Muscle protein synthesis is the process of building muscle mass.
Muscle protein synthesis is essential for exercise recovery and adaptation. As such, it’s a really popular topic in the fitness community.
But the methods used to measure muscle protein synthesis in studies are very complicated. Some basic knowledge of the various methods is essential to draw proper conclusions from the research you’ll read.
The purpose of this article is to provide a comprehensive guide on muscle protein synthesis: what is it, how is it measured, what are the strengths and limitations, how to draw proper conclusions from muscle protein synthesis research, and of course practical guidelines how to optimize it.
I’ve made a table of contents, so you can jump to specific sections of interest or reference a specific section.
Please note that section 3 described the various methods to measure muscle protein synthesis. You might want to skip this section if you just want exercise and nutrition guidelines to optimize gains. Perhaps you can come back to it later when you are ready to become a true muscle protein synthesis research master.
I’ll be covering:
Contents
- 1. What is protein synthesis?
- 2. Why muscle protein breakdown is of less importance
- 3. Methods to measure protein synthesis
- 4. Interpretation and misconceptions
- 5. Advantages of muscle protein synthesis measurements over muscle mass measurements.
- 6. How to optimize muscle protein synthesis: exercise guidelines.
- 7. How to optimize muscle protein synthesis: nutrition guidelines
- 8. Summary
1. What is protein synthesis?
Protein is the main building block of your muscle.
When you ingest protein, the protein is digested into amino acids. These amino acids are absorbed in the gut and subsequently released into the circulation. From there, the amino acids are transported to peripheral tissues where they are taken up and can be build into tissue protein.
Protein synthesis is the process of building new proteins. This process happens in all organs. Muscle protein synthesis is the process of building specifically muscle protein.
Think of a muscle as a wall. Each brick is an amino acid. Muscle protein synthesis is the addition of new bricks to the wall.
Now, this would mean the wall would become larger and larger. However, there is an opposing process. On the other side of the wall, a process called muscle protein breakdown is removing bricks. Muscle protein breakdown is also commonly referred to as muscle proteolysis or muscle degradation.
It’s important to realize that both muscle protein synthesis and breakdown are always ongoing. They are not “on” or “off”, but their speed can increase or decrease. The difference in speed of these two opposing processes determines the net change in muscle protein size.
If muscle protein in synthesis exceeds muscle protein breakdown, the wall will become larger (your muscles are growing). If muscle protein breakdown exceeds muscle protein synthesis, the wall is shrinking (you’re losing muscle mass).
The sum of these two processes determines your net balance:
net muscle protein balance = muscle protein synthesis – muscle protein breakdown.
You can also compare it to your bank account.
balance = income – expenses
2. Why muscle protein breakdown is of less importance
We’ll almost exclusively talk about muscle protein synthesis, and not focus much on muscle protein breakdown.
That might sound like you’re missing out on a whole lot, but you’re not.
Changes in muscle protein synthesis are much greater in response to exercise and feeding than changes in muscle protein breakdown in healthy humans (Phillips, 1997)(Greenhaff, 2008).
While feeding can reduce muscle protein breakdown by approximately 50%, very little is needed to reach this maximal inhibition.
This is best illustrated by a study which clamped (maintained) insulin at different concentrations and also clamped amino acids at a high concentration.
There were five conditions:
- Fasted state
- high amino acids + low insulin
- high amino acids + medium insulin
- high amino acids + high high insulin
- high amino acids + very high insulin
In the illustration below, you see the effects on muscle protein breakdown.
In a fasted state, muscle protein breakdown rates were relatively high (condition 1). Amino acid infusion did not reduce muscle protein breakdown when insulin was kept low (condition 2). But when insulin was infused to reach a moderate concentration, muscle protein breakdown rates went down (condition 3). Further increasing insulin did not have an additional effect on muscle protein breakdown (conditions 4 and 5).
So this study shows us a couple of things.
Firstly, insulin inhibits muscle protein breakdown, but you only need a moderate insulin concentration to reach the maximal effect. In this study the medium insulin concentration already resulted in the maximal 50% muscle protein breakdown, but other research has shown that even half the insulin concentration of the medium group is already enough for the maximal effect (Wilkes, 2009).
Secondly, protein ingestion does not directly inhibit muscle protein breakdown. While protein intake can decrease muscle protein breakdown (Groen, 2015), this is because it increases the insulin concentration.
You only need a minimal amount of food to reach insulin concentrations that maximally inhibit muscle protein breakdown. In agreement, adding carbohydrates to 30 g of protein does not further decrease muscle protein breakdown rates (Staples, 2011).
Therefore, it often doesn’t make much sense to measure muscle protein breakdown in nutrition studies. All study groups that got at least some amount of food will have the 50% inhibition of fasted muscle protein breakdown rates. If the effect on muscle protein breakdown is the same between groups, then changes in muscle protein net balance would be entirely be explained by differences in muscle protein synthesis.
It should be noted that HMB decreases muscle protein breakdown in an insulin independent way (Wilkinson, 2013). It is not known of the effects of HMB and insulin on muscle protein breakdown are synergistic. However, HMB supplementation appears to have minimal effects of muscle mass gains in long-term studies (Rowlands, 2009).
Of course, you can speculate that muscle protein breakdown becomes more relevant during catabolic conditions during which there is significant muscle loss, such as dieting or muscle disuse (e.g. bed rest or immobilization). However, it cannot be simply assumed that the observed muscle loss in such condition is the result of increased muscle protein breakdown. After just 3 days of dieting, there is already a large decrease in muscle protein synthesis. In agreement, there is a large decrease in muscle protein synthesis during muscle disuse. Therefore, muscle loss may be largely (or even entirely) caused by a reduction in muscle protein synthesis, and not by an increase in muscle protein breakdown.
But let’s say that muscle protein breakdown does go up a bit during catabolic conditions. Then the first question would be, could nutrition prevent this? If the answer is no, muscle protein breakdown is still not that relevant to measure. If nutrition does have an effect, how much would it take? Let’s say you need double the amount of insulin you normally need to maximally inhibit muscle protein breakdown. That would still be a small amount of insulin that any small meal would release and all nutritional interventions have the same effect. So even during catabolic conditions, muscle protein synthesis rates are likely much more relevant than muscle protein breakdown.
While it sounds that muscle protein breakdown is a bad thing and we should try to completely prevent it, that is not necessarily true. Muscle proteins get damaged from exercise, physical activity, and metabolism (e.g. oxidative stress, inflammation etc). Muscle protein breakdown allows you to break down those damaged muscle proteins into amino acids and recycle most of them into new functional muscle proteins again.
In fact, muscle protein breakdown has beneficial roles in muscle growth and adaptation! If mice are genetically engineered so that they can’t properly break down muscle protein, they are actually weaker and smaller than normal mouses. This highlights that at least some amount of muscle protein breakdown is necessary to optimally adapt to training and maximize muscle growth (Bell, 2016).
So anytime you eat just about anything, you’ll reduce muscle protein breakdown by 50%. We don’t know how to reduce muscle protein breakdown even further, but it’s not clear if we would even want that, as at least some muscle protein breakdown seems necessary for optimal muscle growth.
3. Methods to measure protein synthesis
3.1 Nitrogen balance
Carbohydrates and fats are made of carbon, hydrogen, and oxygen. In contrast, protein also contains nitrogen. So the nitrogen that we get through our diet has to come from protein.
As protein is broken down by the body, most of the protein derived nitrogen has to be excreted in the urine or it would accumulate and become toxic.
It’s fairly easy to measure nitrogen in food, feces, and urine. By doing so, we can calculate a balance:
nitrogen balance = nitrogen intake – nitrogen excretion
If nitrogen intake is bigger than nitrogen excretion, we are in a positive nitrogen balance. This indicates that your body stores more protein than it’s losing. This gives a general view that the body is in an anabolic (growing) state.
However, this method gives us very little insight into what exactly is going on.
You can have a positive nitrogen balance, while you’re losing muscle tissue. For example, your body might be building gut protein at a rate that exceeds your muscle loss.
As such, nitrogen balance is not that informative for athletes.
Example paper nitrogen balance: (Freeman, 1975)
3.2 Tracers
![1-[13C]-leucine](http://www.nutritiontactics.com/wp-content/uploads/2016/04/1-13C-leucine.jpg)
Before we go on to the next method, I need to introduce a new concept: tracers.
Tracers are compounds that you can trace throughout the body. Amino acid tracers are the most common type of tracers to assess muscle protein synthesis. These are amino acids that have an additional neutron. These amino acid tracers function identically to normal amino acids. However, they weigh slightly more than a normal amino acid, which allows us to distinguish them from normal amino acids.
A normal carbon atom has a molecular weight of 12. When we add a neutron, it has a weight of 13. We indicate these special carbons like this: L-[1-13C]-leucine. This means the amino acid leucine, has a carbon atom with a weight of 13. When you see such a notation in a paper, you know they’re using tracers.
Because you can follow amino acid tracers throughout the body, it allows us to measure various metabolic processes that happen to the amino acids, including protein synthesis.
3.3 Whole-body protein metabolism
Using amino acid tracers, we can measure protein synthesis, breakdown, oxidation and net balance.
Note that protein synthesis refers to protein synthesis of any protein in the body (whole-body protein synthesis). Again, do not mistake it for muscle protein synthesis, which is protein synthesis specifically of muscle protein. Therefore, (whole-body) protein synthesis measurements are not necessarily relevant for athletes and might actually give you the wrong impression (as will be discussed in chapter 3).
However, whole-body protein metabolism data provides more insight than the nitrogen balance method.
Nitrogen balance only indicates an overall anabolic or catabolic state. The whole-body protein metabolism method also indicated this by a positive or negative protein net balance. However, it also shows whether changes in net balance are because of an increase in protein synthesis, a decrease in protein breakdown, or a combination of both.
Please note that this does not contradict the earlier discussion on muscle protein breakdown is not that important. While muscle protein breakdown doesn’t change much, protein breakdown of other tissues can change drastically.
Instinctually, you might think that a more positive whole-body protein balance must be a good thing. However, that’s not really the case. It could simply mean that you’re building more gut protein, which is not something you would necessary want unless you want to have a bloated stomach.
Example paper whole-body protein metabolism: (Borie, 1997)
3.4 Two pool and three pool arteriovenous technique
These methods measure amino acid concentrations in the artery to a muscle, and the vein from that muscle.
Let’s say that the amino acid concentration is low in the artery going to a muscle and high in the vein coming from that muscle. Where did those extra amino acids in the vein come from? They’re released from the muscle, and it would indicate that the muscle is breaking down. Conversely, if the muscle would take up a lot of amino acids from the artery, but releases less amino acids to the vein, it would indicate that the muscle is taking up a lot of amino acids to build muscle proteins.
This method is called the two pool arteriovenous method. A drawback of this method is that you don’t really know for sure what is going on in the muscle. Just because a muscle is taking up amino acids, that does not mean it’s building all of those amino acids into actual muscle tissue.
To solve this problem, this method can be combined with muscle biopsies. This is called the three pool model and allows us to see what happens to the amino acids once they’re taken up by the muscle.
The main advantage of this method is that it measures both muscle protein synthesis and muscle protein breakdown. However, the calculations are depended on blood flow measurements, which we can’t measure all that accurately. Therefore, this is not the preferred method for measuring muscle protein synthesis.
Example paper 3 pool model: (Rasmussen, 2000)
3.5 Fractional synthetic rate
This method combines the infusion of amino acid tracers with muscle biopsies.
The most basic explanation is that you take a pre and post muscle biopsy, and measure the rate at which the amino acid tracer is built into the muscle.
This method gives you a fractional synthetic rate (FSR), expressed as %/h. It shows you how fast a muscle would rebuild itself entirely. An FSR of 0.04 %/h means that each hour, 0.04% of the total muscle is synthesized. This translates to a completely new muscle every 3 months. To regenerate as fast as Wolverine of the X-men, you would need an FSR of 100000 %/h in all your tissues.
This is the most common method of measuring muscle protein synthesis.
A minor drawback of this method is that it requires a ”steady state” to have the most accurate measurements. I don’t want to go into too many details, but it often means plasma amino acid enrichment should stay at the same level (the ratio of the tracer amino acid to the normal amino acid). However, protein ingestion would disturb this steady state, as a lot of normal amino acids will enter the blood, thus throwing off the tracer amino acid to normal amino acid ratio. Therefore, a lot of older studies provided protein in small sips, which wouldn’t disturb the steady state.
A slight disturbed steady state isn’t the end of the world for the measurement, but it’s sometimes something to consider when evaluating the data.
However, our lab has gotten fancy in this area. We have been able to produce highly enriched intrinsically labeled protein. This means that the amino acid tracers have been build into our protein supplements. So as our intrinsically protein supplements are absorbed, both amino acid tracers and normal amino acids enter the blood. Therefore the steady state is not disrupted and FSR can be calculated more accurately.
Example paper FSR (with and without intrinsically labeled protein): (Holwerda, 2016)
3.6 De novo muscle protein synthesis
The highly enriched intrinsically labeled protein has another advantage.
You can trace the amino acids from the protein: first, as they are digested, then as they appear in the blood, subsequently they are taken up by the muscle, and ultimately some of them are built into actual muscle tissue. So we can measure how much of the protein you eat, actually ends up into muscle tissue.
This is called de novo muscle protein synthesis. It’s building new muscle protein from your food, in contrast to building muscle protein by recycling amino acids from protein breakdown.
Example paper de novo muscle protein synthesis: (Trommelen, 2017).
3.7 Specific muscle protein fractions
When measuring muscle protein synthesis, we can measure mixed muscle protein synthesis (all types of muscle protein together). But muscle protein can be further specified into fractions.
The main muscle protein fraction is myofibrillar protein. Myofibrillar proteins contract and represent the majority of the muscle mass. This fraction is highly relevant for building muscle mass and strength.
Mitochondrial proteins only represent a small part of the muscle. Mitochondria are the powerhouses of the muscle, they burn carbohydrate and fat for fuel. Therefore mitochondrial protein synthesis is more informative about energy production capacity in the muscle and more relevant for endurance athletes and metabolic health.
Sarcoplasmic protein contains various organelles such as the endoplasmic reticulum and ribosomes.
Intramuscular connective tissue protein represents collagen protein in the muscle. This collagen helps transfer the muscle force generated by myofibrillar protein. It may be relevant for strength, injury prevention, and mobility, but we don’t know that much about it yet.
Example paper myofibrillar vs mitochondrial protein synthesis: (Wilkinson, 2000), or intramuscular connective tissue protein synthesis (Trommelen, 2020)
- Mixed muscle protein synthesis measures the synthesis of all muscle proteins.
- Myofibrillar protein synthesis measures only contractile proteins and is the most relevant measurement for muscle mass gains.
- Mitochondrial protein synthesis is more relevant for endurance and metabolic health.
3.8 Deuterium oxide
More recently, deuterium oxide (D2O, also called heavy water) is getting popular to measure muscle protein synthesis.
I’m going to skip most of the technical details, but the big difference with amino acid tracers is that this technique can accurately measure muscle protein synthesis days or even weeks, whereas the amino acid tracer technique measures muscle protein synthesis accurately over hours. In the next section, we’ll explain why this matters.
Example paper deuterium oxide: (Brooks, 2015)
3.9 Molecular markers
There is evidence that a variety of signaling molecules are involved in the regulation of muscle protein synthesis. Most notably, the protein from the mTOR pathway. Research of these molecular markers is very important to better understand how physiological processes are regulated and ultimately can be influenced by exercise, nutrition or even drugs.
However, at this point, we don’t understand them well for them to be useful predictors of physiology. In other words, while mTOR activation is involved in the regulation of muscle protein synthesis, an increase in mTOR activation doesn’t necessarily mean that muscle protein synthesis will actually increase.
Therefore, you should be very skeptical to draw conclusions based on studies that only measure molecular markers of muscle protein synthesis and muscle protein breakdown.
Example paper molecular markers (in this paper they don’t reflect actual MPS measurements): (Greenhaff, 2008)
4. Interpretation and misconceptions
Methods are not necessarily good or bad. But the interpretation of the data based on these methods can be wrong.
4.1 Whole-body protein synthesis vs muscle protein synthesis
We recently showed that resistance exercise does not increase whole-body protein synthesis (Holwerda, 2016). So should we conclude that resistance exercise is not effective to build muscle?
Absolutely not.
Whole-body protein metabolism measures the synthesis of all proteins in the body. Resistance exercise specifically builds muscle protein; it doesn’t increase protein synthesis in other organs. Other tissues in the body have much higher synthesis rates, and therefore, the muscle only has a relatively small contribution to the total whole-body protein synthesis rates. Therefore, you don’t see an increase in whole-body protein synthesis following resistance exercise.
In the same study, we also measured muscle protein synthesis (using the FSR method both with and without intrinsically labeled protein) and de novo muscle protein synthesis. All 3 methods showed that resistance exercise was anabolic for the muscle.
So resistance exercise did exactly what it’s supposed to do: build muscle, not build your other organs.
Often, labs don’t have the money or expertise to do many of these measurements. Imagine we would have only measured whole-body protein synthesis. Our study would give the wrong impression that resistance exercise is not anabolic, as we saw no increase in whole-body protein synthesis rates. Therefore it’s important that you understand the difference between whole-body protein synthesis and muscle protein synthesis methods.
Let’s discuss another example:
This study has been getting a lot of attention:
”The anabolic response to a meal containing different amounts of protein is not limited by the maximal stimulation of protein synthesis in healthy young adults” (Kim, 2016).
Shortly, it says that very large protein meals are beneficial because they reduce protein breakdown.
This gathered a lot of attention on social media and some of the comments were:
– See we shouldn’t ignore muscle protein breakdown!
– See that you need more than 40 gram of protein in each meal!
Again, this study gave the wrong impression, because whole-body protein breakdown was mistaken for muscle protein breakdown (the latter was not measured in this study). In case you’re wondering, this study did measure muscle protein synthesis. Both the 40 gram and the 70 gram dose were equally effective at stimulating muscle protein synthesis. So this study doesn’t indicate that you need more than 40 gram of protein each meal as an athlete.
4.2 Correlation muscle protein synthesis and muscle mass gains
One of the purposes of measuring muscle protein synthesis is to study if an intervention helps to build muscle or maintain muscle mass.
On social media, I occasionally see people dismissing muscle protein synthesis studies by claiming:
”it’s just an acute mechanistic study, it doesn’t necessarily translate to long-term changes in muscle mass”.
While there is some truth to the statement, it’s massively overused and often used as a cop-out as they have limited understanding of muscle protein synthesis. In fact, there are strong benefits for acute muscle protein synthesis studies over long-term training studies, which I’ll discuss in the next section.
Let me first get something out of the way: we have no bias for either acute or long-term studies. We run both at our lab, and do some of the most expensive studies in the field of either type.
The concern that muscle protein synthesis may not translate to muscle mass gains got an uprise when the following study was published:
”Acute post-exercise myofibrillar protein synthesis is not correlated with resistance training-induced muscle hypertrophy in young men” (Mitchell, 2014).
A lot of people seem to think that based on this study, muscle protein synthesis measurements do not translate to actual muscle mass gains in the long term.
But that conclusion is way beyond the context of the study. This study measured muscle protein synthesis in the 6 hours after a single exercise bout. However, resistance exercise can increase muscle protein synthesis for several days. So a 6-hour measurement does not capture the entire exercise response. This study showed that measuring muscle protein synthesis for 6 hours does not predict muscle mass gains. That is totally different from the conclusion that muscle protein synthesis (regardless of measurement time) does not predict muscle mass gains.
This was followed up by a study which used the deuterium oxide method to measure muscle protein synthesis rates during all the weeks of training (not just a few hours after one session), and found that muscle protein synthesis did correlate with muscle mass gains during the training program (Brooks, 2015).
More recently, a study found that muscle protein synthesis measured over 48 hours after an exercise bout did not correlate with muscle mass gains in untrained subjects at the beginning of an exercise training program, but it did at three weeks of training and onwards (Damas, 2016). While untrained subjects have a large increase in muscle protein synthesis after their initial exercise sessions, they also have a lot of muscle damage. So muscle protein synthesis is mainly used to repair damaged muscle protein, not to grow. After just 3 weeks of training, muscle damage is diminished, and the increase in muscle protein synthesis is actually used to hypertrophy muscles.
So do these studies show that muscle protein synthesis predicts muscle mass gains, but only in the right context.
- Exercise elevates muscle protein synthesis for 24 hour or longer: ideally you have a muscle protein measurement of 24 hours or longer and have ‘trained’ subjects so training induced muscle damage is attenuated (3 weeks of training is enough)
- Protein ingestion increased muscle protein synthesis for ±3-6 hours, so ideally you have measurement period of 6 hours (longer would actually be detrimental)
5. Advantages of muscle protein synthesis measurements over muscle mass measurements.
A huge benefit of muscle protein synthesis studies is that they are more sensitive than studies that measure actual muscle mass gains. This means that muscle protein synthesis studies can detect an anabolic effect easier than long term studies which simply miss it (long term studies might draw the wrong conclusion that something does not benefit muscle growth when it actually does).
For example, it has been shown time and time again that protein ingestion increases muscle protein synthesis. But the vast majority of long-term protein supplementation studies (80%) have found that protein supplementation does not increase muscle mass gains (Cermak, 2012).
This is because most long term studies are underpowered, aka don’t have enough statistical power to find small positive effects. Muscle mass gain is simply a very slow process. You need to do a huge study, with a huge amount of subjects, who consume additional protein for many months, before you will actually see a measurable effect of protein supplementation.
We performed a meta-analysis (combining the results of individual studies) on the effect of protein supplementation on muscle mass gains. We demonstrated that only 5 studies concluded that protein supplementation had a benefit, while 17 did not! However, most of the studies that showed no significant benefit, did show a small (non-significant) benefit. When you combine all those results, you increase the statistical power and you can conclude that protein supplementation actually does improve muscle mass. So in this case, most long-term studies gave the wrong impression, and muscle protein synthesis studies are actually preferred.
There are a lot of long-term studies that have a relative small number of subjects and a small study duration and conclude that an intervention did not work (for example, protein supplementation, or X versus Y set of exercise for example). However, the studies were doomed to begin with. They needed to be 3 times as big and 2 times as long to have a chance to find a positive effect. These studies unfortunately give people the impression that something doesn’t work, while it actually might/does.
Now if the effect of giving additional protein is already extremely hard to detect in long-term studies, how realistic is it to find smaller effects? For example, optimizing protein intake distribution throughout the day has been shown to optimize muscle protein synthesis rates (Mamerow, 2014)(Areta, 2013). However, this effect is smaller than adding another protein meal. So the effect of protein distribution is almost impossible to find in a long-term study. For such a research question, acute muscle protein synthesis studies are simply much better suited.
The second big benefit of muscle protein synthesis studies is that they give a lot more mechanistic insight. They help you understand WHY a certain protein is good or not that good at stimulating muscle protein synthesis (for example, its digestion properties, amino acid composition etc). These kinds of insights help to better understand what triggers muscle growth and come up with new research questions. These kind of insights are very hard to obtain in long-term studies, which typically only show the end result of the mechanisms.
The benefits of measuring muscle protein synthesis include the sensitivity, controlled environment, and they allow you to investigate questions that are almost impossible to answer in long-term studies. In addition, they’ll give you a lot of mechanistic insight, which opens the door for future research.
But ultimately, it’s not a matter of which type of study is better. Again, we do both and each has its purpose and build on each other. Usually, muscle protein synthesis studies are performed to see if something work (as they are very sensitive) and why it works. Once we think we have a good understanding, then we’ll try to see if the concept has the expected effect in a long-term study. Only when you have both, you have pretty convincing evidence that your intervention does what you claim it to do.
6. How to optimize muscle protein synthesis: exercise guidelines.
Now it’s time to translate the muscle protein synthesis to some practical recommendations.
6. 1 Number of sets
Multiple sets increase muscle protein synthesis more than a single set (Burd, 2010). A higher weekly training volume (number of sets to muscle) results in a greater muscle mass gains (Schoenfeld, 2016).
6.2 Reps per set
It is often recommended that a rep range of 8-12 reps per set is optimal for muscle growth. The American College of Sport Medicine position stand states (ACSM, 2009):
For novice (untrained individuals with no RT experience or who have not trained for several years) training, it is recommended that loads correspond to a repetition range of an 8-12 repetition maximum (RM). For intermediate (individuals with approximately 6 months of consistent RT experience) to advanced (individuals with years of RT experience) training, it is recommended that individuals use a wider loading range from 1 to 12 RM in a periodized fashion with eventual emphasis on heavy loading (1-6 RM) using 3- to 5-min rest periods between sets
However, these recommendations lack evidence. More recently, Stu Phillip’s lab has performed a series of studies demonstrating that repetition load plays a minimal, if not negligible, role in the hypertrophic response to resistance exercise, if sets at the different rep ranges are performed to failure (Burd, 2010)(Morton, 2016).
The main takeaway here is that there are no magic rep ranges that are superior for muscle growth.
6.3 Training to failure
It is unclear whether each set should be taken to failure. Muscular failure decreases performance on subsequent sets, thereby reducing training volume. In addition, it has been suggested that frequent, high volume training with each set to taken to failure results in ‘overtraining’, eventually forcing reduced training volume or intensity for recovery (Stone, 1996).
Perhaps performing a set with 1-2 reps left in the tank will still give a near-maximal stimulus to the muscle, without much of the associated fatigue. If sets are not taken close to failure, the muscle protein synthetic response will be small (Burd, 2010). But at least in untrained subjects, training close to failure appears to produce similar muscle mass gains as training to complete failure (Nóbrega, 2017).
6.4 Rest between sets
A longer rest period between sets increases the larger post-exercise muscle protein synthetic response compared to a short rest period (5 vs 1 min)(McKendry, 2016). In agreement, a longer interset rest period improves muscle mass gains compared to a shorter rest period (3 vs 1 min) (Schoenfeld, 2016).
6.5 Training frequency
A single bout of resistance exercise can stimulate muscle protein synthesis for longer than 72 hour, but peaks at 24 h (Miller, 2005). This suggests that the popular so called ‘bro-split’ (hitting each muscle group once a week on different training days) is suboptimal. Indeed, training each muscle group at least twice a week results in larger muscle mass gains (Schoenfeld, 2016).
6.6 Training status
The total muscle protein synthetic (MPS) response (determined by the increase in MPS rates and the duration of these increased rates) is decreased in trained subjects compared to untrained subjects (Damas, 2015). However, the pattern of this decreased response is differs between mixed muscle protein synthesis (the synthesis of all types of muscle proteins) and myofibrillar protein synthesis (the synthesis of contractile proteins: the relevant measurement for muscle mass).
The increase in mixed muscle protein synthesis is shorter lived in trained subjects. In contrast, myofibrillar protein synthesis rates do not increase as much in trained subjects, but the duration of the increase does not appear impacted.
The larger increase in the total muscle protein synthetic response seems like a logical explanation why untrained people can make faster much gains than experienced lifters. However, this is not necessarily true.
In untrained subjects, there is not only a large increase myofibrillar protein synthesis, but also in muscle damage following resistance exercise. A large portion of the myofibrillar protein synthesis is used to simply repair damaged muscle proteins, rather than growing muscle proteins. In more trained subjects, here is a smaller increase in myofibrillar protein synthesis, but there is also much less or even minimal muscle damage following resistance exercise (just 3-10 weeks of training is enough to see these effects). This means that in a trained state, the increase in myofibrillar protein synthesis can actually be used to actually increase muscle mass. When you correct for muscle damage, myofibrillar protein synthesis rates measured over 48 hour post-exercise recovery are similair in untrained subjects and after 10 weeks of training (Damas, 2016).
Of course, most athletes would hardly consider someone trained after just 10 weeks. Unfortunately, little is know about how years of serious training impacts the muscle protein synthetic response to resistance exercise. While it’s tempting to speculate on how and if advanced athletes should modify training variables compared to untrained subjects, there is no solid evidence to support such suggestions.
7. How to optimize muscle protein synthesis: nutrition guidelines
7.1 Amount of protein
Twenty gram of protein gives a near-maximal increase in MPS after lower body resistance . Going up further to 40 g, results in a approximately 10% higher MPS rates (Moore, 2009)(Witard, 2014).
When data of several studies was combined and the amount of protein was expressed per bodyweight, it was found that on average 0.24 g/kg bodymass (or 0.25 g/kg lean body mass) would optimize muscle protein synthesis. However, the authors suggest a safety margin of 2 standard deviations to account for inter-intervidual variability, resulting in a dose of protein that would optimally stimulate MPS at an intake of 0.40 g/kg/meal (Moore, 2015).
More recently, it has been shown that the amount of lean body mass does not impact the response to protein ingestion (Macnaughton, 2016). In other words: bigger dudes don’t need more protein to get the same response as smaller guys.
However, this study found that 40 g of protein resulted in approximately 20% higher higher MPS rates compared to 20 g. The authors speculated that this was related to the fact that this was following a session of whole-body resistance exercise compared to the lower-body exercise used in previous studies.
7.2 Protein source
Protein sources differ in their capacity to stimulate MPS. The main properties that determine the anabolic effect of protein are it’s digestion rate and it’s amino acid composition (particularly leucine).
This is best illustrated by study which compared the muscle protein synthetic response to casein, casein hydrolysate and whey protein.
Casein is a slowly digesting protein. When intact casein is hydrolyzed (chemically cut into smaller pieces), it resembles the digestion of a fast-digesting protein. Consequently, hydrolyzed casein results in higher MPS rates than intact casein.
However, the muscle protein synthetic response to hydrolyzed is lower than that of whey protein. While both proteins are fast digesting, whey protein has a higher essential amino acid content (including leucine) (Pennings, 2011).
Animal based protein sources are typically have a high essential amino acid content and appears more potent than plant protein to stimulate MPS (Van Vliet, 2015). However, there this can potentially compensated by ingesting a greater amount of plant protein (Gorissen, 2016).
7.3 Leucine
Leucine is the amino acid that is thought to be most potent at stimulating MPS. Peak plasma leucine concentrations following protein ingestion typically correlate with muscle protein synthesis rates (Pennings, 2011). This supports the notion that protein digestion rate and protein leucine content are important predictors for anabolic effect of a protein source.
While leucine is very important, other amino acids also play a role,
This is best illustrated by study (Churchward-Venne, 2014) which compared the muscle protein synthetic response to five different supplemental protocol:
- 6.25 g whey
- 6.25 g whey with 2.25 g leucine for a total of 3 g leucine
- 6.25 g whey with 4.25 g leucine added for a total of 5 g leucine
- 6.25 g whey with 6 g BCAA added (4.25 g leucine, 1.38 g isoluecine for, and 1.35 g valine)
- 25 g whey (contains a total of 3 g leucine)
All five conditions increased muscle protein synthesis rates compared to fasting conditions. As expected from our earlier discussion on the optimal amount of protein, 25 gram of protein increased MPS rates more than just 6.25 gram.
Interestingly, the addition of 2.25 gram leucine to 6.25 gram whey did not further improve MPS. Since this low whey + low leucine amount had the total amount of leucine as 25 g whey (which contains 3 g leucine), it indicates that leucine alone doesn’t determine the muscle protein synthesis response.
The addition of a larger amount of leucine (4.25 gram) to the 6.25 gram whey did further improve MPS, with MPS rates being similar to the 25 gram of whey. This indicates that the addition of a relatively small amount of leucine to a low dose of protein can be as effective as a much larger total amount of protein.
Finally, it’s really interesting that the addition of the 2 other branched-chain amino acids (BCAA) appeared to prevent the positive effect of leucine on MPS. Isoleucine and valine use the same transporter for uptake in the gut as leucine. Therefore, it is speculated that isoleucine and valine compete for uptake with leucine, resulting in a less rapid leucine peak which is thought to be an important determinant of MPS rates.
7.4 Carbohydrate or fat co-ingestion
Carbohydrates slows down protein digestion, but have no effect on MPS (Gorissen, 2014). In agreement, adding large amounts of carbohydrates to protein does not improve post-exercise MPS rates (Koopman, 2007).
In addition to the effects on protein digestion, it has been suggested that carbohydrates stimulate insulin release, which may stimulate muscle protein synthesis and/or muscle protein breakdown rates. However, the addition of carbohydrates to post-exercise protein has no effect on muscle protein synthesis or breakdown rates. The effects of insulin on muscle protein breakdown rates are described in more detail in section 2, and the effects of insulin on muscle protein synthesis are further described in section 7.6.
Adding oil to protein does not slow down protein digestion or MPS (Gorissen, 2015). It possible that oil simply floats on top of a protein shake in the stomach, and that a solid fat would delay digestion. One study has reported a greater increase in net muscle balance following full-fat milk compared to fat-free milk (although this study used the 2 pool arterio-venous model which is not the most reliable measurement).
7.5 Whole food and mixed meals
Most research has looked at isolated protein supplements in liquid form such as whey and casein shakes.
Thirty gram protein provided in the form of 113 gram 90% lean grounded beef results in a similar MPS response as 90 gram protein (340 gram beef). This supports the protein dose-response relationship observed with protein supplements where 20 g of protein gives a near maximal increase in MPS.
Minced beef is more rapidly digested than beef steak, indicating that food texture impacts protein digestion. However, there was no difference in MPS between these protein sources.
Beef protein is more rapidly digested than milk protein. However, milk protein stimulated MPS more than beef in the 2 hours (Burd, 2015). Between 2 and 5 hours, there was no significant difference between the sources. This indicates that digestion speed does not always predict the muscle protein synthetic response of a protein source.
As discussed in the previous section, the addition of carbohydrate powder or oil to a liquid protein shake does not impact muscle protein synthesis. However, it is unknown how the components of (large) mixed meals interact. For example, the addition whole-foods carbohydrates such rice, potatoes, or bread to whole-food protein sources such as chicken.
It can be speculated that the protein in mixed meals is less rapidly digested, which is typically (but not certainly not always) associated with a lower increase in MPS.
7.6 Insulin
As described in my systematic review, insulin does not stimulate MPS (Trommelen, 2015).
This is best illustrated by a study which clamped (maintained) insulin at different concentrations and also clamped amino acids at a high concentration.
There were four conditions:
- high amino acids + low insulin
- high amino acids + medium insulin
- high amino acids + high high insulin
- high amino acids + very high insulin
In the illustration below, you see the effects on muscle protein synthesis.
Regardless whether insulin levels were kept low (similar to fasted levels) or very high, MPS rates were the same in all conditions.
In my systematic review, I describe the effect of insulin in other conditions including in the absence of amino acid infusion, but the conclusion remains that insulin does not stimulate MPS under normal conditions (Trommelen, 2015). However, it should be noted that insulin stimulates MPS at at supraphysiological (above natural levels) doses (Hillier, 1998). In the bodybuilding world, insulin is sometimes injected at supraphysiological doses to stimulate muscle growth.
Insulin inhibits muscle protein breakdown a bit, but only a little is needed for the maximal effect (this is discussed in dept in section 2). A protein shake alone increases enough insulin to maximally inhibit muscle protein breakdown, you don’t need additional carbohydrates (Staples, 2011).
7.7 Protein timing
Exercise improves the muscle protein synthetic response to protein ingestion. Therefore, it has been suggested that protein intake immediately post-exercise is more anabolic than protein ingestion at different time points.
Probably the best evidence to support the concept of protein timing is a study which showed that protein ingestion immediately after exercise was more effective than protein ingestion 3 h post-exercise (though this study used the 2 pool arterio-venous method which is not a great measurement of muscle protein synthesis) (Levenhagen, 2001). In contrast, a different study observed no difference in MPS was found when essential amino acid were ingested 1 h or 3 h post-exercise (Rasmussen, 200).
In addition, resistance exercise enhances the muscle protein synthetic response to protein ingestion for at least 24 hour (Burd, 2011). It is certainly possible that the synergy between exercise and protein ingestion is the largest immediately post-exercise and then slowly declines in the next 24 h hour. However, these data suggest that there is not a limited window of opportunity during which protein is massively beneficial immediately post-exercise, that suddenly closes within a couple of hours.
Overal, no clear benefit to protein timing has been found in studies measuring muscle protein synthesis studies. As such studies are much more sensitive to detect potential anabolic effects compared to long-term studies measuring changes in muscle mass, it unlikely that long-term studies will observe benefits of protein timing.
In agreement, a meta-analysis concluded that protein supplementation ≤ 1 hour before and/or after resistance exercise improved muscle mass gains (Schoenfeld, 2013). However, this effect was largely explained by the fact that the protein supplementation increased total protein intake, rather than the specific timing of protein intake.
From a practical perspective, a protein shake during or after a workout:
- is easy to do
- theoretically may have a very small benefit
- is a simple method to improve total protein intake
- prevents FOMO (fear of missing out on something)
So it could be argued: why not do it? It is mostly up to personal preference.
7.8 Protein distribution
We performed a study to assess protein intake in well-trained Dutch athletes. Even some Olympic athletes were included. We observed that athletes consumed ~1.5 g protein/kg/d based on multiple dietary recalls (Gillen, 2017). However, their real protein intake is likely ~25% higher based on a nitrogen excretion validation study we performed in a subgroup (Wardenaar, 2015).
The majority of the protein was consumed in the three main meals: breakfast, lunch and dinner. While this intake pattern has a reasonable distribution throughout the waking hours, amino acid availability is potentially low during the night.
This begs the question: does protein distribution throughout the day matter for muscle protein synthesis?
Several studies suggest that protein should be reasonably distributed for optimal anabolism. For example, an even balance of protein intake at breakfast, lunch and dinner stimulates MPS more effective than eating the majority of daily protein during the evening meal (Marerow, 2014). But a too high distribution resulting in many mini snacks may also be suboptimal. Providing 20 g of protein every 3 hours stimulates MPS more than providing the same amount of protein in less regular doses (40 g every 6 hours), or more regular doses (10 g every 1.5 hour) (Areta, 2013).
While there are more studies that support the concept of protein distribution, there are even more studies that suggest it has no clear benefit. If your goal is to absolutely maximize gains, it theoretically makes sense to try to aim for at least a reasonable protein distribution (3-4 protein rich meals divided throughout the day). But the impact of protein distribution is likely going to be small at best and you definitely don’t have to set a timer for each meal.
PS: I have some new data on this topic that I can’t share yet….but….it’s exciting 😉
7.9 Muscle full effect
The muscle full effect is the observation that amino acids stimulate MPS for a short period, after which there is a refractory period where the muscle does not respond to amino acids. More specifically, after protein intake, there is an lag period of approximately 45-90 min before MPS goes up and peaks between 90-120 minutes, after which MPS returns rapidly to baseline even if amino acid levels are still elevated (Bohe, 2001)(Atherthon, 2010).
The muscle full effect has given birth to a theory on how to optimize protein intake throughout the day in the online fitness community. It suggests that after amino acids levels have been elevated, you should let them drop down back to fasting levels to sensitize the muscle to amino acids again. Subsequently, protein intake will stimulate MPS again.
There is no evidence to support this theory.
The suggested mechanism seems unlikely as many food patterns result in elevated amino acid levels throughout the whole day. The traditional bodybuilding diet consists of very frequent, very high protein meals (e.g. chicken, rice, broccoli 6 times a day). In fact, it was specifically designed with the goal of keeping amino acids elevated throughout the whole day so there would always be enough building blocks for form new muscle tissue. Or intermittent fasting where all daily protein is eaten in a short time period (usually 8 hours).
These diets would only allow for a single ~90 min increase in MPS during a whole day. Clearly, that’s not what’s happening as these approaches are used by many with great success to improve muscle mass.
More likely, there’s a refractory period and it simply takes some time before the muscle responds to AA again. You don’t have to let amino acids drop to sensitize the muscle.
However, the relevance of the muscle full effect can be questioned in athletes.
This is best illustrated in a study where the effect of protein was assessed in both rested and post-exercise conditions (Churchward-Venne, 2012).
Protein intake alone stimulates MPS in the 1-3 h period after ingestion. Subsequently, MPS rates fall back to basal rates. However, in post-exercise condition, protein stimulated MPS rates in both the 1-3 h and the 3-5 h period.
It appears that the muscle full effect is not present in acute post-exercise conditions. It’s interesting to note that resistance exercise can increase the sensitivity of the muscle to protein for at least 24 h (Burd, 2011).
The muscle full effect is an interesting phenomenon, but we don’t understand it well enough to let it influence our protein intake recommendations.
7.10 Protein prior to sleep
As discussed above, an effective protein distribution optimizes MPS. Therefore, it makes sense to eat protein just prior to overnight sleep, the longest period you can’t eat. 40 g of protein prior to sleep increases MPS during overnight sleep (Res, 2012). Protein supplementation (27.5 g) prior to sleep during a 12-week resistance training program improves muscle mass and strength gains (Snijders, 2015).
7.11 Energy intake
Only three days of dieting already reduce basal MPS (Areta, 2014). This shows that an energy deficit is suboptimal for MPS, however you can grow muscle mass while losing fat (Longland, 2016). It is unclear if eating above maintenance is needed to optimize MPS.
8. Summary
- While muscle protein breakdown is an important process, it doesn’t fluctuate much, which makes it far less important for muscle gains than muscle protein synthesis
- Whole-body protein synthesis is not really relevant for athletes. (often just called protein synthesis in studies, don’t confuse it with muscle protein synthesis)
- Muscle protein synthesis is predictive for muscle hypertrophy.
- Muscle protein synthesis studies are more sensitive to pick up anabolic effects than long-term studies measuring changes in muscle mass
- It’s easy to draw wrong conclusions if you don’t fully understand the methods.
How to optimize muscle protein synthesis: exercise guidelines:
- Train each muscle group at least twice a week with multiple sets
- Rep range doesn’t matter if you train (close?) to failure
- Rest at least 2 minutes between sets
How to optimize muscle protein synthesis: nutrition guidelines:
- Eat 4-5 meals spread throughout the day: e.g. breakfast, lunch, post-workout shake, dinner, and pre-sleep.
- Eat 20-40 g protein at each meal. Amounts above 20 g give a small additional benefit.
- Choose animal protein (whey protein is the best). Or compensate by eating larger amount of plant protein.
- If your main goal is to build muscle, eat at least maintenance calories.
Now I need your help.
Please bookmark this post for a couple of reasons:
First, I will keep this post updated with new research.
Second, I will continue to further elaborate sections based on your feedback and add additional sections in the future.
Lastly, please reference specific sections from this article when you see a discussion on muscle protein synthesis. People mistaking whole-body protein synthesis for muscle protein synthesis: see section 4.1. Someone skeptical about a conclusion from a paper because muscle protein breakdown was not measured? Section 2 buddy. Someone claiming that protein supplementation is not effective based on a long-term study he read that found no improvement in muscle mass: section 5 got you covered.
Feel free to ask me questions about the methods, or interpretation on protein metabolism studies in comments or on Facebook. If certain questions keep popping up I’ll rewrite the related sections to make it more clear for everyone.
Thank you the information. Does high protein intake damage your kidneys?
Protein does not damage healthy kidneys. But if you have pre-existing kidney damage, you have to be careful.
Hi Mr. Trommelen,
I had a question on your systematic review regarding insulin’s effects on MPS rates. It was stated that “exogenous insulin administered systemically induces hypoaminoacidemia which obviates any insulin-stimulatory effect on muscle protein synthesis” and I wasn’t sure if I was misunderstanding the article. Why would insulin cause higher concentrations of amino acids in the bloodstream?
Hi Timothy,
Exogenous insulin administrated systemically induces HYPO-aminoacidemia, which means amino acid in the blood stream drop. Based on your last sentence, I think you thought I wrote HYPER-aminoacidemia, which is the opposite from HYPO-aminoacidemia.
Does that help?
Cheers,
Jorn
When data of several studies was combined and the amount of protein was expressed per bodyweight, it was found that on average 0.25 g/kg would optimize muscle protein synthesis. However, the authors suggest a safety margin of 2 standard deviations to account for inter-intervidual variability, resulting in a dose of protein that would optimally stimulate MPS at an intake of 0.40 g/kg/meal. This is a part of your 7.1 amount of protein section can you tell me in which study this is mention i want to read that study and second it is recommend that eat 0.3 -0.5 g per kg of bw of protein in a meal. The 0.25 and 0.5 figures deprived from studies have person weight 80kg? So 80×0.25-0.5 equals 20 to 40g. But if we take 60kg athlete the 20g is equals to 0.35 so when a low body weight athlete is consuming protein is it better to divide protein by the no like 60kg athlete 1.6g perkg of bw protein equals 96. So divide that into 4 meals equals 24g protein per meal because 20g protein requires to maximise mps. But if we divide it by 0.25 or 0.3 that doesn’t past the 20g threshold. So is it better for low weight athletes to calculate their protein per meal by taking account minimum 20g in a meal rather than 0.25 or 0.3 formula? I know the 20 and 40g protein was whey protein in studies but take all other things equal like leucine content mixed meal etc so you can anwser more specifically to my question. And last question you said in whole and mixed meal section that However, milk protein stimulated MPS more than beef in the 2 hours. Between 2 and 5 hours, there was no significant difference between the sources. Can you also please tell the this study name or link it. Thanks mate💪
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Hi Bhupinder,
Whoops, I somehow missed your first comment.
The study that discussed protein per bodyweight is:
https://pubmed.ncbi.nlm.nih.gov/25056502/
It is not very clear to what extent protein requirement depend on muscle mass, lean body mass, or bodyweight. It’s not clear that someone who’s twice as big, also needs twice as much protein.
I typically recommend for people that are substantially heavier than average (75 kg/165 pound) to use recommendations per bodyweight, because this will result in higher protein intake than absolute amounts.
In contrast, for people that are substantially lighter than average, use the absolute protein recommendations (20-40 g per meal), because those will be higher than the per bodyweight recommendation.
The beef vs milk study is:
https://pubmed.ncbi.nlm.nih.gov/26354539/
(both studies above are now also referenced in the post).
Cheers,
Jorn
Hi Jorn,
This is a great article, I have always trained at around 10.00 but usually fasting. Do you think I need to start consuming breakfast at around 8.00 or would taking an EAA serving before training be suitable as sometimes I struggle to eat early in the morning but, I don’t want to adjust my training time so am looking for other solutions.
Hey Morgan,
You mention that you sometimes struggle to eat early in the morning. If you eat just a small snack, your body will start getting used to this new rhythm, and over time it will become easier to eat in the morning. But yeah, taking an EAA serving sounds like a good solution for your situation.
Hi Jorn,
Great article! Thank you for this. I will be rereading this in depth. I’ve only had an hr or so this morning before work to do so, so excuse me if you do answer these questions already.
Could you please help me clarify some things:
-I’m honestly struggling to grasp the need of EAA supplementation. I understand that they are superior to BCAAs but why do we need them if it takes relatively little to keep MPD at bay and we can amply stimulate MPS through food or protein supplementation? EAA supplementation is obviously particularly popular intra workout. This confuses me as MPS+MPD exist in a fixed timeline in the sense that upon protein consumption, MPS will be elevated for ~3hrs and further protein/amino acid consumption won’t prolong or boost this. If a meal is eaten the standard 30min-1hr pre-workout, wouldn’t MPS already be maximally stimulated for that window yielding an intra workout EAA pointless?
Also, I’ve read, between feedings, EAAs will have no effect on MPD or MPS (I’m assuming this is if 3/4 meals are being eaten).
What if you are to train or do cardio in a fasted state or if you can’t eat a meal due to circumstance i.e. work, would EAA consumption alone be enough to elevate MPS ? In the instance of fasted doing cardio, I know likely whey consumption would be favorable but that wouldn’t exactly be optimal from a digestion standpoint. Could you please explain why/why not to supplement EAAs in these situations?
These questions will likely be a bit mundane but I would appreciate your help.
Hey Fin,
1) There’s no need for EAA supplementation (and definitely not for BCAA) in general. I recommend whole-food sources and whey protein is you like shakes for convenience.
2) Yes, EAA alone is enough to stimulate MPS. EAA consumption would be preferred over nothing (remaining fasted) with respect to anabolism. So if whey or whole-food would give you digestion problems, then yes EAA consumption would be a good option (if you haven’t eaten for 4-5 h before).
Kind regards,
Jorn
Thank you for taking the time to reply to me and so many others.
1) That’s what I was thinking, why then are so many renowned bodybuilding coaches prescribing EAAs and or whey intra workout? Going off what you have said above, it seems the only situation EAAs would have any use would be; breaking a fasted state first thing in the morning pre cardio and not wanting to do so with a gut full of whey or food? Would you agree or are there other scenarios EAAs have use?
2) I also saw you say that if protein intake is high enough, protein quality becomes less important. Although not ideal from health/longevity standpoint, theoretically, does this mean you could have whey as your sole protein source (given a high consumption of ~200g protein daily) at no cost to muscle growth/retention ?
Have a good day.
Hey Jorn,
Thank you for the very informative post, you are doing great work.
Because of COVID-19 I was unable to train optimally. Now I have access to the gym again I’m aiming for body recomposition. I have upped my protein intake from 2.3 g/kg (~170 grams ) to about 2.6 g/kg (~195 grams) because I’m in a ~200-400 calorie deficit (~2200kcal).
Now I saw a study in Jeff Nippard’s video: A High Protein Diet (3.4 G/Kg/D) Combined With a Heavy Resistance Training Program Improves Body Composition in Healthy Trained Men and Women–A Follow-Up Investigation.
This study shows that subjects eating 3.4 g/kg rather than 2.3 g/kg of protein gained the same amount of muscle, but subjects with the 3.4 g/kg intake lost 5x more fat.
My questions for you are: How is this possible if protein that can’t be used for protein synthesis will be used as fuel and will I benefit from upping my protein from almost 200 grams to about 250 grams if I want to achieve body recomposition as fast as possible?
Kind regards,
Mark
Reference video: https://youtu.be/WkwRwSIEzr8?t=220
Hey Mark,
Thank you for your kind words.
I’m a bit skeptical about those results. I don’t see how eating more protein magically decreases fat. I would like to see that study replicated, ideally with better methods and stricter dietary control, before I would advocate such a high protein intake.
2.3 g/kg/d is already pretty high, I would just stick to that.
Kind regards,
Jorn
PS: gyms aren’t open here yet, do an extra set for me please!
Hi Jorn –
I hope you’re doing well! I’m a big fan of your work and have followed your research for a while. I’m curious to get your take on my meal template if you don’t mind: I eat 3 meals a day plus a protein feeding before bed. My goal is to maximize Hypertrophy. I eat at least 1g/lb of protein (total bw).
Typical day is:
– 7:30 breakfast
Train 10:30-11:30
– 12-1pm lunch
– 6pm dinner
– 8:30pm pre-bed yogurt
Would I benefit from a pre- or post- workout shake or small protein feeding? Or maybe moving my breakfast closer to my workout and a mid-afternoon protein feeding ??
Thank you very much in advance,
Hey David,
Your protein intake seems solid. Your total daily intake is high, which you consume in four 4 meals divided over the day. Don’t worry about a pre- or post-workout shake. Your breakfast likely provides enough protein to last you a while. And your lunch is pretty close after your workout anyway. There’s just little to nothing to gain by trying to theoretically improve things further, just more energy take you can better invest in other aspects of your nutrition: high food diversity, micronutrient dense foods etc.
Keep up the good work!
Jorn
Thank you very much, Jorn!
Hi there!
Thank u so much for this, greates article so far about this topic!
I am recently on IF fasting, doing one meal a day. What are your recommendations on best triggering MPS if I would continue doing IF? What are the perfect timing of the meal and protein types I would need to ingest? And timing of workouts as well?
Also, can u really bulk and lost fat (recomposition) while on a one meal a day plan considering a good amount of protein per day is in context?
Thank u
Hi James,
Thank you!
A potential draw back of IF is that protein distribution might be suboptimal. The best way to combat that, is to make sure you get a good amount of protein at the beginning of your feeding window, and a large amount at the end. The large amount at the end will continue to digest and provide your body with amino acids for a long time (so technically you’re not really fasted for a while after your feeding window has stopped).
I would time my workout during the feeding window, so you’re most likely to have energy.
Gaining muscle while fat is possible. In practice, this only happens noticeably in people with a relatively high starting amount of fat and little resistance exercise training experience. The less fat you have, the more difficult it becomes to loss more. The more resistance exercise training experience you have, the more difficult it becomes to gain muscle. Once you’re relatively lean and have some training experience, recomposition might still occur. But it would likely be at such a slow rate you wouldn’t even realize it’s happening. If you’re really advanced in training, you should be happy to make any gains at all. Doing it while losing fat is unlikely at that stage. IF shouldn’t have much impact on any of this.
Cheers,
Jorn
Thank u for ur reply, Jorn!
So this implies that one meal a day or any type of IF is not optimal for MPS, is that right?
What do you recommend for better MPS if I would adjust it to only 16hr fast and 8hr eating window?
My target is about 80kg of overall weight as im pretty heavier than that, twice training a week for upper body and twice also for lower body. Any recommendation for exact days of workout to not waste anabolism, especially when fasting? Or is fasting not good at all for recomposition? Im a bit on a skinny fat level as im a couch potato for about 5 years, but have proper weight training before that and on a regular dieting, not fasting at all. What is best strategy for recomposition for the likes of me? Sorry if i was unclear or confusing. But thanks again dude. Thanks for your effort and hardwork on this!
Best article on the topic ever Jorn! I’ll try to be concise:
I’m 47y, 200lb, 6′. Lifting for 6 months now. Main goal hypertrophy – aesthetics.
From Keto to wanting to be buff, quickly. New macros not so keto: 65% protein, 30% fat, 5% carbs. Carbs mostly from green veggies (broccoli, spinach). That cool?
Is 1g protein per pound of body weight sufficient to build?
Full body training split Mon, Wed, Fri. 4 exercises per day. 4 sets, 10 reps, almost to failure, 2-3 min rest between sets. Compound lifts only. Sufficient?
Drink 25g of protein shake 3 times per night, (wake, piss, shake, drink enough water to repeat in 2-3 hrs). 65% Casein, 35% Whey. Wake through night anyway. Easy to go back to sleep. Night protein doses beneficial?
Thank you sooo much Jorn!
Hey Chandler,
First up: thanks!
Keto is ok if you like it, but realize it’s not better for body composition/performance etc than a ‘regular’ diet. Don’t use it if you expect metabolic magic from it. But if you just like the diet and feel good on it, keep doing it.
Yes, 1 g/pound BW (2.2 g/kg) is more than sufficient. 1.6 g/kg is now often recommended as average requirement, with a safety margin up to 2.1 g/kg. So your intake is pretty much at the upper end of the safety and should definitely have you covered.
Training split seems solid.
Your night time protocol is interesting. There’s more people who use the drink-water-to-wake-up-to-pee trick, but you’re the first I’ve seen who uses it to wake up 3 times at night. I think that is ‘overkill’. You don’t need to consume protein every 2-3 h. In fact, it’s not even very clear you need it every 4-5 h. Waking up once to get another dose in the middle of the night could help a bit, but I’m not sure it does. I typically recommend a large amount of protein before sleep (≥ 40 g), that should get most if not all the MPS during the night.
There is research showing sleep fragmentation is very bad (waking up multiple times during the night). However, in those type of studies, sleep is usually disturbed instead of naturally waking up to pee (I imagine the former being more stressfull and disrupting sleep cycles more). So I don’t know if waking up to pee is harmful to overall sleep quality, but it might be a bit. Not sure if the potential upside from extra protein during the night is worth that risk.
If you keep your current protocol, I would switch all the protein to whey. Because you consume it every 2-3 h, a fast digesting protein would be more beneficial than a slow digesting protein.
Hi Dr Trommelen,
A while ago on the Jeff Nippard Podcast you mentioned 20g protein/meal seems to be the sweet spot for protein/meal with minimal extra benefits at 30g (more improvements at 40g).
Lately I’m seeing 30g being used as the dosage in a lot of studies. I was wondering if there has been any research lately that indicates that 30g/meal is actually better? I saw an article comparing 15g and 30g but it didn’t have a 20g group.
Or have we completely moved on from absolute amounts in meals and changed to .4g – .6g/meal/kgbw?
(For fast absorbing protein)
Thanks and keep up the good work,
Shaun
Hi Shaun,
Yes, the data shows that about 20% of protein gives a near-maximal stimulation of MPS, with a relatively small 10-20% further increase following the ingestion of 40 g protein.
Importantly, the studies on which the above is based have tested several doses below 20 g (which had lower MPS), but no doses between 20 and 40 g. In addition, MPS was measured at rest or after resistance exercise.
The new study you speak of was from our lab, and had a few different aspects.
1) It compared, 0, 15, 30 and 45 g protein.
2) it was after endurance exercise
3) MPS was measured over a longer period
Because of this, it’s difficult to compare the results directly to the earlier studies. But I would say the results fit pretty nicely in the previous data. If you eat 20 g per meal, you’re gonna get most of the results. If you’re someone who wants to optimize things, aim for a bit higher.
The impact of body weight on protein requirements is still quite unclear. I would take a practical approach. If you’re lighter than the subjects in these studies, those absolute amounts should definitely cover you. If you’re heavier and you want to be sure, just go a bit higher to be safe.
At the end of the day, the numbers are just guidelines. Tailor it to your specific wishes (e.g. how safe you want to be).
Kind regards,
Jorn
Is a good way to visualize MPS and the refractory period a right skewed distribution graph? MPS rises then decreases at a steady state due to the refractory aspect.
Will inhibition of myostatin increase MPS by allowing MPS rates to remain higher during that refractory period? Using the visualization above,the peak MPS would last for a unit more of time and have a steeper drop due to its refractory aspect.
Will inhibition of myostatin increase MPS by allowing MPS rates to remain higher during that refractory period but in a different way? It can be visualized as a graph with a less steep slope where Y=0 at a higher X value than the original graph?
Did I properly communicate what I’m trying to ask?
Yep, your questions are clear.
I have to first state that I’m not a big proponent of the ‘muscle full/refractionary period’. There are some data supporting such concept, but there’s a lot of data that seems to be conflicting with such concept. Importantly, there’s no data supporting a muscle full effect/refractionary period after exercise.
Yes, a right skewed distribution makes sense to visualize it. Although it’s not clear how fast MPS goes down, it might go from peak levels to fasting levels very rapidly (that’s what the proponents of the muscle full effect suggest).
I think myostatin would allow MPS to be higher in general. Refractionary period or not.
Hi Jorn
You mention that one study found that 3 days of eating ~33% below maintenance resulted in a ~25% decrease in MPS, Do you know how long it takes to restore that drop in MPS from the deficit once you return to maintenance or a surplus?
Hey Ash,
Unfortunately, that has not been investigated yet.
I can speculate about a few options: perhaps MPS is back to normal once you have compensated the cumulative energy deficiency. Which would be 3 days at a 33% surplus, 1 day at a 99% surplus, or 10 days at 9.9% surplus for example.
But I wouldn’t be surprised if MPS would be back to normal after a couple of days eating at maintenance. Once you eat at maintenance, there’s no real reason for your body to downregulate MPS. The exception to this would be if you’re at a very low body fat percentage. In that condition, your body would still consider you starving (or at risk of starving), and MPS probably won’t be a priority.
I have 3-4 questions. I hope you will give the anwsers in details. I know it will consume time to give the anwser in detail but a person like me who face bit difficulty to understand the papers asking you is my best chance to learn about this.
1:- you mention above about study in which mps decline even if there is elevated amino acids in blood. So my question is that about how much time mps will again going to start responding to amino acids? For example if a person consume 30g whey every 2 hours for like 4 times. After first meal about 2 hours the mps will decline even if the 2nd 30g whey will ingest. The amino acid will be high in blood but mps is not at peak. But about how much time the mps will going to respond for the 2nd meal or high amino acid in blood?
2:- did you know any research which study this refractory period. About how much time mps will be at peak again after declining or after that refractory period where muscle dont respond even amino acid level is high in blood. Please link the study if is there any.
3:- if there is not any study about this refractory period. How much time it will take muscle to respond to amino acid. What is your shot how much time it will take as per your knowledge or the studies you have read. I know this little bit of detail dont make a huge difference in person like you says 20 to 40g protein 4 times a day and 40g before bed is optimal. I know this. But i dont talking about that. I want to know more about this refractory period. So dont think question as for normal person.
Last i want to say please link studies it will be great because i want to read them and i will gain knowledge.
Thank you jorn trommelen sir.
1 – I think the ‘refractionary period’ has get way too much attention for something that is barely understood, not consistently shown in studies, and in my mind has relatively little practical implications. Yes there’s a few studies who suggest there’s a refractionary period (e.g. MPS going down while amino acids are still elevated), but there are also studies suggesting otherwise. And importantly, there’s no evidence of a refractionary period after exercise (or other growing conditions such as early life).So I can’t answer your question about the timeline about when MPS goes down and then goes back up again, because I’m skeptical there is a specific timeline that applies to all contexts.
2 – Here’s a few of the more recent papers. They will refer to older papers.
https://pubmed.ncbi.nlm.nih.gov/28982725/?from_term=Atherton+PJ+muscle+full&from_sort=date&from_pos=2
https://pubmed.ncbi.nlm.nih.gov/26152764/?from_term=Atherton+PJ+muscle+full&from_sort=date&from_pos=3
https://pubmed.ncbi.nlm.nih.gov/25644339/?from_term=Atherton+PJ+muscle+full&from_sort=date&from_pos=4
https://pubmed.ncbi.nlm.nih.gov/31725358/?from_term=burd+loon&from_sort=date&from_pos=2
3 – My best shot is that the refractionary period is irrelevant in people that train a lot.
Thanks sir for your reply and enlightened me about this topic. I have 1 last question. You wrote this article back 2016 and i am sure since then many studies have published about mps. So are you updating this article regularly or you will update this in near future. Thanx sir
Most of the article is still pretty accurate. But yes, I plan on starting to update it in a couple of months.
Which is better for maximising mps 3 or 4 meals or more than 4 meals. Can you link all studies related to these. Or any article you have written about it. Also why protein distribution is better? Disclaimer:- i haven’t read this article. I will read but as of now i havent
Hey Bhupi,
I hope you read the article, protein distribution gets covered a bit in there.
In order to be anabolic, you need to have protein/amino acids coming into the body (in practice this will from nutrition). Even if you take all the steroids in the world and train, you still cannot have an anabolic state because you simply lack the building blocks to grow. Training and steroids would stimulate the body to try to grow, but those growth processes have nothing to work with (they only have building blocks available from protein breakdown, which means you’re just ‘recycling’, not actually growing.
Therefore, in theory, you need to make sure you always have protein coming in. The most practical way to ensure this, is by having a high frequency of protein-rich meals. So this has formed the basis of protein distribution as a concept for maximizing anabolism.
Only a relatively small amount of studies have been done on this topic. Some studies measured muscle protein synthesis over a relatively short period (12-24 h), others measured MPS over a couple of days, and some studies measured changes in muscle mass over weeks.
Some of these studies suggest a benefit from a more balanced protein intake (e.g. spreading your total protein intake about evenly across several meals instead of most during one big meal). But quite a few other studies have found no benefit. It’s important to note that there’s not really evidence that supports that infrequent protein intake (or an unbalanced distribution) is superior.
Theoretically, a decent protein distribution makes sense, there are some studies showing a benefit, and not really studies showing a drawback. Therefore, it may be worthwhile to take protein distribution into account if your goal is to maximize muscle growth. However, based on the number of studies who find no benefit, you could argue that if there’s a benefit from protein distribution, it’s probably not that big. In other words, if you don’t want to focus on it, it’s not likely you leave tons of gains on the table. And whether protein distribution may be relevant might also highly depend on the context (e.g. what is your daily protein intake etc).
My advice is quite practical: if maximizing your gains is important to you, I would recommend 4-5 protein rich meals a day. If protein distribution is simple for you, you might as well do it. If you don’t want to obsess about everything, it’s something you can easily ignore as it might make no or only little difference anyway.
Most people already eat 3 main meals: breakfast, lunch dinner.
If your dinner is 4 or more hours before you go to bed, I would eat another protein rich meal before sleep.
An extra ‘meal moment’ can be planned after a workout. This is not a magic moment where protein is better or something, but it’s just a nice habit to make sure your protein intake is high enough and can help with the distribution.
Here’s the studies that support protein distribution:
https://pubmed.ncbi.nlm.nih.gov/32321161/?from_term=fujita+protein&from_sort=date&from_pos=7
https://pubmed.ncbi.nlm.nih.gov/24477298/?from_term=24-h+distribution+even+protein+synthesis&from_sort=date&from_pos=7
https://pubmed.ncbi.nlm.nih.gov/23459753/?from_term=areta+protien+20+g&from_sort=date&from_exact_term=areta+protein+20+g&from_schema=all&from_pos=2
https://pubmed.ncbi.nlm.nih.gov/25738784/?from_term=phillips+sm+murphy+&from_sort=date&from_pos=8
So i almost get your point. But now i have 1 more question. How long is refractory period? Like muscle stop responding to amino acid in rest state after 2 hours. So after how much time the muscle will again start responding to amino acid? Like 30 min 1 hour. If you dont know exact time. Make a guess( how much is refractory period) with all the data you have and knowledge you have regarding mps. Because if we know even something about the time of refractory period then we can know what is the best meal frequency for maximising mps. For example max mps peak period is 2 hours and if we know refractory period is 30 min so we know that after 2 and half hours we need a meal to give the boost to mps. So by this if some body builder is consuming like 8 meals and we know 7 meals will give the same mps then we will cit the 8th meal.Dont think this question for a normal person i asked this question to know whats best meal frequency for top body builders like top 1%.
Hi Jorn,
That’s a mind blowing piece of work. THANK YOU.
1 quick question, how much protein can a body absorb at 1 time?
I know, the common line is – “all of it” – but, my question is more on the lines of, for Maximal MPS.
Thank you in advance.
Hi Maverick,
Thank you for your kind words!
Absorption is a word that’s often used for different things: absorption from the gut and absorption from the circulation into tissues (the latter I would call uptake instead of absorption).
Most ingested protein is absorbed in the gut. Only a relatively small amount is not absorbed. From the small bit that’s not absorbed, some still gets ‘absorbed’ by bacteria in the colon, that convert the protein to other metabolites that end up in the circulation.
So most protein is absorbed in the gut, and a large portion of it subsequently gets taken up by splanchnic tissues (e.g. the liver). The rest of the protein makes it to the circulation. From there, the protein is taken up into different body tissues such as muscle. But protein uptake by muscle does not necessarily mean the muscle will use if for MPS, it can also be burned as fuel for example.
To put it into numbers:
When you ingest 20 g protein, you absorb most of it from the gut. About 50% is taken up by splanchnic tissues and the other 50% makes it to the circulation. From the protein that makes it to the circulation, about 20% is not only taken up, but also actually used for MPS (in other words, 10% of the 20 g protein).
Note that the exact numbers will depend on the context such amount of protein, type of protein etc. For example, if you have performed exercise, a slightly higher percentage of the absorbed protein will build into muscle tissue for example.
If you simply want to know what is the maximal amount of protein in a single meal that can be used by the body for MPS, then we have no concrete answer yet (as it will likely depend on the context). The first 20 g of protein is highly effective for MPS, going up to 40 g has a small added benefit. I think that even higher doses might have some additional benefit in some situations, but I’m done research on that right now so stay tuned!
Jorn, What is your view on Creatine Monohydrate in building muscle? When combined with Whey?
Creatine monohydrate will help build muscle and strength. Whey protein supplementation builds muscle and strength (if your protein intake wasn’t optimal yet: 1.6-2.2 g/kg/d). Creatine and (whey) work differently, and the combination of both works best! I’ll add some creatine stuff on my infographic to-do list.
Hi Jorn, I have somewhat of a list of questions… If you would be able to answer them that’s great! If not that’s alright too, I am just having trouble finding answers to a few things;
How directly does muscle protein synthesis correspond with muscle mass gain
How do I efficiently and adequately space protein if I consume whey products that digest faster and then consume protein surrounded by carbs or fibers without having a drag where the slower digesting protein hops in on the same train as the faster digesting protein and is not put towards muscle protein synthesis?
Is it better to absorb protein faster or slower to increase muscle protein synthesis?
How much protein in a day will maximize weight gains while in a maintenance caloric intake?
How much of an energy deficit will result in a decrease in muscle protein synthesis and how much can I safely shave down while optimally building muscle?
Is the benefit of animal protein versus plant protein because animal protein has more amino acids and/or
more of a specific set of amino acids?
Sorry it’s a lot! Thank you again!
Hey Noah,
That’s a bunch of questions, which makes it hard to go into a lot of detail on them. Just let me know if you want more explanation on particular answers.
1) How directly MPS correlates with muscle mass gains depends on many factors. MPS definitely does not perfectly correlate with muscle mass gains, but the same thing is true for any measurement that attempts to predict muscle mass gain. I’ll probably write a blog post about this in the future as a lot of people seem confused about this.
2) I wouldn’t worry about this. It’s not entirely clear yet how important protein distribution is to maximize gains. However, it does not seem super important based on what we known so far. If you try to space out 4 solid meals over the course of a day, your protein distribution is pretty good already. Even if protein distribution would have some benefits, I doubt increasing to >4 meals and worrying about how other nutrients impact protein digestion speed would have additional benefits under realistic circumstances.
3) Faster protein absorption is better to increase muscle protein synthesis. However, this is based on various research studies that compare fast or a slow proteins on an otherwise empty stomach (or drink the fast protein in small sips over time to slow it down). In the real world, most protein comes from solid food and you eat other nutrients with it, which will likely slow down the meals. I expect that under circumstances of a meal, the impact of speed of protein becomes a lot less relevant.
One thing that might be of interest, is that faster protein could result in a high but short MPS response, while slower protein may result in a moderate but longer MPS response. This is yet to be convincingly shown, but it could mean that faster proteins are preferred when you will have a new protein meals in the next ~5 h, but that a slower protein might be preferred when you will not have a new protein meal in the next >6 hours.
4) This is not really known exactly. But 1.6 g/kg/d seems like a good average number, and if you want a safety margin to make sure you hit enough, you can go up to about 2.2 g/kg/d.
5) Not a lot known about the exact numbers and how it depends on various factors. But one study found that only 3 days of eating below ~33% below maintenance resulted in a ~25% decrease in MPS. How that number would change with different energy deficits and/or longer dieting is unknown. But it’s clear that higher protein intakes and resistance training can still effective stimulate MPS during an energy deficit.
6) Yes, animal products typically have a higher protein content than plant-based products. Even when matched for protein, animal products have a higher essential amino acid content (amino acids you cannot produce and thus have to get from nutrition). The EAA are important for the stimulation of MPS. Finally, animal protein also tends to have a better balanced profile of EAA. You need to have sufficient of all EAA to get a robust stimulation of MPS. Plant protein sometimes has a decent amount of EAA, but can lack a specific EAA. In that case, that lacking EAA is limiting how much MPS can occur.
Thank you so much Jorn,
Really appreciate you taking the time to reply, I realize how confusing or vague some of my questions were but that was very helpful. Just to touch up;
So the idea is as long as you have a flow of amino acids in your bloodstream (eating fast or slow digesting) and keeping that continual will maximize MPS?
I know this may sound like a very rookie question, but what would be the big difference in MPS and Muscle Mass/Strength Gain? For what I know MPS works more in the direction of repairing cells that are damaged during the process of resistance training but does it also incorporate new myonuclei cells into the muscle to give it more mass and strength? Ir would that be a different function? I do remember reading an article talking about how the two corresponded after about three days once the muscle was repaired from MPS muscle would start to develop new cells, does this sound accurate? I also once dove into a video from Jeff Nippard (I think you worked with him in a video or two about MPS), where he talked about MPS and satellite cells and how once the myonuclei were added to the muscle the nuclei’s cell would grow therefore increasing mass and strength?
Is there a specific EAA that the plant is missing or would it be different EAA’s depending on the food, and are most meats (fish and poultry more specifically, but also other meats) going to contain all the EAAs? Lastly, just confirming, so the study showed earlier that having a large amount of EAAs was as efficient as a moderate amount of whey and a large amount of leucine, so is that just saying that yes all EAA’s are necessary to boost MPS?
Thank you for your time, your works been really inspiring.
You need amino acids coming in from outside the body (which in practice usually means from nutrition) to have a positive protein balance. If you don’t have AA coming in, at best all you can do is recycle the amino acids that are already in the body, but this will not increase overall mass.
If you need to keep them elevated in the blood stream to continually keep MPS at a maximal is a bit more complicated. It’s not entirely clear if we can keep MPS maximal with nutrition, regardless of how we time or protein. One thing that we don’t know much about, is the availability of amino acids in the intracellular space following feeding. For example, you eat a meal, it elevated plasma amino acids in plasma for 4 h. But after those 4 hours, amino acids in your plasma may be low again, but that does not mean that free AA levels in the muscle are low as well (they may just have went from the plasma to the muscle tissue, but not yet build into muscle tissue). But based on what we know, trying to keep elevated amino acids all throughout the day is our best bet at maximizing MPS.
The relationship between MPS and muscle mass gain is not a rookie question at all! It’s a very difficult topic. MPS is the process in which free amino acids are put together to produce a muscle protein. All muscle protein is build through MPS.
You often hear people talking about satellite cells and myonuclei. The short version here is that we don’t know enough about those things that we can make any meaningfull dietary or training strategies based upon them. Anyone who acts like they understand it very well and has advanced training strategies to optimize them is just delusional. I would ignore that topic for now, it will take a while before the scientific community understands them well enough that the fitness world can benefit from that knowledge (don’t get me wrong, we are working hard on satellite cell research in our lab).
Back to MPS. You can’t always translate the findings from an MPS study to muscle growth, muscle repair. MPS is the process of forming new muscle proteins, and what the result of that is depends on the context. For example, following endurance training, there is also an increase in MPS, but the newly synthesized protein are proteins that produce energy (not proteins that contract, give strength and size). Newly produced muscle proteins can be directed to replace proteins that are broken, to muscle growth, to replace damaged proteins from exercise, to replace damaged proteins from metabolism, to adapt non-myofibrillar proteins (who are the proteins that can contract and give size). Whether or not an increase in MPS can be translated to muscle growth depends entirely on the situation in which it’s measured. (but this is true for all most any measurement, you can’t blindly follow long-term measurements of muscle mass either). I realize this might not be a simple answer that gives a lot of clarity, but this is again something were people who try to simplify are just incorrect. A practical takeaway would be that you can generally see an increase in MPS as a good thing. It shows increased adaptation of the muscle going.
Yes, almost all animal proteins have all EAA is good amounts (collagen/gelatin is an exception). It differs per plant protein which EAA they are lacking. Therefore, combining different types of plant protein is potentially good strategy as one plant might be high in AA 1, but low in 2, while the other plant might be low in AA 1 and high in 2, so the combinations balances the AA out. The study you mentioned was adding BCAA or leucine to whey, there was no treatment where free EAA were given. We have done a more recent study, that shows pretty clearly that given a complete protein is better than just BCAA, further supporting that you need all EAA for optimal MPS.
Cheers!
Perfect, that answered everything! Thank you!
Great article…one question. When should BCAA’s be used? When and how much luceine should be used with protein supplementation?
Thank you Megan.
I don’t really see any purpose for BCAA supplementation. In pretty much all conditions, other options are desired. You need all the essential amino acids for a robust stimulation of MPS. So while BCAA are better than nothing, in pretty much all conditions you would rather just have a complete protein source.
Leucine can be beneficial that just a little bit of leucine can make a suboptimal amount of protein more effective. This can be beneficial in for example clinical formulations for patients or older adults who struggle with getting enough protein intake. But for athletes eating large amounts of protein, extra leucine is not going to do much if anything.
When considering peri workout protein intake, I understand that a post workout bolus of 40g of whey protein would optimize the MPS response to the training bout. If one were to work out first thing in the morning right after waking and instead of a traditional pre workout meal, they were to mix an intra workout shake consisting of 25g of whey protein and carbs, ingesting it prior to and throughout the bout, would another 25g dose post workout achieve near optimal MPS since the combined intake of the intra and post would be 50g? Would it be more optimal to train without ingesting protein and just save the full bolus to be taken in one shake?
I understand this is splitting hairs, but I am interested in maximizing as many variables to achieve the most theoretically optimal results. This is of course in the context of sufficient total daily protein intake.
Hey Ian,
Just to confirm, this is indeed splitting hairs. But interesting nonetheless.
There’s data that shows that sipping on a whey protein shake is less effective at stimulating MPS when compared to drinking that shake at once (https://pubmed.ncbi.nlm.nih.gov/21795443/).
Therefore, I wouldn’t sip on it during training. I would drink it first thing upon waking up. Theoretically, this could be advantageous from a protein distribution stand point as you will have low amino acid availability after a night of sleep. My second option would be to add it to the PWO shake. Third: drink it as a single bolus at some point of your training. And least favourite: sip on it during exercise.
I appreciate the reply and the study! That makes total sense. Would you recommend upping the post workout bolus to 40g of whey, or would 25g pre/post be sufficient maximize the response?
Of those two, I would go for 25 g pre and post. If you go for 40 g postexercise, the period until waking untill then is with low amino acid availability. What I would like even better is if you have 40 g whey upon waking (pre-exercise), and then have your next protein meal 4-5 h later.
Absolutely amazing article!!!
First of all I would like to thank you dearly from my heart for such a well written post! Secondly I have been noticing loss of strength and overal muscle loss, due to the Intermittent fasting strategy, In the summer I was consuming 40 grams of protein 5 times a day and feeling bigger and stronger was defintely no joke, now since i am before reading this post, eating most of my daily protein and calories at once. and training fasted. The catabolic effect it had on me was quite severe, and thankfully now I know the reason, Since I am Zerocarb/Fat adapated for 2 years a lot of lifters in the community were recommending me to try Intermittent fasting the 16:9 strategy, for its benefits in reducing constant spikes in insulin, increase in growth hormone and other things. but for me it has been a quite the opposite I feel soo much stronger with a constant flow of amino acids. Eating 5 times 40 gr of protein saved my ass again! thanks for the post
Thank you for the nice words. Happy to hear you’re making good gains again!
When taking leucine in a supplement form (pure amino acid) in combination with proteins with slower absorption rates, such as pea protein or egg white concentrates, what would be the optimal way for dosing leucine, considering the fact that the supplemental leucine would be absorbed much faster than the rest of the amino acids from the protein source ?
For example if a protein in question is absorbed at a rate of about 3 grams per hour, would it be more optimal to take let’s say total of 3g of free form leucine in three separate doses of 1g per dose, every 2-3 hours than to take all 3 grams of leucine in a single dose with a meal ?
Thank you very much.
A fast rise and high concentration of leucine in the blood is an important trigger for MPS. There’s all the leucine at once seems to be a more potent trigger to maximally stimulate MPS than spreading it out. However, spreading it out might result in a more modest increase in MPS, but potentially that modest increase is maintained longer. But we don’t know enough about that yet. Based on what we know, all 3 g at once seems to be the best move. However, once you have a decent amount at once (say 3-5 g), you should have a maximal MPS trigger anyway and then it makes more sense to have leucine later on.
thanks so much for posting this amazing article.
Thank you for your amazing comment! It makes me want to write more!
Jorn, does casein mixed with whey slow absorption of whey?
Hey Miroslav,
No or pretty little. I did a study where we added leucine (a free amino acid) to casein. The leucine was absorbed very rapidly, while the casein was still being absorbed hours later. So it may slow it down a bit, but I expect the whey to still be absorbed fast. Milk (which is 80% casein, 20% whey) also has a fast digesting peak early on. That’s likely the whey component.
t thanks jorn for such a beautiful article ,,
i was wondering if someone does bro splits ( lol like me . time constraints,, early morning fasted heavy resistance training ) , can it be like we need less protein on days we do small muscle groups like shoulder , biceps triceps and we need more protein on days we do bigger muscle groups like quads ( squats) hamstring ( deadlift) back and chest ,, like protein goals depend more on muscle mass which has been worked for that day instead of whole body weight
also does uptake of glycogen and creatine by muscles is depend on the specific muscle worked out ,, so for eg. if i hit quads and then take creatine supplement and glucose ,, then only my quads will take up creatine and glucose to replete creatine and glycogen stores ,,and not the other muscles of my body which were not worked ou
Hey Amit,
Thanks for the kind words.
I would not worry much about changing your protein intake based on which muscle (groups) you’ve trained. Keep in mind that the muscle protein synthetic response to exercise can last quite long. So even if you only train biceps today (or even have a rest day), if you have trained legs yesterday, they still have an increased sensitivity to protein today.
Exercise strongly aguments the uptake of glucose for glycogen synthesis in the trained muscle. But other muscles will still take up glucose/creatine. Even if you don’t train, taking creatine would increase creatine levels in muscle for example.
Hi, I know this is mostly for body builders, but I am trying to build muscle for rock climbing which has an endurance component. Do carbohydrates play a role when it comes to MPS for endurance athletes who are trying to maximize MPS? Or is it, once again, as long as I am not in a calorie deficit state and eat as many grams of protein as needed, I will continue MPS? Or will there be a glycogen depletion at some point which will hinder MPS?
Also, when you say older people benefiting from higher levels of protein, what age group do you refer to?
I enjoyed your podcast interview and found you here. Thanks so much for great info.
Hi Christine,
Thank you for your kind words. The recommendations don’t change for rock climbing. No need to worry about certain timing of carbs. Glycogen levels won’t impact MPS, but if low glycogen levels will impair your training, so you still need to eat carbs for that.
In studies, we usually classify ≥65 years as older adults. However, age-related anabolic resistance is most likely a more gradual process where once you hit middle age, you slowly become less sensitive. But your sensitivity is not just determined by age, how much you exercise, daily physical activity such as step count, genetics, how healthy you have lived previously likely all impact your sensitivity.
First of all I must say that this is the most interesting article on nutrition I have red. I am a novice for nutrition and intermediate of strenght training.
I am trying to ingest the more info I can on this article.
I am on a diet consisting on eating 5 meals per day all including protein from whole sources. The protein amount on each meal is not consistent, 32g on breakfast (eggs and whote eggs), 20g(white egg) on snack 1, 35g (chicken, white fish) on dinner, 20g (fat fish, whey protein shake) on snack 2 and 35g (chicken, beef, white fish or fat fish I cycle) on supper and nothing before sleep.
We saw in the article that increasing the amount from 20 to 40g increase the MPS from 10-20%.
Do you think I should add Leucine supplement to better reach the MPS on snack meals?
We also saw that an amount of protein before sleep can increase the MPS, so a whey protein shake is mandatory?
My paper cal intake maintenance level should be around 1850kcal and my intake is around 1350kcal right now so I’m in deficit. Macro nutriments is around 29% Carbs, 31% Fat (All Healthy Fat), 40% protein.
Do you think my carbs intake is too low which affect my energy level from glucose reduction and low insulin which affect MPS?
Should I increase my calorie intake by ingesting more protein and carbs through the day? I eat each meal from 2.5-3hrs between each.
I train 4 times a week with rest in between and I hit every big groups 2time a week upper and lowe body.
Thanks I really appreciate your time.
David
Hy David,
I’m glad to hear you found this article useful!
Your protein intake is pretty good already. Adding leucine to some of the meals might help a TINY bit, but is probably not worth the hassle.
Pre-sleep you can take a protein shake, but something like a lean fish, lean meat, or a low-kcal high protein yogurt could also be good options.
I wouldn’t worry too much about calculating your calorie/carb intake. Adjust those based on your results. Weigh yourself weekly (ideally daily and take a week average), and based on the results of a 3-4 week period, adjust calorie intake based on if what you see (e.g. increase calorie intake if you lost too much weight, or didn’t gain while that was your goal).
Good luck!
Jorn
Hallo Jorn,
we kennen elkaar niet, ik was erg geboeid door je interview met Jeff Nippard. Leerzaam en interessante informatie die praktisch toepasbaar is voor mij als iemand die MPS wil optimaliseren voor spiergroei.
Het stuk dat 5 minuten rust superieur is over 1 minuut rust is nieuwe informatie voor mij
Echter wat ik me afvraag als ik over de vergelijkende research lees,
hoe zit het eigenlijk met de MPS meting timing ten opzichte van de start van de training.
als training met 1 minuut rust een half uur duurt
en die met 5 minuten rust 1,5 uur en je 4h post exercise meten, heb je in ieder geval te maken met een tijd window die een uur verschoven is. Ik weet zo niet of daar in de studie rekening mee is gehouden?
Maar dat was eigenlijk niet belangrijkste vraag die het bij mij opriep. Die was namelijk of het wel de rust periodes tussen sets was die de verhoogde MPS tot gevolg had. Of dat het misschien totale trainingsduur was is die dit effect sorteerde
Dus als je 1,5 uur traint met 1 minuut rust dat je hetzelfde effect bereikt, versus 1,5 uur met 5 minuten rust.
Of nog weer anders, dat je je half uur training met 1 minuut rust uitrekt naar 1,5 uur door 4x een kwartier rust te nemen. Ergens tijdens de training
Lang verhaal kort volgens mij heeft de research niet een sterkere indicatie gegeven dat het de rust is tussen set versus de totale trainingsduur. Dit wilde ik je graag voorleggen. Als ik het namelijk mis of juist heb dan hoor ik dat graag.
Als je die moeite wilt nemen dan bedankt ik je alvast voor je tijd.
Met vriendelijke groeten,
Alexander
Hey Alexander,
In de 1 min en de 5 min groep is MPS gemeten in de 4 uur na de training. De 1 min training duurt ongeveer een half uur korter (8 sets x (5-1 min), dus de 4 h periode was een half uur eerder dan in de andere groep. Maar dit zou weinig impact moeten hebben.
Waarom denk je dat de totale trainingsduur een impact heeft op MPS? Dat de hoeveelheid rust tussen sets een impact heeft kan ik me wel voorstellen. Als je nog niet helemaal hersteld bent, kun je bijvoorbeeld slechter presteren op je volgende set, waardoor je totale trainingsbelasting lager wordt. Maar als je eenmaal lang genoeg gerust hebt (laten we zeggen 5 min), wat zou extra rust of tijd tussen sets dan voor invloed moeten hebben?
In deze studie had je:
– 8 sets x 5 min rust = 40 min rust + laten we zeggen 8 x 1 min voor de exercise zelf, en laten we de warming up sets negeren) –> 48 min training
– 8 sets x 1 min = 8 min + 8 = 16 min rust
Wat nou als de 1 min rust groep de hele training hetzelfde had gedaan als nu, maar met als enige uitzondering dat ze voor hun laatste set 32 min rust hadden genomen om ook op een totale trainingsduur van 48 min uit te komen. Dan zou ik verwachtten dat het resultaat nagenoeg hetzelfde was als nu (misschien zou dit scenario iets beter zijn dan het originele 1 min rust scenario omdat ze dus betere rust hebben gekregen voor de laatste set). Maar ondanks dat de totale trainingsduur dan hetzelfde zou zijn tussen de groepen, verwacht ik dat de 5 min rust groep nog steeds beter zou zijn.
Wow, this is probably the best bodybuilding relatet article I’ve read so far. And the fact that you are taking the time to answer all these comments even three years after the article has been published makes your work even more impressive.
So you’re recommending to preferably choose animal protein as a protein source, which makes total sense, but is it really necessary to get the full 2g/ kg bodyweight out of animal protein, or would it be sufficient to eat like 1,6g/ kg bw of animal protein and get the rest out of grains, vegetables and legumes?
Hey Jean,
Thank you for the kind words! No, not all protein needs to be animal protein. At an intake of 2 g protein/kg body weight, if half your protein intake is animal-based, you should be more than good. At that level of protein intake, I would not be surprised if the protein quality has relatively little relevance: high protein intakes can compensate for low protein quality.
That’s great to read, as Soy Protein Isolates costs 40%-50% Whey’s cost.
I’ve been complementing Soy SPI + BCAA, but after reading your paragraph about BCAA I think I should only add Leucine!!!
Right?
Paper: https://academic.oup.com/jn/article/149/2/210/5303915
“Postexercise MyoPS and MitoPS rates do not differ after co-ingestion of carbohydrate with 20 g protein from whey, soy, or leucine-enriched soy protein during 360 min of recovery from concurrent resistance- and endurance-type exercise in young, recreationally active men”
“Finally, it’s really interesting that the addition of the 2 other branched-chain amino acids (BCAA) appeared to prevent the positive effect of leucine on MPS. Isoleucine and valine use the same transporter for uptake in the gut as leucine. Therefore, it is speculated that isoleucine and valine compete for uptake with leucine, resulting in a less rapid leucine peak which is thought to be an important determinant of MPS rates.”
Yes, there is some indication that leucine alone is more potent than the same amount of leucine+the two other BCAA added. But even leucine supplementation is not necessarily needed if your total protein intake is high enough. But leucine supplementation could definitely be an effective option if total protein intake is suboptimal.
It seems you can “manipulate” digestion and absorbtion of protein. For example, a High Carb/Low Fat/ Low Protein diet. Carbs push fat into cells (low fat minimizes the fat stored), and slows down the digestion of protein and becomes the bodies prefered source of fuel. Since carbs slow down the digestion of protein shouldn’t this be considered “slow digesting protein”? If so, this should create more Glutamine which directly correlates with MPS and more anabolic affects through growth hormones. If this is the case, then most (if not all) of the protein (and fat) absorbed should go directly where it is needed (fat storage and muscle growth).
On the other end, a Low Carb/High Fat/High Protein diet should have the opposite effect and create more Leucine (through faster protein digestion) which activates Skeletal MPS through the Mtor pathway.
If this is correct, it seems best to utilize the High Carb/Low Fat/Low Proetin diet to maximize muscle growth (when in a surplus) and the Low Carb diet to minimize muscle loss (when in a deficit).
Other important factors such as meal frequency play a key role as well it seems. Eating a high frequency meal (lets say 6 meals a day every 3 hrs) would be best suited for a surplus and make it more convienient to eat added calories throughout the day. Also, eating an equal amount of protein every 3 hrs would increase daily protein synthesis (as well as insulin, which inhibits fat metabolism and MPB), therefore more fat storage and more muscle growth. Lower frequencies (lets say 3 meals a day every 6 hrs) should have a reverse effect while in a deficit with even protein distribution and eating a Low Carb/High Fat/High Protein diet by burning fat and minimizing muscle loss (through more Leucine).
What are your thoughts on this?
Hey Terry,
Carbs do “push” fat into cells, but fat also pushed fat into cells.
The ingestion of food slows down protein digestion, this is not specific to carbohydrates. Moreover, how much you can slow down protein digestion and absorption rates with is not really clear. The research on it so far suggests that the effect is not super big.
I’m not sure where you glutamine info comes from, but to my knowledge it’s incorrect.
I don’t think that there’s a preferred CHO:fat ratio for cutting, and an opposite preferred ratio during bulking.
Your post involves a lot of speculation based on a specific mechanism you think is relevant under certain conditions, but such speculation often does not work out because a lot more is going.
Great article, but one question: which Whey does have 3g leucin per 25g? Whey has circa 10% leucin in protein content and whey has tipically 20g protein per 25g powder?!
The leucine content can differ a bit depending on a couple of factors. In addition, when protein studies report 25 g whey protein, they almost always mean 25 g whey protein (not powder).