APPLIED NUTRICEUTICALS NEOVAR
|PCr-Mono Matrix (Proprietary Blend)||
|Phosphocreatine, Creatine Monohydrate
|Glucovar/Adenylate Cyclase Sensitization Complex (Proprietary Blend)||
|Banaba Extract (Lagerstroemia Speciosa 1% Corosolic Acid), Gymnema Sylvestra (75% Extract), D-Pinitol, Bioperine (95%-98% Piperine) Registered Trademark of Sabinsa Corp. and holds patent #5,536,506).|
* (DV) Daily Value based on a 2,000 calorie diet
** Percent Daily Values not established.
Gelatin, Candurin Silver Fine, FD&C Red #3, FD&C Yellow #5, FD&C Blue #1
Take immediately post-workout with carbohydrates, preferably sugars. Take second dose with any other meal throughout the day containing carbohydrates.
Up to 150 lbs:
DOSE 1: 2 Capsules
DOSE 2: 2 Capsules
(4 Capsules Daily)
DOSE 1: 3 Capsules
DOSE 2: 3 Capsules
(6 Capsules Daily)
DOSE 1: 4 Capsules
DOSE 2: 4 Capsules
(8 Capsules Daily)
This product is only intended to be consumed by healthy adults 18 years of age or older. Do not use if you are pregnant or nursing. Before using product, seek advice from a physician if you are unaware of your current health condition or have any pre-existing medical condition including but not limited to kidney disease or if you are taking any prescription or over the counter medication. Do not use if you are pregnant, nursing, prone to dehydration or exposed to excessive heat. Discontinue use and consult your health care professional if you experience any adverse reaction to this product. Before beginning any weight loss program, consult you health care provider. Store at room temperature and avoid excessive heat. Do not use if inner safety seal is broken or missing.
Applied Nutriceuticals NeoVar - Next Generation Creatine for Maximum Cellular Recovery!
By combining the latest principles of nutritional technology with ancient Ayurvedic medicine, Applied Nutriceuticals research and development team has developed the most potent and biologically efficient post-workout nutrient enhancement product on the market. A precisely proportioned combination of Phosphocreatine and creatine monohydrate (Mono/PCr complex™) is the primary element, which plays a vital role in cellular energy production by regenerating ATP in skeletal muscle and makes it available for explosive exercises (1-5). Another important component of NeoVar, Corosolic Acid is extracted from the Banaba plant, a medicinal herb that grows in India, Southeast Asia, and the Philippines. It has been used for centuries as a treatment for hyperglycemia and diabetes, and the hypoglycemic effect is chemically very similar to that of the hormone insulin (7-11). Insulin is a polypeptide anabolic storage hormone, and is a crucial hormone in creatine transport and is necessary for the deposition of creatine phosphate in skeletal muscle. NeoVar also adds a high-quality extract of gymnema sylvestra, an herb native to central India, where it has been used as a natural treatment for diabetes for over 2,000 years. Gymnemic acid, the main active constituent of gymnema, has anti-sweetener, anti-inflammatory, and anti-diabetic attributes and its effects also closely mimic those of insulin (13-16). Bioperine® (piperine 95%) is also included in the formulation and has been shown in clinical studies to enhance the uptake of amino acids and many other nutrients, allowing protein, carbohydrates, creatine, and other nutrients to be more avaliable to supply hard-working muscle (40). The final component of NeoVar, D-Pinitol, is a cutting-edge compound that enhances nitric oxide production and insulin sensitivity which are key factors in nutrient transport. D-Pinitol has also been shown in human studies to enhance intramuscular creatine deposition in human clinical studies (30). The individual effects of these compounds combine synergistically to produce a dramatic positive impact on the strength, size, and endurance of skeletal muscle tissue.
The theory behind the synergism of the Mono/PCr Complex is quite simple: It aims to match the CRfree 40/PCr 60 ratio of the naturally occurring human skeletal intramuscular creatine pool as closely as possible; allowing for greater absorption and utilization with minimal waste. The product is blended to maximize PCr levels, while at the same time including monohydrate due to its high molar percentage of creatine as the active ingredient. Human skeletal muscle creatine stores are comprised of approximately 40% in the free creatine form (CRfree), while the remaining 60% is in the phosphorylated form; creatine phosphate (CP). The Mono/PCr complex in NeoVar essentially feeds both CRfree levels and phosphocreatine levels in this optimized ratio, which is chemically identical to what is stored in the working muscles (1,3-5). Several animal studies have confirmed that CRfree has better availability for site phosphorylation for the production of ATP, and further studies are currently underway on the validation of this theory in humans. Similarly, research on phosphate has concluded that it has numerous benefits in the athletic realm even without creatine, especially in terms of buffering lactic acid during explosive exercise. Phosphate supplementation raises levels of 2,3-diphosphoglycerate (2,3-DPG), the enzyme that unloads oxygen into muscle. Research has shown that phosphate supplementation reliably raises blood levels of 2,3-DPG, and also improves the production and use of glycogen for fuel Therefore, this blend of both CRfree and PCr could allow skeletal muscle to “recognize” and assimilate the creatine in a more refined manner, allowing for a significant degree of uptake enhancement in skeletal muscle tissue (32-38). Additionally, the insulin mimetic compounds included in the formula may even further enhance these benefits.
A recent trend in creatine supplementation has been the development of exotic esters and alkaline/time-released delivery systems. In developing NeoVar, we researched virtually every creatine derivative currently available before arriving with the final formulation. We analyzed numerous and often conflicting studies regarding the benefits of each and found many of the so-called improvements actually reduced the effectiveness of the products they were used in. Ultimately we elected to avoid this trend, which is proving to be more about company’s efforts to differentiate their products than actual effectiveness. Some of our findings include:
1. Many of the esters and delivery systems included in some of the newer products can be potentially difficult for the body to metabolize; the creatines included in NeoVar are essentially pure creatine, water, and phosphate and contain no other byproducts that could potentially hinder utilization.
2. Esters are simply fatty acid chains attached to a parent substance (in this case, creatine) that delay absorption and/or release; the newer esterified creatines actually contain less creatine, and more fatty acid chains that have no use in any type of physiological process. Several low-quality products use versions with longer esters and are only 20-30% creatine, with the rest being useless fatty acids.
3. Recent human research studies have proven that many of the alkaline creatine delivery systems actually do not work as well as creatine phosphate or creatine monohydrate as far as absorption in the digestive system and ultimately in skeletal muscle (43).
In developing NeoVar, we sought to use the molecules proven in numerous human studies to replicate the exact physiological ratios found in the intramuscular creatine pool in human skeletal muscle so the body can recognize and utilize it readily.
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).
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
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 have 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
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 means±SD. 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-pinitol/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.
References1. Hultman E, Soderlund K, Timmons JA, et al. (1996) Muscle Creatine Loading in Men.
J Appl Physiol (81): 232-37.
2. Juhn MS, (2003). Popular sports supplements and ergogenic aids. Sports Med. 33 (2): 921-39. PMID 12974658.
3. Powers ME et al. (2003) Creatine Supplementation Increases Total Body Water Without Altering Fluid Distribution. Journal of Athletic Training 38 (1): 44-50 PMID 12937471.
4. Dangott B, Schultz E, Mozdziak PE. (2000). Dietary creatine monohydrate supplementation increases satellite cell mitotic activity during compensatory hypertrophy. International Journal of Sports Medicine 2000 Jan (21(1) 13-16 PMID 10683092.
5. Stout JR et al. (1997) The effects of a supplement designed to augment creatine uptake on anaerobic reserve capacity. NSCA National Conference Abstract.
6. Tarnopolsky MA, Parise G, Yardley NJ et al. (2001). Creatine-dextrose and protein-dextrose induce similar strength gains during training. Med Sci Sports Exerc. 33 (12): 2044-52 PMID11740297.
7. Department of Clinical Nutrition, Suzuka University Medical Science (2004). Corosolic Acid induces GLUT4 translocation in genetically type 2 diabetic mice. Biol Pharm Bull 2004 Jul. 27(7): 1103-5.
8. Judy WV, Hari SP, Judy JS, Naguib YM, Passwater R et al. (2003). Antidiabetic activity of a standardized extract (Glucosol) from Lagerstroemia speciosa leaves in Type II diabetics. A dose-dependant study. J Ethnopharmacol 87(1) 115-117.
9. Miura T. et al. (2006). Antidiabetic effects of corosolic acid in KK-Ay in diabetic mice. Biol Pharm Bull 29(3): 585-587.
10. Fukushima M. et al. (2006). Effect of corosolic acid on postchallenge plasma glucose levels. Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, 1-5-4, Minatojimaminamimachi, Chuo-ku, Kobe, Japan.
11. Liu L. et al. (2001). An Extract of Lagerstroemia speciosa L. Has Insulin-Like Glucose Uptake-Stimulatory and Adipoctype Differentiation-Inhibitory Activities in 3T3-L1 Cells. J of Nutr. 131: 2242-47.
12. Hong H, Maeng W (2004). Effects of malted barley extract and banaba extract on blood glucose levels in genetically diabetic mice. J Med Food. 7(4): 487-90.
13. Gholap S, Kar A. Effects of Inula racemosa root and Gymnema sylvestre leaf extracts in the regulation of corticosteroid induced diabetes mellitus: involvement of thyroid hormones. Pharmazie 2003;58(6):413-415.
14. Grover JK, Yadav S, Vats V. Medicinal plants of India with anti-diabetic potential. J Ethnopharmacol 2002;81(1):81-100.
15. Jiang H. [Advances in the study on hypoglycemic constituents of Gymnema sylvestre (Retz.) Schult]. Zhong Yao Cai 2003;26(4):305-307.
16. Kamei K, Takano R, Miyasaka A, et al. Amino acid sequence of sweet-taste-suppressing peptide (gurmarin) from the leaves of Gymnema sylvestre. J Biochem 1992;111:109-112.
17. Khare AK, Tondon RN, Tewari JP. Hypoglycaemic activity of an indigenous drug (Gymnema sylvestre, "Gurmar") in normal and diabetic persons. Indian J Physiol Pharm 1983;27:257-258.
18. Kothe A, Uppal R. Antidiabetic effects of Gymnema sylvestre in NIDDM - a short study. Indian J Homeopath Med 1997;32(1-2):61-62, 66.
19. Lawless HT. Evidence for neural inhibition in bittersweet taste mixtures. J Comp Physiol Psychol 1979;93(3):538-547.
20. Meiselman HL, Halperin BP. Human judgments of Gymnema sylvestre and sucrose mixtures. Physiol Behav 1970;5(8):945-948.
21. Meiselman HL, Halpern BP. Effects of Gymnema sylvestre on complex tastes elicited by amino acids and sucrose. Physiol Behav 1970;5(12):1379-1384.
22. Min BC, Sakamoto K. Influence of sweet suppressing agent on gustatory brain evoked potentials generated by taste stimuli. Appl Human Sci 1998;17(1):9-17.
23. Murakami N, Murakami T, Kadoya M, et al. New hypoglycemic constituents in "gymnemic acid" from Gymnema sylvestre. Chem Pharm Bull 1996;44(2):469-471.
24. Porchezhian E, Dobriyal RM. An overview on the advances of Gymnema sylvestre: chemistry, pharmacology and patents. Pharmazie 2003;58(1):5-12.
25. Narayanan et al (1987), Pinitol- A new anti-diabetic compound from the leaves of Bougainvillaea, Current Science, Vol 56, No 33, pp139-141.
26. Steenge GR, Simpson EJ and Greenhaff PL. Protein- and carbohydrate-induced augmentation of whole body creatine retention in humans. J Appl Physiol 2000;89: 1165-1171.
27. Haugland RB and Chang DT. Insulin effect on creatine transport in skelatal muscle (38464). Proc Soc Exp Biol Med 1975;148: 1-4.
28. Holman GD and Kasuga M. From receptor to transporter: insulin signaling to glucose transport. Diabetologia 1997;40: 991-1003.
29. White MF. The insulin signaling system and the IRS proteins. Diabetologia 1997;40 Suppl 2: S2-17.
30. Bates SH, Jones RB and Bailey CJ. Insulin-like effect of pinitol. Br J Pharmacol 2000;130: 1944-1948.
31. M. GREENWOOD, R.B. KREIDER, C. RASMUSSEN, A.L. ALMADA, AND C.P. EARNEST (2001) D-PINITOL AUGMENTS WHOLE BODY CREATINE RETENTION IN MAN. JEP: 4(4): 41-47.
32. Dale G, et al. Fitness, unfitness, and phosphate. British Medical Journal 1987; 294:939)
33. Kreider RB, et al. Effects of phosphate loading on oxygen uptake, ventilatory anaerobic threshold and in performance. Med Sci Sports Exer 1990; 22:250-255
34. Miller GW, et al. Effects of phosphate loading on anaerobic threshold. Med Sci Sports Exer 1991; 23:S35
35. Farber M et al. Effect of decreased oxygen affininty of hemoglobin on work performance in healthy humans. J Lab Clin med 1984; 104:166-175
36. Cade R, et al. Effects of phosphate loading on 2,3-diphosphoglycerate and maximal oxygen uptake. Med Sci Sports Exer 1984; 16:263-268
37. Stewart I, McNaughton L. Phosphate loading and effects of VO2 Max in trained cyclists. Res Quart 1990; 61:80-84
38. Chasiotis D. Role of cyclic AMP and inorganic phosphate in the regulation of glycogenolysis during exercise. Med Sci Sports Exer 1988; 20:545-550
39. Kreider RB, et al. Effects of phosphate loading on metabolic and myocardial responses to maximal and endurance exercise. Int J Sports Nutr 1992; 2:20-47
40. G. Shoba, D. Joy, T. Joseph, M. Majeed, R. Rajendran and P.S. Srinivas Influence Of Piperine On The Pharmacokinetics Of Curcumin In Animals And Human Volunteers. Planta Med. (1998) 64(4):353-356.
41. Vladimir Badmaev, M.D., Ph.D., Muhammed Majeed, Ph.D. and Edward P. Norkus Ph.D. Piperine, An Alkaloid Derived From Black Pepper, Increases Serum Response Of Beta-Carotene During 14-Days Of Oral Beta-Carotene Supplementation. Nutrition Research (1999) 19(3) 381-388.
42. Vladimir Badmaev, M.D., Ph.D., Muhammed Majeed, Ph.D., and Lakshmi Prakash, Ph.D. Piperine Derived From Black Pepper Increases The Plasma Levels Of Coenzyme Q10 Following Oral Supplementation. J. Nutr. Biochem. (2000) 11: 109-113.
43. Tallon MJ1 and Child R2. Kre-alkalyn® supplementation has no beneficial effect on creatine-to-creatinine conversion rates. 1University of Northumbria, Sport Sciences, Northumbria University, Northumberland Building, Newcastle upon Tyne, United Kingdom.2Department of Life Sciences, Kingston University, Penrhyn Rd, Kingston-upon-Thames, United Kingdom.