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BMP | Body Modify: Phenotype
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"Nature...uh...finds a way." ~ Ian Malcolm
Dinosaurs. Massive eating machines. Strong. Savage. And Extinct.
Though we still don't know exactly what happened, generally we can zero in on a major factor. When you are a huge, muscled beast you require a LOT of resources just to maintain, not to mention grow. Remove or reduce the resources and suddenly that gigantic physique becomes a liability.
And what survived? What came to dominate next? Initially it was the scurrying, furry little mammals. Small, quick, and able to maintain on very little. Though again they started to trend massive, culminating with mammoths, giant cave bears, huge prehistoric rhinos, and saber-toothed cats - they eventually also disappeared.
By my speculation, Nature is pretty badass at controlling for efficiency, and has developed biological mechanisms to both grow and restrict that growth. The bigger you are, the more resources you consume - so let's put a governing mechanism on how big you can get.
In humans, and other mammals, we have multiple pathways to trigger growth. As well, we have multiple pathways to restrict, and even reverse, that same growth. Think of it like a biological Overton Window.
Quite a while back I was walking through downtown Columbus and watching the erection of some tallish buildings, the hardened steel structure resembling a skeleton - everything else built upon that. It got me thinking about the human body. Bone, once thought to be nothing but a stiff dead mineral structure, began to reveal itself as a dynamic organ system, sending and receiving signals from the environment and changing accordingly. Endocrine signals coming and going, making sure our bodies were dialed in to efficient survival. That is where my research began, and what I eventually found confirmed I was in the right place.
The TGF-b1 superfamily of signaling molecules expands as Transforming Growth Factor, and that is what most of this class does – Transforms. Stem cells or satellite cells into fully differentiated cells like Muscle, Bone and Adipose. Then can also transform into destructive type cells like osteoclasts, which leech calcium from bones and dump it into the bloodstream.
As well, Myostatin and the Activins function to limit, and sometimes reverse, tissue growth – reverting our beloved anabolism into catabolism. In some tissues, like the heart, this is essential to maintaining health by making sure the heart doesn’t enlarge, but it certainly does frustrate our desire to be muscular beasts.
BMP, for the sake of our new groundbreaking formula, stands for Body Modify: Phenotype.
For the sake of the physiology it happens to be targeting, it stands for Bone Morphogenetic Protein. Thought initially to simply affect bone turnover, within the last 15 years or so it has been traced to be one of the major master control pathways that control other things - like muscle mass and joint health. There are quite a few BMPs, some of which we still know very little about, but for our updated formula you should be familiar with the 3 types.
BMP 2, 4, and 7
BMP2 plays a major role in bone and cartilage formation, as well as osteoblast differentiation. Differentiation is an important point here, as will be discussed below. BMP2 is the secondary, but no less important, target of this formula, with BMP7 being the primary target.
BMP4, while still important, is comparatively our lowest priority of the three for targeting muscle growth. Like the other BMPs it is involved in bone and cartilage development, although more specifically for teeth and limbs, as well as being a key player during embryonic development.
BMP7 is our priority target for muscle growth. It is a major player in osteoblast differentiation as well as the induction of SMAD 1/5/8 (see below).
Now, going back to MyoStatin since it is most familiar to most of you (you’ve all seen the bulls and dogs with the deleted Myostatin gene and how huge and muscular they are), we also throw in Activins and Atrogin-1, the primary catabolic signals. These signals all seem to converge on SMADs.
SMADs are the molecules that actually communicate the signals deep into the nucleus to trigger our desireable (and undesireable) effects. SMAD 1/5/8, activated by BMP 2, 4, and 7, meet up with SMAD4, which is an escort molecule, to travel to the nucleus. Myostatin, and other catabolic proteins, activate SMAD2/3 which ALSO require SMAD4, and thereby compete with SMAD 1/5/8 for dominance. While the SMADs activated by BMP 2, 4, and 7 usually dominate, the nature of the competition (and partiular environment – like starvation and sleep) can sometimes give the checkered flag to SMAD2/3.
So what we have so far:
•BMP signaling is the fundamental signal for hypertrophy
•Inhibiting BMP signaling causes atrophy, abolishes Myostatin deficient mice from gaining the enormous amount of muscle they normally do, and increases the negative effect from fasting
•BMP plays a critical role in adult muscle growth
Before getting into the meat of the product, let’s do 2 things. Cover SMAD7 quickly, and do a summary.
SMAD7 used to be thought of as a suppressive SMAD, and some studies still indicate functionality there – but it appears to both suppress MyoStatin as well as undesirable inflammatory cytokines. But SMAD7 is also becoming one of the main inducers of new muscle cell differentiation (cellular division of muscle cells rather than drawing from stem cells). This elusive process is highly sought after in terms of muscle strength and size. So what are we doing here with BMP, as a product?
We are increasing expression of BMP 2/4/7 to trigger stem cell differentiation into new bone, connective tissue, and muscle, denying (closing off) their differentiation into destructive cell types or even plain old ugly adipose.
We are increasing expression of SMAD7 to cause muscle cell division and differentiation, making the muscles bigger and stronger.
We are suppressing SMAD2/3 (basically short circuiting Myostatin and Activins at their final step) thus not only blocking catabolism, but enhancing the availability of SMAD4 to complex with SMAD 1/5/8 to amplify the effects. This is the major upgrade to this version.
Let’s get to those ingredients, if you’re still awake.
Kaempferol is a flavanol found in a variety of plants. The Hydroxypropyl-Beta-Cyclodextrin has been added to increase bioavailability due to poor water solubility. In the past Kaempferol has been shown to increase cellular energy expenditure and enhance thyroid function which has landed it a spot in several fat burning formulas, however it has been included in this formula for an entirely different reason.
Kaempferol appears to have quite a strong effect on bone anabolism, and has been called a “promising agent for the prevention or treatment of bone loss”. A 2013 in vitro study demonstrated that Kaempferol enhanced the expression of chondrogenic marker genes, and greatly increased expression of BMP2. In addition to increasing BMP2, it has also been shown to increase the number of BMP2 receptors in animals. More BMP and more places to dock, that’s a solid combo.
Kaempferol also potently activates our BMP7, leading to increased muscle (an important addition here is prevention of fibrosis). Fibrosis (think scar tissue) is the process of converting healthy, functioning tissue into slabs of dysfunctional useless tissue. This is particularly insidious in organs like the kidneys, and in the spongy tissue of the penis, causing major (and previously thought to be permanent) erectile dysfunction.
This was a controversial addition to the last version that had people asking questions. A component of seeds, nuts, and grains, PA can interfere with the absorption of some minerals. However, it has an astounding absorption boosting property for Kaempferol (and Quercetin...see below) and was well worth the inclusion.
Salidroside is an extremely interesting glucoside found in Rhodiola Rosea, which boasts numerous studies demonstrating a wide range of health benefits. Two very recent studies looked at the effect of Salidroside on bone anabolism. In the first study, they found that Salidroside increased the mRNA level of genes controlling the BMP pathway. It elevated BMP2 and BMP7 as well as SMAD 1/5/8 (SMAD 6/7 are the inhibitory ones we don’t want to activate).
The second study, carried out by different researchers, confirmed the increased phosphorylation and expression of SMAD 1/5/8. Then to be sure this was mediated by BMP, they added in a BMP antagonist to block the signaling pathway. As suspected, this attenuated the effect, demonstrating that BMP was indeed the target of Salidroside.
For the new BMP formula, you might have noticed that we slightly reduced the dosage of Salidroside over the old version, finding that we can still get the same benefit with a lower dose and therefore allowing the addition of new ingredients while still making the formula just as cost-effective for the user.
Found in Cnidium monnieri and a few other plants, Osthole is classified as a coumarin. It has been used in supplement form for liver health, cognitive enhancement and vasodilation. Research shows it can activate AMPK and ACC, regulate blood glucose and GLUT4 activity, and decrease liver fat. One study even demonstrated that in mice a high dose of Osthole had an androgenic effect and boosted LH and testosterone levels.
All these things are nice, but what about BMP? Fear not, Osthole has been shown to activate Wnt/beta-catenin signaling, increase BMP2 expression, and stimulate mesenchymal stem cells differentiation (MSC) to osteoblasts. Early phase differentiation involves BMP2, SMAD 1/5/8, RUNX2, and p38, whereas later phase differentiation involves ERK 1/2. Osthole has been shown to enhance both phases, it sticks around until the job is done.
Ligusticum Wallichii Extract (98% ligustrazine)
Isolated from the fermented food Natto, LWE is an interesting compound with well-known anti-inflammatory and nootropic properties. More importantly, however, LWE has recently been shown to significantly elevate BMP7. LWE also favorably works the anabolic bone and muscle signaling pathway by activating something called the SERCA pump, which brings extracellular calcium back into the cell so it can be reused.
To determine the anabolic and/or anti-catabolic ability of a compound, scientists will often use methods such as denervation (cutting off or inhibiting nerve supply to a muscle), or suspension of a muscle (making it weightless). These methods basically make the brain forget these muscles exist, so they tend to atrophy quite rapidly. In multiple studies, when comparing Ligustrazine supplementation to control groups, in which both groups had been subjected to either denervation or muscle suspension, the Ligustrazine groups lost significantly less muscle over controls, both short term (one week) and longer term (one month).
Ligustrazine has also been shown to selectively increase glucose uptake in muscle cells, protect against oxidative damage from high fat and high glucose, block vasoconstriction, and even upregulate mitochondrial biogenesis.
Ligustrazine has also been found, recently, to preserve intervertebral disc integrity and prevent breakdown.
Paeoniflorin is a compound isolated from any number of herbs. Working through multiple mechanisms, Paeoniflorin has a direct stimulatory effect on bone formation signaling. The current research on this compound has looked mainly at the potential beneficial effects in certain bone related disease states, which we can use to make some reasonable assumptions in how it might behave in healthy individuals. Renal fibrosis involves the accumulation of excess fibrous material in the extracellular matrix of kidney cells.
Renal (kidney) fibrosis is the principal process underlying the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD). In this condition, BMP7 expression and SMAD activation tends to become quite disrupted, and Paeoniflorin has been shown to normalize this signaling. This could very well translate to increased BMP7 expression in healthy individuals.
In Rheumatoid Arthritis (RA), the body attacks the joints through an inflammatory cascade, causing pain, joint swelling, bone erosion and cartilage breakdown. Paeoniflorin supplementation has been shown to reverse or severely diminish all of these problems, largely through controlling the inflammatory factors prostaglandin E2, leukotriene B4, ROS, and cytokines IL-1B and TNF-a.
Again with regard to disease state models, we have some data regarding the effect of Paeoniflorin on periodontitis, which is an inflammatory condition that causes shrinking of the gums and bone loss in the teeth. In periodontic subjects supplementing with Paeoniflorin, alveolar bone loss and soft tissue destruction were significantly prevented and the compound exhibited anti-inflammatory and immunoregulatory effects.
Finally, as a bonus point, we’ve got a cool interaction with Heat Shock Proteins (HSPs). When the body undergoes heat stress (like during exercise), the muscle cells have to control potential damage with HSPs. Often referred to as intracellular “chaperones”, they’re basically molecules that act as a clean up crew to facilitate protein transport, prevent mishaps during protein folding, and protect against protein denaturation. They have also been shown to improve insulin sensitivity, reduce oxidative stress, inhibit inflammatory pathways and enhance the metabolic characteristics of muscle cells.
Anything that increases specific HSPs will likely speed up recovery and hypertrophy, and as you may have guessed by now, Paeoniflorin does just that. Scientists looked at the effect of Glycyrrhizin (the active component of licorice) and Paeoniflorin on HSPs. They found that Paeoniflorin was able to induce HSP expression and also enhance the function of the elevated HSPs, whereas Glycyrrhizin was only able to enhance their function.
Hwanggeumchal Sorghum Extract
Another Superstar of the formula, Sorghum refers to a genus of grasses, typically used in livestock feed. As you can probably assume by now, we didn’t just throw some grass clippings in this advanced formula. We have found a very specific extract of Sorghum that boasts some cool properties. HSE works, for our purposes, in a unique way that should synergize with the other ingredients in the formula.
In addition to being an incredibly powerful BMP7 inducer, it also amplifies the GH/IGF-1 pathway (mo’ muscle, mo’ muscle).
Growth Hormone (GH) is a well-known regulator of bone growth. When GH is elevated, it triggers something called the Jak/STAT pathway, which regulates IGF-1, a major player in bone and muscle growth. HSE has been shown to act almost exactly like GH in activating this Jak/STAT pathway, which then increases the expression of GH related proteins, (one of which, STAT5b, triggers BMP7), the GH receptor itself, IGF-1, the IGF-1 receptor, and BMP7. The science nerds might have noticed something particularly intriguing about that. When we trigger more BMP7, we trigger more MSC differentiation towards osteoblasts, giving the (now also elevated by HSE) anabolic IGF-1 more beneficial places to exert its effects.
And for the bonus round, HSE has been shown to reduce plasma total cholesterol and triglycerides when given to obese rats on a high fat diet.
HC (I am NOT typing that over and over) is a flowering plant from China, studied for its positive effects on kidney fibrosis. As analyses progressed, it was found to be an extremely potent inducer of BMP7. As a side bonus, it was also found to increase expression of Adiponectin, which is released by adipocytes to help regulate insulin sensitivity, glucose levels, and control inflammatory cytokines.
Quercetin is a very common and useful component of most edible plants. It also turns out to not just increase expression of BMP2, but enhance BMP signaling overall. It also works as an extremely potent escort molecule to get zinc into cells.
Boron is added to the formula to enhance BMP2 expression, as well as reducing the urinary excretion of calcium and magnesium.
Now that we’ve traveled through our BMP 2/4/7 ingredients (to activate SMAD 1/5/8) to trigger anabolism and muscle cell division/differentiation, as well as stronger bones and joints, let's get to the juicy new additions. While finishing the research on the new MyoSynergy formula (coming soon) it occurred to me that, since Myostatin and the other catabolic signaling proteins converge and cause activation of SMAD2/3 (again, not only very undesirable but competing for SMAD4 escort into the nucleus), we might as well pull the specialized ingredients over to BMP and make it unbeatable for effectiveness. So let’s hit it…
We are going to include the first two sort of together, since that is how they were most studied.
Astragalus Membranaceus-HPBCD Complex
I have been using Astragalus in my formulas (see earlier version of MyoSynergy) for a while, and it has since become a popular ingredient. I always have, and likely always will, use a custom extraction to better be able to control the concentrated compounds. We are using a 50:1 ethanol extract to maximize potency.
AM (combined with SM, see below) has an incredibly potent inhibitory effect on not only SMAD2/3 phosphorylation, but seems to cripple their ability to complex with SMAD4.
If you’ve been following my work for a while, you will recognize this way back in the first version of DCP. In addition to the inhibition of SMAD2/3, SM also acts as a potent DGAT inhibitor. The fatty acids stored in fat cells is in the form of Tri(acyl)Glycerides, which means 3 acyl esters attached to a glycerol backbone. This is the only way they are stored. DGAT (Diacylglycerol Acyl Transferase) pushed that third acyl group onto diglycerides allowing them to be restored. By blocking DGAT, we cause the fatty acids to remain in circulation longer, allowing extra time for them to be burned as fuel. Side bonus there.
There are 2 main components to SM we are looking for, and luckily they have the same solubilities – which means we can use the same solvent to extract them – Tanshinones and Salvianolic acid.
Extracted from Olive Leaves, I'm beginning to suspect that Oleuropein is one of the key players (along with Anthocyanins/Cyanidins) in the health effects seen from the Mediterranean Diet. Oleuropein has a very, very potent effect inhibiting SMAD2 (the more potent of the two, between 2 and 3).
It, along with the other two also inhibit something called PAI-1. This gets messy, so be patient. Blood clotting is a complicated process, that is usually tightly controlled with multiple, redundant pathways – one being Plasminogen. Plasminogen helps to break up clots quickly, but also triggers release of PAI-1 (Plasminogen Activated Inhibitor) to make sure clotting doesn’t get out of hand. Now, several pathological states that I prefer not to cover for...reasons...can cause a hyperactivation of PAI-1, resulting in extreme and uncontrolled clotting by oversuppression of Plasminogen. Oleuropein acts as a PAI-1 inhibitor (yes, it inhibits an inhibitor), normalizing clotting functions.
Sinomenine is an alkaloid extracted from certain vines. It is also getting more expensive and harder to source.
Sinomenine acts as a very potent substrate for the P-Glycoprotein efflux pump – one of the active hurdles to ingredient absorption. As ingredients try to enter the bloodstream, the P-gp pump dumps them back in to the gut for elimination. What a waste. By acting as substrate, it keeps the P-gp pump busy while the rest of the formula freely enters circulation.
Interestingly, Sinomenine has also been found to alleviate peripheral diabetic neuropathy, CNS disorders, and some pain (oddly enough, when combined with Ligustrazine it is extremely effective at blunting acute, non-inflammatory pain).
Things to Avoid/Monitor When Taking BMP
•Synthetic Vitamin E
The synthetic form of Vitamin E (dl-alpha-tocopherol) lowers gamma tocopherol, which potentially interferes with anabolic bone signaling. If you are taking Vitamin E for a medical reason, please consult with your doctor before cessation.
Nicotine has been shown to interfere with bone formation. The addition of mixed tocopherols to the BMP formula could help counteract this, but it would still be a good idea to limit use of nicotine while using this product to prevent negative interactions with the BMP signaling cascade.
Things to stack with BMP.
While certainly not necessary, these should provide a synergistic effect:
•Any anabolic/androgenic steroid or prohormone that you’re currently taking
So here we are. In conclusion, my BMP research was inspired by a passing thought, a flash of inspiration, and has become a labor of love, yielding an absolute powerhouse of a product. All natural, Hormone-Free, safe for women and natties, this new iteration of BMP is easily the most potent natural product for building muscle, bone, and strong joints available in supplement form.
While nature wants to limit us within starkly defined physical parameters, a special breed of man (and woman) exists to break out of those limitations and become BEAST.
EvoMuse: Inspire to Evolve.
BMP > Body Modify: Phenotype
Bone and Muscle Growth Stimulator
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