TopMuscle Elite

 Presale - just waiting on labels. ETA around 3-22.

***Upgraded carrier to be high-potency Phosphatidic Acid Ethosome based, for increased muscle growth***

TopMuscle: Enhanced Hypertrophy Force Multipler

You've got the regimen dialed: deep stretches, lengthened partials, emphasized eccentrics, and the discipline to push yourself to failure...and sometimes beyond. But that's not enough, is it? Because it's never enough.

You think you know how it works? Maybe. Do you know why it works? Do you know how to engage the ultimate force multiplier and make it even better? Do you know how to take away your body's resistance to change and MAKE it grow - quickly.

You bring the steel and EvoMuse will bring the hammer, and I'll meet you at the forge.

TopMuscle is the topical hammer that takes every rep of stretch-induced tension and amplifies it - big time.

You wanna play? Go somewhere else. We are here to work.

What's Hypertrophy you ask? Well, hang around any kid with ADHD and you will probably know what Hyper means. It means, loosely, barely restrained and far beyond "normal" in scope and intensity.

Troph? Will that's an old Greek word that means Feed or Growth.

Hypertrophy? Growth beyond expectations.

Now that we've got you pumped (psychologically...we will get you pumped physically later), let's go through this, pathway by biological pathway, and I'll do my best to seamlessly tie the ingredients in in a way that's simple to understand.

mTorc1

The King Daddy of all growth signals. mTorc1 is essential for tissue growth, especially muscle. Without it you get nothing...good day, sir.

mTorc1 is activated (luckily for us) by a huge array of things - most notably protein intake. Various amino acids (leucine being the most well known) signals to the body that you just had a successful hunt and now you are feasting on delicious bloody fleshy protein. The body then kicks in the process of protein synthesis to both repair any damage you might have sustained during the hunt, but to also make you bigger and stronger. After all, if you are a successful badass animal, nature likes having you around and rewards you. We love being around the beautiful people.

mTorc1 is also activated, potently, by other pathways - especially those that "sense" injuries and activate it downstream.

Around each and every cell in your body is something called a cellular membrane. It is like a sack protecting the innards of your cells, but unlike a sack it is a dynamic active structure of its own. It's comprised mostly of phospholipids (like those contained in egg yolks. All yolking aside, be sure to eat your eggs). One of the main phospholipids is called Phosphatidic Acid.

Phosphatidic Acid (PA) is the simplest phospholipid, but don't let that fool you. When those cellular membranes are disturbed or perturbed, and they sustain tiny injuries, PA is release and reacts with Protein Kinase C. This sets in motion a cascade of signals that results in a massive increase in mTorc1 activity, and protein synthesis.

These "injuries" are highly triggered by aggressive stretching such as tension from resistance training, especially when the muscles are lengthened and at a mechanical (leverage) disadvantage.

Lifters have been using oral PA for quite a while now with great success, but our approach is superior. More of this towards the end so stay with me.

Continuing on with stretch-induced hypertrophy, we now introduce you to the body's QRF (quick reaction force...or first responders for you civilians) - prostaglandins.

If you've ever taken something like Advil, then you have manipulated the prostaglandin system.

When our lovely serene cell membranes are perturbed, again by stretch or injury (usually more acute), the same membrane, in addition to PA, releases something called Arachidonic Acid. ArA reacts with Protein Kinase C (again) and an enzyme called cyclooxygenase (COX) to form, specifically, the 2 series prostaglandins. PGF2a, especially, triggers a potent reaction recruiting stem cells (and also replenishing them, which is great for long-term growth, IGF-1 [insulin-like growth factor], and other hypertrophic pathways). These signals are highly potent and converge on, you guessed it, mTorc1 to trigger repair and protein synthesis.

Now, if the intensity of the injury determines the intensity of the reaction, it would stand to reason that deploying more troops would amplify growth. TopMuscle contains a special blend of ingredients to enhance the prostaglandin reaction. As you might expect, it contains Arachidonic Acid oil, for immediate availability to form PGF2a. It also contains a saponin from Horse Chestnut, called Beta-Escin. Now this wonderful little compound not only strengthens your vascular system, but has a unique ability to directly stimulate PGF2a formation. The inclusion of Methyl Nicotinate also causes a vascular prostaglandin response, hyper-dilating local blood vessels which enhances pump (and outward stretch) and prostaglandin healing. Prostaglandins also transmit pain signals to adjoining cells. After all, if you are injured you shouldn't be making the injury worse so....ouch. This is where Advil comes in. As a COX inhibitor, it blunts the prostaglandins thus blunting certain types of pain. But in our case, no pain, no gain.

Now we move on to the semi-related transient receptors system. The body, in general, is dumb. Without specialized organs and receptors it would know nothing about the world and would quickly perish. For example, light sensing neurons and nerves in your eyes enable you to see. The transient receptors fill a similar function. They are called transient because, unlike your standard ligand-receptor interaction model in which receptors are activated by specific chemicals/hormones, transient receptors are activated by passing and changing stimuli.

The two we are concerning ourselves with are TRPV1 and TRPV4.

To expand a bit, TRPV4, the more significant of the two for TopMuscle, activates when cells are subjected to shear or stretch force (there's that word again). This activation by stretch then begins our familiar cascade of biological response.

TRPV1 reacts to high heat, which normally would mean a burn injury, which is where the body would want to hurry and deploy fast-acting healing methods.

Funny thing, though. Even though these receptors are usually triggered by external stimuli, we can trick them into activating.

For TRPV4 (used to amplify our stretch-induced hypertrophy) we have a highly potent agonist (activator) in Apigenin. By making the body think that the stretch stimulus is far more potent, the resulting hypertrophy is commensurately amplified.

For TRPV1, you have all experienced its activation via hot peppers. Capsaicin, from hot peppers, is an insanely potent agonist. The body perceives severe injury and immediate begins to try to heal. There is, of course, no real injury here. TRPV1 is also activated by normal workout conditions, including stretch and friction (working the muscles creates friction and therefore heat).

The activation of both receptors causes a rapid and intense influx of calcium ions and triggers various systems which all converge on....mTorc1. The purpose here is pure amplification of your already intense workouts....and they absolutely excel.

As another side benefit, both receptors also trigger further prostaglandin response.

BMPs - The Master Control System

BMPs, short for Bone Morphogenetic Proteins (especially BMP2/7) are the master controllers of muscle mass and skeletal strength and integrity - driving hypertrophy while simultaneously crushing atrophy signals (provided you know what to manipulate). Winbanks et al. (2013) showed BMP7/receptor activation causes massive adult muscle growth via Smad1/5/8 signals activating (let's all say it together!) mTOR.

So the BMPs, when activated, trigger SMAD signaling - specifically SMAD1/5/8. These form a complex with SMAD4, which escorts them to the cell nucleus to work their hypertrophic magic.

As usual, signals like tension under load and stretch activate the main BMPs, but we can also use another natural ingredient. Salidroside has been shown to activate both BMP2 and BMP7.

Now we enter into darker territory - the terrain of the enemies of hypertrophy. We will start with Myostatin.

I'm sure you've all seen Jurassic Park. If you haven't, stop reading now and go watch it. Ok...maybe not right this second - we got work to do.

Anyway, I have a wacky hypothesis that, when the dinosaurs ruled, and they were huge, they required massive amounts of food and other resources to even sustain. There was no DoorDash or protein powder. Well, they found out really quickly that, when conditions became harsh, their size was their downfall while the tiny little mammals survived and, eventually, thrived.

In my musings, I picture nature devising ways that are hard programmed into our hardware to restrict our ability to perpetually grow larger. The main one is called Myostatin (another is called Glygogen Synthase Kinase 3b, which we will cover below). Myo means muscle, and Statin (like static) means stop. Myostatin literally stops muscle from growing. Not cool, my friends.

Well, luckily for us, myostatin can be attacked from multiple angles and functionally crippled. One of the main ways is through a compound usually contained in cocoa and tea called Epicatechin. Epicatechin induces something called Follistatin which is nice enough to severely limit what myostatin does, and allows for greater muscle hypertrophy.

That doesn't mean it's perfect and you're gonna be YUUUUGE, but it all adds up.

ABANDON ALL HOPE, YE WHO ENTER HERE

This section gets a bit complicated so....here we go.

The Sad Smads

Now back in the BMP section I explained how Smad1/5/8 (the good ones) need to join with Smad4 in order to get into the prom...err, nucleus. Well, on the dark side of the equation we have other Smads. Notably Smad2/3. Smad2 and (mostly) 3 are one of the final targets of not only myostatin, but other atrophic (the opposite of hypertrophic) pathways. When Smad2/3 is active the battle begins. They compete with Smad1/5/8 for the attention of Smad4, and for the same nuclear purpose. If they win, atrophy city and your muscles get smaller (and turn fibrotic...a kind of nasty scar tissue).

Knowing this, we incorporated several ingredients that target, and inhibit, Smad2/3 - another angle at blocking myostatin. The most potent of these ingredients (there are several that serve multiple purposes) is a citrus flavonoid called Naringenin. It is very good at blocking Smad3 (the more crucial of these). Blocking Smad2/3, but mostly Smad3, in addition to short circuiting myostatin, eliminates the competition for Smad4, thus amplifying BMP 2 and 7 signals for greater hypertrophy.

At the tail end we have an orphan - Smad7. Smad7 is a powerhouse blocker of the atrophic pathways, including but not limited to myostatin. In addition, activation of Smad7 enhances something called MyoD, another key player in muscle hypertrophy by triggering stem cell differentiation into new muscle cells and fibers. Activation of MyoD, interestingly in turn, activates Smad7 which activates MyoD, turning your body into a hypertrophic machine!

Researchers also found that reduced Smad7 signals caused muscle weakness (reduced force generation), loss of muscle size, and a switch away from glycolytic type 2 (badass) towards type1 oxidative (think marathon runner) muscle fibers.

Smad7 is also extremely efficient at keeping ligaments, tendons, and other connective tissues (including fascia) strong yet pliable. If you've ever had your tendons bugging you then you know how detrimental it can be to maximum effort sets. So by activating Smad7 we are breaking new and exciting ground here. I hope you're still with me.

We have a very potent Smad7 activator in Asiatic Acid. Asiatic Acid also happens to be prohibitively expensive in the pure form we need. Luckily an extremely potent extract, called TECA, is more reasonably priced and contains a high % of Asiatic Acid as well as precursors and other biologically active compounds. As a side note, the inclusion of ECGC (which in addition to activating SIRT1 and nerve growth factors) also increases activity of something called TAZ, a co-activator of MyoD, kicking our hypertrophic machine up a few gears.

Ok, let's get a bit more straightforward.

We have two enzymes that are widely expressed (active) in the entire body that, for our purposes (hypertrophy) are mostly undesirable.

The first is Protein Tyrosine Phosphatase 1B (PTP1B). This enzyme is responsible for insulin (and leptin...long story) resistance. By inhibiting this enzyme in the muscle you just worked out, insulin response (and IGF-1) is amplified and those critical nutrients drive into the muscle to supply the energy and raw material to build muscle.

Glycogen Synthase Kinase 3B (GSK3B) can be considered one of the master BRAKES on growth, severely restricting our goals. GSK3B blocks mTORc1 and triggers more catabolic processes to dominate, so by inhibiting this enzyme hypertrophy reigns Supreme. Our major players here are Luteloin and Betulinic Acid (which we expand on below). Inhibition of GSK3B also contributes to glycogen supercompensation post-workout to maximize fed state signaling, telling your body to go ahead and hit that anabolic accelerator.

Stem Cell Activation

To put it briefly, BMPs, prostaglandins, Nicotinamide (NAD+) and Salidroside/EGCG (SIRT1) all activate stem/progenitor cells for differentiation into healthy smooth muscle/endothelium. IGF-1 enhancement (Betaine/Genistein) and HDAC inhibition (Betaine) will support epigenetic reprogramming favoring hypertrophy.

Now something you might be more familiar with: SEX (hormones).

For a long time we figured that maximizing muscle growth was primarily a hormonal battle between two opponents - Estrogen and Testosterone. Turns out that's not the case at all.

A little while back it was discovered that there were, in fact, 2 dominant estrogen receptors - Estrogen Receptor Alpha (ERa) and Estrogen Receptor Beta (ERb). This is highly simplified, as ERa does contribute some anabolism but also brings undesirable effects. For simplicity let's just say that ERb has counter effects to ERa. In addition, it turns out the ERb activation is highly anabolic, spanning multiple pathways, including IGF-1, stem cell recruitment, and mTorc1 activation. So what do we do?

This is kind of cool. It turns out that the combination of Ursolic Acid and Betulinic Acid causes a depletion of ERa as well as inhibiting receptor signaling. In addition, an ingredient called Genistein has a 20x greater affinity for the ERb receptor. The result is we get the highly anabolic ERb, while greatly reducing ERa signals. Yummy.

As far as good old androgens...well, you mostly got what you got. However, as with most hormones, we can manipulate receptors. Carnitine has been shown to increase both the density and sensitivity of the Androgen Receptor. More receptors and higher sensitivity means more gains. The addition of Icariin also has somewhat of a T mimicry effect, increases receptor action, activates BMPs, and IGF-1.

Alright, let's dive into the acute response storm - the cAMP pathway.

cAMP, an essential second messenger that signals energy availability, also triggers a massive cascade that ends with 2 important states - hypertrophy and further blocking atrophy.

cAMP activates a protein kinase, PKA, which is one of the primary anabolic signals - and the machine starts revving. The race commences with cross-talk - cAMP/PKA feeds into mTOR (our old friend the King Daddy), boosts IGF-1 signaling, and amplifies the downstream protein synthesis cascade. It extends the metabolic "pump" window post-training, improving nutrient handling, satellite cell support, and regeneration so your fibers rebuild bigger, not just repaired.

"But EvoMuse", you say, "you also mentioned blocking atrophy." Why yes. Yes I did. You see, elevated cAMP shuts down the essential pathways that activate 2 of the other bad guys stealing your gains - Atrogin-1 and MuRF1. These two bastards are highly potent muscle eaters. By blocking their upstream activation, we essentially block them.

We also revisit our loathsome enemy - myostatin. In conjunction with Epicatechin, cAMP elevation increases expression of follistatin - which suppresses myostatin by binding it and preventing it from becoming active. This, again, amplifies our BMP/Smad7 hypertrophic system. Good stuff.

So how do we boost cAMP in our working muscle? Forskolin! Forskolin is a badass addition to our formula with its ability to dramatically increase cAMP levels, especially localized to our working muscle.

That sounds amazing, Evomuse, but how can you even think you can reach muscles with a topical formula? Well, hold onto your lifting belt and listen to this.

All of our active ingredients have different physiochemical properties. Some are perfect for skin application, but tend to be grabbed quickly and absorbed systemically (which is pretty much worthless for our goals). Some tend to barely absorb at all. So what did I do?

Remember our Phosphatidic Acid Goliath? Well, as a phospholipid we are able to use it to form phytosomes (actually ethosomes, since we will retain some of the alcohol in the carrier). These are small vesicles that, incredibly, can complex with pretty much all of our actives, enabling rapid absorption through the skin layers, past the deeper layers and subcutaneous fat, and right into our target muscles. We not only get the massive benefit of the mTORC1 activation by the PA, but we've now increased the effectiveness of the entire formula array to do exactly what we want - enhance hypertrophy wherever we apply it pre-workout. Another benefit? The PA "envelope" protects the skin surface from the irritating effects of Capsaicin and Methyl Nicotinate (burning, itchiness, redness, gangrene...ok, made that last one up), so we can benefit from prostaglandin/IGF-1/vasodilation even more while still having an enjoyable experience. Note - you're still going to want to wash your hands after applying and not rub your eyes or junk.

As if that isn't enough (again, it never is...is it?), I spent a ridiculous amount of time and energy developing a special hybrid hydrogel, which contains special components which also accelerate local absorption onto the muscle while totally minimizing systemic spillover.

Once in a while frustration boils over, and you find yourself impatient for the most rapid growth. There's something to be said about a targeted approach over pills that deliver ingredients systemically, rather than right where and when you need them. TopMuscle is a quick fuse that you apply before workout that is timed to explode when you need it - right at peak intensity.

This is something you will feel. Something you will see. Something that will bring you what crave. A cutting edge formula that brings gains for the pain.

Muscle your way to the Top.