PHENBUTEROL: UCP-1 Activator
PHENBUTEROL introduces a new development in advanced fat burning technology through the activation of Uncoupling Protein 1 (UCP-1). UCP-1 enhances fat burning in brown adipose tissue (BAT) by shuttling fatty acids from stored body fat into the mitochondria to generate heat and trigger thermogenesis. Utilizing fatty acids from stored body fat, rather than ATP from muscle tissue, is a unique fat burning mechanism of UCP-1 and brown adipose tissue – and one of the key fat burning actions and benefits of PHENBUTEROL.
To optimize the fat burning potential of UCP-1 and BAT, in the development of PHENBUTEROL MuscleMeds researchers explored the key mechanisms of action and identified some newly discovered highly standardized natural compounds. One of their key finding was a potent clinically researched compound called 6-Paradol. This compound is derived from a plant native to West Africa called Grains of Paradise, and it has been show in clinical studies to upregulate UCP-1. Other naturally derived compounds such as hordenine, octopamine, synepherine, llex paraguariensis and Rouwolfia serpentia provide synergistic fat burning effects. In addition, these select active ingredients in PHENBUTEROL also exert powerful energizing and mood enhancing effects to take the edge off dieting. PHENBUTEROL is a potent fat burning catalyst for serious athletes looking to lose excess body fat quickly and effectively.
NOTE: PHENBUTEROL is a trade name and is not intended to depict any comparison to any pharmaceutical or other product or any particular benefit thereof.
PHENBUTEROL:
This is the first fat burning supplement targeting the activation of UCP-1 and BAT from MuscleMeds.
Since BAT tissue is activated through Beta 1, 2 and 3 (and to some extent Alpha) adrenergic receptors and is highly activated by norepinephrine, a unique combination of ingredients was assembled to maximize the fat burning potential of BAT by activating several receptors. In addition, ingredients were chosen for their potential to stimulate norepinephrine, which acts on Beta-3 and is by far the most potent activator of BAT.
THE SCIENCE OF UCP-1 THERMOGENESIS
Uncoupling Protein 1:
Uncoupling Protein 1 (aka UCP-1) is a protein known to be required for a specific fat cell’s heat-generating capabilities. Originally coined “Thermogenin,” UCP-1 is used by specific tissues to generate heat via non-shivering thermogenesis, which is the primary means of heat generation in certain mammals (hibernating mammals for example) and in human infants. The name was originally used to describe an oxidative process for energy generation not coupled to ATP synthesis. 15
UCP-1 is a mitochondrial transport protein found within the inner membrane of mitochondria in all mammals and in plants. Mitochondria themselves are organelles within cells where respiration occurs. In this case, respiration refers to the process by which a cell obtains energy from organic compounds. In other words, the burning of a fuel source to generate heat. Or more simply put, thermogenesis.1
The citric acid cycle, fatty acid oxidation and gluconeogenesis are other actions that also take place within mitochondria. The energy produced by respiration within the mitochondria is used for ATP synthesis via oxidative phosphorylation. What is unique about UCP-1 is that it can cause a rapid, uncoupled respiration that does not rely upon ATP synthesis, rather it shuttles fatty acids into the cell to burn with an end result of heat generation. In other words, UCP-1 is the equivalent of a “regulated uncoupler” that can control heat production. 1
UCP-1 works by decreasing the proton gradient thereby increasing the permeability of the inner mitochondrial membrane. It is thought that with this reduced gradient/increased permeability; protons can grab fatty acids and pour them into the cell to burn. Not all cells contain UCP-1. In fact, it is unique to a specific tissue, sometimes referred to as an organ, called Brown Adipose Tissue (BAT). The rate of metabolism in all tissues, other than BAT, is determined by utilization of ATP. UCPI and BAT are unique in that they do not follow this same metabolic pathway. The physiological action of UCP-1 on BAT can be called “unrestrained oxidation of fuels with the sole byproduct being the generation of heat.” 12
Brown Adipose Tissue (BAT):
We have at least two functionally different types of adipose tissue in our bodies. Brown Adipose Tissue and White Adipose Tissue (WAT). WAT is the primary place in the body where energy is stored. It is also involved in the release of hormones and cytokines that are involved in both metabolism and modulation of insulin resistance. The simplest way to describe the difference between these two types of fat is to describe the difference between gaining and losing weight as it is well known at this point that excess WAT = overweight! BAT, although a fat cell as well, is functionally very different. BAT is important for basal body temperature, the temperature you essentially wake up at before moving or eating. In addition BAT is important for thermogenesis mediated by UCP-1.2,15 BAT is the mechanism by which the sympathetic nervous system produces heat during non-shivering thermogenesis. 11,15
Brown adipocytes are smaller than white adipocytes, contain less fat, are highly vascular, have an abundance of nerves and can contain high concentrations of triiodothyronine (T3), an endogenous thyroid hormone. Further, Beta-3 Adrenergic Receptors are highly abundant in this tissue while being markedly absent in WAT. 12
When you picture “fat” in a human, most people immediately think of large protruding bellies, round thighs and “chicken wings.” BAT is very different in that these deposits are not found in any of these areas. Rather they are found in supraclavicular deposits in the neck area.3 Older studies have “estimated a prevalence of BAT as low as 5% in adult humans” however testing methodologies, sensitivity and reproducibility have been difficult leading most researchers to believe this number to be greater. Lee et al., looked at this and concluded a universal prevalence of BAT in human adults, which far exceeds 5% 3 and Chen et al., concluded via nuclear medicine that BAT is clearly present in adult humans. 10
Why Scientists Are Studying BAT In Overweight People:
BAT is an efficient heat generating “organ” within the body. Under different conditions, such as exposure to cold, UCP-1 will activate BAT and start to burn the fatty acids that are shuttled into the cell. In other words, BAT burns fat to generate heat! BAT is regulated by the sympathetic nervous system and can be stimulated by the Beta-Adrenergic system. 3 This means that noradrenaline, for example, can stimulate BAT to generate heat by burning fat. Further, BAT can be activated by diet5 and a single meal can activate BAT. 15 Where WAT stores lipids for energy to be used at a future point, BAT has evolved to ensure mammals maintain a core body temperature by burning lipids.13
The heat generating capability of BAT has been talked about for decades and researched extensively in animals.4 It is only in recent years that scientists have been able to determine the purpose and use of BAT within the human body.3 It is thought that BAT serves two primary purposes – to maintain body temperature during exposure to cold and to waste food energy.5 This leads one to inquire about overweight people and how BAT is affected. It is understood that BAT can grow when stimulated or it can atrophy. In most models within animals, BAT is usually atrophied.5 Also, in most models BAT is low or absent and so it is hypothesized that lifestyle and body composition can create differences in the amount and in the activity of BAT. 11 Atrophied BAT may even be associated with insulin resistance.
Scientific discovery that BAT uses fat and not ATP for fuel is a major breakthrough for weight loss and extremely beneficial for athletes and bodybuilders.
The principal fuel for BAT that has been stimulated is fatty acids in the form of endogenously stored lipids. BAT has “a huge capacity to remove lipids from the circulatory system to fuel thermogenesis” and when “thermogenically active, the high rates of oxidative phosphorylation mean it requires large quantities of lipids.”13 BAT is capable of obtaining fatty acids from four basic sources. The first of four endogenous stores is fat, the second is from plasma lipoproteins, the third is from free fatty acids in the blood and the fourth is from glucose, as BAT can synthesis fatty acids to burn from glucose although glucose is not the major fuel source for BAT.5 For UCP-1 to stimulate BAT, fatty acids are necessary in furthering the knowledge that BAT is a built in and potent fat burning organ in the human body.11
All of the thermogenic activation changes that take place in BAT are mediated through adrenergic receptors, either Alpha or Beta. 15 An increased rate of lipolysis is observed when norepinephrine is acting on Beta-adrenergic receptors. Other related compounds that have been shown to stimulate BAT include nicotine, ephedrine, caffeine and theophylline as well as the drug fenfluramine.5† BAT “reactivation” and its potential use in combating overweight has garnered the attention of the medical and nutritional industries for some time now.6 Some of the research has even looked at increases in oxygen consumption via BAT activation in animal models. Various substances with Beta-Andrenoceptor mechanisms have been looked at for their potential as a potential BAT activator, 8,9 particularly since BAT has such a high density of Beta-adrenoceptors. It has been hypothesized that ephedrine’s ability to reduce weight via its fat burning mechanism was due to its Beta-receptor stimulation of BAT, although at the time limited methods to look at BAT were available. Exactly how ephedrine worked remains unknown, but new data from rats show that part of its affect is by BAT activation. 14
Of the beta-receptors, beta-3 may be the most significant mediator of thermogenesis. However alpha, beta-1 and 2 receptors are also found within BAT.11 Potential targets to activate BAT continue to be identified and include cold exposure, insulin, thyroid hormone, beta-agonists11 and even exercise13.
Perhaps the most interesting compound shown to activate BAT is 6-paradol found in PHENBUTEROL – in particular the highly standardized 6-paradol contained in Aframomum melegueta, a plant with the common name Grains of Paradise (GOP) that is a member of the ginger family. GOP has been shown in both animal and humans studies to activate BAT and increase whole-body energy expenditure. 17,18 However, its important to mention that not just any form of GOP will provide the necessary levels of standardized 6-paradol needed to be effective. In fact, very few manufacturers are capable of providing the potency used in PHENBUTEROL.
Activating UCP-1 may help dieters breakthrough plateaus and reach their weight loss goals.
Attempts have been made to summarize the fat burning potential of activated BAT14. Whittle suggests that just a few grams of BAT might increase daily energy expenditure by 20%.13 Cypress, et al., postulates that 50 grams could account for 20% daily energy expenditure.2 The overall point is that where many adults in the U.S. carry kilograms of extra WAT, very small amounts of BAT may help burn some of that excess off. The first question that comes to mind is what has happened to BAT in overweight people? UCP-1 has been shown to decrease in models of fasting and food restriction.15 Decreased UCP-1 leads to decreased activity of BAT leading to the hypothesis that Western dieting techniques only serve to deactivate BAT. This may help explain why dieters often plateau and find it more difficult to lose weight after only a few weeks of dieting and caloric restriction. PHENBUTEROL may actually be able to reduce the diet induced down-regulation of UCP-1 and help dieters break through those plateaus.
PHENBUTEROL ACTIVE INGREDIENTS:
Aframomum melegueta (Grains of Paradise)
Grains of Paradise, also known as Aframomum melagueta, is a spice native to West Africa that has been shown to activate brown adipose tissue (BAT) while increasing whole-body energy expenditure. 18 Therefore, Aframomum melagueta may increase the reduction of body fat through activation of BAT and subsequent thermogenesis. 49,50,51,52,53
Brown adipose tissue is one of two types of fats in the body, with the other being white adipose tissue (WAT). BAT has thermogenic properties, as its primary function is to generate body heat, while WAT stores triglycerides into fat cells, causing us to store fat. The problem being is that WAT is more predominant in the human body and BAT is only highly active when we are infants. While there are still small amounts in our body, as we get older, studies have shown that there are higher amounts of BAT in people with a lower body weight. 17 However, BAT may continue to decrease as we get older 54, increasing the importance of finding ways to activate it to help reduce body fat.
When the human body is exposed to a cold environment, BAT functions as a non-shivering thermogenesis. It acts as a heater organ to raise the internal body temperature to keep the body warm. Stimulating the sympathetic nerve system will increase norepinephrine, which can activate the thermogenesis effects of BAT. Phenbuterol, through the administration of Aframomum melagueta, supports the natural increase of norepinephrine.
Besides the warming properties of Aframomum melagueta, the spice is a strong antioxidant that has beneficial digestive properties. 55,56 Antioxidants are vital for overall health because they support all the functions of your organs and they fight free radical cells in your body that support the decrease in fat storage and an increase in the use of fat to be burned as energy.
Caffeine
Caffeine is a central nervous system and metabolic stimulant.28 Caffeine has been shown to increase energy, reduce fatigue and improve clarity and mental focus. 29,30 Caffeine also contributes to increasing the lipolysis process, therefore helping to mobilize fatty acids to aid in fat loss. This mechanism can at least in part be explained by not only increased metabolism by raising resting energy expenditure, but by activation of BAT.
Rauwolfia serpenia
Rauwolfia serpenia acts primarily as an alpha-2 antagonist. 45 Alpha-2 receptors hinder the release of norepinephrine and are highly anti-lipolytic. This means that it is harder for the fat to break down in stubborn fat areas when alpha-2 receptors are present. Rauwolfia acts to help suppress alpha-2 receptors, thus allowing the release of norepinephrine. The blocking of the alpha-2 receptors in turn helps maximize powerful thermogenic effects and, as discussed earlier, when norepinephrine is released, BAT can be activated.
It is through the above mechanism that Rauwolfia acts as a CNS stimulant. Therefore, this compound promotes lipolysis and may actually help you burn fat in problem areas such as the abdomen and glutes. 46,47 This is made possible by allowing the fat burning beta-receptors to work more freely. Rauwolfia contains another very important benefit: It has nitric oxide benefits that help blood flow into the muscle that can result in greater muscle pumps.
While Rauwolfia naturally contains small amounts of yohimbine, it does not carry the same side effects associated with high doses of this herb. It only contains enough yohimbine to help assist Rauwolfia serpenia in alpha-2 receptor suppression. 48
† Phenbuterol contains no ephedrine, fenfluramine or any synthetic drug. For informational and educational purposes only.
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NOTE: PHENBUTEROL is a trade name and is not intended to depict any comparison to any pharmaceutical or other product or any particular benefit thereof.
*THESE STATEMENTS HAVE NOT BEEN EVALUATED BY THE FOOD AND DRUG ADMINISTRATION. MUSCLEMEDS PRODUCTS ARE NOT INTENDED TO DIAGNOSE, TREAT, CURE OR PREVENT ANY DISEASE.