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Napalm is a unique and “explosive” mixture of ingredients that is sure to help you make quick work of enemy fat cells dug in deep on the battlefield of your body. By applying it to specific areas of your body, such as your abdominals, glutes, or thighs, the scientific concoction of glycyrrhetinic acid, raspberry ketones, SesaThin, yohimbine HCl, and synephrine HCl, all work together through different physiological pathways to help you take out stubborn body fat that doesn’t go away fast enough.
Napalm: Buy or Die – or both (if you’re a fat cell)!
When Caleb Stone, the founder and CEO of Avant Labs and Avant Research, wrote the first write up on transdermal fat loss products or ‘topicals’, he soundly stated his confidence – but cautiously avoided firm assurance — with respect to the efficacy of these products. Touted as the next best thing in phenotypic enhancement, topical fat loss products have evolved from an area once met with dubious skepticism into one with increasing acceptance and praise. The maturation of topicals into the forefront of physique improvement has been driven by the emphatic support for the gold standard in its class: Avant Labs’ Lipoderm-Ultra. With a flourish of positive feedback from both amateur and professional fitness enthusiasts following the release of the revolutionary Lipoderm series, critics and skeptics now view the science and effectiveness of topicals favorably and hold it in the highest regard. However, with success came copycats and bandwagon jumpers who’ve saturated the market and left the customers confused and unfulfilled.
This unsavory combination has prompted the innovative brain trust at Avant Research to create a new topical formula set to exceed our lofty historical standard of excellence. Through our various investments in personnel, research & development and customer feedback, we can proudly offer the assurance that our new and improved topical, Napalm, will provide unsurpassed local fat loss. Napalm contains a mixture of proven and innovative ingredients that focuses on enhancing local fat loss to its fullest potential.
The Science Of Topical Fat Loss Try explaining to a baby boomer that a cream can make fat disappear and s/he will likely offer you some of their anti-psychotic meds. After politely declining, explain that a revolutionary chemical milieu containing ample active ingredients, a skin-penetrating carrier solution, and localizing matrix will effectively spot reduce your trouble areas. Abs, obliques, thighs, buttocks, chest – you rub it on, let it dry and enjoy the results. The full, original article can be found here. But or the purposes of information, a terse summary is found below.
Percutaneous Delivery Targeting the delivery to the adipose tissue was the most substantial problem facing efficacious topical formulations. Atop that, is the role of the skin: it is an essential physical barrier which evolved for our protection. Thus, the necessity for a penetration enhancer emerged to loosen, or ease, the passage of ingredients within the topical matrix through the dermal layers and into the adipose. Pioneering scientific literature using common therapeutic drugs (1,2,3,4,5) proved that skin penetration and local deliver is attainable and feasible for certain compounds. But, why only certain compounds?
As you might expect chemicals, drugs, nutraceuticals, etc. come in all shapes and sizes. Finding the ideal combination triumphantly yielded the formulation for the Lipoderm Series, which has been adopted and improved upon by Avant Research to create the most effective all-in-one topical to date- Napalm.
Blood Flow Adipose tissue, which is renowned for its poor perfusion (or relative blood supply), is another important physiological barrier that can impede our body’s natural efforts to get skinny. Since fat must first be broken down prior to oxidation, an increase in perfusion to concentrated areas of stubborn fat will facilitate a reduction in fat mass by shuttling away liberated free fatty acids. Our knowledge of the adrenergic system tells us this is easily achievable by coupling alpha-2 antagonism (yohimbine) and beta-receptor activation (synephrine).
Performing adrenergic stimulation from the topical angle is particularly advantageous to the athlete looking to avoid the central (CNS) affects manifesting from the beta agonism. Our specialized carrier allows users to skirt this potentially unwanted side effect, but spares no assault on the fatty area of application. [Once again, please see the link above for a more detailed explanation of penetration enhancement and topical delivery.]
The Cast and Crew The Old Boys We know enough to know not to mess with a good thing. True to form synephrine and yohimbine have made the grade and are included in Napalm. But just in case you forgot why they are so effective in topical fat loss products, here’s a friendly reminder.
Yohimbine Reviewing the role of yohimbine in the adrenergic system can be simplified down to its actions at the alpha-2 adreoreceptor(AR), where it is a selective antagonist (or simply, but misleadingly: an inhibitor). The functional properties of the alpha-2 AR are noteworthy for athletes since they play a key role in the regulation of lipolysis by inhibiting the release of norepinephrine (NE). This is achieved through a self-generated negative feedback loop following NE binding at the alpha-2 AR. The role of yohimbine here is to bind selectively at the alpha-2 AR and inhibit the stimulatory actions of circulating catecholamines, such as NE, and its mimetics, such as ephedrine. An adequate dosage of topical yohimbine will concomitantly increase blood flow in adipose tissue (at the site of application) (6), and ensure liberated fat will not be retained(7) – all without the deleterious and unwanted effects in the CNS and cardiovascular systems. Furthermore, the negative feedback loop alluded to earlier is now essentially ‘short circuited’ allowing hyperactivation of Beta receptors and potentiation of downstream lipolytic effectors, namely cAMP and adenosine antagonism. Moving forward we’ll see the critical interplay between these processes and those incited by other actives found in Napalm.
SesaThin You know it and you love it. No stranger to inclusion in successful topicals, SesaThin can be found in identical concentrations as is in Lipoderm Ultra. The active ingredient in SesaThin — sesamin — acts just like certain fish fats as a ligand for PPARalpha (peroxisome proliferator receptor alpha), a type of ligand-activated transcription factor in human cells which plays an important role in fat-metabolism, fat-storage, and glucose homeostasis(8,9,10). Moreover, studies have shown that sesamin-induced PPAR-alpha activation elevates fatty acid oxidation as much as 10-fold over normal levels (11,12,13). Couple its ability to increase fatty acid utilization while suppressing fat-storage (8,13,14,15) and it’s clear to see why it works so well with the other active ingredients in Napalm.
Synephrine: Another carry-over from the Lipoderm series included in Napalm is synephrine. Commonly found in ‘ephedra/epherine free’ fat loss products, it shares some of the well know characteristics of this famous symphathomimetic, while offering some unique addition benefits. It is an agonist of the alpha-1 adrenoreceptor (16,17) which is involved in variety of roles in adipose tissue, inclusive to modulating intracellular Ca2+ and protein kinase C levels and glycogenolysis(18), as well as serving to increase lipolysis in human adipose tissue (19). Without getting overly technical, this creates a significant degree of synergism between cAMP-inducing mechanisms offered by other component of Napalm (see below & RK’s). Additional synergism lies in synephrines’ ability to stimulate beta receptors, albeit to a lesser degree than other more specific beta-1 and beta-2 agonists (20).
The Newcomers Raspberry Ketones Raspberries are appropriately touted as a wonderfully nutritious fruit and snack. Interestingly, several of its chemical constituents — when extracted and isolated — are found to have medicinal benefits. Such is the case with the raspberry ketone (4-(4-hydroxyphenyl) butan-2-one; abv. RK). Researchers were curious to contrast its affects to structurally similar drugs: synephrine and capsaicin.
As one might expect the physical characteristics of RK elicit a unique response at the cellular level. Whereas synephrine has been shown to directly bind and activate beta receptors, a quality that RK’s lack, their key functional role lies in the potentiation of the rate limiting step in the fat burning process: the hydrolysis of triacylglycerol (TAG). This process is mediated by the catalytic protein HSL, or hormone-sensitive lipase, which is recruited to lipid droplets in the cytoplasm in a cAMP-dependent manner (21). RK’s have been shown to sufficiently enhance the localization of HSL within the cell to dramatically increase the rate of this crucial reaction (22).
Unfortunately, the literature has yet to characterize RK’s to the degree in which its structural analogs, notably capsaicin, have been scrutinized and investigated. With caution, we can extend their physical similarity unto the potential for paralleled signaling pathways, and thus observe commonalities in downstream cellular events. In this vein, the warming sensation observed in our beta testing suggests that RK’s do have similar metabolic consequences when administered in a topical matrix. Offering support are the observations made by Kawada et al (1986) whose group documented comparable increases in oxygen consumption following ingestion of either capcaisin, or RK’s (23). Additionally, unpublished data recorded the ability for RK’s to enhance a critical marker of mitochondrial activity, cytochrome C oxidase, demonstrating RK’s ability to increase cellular metabolism, albeit in a mouse model.
Further consideration should be given to the capsaicin-like properties of RK’s given their potency as a vasodialator, and its ability to induce transient insulin insensitivity. The latter, through stimulation of vanilliod receptors prompting the release of Calcitonin Gene Related Peptide (CGRP), another highly potent vasodialator. CGRP is highly instrumental in reducing the capacity of the adipocyte to absorb glucose through the insensitivity alluded to above. While this property is unfavorable in other tissues, starving adipocytes of the necessary energy supply is a novel mechanism to induce apoptosis and consequently lose fat! This brilliant hypothesis brought us SpookyDerm, a vicious blend of Lipoderm Ultra, pain-inducing capsaicin, and nicotine. While we have Spook to thank for the original concept, we have RK’s to thank for the widespread popularity of this pain-free approach to unsurpassed topical fat loss.
Glycyrrhetinic acid Licorice has a lengthy historical association with reduction fat mass and weight loss dating back to the 4th century BC. The Greek physician Theophrastus noted that licorice root granted his patience ‘freedom from hunger and thirst'(24), an observation that was reaffirmed in the 1st century BC by Plinius (25). It wasn’t until modern technological advancements allowed us to characterize the licorice root in order to reveal the main active ingredient: glycyrrhetinic acid (GA).
These ancient observations are supported thoroughly by modern literature which documents the relationship between GA and 11?-hydroxysteroid dehydrogenase (11HSD) (26). For our purposes we will concern ourselves with the first of two 11HSD subtypes. 11HSD1 is found in subcutaneous adipocytes in a relatively lesser abundance than it’s visceral counterpart (27). However, 11HSB-1 is sufficiently concentrated to perform its primary function and influence the level of cortisol by reactivating the inactive cortisone. A hyperactive mutant form of 11HSD-1 is observed in cases of the pathologically obese, suggesting that inhibition of this enzyme will facilitate reduction in adipocytic mass.
This is where GA performs its duties and helps you get skinny, the ultimate result can be attributed to a few proximate causes. Firstly, the vital role of GA and cortisol. By reducing the local availability of cortisol via 11HSD-1 inhibition (28), GA causes a reduction in the concentration of intracellular triglycerides (29), in addition to impeding the differentiation preadipocytes(30).
The merits for topical applications of GA are not limited to the above, but further investigation also showed the ability for GA to positively affect fat metabolism by inactivating fat lipase and increasing mobilization of adipose stores (31).
Conclusions The degree of intracellular cross-talk and synergism between the active in Napalm was custom designed to provided unsurpassed local fat loss. To summarize:
Increased blood flow Accelerated lipolysis Functional enhancement of lipolytic machinery Positive shift in glucose utilization and insulin responsiveness Unsurpassed fat loss References 1. Singh P, Roberts MS. Skin permeability and local tissue concentrations of nonsteroidal anti- inflammatory drugs after topical application. J Pharmacol Exp Ther 1994 Jan;268(1):144-51
2. Singh P, Roberts MS Dermal and underlying tissue pharmacokinetics of lidocaine after topical application..J Pharm Sci 1994 Jun;83(6):774-8219
3. Mikulak SA, Vangsness CT, Nimni ME. Transdermal delivery and accumulation of indomethacin in subcutaneous tissues in rats. J Pharm Pharmacol 1998 Feb;50(2):153-8
4. Peng L, Nimni ME. Delivery of erythromycin to subcutaneous tissues in rats by means of a trans- phase delivery system. J Pharm Pharmacol 1999 Oct;51(10):1135-41
5. Nimni ME, Ertl D, Oakes RA. Distribution of griseofulvin in the rat: comparison of the oral and topical route of administration. J Pharm Pharmacol 1990 Oct;42(10):729-31
6. Millet L, Barbe P, Lafontan M, Berlan M, Galitzky J. Catecholamine effects on lipolysis and blood flow in human abdominal and femoral adipose tissue. J Appl Physiol. 1998 Jul;85(1):181-8
7. Galitzky J, Lafontan M, Nordenstrom J, Arner P. Role of vascular alpha-2 adrenoceptors in regulating lipid mobilization from human adipose tissue. J Clin Invest. 1993 May;91(5): 1997-2003
8. Zhang J et al. Human skeletal muscle PPAR expression correlates with fat metabolism gene expression but not BMI or insulin sensitivity. Am J Physiol Endocrinol Metab 286: E168-E175, 2004.
9. Gibbons G et al. The functional efficiency of lipogenic and cholesterogenic gene expression in normal mice and in mice lacking the peroxisomal proliferator-activated receptor-alpha (PPAR- alpha). Adv Enzyme Regul. 2002;42:227-47.
10. Erol A. PPARalpha activators may be good candidates as antiaging agents. Med Hypotheses. 2005 Jan;65(1):35-8.
11. Ashakumary L et al. Sesamin, a sesame lignan, is a potent inducer of hepatic fatty acid oxidation in the rat. Metabolism. 1999 Oct;48(10):1303-13.
12. Takashi et. al. Sesamin, a sesame lignan, as a potent serum-lipid lowering component. JARQ 37(3), 151-158.
13. Sampath H, Ntambi JM. Polyunsaturated fatty acid regulation of gene expression. Nutr Rev. 2004 Sep;62(9):333-9.
14. Gibbons G. Old fat, make way for new fat. 2005, Nature Medicine vol. 11: 722-723.
15.Ide T et al. Sesamin, a sesame lignan, decreases fatty acid synthesis in rat liver accompanying the down-regulation of sterol regulatory element binding protein-1. Biochim Biophys Acta. 2001 Nov 30;1534(1):1-13.
16. Song DK, Suh HW, Jung JS, Wie MB, Son KH, Kim YH. Antidepressant-like effects of p- synephrine in mouse models of immobility tests. Neurosci Lett. 1996 Aug 23;214(2-3):107-10.
17. Brown CM, McGrath JC, Midgley JM, Muir AG, O’Brien JW, Thonoor CM, Williams CM, Wilson VG. Activities of octopamine and synephrine stereoisomers on alpha-adrenoceptors. Br J Pharmacol. 1988 Feb;93(2):417-29.
18. Flechtner-Mors M, Jenkinson CP, Alt A, Adler G, Ditschuneit HH. In vivo alpha(1)-adrenergic lipolytic activity in subcutaneous adipose tissue of obese subjects. J Pharmacol Exp Ther. 2002 Apr;301(1):229-33.
19. Boschmann M, Krupp G, Luft FC, Klaus S, Jordan J. In vivo response to alpha(1)-adrenoreceptor stimulation in human white adipose tissue. Obes Res. 2002 Jun;10(6):555-8.
20. CarpTnT C, Galitzky J, Fontana E, AtgiT C, Lafontan M, Berlan M. (1999) Selective activation of beta3-adrenoceptors by octopamine: comparative studies in mammalian fat cells. Naunyn Schmiedebergs Arch Pharmacol. 359(4):310-21.
21. McKnight G S, Cummings D E, Amieux P S, Sikorski M A, Brandon E P, Planas J V, Motamed K, Idzerda R L. Recent Prog Horm Res. 1998;53:139-159.
22. Chie Morimoto, Yurie Satoh, Mariko Hara, Shintaro Inoue, Takahiro Tsujita and Hiromichi Okuda. Anti-obese action of raspberry ketone. Life Sci. 2005. 77(2):194-202. PMID: 15862604
23. T. Kawada, T. Watanabe, T. Takaishi, T. Tanaka and K. Iwai, Capsaicin-induced ?-adrenergic action on energy metabolism in rats: influence of capsaicin on oxygen consumption, the respiratory quotient, and substrate utilization, Proceedings of the Society for Experimental Biology and Medicine 183 (1986), pp. 250-256.
24. Decio Armanini, Davide Nacamulli, Francesco Francini-Pesenti, Giuliana Battagin, Eugenio Ragazzi and Cristina Fiore, Glycyrrhetinic acid, the active principle of licorice, can reduce the thickness of subcutaneous thigh fat through topical application, Steroids, Volume 70, Issue 8, July 2005, pp 538-542.
25 C. Fiore, L.A. Cal*, E. Ragazzi, J. Bielenberg and D. Armanini, Licorice from antiquity to the end of the 19th century: applications in medical therapy, J Nephrol 17 (2004), pp. 337-341.
26. P.M. Stewart and Z. Krozowski, 11?-hydroxysteroid dehydrogenase, Vitam Hormon 57 (1999), pp. 249-324.
27. J.R. Seckl, N.M. Morton, K.E. Chapman and B.R. Walker, Glucocorticoids and 11?- hydroxysteroid dehydrogenase in adipose tissue, Recent Prog Horm Res 59 (2004), pp. 359- 393.
28. A. Kumagai, K. Nishino, M. Yamamoto, M. Nanaboshi and Y. Yamamura et al., An inhibitory effect of glycyrrhizin on metabolic actions of cortisone, Endocrinol Jpn 13 (1966), pp. 416- 419.
29. T. Baeder, E. Zoumakis, M. Friedberg, G.P. Chrousos and Z. Hochberg, Human adipose tissue under in vitro inhibition of 11?-hydroxysteroid dehydrogenase type 1. Differentiation and metabolism changes, Horm Metab Res 34 (2002), pp. 752-757.
30. I.J. Bujalska, S. Kumar, M. Hewison and P.M. Stewart, Differentiation of adipose stromal cells: the roles of glucocorticoids and 11?-hydroxysteroid dehydrogenase, Endocrinology 140 (1999), pp. 3188-3196.
31. B. Fuhrman, S. Buch, J. Vaya, P.A. Belinky, R. Coleman and T. Hayek et al., Antiatherosclerotic effects of licorice extracts supplementation on hypercholesterolemic patients: increased resistance of LDL to atherogenic modifications, reduced plasma lipid level: in vitro and ex vivo studies in humans and in atherosclerotic apolipoprotein E deficient mice, Am J Clin Nutr 66 (1997), pp. 267-275.
Serving Size: 1-3 pumps (1-3 mL)
Servings Per Container: 30-60 (lasts 20-60 days)
Glycyrrhetinic acide, Raspberry Ketones, SesaThinTM, Yohimbine HCl, Synephrine HCl
Other Ingredients:Benzyl Alcohol, Water, Isopropyl Alcohol, Triglyceride Complex, n-methyl-2-Pyrrolidinone, Laurocapram, l-Menthol, and Carbomer
Suggested Use: As explained in the Performance Pyramids, rub gel into skin, twice daily, where fat loss effects are desired. Allow skin to dry for 2-3 minutes and wash hands. Begin with 1 pump and increase daily. Stop if side effects become apparent. Do not exceed 3 pumps at one time.
WARNING: KEEP OUT OF REACH OF CHILDREN.
Nor for use by individuals under the age of 18 or elderly. consult a physician before using this or any dietary supplements. Do not use if pregnant, nursing, or chronically ill. This product is not intended for individuals who are at risk of or have been treated for high blood pressure, heart, disease, thyroid disease, depression, or other psychiatric condition, renal disease, reoccuring headaches, spasms, has asthma, or taking asthma medications or if you are using a MAO inhibitor.
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