EvoMuse BMP - Body Modify:Phenotype Writeup

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  1. EvoMuse BMP - Body Modify:Phenotype Writeup

    This was a long process to refine to the point of making it easy to understand. The mechanisms aren't hugely difficult, and came from a hypothesis that Bone is one of the primary control organs of phenotype expression - whether weak bones, low muscle mass, and higher fat or lean, mean and ready to rumble.

    The longer research goes on, and the more we understand, it becomes clear that the human body is always in a state of dynamic crosstalk and metabolic interplay. It's not ideal to simply hit one pathway strong and expect the best results possible. We're zeroing in on the master control switches of phenotype expression, and this is good news for those of us that strive to be our best. Now, without any more of my rambling or overexplanation, here we are:

    BMP Write-up
    We are extremely excited to open the door to a new frontier in anabolic supplementation. The pathway targeted in this formula doesn’t involve any of the well-known traditional methods, and will require no PCT or additional supplements to counteract side effects, because there aren’t any. Once user feedback gets around, you will certainly start seeing copycat formulas, as the concept of this formula has huge potential to accelerate muscle growth.

    BMP, for the sake of our new groundbreaking formula, stands for Body Modify- Phenotype.

    For the sake of the physiology it happens to be targeting, it stands for Bone Morphogenetic Protein.

    Based on new research, it turns out that a pathway once thought to only regulate bone growth/turnover is actually tightly and crucially linked to muscle growth as well. Since this research began to surface, we’ve been watching it like a hawk and researching ingredients that might take advantage of this pathway. Now that more and more research has confirmed the previous conclusions, we are confident that EvoMuse BMP is about to dig its heels in as a serious player in the toolbox for natural and assisted bodybuilders.

    Much of the research we have at this point is looking at bone anabolism as opposed to muscle, as the BMP-muscle link is such a new area. So we will have to extrapolate a bit and look at implications of the ingredients’ effects on bone growth through BMP, knowing that the same pathway is going to target muscle growth as well. At this point, when we find something that targets bone growth through supporting the BMP pathway, we can assume increased rates of muscle growth will accompany.
    Since this is quite a dense topic, it will be exponentially easier to understand, and flow through reading the write-up if several terms/concepts are at least superficially understood. Scan through these definitions first, and then refer back to them as you go through the write-up as you need clarification.

    Bone Morphogenetic Proteins (BMPs)
    BMPs are a class of growth factors belonging to the Transforming Growth Factor beta (TGF-b) superfamily. Another, contrasting part of this superfamily is the myostatin/activin subfamily.

    These two subfamilies have directly opposing functions on muscle mass, namely that BMPs are anabolic and myostatin is catabolic. Originally it was thought that BMPs were responsible, solely, for bone and cartilage formation, but recently it has been discovered that they are also key players in skeletal muscle growth.

    Interestingly, BMPs are actually dominant over myostatin signaling; when levels are high they win the anabolic/catabolic battle. BMPs are divided into specific proteins, namely BMP2, BMP4, and BMP7.

    BMP’s promote chondrocyte proliferation AND hypertrophy, and SMAD signaling (see below) regulates chondrocyte hypertrophy (1). BMP’s are unique in that they not only induce differentiation of mesenchymal stem cells to osteoblasts, and they also enhance the function of the osteoblast once differentiated (2).

    A 2013 study published in the journal Nature Genetics provided some compelling conclusions about BMP and muscle tissue (3).

    BMP signaling is the fundamental signal for hypertrophy.
    Inhibiting BMP signaling causes atrophy, abolishes myostatin deficient mice from gaining the enormous amount of muscle they normally do, and increases the negative effect from fasting.
    BMP plays a critical role in adult muscle growth.

    Now we’ll take a look at the specific types of BMPs.

    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 target of this formula, with BMP7 being the primary target.

    BMP4, while still important, is our lowest priority of the three for targeting muscle growth. Like the other BMPs it is involved in bone and cartilage development, although more specifically for teeth and limbs, as well as being a key player during embryonic development.

    BMP7 is our priority target for muscle growth. It is a major player in osteoblast differentiation as well as the induction of SMAD1 and SMAD5 (see below).

    SMADs are a family of nine proteins that live inside the cell, which fall into one of three categories (receptor-regulated, common-mediator, or inhibitory). The first two classes help to mediate BMP by bringing the extracellular signal into the nucleus of the cell where they trigger gene transcription downstream.

    SMAD4, which makes up the entirety of the common-mediator class, is a helper protein for SMAD1/2/3/5/8/9, which make up the receptor-regulated class. Once BMPs hit the cell membrane, this triggers the phosphorylation of SMAD1/5/8; they then form a complex with SMAD4 and are translocated to the nucleus. SMADs basically act as an executive assistant to BMPs.

    This is just a cartilage cell. That was easy.

    The formation of cartilage. Another gimmie.

    Mesenchymal Stem Cell (MSC)
    MSC’s are stem cells located in connective tissue throughout the body, which can differentiate down different pathways into chondrocytes, osteoblasts, or adipocytes.

    Formed from MSC’s, these cells, once grouped together are responsible for synthesizing bone. Since bone is a dynamic tissue, these cells are constantly working in anabolic opposition to the catabolic osteoclasts.

    A catabolic bone cell, osteoclasts oppose osteoblasts and encourage bone resorption (the process of breaking down bones which pushes calcium into the blood).

    Wnt Signaling Pathways
    These pathways are made up of proteins that function in a way similar to SMADs, helping pass signals from outside to inside a cell, as well as regulating b-catenin from the cytoplasm to the nucleus. This pathway is also responsible for regulating calcium inside the cell, as well as aiding in differentiation and proliferation.

    Notch Signaling Pathway
    This pathway involves cell to cell communication; for example when one cell expresses a specific trait, this pathway can be used to switch that trait off in a neighboring cell to allow a process of many cells gathering together to form large structures. It is also upstream of several differentiation processes, and encourages the osteoblast pathway from stem cells (4).

    Proliferation is simply the increase in cell number through the process of cell division.

    This is the process where a non-specific stem cell becomes a specific type of cell, like an osteoblast.

    Feel smarter? Good. Time to break down the ingredients in the formula and see what this stuff is all about.
    Kaempferol Cyclodextrin
    Kaempferol is a flavonol found in a variety of plants. The Cyclodextrin has been added to increase bioavailability. 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 (5).

    Kaempferol appears to have quite a strong effect on bone anabolism, and has been called a possible “promising agent for the prevention or treatment of bone loss” (6). A 2013 in vitro study demonstrated that Kaempferol enhanced the expression of chondrogenic marker genes, and greatly increased expression of BMP2 (7). In addition to increasing BMP2, it has also been shown to increase the number of BMP2 receptors in animals (8). More BMP and more places to dock, that’s a solid combo.

    Through a complex signaling cascade involving TAZ, RUNX2, and PPARy, MSC’s differentiate into osteoblasts or adipose tissue. Kaempferol facilitates the ability of TAZ and RUNX2 to suppress gene transcription of PPARy targets (9). Yeah, that’s confusing. So what that means to us, is that Kaempferol causes those undifferentiated MSC’s to shift to bone cells instead of fat cells. Which is pretty cool.

    Finally, Kaempferol has been shown to have a significant inhibitory effect on bone resorption, shifting the pendulum in favor of bone anabolism (10). It is worth noting, that at least part of this effect is attributable to bone specific estrogenic activity from Kaempferol which is the mechanism in which drugs like tamoxifen and toremifene help increase bone density.

    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 SMAD1/5/8 (SMAD6/7 are the inhibitory ones we don’t want to activate) (11).

    The second study, carried out by different researchers, confirmed the increased phosphorylation and expression of SMAD1/5/8. 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 (12).
    Osthole Cyclodextrin
    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 (13–15). One study even demonstrated that in mice, a high dose of Osthole had an androgenic effect and boosted LH and testosterone levels (16).

    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 MSC differentiation to osteoblasts (17). Early phase differentiation involves BMP2, SMAD1/5/8, RUNX2, and p38, whereas later phase differentiation involves ERK1/2. Osthole has been shown to enhance both phases, it sticks around until the job is done (18,19).
    Tocopherols (Mixed)
    Vitamin E is a fat soluble vitamin made up of four tocotrienols and four tocopherols, all with different functions. We have selected mixed tocopherols for this formula based on their potential benefits for BMP signaling.

    In certain conditions where BMP7 is reduced, Vitamin E has been shown to prevent this (20). However, supplementation with normal synthetic Vitamin E will increase alpha tocopherol while lowering gamma tocopherol in the blood. High gamma:alpha ratios are associated with increased biomarkers of bone formation. The mixed tocopherols in the formula will help tip the balance in favor of Gamma Tocopherol over a traditional Vitamin E supplement. Gamma tocopherol demonstrates the ability to facilitate uncoupling of bone turnover, encouraging more bone formation than resorption (21). We know when this is happening, that the BMPs are working in our favor. If you typically take a synthetic Vitamin E supplement, you may want to consider shelving that while you’re taking BMP.
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  2. Alfacalcidol
    Alfacalcidol can be considered sort of a “super” Vitamin D3. Research has shown that elevated levels of Vitamin D3 plus BMP4/6 has a potent bone inducing effect (22). Typically during high stress, one of the things that gets left behind as the body redirects its resources, is optimal bone turnover. In rats treated with glucocorticoids to mimic stress, alfacalcidol preserved bone mineral density, strength, muscle volume, and prevented fatigue vs. controls (23). Research has also shown that alfacalcidol, but not regular Vitamin D, has pleiotropic effects improving bone and muscle metabolism (24).
    Retinoic Acid
    Retinoic Acid (RA) is a Vitamin A metabolite, which aids the functions of Vitamin A necessary for growth and development. Due to the preferred differentiation of MSC’s to adipocytes in obesity, overweight or obese people are at a higher risk for osteoporosis due to less MSC’s converting to osteoblasts. RA has been shown to activate BMP & SMAD signaling, thereby shifting the direction of MSC’s to the osteoblast pathway (25). Interestingly, an increase in BMP2 stimulates MSC proliferation, but not always towards the osteoblast pathway. The addition of RA to elevated BMP2 seems to cooperate with BMP2 to further enhance proliferation, yet inhibits conversion of MSC’s to adipocytes, promoting early osteoblastic differentiation (26). Another study showed that RA was also synergistic with BMP9 in promoting the osteoblastic pathway (27). RA has also been shown to directly upregulate BMP7 activity (28).

    Lactoferrin is a bioactive protein with “unique properties towards musculo-skeletal cells and anabolic to bone in vivo”, according to a new 2014 study (29). It is derived from whey protein, and will typically make up less than 1% of the protein content of an average whey supplement, yet a whopping 15% of mother’s milk. Ironically whey concentrate powders contain much higher levels than the more expensive isolate forms. While some lactoferrin can be obtained from food and/or protein powders, the average American male consumes less than 100mg/day from dietary sources, whereas we have included a large dose of 400mg in our formula.

    Lactoferrin appears to have diverse pathways, signaling through multiple membrane bound receptors to initiate anabolic muscle and bone effects (30). Quite a bit of research in the past few years has looked at the anabolic effect of lactoferrin on bone, so lets take a look at the bullet points:

    Accelerates bone regeneration/anabolic in bone (31–37).
    Promotes proliferation, differentiation, and anti-apoptosis in MSC’s & osteoblasts (32,34,35).
    Inhibits osteoclastogenesis/bone resorption (32,34–36).
    Taken orally, preserves bone mass and improves bone microarchitecture, and is an “important physiological regulator of bone growth (35,36).
    Specifically targets BMP7 over BMP2/4, through the MAPK/ERF and RANKL pathways (36,37).

    So in summary, lactoferrin does exactly what we want it to do across the board for anabolism, while also including several bonuses such as supporting immune function, optimal insulin/glucose levels, fat loss, blood lipids, and more. For those interested, Will Brink has some great info on his site here. (http://www.brinkzone.com/articles/la...r-weight-loss/)
    Hwanggeumchal Sorghum Extract (HSE)
    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.

    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 (38). The science nerds might have noticed something particularly intriguing about that. When we trigger more BMP7, we trigger more MSC differentiation towards osteoblasts, giving the (now also elevated by HSE) anabolic IGF-1 more beneficial places to exert its effects.

    And for the bonus round, HSE has been shown to reduce plasma Total Cholesterol and Triglycerides when given to obese rats on a high fat diet (39).
    Aspergillus Awamori (AA)
    AA (not to be confused with Aspergillus niger), in addition to being a possible bonus source of lactoferrin (40), has several interesting properties relating to muscle building and blood lipid support. Most of the current research on AA has used broiler chicks as subjects, which are basically the chickens that supply the breast meat for you to eat insane quantities of. It turns out that AA causes a major shift in feed efficiency, so that every gram of protein eaten becomes more anabolic. So in these chickens (and one rat study) here’s the consensus from AA supplementation:

    Protein digestibility, protein utilization, and feed efficiency improved (41–44).
    Increased expression of GH and IGF-1 and their receptors (41).
    Improved muscle growth by favorably shifting anabolism/catabolism (41,43).
    Even with decreased food intake, muscle mass increased (43,44).
    Improved blood lipids and glucose (lower total cholesterol, LDL, TAG, BG, with an increase in HDL) (41,42,44).
    Things to Avoid/Monitor When Taking BMP
    Synthetic Vitamin E
    The synthetic form of Vitamin E (dl-alpha tocopherol) lowers gamma tocopherol, which potentially interferes with anabolic bone signaling. If you are taking Vitamin E for a medical reason, please consult with your doctor before cessation.

    Nicotine has been shown to interfere with bone formation. The addition of mixed tocopherols to the BMP formula could help counteract this, but it would still be a good idea to limit use of nicotine while using this product to prevent negative interactions with the BMP signaling cascade.
    Things to stack with BMP
    While certainly not necessary, these should provide a synergistic effect. For more information on the specifics, see the post on Anabolic Minds here.
    MyoSynergy http://www.nutraplanet.com/product/e...-capsules.html
    X-Factor http://www.nutraplanet.com/product/m...-softgels.html
    Any current anabolic
    As you can see, we have found a highly specific combination of ingredients to optimize this exciting, untapped pathway for muscle growth. In consistent EvoMuse fashion, we have spared no cost ensuring optimal dosing of each ingredient for maximum effect. If you’re working out hard and eating right, you owe it to yourself to include EvoMuse BMP in your arsenal.

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    39. Chung I-M, Yeo M-A, Kim S-J, Kim M-J, Park D-S, Moon H-I. Antilipidemic activity of organic solvent extract from Sorghum bicolor on rats with diet-induced obesity. Hum Exp Toxicol [Internet]. 2011 Nov [cited 2014 Aug 18];30(11):1865–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21078773
    40. Sun XL, Baker HM, Shewry SC, Jameson GB, Baker EN. Structure of recombinant human lactoferrin expressed in Aspergillus awamori. Acta Crystallogr D Biol Crystallogr [Internet]. 1999 Feb [cited 2014 Sep 11];55(Pt 2):403–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10089347
    41. Saleh AA, Amber K, El-Magd MA, Atta MS, Mohammed AA, Ragab MM, et al. Integrative effects of feeding Aspergillus awamori and fructooligosaccharide on growth performance and digestibility in broilers: promotion muscle protein metabolism. Biomed Res Int [Internet]. 2014 Jan [cited 2014 Sep 11];2014:946859. Available from: http://www.pubmedcentral.nih.gov/art...rtype=abstract
    42. Saleh AA, Ohtsuka A, Yamamoto M, Hayashi K. Aspergillus awamori feeding modifies lipid metabolism in rats. Biomed Res Int [Internet]. 2013 Jan [cited 2014 Sep 11];2013:594393. Available from: http://www.pubmedcentral.nih.gov/art...rtype=abstract
    43. Saleh AA, Eid YZ, Ebeid TA, Ohtsuka A, Yamamoto M, Hayashi K. Feeding Aspergillus awamori reduces skeletal muscle protein breakdown and stimulates growth in broilers. Anim Sci J [Internet]. 2012 Aug [cited 2013 Nov 11];83(8):594–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22862929
    44. Saleh AA, Eid YZ, Ebeid TA, Ohtsuka A, Hioki K, Yamamoto M, et al. The modification of the muscle fatty acid profile by dietary supplementation with Aspergillus awamori in broiler chickens. Br J Nutr [Internet]. 2012 Nov 14 [cited 2014 Sep 11];108(9):1596–602. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22289635
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  3. Good read. You sir are a genius.
    Use code "fl3x10" to get a free shirt with your purchase at Mind and Muscle

  4. Quote Originally Posted by FL3X MAGNUM View Post
    Good read. You sir are a genius.
    We're throwing this to the front of the line...well, after we restock Nerve Restore.
    Evolutionary Muse - Inspire to Evolve
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  5. That...is a damned good write up.

  6. Quote Originally Posted by ThaPeoplesChamp View Post
    That...is a damned good write up.
    This was well-worth the wait. My version would have easily been 20 pages of minutia. Marc did a superior job by a long shot. Can't stress enough the bottom section, as far as stackable products....you're going to be impressed.

    Once BRITE goes into its final stage, the leaning out will be exponentially improved - all while staying highly anabolic.
    Evolutionary Muse - Inspire to Evolve
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  7. AnabolicMinds Site Rep
    Driven2lift's Avatar

    Great information here. Definitely a product I will try out
    PEScience Representative; Use the code Driven for 30% off at pescience.com

  8. good read, can't wait for this product

  9. What will the dosing look like?

  10. Quote Originally Posted by baldymcgee View Post
    What will the dosing look like?
    Right now, we have ranged dosing, which we are dialing in via the beta testers. I will have complete details for you all in about 2 weeks. Since the Cyclo-complexed ingredients are a whole different ballgame, it changes the dosing versus if we just went with the dismal oral availability of those two ingredients - but at the same time, we don't want to put in too much (for several reasons.)
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    Flawless Skin Couture - We give you the tools to make you Flawless

  11. subbed!

  12. Need this nowwww!
    E-Pharm Rep... PM me with any questions or concerns

  13. I don't know...I think I would like to see a few more references. ? lol

  14. Subbed for future info. Extremely impressive write-up.

  15. More info on Gamma-Tocopherol, the form I used way back for NOxidant. In addition to enhancing NO levels and signalling, it has a potent effect reducing Nitrogenous Free Radicals.

    Gamma-tocopherol detoxification of nitrogen dioxide: superiority to alpha-tocopherol.

    R V Cooney,
    A A Franke,
    P J Harwood,
    V Hatch-Pigott,
    L J Custer, and
    L J Mordan

    Author Affiliations

    Authors & Info
    Related Content


    In the vitamin E group, alpha-tocopherol is generally considered to be the most potent antioxidant with the highest vitamin bioactivity, yet gamma-tocopherol is produced in greater amounts by many plants and is the principal tocopherol in the United States diet. This report describes a fundamental difference in the chemical reactivities of alpha-tocopherol and gamma-tocopherol with nitrogen dioxide (NO2), which leads to the formation of a nitrosating agent from alpha-tocopherol, but not from gamma-tocopherol. Nitric oxide (NO) is a major product of the reaction of gamma-tocopherol with NO2, while alpha-tocopherol reacts with NO2 to form an intermediate tocopheroxide analogue. The biological significance of gamma-tocopherol is suggested by limited epidemiological data as well as the observation that it is a more potent inhibitor than alpha-tocopherol of neoplastic transformation during the postinitiation phase in 3-methylcholanthrene-treated C3H/10T1/2 murine fibroblasts. This latter property suggests the superiority of gamma-tocopherol in a mammalian biological assay and a role for endogenous NO production in promotion of neoplastic transformation.
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  16. Another Vitamin E study supporting our hypothesis...

    J Bone Miner Metab. 2010 Sep;28(5):503-9. doi: 10.1007/s00774-010-0159-2. Epub 2010 Feb 10.
    Beneficial effects of vitamin E isomer supplementation on static and dynamic bone histomorphometry parameters in normal male rats.
    Mehat MZ1, Shuid AN, Mohamed N, Muhammad N, Soelaiman IN.
    Author information

    Bone is a specialized connective tissue that functions as the load-bearing structure of the body. Free radicals may affect bone remodeling by regulating osteoclast activity in either the physiological or pathological condition. Vitamin E, a lipid-soluble antioxidant, has been demonstrated to offer protection against osteoporosis and to improve the bone material and structure of animal models. The aim of this study was to observe and compare the effects of alpha-tocopherol (alpha-tocopherol), delta-tocotrienol (delta-tocotrienol), and gamma-tocotrienol (gamma-tocotrienol) on the static and dynamic bone histomorphometric parameters in normal male rats. Thirty-two normal Sprague-Dawley male rats aged 3 months and weighing 200-250 g were randomly divided into four groups. The control group was supplemented with oral gavages of olive oil (vehicle), whereas the alpha-tocopherol, delta-tocotrienol, and gamma-tocotrienol groups were given oral gavages of 60 mg/kg alpha-tocopherol, delta-tocotrienol, and gamma-tocotrienol, respectively. The rats were injected twice with calcein to fluorochrome-label the bones. After 4 months of treatment, the rats were killed, and the left femurs were dissected out and prepared for bone histomorphometry. Both the static and dynamic parameters of the vitamin E-treated groups were better than those of the normal control group. Among the vitamin E-treated groups, the tocotrienol groups showed better histomorphometry results compared to the α-tocopherol group, with the γ-tocotrienol group demonstrating the best effects on both sets of parameters. We concluded that vitamin E can promote bone formation in normal rats, with gamma-tocotrienol being the most potent form of vitamin E.

    [PubMed - indexed for MEDLINE]

    The ingredient we are using is gamma heavy with both Tocopherols and Tocotrienols.
    Evolutionary Muse - Inspire to Evolve
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  17. Great writeup. I'm a tester - do your last few posts mean I can continue taking my Noxidant? Also, are we all receiving the ingredient that we need to wear the mask for? Or is that something else?

    I'll be logging on here, excited to try this out.

  18. Quote Originally Posted by warnerve View Post
    Great writeup. I'm a tester - do your last few posts mean I can continue taking my Noxidant? Also, are we all receiving the ingredient that we need to wear the mask for? Or is that something else?

    I'll be logging on here, excited to try this out.
    the Aspergillus Awamori....no you won't need a mask, just don't snort it.

  19. Very interesting and can't wait to try it.

  20. Amazing write-up. Sounds very promising. I trust your work. Looking forward to it.

  21. incredible man.

  22. I told Marc to leave this angle out, but this is decently important to the Phenotype Modification, as mentioned, along with BRITE.


    BMP4 and BMP7 induce the white-to-brown transition of primary human adipose stem
    Am. J. Physiol., Cell Physiol. 2014 (5):C431-40
    Manuela Elsen, Silja Raschke, Norbert Tennagels, Uwe Schwahn, Tomas Jelenik,
    Michael Roden, Tania Romacho, Jürgen Eckel

    While white adipose tissue (AT) is an energy storage depot, brown AT is
    specialized in energy dissipation. Uncoupling protein 1 (UCP1)-expressing
    adipocytes with a different origin than classical brown adipocytes have been
    found in white AT. These "brite" (brown-in-white) adipocytes may represent a
    therapeutic target to counteract obesity. Bone morphogenetic proteins (BMPs)
    play a role in the regulation of adipogenesis. Based on studies with murine
    cells, BMP4 is assumed to induce stem cell commitment to the white adipocyte
    lineage, whereas BMP7 promotes brown adipogenesis. There is evidence for
    discrepancies between mouse and human AT. Therefore, we compared the effect of
    BMP4 and BMP7 on white-to-brown transition in primary human adipose stem cells
    (hASCs) from subcutaneous AT. Long-term exposure of hASCs to recombinant BMP4 or
    BMP7 during differentiation increased adipogenesis, as determined by lipid
    accumulation and peroxisome proliferator-activated receptor-γ (PPARγ)
    expression. Not only BMP7, but also BMP4, increased UCP1 expression in hASCs and
    decreased expression of the white-specific marker TCF21. The ability of hASCs to
    induce UCP1 in response to BMP4 and BMP7 markedly differed between donors and
    could be related to the expression of the brite marker CD137. However,
    mitochondrial content and oxygen consumption were not increased in hASCs
    challenged with BMP4 and BMP7. In conclusion, we showed for the first time that
    BMP4 has similar effects on white-to-brown transition as BMP7 in our human cell
    model. Thus the roles of BMP4 and BMP7 in adipogenesis cannot always be
    extrapolated from murine to human cell models.

    -send by Go PubMed iPhone App.

    PLoS One. 2013 Sep 16;8(9):e74083. doi: 10.1371/journal.pone.0074083. eCollection 2013.
    BMP7 activates brown adipose tissue and reduces diet-induced obesity only at subthermoneutrality.
    Boon MR1, van den Berg SA, Wang Y, van den Bossche J, Karkampouna S, Bauwens M, De Saint-Hubert M, van der Horst G, Vukicevic S, de Winther MP, Havekes LM, Jukema JW, Tamsma JT, van der Pluijm G, van Dijk KW, Rensen PC.
    Author information

    Brown adipose tissue (BAT) dissipates energy stored in triglycerides as heat via the uncoupling protein UCP-1 and is a promising target to combat hyperlipidemia and obesity. BAT is densely innervated by the sympathetic nervous system, which increases BAT differentiation and activity upon cold exposure. Recently, Bone Morphogenetic Protein 7 (BMP7) was identified as an inducer of BAT differentiation. We aimed to elucidate the role of sympathetic activation in the effect of BMP7 on BAT by treating mice with BMP7 at varying ambient temperature, and assessed the therapeutic potential of BMP7 in combating obesity.

    High-fat diet fed lean C57Bl6/J mice were treated with BMP7 via subcutaneous osmotic minipumps for 4 weeks at 21 °C or 28 °C, the latter being a thermoneutral temperature in which sympathetic activation of BAT is largely diminished. At 21 °C, BMP7 increased BAT weight, increased the expression of Ucp1, Cd36 and hormone-sensitive lipase in BAT, and increased total energy expenditure. BMP7 treatment markedly increased food intake without affecting physical activity. Despite that, BMP7 diminished white adipose tissue (WAT) mass, accompanied by increased expression of genes related to intracellular lipolysis in WAT. All these effects were blunted at 28 °C. Additionally, BMP7 resulted in extensive 'browning' of WAT, as evidenced by increased expression of BAT markers and the appearance of whole clusters of brown adipocytes via immunohistochemistry, independent of environmental temperature. Treatment of diet-induced obese C57Bl6/J mice with BMP7 led to an improved metabolic phenotype, consisting of a decreased fat mass and liver lipids as well as attenuated dyslipidemia and hyperglycemia.

    Together, these data show that BMP7-mediated recruitment and activation of BAT only occurs at subthermoneutral temperature, and is thus likely dependent on sympathetic activation of BAT, and that BMP7 may be a promising tool to combat obesity and associated disorders
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  23. Nature. 2008 Aug 21;454(7207):1000-4. doi: 10.1038/nature07221.
    New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure.
    Tseng YH1, Kokkotou E, Schulz TJ, Huang TL, Winnay JN, Taniguchi CM, Tran TT, Suzuki R, Espinoza DO, Yamamoto Y, Ahrens MJ, Dudley AT, Norris AW, Kulkarni RN, Kahn CR.
    Author information

    Adipose tissue is central to the regulation of energy balance. Two functionally different types of fat are present in mammals: white adipose tissue, the primary site of triglyceride storage, and brown adipose tissue, which is specialized in energy expenditure and can counteract obesity. Factors that specify the developmental fate and function of white and brown adipose tissue remain poorly understood. Here we demonstrate that whereas some members of the family of bone morphogenetic proteins (BMPs) support white adipocyte differentiation, BMP7 singularly promotes differentiation of brown preadipocytes even in the absence of the normally required hormonal induction cocktail. BMP7 activates a full program of brown adipogenesis including induction of early regulators of brown fat fate PRDM16 (PR-domain-containing 16; ref. 4) and PGC-1alpha (peroxisome proliferator-activated receptor-gamma (PPARgamma) coactivator-1alpha; ref. 5), increased expression of the brown-fat-defining marker uncoupling protein 1 (UCP1) and adipogenic transcription factors PPARgamma and CCAAT/enhancer-binding proteins (C/EBPs), and induction of mitochondrial biogenesis via p38 mitogen-activated protein (MAP) kinase-(also known as Mapk14) and PGC-1-dependent pathways. Moreover, BMP7 triggers commitment of mesenchymal progenitor cells to a brown adipocyte lineage, and implantation of these cells into nude mice results in development of adipose tissue containing mostly brown adipocytes. Bmp7 knockout embryos show a marked paucity of brown fat and an almost complete absence of UCP1. Adenoviral-mediated expression of BMP7 in mice results in a significant increase in brown, but not white, fat mass and leads to an increase in energy expenditure and a reduction in weight gain. These data reveal an important role of BMP7 in promoting brown adipocyte differentiation and thermogenesis in vivo and in vitro, and provide a potential new therapeutic approach for the treatment of obesity.
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  24. Very interested in testing possibly. What is the usual time frame to see results from this? Also, Is this another "no need to cycle" product?

  25. Quote Originally Posted by chedapalooza View Post
    Very interested in testing possibly. What is the usual time frame to see results from this? Also, Is this another "no need to cycle" product?
    this won't be instant like MyoSynergy, but you should start to notice this kicking in within 2 weeks, depending on your total stack.


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