Maximization of protein synthesis

NPB = MPS - MPA

What does this equation mean?

Net protein balance (in our case muscle mass) = muscle protein synthesis - muscle protein breakdown.

Bring this equation to a positive result and you will be on your way to true greatness.

Muscle remodeling

You need to eat right to rebuild your muscle tissue after you've destroyed it in the gym. This is a foundation of muscle building. Under normal circumstances, skeletal muscle has a high turnover rate - about 1 to 2% of muscle protein is broken down and rebuilt each day.

Both exercise and nutrient intake are potent activators of protein synthesis, although diet-induced increases are short-lived. Exercise has a greater impact - it increases the rate of protein synthesis for 24 hours after exercise.

The problem here, however, is that training also activates muscle protein breakdown. Without the right nutritional intake at the right time, any potential gains from increased protein synthesis can be negated by protein breakdown. You can see how this works in the illustration below. Without a training stimulus, muscle protein synthesis and muscle protein breakdown cancel each other out in their overall magnitude.

Figure 1: Changes in muscle protein synthesis and muscle protein breakdown in the fed and fasted states in the absence of a training stimulus.

But add an intense training session with the right nutrient intake at the right time and things will change. Protein synthesis is activated and protein breakdown is suppressed. The result is an accumulation of muscle protein over time, as shown in the figure below.

Figure 2: Changes in muscle protein synthesis and muscle protein degradation in the fed and fasted states in the presence of an exercise stimulus.

The activator of protein synthesis: it's all about mTOR

To understand protein synthesis, it is important to familiarize yourself with mTOR. Scientific research shows us that when you force a muscle to contract against a heavy resistance, the primary response is an activation of protein synthesis. In turn, the activation of protein synthesis is controlled by a series of phosphorylation events that are fine-tuned by a protein called Mammalian Target of Rapamycin, or mTOR for short.

mTOR is undoubtedly the most important cell signaling complex for muscle growth. It is the master controller of protein synthesis in the cell and there is a direct relationship between muscle growth and mTOR activation - the more a training session activates mTOR, the more proteins the protein synthesis machinery makes for muscle growth and repair.

mTOR is activated by three things:

• Mechanical stress (through heavy training loads)
• Growth factors (IGF, growth hormones, insulin, etc.)
• Amino acids (especially leucine)

The "anabolic time window"

So what can we do nutritionally to achieve more than simply replacing the muscle tissue you've just broken down in the gym with a comparable amount of new muscle protein?

You use the anabolic window to your advantage: To get as muscular as possible, you need to use the anabolic window for maximum effect. It's time to talk about what you should eat and when you should eat it.

There are three times to increase protein/amino acid availability to amplify the acute increase in protein synthesis caused by training:

• Pre-workout: within an hour or so before your training session begins
• During the workout
• Post-workout: Less than 2 hours after your workout

The $10,000 question is which of these time(s) is best to achieve the maximum growth response from your workout.

Scientists have investigated this further and the results of several studies can be seen in the figure below.

Figure 3: Effects of resistance training on the timing of nutrients (leucine-enriched essential amino acids + carbohydrates) on muscle protein synthesis in young human subjects. The data are presented as a percentage change in fractional synthesis rate (FSR) from baseline.

The conclusion of this plot is that post-exercise food intake increases the acute, exercise-induced increase in protein synthesis more than pre-exercise food intake. This is good information, but there is more.

Before training

During exercise, ATP is used to provide energy for muscle contractions, which increases AMP levels. This activates a protein called AMP kinase (AMPK). AMPK reduces protein synthesis by inhibiting mTOR.

You can think of it this way - if mTOR is like the gas pedal for protein synthesis, then AMPK is like the brake. Even though it has been shown that pre-workout nutrition does not increase post-workout protein synthesis more than training alone, pre-workout amino acid intake does reduce AMPK-mediated inhibition of mTOR.

Conclusion: Don't forget to eat before training. It prevents the protein synthesis machinery from being switched off during training.

During training

Scientific studies have compared the effects of food intake during training with the effects of food intake after training on protein synthesis. The results of these studies are similar to the results of the studies on pre-exercise nutrition: protein intake during exercise resulted in increased protein synthesis, although this increase was much lower than with protein intake after exercise. Even though amino acids taken during exercise have only a subtle effect on protein synthesis, this protein intake still elicits an insulin response. This is important as insulin is a powerful inhibitor of protein breakdown.

This insulin response is also the reason why it makes sense to consume carbohydrates as well as amino acids during training. It has not only been shown that carbohydrates consumed during training inhibit protein breakdown - they also reduce the inhibition of mTOR mediated by AMPK.

Conclusion: Carbohydrates consumed during training not only inhibit protein breakdown, but also help to keep the protein synthesis machinery running.

After training

The post-workout meal is most important for increasing the rate of protein synthesis after training. Muscle cells are primed for protein synthesis during the hours after exercise, but this only occurs when the right food is available.

To build more muscle mass we need protein and it has been shown that the type and timing of protein intake during the post-workout phase controls the overall increase in protein synthesis that occurs immediately after exercise.

Importantly, the short-term activation of protein synthesis appears to ultimately determine how well we respond to training in the long term. This means that not only are intense training sessions needed to maximally activate protein synthesis, but the right nutrition must be there at just the right time for this to happen. This window of opportunity is only open for a short period of time and long-term gains can be compromised by delaying protein intake for just two hours after training. If you hit this window right, you'll grow significantly more - and if you miss it, you may not grow at all! There is a huge amount of research that has looked at exactly what types of nutrients are needed to maximally activate the protein synthesis process. We will go into the specifics later. At this point, it is sufficient to know that it has been shown that only the essential amino acids (EAAs) can activate protein synthesis, with leucine in particular being the most important for activating the protein synthesis machinery.

The scientific literature also shows quite clearly that carbohydrates are not needed to activate protein synthesis after training, but that there are other reasons to add carbohydrates to the post-workout meal, which we will discuss later.

How much protein should you eat?

It would be great if we could simply consume 1000 grams of protein or amino acids before, during or after training and achieve maximum growth. Unfortunately, in reality, excess amounts of protein are simply burned for energy or converted into body fat.

Protein acts synergistically with weight training to stimulate protein synthesis, but just as there is an upper limit to the amount of training we can productively recover from, there also appears to be an upper limit to the amount of protein we can use to maximize protein synthesis.

This topic has been investigated several times in scientific studies, but the amounts of protein or amino acids used in these studies are not necessarily transferable to real-world scenarios. Scientists have rarely used a training stimulus that comes anywhere close to what most exercisers do in the gym, making it difficult to extrapolate and make specific recommendations regarding the amount of protein needed.

For example, one study found that whey protein-induced increases in protein synthesis after exercise peaked at 20 grams of protein and that higher amounts of protein failed to further increase protein synthesis rates. Similar dose-dependent studies have been conducted to determine maximum leucine requirements. It is important to recognize that the type of intense training that many exercisers do in the gym likely activates protein synthesis to a greater extent than what these scientists used in the lab.

used in the lab. For this reason, it's possible that most exercisers could need more than 20 grams to achieve a maximum response. So what is the optimal amount and when should it be consumed? We can only give rough recommendations on this, although it is important to experiment and find the right formula for yourself.

Arguments in favor of carbohydrates

The scientific literature has conclusively shown that an insulin signal is not needed to activate exercise-induced protein synthesis - only leucine is needed, suggesting that carbohydrates are not important.

This initially came as a surprise as insulin is a potent activator of protein synthesis. Insulin activates mTOR via PI3K/akt signaling, which parallels the pathway used by amino acids and mechanical stress to activate mTOR.

While insulin signaling may not be needed for protein synthesis during the hours after exercise, that's not the whole story. Insulin is also a powerful inhibitor of protein degradation.

Studies have found that both hyperinsulinemia and carbohydrate consumption inhibit protein breakdown without having a significant effect on protein synthesis. When this was looked at specifically in the post-workout phase, it was found that eating glucose after exercise, even if it did not activate protein synthesis, had a strong inhibitory effect on protein breakdown.

This means that we should not ignore carbohydrates simply because they have no direct effect on protein synthesis. They increase insulin levels, which can be important. Muscles are primed for increased protein synthesis over a 24+ hour period after exercise, but the actual increase in protein synthesis that occurs as a result of exercise or amino acid supplementation only lasts for a few hours. Mechanical stress resulting from exercise, amino acid intake and insulin/growth factors all activate mTOR via different but complementary pathways, suggesting that we may benefit from a synergistic effect when multiple mTOR activating pathways are activated.

It is well established that mechanical stress induced by exercise and leucine/EAAs synergistically enhance protein synthesis. Similarly, insulin may contribute to the overall increase in protein synthesis via activation of mTOR through the PI3K/akt pathway.

Although some studies that have looked specifically at resistance training-induced protein synthesis have shown that the addition of carbohydrates to amino acids did not result in an additive effect on protein synthesis when sufficient amounts of amino acids were consumed, one must look closely at the experimental model when translating scientific research to the real world.

More recent studies that have looked at a more general model of protein synthesis have concluded that insulin + amino acids may well have a synergistic positive effect on protein synthesis and together produce the greatest possible mTOR activation. Taking all these studies together, it is safe to say that even though insulin does not appear to increase exercise-induced protein synthesis, carbohydrates may help keep the protein synthesis machinery running longer after exercise.

If insulin really is capable of enhancing or prolonging the increase in protein synthesis rates after exercise, then adding carbohydrates to a post-workout plan would obviously have huge benefits.

Let's put it all together

Studies and scientific literature are the backbone of the scientific method, but all of this is worthless if you don't have a way to put this information into practice. With that in mind, here's an example of how you can put what you've learned in this article into practice:

Pre-workout (30 to 60 minutes before starting your workout)

• Protein source: 30 to 50 grams of any medium or fast digesting protein source. Whole foods are fine, but in this case you should consume the protein 60 minutes rather than 30 minutes before your workout. Examples of fast-digesting protein sources include whey protein isolates, concentrates and hydrolysates.
• Carbohydrate source: Carbohydrates are optional, but if you plan to train hard, you should consume 26 to 75 grams of medium GI carbohydrates. Examples of this would be a cup of oatmeal or a cup of blueberries.
• John's favorite pre-workout meal: Lean animal protein, 30 grams of carbohydrates (oatmeal) and 1 to 2 tablespoons of almond or peanut butter mixed with the oatmeal.
• Bill's favorite pre-workout meal: Whey protein isolate with about 45 grams of carbohydrates from ½ cup of oatmeal mixed with ½ cup of unsweetened apple sauce.

During the workout

• Protein source: 10 to 20 grams of BCAAs or 20 to 30 grams of a whey protein isolate/hydrolyzate
• Carbohydrate source: Optionally 35 to 50 grams of high-glycemic carbohydrates, which are drunk in sips throughout the workout.

The insulin response to these carbohydrates may synergistically enhance protein synthesis in the presence of amino acids. Insulin is also a powerful inhibitor of protein breakdown.

For exercisers during contest preparation or those who have poor insulin sensitivity, keeping insulin levels low could have a fat-burning benefit, meaning that some people may be better off avoiding these carbohydrates. During the off-season or for hardgainers, however, this insulin response can be very helpful.

• John's favorite intra-workout meal: 30 to 50 grams of whey protein hydrolysate and 40 grams of potato starch during the off-season.
• Bill's favorite intra-workout meal: 20 grams of BCAAs and 40 to 50 grams of dextrose/glucose polymers during the off-season.

Post-workout (up to 60 minutes after training)

• Protein source: 30 to 50 grams of rapidly digestible protein such as whey protein isolate or hydrolysate
• Carbohydrates: Optional but highly advisable if you are not in a drastic fat loss phase.

The type of carbohydrate intake strongly depends on the individual, the goals and the training phase.

Use 25 to 75 grams of carbohydrates with a medium to low GI. Off-season exercisers or hardgainers can use a 50 to 100 gram mix of medium to high GI carbohydrates. True hardgainers can benefit significantly from the protein degradation inhibiting effects of insulin at this point. The strong insulin spike from the high-glycemic carbohydrates and the sustained increase in insulin levels from the medium GI carbohydrates could keep protein synthesis rates high for longer.

If you are preparing for a competition or have poorer insulin sensitivity, then you can occasionally avoid these carbs completely.

- John's favorite post-workout meal: 50 grams of whey protein isolate 10 minutes after training, mixed with 1 to 2 cups of raw milk during the off-season. An hour later, fish and Ezekiel toast with jam.
- Bill's favorite post-workout meal: 50 grams of whey protein isolate. During the off-season, an additional 1 cup of oatmeal with 1 cup of blueberries. One hour later a regular meal.

Summary

Nutrients have a potent effect on the protein synthesis machinery and the right timing can make the difference between success and failure in your training progress. While there is no ideal solution for everyone, as it depends on individual insulin sensitivity, individual metabolism, individual body type and individual goals, in this article we have put together a strategy for nutritional intake around training that is based on the latest scientific evidence and can be easily modified to suit your individual needs. Use this strategy to maximize your protein synthesis and grow like never before.

References

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by John Meadows, Bill Willis, PhD