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I will have to compose a refresher on Methylation for you guys this coming week, but I did want to go ahead and get this posted for you. Looks like we will be clearing customs this coming week, and hopefully have the final product out for you the following week.
I realize there is a style disturbance....while Marc McDougal did the majority of the writeup, I asked Jason Cholewa, one of the foremost Betaine researchers, to handle to section on betaine.
Strafe Write Up
Intro
EvoMuse is excited to bring you the newest addition to our innovative supplement line, an anabolic/anti-catabolic pre-bed supplement delivered in an impossibly great tasting honeydew-cantaloupe powder. If you’ve ever tasted any of these ingredients individually, you’ll understand how hard we had to work to make this formula something you’ll actually look forward to drinking.
The word Strafe is a verb meaning “to attack by airplanes with machine gun fire”. Metaphorically, the enemy’s troops on the ground represent the numerous physiological mechanisms in your body accelerating muscle breakdown, and crushing anabolism. Strafe is here to annihilate those enemy troops and allow serious muscle growth.
Take one serving of Strafe every night before bed, and let it work while you’re sleeping. You can use it continuously; there is no need to cycle.
Before we get into the specific ingredients, let’s run through a quick overview of mTOR, since this is the main target of the Strafe formula.
Mammalian Target of Rapamycin (mTOR)
Most people that have spent any appreciable amount of time trying to gain muscle have heard quite a bit about mTOR in the past few years since the discovery of its crucial relevance to muscle growth. And for good reason, this protein is one of the most important cellular gatekeepers of anabolism.
Even if you understand the basics of mTOR, this will still be a good read to brush up on some specifics, as Strafe is largely focused on mTOR activation, and we’ll be using some important terms in the individual ingredient sections that will be clarified here.
mTOR doesn’t care about the majority of what’s going on in the body, but it pays particular attention to things like insulin, ATP, IGF-1, and the branched chain amino acid Leucine. When mTOR is activated, it increases protein synthesis through two at least two distinct mechanisms, which we will briefly cover. This can be complex stuff, so we’re going to try to keep it simple with some ridiculous metaphors, so stay with us.
1st Way mTOR Activates Protein Synthesis
mTOR inactivates a specific binding protein called 4E-BP1. When 4E-BP1 is left to its own devices, it prevents another protein (eIF4E) from doing its job. This job is to associate with a final protein called eIF4G, creating a complex, which is crucial to protein synthesis. Without this complex, there’s no muscle building.
Kind of confusing, right? Think of it like this, you’re Scarface. You’ve got a guy (eIF4E) delivering a briefcase full of drugs to another guy (eIF4G), in trade for a briefcase full of money.
But, there’s a sniper on the roof (4E-BP1) across the street from the drop point, ready to pick off your guy (eIF4E). If he succeeds, you lose all the drugs and the cash.
mTOR is a Special-Ops guy you hired (Liam Neeson) that sneaks up behind the sniper and jabs him in the neck with a syringe full of paralytic. The transaction goes through, and you get your cash (protein synthesis/muscle).
2nd Way mTOR Activates Protein Synthesis
mTOR activates (phosphorylates) an enzyme called p70 S6 kinase (p70S6K), which, for our purposes, regulates cell size and activates protein synthesis. It does this in a pretty cool way, by upregulating specific proteins that mTOR can then act on (1).
So, think of it like this. mTOR is the New England Patriots, and they’re playing the Baltimore Ravens in the playoffs. Tom Brady decides to hand off the ball to Julian Edelman (p70S6K), a wide receiver. Edelman then throws a pass to Amendola for a touchdown. Even if you hate the Patriots, like most people do, that was still a pretty sweet play. And that’s another way mTOR turns on muscle building, by recruiting other/more players to score points, instead of just relying on the quarterback.
With that out of the way, let’s look at ingredients and function:
BCAAs 2:1:1
While all three Branched Chain Amino Acids are important, the main purpose for including BCAAs in Strafe is the Leucine content, which we have provided at 2.5g per serving. Leucine has been established as the gold standard for mTOR activation from dietary means, stated succinctly here, “Of all nutrients, the single amino acid leucine possesses the most marked anabolic characteristics in acting as a trigger element for the initiation of protein synthesis” (2).
So why not just use Leucine? It turns out that the other two BCAAs, Isoleucine and Valine likely play a small but important role in protein synthesis due to the body’s ability to closely monitor Leucine levels in the blood stream, so just supplying a bolus of Leucine by itself can be problematic (3,4).
Ok, so if a little Leucine is good, is a lot of Leucine great? Nope. A huge amount of Leucine is unnecessary for mTOR activation (hence why we didn’t go with a 4:1:1 or 8:1:1 ratio). Research shows that even a dose as low as 1.7g is sufficient to kick-start protein synthesis in non-elderly populations (5).
When blood levels of Leucine start to drop (like during eight hours of sleep), the body senses this and rapidly inhibits protein synthesis, while concurrently triggering breakdown of muscle tissue to compensate and get blood levels back up (6,7).
So why not just knock down a casein shake before bed to take advantage of the slow release of amino acids into the bloodstream? You can certainly still do this, but you’ll still benefit greatly by adding a serving of Strafe to your casein shake. A recent study demonstrated that adding 2.5g of Leucine to 20g of casein protein stimulated muscle protein synthesis above and beyond the casein alone (8). Another recent study showed that a low protein meal containing only 6g of protein was as effective at stimulating protein synthesis as a meal containing 25g of protein when adding 5g of Leucine (9).
When you’re counting calories, this can become quite important. This is also highly relevant for those on a ketogenic plan, where total protein has to be limited to a moderate level…a little bit of Leucine can replace quite a bit of protein.
We also know that Leucine stimulates a monophasic insulin release, which, contrary to popular belief, insulin aids in muscle protein turnover by inhibiting muscle breakdown moreso than triggering anabolism (10). On top of that, Leucine also concurrently increases insulin sensitivity (11).
So, to put it simply, we get a direct anabolic trigger through mTOR (taking out that 4E-BP1 sniper and activating the Portuguese speaking p70S6K crew), as well as sending off an additional signal to stop catabolism through a controlled release of insulin, while priming the muscle cells for enhanced sensitivity.
Ketoisocaproate (KIC)
KIC is one of the first steps of Leucine metabolism, meaning that some of your ingested Leucine from Strafe or even a protein meal will turn into KIC. While Leucine itself can activate mTOR, as shown in the graphic below, KIC can further activate mTOR by itself, as well as converting back to Leucine (12).
KIC has been shown to decrease proteolysis (muscle breakdown) as well as stimulate protein synthesis (12,13).
In muscle cells, a small percentage (about 5%) of KIC converts to HICA (more to come on that). In the liver, an even smaller amount of KIC (about 1%) converts to HMB.
The presence of KIC triggers an enzyme called BCKDH (displayed in red in the above graphic), which acts as a negative feedback mechanism for Leucine. BCKDH oxidizes Leucine and eventually inhibits further conversion of Leucine to the downstream metabolites that creates a “Leucine threshold”, which is why we can’t just keep pumping endless amounts of Leucine and KIC into the bloodstream and expect never-ending protein synthesis.
Even though KIC triggers BCKDH, it gets some work done before this starts to happen. Studies looking at direct supplementation of KIC have shown an increase in leg press 1RM, reduction in fatigue during weight training, increased work capacity, and enhanced maintenance in peak power during repeated cycle sprints (Wells, Wilson).
HICA
As shown in the above graphic, some of the ingested Leucine and KIC will convert to HICA, also known as Hydroxyisocaproic Acid, or Leucic Acid. HICA is found in whole milk and yogurt, although in largely insufficient doses to achieve any sort of ergogenic benefit (14). Of further note, although ingesting high protein foods can supply the precursor Leucine, research shows that this doesn’t effect blood levels of HICA much at all, and the only way you’re going to get a HICA spike from dietary means is by fasting for 2-3 days at a time (15).
We’ve included additional HICA in the Strafe formula for three reasons. For one, HICA directly triggers mTOR by itself. Second, we’re really not getting a large amount of HICA from downstream conversions. Third, (and admittedly theoretically) HICA can sneak by the regulatory mechanisms that trigger BCKDH, therefore allowing more MTOR activation before the party gets shut down by negative feedback.
As far as what we can expect from HICA on its own, let’s take a look at the data. A recent study published in the ISSN Journal looked at the effect of HICA supplementation for four weeks in male soccer players. The results showed an increase in lean body mass, 23% reduction in DOMS, and improved training alertness in the HICA group compared to placebo (16).
Another study looked at rats with one leg immobilized in a cast, which caused serious muscle atrophy in the casted leg vs. the functional leg. They found that supplementation with HICA allowed the rats with the atrophied, casted leg to return to full muscle mass after 14 days of normal use, vs. the control group which still had significant atrophy (17).
CaHMB
Beta-hydroxy-methylbutyrate or HMB, was first popularized in the late 1990’s, being marketed as a supplement to increase strength, build muscle and accelerate fat loss. Since then, numerous studies have looked at these claims with contradictory results. Some studies make it look like everything we’ve ever wanted in an ergogenic supplement while others show no effect. We’ve seen a recent revival in the research looking at a free acid form (HMB-FA) vs. the traditional Calcium HMB or CaHMB, and also new and different study designs on the CaHMB form.
So why the conflicting results in the research? We feel that it largely comes down to the individual user, as often times even in the same study some subjects respond extremely well while others don’t at all. For HMB only products, some users will likely see great results, but many people would be non-responders. However, we believe using HMB in a combo formula with multiple other pathways to trigger mTOR and protein synthesis makes a great inclusion that will offer additional benefits to the other ingredients.
Although HMB is a metabolite of both Leucine and KIC, it won’t be created at high enough levels through these conversions to have a strong effect. Additionally, HMB activates mTOR without triggering the negative feedback from BCKDH.
Recently a study was done that looked at HMB-FA vs. CaHMB, and the FA form was found to be far superior in the parameters investigated. However, this has been shown to be unrepeatable, with the Ca form actually showing 80% greater bioavailability over the FA form (18).
I realize there is a style disturbance....while Marc McDougal did the majority of the writeup, I asked Jason Cholewa, one of the foremost Betaine researchers, to handle to section on betaine.
Strafe Write Up
Intro
EvoMuse is excited to bring you the newest addition to our innovative supplement line, an anabolic/anti-catabolic pre-bed supplement delivered in an impossibly great tasting honeydew-cantaloupe powder. If you’ve ever tasted any of these ingredients individually, you’ll understand how hard we had to work to make this formula something you’ll actually look forward to drinking.
The word Strafe is a verb meaning “to attack by airplanes with machine gun fire”. Metaphorically, the enemy’s troops on the ground represent the numerous physiological mechanisms in your body accelerating muscle breakdown, and crushing anabolism. Strafe is here to annihilate those enemy troops and allow serious muscle growth.
Take one serving of Strafe every night before bed, and let it work while you’re sleeping. You can use it continuously; there is no need to cycle.
Before we get into the specific ingredients, let’s run through a quick overview of mTOR, since this is the main target of the Strafe formula.
Mammalian Target of Rapamycin (mTOR)
Most people that have spent any appreciable amount of time trying to gain muscle have heard quite a bit about mTOR in the past few years since the discovery of its crucial relevance to muscle growth. And for good reason, this protein is one of the most important cellular gatekeepers of anabolism.
Even if you understand the basics of mTOR, this will still be a good read to brush up on some specifics, as Strafe is largely focused on mTOR activation, and we’ll be using some important terms in the individual ingredient sections that will be clarified here.
mTOR doesn’t care about the majority of what’s going on in the body, but it pays particular attention to things like insulin, ATP, IGF-1, and the branched chain amino acid Leucine. When mTOR is activated, it increases protein synthesis through two at least two distinct mechanisms, which we will briefly cover. This can be complex stuff, so we’re going to try to keep it simple with some ridiculous metaphors, so stay with us.
1st Way mTOR Activates Protein Synthesis
mTOR inactivates a specific binding protein called 4E-BP1. When 4E-BP1 is left to its own devices, it prevents another protein (eIF4E) from doing its job. This job is to associate with a final protein called eIF4G, creating a complex, which is crucial to protein synthesis. Without this complex, there’s no muscle building.
Kind of confusing, right? Think of it like this, you’re Scarface. You’ve got a guy (eIF4E) delivering a briefcase full of drugs to another guy (eIF4G), in trade for a briefcase full of money.
But, there’s a sniper on the roof (4E-BP1) across the street from the drop point, ready to pick off your guy (eIF4E). If he succeeds, you lose all the drugs and the cash.
mTOR is a Special-Ops guy you hired (Liam Neeson) that sneaks up behind the sniper and jabs him in the neck with a syringe full of paralytic. The transaction goes through, and you get your cash (protein synthesis/muscle).
2nd Way mTOR Activates Protein Synthesis
mTOR activates (phosphorylates) an enzyme called p70 S6 kinase (p70S6K), which, for our purposes, regulates cell size and activates protein synthesis. It does this in a pretty cool way, by upregulating specific proteins that mTOR can then act on (1).
So, think of it like this. mTOR is the New England Patriots, and they’re playing the Baltimore Ravens in the playoffs. Tom Brady decides to hand off the ball to Julian Edelman (p70S6K), a wide receiver. Edelman then throws a pass to Amendola for a touchdown. Even if you hate the Patriots, like most people do, that was still a pretty sweet play. And that’s another way mTOR turns on muscle building, by recruiting other/more players to score points, instead of just relying on the quarterback.
With that out of the way, let’s look at ingredients and function:
BCAAs 2:1:1
While all three Branched Chain Amino Acids are important, the main purpose for including BCAAs in Strafe is the Leucine content, which we have provided at 2.5g per serving. Leucine has been established as the gold standard for mTOR activation from dietary means, stated succinctly here, “Of all nutrients, the single amino acid leucine possesses the most marked anabolic characteristics in acting as a trigger element for the initiation of protein synthesis” (2).
So why not just use Leucine? It turns out that the other two BCAAs, Isoleucine and Valine likely play a small but important role in protein synthesis due to the body’s ability to closely monitor Leucine levels in the blood stream, so just supplying a bolus of Leucine by itself can be problematic (3,4).
Ok, so if a little Leucine is good, is a lot of Leucine great? Nope. A huge amount of Leucine is unnecessary for mTOR activation (hence why we didn’t go with a 4:1:1 or 8:1:1 ratio). Research shows that even a dose as low as 1.7g is sufficient to kick-start protein synthesis in non-elderly populations (5).
When blood levels of Leucine start to drop (like during eight hours of sleep), the body senses this and rapidly inhibits protein synthesis, while concurrently triggering breakdown of muscle tissue to compensate and get blood levels back up (6,7).
So why not just knock down a casein shake before bed to take advantage of the slow release of amino acids into the bloodstream? You can certainly still do this, but you’ll still benefit greatly by adding a serving of Strafe to your casein shake. A recent study demonstrated that adding 2.5g of Leucine to 20g of casein protein stimulated muscle protein synthesis above and beyond the casein alone (8). Another recent study showed that a low protein meal containing only 6g of protein was as effective at stimulating protein synthesis as a meal containing 25g of protein when adding 5g of Leucine (9).
When you’re counting calories, this can become quite important. This is also highly relevant for those on a ketogenic plan, where total protein has to be limited to a moderate level…a little bit of Leucine can replace quite a bit of protein.
We also know that Leucine stimulates a monophasic insulin release, which, contrary to popular belief, insulin aids in muscle protein turnover by inhibiting muscle breakdown moreso than triggering anabolism (10). On top of that, Leucine also concurrently increases insulin sensitivity (11).
So, to put it simply, we get a direct anabolic trigger through mTOR (taking out that 4E-BP1 sniper and activating the Portuguese speaking p70S6K crew), as well as sending off an additional signal to stop catabolism through a controlled release of insulin, while priming the muscle cells for enhanced sensitivity.
Ketoisocaproate (KIC)
KIC is one of the first steps of Leucine metabolism, meaning that some of your ingested Leucine from Strafe or even a protein meal will turn into KIC. While Leucine itself can activate mTOR, as shown in the graphic below, KIC can further activate mTOR by itself, as well as converting back to Leucine (12).
KIC has been shown to decrease proteolysis (muscle breakdown) as well as stimulate protein synthesis (12,13).
In muscle cells, a small percentage (about 5%) of KIC converts to HICA (more to come on that). In the liver, an even smaller amount of KIC (about 1%) converts to HMB.
The presence of KIC triggers an enzyme called BCKDH (displayed in red in the above graphic), which acts as a negative feedback mechanism for Leucine. BCKDH oxidizes Leucine and eventually inhibits further conversion of Leucine to the downstream metabolites that creates a “Leucine threshold”, which is why we can’t just keep pumping endless amounts of Leucine and KIC into the bloodstream and expect never-ending protein synthesis.
Even though KIC triggers BCKDH, it gets some work done before this starts to happen. Studies looking at direct supplementation of KIC have shown an increase in leg press 1RM, reduction in fatigue during weight training, increased work capacity, and enhanced maintenance in peak power during repeated cycle sprints (Wells, Wilson).
HICA
As shown in the above graphic, some of the ingested Leucine and KIC will convert to HICA, also known as Hydroxyisocaproic Acid, or Leucic Acid. HICA is found in whole milk and yogurt, although in largely insufficient doses to achieve any sort of ergogenic benefit (14). Of further note, although ingesting high protein foods can supply the precursor Leucine, research shows that this doesn’t effect blood levels of HICA much at all, and the only way you’re going to get a HICA spike from dietary means is by fasting for 2-3 days at a time (15).
We’ve included additional HICA in the Strafe formula for three reasons. For one, HICA directly triggers mTOR by itself. Second, we’re really not getting a large amount of HICA from downstream conversions. Third, (and admittedly theoretically) HICA can sneak by the regulatory mechanisms that trigger BCKDH, therefore allowing more MTOR activation before the party gets shut down by negative feedback.
As far as what we can expect from HICA on its own, let’s take a look at the data. A recent study published in the ISSN Journal looked at the effect of HICA supplementation for four weeks in male soccer players. The results showed an increase in lean body mass, 23% reduction in DOMS, and improved training alertness in the HICA group compared to placebo (16).
Another study looked at rats with one leg immobilized in a cast, which caused serious muscle atrophy in the casted leg vs. the functional leg. They found that supplementation with HICA allowed the rats with the atrophied, casted leg to return to full muscle mass after 14 days of normal use, vs. the control group which still had significant atrophy (17).
CaHMB
Beta-hydroxy-methylbutyrate or HMB, was first popularized in the late 1990’s, being marketed as a supplement to increase strength, build muscle and accelerate fat loss. Since then, numerous studies have looked at these claims with contradictory results. Some studies make it look like everything we’ve ever wanted in an ergogenic supplement while others show no effect. We’ve seen a recent revival in the research looking at a free acid form (HMB-FA) vs. the traditional Calcium HMB or CaHMB, and also new and different study designs on the CaHMB form.
So why the conflicting results in the research? We feel that it largely comes down to the individual user, as often times even in the same study some subjects respond extremely well while others don’t at all. For HMB only products, some users will likely see great results, but many people would be non-responders. However, we believe using HMB in a combo formula with multiple other pathways to trigger mTOR and protein synthesis makes a great inclusion that will offer additional benefits to the other ingredients.
Although HMB is a metabolite of both Leucine and KIC, it won’t be created at high enough levels through these conversions to have a strong effect. Additionally, HMB activates mTOR without triggering the negative feedback from BCKDH.
Recently a study was done that looked at HMB-FA vs. CaHMB, and the FA form was found to be far superior in the parameters investigated. However, this has been shown to be unrepeatable, with the Ca form actually showing 80% greater bioavailability over the FA form (18).
