EvoMuse BMP Writeup (UPDATED)

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Ok, guys - here is the writeup covering the updated formula.

BMP 2.0 Write Up
Intro
EvoMuse released the original BMP formula almost a year ago and it became extremely popular with tons of great user feedback, fully delivering on the muscle building hype. During this time however, we’ve found a way to make BMP even better while still keeping it just as cost-effective. If you’re familiar with the original formula, you’ll notice quite a few similarities, but also a few key changes that we’re confident will give users even better results.

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

BMP7
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
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.

Chondrocyte
This is just a cartilage cell. That was easy.

Chondrogenesis
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.

Osteoblast
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.

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

Differentiation
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.
 
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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 “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
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).

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.

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.
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 (producing multiple actions from a single gene) 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).
Ligustrum Wallichii Extract (55% ligustrazine)
Isolated from the fermented food Natto, LWE is an interesting compound with well known anti-inflammatory and nootropic properties (29,30). More importantly, however, LWE has recently been shown to significantly elevate BMP7 (30). 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 re-used (31).

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) (32,33).

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 (30,34).
Paeoniflorin
Paeoniflorin is a compound isolated from a fresh water fern by the name of Salvinia molesta. Working through multiple mechanisms, Paeoniflorin has a direct stimulatory effect on bone formation signaling (35). The current research on this compound has looked mainly at the potential beneficial effects in certain bone related disease states, which we can use to make some reasonable assumptions in how it might behave in healthy individuals. Renal fibrosis involves the accumulation of excess fibrous material in the extracellular matrix of kidney cells,

Renal (kidney) fibrosis is the principal process underlying the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD). In this condition, BMP-7 expression and SMAD activation tends to become quite disrupted, and Paeoniflorin has been shown to normalize this signaling (36). This could very well translate to increased BMP-7 expression in healthy individuals.

In Rheumatoid Arthritis (RA), the body attacks the joints through an inflammatory cascade, causing pain, joint swelling, bone erosion and cartilage breakdown. Paeoniflorin supplementation has been shown to reverse or severely diminish all of these problems, largely through controlling the inflammatory factors prostaglandin E2, leukotriene B4, ROS, and cytokines IL-1B and TNF-a (37,38).

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 (39).

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 (40–42). They have also been shown to improve insulin sensitivity, reduce oxidative stress, inhibit inflammatory pathways and enhance the metabolic characteristics of muscle cells (43).

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 (44).
Sorghum Extract (SE)
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. SE 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 (45). 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, SE has been shown to reduce plasma Total Cholesterol and Triglycerides when given to obese rats on a high fat diet (46).

For the new BMP formula we have increased the dose from 125mg up to 200mg to get even more of a boost from this powerful compound.
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
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 Elite
X-Factor
Any anabolic/androgenic steroid or prohormone that you’re currently taking


Conclusion
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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1. Tsumaki N, Horiki M, Murai J, Yoshikawa H. [Role of BMPs and Smads during endochondral bone formation]. Clin Calcium. 2004 Jul;14(7):52–7.

2. Canalis E, Economides AN, Gazzerro E. Bone morphogenetic proteins, their antagonists, and the skeleton. Endocr Rev. 2003 Apr;24(2):218–35.

3. Sartori R, Schirwis E, Blaauw B, Bortolanza S, Zhao J, Enzo E, et al. BMP signaling controls muscle mass. Nat Genet. 2013 Nov;45(11):1309–18.

4. Nobta M, Tsukazaki T, Shibata Y, Xin C, Moriishi T, Sakano S, et al. Critical regulation of bone morphogenetic protein-induced osteoblastic differentiation by Delta1/Jagged1-activated Notch1 signaling. J Biol Chem. 2005 Apr;280(16):15842–8.

5. Da-Silva WS, Harney JW, Kim BW, Li J, Bianco SDC, Crescenzi A, et al. The small polyphenolic molecule kaempferol increases cellular energy expenditure and thyroid hormone activation. Diabetes. 2007 Mar;56(3):767–76.

6. Miyake M, Arai N, Ushio S, Iwaki K, Ikeda M, Kurimoto M. Promoting effect of kaempferol on the differentiation and mineralization of murine pre-osteoblastic cell line MC3T3-E1. Biosci Biotechnol Biochem. 2003 Jun;67(6):1199–205.

7. Nepal M, Li L, Cho HK, Park JK, Soh Y. Kaempferol induces chondrogenesis in ATDC5 cells through activation of ERK/BMP-2 signaling pathway. Food Chem Toxicol Int J Publ Br Ind Biol Res Assoc. 2013 Dec;62:238–45.

8. Long M, Li S-X, Xiao J-F, Wang J, Scott L, Zhang Z-G, et al. Kidney tubular-cell secretion of osteoblast growth factor is increased by kaempferol: A scientific basis for “The Kidney Controlling the Bone” theory of chinese medicine. Chin J Integr Med [Internet]. 2014 Jul; Available from: http://www.ncbi.nlm.nih.gov/pubmed/25012631

9. Byun MR, Jeong H, Bae SJ, Kim AR, Hwang ES, Hong J-H. TAZ is required for the osteogenic and anti-adipogenic activities of kaempferol. Bone. 2012 Jan;50(1):364–72.

10. Wattel A, Kamel S, Mentaverri R, Lorget F, Prouillet C, Petit J-P, et al. Potent inhibitory effect of naturally occurring flavonoids quercetin and kaempferol on in vitro osteoclastic bone resorption. Biochem Pharmacol. 2003 Jan;65(1):35–42.

11. Chen J-J, Zhang N-F, Mao G-X, He X-B, Zhan Y-C, Deng H-B, et al. Salidroside stimulates osteoblast differentiation through BMP signaling pathway. Food Chem Toxicol Int J Publ Br Ind Biol Res Assoc. 2013 Dec;62:499–505.

12. Zhao H-B, Qi S-N, Dong J-Z, Ha X-Q, Li X-Y, Zhang Q-W, et al. Salidroside induces neuronal differentiation of mouse mesenchymal stem cells through Notch and BMP signaling pathways. Food Chem Toxicol Int J Publ Br Ind Biol Res Assoc. 2014 Sep;71:60–7.

13. Lee W-H, Lin R-J, Lin S-Y, Chen Y-C, Lin H-M, Liang Y-C. Osthole enhances glucose uptake through activation of AMP-activated protein kinase in skeletal muscle cells. J Agric Food Chem. 2011 Dec;59(24):12874–81.

14. Liang H-J, Suk F-M, Wang C-K, Hung L-F, Liu D-Z, Chen N-Q, et al. Osthole, a potential antidiabetic agent, alleviates hyperglycemia in db/db mice. Chem Biol Interact. 2009 Oct;181(3):309–15.

15. Zhang Y, Xie M, Xue J, Gu Z. Osthole improves fat milk-induced fatty liver in rats: modulation of hepatic PPAR-alpha/gamma-mediated lipogenic gene expression. Planta Med. 2007 Jul;73(8):718–24.

16. Yuan J, Xie J, Li A, Zhou F. [Effects of osthol on androgen level and nitric oxide synthase activity in castrate rats]. Zhong Yao Cai Zhongyaocai J Chin Med Mater. 2004 Jul;27(7):504–6.

17. Tang D-Z, Hou W, Zhou Q, Zhang M, Holz J, Sheu T-J, et al. Osthole stimulates osteoblast differentiation and bone formation by activation of beta-catenin-BMP signaling. J Bone Miner Res Off J Am Soc Bone Miner Res. 2010 Jun;25(6):1234–45.

18. Kuo P-L, Hsu Y-L, Chang C-H, Chang J-K. Osthole-mediated cell differentiation through bone morphogenetic protein-2/p38 and extracellular signal-regulated kinase 1/2 pathway in human osteoblast cells. J Pharmacol Exp Ther. 2005 Sep;314(3):1290–9.

19. Ming L-G, Zhou J, Cheng G-Z, Ma H-P, Chen K-M. Osthol, a coumarin isolated from common cnidium fruit, enhances the differentiation and maturation of osteoblasts in vitro. Pharmacology. 2011 Jan;88(1-2):33–43.

20. Tasanarong A, Kongkham S, Thitiarchakul S, Eiam-Ong S. Vitamin E ameliorates renal fibrosis in ureteral obstruction: role of maintaining BMP-7 during epithelial-to-mesenchymal transition. J Med Assoc Thail Chotmaihet Thangphaet. 2011 Dec;94 Suppl 7:S10–8.

21. Hamidi MS, Corey PN, Cheung AM. Effects of vitamin E on bone turnover markers among US postmenopausal women. J Bone Miner Res Off J Am Soc Bone Miner Res. 2012 Jun;27(6):1368–80.

22. Sammons J, Ahmed N, El-Sheemy M, Hassan HT. The role of BMP-6, IL-6, and BMP-4 in mesenchymal stem cell-dependent bone development: effects on osteoblastic differentiation induced by parathyroid hormone and vitamin D(3). Stem Cells Dev. 2004 Jun;13(3):273–80.

23. Miyakoshi N, Sasaki H, Kasukawa Y, Kamo K, Shimada Y. Effects of a vitamin D analog, alfacalcidol, on bone and skeletal muscle in glucocorticoid-treated rats. Biomed Res Tokyo Jpn. 2010 Jan;31(6):329–36.

24. Scharla SH, Schacht E, Lempert UG. Alfacalcidol versus plain vitamin D in inflammation induced bone loss. J Rheumatol Suppl. 2005 Sep;76:26–32.

25. Liu Y, Liu Y, Zhang R, Wang X, Huang F, Yan Z, et al. All-trans retinoic acid modulates bone morphogenic protein 9-induced osteogenesis and adipogenesis of preadipocytes through BMP/Smad and Wnt/β-catenin signaling pathways. Int J Biochem Cell Biol. 2014 Feb;47:47–56.

26. Skillington J, Choy L, Derynck R. Bone morphogenetic protein and retinoic acid signaling cooperate to induce osteoblast differentiation of preadipocytes. J Cell Biol. 2002 Oct;159(1):135–46.

27. Zhang W, Deng Z-L, Chen L, Zuo G-W, Luo Q, Shi Q, et al. Retinoic Acids Potentiate BMP9-Induced Osteogenic Differentiation of Mesenchymal Progenitor Cells. Linden R, editor. PLoS ONE. 2010 Jul;5(7):e11917.

28. Paralkar VM, Grasser WA, Mansolf AL, Baumann AP, Owen TA, Smock SL, et al. Regulation of BMP-7 expression by retinoic acid and prostaglandin E(2). J Cell Physiol. 2002 Feb;190(2):207–17.

29. Wu W, Yu X, Luo X-P, Yang S-H, Zheng D. Tetramethylpyrazine protects against scopolamine-induced memory impairments in rats by reversing the cAMP/PKA/CREB pathway. Behav Brain Res. 2013 Sep 15;253:212–6.

30. Yuan X, Liu L, Fu Q, Wang C. Effects of ligustrazine on ureteral obstruction-induced renal tubulointerstitial fibrosis. Phytother Res PTR. 2012 May;26(5):697–703.

31. Ulianich L, Elia MG, Treglia AS, Muscella A, Di Jeso B, Storelli C, et al. The sarcoplasmic-endoplasmic reticulum Ca2+ ATPase 2b regulates the Ca2+ transients elicited by P2Y2 activation in PC Cl3 thyroid cells. J Endocrinol. 2006 Sep;190(3):641–9.

32. Wang H, Liang B, Peng C, Wang P. [Effect of Ligustrazine on expressions of FoXO3a, MAFbx, and MuRF1 in denervated skeletal muscle atrophy rats]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi Zhongguo Xiufu Chongjian Waike Zazhi Chin J Reparative Reconstr Surg. 2012 May;26(5):597–600.

33. Zhang H, He Z, Gao Y, Hinghofer-Szalkay HG, Fan X. Muscle composition after 14-day hindlimb unloading in rats: effects of two herbal compounds. Aviat Space Environ Med. 2007 Oct;78(10):926–31.

34. Gao X, Zhao X, Zhu Y, Li X, Xu Q, Lin H, et al. Tetramethylpyrazine protects palmitate-induced oxidative damage and mitochondrial dysfunction in C2C12 myotubes. Life Sci. 2011 Apr;88(17-18):803–9.

35. Yen PH, Kiem PV, Nhiem NX, Tung NH, Quang TH, Minh CV, et al. A new monoterpene glycoside from the roots of Paeonia lactiflora increases the differentiation of osteoblastic MC3T3-E1 cells. Arch Pharm Res. 2007 Oct;30(10):1179–85.

36. Zeng J, Dou Y, Guo J, Wu X, Dai Y. Paeoniflorin of Paeonia lactiflora prevents renal interstitial fibrosis induced by unilateral ureteral obstruction in mice. Phytomedicine Int J Phytother Phytopharm. 2013 Jun 15;20(8-9):753–9.

37. Wu D, Chen J, Zhu H, Xiong X-G, Liang Q-H, Zhang Y, et al. UPLC-PDA determination of paeoniflorin in rat plasma following the oral administration of Radix Paeoniae Alba and its effects on rats with collagen-induced arthritis. Exp Ther Med. 2014 Jan;7(1):209–17.

38. Zhang W, Dai S-M. Mechanisms involved in the therapeutic effects of Paeonia lactiflora Pallas in rheumatoid arthritis. Int Immunopharmacol. 2012 Sep;14(1):27–31.

39. Ni J, Yang D, Song L, Li C. Protective effects of paeoniflorin on alveolar bone resorption and soft-tissue breakdown in experimental periodontitis. J Periodontal Res. 2015 Jul 14;

40. Hu B, Mayer MP, Tomita M. Modeling Hsp70-mediated protein folding. Biophys J. 2006 Jul 15;91(2):496–507.

41. Hu B, Tomita M. The Hsp70 chaperone system maintains high concentrations of active proteins and suppresses ATP consumption during heat shock. Syst Synth Biol. 2007 Mar;1(1):47–58.

42. Frier BC, Locke M. Heat stress inhibits skeletal muscle hypertrophy. Cell Stress Chaperones. 2007;12(2):132–41.

43. Geiger PC, Gupte AA. Heat Shock Proteins Are Important Mediators of Skeletal Muscle Insulin Sensitivity. Exerc Sport Sci Rev. 2011 Jan;39(1):34–42.

44. Yan D, Saito K, Ohmi Y, Fujie N, Ohtsuka K. Paeoniflorin, a novel heat shock protein–inducing compound. Cell Stress Chaperones. 2004 Oct;9(4):378–89.

45. Joung YH, Lim EJ, Darvin P, Jang JW, Park KD, Lee HK, et al. Hwanggeumchal sorghum extract enhances BMP7 and GH signaling through the activation of Jak2/STAT5B in MC3T3‑E1 osteoblastic cells. Mol Med Rep. 2013 Sep;8(3):891–6.

46. 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. 2011 Nov;30(11):1865–8.
 
cubsfan815

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Brain exploded, subbed to reread after work.
 

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It says Sorghum Extract (SE) in the title for that ingredient but in the next paragraph it goes to HSE, from the previous write-up where the ingredient was listed as Hwanggeumchal Sorghum Extract (HSE).
 
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Same ingredient
 
Auslifter

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slintensity and popcorn at the ready, waiting for the USPS Van today :D
 
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It says Sorghum Extract (SE) in the title for that ingredient but in the next paragraph it goes to HSE, from the previous write-up where the ingredient was listed as Hwanggeumchal Sorghum Extract (HSE).
This section was mostly a copy/paste from the original write up, because as Matt said, same ingredient. But good catch, I swapped a few HSE's for SE's but I missed that one.
 

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Cool stuff. Today is my 2nd day of EvoMuse BMP. Not sure what I should be noticing but I'll keep things posted. Right now I'm on OG MyoSynergy/BRITE (for about a month)/BMP.
 
Geoforce

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Looking good. Can't wait to run it myself!
 

ma70

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Whew, BMP + BRITE stacked together are making me run hot as hell!
 
dsade

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Whew, BMP + BRITE stacked together are making me run hot as hell!
I can't find my BRITE, but the BMP is working just as promised.

I jumped to 194 today with no fat gain.
 

ma70

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I can't find my BRITE, but the BMP is working just as promised.

I jumped to 194 today with no fat gain.
How long have you been on BMP? I've noticed a weird phenomenon where my scale weight is going up but I'm not looking fatter.
 
dsade

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After I came out of the Hospital at around 180, I started the following week. MyoElite and BMP and I am adding 3 lbs or so a week.
 

ma70

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After I came out of the Hospital at around 180, I started the following week. MyoElite and BMP and I am adding 3 lbs or so a week.
Increased glycogen/water is probably some of the weight, right?
 
dsade

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Yeah that's definitely part of it, though doc has me on a diuretic.
 
Geoforce

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Check around for some amazing deals. Google can lead you to BMP+MyoElite+Free Java Lather and a 5 dollar discount on the entire stack.
 

ma70

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Weird, I've been feeling a mix of spaced out or nauseous when combining caffeine+BMP+BRITE together. Should I be drinking more water or something?
 
dsade

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Caffeine and BMP has some potential amplification. Is it like caffeine overdose?
 

ma70

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Caffeine and BMP has some potential amplification. Is it like caffeine overdose?
Never had caffeine overdose, but I'm taking 200mg caffeine pre-workout with BRITE/BMP. With BRITE, it was okay, but adding BMP makes me feel a bit weird.
 
cubs1987

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Would you suggest lowering caffeine around the BMP dose? I typically dose around 250mg preworkout
 
dsade

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Would you suggest lowering caffeine around the BMP dose? I typically dose around 250mg preworkout
Has it hit you extra hard?
 
dsade

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Maybe a little more focused and in the zone... But I just started BMP so my sample size is pretty small (a few days).
I would keep going as-is, just monitor yourself for any signs of problems.
 

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I'm assuming that this isn't recommended for females??
 

Drock1234

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I'm stoked to run this. Any update on the BMP back order for those who purchased the TPS stack a while back??
 

ma70

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Okay, today was much better. I drank a LOT more water. I guess the combined heat of BMP/BRITE was too much for me and I was probably just dehydrated.
 
GiftedNatty

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Has it hit you extra hard?
I've taken Alphamine with BMP the past two days and it has seriously wrecked me like never before. In a good way, just surprised at the alertness because I've taken stims consistently higher for a while
 

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Noticing rapid weight gain. It's been about a week and my waist is the same, but my weight is up. Since I'm on a periodized powerlifting program, I'm also noticing that weights are becoming almost too easy but for now, I'm not going to deviate from the program. I'll just focus on perfect form/range of motion, and maybe I'll shorten rest between sets.
 
dsade

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I'm working rest periods manipulation as well.
 

max silver

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After I came out of the Hospital at around 180, I started the following week. MyoElite and BMP and I am adding 3 lbs or so a week.
How would you categorize your calorie intake with regards to maintenance levels?
 
dsade

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How would you categorize your calorie intake with regards to maintenance levels?
I've been eating right around 2300 and only making sure on getting 250g of protein in.

I don't have access to any kitchens at the moment so it's been tough.
 

ma70

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I've been eating right around 2300 and only making sure on getting 250g of protein in.

I don't have access to any kitchens at the moment so it's been tough.
So is 2300 your maintenance? (Just curious)

Cause I'm confused as to why my scale weight is shooting up when I'm eating near maintenance. I'm worried I'm getting fat (even though I'm not)
 
dsade

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So is 2300 your maintenance? (Just curious)

Cause I'm confused as to why my scale weight is shooting up when I'm eating near maintenance. I'm worried I'm getting fat (even though I'm not)
It's within 100 cals of my maintenance intake.
In the past 3 days I've gained 10 lbs (192 to 202) with no explanation. I'm going to go check out the full length mirror and see what this is about. I haven't out on much, if any, fat.
 

ma70

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It's within 100 cals of my maintenance intake.
In the past 3 days I've gained 10 lbs (192 to 202) with no explanation. I'm going to go check out the full length mirror and see what this is about. I haven't out on much, if any, fat.
Okay, so it's not only me. I went from 200 to 211 and it's been about a week. Waist is consistent, but I'm noticing leg hypertrophy (certain underwear is tight around my thighs now), and my upper body leaning out (or looking more muscular, I don't know). Feeling stronger on most lifts, but I was assuming it's because my bodyweight increased (which makes upper body lifts like the bench easier). Combining it with BRITE though, so maybe they're synergistic for leaning out.

For now, just assuming it's glycogen and water mostly.
 
dsade

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Okay, so it's not only me. I went from 200 to 211 and it's been about a week. Waist is consistent, but I'm noticing leg hypertrophy (certain underwear is tight around my thighs now), and my upper body leaning out (or looking more muscular, I don't know). Feeling stronger on most lifts, but I was assuming it's because my bodyweight increased (which makes upper body lifts like the bench easier). Combining it with BRITE though, so maybe they're synergistic for leaning out.

For now, just assuming it's glycogen and water mostly.
I'm just happy I broke 200lbs again.
 

ma70

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I'm just happy I broke 200lbs again.
Generally tracking my diet to hit 200g protein and not looking too much at carbs/fats, I generally maintain 198-207 (I seem to hold water easily on some days) effortlessly. Hitting 211 randomly is weird for me.
 

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Quick question for you Dsade, although somewhat unrelated to this particular thread. When on a lean gaining phase what dosage of DCP would you recommend to keep fat gain at bay? I have a few bottles of DCP 2.0 which expire in November that I should think about using up.
 
dsade

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Quick question for you Dsade, although somewhat unrelated to this particular thread. When on a lean gaining phase what dosage of DCP would you recommend to keep fat gain at bay? I have a few bottles of DCP 2.0 which expire in November that I should think about using up.
During a lean bulk I would up the dosage a bit...2 caps morning, 3 caps preworkout, 2 caps spaced depending on your workout time (afternoon, evening) than add in 1 cap right before bed. That's an extra 2 caps per day, but it does work for a lean bulk.
 

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During a lean bulk I would up the dosage a bit...2 caps morning, 3 caps preworkout, 2 caps spaced depending on your workout time (afternoon, evening) than add in 1 cap right before bed. That's an extra 2 caps per day, but it does work for a lean bulk.
Interesting, I'll slowly increase my dosage over the next while then. I've found that when in a low calorie state I actually need to take a lower dose due to some pretty severe lethargy I suffer, particularly while ingesting a lower amount of carbs. 4-5 caps a day was the tops I could manage with the lethargy kicking my butt.

What is the reasoning for the large dose preworkout?
 
dsade

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Ppar delta activation increases with exercise, so you want the stronger hit preworkout.
http://www.ncbi.nlm.nih.gov/m/pubmed/16328010/

Peroxisome proliferator-activated receptors (PPARs) alpha, delta and gamma are nuclear transcription factors that control key genes involved in fatty acid metabolism and energy homeostasis. Little is known about PPAR activation in vivo and the existence of overlapping functions between PPARalpha, -delta and -gamma. As skeletal muscle is an important site for insulin action and acts as a significant sensor for life-style-induced influences in whole-body energy metabolism, we investigated the expression of PPARalpha, -delta and -gamma in rat skeletal muscle in response to exercise after four- and twelve-weeks of high-fat feeding, respectively. PPARalpha mRNA expression in skeletal muscle increased in parallel with other signs of developing metabolic syndrome such as increased visceral fat pad volymes, plasma free fatty acids and muscle triglyceride concentrations. PPARalpha mRNA expression was up-regulated 3-fold after four weeks of high-fat feeding (p<0.01). Exercise reversed the high-fat induced increase in PPARalpha expression in young lean rats (p<0.05), but did not change the PPARalpha, -delta and -gamma expression in the skeletal muscle in the normal nutritional state. The increase in PPARalpha expression declined during a longer term of high-fat feeding. In contrast, exercise increased PPARdelta mRNA and protein expression 3- to 6-fold in skeletal muscle after longer-term high-fat feeding (p<0.05). This effect was accompanied by a reduction in skeletal muscle fat content. These findings suggest that parallel activation of PPARalpha and -delta expression in skeletal muscle may be an important adaptive mechanism in response to increased fatty acid loads in young, lean animals, protecting them from insulin resistance, whereas exercise might be needed to mediate the same positive effects in older animals.


Trying to copy paste from phone, so hope it comes out ok.
 

ma70

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Just weighed myself first thing this morning. 206.8 lbs on the digital scale without eating anything today. Not looking fatter. I'll try lowering my cals to see if the recomping effect gets stronger.
 

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I'm assuming those of you who are seeing increased weight but not seeing additional fat are also not seeing a increase in muscular development that would correspond to such a gain in weight.

Could the increased weight be bone density? Maybe I'm misinterpreting the write-up, but it seems like increased bone mass / density would be a likely effect.

If so, hey, that's like adding weights onto your reps! Additional resistance training and stronger bones!
 

ma70

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I'm assuming those of you who are seeing increased weight but not seeing additional fat are also not seeing a increase in muscular development that would correspond to such a gain in weight.

Could the increased weight be bone density? Maybe I'm misinterpreting the write-up, but it seems like increased bone mass / density would be a likely effect.

If so, hey, that's like adding weights onto your reps! Additional resistance training and stronger bones!
If it means anything, my left shoulder (which is generally a bit "creaky" and problematic") feels rock solid. I'm not going to accustom this to BMP or anything, but it's a weird change I've noticed. Anyways, I don't know if it's because I've been running BRITE for a month, or if BMP stacks awesomely with BRITE, but I'm seeing noticeable changes left and right now. Increased weight, maintaining leanness, and feeling way stronger.
 
MidwestBeast

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I've got BMP on the way and I'm planning on an extended run with Myo, BRITE, and LipoMorph -- very excited to see what will happen based on everyone's notes so far.
 

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I've got BMP on the way and I'm planning on an extended run with Myo, BRITE, and LipoMorph -- very excited to see what will happen based on everyone's notes so far.
You're probably going to be running pretty hot. BRITE + BMP + Caffeine is making me feel feverish all the time if I even walk a couple of minutes.
 
MidwestBeast

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You're probably going to be running pretty hot. BRITE + BMP + Caffeine is making me feel feverish all the time if I even walk a couple of minutes.
I'm actually really excited to test it out because I have a pituitary problem that's led to jacked up thyroid levels among other things. And I've previously dabbled in some things that should really elevate body temp and only once did I break that 99* threshold where I felt awful. And I recall reading several people on BRITE mentioning levels around that on numerous occasions, so it will be very interesting to test out.

That said, I'm glad Fall is approaching, because that will make it much easier to handle assuming it does get the ol' temps up.
 
DieselNY

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Is the BMP 2.0 available for purchase yet?
 
DieselNY

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Ppar delta activation increases with exercise, so you want the stronger hit preworkout.
http://www.ncbi.nlm.nih.gov/m/pubmed/16328010/

Peroxisome proliferator-activated receptors (PPARs) alpha, delta and gamma are nuclear transcription factors that control key genes involved in fatty acid metabolism and energy homeostasis. Little is known about PPAR activation in vivo and the existence of overlapping functions between PPARalpha, -delta and -gamma. As skeletal muscle is an important site for insulin action and acts as a significant sensor for life-style-induced influences in whole-body energy metabolism, we investigated the expression of PPARalpha, -delta and -gamma in rat skeletal muscle in response to exercise after four- and twelve-weeks of high-fat feeding, respectively. PPARalpha mRNA expression in skeletal muscle increased in parallel with other signs of developing metabolic syndrome such as increased visceral fat pad volymes, plasma free fatty acids and muscle triglyceride concentrations. PPARalpha mRNA expression was up-regulated 3-fold after four weeks of high-fat feeding (p<0.01). Exercise reversed the high-fat induced increase in PPARalpha expression in young lean rats (p<0.05), but did not change the PPARalpha, -delta and -gamma expression in the skeletal muscle in the normal nutritional state. The increase in PPARalpha expression declined during a longer term of high-fat feeding. In contrast, exercise increased PPARdelta mRNA and protein expression 3- to 6-fold in skeletal muscle after longer-term high-fat feeding (p<0.05). This effect was accompanied by a reduction in skeletal muscle fat content. These findings suggest that parallel activation of PPARalpha and -delta expression in skeletal muscle may be an important adaptive mechanism in response to increased fatty acid loads in young, lean animals, protecting them from insulin resistance, whereas exercise might be needed to mediate the same positive effects in older animals.


Trying to copy paste from phone, so hope it comes out ok.
This is in regards to DCP not BMP correct?
 

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