Creatine Phosphate Molecule
Creatine provides a variety of anabolic effects on skeletal muscle, increasing lean body mass while being a source of ATP (adenosine tri-phosphate, a source of cellular energy that aids in muscle contraction). Increased creatine phosphate inside the muscle cell is a powerful anabolic stimulus for muscle hypertrophy. Increased CP stores in the muscle allow for greater intracellular water retention. Greater intracellular water retention from increased CP raises osmotic pressure within the cell, allowing for heightened protein synthesis and nitrogen retention. Heightened protein synthesis and nitrogen retention create an optimal anabolic environment for intense muscular growth (2-4). Creatine uptake into the muscle can also be influenced by glucose, insulin and insulin-sensitizing agents, as the correct manipulation of these entities can allow for much larger amounts of creatine to be stored within the muscle cells. This is the main goal of NeoVar- to allow for the greatest amounts of creatine to be stored in working muscle through the manipulation of different nutrients, because as we all know, the more creatine you can hold in your muscles, the more your muscles will recover and grow (1-6).
ATP-PCr System
There are many other potential benefits to creatine supplementation. Creatine boosts the activity of myogenic cells, which are satellite stem cells that have the ability to turn themselves into new muscle cells if instructed to do so by the genetic code of the body. These satellite cells fuse with an adjacent damaged muscle fiber, thereby increasing myonucleii numbers necessary for growth and repair. This process of myogenic maturation is called hyperplasia, and the subsequent new muscle cells formed by hyperplasia also have the ability to enable muscle hypertrophy (growth) if combined with weight training (4).
As we know, creatine supplementation increases intramuscular creatine stores, but to greatly varying extents. Many manufacturers suggest an initial loading dose to accelerate creatine saturation within the cell; however this method commonly produces uncomfortable abdominal cramps and bloating. In the early 90's researchers discovered that ingesting creatine w/ high glycemic carbohydrates such as dextrose dramatically raised skeletal muscle concentrations of creatine beyond regular oral supplementation alone. More recent research has found that taking creatine with glucose (25-100 g), or with combinations of glucose and protein (around 30-40 grams of each macronutrient) allows for larger amounts of creatine storage due to the increased insulin secreted in response to the carbohydrate intake (1,5,6). Up to 60% increases in intracellular creatine were noted in some subjects (a 20% raise is considered normal in most studies) using these methods, but the results varied greatly (6). While moderately effective, these techniques fall short because most ingested creatine is still not absorbed. The unabsorbed creatine accumulates outside of the targeted cells, causing a multitude of negative side effects including bloating, cramping and dehydration. The objective when developing NeoVar was to discover other compounds that can further aid in greater uptake of intramuscular creatine.
The level of creatine uptake into muscle is influenced greatly by intramuscular creatine concentration and extracellular concentrations of glucose and insulin. The ingestion of high glycemic carbohydrates (such as dextrose, fructose, and sucrose) causes a large increase in blood glucose, and concurrent to this rise in blood glucose, a surge (or “spike”) of insulin is released from the pancreas in order to control the amount of sugar in the blood. Since insulin is necessary in transporting creatine and blood glucose into skeletal muscle, the increased insulin drives greater creatine uptake into muscle (1,5,6). The amount of intramuscular creatine concentration and extracellular concentrations of glucose and insulin influence the degree of absorption into the cell. This is important, in that individuals who supplement with creatine and who have low muscle creatine and phosphocreatine levels are more responsive to creatine supplementation. The additional insulin released in response to the ingestion of carbohydrates (which convert to glucose) helps drive more creatine into the cell (6).
Therefore, taking creatine with products that can safely and effectively alter insulin levels and/or sensitivity such as banaba extract and gymnema sylvestre may enhance creatine uptake and retention. While these two herbs have been used for years in Eastern medicine to control diabetes, they are very new compounds to Western science. Corosolic acid (the active ingredient in Banaba extract) and gymnemic acid (the active ingredient in Gymnema sylvestre) closely mimic insulin by SAFELY stimulating much greater glucose into cells while not allowing plasma insulin levels to increase. It has also been plausibly theorized that with this increased cellular transport of glucose, there will also be an increased transport of creatine phosphate into the cell (7-19). In some studies where they conducted direct comparisons with insulin, corosolic acid and gymnemic acid actually performed just as well as insulin at controlling blood
Insulin Sensitivity Graphically Illustrated
sugar in patients with Type II diabetes. Therefore while corosolic acid and gymnemic acid have a mechanism of action similar to insulin, they do have a distinct advantage over insulin, in that it is not an “equal opportunity” deposition agent, like insulin. In other words, insulin can be problematic and beneficial at the same time, in that while it can increase deposition of glucose, protein and creatine into the muscles, it can also have a negative effect by increasing body fat levels. Plus, when the body produces too much insulin over time, it begins to become insensitive to the hormone, resulting in a down-regulation of insulin receptors on target tissue (7-10, 13-21).
Gymnemic acid has also been shown to interact with receptors on the tongue to decrease the sensation of sweetness in many foods. This action has been shown to reduce blood sugar and cholesterol levels in diabetic animals and humans and may provide some benefits in terms of regulating appetite control and food cravings (19,20). Research has isolated at least nine different fractions of gymnemic acid, with each fraction possessing glucose-repartitioning activity (21-24). The effect of gymnemic acid on lowering glucose levels in the blood is gradual, usually typically taking a few days. Very high doses of gymnemic acid may even help to repair the cellular damage that causes diabetes (by helping to regenerate the insulin producing beta-cells in the pancreas). Human studies on gymnema in diabetes treatment have shown significant reduction in blood glucose, glycosylated hemoglobin (an index of blood sugar control) and insulin requirements (so insulin therapy could be reduced) (23). There appears to be due to an increase in the effectiveness of insulin with gymnema, rather than causing the body to produce more – although the precise mechanism by which this occurs remains unknown. As with other natural ingredients for control of blood sugar and insulin levels, such as corosolic acid, a common “side effect” is weight loss – probably due to a combination of appetite suppression and control of food cravings (especially for carbohydrates and sweets) (19-24).
Insulin, Glucose, and Glut-4 Translocation
Corosolic Acid (the active ingredient in Banaba Extract) has been shown to increase GLUT4 translocation in human studies. GLUT4 (muscle facilitative glucose isoform 4, a transporter protein) translocation is important because GLUT4 is a transporter protein that regulates the amount of glucose allowed into skeletal muscle cells. Corosolic acid increases the ability of the body to regulate the amount of glucose coming into a cell, and in diabetic patients, this allows for greater glucose disposal in the muscle cells. This keeps plasma insulin levels the same, meaning that the intake of corosolic acid as an insulin mimicking/glucose control agent has significant nutrient repartitioning effects (7-11). In this case, nutrient repartitioning means that while creatine, glucose, and protein are being deposited in the muscle cells, fat is not being deposited in adipocytes (fat cells), as is the case with insulin (8). This is very important, because when more simple carbohydrates are ingested after a workout, it can be theorized that more blood glucose (and creatine) are deposited into the muscle. This can help the athlete retain a more positive nitrogen balance, thus enhancing recovery and building mass, making corosolic acid and gymnemic acid important components that contribute to the profound affects of NeoVar (8-10).
Bioperine®
Bioperine (piperine 95%) is a revolutionary compound that can increase the uptake of protein, amino acids, and creatine, as well as other supplements and nutrients. A simple 10-20 mg daily dose of this substance can increase the uptake of all of these components from 30-150%. Bioperine is hugely important in the formulation of NeoVar as an effective post-workout recovery and growth enhancement product, because it allows the stomach and small intestine to absorb much greater proportions of the other active ingredients in NeoVar, along with post-workout protein and carbohydrates. Bioperine also decreases the breakdown of many nutrients by the liver, allowing for greater amounts of active ingredients to stay in the bloodstream for a longer period of time; making them more available for uptake by hard-working muscles. This helps users of NeoVar recover much faster, therefore allowing for quicker gains in strength, lean muscle mass, and overall physique enhancement (40-42).
Increased Nutrient Uptake of Coenzyme Q-10 (top) and Curcumin (bottom) with Bioperine
D-Pinitol
The cutting-edge compound D-Pinitol is also an integral component of NeoVar. In recent studies, d-pinitol stimulated glucose uptake to an extent similar to that of insulin (26-30). In the presence of a low insulin concentration a synergistic effect was observed between pinitol and insulin, namely pinitol increased the effectiveness of insulin. In addition, d-pinitol can increase glycogen synthesis in the muscle cells, particularly in the absence of insulin. However, the main reason D-Pinitol truly shines in this formulation is that it has been clinically proven to enhance creatine storage in human subjects. Creatine loading alone has been reported to increase muscle creatine and phosphocreatine stores by 5 to 30% (1-4).
Percentage of creatine retained during the 3 day loading period for the placebo (P), creatine monohydrate (CM), low-dose D-pinitol (LP), high-dose D-Pinitol (HP), and pre-D-Pinitol loading (Pre-P) groups. Data are meansSD. a = p<0.05 from placebo ; b=p<0.05 from CM ; c=p<0.05 from LP ; d=p<0.05 from HP ; e=p<0.05 from Pre-P.
A study done by Greenwood in 2001 (see above) found that low-dose d-pinitol supplementation can indeed enhance whole-body creatine deposition more so than creatine alone, or creatine and high-dose d-pinitol. Another important factor to note is that this increase in creatine storage occurred completely independent of carbohydrate intake, meaning that the user could potentially have the same effects from a d-pinnitol/creatine mixture as they would with a carbohydrate/d-pinitol/creatine mixture (see below) (31).
Insulin-Like Response of D-Pinitol
Essentially, NeoVar combines the benefits of the most biologically available creatines with compounds that channel them into hard-working muscle cells more quickly, efficiently and completely than any other product ever produced. Precisely dosed, and in convenient capsules, no other product delivers the goods like NeoVar…at any price.
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