Slintensity by EvoMuse

Slintensity by EvoMuse

Be an Apex Predator. What is an Apex Predator? They are Lean, fully muscled, and powerful. So beyond the obvious of genetics and species, how does an apex predator like a tiger build, maintain, and even increase his muscle and power?

One of the main secrets is what happens when the hunt is successful. The Feast.

Hunting, at least from an animal perspective, is one of the most demanding things you can engage in. Since nature didn’t see fit to equip a tiger with a bright orange vest and scoped .30-06, it uses what it DOES have. Stealth and powerful muscle.

When a kill occurs, the tiger is driven uncontrollably to gorge on flesh and blood until it is satiated. That feast not only triggers its body to rebuild the muscle that was damaged during the hunt, but to build even more. To give it a boost up to the next level of an efficient killing machine. Nature rewards success.

But alas, we are too successful for our own good, sometimes. A trip to the fridge or the drive-thru is hardly a triumph of raw primitive instinct. Look around you and you will see what happens to those that gorge without putting in the work. But we? We are a different breed. We who battle gravity and sloth. We who suffer and scream our barbaric yawp surrounded by spandex (hey...HEY...don’t get distracted) and iron, and who do so willingly because we understand the Machina of our bodies.

But the analogy works, somewhat. While we aren’t pure carnivores, so pathways are different from a tiger – utilizing these things called Carbs as well as the pure-bloody proteins (unless you eat chicken, then cook that sh*t all the way) – to trigger adaptation, repair, and most importantly GROWTH.

POWER!!! UNLIMITED POWER!!!

CLEVER PATHWAY SUMMARY

Ingredients:

Berberine:Nicotinamide Cocrystals

As mentioned at the beginning, the Tiger analogy breaks down a bit, since we are not pure carnivores. We bring a significant number of carbs into the game – or at least you should be if you’re trying to maximize growth. Carbs tie in to insulin which, I’m sure you’ve heard, is an extremely anabolic hormone. But insulin is also something to be feared, as shuttling nutrients into our muscle also comes with the caveat of your hungry, hungry hippo...err, fat cells trying to greedily suck up nutrients as well. Here we use an inducible receptor – which means it isn’t bound to the membrane necessarily but must be signaled to emerge from deep inside the cell out to the membrane to interact with, mostly, glucose. This receptor is called a GLUT4 receptor (side note, we will touch briefly on the GLUT1 receptor, also a glucose transporter, but we know a bit less about it)

GLUT4 – Berberine causes dramatic increases in expression of the GLUT4 transporter, and the effects seem to be dominant in muscle cells rather than fat cells.

Berberine inhibition of HPA axis, IR, fasting glucose. AMPk activation, increase GLUT4 muscle, Lower total cholesterol and LDL, increase HDL

By increasing GLUT4 activity in muscle cells, especially when timed after some glycogen depletion and a hearty carb intake post workout, we can stuff dem dere muscle cells right back up to full, creating an environment ripe for muscle growth. Remember, when the body is given ample nutrients, it interprets this as you are evolutionarily successful, and will be rewarded with “access” to more resources (muscle, strength, stamina...and downstream from that – better choice of mates.

Berberine sounds amazing! Why not just load up? Well, grasshopper, berberine has some drawbacks. For one, it has absolutely dismal oral absorption. And if you try to make up for that by taking more, well make sure you stay close to a bathroom. Intestinal irritation comes with high doses. Instead what I have done is dialed in a Berberine-Nicotinamide (more in a second) Cocrystal. Recall that cocrystals can be formed by dissolving 2 or more compounds in a commonly effective solvent, applying some initial heat, and then allowing the solvent to evaporate. As the fluid volume decreases, our compounds are forced together where physics does its thing – and they form a crystalline lattice, which changes the physical properties such as solubility and absorption. In this case, the crystals are beautiful and very effective.
Berberine has also been shown to inhibit the Devil Incarnate of bodybuilding….MYOSTATIN (boo, boo, hiss). It also inhibits expression of SMAD 2/3. See the BMP writeup, but SMAD 2/3 are the bad ones for muscle building. Using Slintensity in conjunction with BMP will amplify the effects. Yes way. 

Berberine also has the unfortunate property of increasing expression of Atrogin-1, a highly catabolic/atrophic pathway. So while you are waiting like Christmas Eve for Santa to bring you muscle, Krampus shows up to undo it. So what did I do about that? Good question:

Puerarin

Puerarin comes from a few plants, but luckily for your wallet it can be easily extracted from Kudzu. Anyone who has spent time in the South knows that Kudzu is an incredibly hearty INVASIVE species that grows insanely long and as yet has been laughing off attempts to control it. So come on, the more Slintensity you buy the more Kudzu we can eliminate. Do the right thing!
Anyway, Puerarin has a wonderful property here, namely inhibiting expression of Atrogin-1.

Please hold your applause until the end because it doesn’t end there. Puerarin also enhances GLUT4 translocation, increases PPAR-a expression and, to a lesser extent PPAR-gamma while also suppressing gluconeogenesis in the liver while also at the same time increasing fatty acid oxidation, and triggering mitochondrial biogenesis. Puerarin also inhibits PTP-1b (see the Epitome writeup) leading to enhanced insulin sensitivity and vascular restoration. Finally, additive to the Berberine, Puerarin inhibits the anti-anabolic SMAD2 pathway, while increasing several ROS scavenging pathways.

Nicotinamide

The coformer for the Berberine cocrystals is Nicotinamide, a form of Niacin.
There is conflicting data with regards to Nicotinamide (and its metabolized form, Nicotinamide Mononucleotide) on insulin sensitivity and mitochondrial adaptation to exercise, with some studies showing benefit while others show impediment. However, as precursors to NAD+ the overall effect does appear to be positive as well as showing decent activation of the sirtuin pathways, especially SIRT1.

FMOC-L-Leucine

FMOC-L-Leucine is a very unique amino acid derivative. As a partial PPAR-gamma agonist, it does wonders for insulin sensitivity, while at the same time only weakly contributing to adipogenesis. This makes it far superior to other full PPAR-g agonists for keeping your muscle cells highly responsive to insulin.

4OH-Isoleucine

4OH is a really cool compound that I have been a fan of for 20 years. By potentiating insulin release per unit of glucose, 4OH allows for a bigger insulin spike, which speeds up the process of nutrient entry, before allowing insulin levels to fall back to baseline. Basically like hitting the nitrous for a quick burst, then shutting it down before engine damage occurs. In our approach to this new product, the Glucose Disposal angle needs to be hard and fast – contributing its part in mTORc1 activation- then backing off to watch from the sidelines as Muscle Protein Synthesis goes wild. More of a tactical nuke.

TGR-5/Corosolic Acid

Corosolic Acid? From Banaba? YAWN...I thought you were innovative. Well, hang on. In the previous version of Slintensity, we first addressed the role of the TGR5 Bile Acid receptor using Obacunone. Obacunone was co-extracted with Berberine from the Phellodendron Cortex plant. Unfortunately, as I moved on with my experiments using purified Berberine cocrystals, my engineers were unable to separate the two, which means Obacunone was no longer an option. Having moved through several other compounds, each with steep absorption problems and an even steeper price tag, I wound up finding an obscure study comparing TGR5 activators. The most potent in the study was none other than Corosolic Acid. But, at much higher dosage than was being used. This took a ton of work to get made, and still isn’t cheap, but fortunately CA has excellent absorption.

TGR5 – let's revisit our Tiger Analogy. Remember, without receptors and other sensors the body is blind and stupid. Nutrient sensors in particular signal to the body WHAT and HOW MUCH you are eating. There are carb and protein sensors, but what macronutrient is left behind? Yep….fat. One of the ways the body is able to digest fat is using bile acids. What does that have to do with our Tiger you might ask? Well, when a successful kill is made our tiger begins his feast – and it ain’t frosted flakes he’s eating. Flesh, blood, muscle – protein, and quite a bit of fat. Nature in it’s brilliance uses a TGR5 receptor to detect the bile response to fatty acid intake, and with a strong enough signal, indicating a successful hunt, again Nature LOVES a winner. More resources, in this case again MUSCLE. The TGR5 receptor activation, especially when combined with or after strenuous exercise, triggers not only muscle protein synthesis leading to muscle hypertrophy, but actually causes new muscle cells to differentiate. This increases not only current size and strength, but increases the pool of muscle cells that we can grow.

Remember - There is no such thing as too strong. Strength can be tempered with gentleness and controlled with restraint.
Thus there is only too weak. Strength lies in reserve and can be called upon when needed. Weakness will fail you every time. m.p.
Beyond fatty acid intake sensing, the body contains TGR5 receptors in both muscle and brown fat. Activation causes an increase in thermogenic energy expenditure, as well as increasing the activity of type 2 deiodinase (converting T4 to T3 and subsequently enhancing thyroid mediated energy expenditure), enhancing a leaning effect. TGR5 activation in enterocytes causes substantial release of GLP-1 (Glucagon-like Peptide 1), and systemwide increases the full body ratio of ATP/ADP, and also influences both mitochondrial efficiency and biogenesis. Finally, TGR5 activation helps to purge the liver of fatty deposits and improves both function and regeneration. And, as the coup de grace, I mentioned glycogen synthesis in muscle. TGR5 activation enhances Akt phosphorylation, thus reversing insulin resistance in muscle and enhancing glycogen synthesis. 

So, corosolic acid. We needed a target range of 40-50mg for ideal activation of TGR5. Since the most common CA Banaba extract is 1%, there was no way to make it viable. That is why I contracted a %.
To wrap it up, the combination of post-workout protein and carbohydrate ingestion (the omnivore version of a post-kill feast) creates a highly anabolic environment with little to no drawback. By keeping muscle cells highly sensitized to insulin signaling, we can take advantage of that metabolic flux and replenish any glycogen used to fuel our workouts. Ingesting excess fat during this window has drawbacks, including slowing down absorption of those carbs and blunting the response, so by using purified Corosolic Acid as a TGR5 agonist, we enter a new realm where hyper response to nutrients can cause dramatic muscle gain.

Sources: 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731988/

https://diabetesjournals.org/diabetes/article/55/8/2256/12348/Berberine-a-Natural-Plant-Product-Activates-AMP

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695611/

https://pubmed.ncbi.nlm.nih.gov/33249280/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8764238/

https://www.sciencedirect.com/science/article/abs/pii/S0026049519301362