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.<\/p>\r\n
BMP4<\/p>\r\n
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.<\/p>\r\n
BMP7
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).<\/p>\r\n
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.<\/p>\r\n
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.<\/p>\r\n
So what we have so far:<\/p>\r\n
•BMP signaling is the fundamental signal for hypertrophy<\/p>\r\n
•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<\/p>\r\n
•BMP plays a critical role in adult muscle growth<\/p>\r\n
Before getting into the meat of the product, let’s do 2 things. Cover SMAD7 quickly, and do a summary.<\/p>\r\n
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?<\/p>\r\n
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.<\/p>\r\n
We are increasing expression of SMAD7 to cause muscle cell division and differentiation, making the muscles bigger and stronger.<\/p>\r\n
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.<\/p>\r\n
Let’s get to those ingredients, if you’re still awake.<\/p>\r\n
Kaempferol Cyclodextrin<\/p>\r\n
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.<\/p>\r\n
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.<\/p>\r\n
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.<\/p>\r\n
https:\/\/pubmed.ncbi.nlm.nih.gov\/32115512<\/p>\r\n
Phytic Acid<\/p>\r\n
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.<\/p>\r\n
Salidroside<\/p>\r\n
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).<\/p>\r\n
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.<\/p>\r\n
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.<\/p>\r\n
Osthole Cyclodextrin<\/p>\r\n
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.<\/p>\r\n
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.<\/p>\r\n
Ligusticum Wallichii Extract (98% ligustrazine)<\/p>\r\n
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.<\/p>\r\n
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).<\/p>\r\n
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.<\/p>\r\n
Ligustrazine has also been found, recently, to preserve intervertebral disc integrity and prevent breakdown.<\/p>\r\n
https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S1529943013014630<\/p>\r\n
Paeoniflorin<\/p>\r\n
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.<\/p>\r\n
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.<\/p>\r\n
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.<\/p>\r\n
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.<\/p>\r\n
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.<\/p>\r\n
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.<\/p>\r\n
Hwanggeumchal Sorghum Extract<\/p>\r\n
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.<\/p>\r\n
In addition to being an incredibly powerful BMP7 inducer, it also amplifies the GH\/IGF-1 pathway (mo’ muscle, mo’ muscle).<\/p>\r\n
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.<\/p>\r\n
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.<\/p>\r\n
Houttuynia Cordata<\/p>\r\n
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.<\/p>\r\n
https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0254627212600326<\/p>\r\n
Quercetin Dihydrate<\/p>\r\n
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.<\/p>\r\n
https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5875037<\/p>\r\n
Boron Citrate<\/p>\r\n
Boron is added to the formula to enhance BMP2 expression, as well as reducing the urinary excretion of calcium and magnesium.<\/p>\r\n
https:\/\/pubmed.ncbi.nlm.nih.gov\/32676937<\/p>\r\n
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…<\/p>\r\n
We are going to include the first two sort of together, since that is how they were most studied.<\/p>\r\n
Astragalus Membranaceus-HPBCD Complex<\/p>\r\n
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.<\/p>\r\n
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.<\/p>\r\n
https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S0378874108002110<\/p>\r\n
https:\/\/onlinelibrary.wiley.com\/doi\/abs\/10.1111\/jgh.12490<\/p>\r\n
Salvia Miltiorrhiza<\/p>\r\n
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.<\/p>\r\n
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.<\/p>\r\n
Oleuropein<\/p>\r\n
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).<\/p>\r\n
https:\/\/www.mdpi.com\/2076-3921\/12\/6\/1140\/<\/p>\r\n
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.<\/p>\r\n
https:\/\/link.springer.com\/article\/10.1007\/s10549-020-06054-x\/<\/p>\r\n
Sinomenine<\/p>\r\n
Sinomenine is an alkaloid extracted from certain vines. It is also getting more expensive and harder to source.<\/p>\r\n
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.<\/p>\r\n
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).<\/p>\r\n
https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7900506\/<\/p>\r\n
Things to Avoid\/Monitor When Taking BMP<\/p>\r\n
•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.<\/p>\r\n
•Nicotine
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.<\/p>\r\n
Things to stack with BMP.<\/p>\r\n
While certainly not necessary, these should provide a synergistic effect:<\/p>\r\n
•MyoSynergy Elite
•X-Factor
•Any anabolic\/androgenic steroid or prohormone that you’re currently taking<\/p>\r\n
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.<\/p>\r\n
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.<\/p>\r\n
EvoMuse: Inspire to Evolve.<\/p>\r\n
BMP > Body Modify: Phenotype<\/strong><\/span> BMP 2023 | Body Modify: Phenotype<\/p> \r\n \"Nature...uh...finds a way.\" ~ Ian Malcolm<\/p>\r\n Dinosaurs. Massive eating machines. Strong. Savage. And Extinct.<\/p>\r\n 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.<\/p>\r\n 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.<\/p>\r\n 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.<\/p>\r\n 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.<\/p>\r\n 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.<\/p>\r\n BMP\/TGF-b1\/SMAD<\/p>\r\n 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.<\/p>\r\n 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.<\/p>\r\n BMP<\/p>\r\n BMP, for the sake of our new groundbreaking formula, stands for Body Modify: Phenotype.<\/p>\r\n 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.<\/p>\r\n BMP 2, 4, and 7<\/p>\r\n BMP2 BMP4<\/p> \r\n 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.<\/p>\r\n BMP7 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.<\/p>\r\n 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.<\/p>\r\n So what we have so far:<\/p>\r\n •BMP signaling is the fundamental signal for hypertrophy<\/p>\r\n •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<\/p>\r\n •BMP plays a critical role in adult muscle growth<\/p>\r\n Before getting into the meat of the product, let’s do 2 things. Cover SMAD7 quickly, and do a summary.<\/p>\r\n 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?<\/p>\r\n 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.<\/p>\r\n We are increasing expression of SMAD7 to cause muscle cell division and differentiation, making the muscles bigger and stronger.<\/p>\r\n 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.<\/p>\r\n Let’s get to those ingredients, if you’re still awake.<\/p>\r\n Kaempferol Cyclodextrin<\/p>\r\n 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.<\/p>\r\n 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.<\/p>\r\n 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.<\/p>\r\n https:\/\/pubmed.ncbi.nlm.nih.gov\/32115512<\/p>\r\n Phytic Acid<\/p>\r\n 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.<\/p>\r\n Salidroside<\/p>\r\n 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).<\/p>\r\n 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.<\/p>\r\n 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.<\/p>\r\n Osthole Cyclodextrin<\/p>\r\n 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.<\/p>\r\n 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.<\/p>\r\n Ligusticum Wallichii Extract (98% ligustrazine)<\/p>\r\n 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.<\/p>\r\n 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).<\/p>\r\n 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.<\/p>\r\n Ligustrazine has also been found, recently, to preserve intervertebral disc integrity and prevent breakdown.<\/p>\r\n https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S1529943013014630<\/p>\r\n Paeoniflorin<\/p>\r\n 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.<\/p>\r\n 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.<\/p>\r\n 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.<\/p>\r\n 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.<\/p>\r\n 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.<\/p>\r\n 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.<\/p>\r\n Hwanggeumchal Sorghum Extract<\/p>\r\n 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.<\/p>\r\n In addition to being an incredibly powerful BMP7 inducer, it also amplifies the GH\/IGF-1 pathway (mo’ muscle, mo’ muscle).<\/p>\r\n 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.<\/p>\r\n 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.<\/p>\r\n Houttuynia Cordata<\/p>\r\n 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.<\/p>\r\n https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0254627212600326<\/p>\r\n Quercetin Dihydrate<\/p>\r\n 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.<\/p>\r\n https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5875037<\/p>\r\n Boron Citrate<\/p>\r\n Boron is added to the formula to enhance BMP2 expression, as well as reducing the urinary excretion of calcium and magnesium.<\/p>\r\n https:\/\/pubmed.ncbi.nlm.nih.gov\/32676937<\/p>\r\n 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…<\/p>\r\n We are going to include the first two sort of together, since that is how they were most studied.<\/p>\r\n Astragalus Membranaceus-HPBCD Complex<\/p>\r\n 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.<\/p>\r\n 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.<\/p>\r\n https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S0378874108002110<\/p>\r\n https:\/\/onlinelibrary.wiley.com\/doi\/abs\/10.1111\/jgh.12490<\/p>\r\n Salvia Miltiorrhiza<\/p>\r\n 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.<\/p>\r\n 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.<\/p>\r\n Oleuropein<\/p>\r\n 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).<\/p>\r\n https:\/\/www.mdpi.com\/2076-3921\/12\/6\/1140\/<\/p>\r\n 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.<\/p>\r\n https:\/\/link.springer.com\/article\/10.1007\/s10549-020-06054-x\/<\/p>\r\n Sinomenine<\/p>\r\n Sinomenine is an alkaloid extracted from certain vines. It is also getting more expensive and harder to source.<\/p>\r\n 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.<\/p>\r\n 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).<\/p>\r\n https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7900506\/<\/p>\r\n Things to Avoid\/Monitor When Taking BMP<\/p>\r\n •Synthetic Vitamin E •Nicotine Things to stack with BMP.<\/p>\r\n While certainly not necessary, these should provide a synergistic effect:<\/p>\r\n •MyoSynergy Elite 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.<\/p>\r\n 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.<\/p>\r\n EvoMuse: Inspire to Evolve.<\/p>\r\n BMP > Body Modify: Phenotype<\/strong><\/span> BRITE | Adipocyte Conversion Formula<\/p>\r\n \"A cold, starving animal doesn't care about a 6-pack.\"<\/p>\r\n Perspective is a complex thing. From the perspective of an undisciplined modern human, life is surrounded by plenty and our worries can consist of trying to reach our most aesthetically pleasing selves. However, perspective for most of the creatures on the planet is harsh, difficult, and a never-ending quest for precious resources.<\/p>\r\n Heat is one of the most precious resources, as the universe contends with \"hot spots\" in its quest to finally attain perfect order and energy distribution – namely heat death.<\/p>\r\n Nature, on the other hand – if it can be separated from the Universe – seems obsessed with continuing bright hot spots of life, without caring about individuals. The mechanistic viewpoint of our bodies, which still reigns supreme, follows laws of thermodynamics and thus life and heat can almost be interchangeable.<\/p>\r\n As we have covered countless times, humans, in our dominant but highly artificial state, are an aberration from the general rules. Nature drives numerous animals into dormancy when resources become scarce and more energy would be spent finding calories (heat, fuel) than could be replenished. Hibernation is the name of the game for Winter. Hibernation must be prepared for, which is why hibernating animals begin gorging and getting fat during Fall. Those fat stores are our point of interest, as much of it is stored in specialized cells.<\/p>\r\n The key to thermogenesis is adrenergic signaling (meaning related to adrenaline and noradrenaline). While humans have come to rely more on B2 (and A2) signaling for active lipolysis resulting in ATP formation with increases in heat a secondary effect (to fuel activity), the animals that hibernate during cold weather rely on different receptors (B3, A1) to generate heat via thermogenesis to go along with a more passive release of adrenaline\/noradrenaline, since for the most part they aren't moving much.<\/p>\r\n Human B3 receptors have lost importance, which means the first step is to increase activity here…<\/p>\r\n …but before we do that, let's take a quick step back for all those who are new to this here do-si-do.<\/p>\r\n A full decade ago, Evolutionary Muse released a first-in-kind product designed to facilitate the browning of white fat. Aptly named BRITE™, it shares the same name as those adipocytes which are named for being BROWN-IN-WHITE cells – white adipocytes which behave like brown adipocytes. Brown adipocytes are metabolically active cells which use their fat stores to generate body heat...the life hack of all life hacks, if you will. But there was one glaring problem – modern living was all but making this phenomenon a thing of the past. No problem, we should just reject modernity and embrace tradition. Right?<\/p>\r\n Wrong.<\/p>\r\n Evolutionary Muse: Inspire to Evolve. (Translation: We take a pill for that now.)<\/p>\r\n DIFFERENCE BETWEEN WAT AND BAT<\/p>\r\n BAT works quite differently, if not opposite, to White Adipose Tissue (WAT). BAT is dense in mitochondria and considered a highly thermogenic fat cell, responsible for creating heat through a process called “non-shivering thermogenesis”. This process burns calories through a futile cycle of shuttling protons to the mitochondria to generate heat. WAT, however, is what we all think of when we hear the term “body fat”. It stores calories so they can be used later during periods of hunger or famine, and secretes various adipokines.<\/p>\r\n Even more recently, we have discovered another player in the adipocyte story – Brown-in-White cells, or “BRITE”. At a microscopic level, these cells display a color between brown and white, and behave in a similar thermogenic fashion to BAT cells. While we don’t know yet if reduced thermogenic activity is a cause or consequence of obesity, we do know that an increase in BAT and\/or brite cells improves glucose tolerance and insulin sensitivity.<\/p>\r\n Two distinct pathways exist towards increasing brite cells in adult humans, (1) triggering precursor cells into becoming brite cells, and (2) turning mature WAT cells into brite cells. We want to target these pathways directly so that we can increase the ratio of brite cells to WAT cells, allowing your body to constantly burn more calories. So, let’s dive into some of the known methods of brite cell creation and activation.<\/p>\r\n COLD THERAPY, B3 ADRENERGIC ACTIVATORS<\/p>\r\n Cold exposure triggers macrophages in BAT to produce catecholamines like norepinephrine. Norepinephrine agonizes b-adrenergic receptors on fat cells. Cold also activates beige cell development and function. The effect can be mimicked with B3 adrenergic activators, which also trigger PGC-1a and brite cell development. It can also be mimicked with TRPM, or cold-sensor activators.<\/p>\r\n IRISIN AND PGC-1 ALPHA<\/p>\r\n Exercise causes increased expression in muscle of PPARg coactivator 1-alpha (PGC-1a), which downstream results in a hormone\/myokine called irisin. This irisin contributes to a browning of WAT cells. So not only does exercise burn calories directly, but also secondarily through triggering the browning process with irisin. Fortunately, this is an exploitable angle independent of exercise by triggering the PPARg cascade.<\/p>\r\n PRDM16, BMP-7<\/p>\r\n Prdm16 is a transcriptional cofactor, substantially enriched in human BAT compared to adjacent WAT. It acts by binding to and modulating other factors like C\/EBPb, PPARy, PPARa, and the aforementioned PGC-1a. Knocking out Prdm16 negates the thermogenic effect of brown cells, and increases WAT. Considered a key driver of brown fat cell fate, this cofactor is quite important. Bone Morphogenetic Protein-7 (BMP-7) increases expression of Prdm16 in precursor cells, and is essential for brown fat development. BMP-7 is fortunately something we can target with supplementation.<\/p>\r\n ADENYLYL CYCLASE AND ALPHA-1 ADRENERGIC ACTIVATION<\/p>\r\n Adenylyl cyclase is an enzyme that catalyzes the conversion of ATP to cyclic AMP. We mentioned beta-adrenergic receptor agonism, but it turns out this is greatly enhanced with simultaneous adenylyl cyclase upregulation and alpha-1 activation. So, targeting adenylyl cyclase, alpha-1, and beta-adrenergic agonism together causes enhanced brite cell creation.<\/p>\r\n UCP1<\/p>\r\n BAT mitochondria respond to something called UCP1 (uncoupling protein 1) to burn fat and generate heat, while brite cells seem to express lower levels of UCP1. However, brite cells potentially burn fat independently of UCP1 signaling, and furthermore, with the proper triggers, brite fat can actually turn on high levels of UCP1. Multiple ingredients in the BRITE formula will encourage WAT cells to upregulate UCP1 levels. Some of you may be familiar with a somewhat popular drug in the bodybuilding community years ago called DNP (which actually has roots in the 1930s as a weight loss drug). DNP was meant to mimic activated UCP1, which drastically elevated thermogenesis. While extremely effective, unregulated uncoupling can (and did) cause hyperthermia and death. Fortunately, we now have effective ways of targeting UCP1 safely.<\/p>\r\n PHOSPHODIESTERASES<\/p>\r\n Phosphodiesterases (or PDEs from here on out) are a family of enzymes that catalyze the inactivity (and therefore homeostasis) of the cAMP and\/or cGMP systems. An example we should all be familiar with is PDE5, which reduces cGMP in the erectile tissues, suppressing erectile response. Viagra, Cialis, etc., all inhibit the PDE5 enzyme, which leads to accumulation of cGMP, relaxation of penile tissues, dilation of blood vessels and eventually an erection.<\/p>\r\n The cAMP and cGMP systems are tightly controlled by physiological signals in order to maximally preserve resources. The cAMP system, for example, is related to energy states using Adenosine as a backbone (think highly depleted ATP – Adenosine Triphosphate). Elevation of cAMP leads to lipolysis, the freeing of fatty acids for transport to metabolically active tissue for either conversion to ATP or, in our case, thermogenesis.<\/p>\r\n There are two members of the PDE family that are of interest to us. One is PDE3b, the enzyme form activated by insulin to suppress lipolysis, allowing for the opposite to occur (storage of fat\/carbs). By suppressing PDE3b, we preserve a state of lipolysis and fat continues to be \"burned\" even after eating. Inhibition of PDE3b also removes the barriers of induction of UCP1, which causes non-shivering thermogenesis (the use of fatty acids to generate heat).<\/p>\r\n The other member is a newer player, PDE4D. Working hand-in-hand with PDE3b inhibition, PDE4D inhibition amplifies adrenergic signaling, UCP1 expression, lipolysis, and amplification of thermogenesis – especially basal (baseline) levels which means the rate of lipolysis without additional stimulation. The higher the basal rate, the more fat burned\/heat generated.<\/p>\r\n At the end of this inhibition, we go back to that Adenylyl Cyclase (and in the case of cGMP, Guanylyl Cyclase) creating the energy usage and replenishment cycle.<\/p>\r\n INGREDIENTS AND FUNCTION<\/p>\r\n Butcher’s Broom 50:1 Extract<\/p>\r\n Butcher’s Broom is a herb also known as Ruscus aculeatus. It gets its name from the practice of butchers using it for its supposed antibacterial properties to clean their cutting boards. It has been used in traditional medicine for its vasoconstrictive and anti-inflammatory actions (reducing swelling, preventing hemorrhoids, etc.).<\/p>\r\n The plant contains a variety of saponins, which have been shown to activate alpha-1 adrenergic receptors and stimulate the release of norepinephrine. It also has a protective effect on capillaries, strengthens blood vessels, and helps maintain healthy circulation.<\/p>\r\n As discussed previously, this alpha-1 activation is important and has been shown to shift preadipocytes to beige cells as opposed to white adipose tissue. As well, recent research shows that when hibernating, animals’ thermosensitive mechanisms will detect ambient and body temperatures and, if falling under threshold, the SNS will release norepinephrine to activate BAT in order to maintain viable body temperatures.<\/p>\r\n Gypenosides (75%)<\/p>\r\n Gypenosides are saponins found in the jiaogulan plant. This ingredient targets both WAT and BAT. With it we get WAT browning and an increase in fat oxidation genes in both WAT and BAT. Obesogenic diet mice treated with Gypenosides had a significantly reduced bodyweight vs. control, with lower cholesterol and insulin resistance. Gypenosides potently activate AMPk, which is tied directly to the cGMP\/cAMP systems and sympathetic\/parasympathetic nervous systems (metabolic autopilots), and amplify the lipolytic\/thermogenic effects on brite cells.<\/p>\r\n Menthol Crystals<\/p>\r\n Aside from B3 adrenergic receptor activation, the other most important way to start the browning process of WAT browning, as previously discussed, is through cold exposure. By exposing the body to cold temperatures long-term, it activates the TRPM8 receptor, which triggers browning in order to more effectively use WAT to create body warmth.<\/p>\r\n TRPM8 activation also enhances the thermogenic function of brown adipocytes through UCP1 and the b-adrenergic pathway.<\/p>\r\n So Menthol mimics long-term cold exposure by activating the TRPM8 channel, which has been shown to induce WAT browning as well as an upregulation in BAT thermogenesis. This has been shown to increase core temperature, reduce body fat and improve glucose metabolism.<\/p>\r\n Vanillin<\/p>\r\n An ingredient used in fake vanilla extracts for baking, Vanillin (and its metabolite Vanillic Acid) are metabolic derivatives from Anthocyanins. In addition to favorably reducing the ratio of Firmicutes to Bacteroides, resulting in a favorable gut environment for fat loss, Vanillin potently induces both browning of white fat and expression of UCP1.<\/p>\r\n Vanillin also increases glucose uptake in muscle tissue as well as regulating redox imbalances and inflammation.<\/p>\r\n Black Pepper Extract (20% Piperine)<\/p>\r\n TRPV1 is a capsaicin and vanilloid receptor in the body that is responsible for detection and regulation of body temperature and pain. More recently this receptor has been identified as a major player in obesity and body fat regulation. Stimulation of TRPV1 has been shown to upregulate BAT and increase fat oxidation and energy expenditure. TRPA1 is a similar receptor that functions to recognize cold and pain. Piperine, as well as several other compounds in black pepper, have been shown to be TRPV1 and TRPA1 agonists, with an even greater efficacy than capsaicin.<\/p>\r\n Trans-Cinnamaldehyde<\/p>\r\n Trans-Cinnamaldehyde is a pungent compound from cinnamon or dried cassia bark. It has been shown to increase UCP1 in both WAT and BAT, inducing browning of WAT cells. It also activates the cold receptor TRPA1. Back to those rodents fed obesogenic diets, Trans-Cinnamaldehyde inhibited hypertrophy of adipose cells, decreased body fat (including visceral fat), decreased voluntary food intake, and improved insulin sensitivity.<\/p>\r\n Salvia Miltiorrhiza 20:1 (Ethanol Extract)<\/p>\r\n Salvia Miltiorrhiza is a fascinating plant containing potent compounds that inhibit an enzyme called DGAT (diacylglycerol acyltransferase). Salvia Miltiorrhiza is able to prevent the final step in esterifying lipids into the form that WAT need them in – namely triacylglycerides (triglycerides). This keeps the lipids circulating in the bloodstream to be picked up and used by peroxisomes and mitochondria, and thrown off as heat.<\/p>\r\n Salvia Miltiorrhiza also inhibits SMAD2\/3 expression (see the BMP writeup), which suppresses myostatin activity and preserves muscle mass.<\/p>\r\n Salvia Miltiorrhiza has a dramatic effect on mitochondrial function in brite cells, basically turbocharging their activity by amplifying UCP1 activity.<\/p>\r\n Rutaecarpine<\/p>\r\n Contained in large quantities in the evodia fruit, it was first thought the Evodiamine was the compound responsible for the increase in non-shivering thermogenesis. Evodiamine turned out to be a huge disappointment, because it turns out the Rutaecarpine was what we were looking for.<\/p>\r\n Potently activating both AMPk and PGC-1a, Rutaecarpine also very strongly increases thermogenesis as well as mitochondrial biogenesis in brite cells. The more mitochondria, the more uncoupling and thus more thermogenesis and more fat burned.<\/p>\r\n Rutaecarpine also inhibits adipogenesis and lipogenesis, preventing lipid accumulation in WAT. Remember lipids in WAT have to be removed through a process of lipolysis before they can be transferred to metabolically active tissue and organelles (peroxisomes, mitochondria). By preventing WAT from accumulating lipids as well as crippling the body’s ability to simply make more white fat cells, all while shutting the lipids into the metabolically active brown\/brite fat cells, the process of thermogenesis becomes more efficient.<\/p>\r\n Sesamol<\/p>\r\n Sesamol is a phenol derivative of sesame oil with antioxidant and anti-inflammatory properties. This is another ingredient in the formula with the aforementioned two-pronged attack. It downregulates adipogenic differentiation factors (C\/EBPa, PPARy, SREBP-1) and decreases fat accumulating enzymes like fatty acid synthase (FAS), while upregulating fat oxidizing enzymes like HSL, LPL and AMPk. In mice on an obesogenic diet, it decreased fat mass and adipocyte size in both WAT and BAT by increasing UCP1 and PCG-1a.<\/p>\r\n Borneol<\/p>\r\n Borneol is a very potent P-glycoprotein efflux pump inhibitor. While “distracting” the P-gp pump, the ingredients of BRITE are able to enter the body unhindered by this physiochemical saboteur. As an additional benefit, Borneol also activates the TRPM8 cold receptor.<\/p>\r\n Myricetin-Nicotinamide Crystalline Complex<\/p>\r\n The primary superstar of the new formula, Myricetin is an incredibly diverse and hugely potent ingredient.<\/p>\r\n Let’s do a quick functional run through.<\/p>\r\n GLP-1 agonist – GLP-1 agonists are all the rage for weight loss right now. GLP-1 stands for Glucagon-like Peptide 1. Initially targeted to reverse type 2 diabetes, GLP-1 agonists soon manifested an interesting secondary effect – massive and rapid fat loss. As research gains traction, several explanations are emerging. A potent appetite suppression pathway, GLP-1 appears to be extremely active in the brain, activating brain-specific AMPk (hypothalamus, etc.) and stimulating central activation of brown\/brite fat thermogenesis. They also are highly active in increasing muscle-specific glucose uptake, and are effective at improving cardiac function. GLP-1 agonists are inactivated by something called dipeptidyl peptidase-4 (DPP-4). Interestingly enough, Myricetin inhibits DPP-4, thus amplifying and prolonging its own effect.<\/p>\r\n Myricetin has also been shown to be incredibly potent at inducing brite cell conversion, activating non-shivering thermogenesis, and dramatically increasing mitochondrial biogenesis (formation of new mitochondria).<\/p>\r\n GSK3b – Touched on briefly in the TopMuscle writeup, Glycogen Synthase Kinase 3b functions to inhibit a ton of growth associated positive effects in the body. This includes muscle growth, glycogen formation, and most importantly, brown\/brite fat thermogenesis. In fact, its potency at shutting down non-shivering thermogenesis is stunning. As luck (or design) would have it, Myricetin is the most potent GSK3b inhibitor so far found in natural form, with an IC50 of 900 nanomoles – incredibly potent.<\/p>\r\n PDE3b – as mentioned elsewhere, in order for BAT\/BRITE thermogenesis to be maximized, both PDE3b and PDE4D need to be inhibited. As if Myricetin hasn’t already shown to be badass, it also inhibits PDE3b.<\/p>\r\n Myricetin sounds great – let’s toss that in. Well, being a flavonoid, Myricetin has one of the worst oral absorption profiles I’ve ever seen, at very low single digit %. Other absorption enhancing methods (cyclodextrin, etc.) also turned out to be disappointing. However, I worked out a crystallization process with Nicotinamide that yielded some absolutely gorgeous, and highly absorbable, crystals – enabling us to include this spectacular ingredient in the formula.<\/p>\r\n The best part? Nicotinamide is also a highly potent brown fat activating ingredient, by both amplifying adrenergic signaling at the B3 receptor and by triggering mitochondrial biogenesis, as well as increasing expression of PPARa and PGC-1a.<\/p>\r\n Fucoxanthin 40%<\/p>\r\n Fucoxanthin is a simple ingredient. It dramatically increases expression of UCP1, which should be clear by now.<\/p>\r\n Ginger-6 Specialized Extract (std for 6-Paradol, 6-Shogaol, 6-Gingerol)<\/p>\r\n Ginger is absolutely one of the most popular plants for digestion, soothing a dysfunctional stomach, and tossing back after sushi and wasabi. It is also popular for fat loss, though in previous usages sort of haphazardly tossed in. I’m sure you’ve also seen something called Grains of Paradise (6-Paradol) used in competing formulas, though with highly mixed, often disappointing results. Turns out, if you know the correct solvents to use and in what order, you can extract the 3 main “browning” compounds from Ginger in high concentrations.<\/p>\r\n 6-Paradol – As mentioned it has become a commonly used ingredient. Another compound used to increase WAT browning, 6-Paradol also increases expression of PCG-1a and UCP1, resulting in increased thermogenesis with measurable temperature increases in brite\/brown adipose. However, of the three it appears to be the weakest.<\/p>\r\n 6-Shogaol – The immediate precursor of 6-Paradol, 6-Shogaol shows extreme promise as a thermogenic and browning agent, both in mature and preadipocytes. Increasing expression of the usual suspects (PCG-1a, UCP1), 6-Shogaol also increases mitochondrial turnover and biogenesis, increases the binding energy of ligands in the essential B3 adrenoreceptors (amplified signaling), and provides for a dramatic upregulation of beige markers, indicating significant browning of WAT.<\/p>\r\n 6-Gingerol – Along with 6-Shogaol, the most dominant compound in ginger – and the most potent. Sharing functionality with 6-Shogaol (all pathways similarly, but more potently, activated), 6-Gingerol also inhibits lipogenesis. 6-Gingerol also shows an extremely potent ability to break the giant lipid droplet which characterizes WAT into smaller, multiple droplets – enabling the shift to classical brite characteristics more easily.<\/p>\r\n Humulus Japonicus Extract 50:1 (Water)<\/p>\r\n Humulus Japonicus Extract is a new and exciting addition to the formula. In addition to inducing browning of WAT, it exerts potent antioxidant effects and increases expression of both AMPk and UCP1, as well as being a decent PPAR-delta agonist. The difference in hibernating animals using more PPARa to provide mitochondrial substrate in the liver is that they generally spend the winter dormant, whereas humans have the added benefit of physical motion, thus adding PPAR-delta, which is dominant in skeletal muscle, to the mix.<\/p>\r\n Quercetin-Theobromine Crystalline Complex<\/p>\r\n An absolute thermonuclear addition to the new formula is an ingredient combination I’ve been trying to fit for years, and this is an incredibly fortuitous (that means lucky) addition. Though they are grown together into a crystalline complex, which mostly enhances absorption by several fold, we will take each ingredient separately.<\/p>\r\n Quercetin – The Big Q is an extremely common compound in most plants. In addition to acting as a potent zinc ionophore (escort molecule into the cells), it is quite the potent antioxidant. But let’s get to the good stuff…<\/p>\r\n A 2021 study showed Quercetin to do a whole host of things related to BAT\/brite activation. It increases expression of PGC-1a (necessary for brite conversion) and UCP1, reduces plasma cholesterol, increases expression of the elusive (in humans) B3 adrenoreceptor (which is a key in the whole package), and as well induces mitochondrial transcription factors. Best of all? It was also discovered to be a very potent PDE4D inhibitor (see the section on phosphodiesterases\/cAMP) and, less potently, a PDE3b inhibitor. Recall that both PDE3b inhibition and PDE4D inhibition are required for both browning and optimized non-shivering thermogenesis.<\/p>\r\n As a side note, Quercetin decreases Firmicutes (starts with F for Fatty) to Bacteroides ratio in the gut, thus leading to a leaner phenotype expression.<\/p>\r\n Now Quercetin, while relatively inexpensive, has horrible solubility in water and dismal oral absorption. The crystallization with Theobromine increases oral absorption substantially.<\/p>\r\n Theobromine – Starting where we left off with Quercetin, Theobromine is ALSO quite a potent PDE4D inhibitor, the combination pretty much providing everything we need to preserve SNS cAMP signaling and optimized thermogenesis. But wait...there’s more!<\/p>\r\n Theobromine is a major component of cocoa. It has been toyed with, mostly unsuccessfully, in fat burning formulas for decades. Knowing what we know now about mechanisms, it makes sense why it didn’t deliver as promised.<\/p>\r\n Theobromine increases non-shivering thermogenesis, increases expression of PGC-1a, UCP1, other brite specific markers (we won’t be delving into those here quite yet) as well as increasing transport molecules like CPT1, which escorts shortened fatty acids from peroxisomes into the mitochondria for further beta-oxidation (and in our case, uncoupling\/heat production rather than ATP yield). In addition, Theobromine activates both B3 adrenoreceptors and AMPk, with the end result being a backblast of thermogenesis. As well, Theobromine suppresses preadipocyte differentiation, lipogenesis, and extends the browning effect to sub-mature adipocytes.<\/p>\r\n Oleuropein 50%<\/p>\r\n Oleuropein, contained in the olive plant, appears to be one of the main compounds contributing to the healthiness of the Mediterranean Diet. A unique compound, Oleuropein both dramatically increases UCP1 expression, and increases adrenaline\/noradrenaline secretion (absolutely essential for any kind of lipolysis, and therefore thermogenesis). Adrenaline\/noradrenaline acts as a ligand at the B3 adrenoreceptor (which, if you have been following has had both quantity increased as well as binding increased and signal amplified), the end result being hyperactivation of non-shivering thermogenesis.<\/p>\r\n We mentioned BMP7 also being essential to brown\/brite thermogenesis. While we are using a 50% oleuropein extract here, the other polyphenols in Olive (the “other” 50%) have been demonstrated to increase expression of BMP7, thus completing the perfection of our formula.<\/p>\r\n CONCLUSION<\/p>\r\n As you can see, we have exhaustively targeted all of the known pathways of creating and activating brite cells in the body through either recruiting precursor cells or converting mature white cells. Regular supplementation should encourage fat loss and mimicking of a lean phenotype acutely, and even more so when taken chronically – as brite cells don’t immediately revert back to white adipose upon cessation of the product. BRITE is a long-term solution to an ongoing, serious problem plaguing modern society.<\/p>\r\n <\/p>\r\n <\/p>","gtin13":"0758381476494","image":["https:\/\/siteimgs.com\/10017\/item\/brite-rendering_1703084216-0.jpg"],"brand":"EvoMuse","url":"https:\/\/www.dpsnutrition.net\/i\/28735\/evomuse-brite-capsules-120-cap.htm","offers":{"@type":"Offer","priceCurrency":"USD","price":"59.99","url":"https:\/\/www.dpsnutrition.net\/i\/28735\/evomuse-brite-capsules-120-cap.htm","itemCondition":"http:\/\/schema.org\/NewCondition","availability":"http:\/\/schema.org\/InStock"}},{"@type":"Product","name":"EvoMuse Brite Capsules - 360 Capsule (2 x 180 Capsule Bottles) TWINPACK *New Formula","sku":"EM2036","description":" BRITE | Adipocyte Conversion Formula<\/p>\r\n \"A cold, starving animal doesn't care about a 6-pack.\"<\/p>\r\n Perspective is a complex thing. From the perspective of an undisciplined modern human, life is surrounded by plenty and our worries can consist of trying to reach our most aesthetically pleasing selves. However, perspective for most of the creatures on the planet is harsh, difficult, and a never-ending quest for precious resources.<\/p>\r\n Heat is one of the most precious resources, as the universe contends with \"hot spots\" in its quest to finally attain perfect order and energy distribution – namely heat death.<\/p>\r\n Nature, on the other hand – if it can be separated from the Universe – seems obsessed with continuing bright hot spots of life, without caring about individuals. The mechanistic viewpoint of our bodies, which still reigns supreme, follows laws of thermodynamics and thus life and heat can almost be interchangeable.<\/p>\r\n As we have covered countless times, humans, in our dominant but highly artificial state, are an aberration from the general rules. Nature drives numerous animals into dormancy when resources become scarce and more energy would be spent finding calories (heat, fuel) than could be replenished. Hibernation is the name of the game for Winter. Hibernation must be prepared for, which is why hibernating animals begin gorging and getting fat during Fall. Those fat stores are our point of interest, as much of it is stored in specialized cells.<\/p>\r\n The key to thermogenesis is adrenergic signaling (meaning related to adrenaline and noradrenaline). While humans have come to rely more on B2 (and A2) signaling for active lipolysis resulting in ATP formation with increases in heat a secondary effect (to fuel activity), the animals that hibernate during cold weather rely on different receptors (B3, A1) to generate heat via thermogenesis to go along with a more passive release of adrenaline\/noradrenaline, since for the most part they aren't moving much.<\/p>\r\n Human B3 receptors have lost importance, which means the first step is to increase activity here…<\/p>\r\n …but before we do that, let's take a quick step back for all those who are new to this here do-si-do.<\/p>\r\n A full decade ago, Evolutionary Muse released a first-in-kind product designed to facilitate the browning of white fat. Aptly named BRITE™, it shares the same name as those adipocytes which are named for being BROWN-IN-WHITE cells – white adipocytes which behave like brown adipocytes. Brown adipocytes are metabolically active cells which use their fat stores to generate body heat...the life hack of all life hacks, if you will. But there was one glaring problem – modern living was all but making this phenomenon a thing of the past. No problem, we should just reject modernity and embrace tradition. Right?<\/p>\r\n Wrong.<\/p>\r\n Evolutionary Muse: Inspire to Evolve. (Translation: We take a pill for that now.)<\/p>\r\n DIFFERENCE BETWEEN WAT AND BAT<\/p>\r\n BAT works quite differently, if not opposite, to White Adipose Tissue (WAT). BAT is dense in mitochondria and considered a highly thermogenic fat cell, responsible for creating heat through a process called “non-shivering thermogenesis”. This process burns calories through a futile cycle of shuttling protons to the mitochondria to generate heat. WAT, however, is what we all think of when we hear the term “body fat”. It stores calories so they can be used later during periods of hunger or famine, and secretes various adipokines.<\/p>\r\n Even more recently, we have discovered another player in the adipocyte story – Brown-in-White cells, or “BRITE”. At a microscopic level, these cells display a color between brown and white, and behave in a similar thermogenic fashion to BAT cells. While we don’t know yet if reduced thermogenic activity is a cause or consequence of obesity, we do know that an increase in BAT and\/or brite cells improves glucose tolerance and insulin sensitivity.<\/p>\r\n Two distinct pathways exist towards increasing brite cells in adult humans, (1) triggering precursor cells into becoming brite cells, and (2) turning mature WAT cells into brite cells. We want to target these pathways directly so that we can increase the ratio of brite cells to WAT cells, allowing your body to constantly burn more calories. So, let’s dive into some of the known methods of brite cell creation and activation.<\/p>\r\n COLD THERAPY, B3 ADRENERGIC ACTIVATORS<\/p>\r\n Cold exposure triggers macrophages in BAT to produce catecholamines like norepinephrine. Norepinephrine agonizes b-adrenergic receptors on fat cells. Cold also activates beige cell development and function. The effect can be mimicked with B3 adrenergic activators, which also trigger PGC-1a and brite cell development. It can also be mimicked with TRPM, or cold-sensor activators.<\/p>\r\n IRISIN AND PGC-1 ALPHA<\/p>\r\n Exercise causes increased expression in muscle of PPARg coactivator 1-alpha (PGC-1a), which downstream results in a hormone\/myokine called irisin. This irisin contributes to a browning of WAT cells. So not only does exercise burn calories directly, but also secondarily through triggering the browning process with irisin. Fortunately, this is an exploitable angle independent of exercise by triggering the PPARg cascade.<\/p>\r\n PRDM16, BMP-7<\/p>\r\n Prdm16 is a transcriptional cofactor, substantially enriched in human BAT compared to adjacent WAT. It acts by binding to and modulating other factors like C\/EBPb, PPARy, PPARa, and the aforementioned PGC-1a. Knocking out Prdm16 negates the thermogenic effect of brown cells, and increases WAT. Considered a key driver of brown fat cell fate, this cofactor is quite important. Bone Morphogenetic Protein-7 (BMP-7) increases expression of Prdm16 in precursor cells, and is essential for brown fat development. BMP-7 is fortunately something we can target with supplementation.<\/p>\r\n ADENYLYL CYCLASE AND ALPHA-1 ADRENERGIC ACTIVATION<\/p>\r\n Adenylyl cyclase is an enzyme that catalyzes the conversion of ATP to cyclic AMP. We mentioned beta-adrenergic receptor agonism, but it turns out this is greatly enhanced with simultaneous adenylyl cyclase upregulation and alpha-1 activation. So, targeting adenylyl cyclase, alpha-1, and beta-adrenergic agonism together causes enhanced brite cell creation.<\/p>\r\n UCP1<\/p>\r\n BAT mitochondria respond to something called UCP1 (uncoupling protein 1) to burn fat and generate heat, while brite cells seem to express lower levels of UCP1. However, brite cells potentially burn fat independently of UCP1 signaling, and furthermore, with the proper triggers, brite fat can actually turn on high levels of UCP1. Multiple ingredients in the BRITE formula will encourage WAT cells to upregulate UCP1 levels. Some of you may be familiar with a somewhat popular drug in the bodybuilding community years ago called DNP (which actually has roots in the 1930s as a weight loss drug). DNP was meant to mimic activated UCP1, which drastically elevated thermogenesis. While extremely effective, unregulated uncoupling can (and did) cause hyperthermia and death. Fortunately, we now have effective ways of targeting UCP1 safely.<\/p>\r\n PHOSPHODIESTERASES<\/p>\r\n Phosphodiesterases (or PDEs from here on out) are a family of enzymes that catalyze the inactivity (and therefore homeostasis) of the cAMP and\/or cGMP systems. An example we should all be familiar with is PDE5, which reduces cGMP in the erectile tissues, suppressing erectile response. Viagra, Cialis, etc., all inhibit the PDE5 enzyme, which leads to accumulation of cGMP, relaxation of penile tissues, dilation of blood vessels and eventually an erection.<\/p>\r\n The cAMP and cGMP systems are tightly controlled by physiological signals in order to maximally preserve resources. The cAMP system, for example, is related to energy states using Adenosine as a backbone (think highly depleted ATP – Adenosine Triphosphate). Elevation of cAMP leads to lipolysis, the freeing of fatty acids for transport to metabolically active tissue for either conversion to ATP or, in our case, thermogenesis.<\/p>\r\n There are two members of the PDE family that are of interest to us. One is PDE3b, the enzyme form activated by insulin to suppress lipolysis, allowing for the opposite to occur (storage of fat\/carbs). By suppressing PDE3b, we preserve a state of lipolysis and fat continues to be \"burned\" even after eating. Inhibition of PDE3b also removes the barriers of induction of UCP1, which causes non-shivering thermogenesis (the use of fatty acids to generate heat).<\/p>\r\n The other member is a newer player, PDE4D. Working hand-in-hand with PDE3b inhibition, PDE4D inhibition amplifies adrenergic signaling, UCP1 expression, lipolysis, and amplification of thermogenesis – especially basal (baseline) levels which means the rate of lipolysis without additional stimulation. The higher the basal rate, the more fat burned\/heat generated.<\/p>\r\n At the end of this inhibition, we go back to that Adenylyl Cyclase (and in the case of cGMP, Guanylyl Cyclase) creating the energy usage and replenishment cycle.<\/p>\r\n INGREDIENTS AND FUNCTION<\/p>\r\n Butcher’s Broom 50:1 Extract<\/p>\r\n Butcher’s Broom is a herb also known as Ruscus aculeatus. It gets its name from the practice of butchers using it for its supposed antibacterial properties to clean their cutting boards. It has been used in traditional medicine for its vasoconstrictive and anti-inflammatory actions (reducing swelling, preventing hemorrhoids, etc.).<\/p>\r\n The plant contains a variety of saponins, which have been shown to activate alpha-1 adrenergic receptors and stimulate the release of norepinephrine. It also has a protective effect on capillaries, strengthens blood vessels, and helps maintain healthy circulation.<\/p>\r\n As discussed previously, this alpha-1 activation is important and has been shown to shift preadipocytes to beige cells as opposed to white adipose tissue. As well, recent research shows that when hibernating, animals’ thermosensitive mechanisms will detect ambient and body temperatures and, if falling under threshold, the SNS will release norepinephrine to activate BAT in order to maintain viable body temperatures.<\/p>\r\n Gypenosides (75%)<\/p>\r\n Gypenosides are saponins found in the jiaogulan plant. This ingredient targets both WAT and BAT. With it we get WAT browning and an increase in fat oxidation genes in both WAT and BAT. Obesogenic diet mice treated with Gypenosides had a significantly reduced bodyweight vs. control, with lower cholesterol and insulin resistance. Gypenosides potently activate AMPk, which is tied directly to the cGMP\/cAMP systems and sympathetic\/parasympathetic nervous systems (metabolic autopilots), and amplify the lipolytic\/thermogenic effects on brite cells.<\/p>\r\n Menthol Crystals<\/p>\r\n Aside from B3 adrenergic receptor activation, the other most important way to start the browning process of WAT browning, as previously discussed, is through cold exposure. By exposing the body to cold temperatures long-term, it activates the TRPM8 receptor, which triggers browning in order to more effectively use WAT to create body warmth.<\/p>\r\n TRPM8 activation also enhances the thermogenic function of brown adipocytes through UCP1 and the b-adrenergic pathway.<\/p>\r\n So Menthol mimics long-term cold exposure by activating the TRPM8 channel, which has been shown to induce WAT browning as well as an upregulation in BAT thermogenesis. This has been shown to increase core temperature, reduce body fat and improve glucose metabolism.<\/p>\r\n Vanillin<\/p>\r\n An ingredient used in fake vanilla extracts for baking, Vanillin (and its metabolite Vanillic Acid) are metabolic derivatives from Anthocyanins. In addition to favorably reducing the ratio of Firmicutes to Bacteroides, resulting in a favorable gut environment for fat loss, Vanillin potently induces both browning of white fat and expression of UCP1.<\/p>\r\n Vanillin also increases glucose uptake in muscle tissue as well as regulating redox imbalances and inflammation.<\/p>\r\n Black Pepper Extract (20% Piperine)<\/p>\r\n TRPV1 is a capsaicin and vanilloid receptor in the body that is responsible for detection and regulation of body temperature and pain. More recently this receptor has been identified as a major player in obesity and body fat regulation. Stimulation of TRPV1 has been shown to upregulate BAT and increase fat oxidation and energy expenditure. TRPA1 is a similar receptor that functions to recognize cold and pain. Piperine, as well as several other compounds in black pepper, have been shown to be TRPV1 and TRPA1 agonists, with an even greater efficacy than capsaicin.<\/p>\r\n Trans-Cinnamaldehyde<\/p>\r\n Trans-Cinnamaldehyde is a pungent compound from cinnamon or dried cassia bark. It has been shown to increase UCP1 in both WAT and BAT, inducing browning of WAT cells. It also activates the cold receptor TRPA1. Back to those rodents fed obesogenic diets, Trans-Cinnamaldehyde inhibited hypertrophy of adipose cells, decreased body fat (including visceral fat), decreased voluntary food intake, and improved insulin sensitivity.<\/p>\r\n Salvia Miltiorrhiza 20:1 (Ethanol Extract)<\/p>\r\n Salvia Miltiorrhiza is a fascinating plant containing potent compounds that inhibit an enzyme called DGAT (diacylglycerol acyltransferase). Salvia Miltiorrhiza is able to prevent the final step in esterifying lipids into the form that WAT need them in – namely triacylglycerides (triglycerides). This keeps the lipids circulating in the bloodstream to be picked up and used by peroxisomes and mitochondria, and thrown off as heat.<\/p>\r\n Salvia Miltiorrhiza also inhibits SMAD2\/3 expression (see the BMP writeup), which suppresses myostatin activity and preserves muscle mass.<\/p>\r\n Salvia Miltiorrhiza has a dramatic effect on mitochondrial function in brite cells, basically turbocharging their activity by amplifying UCP1 activity.<\/p>\r\n Rutaecarpine<\/p>\r\n Contained in large quantities in the evodia fruit, it was first thought the Evodiamine was the compound responsible for the increase in non-shivering thermogenesis. Evodiamine turned out to be a huge disappointment, because it turns out the Rutaecarpine was what we were looking for.<\/p>\r\n Potently activating both AMPk and PGC-1a, Rutaecarpine also very strongly increases thermogenesis as well as mitochondrial biogenesis in brite cells. The more mitochondria, the more uncoupling and thus more thermogenesis and more fat burned.<\/p>\r\n Rutaecarpine also inhibits adipogenesis and lipogenesis, preventing lipid accumulation in WAT. Remember lipids in WAT have to be removed through a process of lipolysis before they can be transferred to metabolically active tissue and organelles (peroxisomes, mitochondria). By preventing WAT from accumulating lipids as well as crippling the body’s ability to simply make more white fat cells, all while shutting the lipids into the metabolically active brown\/brite fat cells, the process of thermogenesis becomes more efficient.<\/p>\r\n Sesamol<\/p>\r\n Sesamol is a phenol derivative of sesame oil with antioxidant and anti-inflammatory properties. This is another ingredient in the formula with the aforementioned two-pronged attack. It downregulates adipogenic differentiation factors (C\/EBPa, PPARy, SREBP-1) and decreases fat accumulating enzymes like fatty acid synthase (FAS), while upregulating fat oxidizing enzymes like HSL, LPL and AMPk. In mice on an obesogenic diet, it decreased fat mass and adipocyte size in both WAT and BAT by increasing UCP1 and PCG-1a.<\/p>\r\n Borneol<\/p>\r\n Borneol is a very potent P-glycoprotein efflux pump inhibitor. While “distracting” the P-gp pump, the ingredients of BRITE are able to enter the body unhindered by this physiochemical saboteur. As an additional benefit, Borneol also activates the TRPM8 cold receptor.<\/p>\r\n Myricetin-Nicotinamide Crystalline Complex<\/p>\r\n The primary superstar of the new formula, Myricetin is an incredibly diverse and hugely potent ingredient.<\/p>\r\n Let’s do a quick functional run through.<\/p>\r\n GLP-1 agonist – GLP-1 agonists are all the rage for weight loss right now. GLP-1 stands for Glucagon-like Peptide 1. Initially targeted to reverse type 2 diabetes, GLP-1 agonists soon manifested an interesting secondary effect – massive and rapid fat loss. As research gains traction, several explanations are emerging. A potent appetite suppression pathway, GLP-1 appears to be extremely active in the brain, activating brain-specific AMPk (hypothalamus, etc.) and stimulating central activation of brown\/brite fat thermogenesis. They also are highly active in increasing muscle-specific glucose uptake, and are effective at improving cardiac function. GLP-1 agonists are inactivated by something called dipeptidyl peptidase-4 (DPP-4). Interestingly enough, Myricetin inhibits DPP-4, thus amplifying and prolonging its own effect.<\/p>\r\n Myricetin has also been shown to be incredibly potent at inducing brite cell conversion, activating non-shivering thermogenesis, and dramatically increasing mitochondrial biogenesis (formation of new mitochondria).<\/p>\r\n GSK3b – Touched on briefly in the TopMuscle writeup, Glycogen Synthase Kinase 3b functions to inhibit a ton of growth associated positive effects in the body. This includes muscle growth, glycogen formation, and most importantly, brown\/brite fat thermogenesis. In fact, its potency at shutting down non-shivering thermogenesis is stunning. As luck (or design) would have it, Myricetin is the most potent GSK3b inhibitor so far found in natural form, with an IC50 of 900 nanomoles – incredibly potent.<\/p>\r\n PDE3b – as mentioned elsewhere, in order for BAT\/BRITE thermogenesis to be maximized, both PDE3b and PDE4D need to be inhibited. As if Myricetin hasn’t already shown to be badass, it also inhibits PDE3b.<\/p>\r\n Myricetin sounds great – let’s toss that in. Well, being a flavonoid, Myricetin has one of the worst oral absorption profiles I’ve ever seen, at very low single digit %. Other absorption enhancing methods (cyclodextrin, etc.) also turned out to be disappointing. However, I worked out a crystallization process with Nicotinamide that yielded some absolutely gorgeous, and highly absorbable, crystals – enabling us to include this spectacular ingredient in the formula.<\/p>\r\n The best part? Nicotinamide is also a highly potent brown fat activating ingredient, by both amplifying adrenergic signaling at the B3 receptor and by triggering mitochondrial biogenesis, as well as increasing expression of PPARa and PGC-1a.<\/p>\r\n Fucoxanthin 40%<\/p>\r\n Fucoxanthin is a simple ingredient. It dramatically increases expression of UCP1, which should be clear by now.<\/p>\r\n Ginger-6 Specialized Extract (std for 6-Paradol, 6-Shogaol, 6-Gingerol)<\/p>\r\n Ginger is absolutely one of the most popular plants for digestion, soothing a dysfunctional stomach, and tossing back after sushi and wasabi. It is also popular for fat loss, though in previous usages sort of haphazardly tossed in. I’m sure you’ve also seen something called Grains of Paradise (6-Paradol) used in competing formulas, though with highly mixed, often disappointing results. Turns out, if you know the correct solvents to use and in what order, you can extract the 3 main “browning” compounds from Ginger in high concentrations.<\/p>\r\n 6-Paradol – As mentioned it has become a commonly used ingredient. Another compound used to increase WAT browning, 6-Paradol also increases expression of PCG-1a and UCP1, resulting in increased thermogenesis with measurable temperature increases in brite\/brown adipose. However, of the three it appears to be the weakest.<\/p>\r\n 6-Shogaol – The immediate precursor of 6-Paradol, 6-Shogaol shows extreme promise as a thermogenic and browning agent, both in mature and preadipocytes. Increasing expression of the usual suspects (PCG-1a, UCP1), 6-Shogaol also increases mitochondrial turnover and biogenesis, increases the binding energy of ligands in the essential B3 adrenoreceptors (amplified signaling), and provides for a dramatic upregulation of beige markers, indicating significant browning of WAT.<\/p>\r\n 6-Gingerol – Along with 6-Shogaol, the most dominant compound in ginger – and the most potent. Sharing functionality with 6-Shogaol (all pathways similarly, but more potently, activated), 6-Gingerol also inhibits lipogenesis. 6-Gingerol also shows an extremely potent ability to break the giant lipid droplet which characterizes WAT into smaller, multiple droplets – enabling the shift to classical brite characteristics more easily.<\/p>\r\n Humulus Japonicus Extract 50:1 (Water)<\/p>\r\n Humulus Japonicus Extract is a new and exciting addition to the formula. In addition to inducing browning of WAT, it exerts potent antioxidant effects and increases expression of both AMPk and UCP1, as well as being a decent PPAR-delta agonist. The difference in hibernating animals using more PPARa to provide mitochondrial substrate in the liver is that they generally spend the winter dormant, whereas humans have the added benefit of physical motion, thus adding PPAR-delta, which is dominant in skeletal muscle, to the mix.<\/p>\r\n Quercetin-Theobromine Crystalline Complex<\/p>\r\n An absolute thermonuclear addition to the new formula is an ingredient combination I’ve been trying to fit for years, and this is an incredibly fortuitous (that means lucky) addition. Though they are grown together into a crystalline complex, which mostly enhances absorption by several fold, we will take each ingredient separately.<\/p>\r\n Quercetin – The Big Q is an extremely common compound in most plants. In addition to acting as a potent zinc ionophore (escort molecule into the cells), it is quite the potent antioxidant. But let’s get to the good stuff…<\/p>\r\n A 2021 study showed Quercetin to do a whole host of things related to BAT\/brite activation. It increases expression of PGC-1a (necessary for brite conversion) and UCP1, reduces plasma cholesterol, increases expression of the elusive (in humans) B3 adrenoreceptor (which is a key in the whole package), and as well induces mitochondrial transcription factors. Best of all? It was also discovered to be a very potent PDE4D inhibitor (see the section on phosphodiesterases\/cAMP) and, less potently, a PDE3b inhibitor. Recall that both PDE3b inhibition and PDE4D inhibition are required for both browning and optimized non-shivering thermogenesis.<\/p>\r\n As a side note, Quercetin decreases Firmicutes (starts with F for Fatty) to Bacteroides ratio in the gut, thus leading to a leaner phenotype expression.<\/p>\r\n Now Quercetin, while relatively inexpensive, has horrible solubility in water and dismal oral absorption. The crystallization with Theobromine increases oral absorption substantially.<\/p>\r\n Theobromine – Starting where we left off with Quercetin, Theobromine is ALSO quite a potent PDE4D inhibitor, the combination pretty much providing everything we need to preserve SNS cAMP signaling and optimized thermogenesis. But wait...there’s more!<\/p>\r\n Theobromine is a major component of cocoa. It has been toyed with, mostly unsuccessfully, in fat burning formulas for decades. Knowing what we know now about mechanisms, it makes sense why it didn’t deliver as promised.<\/p>\r\n Theobromine increases non-shivering thermogenesis, increases expression of PGC-1a, UCP1, other brite specific markers (we won’t be delving into those here quite yet) as well as increasing transport molecules like CPT1, which escorts shortened fatty acids from peroxisomes into the mitochondria for further beta-oxidation (and in our case, uncoupling\/heat production rather than ATP yield). In addition, Theobromine activates both B3 adrenoreceptors and AMPk, with the end result being a backblast of thermogenesis. As well, Theobromine suppresses preadipocyte differentiation, lipogenesis, and extends the browning effect to sub-mature adipocytes.<\/p>\r\n Oleuropein 50%<\/p>\r\n Oleuropein, contained in the olive plant, appears to be one of the main compounds contributing to the healthiness of the Mediterranean Diet. A unique compound, Oleuropein both dramatically increases UCP1 expression, and increases adrenaline\/noradrenaline secretion (absolutely essential for any kind of lipolysis, and therefore thermogenesis). Adrenaline\/noradrenaline acts as a ligand at the B3 adrenoreceptor (which, if you have been following has had both quantity increased as well as binding increased and signal amplified), the end result being hyperactivation of non-shivering thermogenesis.<\/p>\r\n We mentioned BMP7 also being essential to brown\/brite thermogenesis. While we are using a 50% oleuropein extract here, the other polyphenols in Olive (the “other” 50%) have been demonstrated to increase expression of BMP7, thus completing the perfection of our formula.<\/p>\r\n CONCLUSION<\/p>\r\n As you can see, we have exhaustively targeted all of the known pathways of creating and activating brite cells in the body through either recruiting precursor cells or converting mature white cells. Regular supplementation should encourage fat loss and mimicking of a lean phenotype acutely, and even more so when taken chronically – as brite cells don’t immediately revert back to white adipose upon cessation of the product. BRITE is a long-term solution to an ongoing, serious problem plaguing modern society.<\/p>\r\n <\/p>\r\n <\/p>","gtin13":"0758381476494","image":["https:\/\/siteimgs.com\/10017\/item\/2brite_1703091174-0.jpg"],"brand":"EvoMuse","url":"https:\/\/www.dpsnutrition.net\/i\/33659\/evomuse-brite-capsules-120-cap.htm","offers":{"@type":"Offer","priceCurrency":"USD","price":"95.99","url":"https:\/\/www.dpsnutrition.net\/i\/33659\/evomuse-brite-capsules-120-cap.htm","itemCondition":"http:\/\/schema.org\/NewCondition","availability":"http:\/\/schema.org\/InStock"}},{"@type":"Product","name":"EvoMuse DCP Ultra - 180 Capsules","sku":"EM051","description":"","image":["https:\/\/siteimgs.com\/10017\/item\/dcp_1655572491-0.jpg"],"brand":"EvoMuse","url":"https:\/\/www.dpsnutrition.net\/i\/32043\/evomuse-dcp-ultra-180-cap.htm","offers":{"@type":"Offer","priceCurrency":"USD","price":"56.99","url":"https:\/\/www.dpsnutrition.net\/i\/32043\/evomuse-dcp-ultra-180-cap.htm","itemCondition":"http:\/\/schema.org\/NewCondition","availability":"http:\/\/schema.org\/InStock"}},{"@type":"Product","name":"EvoMuse DCP Ultra - 2 x 180 Capsule Bottles TWINPACK","sku":"EM22051","description":"","image":["https:\/\/siteimgs.com\/10017\/item\/dcp-tw_1655572629-0.jpg"],"brand":"EvoMuse","url":"https:\/\/www.dpsnutrition.net\/i\/32125\/evomuse-dcp-ultra-180-cap.htm","offers":{"@type":"Offer","priceCurrency":"USD","price":"99.99","url":"https:\/\/www.dpsnutrition.net\/i\/32125\/evomuse-dcp-ultra-180-cap.htm","itemCondition":"http:\/\/schema.org\/NewCondition","availability":"http:\/\/schema.org\/InStock"}},{"@type":"Product","name":"EvoMuse Defuse - 180 Cap","sku":"EM013","description":" Defuse The feeding of Calories into the system known as the Human Body, and where those Calories finally end up, is a highly complex process. A number of sensing and processing pathways are put into play, each dealing with different nutrients (fat, carbs, etc), that either direct nutrients to be used as fuel, or stored as fat. The fat storage pathways are numerous but, lucky for us, can be manipulated, or inhibited, leaving potential jiggly ugliness circulating in the body to be burned for metabolic fuel.<\/SPAN><\/P> We can\u2019t always remain perfectly strict on our diets (and let\u2019s be honest who wants to?) so for those times (muscle gaining cycles, holidays, vacations) we need a new approach to keeping lean. With Defuse, we have done just that.<\/SPAN><\/P> The Defuse formula helps to prevent fat gain by preventing the mechanisms for fat storage from working optimally, leaving the body with no choice but to burn that fat away.<\/SPAN><\/P> Defuse Fat Gain Inhibitor <\/SPAN><\/P> We can't always be completely strict on diet. Sometimes Holidays come up...sometimes we are looking to increase muscle gain. Either way, the goal is to maintain physique and prevent fat gain. Defuse was designed for just that purpose. There are multiple biological pathways that calories can travel through to cause fat storage. The more you are able to block those pathways, the more your body will change preference to burn that fat off as energy rather than store it. Using a comprehensive and dynamic formula, Defuse helps to prevent fat gain normally caused by short periods of extra calories.<\/SPAN><\/P> Directions: Take 3 capsules, 30 minutes prior to largest meals of the day<\/SPAN><\/P> Pre-Glossary<\/SPAN><\/P>
Bone and Muscle Growth Stimulator<\/strong><\/span>
120 Capsules<\/strong><\/span><\/p>\r\n\r\n Cyclodextrin-Kaempferol Complex<\/strong><\/span><\/td>\r\n 100 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Cyclodextrin-Osthole Complex<\/strong><\/span><\/td>\r\n 100 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Rhodiola Rosea (8% Salidroside)<\/strong><\/span><\/td>\r\n 240 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Ligusticum Wallichii Extract (std for 98% Ligustrazine)<\/strong><\/span><\/td>\r\n 100 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Hwanggeumchal Sorghum 100:1<\/strong><\/span><\/td>\r\n 200 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Paeoniflorin<\/strong><\/span><\/td>\r\n 100 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Sinomenine<\/strong><\/span><\/td>\r\n 75 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Quercetin<\/strong><\/span><\/td>\r\n 200 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Phytic Acid\/IP6<\/strong><\/span><\/td>\r\n 250 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Houttuynia Cordata 20:1<\/strong><\/span><\/td>\r\n 75 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Boron Citrate<\/strong><\/span><\/td>\r\n 2 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Astragalus Membranaceus 50:1 Ethanol - HPBCD Complex<\/strong><\/span><\/td>\r\n 400 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Salvia Miltiorrhiza 20:1 Water Extract<\/strong><\/span><\/td>\r\n 200 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Olive Leaf Extract (50% Oleuropein)<\/strong><\/span><\/td>\r\n 150 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Chitosan<\/strong><\/span><\/td>\r\n 50 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\n<\/div>\r\n
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.<\/p>\r\n
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).<\/p>\r\n
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.<\/p>\r\n
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.<\/p>\r\n
•X-Factor
•Any anabolic\/androgenic steroid or prohormone that you’re currently taking<\/p>\r\n
Bone and Muscle Growth Stimulator<\/strong><\/span>
120 Capsules<\/strong><\/span><\/p>\r\n\r\n Cyclodextrin-Kaempferol Complex<\/strong><\/span><\/td>\r\n 100 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Cyclodextrin-Osthole Complex<\/strong><\/span><\/td>\r\n 100 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Rhodiola Rosea (8% Salidroside)<\/strong><\/span><\/td>\r\n 240 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Ligusticum Wallichii Extract (std for 98% Ligustrazine)<\/strong><\/span><\/td>\r\n 100 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Hwanggeumchal Sorghum 100:1<\/strong><\/span><\/td>\r\n 200 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Paeoniflorin<\/strong><\/span><\/td>\r\n 100 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Sinomenine<\/strong><\/span><\/td>\r\n 75 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Quercetin<\/strong><\/span><\/td>\r\n 200 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Phytic Acid\/IP6<\/strong><\/span><\/td>\r\n 250 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Houttuynia Cordata 20:1<\/strong><\/span><\/td>\r\n 75 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Boron Citrate<\/strong><\/span><\/td>\r\n 2 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Astragalus Membranaceus 50:1 Ethanol - HPBCD Complex<\/strong><\/span><\/td>\r\n 400 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Salvia Miltiorrhiza 20:1 Water Extract<\/strong><\/span><\/td>\r\n 200 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Olive Leaf Extract (50% Oleuropein)<\/strong><\/span><\/td>\r\n 150 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n \r\n Chitosan<\/strong><\/span><\/td>\r\n 50 mg<\/strong><\/span><\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\n<\/div>\r\n
Thermodynamics and Biochemistry.... A couple of mouthfuls that don\u2019t have the potential to make you fat. Calories, on the other hand, do.<\/SPAN><\/P>
Servings per container: 60<\/SPAN><\/DIV>
Acacia Catechu Catechins 200 mg
Platycodon Grandiflorum Saponins 250 mg
Baicalin 75 mg
Rose Ellagitannins 150 mg
18b-Glycyrrhetinic Acid 50 mg
Cinchinone Bark Alchohol extract 20:1 75 mg
(-)hydroxyCitric Acid 125 mg
Dragon Fruit Extract 100 mg
Taxilus Tieghiem 20:1 100 mg
Citrus Aurantium 100 mg
Lotus Leaf 20:1 150 mg
Phospholipid Blend 250 mg
Olive Leaf 20:1 200 mg
Galega Officionalis 20:1 250 mg
Fermented Panax Ginseng Berry 20:1 175 mg
Forskolin 60% 20 mg
Methyl Cinnamate 75 mg
Raspberry Ketones 250 mg
<\/DIV><\/SPAN><\/SPAN>