Epidermal growth factor

Why protein?

Pumpkin Apple Breakfast Bake
Indeed, training each muscle group at least twice a week results in larger muscle mass gains Schoenfeld, In the past few years, we've discovered that chemo frequently causes secondary cancers, can actually FEED tumors, and that chemo traumatizes the brain for years. For persons with elevated plasma triglycerides, reduced HDL cholesterol, and small dense LDL cholesterol the metabolic syndrome , improved glycemic control, modest weight loss, dietary saturated fat restriction, increased physical activity, and incorporation of monounsaturated fats may be beneficial. In persons with controlled type 2 diabetes, ingested protein does not increase plasma glucose concentrations, although protein is just as potent a stimulant of insulin secretion as carbohydrate. He became a nervous wreck when the PSA test came back with a 4. Maclean states, has been improved upon to make it more efficacious and safe.

MEDICAL NUTRITION THERAPY FOR TYPE 1 AND TYPE 2 DIABETES

Nitrogen balance

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Warranty plan Walmart Product Care Plans. A limited product warranty is included free for most items. With an optional Walmart Care Plan you can enhance the manufacturer's coverage from the date of purchase. We'll show you Care Plan options and pricing at checkout if applicable, or go to www. NorCross Marine Products, Inc. If the unit fails to perform as described in the products written specifications, due to a defect in materials or workmanship, we will repair it free of charge for parts or labor.

The customer, however, is responsible for any costs associated with returning the unit to NorCross. This warranty is void if damage or malfunction is due to abuse, misuse, accident, failure to reasonably maintain, improper installation or use, or unauthorized alteration or repairs. Therefore, this is not the preferred method for measuring muscle protein synthesis.

Example paper 3 pool model: 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.

It shows you how fast a muscle would rebuild itself entirely. An FSR of 0. This translates to a completely new muscle every 3 months. 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. 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: You can trace the amino acids from the protein: 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. Example paper de novo muscle protein synthesis: When measuring muscle protein synthesis, we can measure mixed muscle protein synthesis all types of muscle protein together.

But you can further specify what type of proteins are being synthesized. You can measure myofibrillar protein synthesis. This specifically measures myofibrillar protein synthesis, the protein that contract and gives you mass.

This fraction is highly relevant for building muscle mass. You can also measure mitochondrial protein synthesis. Mitochondria are the powerhouses of the muscle, they burn carbohydrate and fat as fuel. Therefore mitochondrial protein synthesis is more informative about energy production capacity in the muscle and more relevant for endurance athletes.

Sarcoplasm hypertrophy does not occur without myofibrillar hypertrophy. Example paper myofibrillar vs mitochondrial protein synthesis: More recently, deuterium oxide D2O, also called heavy water is getting popular to measure muscle protein synthesis. Example paper deuterium oxide: 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.

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. Methods are not necessarily good or bad. But the interpretation of the data based on these methods can be wrong. We recently showed that resistance exercise does not increase whole-body protein synthesis Holwerda, So should we conclude that resistance exercise is not effective to build muscle?

Whole-body protein metabolism measures the synthesis of all proteins in the body. 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. 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. 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.

This study has been getting a lot of attention: 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: 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. Both the 40 gram and the 70 gram dose were equally effective at stimulating muscle protein synthesis.

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: Let me first get something out of the way: 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: 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, 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, 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. 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. 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. 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, Areta, 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.

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. Only when you have both, you have pretty convincing evidence that your intervention does what you claim it to do.

Multiple sets increase muscle protein synthesis more than a single set Burd, A higher weekly training volume number of sets to muscle results in a greater muscle mass gains Schoenfeld, It is often recommended that a rep range of reps per set is optimal for muscle growth.

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 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 RM using 3- to 5-min rest periods between sets.

However, these recommendations lack evidence. The main takeaway here is that there are no magic rep ranges that are superior for muscle growth. It is unclear whether each set should be taken to failure. Muscular failure decreases performance on subsequent sets, thereby reducing training volume. Perhaps performing a set with 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, But at least in untrained subjects, training close to failure appears to produce similar muscle mass gains as training to complete failure Nóbrega, 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, In agreement, a longer interset rest period improves muscle mass gains compared to a shorter rest period 3 vs 1 min Schoenfeld, A single bout of resistance exercise can stimulate muscle protein synthesis for longer than 72 hour, but peaks at 24 h Miller, Indeed, training each muscle group at least twice a week results in larger muscle mass gains Schoenfeld, 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, 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 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 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, 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.

Twenty gram of protein gives a near-maximal increase in MPS after lower body resistance. When data of several studies was combined and the amount of protein was expressed per bodyweight, it was found that on average 0. 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.

More recently, it has been shown that the amount of lean body mass does not impact the response to protein ingestion Macnaughton, 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.

Protein sources differ in their capacity to stimulate MPS. 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 hydrolysed chemically cut into smaller smaller pieces , it resembles the digestion of a fast digesting protein. Consequently, hydrolyzed whey results 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, 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, However, there this can potentially compensated by ingesting a greater amount of plant protein Gorissen, 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, This supports the notion that protein digestion rate and protein leucine content are important predictors for anabolic effect of a protein source. This is best illustrated by study which compared the muscle protein synthetic response to five different supplemental protocol:.

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. Interestingly, the addition of 2. The addition of a larger amount of leucine 4. 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. 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. Carbohydrates slows down protein digestion, but have no effect on MPS Gorissen, In agreement, adding large amounts of carbohydrates to protein does not improve post-exercise MPS rates Koopman, 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. Adding oil to protein does not slow down protein digestion or MPS Gorissen, 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.

Most research has looked at isolated protein supplements in liquid form such as whey and casein shakes. 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.

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. As described in my systematic review, insulin does not stimulate MPS Trommelen, 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, 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 XXX.

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, 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, In addition, resistance exercise enhances the muscle protein synthetic response to protein ingestion for at least 24 hour Burd, 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.

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. 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, 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.

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 min before MPS goes up and peaks between minutes, after which MPS returns rapidly to baseline even if amino acid levels are still elevated Bohe, Atherthon, 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. 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. 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. This is best illustrated in a study where the effect of protein was assessed in both rested and post-exercise conditions Churchward-Venne, Protein intake alone stimulates MPS in the h period after ingestion.

Subsequently, MPS rates fall back to basal rates. However, in post-exercise condition, protein stimulated MPS rates in both the h and the h period. It appears that the muscle full effect is not present in acute post-exercise conditions. As discussed above, an effective protein distribution optimizes MPS.

Only three days of dieting already reduce basal MPS Areta, This shows that an energy deficit is suboptimal for MPS, however you can grow muscle mass while losing fat Longland, It is unclear if eating above maintenance is needed to optimize MPS. 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: Someone skeptical about a conclusion from a paper because muscle protein breakdown was not measured? Someone claiming that protein supplementation is not effective based on a long-term study he read that found no improvement in muscle mass: Feel free to ask me questions about the methods, or interpretation on protein metabolism studies in comments or on Facebook.

Especially the difference between mixed protein synth and myofibr protein synth. The mixed protein synthesis data is often used by proponents of very high frequencies Damas study as they point out MPS drops strongly after 10 hours in trained individuals. The mixed protein synthesis data is not that relevant when you also have myofibrilar protein synthesis data that suggests otherwise.

The current picture we now have on myoPS does not support an increased frequency, at least not higher than in untrained subjects where the duration of myoPS appears the same.

It could be speculated that in a more trained status, you need a higher volume number of sets close to failure to get a robust increase in myoPS again, but that is pure speculation. You mentioned in your summary how you just need to eat at maintenance to build muscle. In your opinion, is body recomposition possible then? But we know very little on how energy intake influences muscle protein synthesis. In practice, people report that bulking helps to gain muscle. If bulking helps to gain muscle, how big should be caloric surplus be to optimize muscle mass gains without disproportional large increases in fat mass?

Personally, I would go for a very small caloric deficits when cutting and a very small caloric surplus during bulking. What a briljant article once again. I believe, that this is one of the few sites that literally, contains the key of an better progress….. Somewhere, and im not sure if it was you,, but perhaps on another site there was a article about optimal training for MPS..

It seems that a FB routine is optimal for MPS as it is elevated for certain time and you train again when the mps is down to base-lines again.

But what about a FB while cutting? Would it still be optimal you think? There is a lot of people speculating on optimal training frequencies based on MPS data. I like keeping your training the same as much as possible while cutting. So much info that needs to be unpacked with so many questions. I just read an article from Eric Bach, regarding Norwegian study of two groups performing same volume.

Both groups recently competed in powerlifting event within 6 months. The groups tested the same volume of work and one group trained 3 days a week, but did twice the volume while the other group trained 6 days a week. Now they did the same workouts on the same reoutine days. The group who worked out 6 days a week had an increase in muscle growth and strength. Not by much, as they are seasoned trainers, but gains are gains. Thanks for diligent research for pleasure.

What I find disturbing of the Areta et al. I would love to see a similar design with a higher protein intake. In the work by Areta et al, there were 2 muscle biopsies: Both time points are used to get 1 value: I understand your other concerns. In short, this was the first study to investigate if protein distribution can impact post-exercise MPS and was designed in such a way that it would be most likely a positive effect would detected if it exists.

Indeed it found that protein distribution could impact MPS. As it was the first study to ever investigate and show this, it has a very high scientific value. In contrast, in has much less value in practitioners eyes, because you can question if the results from this study would extend to more real life situations.

Being the first to show evidence of a concept protein distribution can impact MPS is a big deal in science. Of course this concept now needs to be studied under different, more real life conditions. Practitioners are going to say that these studies are designed better, but such follow up studies will be less impactful in the science community.

Simply 2 different worlds with different interests. It appears you need a slightly longer energy deficit period before energy intake starts limiting MPS 3 days of dieting, see Areta What I think you should take away from this study from a practical point of view: Muscle biopsies were taken at -0 pre-exercise, and 1, 4, 6, 7 and 12 h post-exercise.

But more importantly, the dose of 10 gr in the spread group is simply sub-optimal, regardless of distribution. The exact same experiment could be conducted with more protein and that would take away a lot of the doubt concerning the sub-optimal dose issue with the pulse group imo. Do you mean this study with Areta et al.

And what objections are there to carrying out an experiment like this in the non-fasted state? The main outcome of that study is the FSR measured between h, The FSR assessed during specific intervals is interesting to provide some additional insight in how protein distribution patterns modulate the MPS time course.

However, the aggregate response is what actually matters. In the olympic spirit: But in the end, the medal goes to the one with the highest average speed over the entire race in this case: There is not really such a threshold, there is a linear increase in MPS following protein intake. Furthermore, if you look at the plasma data, the pulse group actually reaches a higher peak leucine than the 20 g group, and is higher at more time points than the leucine group.

With higher protein intakes, it is likely there would be no difference between the 3 groups. All 3 would likely maximally stimulate MPS. This study simply tried to demonstrate for the that protein distribution can impact MPS. It was the first study to demonstrate this, and therefore it is a big deal in our field. It did not try to demonstrate that that a pulse pattern or eating every 1. Obviously, that depends on the total amount of protein ingested.

Note that the 80 g protein ingested in 12 h translates to g protein in 16 waking hours, or a protein intake of 1. That is exactly the amount athletes typically eat. If total protein intake was much higher, likely all 3 groups would have had maximal MPS rates with no difference between groups.

From a scientific point of view, that finding would not not really be valuable. I can come up with another couple of thousand study ideas that do not modulate MPS. Finding new things that actually can modulate MPS is much more valuable. Having said that, now it is established that protein distribution can modulate MPS, a follow up study that shows that protein distribution has little impact on MPS when total protein intake is high, would be valuable. With regards to energy intake: That was after eating nothing except the protein with or without the carbs in the last 18 h.

An objection to doing the study in a non-fasted state would be that other food intake would delay protein digestion. As a result, it would be less likely that the bolus group would differ from the intermediate group, and less likely that the intermediate group from the pulse group. Another design consideration is the protein source. It is likely that you would see much less of an effect of protein distribution when you have a slowly digesting protein source.

Again, it is much more valuable to first establish that a concept that have influence, and then do follow up work to see if that concept also works in different concepts.

Like I mentioned in my previous post, that is the difference between scientific relevance, and relevance to practitioners. They simply have other priorities. Yes, 4 four meals of 60 g spaced by hour should be very to close to maximizing your gains. Do you mean actual protein researchers? Because none of the top muscle metabolism labs use nitrogen balance anymore as measurement tool to evaluate the anabolic effect on muscles.

I am confused because Dr. And get this, they have science to support their recommendations. This is based on research showing that if you consume a protein meal or essential amino acids , it boosts muscle protein synthesis for only about two hours without another boost in protein synthesis coming for at least another six hours even when adequate amino acids are present.

If you then consume more protein say, another protein shake two hours later, there would be no additional boost in muscle protein synthesis. However, if you wait about six hours or longer to consume that second protein shake, you would get another big increase in muscle protein synthesis. So it makes sense that to maximize muscle growth, you should wait a good six hours between meals so that every meal you eat boosts muscle protein synthesis.

Granted, protein synthesis is very important. However, just because you have a boost in muscle protein synthesis does NOT mean you get an increase in muscle growth. Muscle growth is a balance between muscle protein synthesis the build up of muscle protein and muscle protein breakdown the breaking down of muscle protein. To get an increase in muscle growth means that muscle protein synthesis must be greater than muscle protein breakdown.

Muscle protein breakdown is happening all the time. What the aforementioned experts are missing by suggesting that you should wait up to six hours between meals is that, while protein synthesis may be maximized, so is muscle protein breakdown, which minimizes any gains you would get in muscle growth. The best way to maximize muscle growth is to eat a high protein meal at least grams of protein, depending on the protein source every hours. How do I know this?

The first year of life is the most critical for rapidly gaining mass. And to ensure that this happens, we have evolved to eat every hours.

As soon as they step up their meal frequency they also step up their muscle mass and strength gains. The Aussie researchers had subjects perform a leg workout and then fed them a total of 80 grams of whey protein over the next 12 hours in three different methods: Greater protein net balance essentially means more muscle growth. Latency and duration of stimulation of human muscle protein synthesis during continuous infusion of amino acids.

Daytime pattern of post-exercise protein intake affects whole-body protein turnover in resistance-trained males. You wrote that Jim says that a positive nitrogen balance is more important than MPS, but from his article I think you ment he says a positive protein balance is more important? Protein balance is not the same as nitrogen balance see section 3. In section 2, I explain that muscle protein balance almost entirely depends on MPS muscle protein breakdown has little influence.

So the measurements in that study are not relevant for muscle. And the funny thing is, is that even if the measurements were relevant to building muscle, the WHOLE-BODY protein breakdown was the same for the group that ate every 3 hours and the group that ate every 6. Although I got the PhD, I am much more of a practitioner, and need to dispel a lot of misinformation my patients received from online communities.

Having someone else with a PhD saying it makes it even harder. In regards to the nitrogen balance issue, most exercise physiologists I took classes under flatly denounced any benefit to eating beyond neutral nitrogen balance. Not sure if this was just an old school mentality, or the fact that they did no research in the realm of resistance training or muscle synthesis, but it was surprisingly pervasive.

It was especially alarming as a nutrition grad student, where it was basically common knowledge that nitrogen balance was not all that useful in relation to increased muscle protein. Great article — I will definitely add your website to my list of evidence-based fitness and nutrition.

If I go to the gym early in the morning with an empty stomach is that a bad strategy for maximize gains??? In the same situation how can u spread the meals throughout the day?? Fasting is not going to be optimal for muscle mass gains. For optimal muscle mass gains, you should try to never be fasted and always have some protein in your system probably meals spread out throughout the day. However, the befit of optimally distributing protein over the day compared to intermittent fasting is relatively small.

So if you love intermittent fasting and it allows you to not obsess over food, helps with diet adherence, makes you more productive etc, it can be a very effective approach for you. But for the absolute the best effect on muscle mass gains, a higher meal frequency would be a little bit better.

Jorn it might be worth mentioning in the sections on protein intake that the bolus needed does go up with age. Just in case some old guy like me reads your piece, which they will if I have anything to do with it! In older adults, 40 g protein clearly outperforms smaller amounts of protein. Higher doses of protein have not been tested. So ideally, you want at least 40 g protein at each meal as an older adult.

Leucine supplementation might be an effective strategy to enhance the MPS response to meals that contain less than 40 g of protein.

Can you comment on this belief? A friend advised me that a very effective way to lose weight was to cycle to exhaustion and then not eat for several hours after completion. My fear is that this would promote muscle loss, like doing a resistant work-out and not eating afterwards.

Can you comment on this? Protein can be converted to glucose. Your liver glycogen sustains you plasma glucose levels. There are dozens of studies done where subjects get protein without carbs after not eating in the last 10 hours. In addition, adding carbs to protein does not help to build more muscle. There is absolutely nothing magical about cycling to exhaustion other that it burns some calories.

There is absolutely nothing magical about not eating for several hours after exercise, other than that is helps with lowering your caloric intake. Not eating directly after exercise is not necessarily a big deal with regards to muscle loss, as total protein intake during the day is the most important variable for muscle mass.

However, there is no logical reason to wait hours. Ideally, you eat meals high in protein a protein shake can already count as one of those meals to maximally stimulate muscle protein synthesis rates throughout the day. If I am reading your reply right, you are saying that with regards to protein synthesis, protein is the only macro-nutrient that affects it, the amount of carbohydrates and fats consumed is of little significance.

Am I understanding you right? If this is true then one should be able to achieve maximum muscle gain while simultaneously achieving maximum fat loss by being on a high protein low calorie diet. In other words, you just need some protein to maximize MPS regardless of what you eat along with it or have eaten in the previous 12 h.

However, that only works short-term. In general, you do need to be in energy balance or MPS will go down. You can be in a large energy deficit for 12 hours, without negative effects on MPS. However, being in an energy deficit for 3 days reduces MPS see section 7. Jon thank-you for your great kindness in taking the time to answer my questions and sharing your vast knowledge with me and others!

Would an effective strategy for maximum muscle gains be: Or simply eating meals consisting of only protein inter-spaced with meals consisting of only carbohydrate? Eating protein by itself should raise the MPS rate, since it will be absorbed into the blood stream faster, since there is no carbohydrate to slow down absorption.

Are there any micro-nutrients that are necessary for MPS? If the answer is yes then should one take multi-vitamins several times a day to maximize MPS? I have read that during long endurance exercise events that the body utilizes protein for energy along with fat and carbohydrate, a.

Is this phenomenon mostly the result of cortisol being released into the blood stream and so a mechanism that is unique to endurance exercise?. Jon thanks for the re-education! So many myths that I believed have now been dispelled and I understand things much better now.

There is no research to show that eating carbs with protein will actually lower MPS though it might a bit. Because when there is a micro-nutrient deficicy, many body processes may be suboptimal, such as protein digestion, blood flow to the muscle, hormone levels etc.

Micro-nutrient status does not change from hour to hour. Just make sure you get enough micro-nutrients on a weekly basis. Yes, protein is broken down during long endurance events and indeed this is worse when glycogen levels are depleted.

It seems likely cortisol plays a role in this. Though cortisol also goes up with dieting for example. First of all thank you for this great sum-up. I really appreciate it. What is your opinion on the usage of metformin in the case of type two diabetes mg tree times a day , would it have an detrimental effect on muscle gain?

Jorn is there any benefit to lifting heavy weights while on a severe calorie restricting diet? Will it help to preserve muscle mass? If on a normal diet and taking insulin for a diabetic condition when should the insulin be taken in relation to a heavy resistance work-out to achieve the most muscle gains? Lifting is absolutely beneficial to preserve muscle mass during caloric restriction. For example, whether taking insulin close to exercise is beneficial for muscle gain?

Thank you for the answer. Can I eat protein every 3 hours in the form of whey protein shakes: Sort of like IF but with shakes every 3 hours. Egg protein powder has been used and appears to be a very good source. Whole eggs have not been used, but I would expect them to be pretty good. Whey is theoretically the king, because it has everything you want: Most whole-food will be digesting a bit slower, which would theoretically be slightly worse.

Your suggested meal pattern would combine optimal protein frequency with the convenience of IF. I think it would be very effective. I think you could even get away with a shake every 4 h. I eat meals 2pm and 8pm covering the rest of my macros. I actually experience fat gain and muscle loss with a 50 kcal deficit, while I always feel bloated.

At the end of last year I gained 15kg weight of which was about 6kg muscle and 9kg fat. I was kg when I started cutting. Do you have any idea of what may be causing this effect and how I could fine-tune my diet to avoid this bloating, fatty feeling? How did you determine the kcal deficit? Any formula is just an estimation.

Likewise, how did you determine fat mass and muscle mass? Almost all options consumers have access to are quite unreliable on an individual level.

You mentioned a severe caloric deficit while cutting and losing all your muscle in 2 months. Dieting should be a very slow process. You should try to cut that amount on 2 months. You should at most lose 0. I suggest to not gain more than 0. When you gain weight fast, a disproportional amount will be fat mass. When you lose weight fast, a disproportional amount will be lean mass.

It shows you really know your stuff! Leucine or carbohydrate supplementation reduces AMPK and eEF2 phosphorylation and extends postprandial muscle protein synthesis in rats. Jorn what do you think of this study? It is an interesting study.

It is based on the muscle full effect described in section 7. In this study, leucine supplementation about 2 h after a meal prolonged the MPS response. So my guess would be that protein itself would do the same. In addition, carbs appeared to prolonged the MPS response to a meal. This is really interessing! Offcourse, i known a lot of this allready but.. There is some new facts that i had learned from this! What do you think about kcal surplus in bulking, how much do you think you need to build muscle.

Maybe i think it is likely that you can build allready muscle with a surplus of maybe I think you can even build muscle without a caloric surplus, but that you can gain more muscle but also fat when bulking. For example, if you eat a maintenance, you might gain a little bit of muscle, but no fat.

Bulking with a kcal surplus, you would gain muscle a bit faster, and some minimal fat gain. Bulking with surplus, you would likely gain muscle a bit faster gain, but now also gain significant amounts of fat.

Eating above a kcal surplus will likely have little incremental value for muscle gain, but will massively promote fat gain. My guess would be that small deficits are optimal for body composition. Normally i switch between these 2 forms now and than. Again, great articel and i hope to find much more soon about this subjects on ur site soon!

As long as a set if taken to close to failure, it will give the maximal stimulation to the muscle. I would do the majority of your training with strict form but not intentionally slow down , and do a bit of cheating every now and then.

By the way, i train in my home. Would it even make my GH larger and optimize my gains? Elevating GH for 2 hours will do very little. I would make sure my total amount of sleep is solid, and not try to break it up.

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