthesis?

Norton recommends 4-5 hours. While Phillips recommends equally spaced meals, which could be 3 hours for example. Listening to Norton he seems to believe 3 hours is too early for another meals because of certain things (forgot which) that are still elevated. According to him after four hours the body is more sensitive again to protein.

Ps. I realize this is probably only interesting for people who are interested in minute details.

Its a refreshing change to the section, keep it up, although I am lurking, I am interested.

[MichielN]

Any ideas about optimal meal spacing for those who want to maximise muscle protein synthesis?

Norton recommends 4-5 hours. While Phillips recommends equally spaced meals, which could be 3 hours for example. Listening to Norton he seems to believe 3 hours is too early for another meals because of certain things (forgot which) that are still elevated. According to him after four hours the body is more sensitive again to protein.

Ps. I realize this is probably only interesting for people who are interested in minute details.

I think this recommendation is excellent:



I would say eating every 3 to 4,5 hours would be optimal. If your protein dose in a meal is more cassein rich, is higher in total protein, etc, you can wait a bit longer probably. Either way, I think a moderate meal frequency (4-6) would be ideal, assuming the protein is evenly spread across the day (since a prolonged state of hyperaminoacidemia is likely important). I do not think IF (or similar) protocols are optimal, they are perfectly fine for retaining muscle mass, less so for adding more of it.

4 to 6 meals likely isn't a big game changer for anyone, as long as you focus a bit on spreading your protein intake evenly this still allows for a flexible life style imo.

As for even a higher meal frequency (should that be your preference for some strange reason), that should be fine too. I think this part explains it nicely:

The idea however that more meals are less desirable is usually based on a single study (13) showing that muscle protein synthesis tapers off with a continuous infusion of proteins during parenteral nutrition. They use this as a means to claim that more meals would lead to lower protein synthesis. However, if you know how this process works, you understand that a continuous infusion would lead to a stable level of amino acids in the intra- and extra-cellular space that would shut down the amino acid shuttles needed to transport amino acids into the cell, elevate intra-cellular levels and initiate or maintain protein synthesis. No matter how you eat, digestion is never going to lead to such a pattern of amino acid supply, it’s always going to lead to an oscillating pattern with highs and lows. So there is nothing wrong with more meals. It then becomes a question of “is it necessary to consume more meals”, and as you may have gathered from my agreement with Mr.Aragon’s stance in his article, the answer is, in most cases, no. I’m of the same opinion as (supposedly) Dr.Phillips, that 4-5 meals is more than sufficient for most people to supply the needed calories and protein. However, just as research proves a reduced meal frequency is better for satiety, it implies a higher frequency is better to reduce it. And in all my years training people, if there has been one huge bottleneck with a lot of people, it has been getting them to consume enough calories and protein to get them to accrue the muscle mass they desire. And believe me, for those people, one or two extra meals make all the difference. I personally was a hard-gainer until my Football coach taught me to set my alarm to go off every hour and eat something small, anything. I guarantee you within a week I was ravenous with hunger all the time, and after just 10 months I had gained more mass than in the previous or following years combined.

Source: http://muscleandsportsscience.com/me...ient-fat-loss/

[Mrpb]

Thanks MichielN, this is the piece by Layne:

Now there is the issue of meal frequency and time between meals. Assuming we maximize protein synthesis by achieving the required leucine/protein threshold, how long does the effect last? Several studies have shown that the duration of protein synthesis in response to an oral leucine dose or an essential amino acid infusion is approximately two hours long4,5. However, these are purified amino acid solutions and are likely to be digested rapidly and in the case of an infusion, no digestion is required at all. So it is possible that a whole food meal will have a different impact on the duration of protein synthesis than pure amino acids. Our lab has recently shown that the duration of protein synthesis in response to a complete meal containing protein, carbohydrates, and fats is approximately 3 hours long6. Therefore, it appears that a complete meal slightly prolongs the duration of protein synthesis. What is interesting about our findings is that while protein synthesis had returned to baseline after 3 hours, plasma amino acid levels were still elevated above baseline and plasma leucine was elevated almost 3x above baseline! Accordingly, the phosphoryation of the initiation factors 4E-BP1 & p70S6K followed plasma leucine levels and maintained elevated levels of phosphorylation at 3 hours (phosphorylation of these initiation factors is required to start the process of protein synthesis). Thus it appears that the signal to maintain elevated protein synthesis is still being ‘transmitted’ but for some reason protein synthesis is becomes refractory after a certain period of time. This is also supported by data from Bohe et al which showed that the duration of protein synthesis in response to an infusion of essential amino acids was only 2 hours long even though the essential amino acids were infused for six hours5! It is unlikely that eating another meal 2-3 hours after the first meal would be sufficient to induce another rise in protein synthesis since amino acid/leucine levels are already elevated anyway. It may therefore be more useful to consume larger amounts of protein at a meal and wait longer between protein doses than the typical 2-3 hours that is typically recommended in the bodybuilding community.
[...]
What I am implying is that it is better to consume larger protein doses spaced further apart and maximize protein synthesis, rather than consume smaller doses of protein throughout the day, since research has shown that protein synthesis will become refractory to constantly elevated levels of amino acids. It may be that a period where amino acids return to baseline or near baseline is required in order to initiate another bout of protein synthesis. I therefore suggest that one consume 4-6 larger protein doses per day instead of 6-8 meals and wait 4-5 hours between meals rather than 2-3 hours.

You think he has a point? If so, why not?

[MichielN]

I think my quote would (or could) be an explanation/response to Layne's ideas, lol

[Jasonk282]

So, will the optimal protein synthesis balance out the added cortisol from stressing about meal timing?

To each their own, but I've had better success since giving up focusing on the minor things, and putting my effort into getting the proper macros and correct training.

I'm worried that posts like this will get newbies over thinking things that should only concern competitive athletes.

This /thread.

Just hit your macros and training and everything else will fall into place. People really over complicate a very simple process for some unknown reason.

[Mrpb]

I think my quote would (or could) be an explanation/response to Layne's ideas, lol

Yeah I read that but for me it didn't really refute Laynes idea that you get a more robust response if you wait a bit longer.

[MichielN]

Yeah I read that but for me it didn't really refute Laynes idea that you get a more robust response if you wait a bit longer.

I think that, asuming a moderate meal frequency evenly spread across the day, the difference between waiting 3-4 hours or 4-5 hours is negligable.

[ZMan45]

This /thread.

Just hit your macros and training and everything else will fall into place. People really over complicate a very simple process for some unknown reason.

Intelligent discussions such as these will only be good for this section. In a forum that is 90% dumb/obvious questions that have been answered ad nauseam, it's nice to be able to actually debate and reach a higher understanding of the topic at hand.

[Mrpb]

Just hit your macros and training and everything else will fall into place. People really over complicate a very simple process for some unknown reason.

In case you're really interested in the reason why, in the words of Alan Aragon & Eric Helms:

A relatively recent concept with potential application to meal frequency is that a certain minimum dose of leucine is required in order to stimulate muscle protein synthesis. Norton and Wilson [116] suggested that this threshold dose is approximately 0.05 g/kg, or roughly 3 g leucine per meal to saturate the mTOR signaling pathway and trigger MPS. A related concept is that MPS can diminish, or become 'refractory' if amino acids are held at a constant elevation. Evidence of the refractory phenomenon was shown by Bohé et al. [117], who elevated plasma amino acid levels in humans and observed that MPS peaked at the 2-hour mark, and rapidly declined thereafter despite continually elevated blood amino acid levels. For the goal of maximizing the anabolic response, the potential application of these data would be to avoid spacing meals too closely together. In addition, an attempt would be made to reach the leucine threshold with each meal, which in practical terms would be to consume at least 30–40 g high-quality protein per meal. In relative agreement, a recent review by Phillips and Van Loon [28] recommends consuming one's daily protein requirement over the course of three to four isonitrogenous meals per day in order to maximize the acute anabolic response per meal, and thus the rate of muscle gain.

It is important to note that the leucine threshold and the refractory nature of MPS are not based on human feeding studies that measure concrete outcomes over the long-term. These ideas are largely based on mechanistic studies whose data was derived via steady intravenous infusion of amino acids [117,118]. Long-term studies are needed to determine if the refractory nature of MPS seen in acute infusion data would have any real impact on the gain or preservation of LBM at various meal frequencies.

source: http://www.jissn.com/content/11/1/20

Some studies have shown more muscle gain with a better protein spread, Burk et al. 2009 for example.

As Alan and Eric point out, long term studies will be needed to find out if it really makes a significant difference or not.

I think that, asuming a moderate meal frequency evenly spread across the day, the difference between waiting 3-4 hours or 4-5 hours is negligible.

Ok got ya.

[BrickNmortar]

so why not supp with l-leucine instead of (or on top of) eating all that chicken?

[gansi1]

Stuart Phillips' research - as well as that done by others - on effects of amino acid and/or protein ingestion has limitations that are study- and context- specific. Looking at protein ingestion in the sole context of protein synthesis is misleading. Moreover, these studies are very individual-specific and mostly short-term.

But let's and take their data at face value.

From Stuart Phillips' highly-cited paper from The American Journal of Clinical Nutrition:

"...we speculate that no more than 5–6 times daily could one ingest this amount (≈20 g) of protein and expect muscle protein synthesis to be maximally stimulated."

This would result in between 100-120 g protein/day. Firstly, this statement is, as they admit, speculative.

Secondly, many studies indicate this to be incorrect. Tarnopolsky et al. have shown the limit for protein oxidation to be about 1.8 g/protein/kg/day. Other more recent studies and review papers have put this limit in a similar range or even higher. This either results in more than 5-6 meals of 20 g/protein each, or in 5-6 meals with more than the amount Stuart recommends.

This is, admittedly, a touchy subject and all I'm showing here is that there is evidence from both sides of the argument.

Next, Phillips claims that spacing out protein is beneficial for maximal MPS.

Arnal MA and colleagues found the opposite: They reported that there was no difference in protein retention or protein synthesis/turnover when test subjects ate all of their protein in one single meal (about 55 grams) or whether they spread it among 4 smaller meal throughout the day. Elsewhere, more recently, others have shown that there was no difference in muscle protein whether test subjects consumed all of their protein (101 grams) in one meal or across multiple meals.

On the topic of leucine stimulation of protein synthesis, there is evidence that it indeed stimulated protein synthetic pathways. However, research data increasingly suggests that the effect of leucine on protein synthesis is age-dependent, with stimulation of MPS requiring greater amounts of leucine with increasing age.

This begs the question, why not supplement with leucine? Looking at leucine alone is also being questioned.

A recent study showed that supplementation of leucine together with minimal protein (6.25 g) does not in fact lead to effective MPS compared to a larger (25 g) ingestion of whey protein alone without leucine supplementation. Another study (this one age-focused) reached a similar conclusion.

On a more general note, Balage and Dardevet concluded that there is no compelling evidence that leucine supplementation leads to increased MPS, and that a balanced mixture of BCAAa may be more efficacious than leucine alone.

[Mrpb]

Arnal MA and colleagues found the opposite: They reported that there was no difference in protein retention or protein synthesis/turnover when test subjects ate all of their protein in one single meal (about 55 grams) or whether they spread it among 4 smaller meal throughout the day.

According to Layne Norton the amount of protein in the smaller meals that were spread over the day were too small to reach the threshold. At 10:55 in this video.

On a more general note, Balage and Dardevet concluded that there is no compelling evidence that leucine supplementation leads to increased MPS, and that a balanced mixture of BCAAa may be more efficacious than leucine alone.

Would a balanced mixture of BCAAs have the same effects on MPS as a complete meal with similar amount of EAA?

Would the mixture have to contain 9 BCAAs?