EvoMuse Defuse Writeup - AnabolicMinds.com

EvoMuse Defuse Writeup

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    EvoMuse Defuse Writeup


    Defuse Write Up

    Thermodynamics and Biochemistry.... A couple of mouthfuls that don’t have the potential to make you fat. Calories, on the other hand, do.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.

    We can’t always remain perfectly strict on our diets (and let’s 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.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.
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    Pre-Glossary

    The science behind Defuse is thick, but very digestible if you understand some key physiological terms. Give this pre-glossary a quick read, then as you go through the write up and come across one of these terms you may want to revisit the definition to get a better grasp. Or if you're already a super science nerd, feel free to skip over this section and get right to the meat.
    Pre-adipocytes & pre-adipocyte differentiation
    Pre-adipocytes are immature fat cells that have not yet developed distinguishing characteristics. Basically like the Army Reserve, they're called upon when needed, but instead of going into battle they are transformed into full-fledged fat cells through a process called differentiation. At this point they can start storing lipid droplets containing fats, cholesterol, and various metabolic machinery.



    Peroxisome proliferator-activated receptor gamma (PPARy)
    Of the three known PPAR subtypes (alpha, delta, gamma), PPARy is the only one that encourages nutrient storage upon activation. It is intricately involved in the uptake of carbohydrate and fat into adipose tissue, as well as being a key signal to trigger adipocyte differentiation.
    CCAAT-enhancer binding proteins (C/EBP's)
    C/EBP's include a family of six transcription factors, for our purposes we are just concerned with C/EBPa and C/EBPb. Both of these are directly involved in pre-adipocyte differentiation and work in conjunction with PPARy.
    AMP-activated protein kinase (AMPk)
    AMPk is a major regulator of cellular energy signaling. Upregulation triggers skeletal muscle fatty acid oxidation (fat burning), increased insulin sensitivity, and glucose uptake.



    Normally, AMPk is triggered during conditions of low cellular energy (low glycogen storage, energy depletion during exercise, calorie restriction, etc). During times of caloric excess (which is exactly when you'll be using Defuse), AMPk is significantly downregulated, which is quite detrimental for fat loss; hence the inclusion of AMPk activators in the formula.
    Transient receptor potential vanilloid receptor 1 (TrpV1)
    A few years ago some groundbreaking research came out implicating this receptor as a major player in obesity. This is the receptor that capsaicin from chili peppers interacts with, and quite a bit of research has demonstrated that triggering TrpV1 has a significant effect on fat burning.
    Hormone Sensitive Lipase (HSL)
    HSL is crucial for the initial phase of fat loss. It is imperative for breaking down the stored triglyceride in a fat cell into free fatty acids (FFA's) so they can be transported for oxidation (burning). The breakdown of stored triglyceride into FFA's (before transport and oxidation of the fat even occur) is a three-step process, and HSL governs the first step, and is also the rate-limiting step. Boosting HSL allows the other two steps to do more work, which allows for more fat to be burned.
    Fatty Acid Synthase (FAS)
    Think of FAS as the anti-HSL, basically performing the opposite function, encouraging the storage of fat. It is comprised of a group of enzymes regulated upstream by SREBP-1c, which is triggered by insulin. Research shows a significant upregulation of FAS in obesity, coupled with suppressed HSL.
    Brown Adipose Tissue (BAT)
    BAT is structurally and functionally different from white adipose tissue (WAT). BAT contains several, small lipid droplets surrounding the large nuclear machinery in the middle, whereas WAT contains one huge lipid droplet with a small nucleus near the cell wall. That right there gives some indication of the function of the BAT cell, along with its high mitochondria density and UCP1 expression. BAT's main function is generating heat by burning calories; the numerous small lipid droplets release their fat in response to cold in order to elevate body temperature. People with higher BAT levels (or better BAT signaling) take longer to start shivering in the cold, as their bodies are able to maintain better homeostatic thermoregulation.
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    Acacia Catechins
    Where does it come from?
    Found growing in various parts of China and India, Acacia Catechu is a tall thorny tree. It was selected for inclusion in Defuse as a source of epicatechin and EGCG.
    Primary Effects
    PPARy and C/EBP
    Acacia Catechins have been shown to suppress pre-adipocyte differentiation through the blockade of two important fat storage proteins, C/EBP and PPARy, which has a downstream inhibition on the master fat storing gatekeeper, FAS (1).

    Platycodon saponins
    Where does it come from?
    Platycodin d. is isolated from the roots of the Platycodon grandiflorum plant, found in East Asia.
    Primary Effects
    AMPk Activation
    Fat loss and fat gain are moderated by numerous complex mechanisms, and AMPk is a key player in this flux. Generally speaking, bolstering AMPk activation is great for fat loss, in the right amount. Platycodin d. has been shown in multiple studies to significantly inhibit fat gain and increase fat burning through AMPk activation. Downstream, this AMPk activation attenuates activation of SREBP-1 and fatty acid synthase (FAS), two hormones responsible for fat storage. This is done in a novel way by triggering SIRT1 and CaMMK-b (2–4).

    PPAR-y and C/EBPa Modulation
    Platycon d. has been shown to reduce abdominal and whole body fat accumulation in mice fed an obesogenic diet by PPAR-y and C/EBPa (3). Basically they gave mice Platycodon d., tried to make them fat, and couldn't do it.

    Adipokine and Glucose Management
    Another recent study trying to fatten up mice found that Platycodon d. was able to kick-start adiponectin (a fat burning adipokine) locally in fat cells while keeping it stable in serum compared to the placebo group. It was also able to suppress TNFa (an inflammatory cytokine) locally in fat cells. This resulted in reduced food intake and reduced fat accumulation while increasing glucose uptake in skeletal muscle (5). With regards to glucose, another study showed it was able to reduce blood sugar without stimulating insulin release, which is great for enhancing fat burning as well as long term health (6).

    Baicalin
    Where does it come from?
    Baicalin is a flavone found in the herb blue skullcap.
    Primary Effects
    AKt, CaMKKb, AMPk, ACC, PPARy, C/EBP, FAS, KLF-2 & KLF-15
    Baicalin has been shown to downregulate PPAR-y and C/EBPs; it does this by suppressing Akt phosphorylation through inhibition of PDK1 (7,8). The net result of this, among other things, is going to be inhibiting fat accumulation by attenuating preadipocyte differentiation.

    Baicalin is another AMPk activator, which does so through the favorable CaMMK pathway like Platycodin d. (9). Researchers in Shanghai conducted a profound study in mice fed a high fat diet (HFD) with or without baicalin supplementation (10). Keep in mind that mice don't normally eat a high fat diet, and their metabolic machinery is ill adapted to do so. After 16 weeks, the bicalin group saw the following effects:
    Suppression of body weight gain normally caused by the HFD
    Reduced visceral fat
    Decreased cholesterol
    Decreased circulating FFA's (a sign of increased fat oxidation)
    Decreased circulating insulin
    Reduced TNF-a (a potent inflammatory cytokine)
    Reduced liver fat gain
    Stimulation of AMPk and ACC
    Decreased SREBP-1c and FAS

    Another study out of Korea supported the previously seen fat loss potential and concluded that baicalin upregulates anti-fat storage regulators (KLF-2) and downregulates pro-fat storing regulators (KLF-15) which results in an inhibition of cellular fat accumulation (8). This is a perfect storm for prevention of fat gain.

    Methyl Cinnamate
    Where does it come from?
    Methyl Cinnimate (MC) is an ester of cinnamic acid found in several plants and spices.
    Primary Effects
    MC again targets pre-adipocytes through modulation of PPAR-y, SREBP-1, and C/EBPa, CaMMK2, and AMPk, thereby reducing the ability of the body to accumulate fat storage (11).

    Salvia miltiorrhiza
    Where does it come from?
    Salvia miltiorrhiza is an Asian perennial plant from the Salvia genus.
    Primary Effects
    DGAT, Glucose Sensitivity, Hepatic Lipid Metabolism
    Diglyceride acetyltransferase (DGAT) is the enzyme responsible for the third and final step in producing a triglyceride from glycerol and fatty acids. Inhibit DGAT, which Salvia m. has been shown to do, and you reduce fat accumulation and increase leptin sensitivity significantly (12) . If your body wants to store more fat; it cranks up DGAT activity.

    Salvia m. has also been shown in research to improve uptake of glucose in skeletal muscle, thereby reducing fat storage through a 2nd angle (13).

    When feeding two groups of rats a fattening diet for six weeks, the control group showed increased body fat accumulation, hyperinsulinemia, hyperlipidemia, and increased liver enzymes. The group fed the same diet in conjunction with Salvia m. did not show any of these negative effects from the high fat diet (14).

    Raspberry Ketone
    Where does it come from?
    Raspberry Ketone (RK) is a natural phenolic, aromatic compound found in raspberries, cranberries and blackberries.
    Primary Effects

    TRPV1, NE, HSL
    Activating the Transient Receptor Potential Vanilloid Type 1 protein (TRPV1) offers numerous benefits for fat loss and general health, including prevention of adipogenesis and obesity (15).

    Through modulation of norepinephrine (NE) and hormone sensitive lipase (HSL), RK appears to be a powerhouse for encouraging fat loss and prevention of fat gain. When mice were fed fattening diet, RK prevented visceral and liver fat accumulation as well as reversing the fat gain in previously obese mice (16). Recently liver fat has been implicated in metabolic disturbances to an even greater degree than the previous villain, visceral fat, so this is a benefit of great magnitude for overall health (17).


    18b-glycyrrhetinic acid
    Where does it come from?
    18b-glycyrrhetinic acid (18b-GA) is a metabolite of glycyrrhetinic acid with very unique properties found in the licorice herb.
    Primary Effects
    While high doses of licorice/glycyrrhetinic acid have been shown to inhibit the enzyme 11b-HSD, which is responsible for converting cortisol to the inactive form cortisone (18), the low dose of this specific 18b metabolite have some important yet unrelated effects.

    PPARy, C/EBPa, HSL, HbA1c, Inflammation
    18b-GA is another ingredient in DeFuse selected for its potent inhibitory effect on the likely now familiar PPARy and C/EBPa pathway. A recent university study out of South Korea found that 18b-GA was able to decrease lipid accumulation by downregulation of PPARy and C/EBPa in maturing pre-adipocytes. In addition to this effect on pre-adipocytes, it was also able to increase fat release, upregulate HSL, adipose TG lipase and perilipin in mature fat cells (19). So basically 18b-GA is going to prevent immature fat cells from becoming fat cells, and increase lipolysis in mature fat cells, a perfect two pronged attack.

    Another study out of India showed that 18b-GA was able to control blood glucose and HbA1c in diabetic rats on par with the potent pharmaceutical glibenclamide (20). It also appears to have a significant effect on preventing free fatty acid induced lipid accumulation and lipotoxicity by stabilizing mitochondrial lysosomes and improving liver function (21). Finally, 18b-GA has also been shown to be anti-inflammatory by reducing IL-8 (22). Current research shows that inflammation is likely a major contributing factor to fat gain, so by reducing inflammatory interleukins we can help create a more optimal hormonal environment.


    6-gingerol
    Where does it come from?
    Gingerol, found in ginger, is chemically similar to capsaicin and piperine. Once cooked, gingerol becomes zingerone.
    Primary Effects
    PPARy, C/EBPa, FAS, SREBP-1c, Acetyl-CoA, Akt, AP2/4, ROS, Inflammation
    In a university study out of Tokyo, researchers looked at the effect of gingerol on rats fed a fattening diet to see if it could alleviate any of the damage. They found it was able to reduce plasma insulin, SREBP-1c, and liver acetyl-CoA carboxylase, which attenuated both body weight gain and fat accumulation (23).

    6-gingerol is also an effective player in our main theme of targeting pre-adipocyte differentiation. Both in vitro and in vivo, we see anti-adipogenic properties through reduction in PPARy, C/EBPa and FAS (24,25). The researchers performing these studies also found that it was able to reduce levels of something called adipocyte-specific fatty acid binding protein (aP2, also called FABP4), which is a carrier protein for fatty acids and has become an emerging target protein for treating diabetes and obesity (26,27).
    In addition to the direct anti-adipogenic effects, gingerol can also control oxidative damage by reducing intracellular ROS and boosting glutathione, as well as reduce inflammation by blocking TNF-a, NF-kB and PKC signaling (28,29).

    Cinchonine
    Where does it come from?
    Cinchonine is a natural compound found in Cinchona bark, indigenous to the Western Andes.
    Primary Effects
    During overfeeding, cinchonine supplemented subjects gained 40% less weight, 25% less visceral fat, and had lower levels of triglycerides, glucose, serum cholesterol and free fatty acids (30). It also inhibited the diet induced upregulation of inflammatory cytokines by inhibiting Toll Like Receptor 2 (TLR2). In summary, it was shown to reduce fat gain and inflammation compared to control groups when given a fattening diet.

    (-)Hydroxycitric acid
    Where does it come from?
    Hydroxycitric Acid (HCA) is found in the tropical plant Garcinia cambogia.
    Primary Effects
    HCA has been shown to favorably alter the expression of genes that regulate adipogenesis and lipolysis, which makes it a great addition to the Defuse formula (31). New research shows that it appears to do so by blocking a key enzyme called atp-citratelyase (32). In a previous study, HCA was also shown to reduce fatty acid synthesis from glucose (33).

    Anthocyanins/betalains
    Where does it come from?
    Anthocyanins and betalains are a class of pigmentations found in various plants, fruits and flowers, with numerous health-promoting effects.
    Primary Effects
    PPARy, Adiponectin, NPY, Glucose, Leptin, Resistin
    Once again, we're targeting inhibition of PPARy to suppress fat storage. Anthocyanins have been shown to do just this, causing suppressed pre-adipocyte differentiation and lipid accumulation (34). A brand new university study out of Korea looked at rats on a normal diet vs. rats on a normal diet plus anthyocyanins for 40 days (35). Here's what they found in the supplemented group:
    Significantly lower body weight
    Reduced fat cell size
    Reduced expression of neuropeptide Y (a neurotransmitter that signals increased food intake and fat storage) and of protein kinase A (a regulator of cellular energy storage).

    Another study looked at the effects of anthocyanin supplementation over 10 weeks and found that it lowered total cholesterol, triglycerides, serum leptin and resistin. The researchers concluded that anthocyanins "…posess a preventative potential for obesity-associated diseases" (36).

    Other studies have shown an anti-obesity effect as well, demonstrating resistance to fat gain with supplementation (37,38). Betalains specificaly have been shown to boost adiponectin, act as an antioxidant, and prevent LDL oxidation (39–41).

    Loranthus
    Where does it come from?
    Loranthus is a parasitic plant found growing on branches of woody trees, from the Loranthaceae family.
    Primary Effects
    FAS inhibition, glucose
    Loranthus has several studies supporting its ability to potently inhibit FAS, making it a perfect choice to prevent fat gain, and a key ingredient in the formula.

    Initially, Tian et. al, discovered that loranthus potently inhibits FAS to a greater extent than cerulenin and C75 (currently used to inhibit FAS in a laboratory setting), and also reduced body weight in tested subjects (42). Next, they established an IC50 value (a measurement used to determine the inhibitory potency of a compound) and found that loranthus has both a fast acting and long acting effect on FAS inhibition (43). Finally, they determined that the FAS inhibitory activity of loranthus comes from a specific family (Loranthaceae), so it is important to use this form, which we have done in Defuse (44).

    At least two other studies have shown the ability of loranthus to favorably regulate blood glucose levels, in diabetic and non-diabetic subjects (45,46).

    Citrus aurantium
    Where does it come from?
    Citrus aurantium (CA) refers to a citrus tree and its fruit, which contains N-methyltyramine, octopamine and synephrine.
    Primary Effects
    PPARy, C/EBP (a&b), FAS, aP2
    Quite a bit of research has been done on CA, for now we just want to focus on a couple of studies that make it highly relevant for its inclusion in the Defuse formula.

    The first noteworthy study looked at CA's effect on pre-adipocyte differentiation, and it turned out to do pretty much everything we want in an anti-fat gain compound. It was shown to downregulate PPARy, C/EBPb and C/EBPa (expression of C/EBPa makes fat cells more sensitive to insulin). In addition to this, it also dramatically decreased FAS and aP2, as well as other fat signaling pathways. This demonstrates CA's ability to positively manipulate the fat storage vs. fat burning pathway and inhibit adipocyte differentiation (47).

    Finally, a recent meta-analysis looking at a combination of 20 published and unpublished studies including 360 human subjects concluded that supplemental CA increases resting metabolic rate and energy expenditure (48).

    Lotus leaf
    Where does it come from?
    Lotus leaf comes from the aquatic lotus plant in the Nelumbonaceae family.
    Primary Effects
    SREBP-1c, REE, a-glucosidase, GLUT4, AGEs
    Keeping with the recurring theme of attacking pre-adipocyte differentiation, lotus leaf could be a potentially big player in this assault. Research has demonstrated the ability of lotus to decrease SREBP-1c and triglyceride accumulation during adipogenesis, increase lipolysis, and decrease adipocyte differentiation capacity (49).

    In a study out of Japan, researchers took the now hopefully familiar route of trying to fatten up mice and rats with and without lotus supplementation and measured various obesity related parameters. They found that the supplemented group was able to prevent fat gain as well as hepatic triglycerides, coupled with an inhibited ability to absorb lipids and an accelerated rate of fat oxidation and resting energy expenditure (50).

    A 2013 study out of Korea looked at the effect of lotus supplementation for 7 weeks in animals with diabetes. They found that lotus was an extremely potent inhibitor of an enzyme called a-glucosidase, which lowers the rate of glucose absorption and extends digestion time, leading to a lower post-prandial glucose response (51). The same study also demonstrated the ability of lotus to lower plasma triglycerides and total cholesterol. Inhibition of a-glucosidase has been shown to reduce triglyceride uptake into fat cells, decrease hepatic lipogenesis, favorably effect skeletal muscle GLUT4 receptor density density, and diminish the production of Advanced Glycation End products (AGEs) (52).

    Olive Leaf extract
    Where does it come from?
    Olive leaf extract (OLE) is derived from the leaves of the olive plant; we have selected an extract with a high potency of oleuropein, a phenolic compound with some interesting properties relating to prevention of fat gain.
    Primary Effects
    PPARy, C/EBPa, RQ, AGEs, Insulin, Glucose
    We'll kick this one off with the current theme, OLE is yet another ingredient in the Defuse formula that prevents adipocyte differentiation through inhibition/downregulation of PPARy and C/EBPa (53).

    A study published in the Journal of Nutrition found that OLE supplementation increased V02, reduced myocardial oxidative stress, and lowered respiratory quotient (RQ- lower levels indicate more fat oxidation vs. carbohydrate oxidation) (54). In another study published in Nutrition, researchers overfed two groups of rats for eight weeks, then gave one group OLE and continued to overfeed both groups for another eight weeks. The non-supplemented group developed metabolic syndrome, including elevated abdominal and liver fat, collagen accumulation in the heart and liver, elevated oxidative stress markers, abnormal cholesterol and impaired glucose tolerance. The group supplemented with OLE either improved or normalized all of those parameters, demonstrating a potent protective effect against overfeeding (53).

    In a brand new human study out of The University of Aukland, overweight men at risk for metabolic syndrome were given supplementation with OLE for 12 weeks; researchers noted a 15% improvement in insulin sensitivity along with an almost 30% improvement in pancreatic beta cell responsiveness (the cells that produce insulin) (55). An improvement in fasting insulin and HbA1c was also noted in a previous human study with 79 diabetic adults (56).

    Finally, OLE is another ingredient in the formula that acts as an anti-glycation agent, reducing production of AGEs (57).

    Galega officionalis
    Where does it come from?
    Galega officinalis is an herbaceous plant in the Faboideae family native to the Middle East, containing a potent compound called guanidine.
    Primary Effects
    AMPK, FAS, Acetyl-CoA, GLUT4, Glucose
    Galega is going to contribute to fat gain inhibition through some familiar mechanisms, and looks to be quite a promising compound. It has been shown to activate AMPk, increase GLUT4 translocation, and increase skeletal muscle glucose uptake in vitro and in vivo (58,59).

    An animal study out of Glasgow again demonstrated AMPk activation, as well as inhibition of Acetyl-CoA carboxylase and FAS, increased fat oxidation, and a reduction in body weight (60).

    The most impressive research on galega looked at the effect of supplementation for 28 days on normal and obese mice and measured several parameters. In normal mice, supplementation caused weight loss and a voluntary reduction of food intake. Interestingly, after cessation of the supplement, food intake increased back to normal but the weight loss was maintained. The obese mice supplementing with galega also showed reduced food intake, and the researchers noted a "striking absence of body fat" during post-mortem examinations. Both groups showed a reduction in fasting blood glucose, and the obese group also showed a reduction in serum insulin (61).
    Panax ginseng berry extract
    Where does it come from?
    Panax ginseng berry extract (GBE) comes from Ginseng; a perennial plant from the Araliaceae family.
    Primary Effects
    AMPk, FAS, glucose, SREBP-1c
    GBE has been shown to inhibit lipogenesis during overfeeding by suppressing FAS and SREBP-1c, while upregulating AMPk. Supplementation was also shown to reverse diet-induced blood sugar cholesterol elevations, while reducing hepatic glucose output (62). Several studies in obese and/or diabetic animals have demonstrated a favorable modulation of blood glucose, loss of body weight, and even pancreatic beta cell regeneration (63–66).

    Forskolin 60%
    Where does it come from?
    Forskolin is a diterpene from the Coleus forskohlii plant.
    Primary Effects
    Forskolin is well known to effectively target cAMP in adipose tissue, which, among other things, mimics exercise and caloric restriction.

    A 12 week randomized, double-blind placebo study out of the University of Kansas found that forskolin supplementation caused a decrease in body fat and an increase in lean body mass compared to the placebo group (67). The even better news is that this study only used a 10% extract; we have obtained a far more potent 60% extract for Defuse. It has also been suggested to help mitigate weight gain in overweight human subjects (68).
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    Silibinin
    Where does it come from?
    Silibinin comes from milk thistle seeds, and is the main active component of silymarin.
    Primary Effects
    Most people are well aware of Milk Thistle's profound effect on liver health, but silibinin is included in Defuse for a different reason.

    ATGL, Insulin, FFA's, Resistin, TNFa, oxLDL
    Silibinin is the first ingredient in the formula to upregulate something called adipose triglyceride lipase (ATGL), which is an enzyme responsible for initiating the breakdown of stored fat (triglyceride) inside the adipocyte (69). Silibinin has also been shown to reduce serum fatty acids, improve skeletal muscle insulin resistance, reduce visceral fat, downregulate resistin, and improve glucose metabolism by downregulating gluconeogenesis genes and supporting the Akt pathway (69–71).

    And for some bonus points, silibinin also inhibits oxidation of LDL particles, decreases lipid peroxidation and lowers TNFa (71,72)

    Rosemary Leaf Extract (carnosic acid)
    Where does it come from?
    Rosemary is a Mediterranean perennial herb; the leaf extract is a source of a natural diterpene called carnosic acid.
    Primary Effects
    PPARy, C/EBP, Glucose, Gastric Lipase, Hepatic Lipase
    Carnosic acid (CA) does pretty much everything you could ask from an anti-adipogenic compound. Again we're going after PPARy and C/EBPa inhibition, and CA has a unique effect on restructuring the ratios of different forms of C/EBPb, the combined result being inhibition of adipogenesis (73,74).

    A recent study out of Switzerland boasted some impressive results in overfed mice supplemented with Rosemary leaf extract for 50 days, showing almost a 60% reduction in fat gain and 40% reduction in hepatic triglyceride levels. The researchers determined this effect was likely due to an inhibition of pancreatic lipase activity, and concluded Rosemary extract "…can limit weight gain induced by a high-fat diet and protect against obesity-related liver steatosis" (75).

    CA has been shown in several other studies to significantly reduce body weight and body fat in lean and obese individuals, lower triglycerides, total cholesterol and insulin, reduce visceral fat, improve liver enzymes, favorably modulate glucose and glucose tolerance, inhibit gastric lipase (thereby reducing fat absorption), and inhibit pre-adipocyte differentiation (74,76–78).

    Stearoyl Vanillylamide (capsaicin analogue)
    Where does it come from?
    Stearoyl Vanillylamide (SV) is a non-pungent analogue of capsaicin, the active component of chili peppers.
    Primary Effects
    TrpV1, BAT, REE
    If you've been paying attention to obesity research the past few years, you've likely heard of the transient receptor potential vanilloid (TrpV1). See the description in the intro of the article if you need a quick explanation. Multiple studies have demonstrated SV/capsaicin's ability to act as a potent TrpV1 agonist leading to decreases in body fat and increases in energy expenditure (80,81).
    Brown Adipose Tissue (BAT) has taken an interesting journey in the research over the years, and for a long time was suspected to be negligible in adult humans, and therefore an unfruitful target for obesity and weight loss. However, new research is showing we were likely wrong all along, and that BAT is indeed a "…regulator of whole-body energy expenditure and body fat in humans as in small rodents, and a hopeful target combating obesity and related disorders" (82). SV has been shown to have a profound effect in several studies on BAT upregulation through TrpV1 binding (80–83). The net effect of this BAT activation is a significant increase in fat oxidation and energy expenditure. Two recent meta-analyses looking at the summation of the data determined that capsaicin supplementation increases VO2, energy expenditure and fat loss in humans (84,85).

    Summary
    Psychologically and emotionally we need time off, and often that time off involves eating and drinking large meals with friends and family. While we want, and need, to participate we can often find our other, fitness-related, goals compromised.

    Defuse gives us a much-needed tool for physique enhancement. Defuse helps prevent fat gain that happens with occasional caloric surplus (vacation and Holidays), and short burst muscle gaining cycles. Incorporating Defuse strategically as directed will minimize fat gain and help to maintain your much-desired leanness.
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    Bibliography

    1. Furuyashiki T, Nagayasu H, Aoki Y, Bessho H, Hashimoto T, Kanazawa K, et al. Tea catechin suppresses adipocyte differentiation accompanied by down-regulation of PPARgamma2 and C/EBPalpha in 3T3-L1 cells. Biosci. Biotechnol. Biochem. [Internet]. 2004 Nov [cited 2013 Oct 7];68(11):2353–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15564676
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    60. Mooney MH, Fogarty S, Stevenson C, Gallagher AM, Palit P, Hawley SA, et al. Mechanisms underlying the metabolic actions of galegine that contribute to weight loss in mice. Br. J. Pharmacol. [Internet]. 2008 Apr [cited 2013 Nov 4];153(8):1669–77. Available from: http://www.pubmedcentral.nih.gov/art...rtype=abstract
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    78. Takahashi T, Tabuchi T, Tamaki Y, Kosaka K, Takikawa Y, Satoh T. Carnosic acid and carnosol inhibit adipocyte differentiation in mouse 3T3-L1 cells through induction of phase2 enzymes and activation of glutathione metabolism. Biochem. Biophys. Res.
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    Meh...today was a bad day so I posted it early. Knock yourselves out.
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    I'll be grabbing a few bottles it available soon?


    I need it big time for post contest
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    Should be done end of next week.
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    Yay! I can't wait for this. This and Slintensity should be just the ticket I need to keep holiday pounds at bay.)
    Building my best body "for me"!
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    Man, the only I didn't see in there was the kitchen sink...quite impressive!
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    Quote Originally Posted by jjobe6 View Post
    Man, the only I didn't see in there was the kitchen sink...quite impressive!
    You should see what didn't make the cut. One ingredient in particular you will actually see as a standalone very soon, and I you know my work you know I don't tend to do standalone products.
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    Quote Originally Posted by dsade View Post
    You should see what didn't make the cut. One ingredient in particular you will actually see as a standalone very soon, and I you know my work you know I don't tend to do standalone products.
    Garcinol is interesting
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    Any sense in using this and DCP at the same time?
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    Quote Originally Posted by megadeth View Post
    Any sense in using this and DCP at the same time?
    Actually yes, and you will see some good stacks. Enhancement of peroxisomal oxidation is pretty important for the ultimate disposal of the free fatty acids. You can also stack this very effectively with a thermogenic.
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    So totally in for this. I have been eagerly waiting for such a long time. I cant wait to run it during my Helladrol cycle. Now all I need to concern myself with is just picking things up and then putting them down lol.

    Amazing job

    dsade
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    Only 78 references? What are we paying you for?!
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    Looking forward to Matt's creation
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    Another product i am interested in!

    Mike
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    Interested in this product. Love how you always give great study reads and references that go for days lol.
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    Looking for a replacement to TTA as my PPAR agonist for stim free night time fat loss
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    Quote Originally Posted by EBF_2356 View Post
    Looking for a replacement to TTA as my PPAR agonist for stim free night time fat loss
    Agreed, i was an avid tta user.. Especially post contest.

    Mike
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    Quote Originally Posted by EBF_2356 View Post
    Looking for a replacement to TTA as my PPAR agonist for stim free night time fat loss
    What about DCP 2.0?
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    This has me super excited as I am on a bulk currently... About 2 whole months in and the body fat is ever so slightly starting to accumulate while muscle growth seems to be remaining consistent.. But i can't be adding no fat!!

    Carbs are super high and I don't wanna reduce n Stop growing.... So go ahead and send me this stuff now please and thanks!
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    We are blending today, and capping tomorrow...so I would say we might have it up as soon as Monday.
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  28. jjobe6's Avatar
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    Do you know the price? I will be ordering this.
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    Quote Originally Posted by dsade View Post
    We are blending today, and capping tomorrow...so I would say we might have it up as soon as Monday.
    Nicee. Def in on this
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  30. dsade's Avatar
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    Quote Originally Posted by jjobe6 View Post
    Do you know the price? I will be ordering this.
    The intro sale will be about $32.
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    Looks sweet. My only question is what would you label this product exactly? I guess I'm wondering how one would use this alongside a GDA in a bulk? Would Defuse be best left for binges and Slintensity/Recompadrol/etc for regular use, for example? Or would it be better to use Defuse on a daily basis? Just trying to figure out how to fit this into my bulking stack
  32. dsade's Avatar
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    Quote Originally Posted by SiLkPaDrE View Post
    Looks sweet. My only question is what would you call this product exactly? I guess I'm wondering how one would use this alongside a GDA in a bulk? Would Defuse be best left for binges and Slintensity/Recompadrol/etc for regular use, for example? Or would it be better to use Defuse on a daily basis? Just trying to figure out how to fit this into my bulking stack
    Best word for it is Fat Gain Inhibitor. Daily use is not right, at least not long term (you can't counter an overall bad diet with supplements)...but a few weeks of less than great diet (bulking cycle, vacation, holidays) would be ideal.
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    just saw this on the front page, and definitely in on this! This will help with the holidays!
  34. chedapalooza's Avatar
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    Quote Originally Posted by dsade View Post
    Best word for it is Fat Gain Inhibitor. Daily use is not right, at least not long term (you can't counter an overall bad diet with supplements)...but a few weeks of less than great diet (bulking cycle, vacation, holidays) would be ideal.
    Interesting concept... Similar to a cheaters relief from BSN... Whic is discontinued and I stopped cheating SO I have 2 unused bottles (smacks forehead)
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    Quote Originally Posted by chedapalooza View Post
    Interesting concept... Similar to a cheaters relief from BSN... Whic is discontinued and I stopped cheating SO I have 2 unused bottles (smacks forehead)
    Wasn't that a fat absorption blocker? Defuse definitely doesn't take that as primary approach (check the writeup.)
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    Quote Originally Posted by dsade View Post

    Wasn't that a fat absorption blocker? Defuse definitely doesn't take that approach (check the writeup.)
    Hmm yes I suppose it was. I did read the whole thing, I'm anxious to try it out. But yes cheaters used was mostly to block absorption
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    Quote Originally Posted by dsade View Post
    Best word for it is Fat Gain Inhibitor. Daily use is not right, at least not long term (you can't counter an overall bad diet with supplements)...but a few weeks of less than great diet (bulking cycle, vacation, holidays) would be ideal.

    Cool, so when I'm in jamaica at an all inclusive for my honeymoon eating my brains out all day.. this will be there!! Sounds like for bodybuilders post show would be a good time for this as well since most typically tend to eat a lot of crap for the month after.

    Mike
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    Quote Originally Posted by MidwestBeast View Post
    I have a feeling this supp is going to Be huge....
    I'm thinking ill use it on either on off days so I can still eat big and get great recovery OR use it on training days and eat even bigger..... Thoughts?
    "no failure is final, nor is any success"
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    How does this compare to dcp 2.0? Would i be able to run this indefinitely like dcp?
  

  
 

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