VPX Sports Meltdown??®: Impact on blood norepinephrine and lipolysis by
Richard J. Bloomer
Introduction
The quest for a leaner physique is a path sought by many, from average fitness enthusiasts to advanced bodybuilders. To this end, multiple products currently exist within the category of lipolytic (i.e., fat loss) agents, with several new products emerging each year. While it is clear that there are few human clinical trials in which the actual product of sale has been used within the research design, there does at least exist some scientific rationale behind the blend of ingredients found in some of these preparations. A prime example is the lipolytic agent Meltdown??®, which has been recently developed by VPX Sports. Unsolicited consumer testimonials surrounding this product have been quite positive, and anecdotal evidence indicates that Meltdown??® is a real contender in this class, possibly in line to dominate in the near future.
The purpose of this article is to provide a brief overview of the process of fat mobilization and â?????burningâ???, in addition to providing a look into the science related to the proposed benefits of Meltdown??®. An attempt has been made to limit scientific jargon and detailed scientific discussion, in order to provide a more reader-friendly article. Individuals interested in a more detailed discussion of the scientific rationale and process of engineering behind Meltdown??® are referred to the article on this topic written by Jack Owoc, available at
VPX Sports.
Lipolysis 101
Although the goal of fat loss may appear rather simplistic, the actual process of fat metabolism is quite complex. In fact, in most graduate level textbooks focused on metabolism, the process is separated into seven distinct steps, as listed below and shown in Figure 1.
1.Mobilization of fatty acids from storage form (triglycerides) from within adipocytes (i.e., fat cells)
2.Transport of fatty acids to the target tissue (via carrier protein albumin)
3.Uptake of fatty acids into the cell (via sarcolemma fatty acid binding protein and fatty acid transporter)
4.Activation of fatty acids (via ATP dependent process)
5.Translocation of activated fatty acids into inner mitochondrial matrix (via carnitine dependent enzymes: carnitine acyl tranferase 1 and 2â??????CAT1 and CAT2 [for long chain fatty acids])
6.Beta oxidation (the actual process of degrading fatty acids into products which will eventually be used for energy productionâ??????acetyl CoA and the electron carriers NADH and FADH2)
7.Krebs/Citric acid cycle/tricarboxylic acid cycle and electron transport chain (where ATP energy is actually produced from products created within beta oxidationâ??????hence fat is now available as energy and ready to be â?????burnedâ??? as fuel)
Although each step is indeed important to the ultimate goal of â?????burningâ??? fat, many lipolytic agents target the first step of this process in an attempt to make more fatty acids available in the circulation, in order to be picked up by active tissue to be used as fuel. With this in mind, the logical question becomes â?????What can be done to stimulate fatty acid mobilization?â???
First, understand that this process itself typically involves the interplay between the enzyme hormone sensitive lipase (HSL), the specific hormones acting to stimulate HSL, and the receptors that bind to these hormones in order for them to exert their effect. Although other hormones are certainly involved in fatty acid metabolism (e.g., growth hormone, thyroid hormone, ACTH, cortisol), the chief hormones related to our discussion here are the catecholamines, epinephrine (EPI) and norepinephrine (NE). These interact with both beta adrenergic receptors (EPI and NE), as well as alpha-adrenergic receptors (NE). Depending on which receptors are activated, lipolysis can be either stimulated (beta) or inhibited (alpha), with optimal HSL activity observed in the presence of low insulin levels.
While certain drugs/nutrients can act directly on beta receptors in order to stimulate lipolysis, others act indirectly by stimulating an increase in NE, which subsequently binds these adrenergic receptors to allow for an effect. Unfortunately, as indicated above, NE is not selective in its binding. That is, while it can bind beta (1, 2, and 3 sub-class) receptors, it also binds alpha (1 and 2 sub-class) receptors. Hence, in a way, NE may both â?????stimulateâ??? and â?????inhibitâ??? fatty acid mobilization. Specifically, activation of alpha 2 receptors inhibits further release of NE, allowing NE to act as its own negative feedback signal. That is to say, it shuts off its own release. If fat loss is the goal, this is a highly undesirable effect.
Meltdown??® Science: What and Why?
This is where the science of Meltdown??® technology comes into play. First, while it should be noted that multiple key ingredients exist within this formulation, three include specialized forms of the nutrient Yohimbine (Yohimbine HCl, alpha-Yohimbine, and 11-hydroxy Yohimbineâ??????with extended half-life). Yohimbine is the principle alkaloid from the herb Yohimbe, and acts as a selective alpha 2 antagonist. Hence, it can function to impair the negative feedback loop specific to NE. Moreover, it has been demonstrated that short-term Yohimbine supplementation can stimulate a significant rise in blood NE levels. Hence, Yohimbine supplementation may serve to optimize blood NE to allow for enhanced fatty acid mobilization. Coupled with regular exercise training (which by itself can improve all steps of fatty acid metabolism as described above), this approach may serve to maximize fat loss.
Aside from fatty acid mobilization, Yohimbine may also aid in lipolysis by acting to improve blood flow, and hence, transport of fatty acids to tissue to undergo oxidation. This is because alpha receptor activation promotes smooth muscle contraction leading to vasoconstriction (a decrease in blood flow). Thus, an alpha 2 receptor antagonist combination such as the three component Yohimbine matrix found in Meltdown??® may be expected to improve blood flow. Indeed, isolated Yohimbine has been shown repeatedly in the literature to improve blood flow in regards to individuals with diseases that are associated with blood flow restriction. However, admittedly, studies would need to be done in healthy fitness enthusiasts/ bodybuilders in order to make such claims for Meltdown??® specifically.
As mentioned earlier, Meltdown??® contains several other key ingredients besides Yohimbine, including methyl Synephrine, a beta adrenergic agonist (beta 3 in particular). This functions to increase the metabolic rate while having little effect on heart rate or blood pressureâ??????less anxiety/jitteriness. Coupled with the alpha antagonistic effects of the Yohimbine matrix, methyl Synephrine has the potential to further promote lipolysis. Furthermore, the addition of caffeine to this mix adds even greater potential.
The scientific team at VPX has also engineered two new forms of the amphetamine-like/thyroid stimulating agent Phenylethylamine (PEA). Because ordinary PEA was found to be metabolized far too rapidly, the novel compounds R-??Ÿ-Methylphenylethylamine (R-??Ÿ-M-PEA) and n-Methyl-??Ÿ-Phenylethylamine (n-Methyl-??Ÿ-PEA) were developed, and are contained within Meltdown??®. The VPX scientists hypothesize that by adding a monoamine oxidase (MAO) inhibitor such as methyl Hordidine to the mix could significantly increase the duration of action of R-??Ÿ-M-PEA and n-Methyl-??Ÿ-PEA, while possibly allowing entry and transport across the blood brain barrier. This latter effect may bring with it mild feelings of euphoria. In addition to the effects on PEA metabolism, evidence is clear that MAO inhibition can extend the effects of Yohimbine, possibly improving the outcome of this three component Yohimbine matrix. This is because when used in combination, Yohimbine increases NE release, whereas MAO inhibitors hinder the typically observed NE degradation. The resultâ??????more NE available to promote lipolysis.
In addition to the above ingredients, Meltdown??® contains methyl Tetradecylthioacetic acid, an agent with lipolytic properties related to the prevention of diet-induced insulin resistance and adiposity, in addition to induction of programmed cell death (i.e., apoptosis) within adipocytes. Meltdown??® also contains Cholecystokinin (CCK-8), a hormone of the gastrointestinal system known for its effect on increasing satiety (feeling of â?????fullnessâ???). This may have an impact on hunger, which is believed to be related to a decrease in the rate of gastric emptying. Lastly, Meltdown??® contains cyclic AMP, a key â?????second messengerâ??? system involved in hormone-receptor interaction associated specifically with beta receptors. Considering the collective matrix of potentially synergistic ingredients, in addition to the pharmaceutically inspired polymer based lipid delivery system (PolyLipid) which allows for â?????steady stateâ??? technology delivering both rapid and sustained controlled-release of the active ingredients, Meltdown??® is certainly a product that has great potential as a lipolytic agent, ultimately leading to decreased body weight/fat.
Meltdown??® Research Studies: Randomized, double blind, placebo controlled trials.
Although anecdotal reports indicating the effectiveness of Meltdown??® are indeed exciting, the efficacy of this product needs to be evaluated in well-designed, randomized, placebo controlled trials. This is exactly what is currently being planned between VPX Sports and the University of Memphis. In the text below I present a summary of the work we will soon begin related to clinical testing of Meltdown??®.
First of all, let me stress the fact that behind the extreme hype and marketing tactics of many sports nutrition companies, it is clear that few products have actually been tested in well-designed human clinical trials focused on weight/fat loss. Of course, in some instances, one of the â?????keyâ??? ingredients contained within the product may have been reported to have efficacy. However, the research design in many of these situations often has absolutely nothing to do with the product of sale! That is, many studies contain dosages of a certain ingredient at quantities that far exceed those provided within the actual product of sale. Also, the route of administration used within many of the research studies may not be the same (e.g., intravenous injection vs. oral intake). Finally, and perhaps most importantly, the subject population is often quite different. That is, most clinical studies focused on weight/fat loss have included obese individuals/animals as the target population. The reason for this is simpleâ??????such â?????subjectsâ??? typically experience a greater magnitude of change because they simply have more weight/fat to lose. Most consumers who do not fall within the same category as such test subjects should not expect the same degree of effect in terms of weight/fat loss. Of course, this is seldom mentioned in the advertisements. In our studies with Meltdown??® we are attempting to mimic real-life scenarios in which consumers will be using this exact product.
For example, in our acute (short-term) study we will be measuring blood NE concentrations, in addition to metabolic rate for up to 90 minutes following intake of Meltdown??®. In this study we will use resistance trained men (e.g., bodybuilders, powerlifters) who will ingest the actual product of sale (not simply one of the â?????keyâ??? ingredients), and will be provided the same dosage taken by most consumers.
In our chronic (intervention) study, we will enroll both men and women who are recreationally fit (i.e., who exercise 3-4 days per week) and who are in â?????averageâ??? physical condition (e.g., men 15-20% body fat; women 20-30% body fat). Although the magnitude of our observed change in weight/fat loss may not be as robust as if using obese individuals as subjects, consumers can be assured that the type of change reported in our work will likely be obtainable for them as well. Of course, individuals who are carrying more weight/fat than those in our study may expect to experience more pronounced effects. Aside from the issue of subject criteria, as with our acute study, we will be using the same product (Meltdown??®) and dosing schedule as recommended to consumers. Our outcome variables (i.e., things we are most interested in measuring) will be multiple, including a variety of anthropometric tests (including dual energy x-ray absorptiometry for measurement of fat and fat free mass), metabolic tests (including resting metabolic rate), and bloodborne variables (including NE, lipids, glucose, inflammatory and neuronal cell health markers, etc.).
To our knowledge, this will be the most comprehensive clinical trial to date involving a nutritional supplement marketed as a lipolytic agent. To the credit of VPX Sports, they are interested and committed to invest the time and expense needed to test the efficacy of Meltdown??®. In this way, we may generate evidence in support of the information discussed within this article. We hope to have preliminary data available by summer 2008. Stay tuned for more information related to this exciting work!
