Sunday, March 23, 2014

When Patrick Arnold talks performance enhancement, you should listen.

Who is Patrick Arnold from his blog:

Patrick Arnold is an organic chemist who is renowned in the field of performance enhancement and sports supplements.  Patrick first hit the public eye in the late 1990’s when he introduced androstenedione (“andro”) to the market place.   Andro became widely known after it was linked to Mark Maguire in 1998 – the year he broke the seasonal home run record.  Patrick later went on to develop several other “prohormone” supplements such as 4-AD and 1-AD.  1-AD was considered by many to be the most effective and most popular prohormone ever developed.

Patrick is unique in the supplement industry because not only does he discover and introduce novel ingredients, but he uses his skills in organic synthesis to develop manufacturing processes for these ingredients.  Together with his business partner Lakhan Boodram, he actually carries out the commercial production of many of these ingredients and maintains his own strict quality oversight.
Despite all these accomplishments, Patrick may be best known as the man who developed the designer steroids that were behind the Balco scandal.  The most widely known of these steroids was tetrahydrogestrinone, also known as THG or “The Clear”.  Patrick was convicted for his role in the Balco scandal and served prison time.

In addition to Patrick’s work with prohormones and steroids he also is credited with introducing many successful ingredients to the supplement market place such as ipriflavone, 1,3-dimethylamylamine (i.e. Geranamine®), and phenibut.

Patrick currently produces products for the nutritional supplement company E-pharm Nutrition, as well as for Prototype Nutrition.  He continues to be perhaps the number one driving force in the advancement of performance enhancing nutritional supplementation.

Patrick Arnold's Prototype Nutrition.
Pump Spray Information from the E-Pharm website:

Pump Spray - Arginine Ursolic Acid
Arginine ursolic acid is an enhanced version of a natural compound known as ursolic acid. You may have never heard of ursolic acid before, but take my word for it when I tell you that it has more potential to change the way your body looks and functions than any chemical compound available outside of drugs and hormones. In fact, it has the potential to actuallyoutperform many of these drugs and hormones. The key word here is potential. For ursolic acid to really work – to unlock its potential – one needs to do a little chemical magic to it. But before I explain all that in detail, let’s first briefly look at what ursolic acid is.

Ursolic Acid
Ursolic acid is found in many plants, fruits, and vegetables and it belongs to class of compounds called pentacyclic triterpene acids.
Pentacyclic Triterpene Acids Compound Structure
Ursolic acid has been studied for decades. Scientists have known for quite some time that it has a wide variety of health benefits ranging from antioxidant potential and cancer prevention to protection against diabetes. Scientists have also made intriguing findings regarding ursolic acid’s effects on fat metabolism and storage that seem to suggest the compound may be a dieter’s dream. But it wasn’t until a couple of years ago that research came out that really caught everyone’s eye. Since then, two landmark papers have been published by a research team from a major American university and these papers have made ursolic acid front page headlines.

The papers showed that ursolic acid given to mice caused them to lose fat and gain muscle – not just a little bit, but a lot. Their muscles produced much more of a growth factor known as IGF-1, and the levels of protein synthesis and storage were increased. The ursolic acid mice could even eat more than other mice and they would still burn a lot more fat. This was due to their greater amounts of calorie burning muscle tissue as well as increased levels of a unique kind of metabolically active fat called brown fat. Brown fat is full of an enzyme called UCP-1, and this enzyme burns calories and releases heat in a process known as thermogenesis (you may notice an increased body temperature after using Pump Spray due to this thermogenesis as well as due to peripheral vasodilation effects).
A very interesting aspect of ursolic acid is something that was hinted at in older researched and then confirmed by this latest research. It has to do with increased production of endothelial nitric oxide. This is the nitric oxide that is produced in the blood vessels and causes them to expand and increase blood flow. The research scientists also discovered that ursolic acid activated a substance called vascular endothelial growth factor-A. This substance actually stimulates the production of new blood vessels. New blood vessels are needed to support the metabolic needs of growing tissue such as muscle. It is these effects on blood vessel physiology that are at the heart of the “pump” inducing and vascular enhancement properties of Pump Spray.

How we made Ursolic Acid work
Straight up ursolic acid is strange stuff. It dissolves very poorly in most fatty like solvents and it completely repels water (if you stick it in water it actually floats and stays completely dry). These properties make it extremely poorly absorbed. You see, for things to get absorbed they have to have some sort of solubility in either oil or water, and since ursolic acid is so poor in both regards the lion’s share of material just doesn’t get where it needs to go. This applies for both orally and topically applied ursolic acid.

So the challenge is to improve ursolic acid’s solubility characteristics such that it is able to be absorbed efficiently. We used what is known as the “pro-drug” approach (in our case, the term “pro-nutrient” would be more applicable). With this approach one alters the structure of the compound with hydrolysable functional groups in such a way that its chemical properties are improved. A hydrolysable group is something like an ester, certain ethers, amides etc. that your body will be able to efficiently convert back into the parent compound once it has been absorbed.

We took advantage of the chemistry of ursolic acid to add an acetate ester (forming ursolic acetate, which is itself actually a known natural derivative of ursolic acid). However, esterification was not enough since although ursolic acid’s lipid solubility was greatly improved, it still suffered from poor aqueous solubility. So we developed a method to link up the acid group of ursolic acid with the highly basic amino acid arginine. Acids react with bases to form salts, and salts are have superior solublity in water compared to their parent acids.

The resulting compound – arginine ursolic acid – has remarkable solubility characteristics. It dissolves fantastically in most organic solvents and disperses like soap in water. Consequently, it absorbs and penetrates very effectively.
Arginine Ursolic Acetate Compound Structure
When applied to the skin it absorbs rapidly and efficiently. The end effect is the initiation of subcutaneous fat dissolution and vasodilation effects that over time lead to dramatic changes in muscular definition and fullness. The benefits of ursolic acid can thusly be achieved in a manner that is impossible to match by any other means currently available.

Arginine ursolic acetate is but one half of the magic of Pump Spray. The other half is triacetyladenosine. Together these ingredients in our special topical base will give you unbelievable fat burning, muscle pumping, and vascularizing effects that you never thought possible from a natural supplement.

*Arginine ursolic acetate and other amino acid and amino acid derivative salts of ursolic acid esters are covered under a pending patent.

Pump Spray - Triacetyladenosine
Adenosine is an important molecule that serves a wide variety of roles in the function of cells throughout the body. You may be familiar of it as a component of adenosine triphosphate (ATP), which is the energy transfer molecule that keeps our body and brains working. You may also have heard of cyclic AMP, which is a cellular messenger that carries the signal for such things as adrenaline to fat and muscle. Less well known though is the fact that adenosine itself is a very important signaling molecule, especially in regards to blood flow. In particular (and of most interest to us) is the effect of adenosine on blood flow to muscles.
Adenosine Compound Structure

When muscles are exercised, ATP starts to become depleted. This cascade of depletion leads first to adenosine diphosphate (ADP), then to adenosine monophosphate (AMP), and finally to free adenosine. This free adenosine formed is then released from the muscle during contraction under conditions of low pH (as lactic acid accumulates). Outside the muscle it then interacts with adenosine receptors on the surface of the muscle cell, the neuromuscular junction, as well as the capillaries that feed the muscle. Adenosine serves to open up the capillaries to help the working muscle stay supplied with nutrients and oxygen, as well as to take away metabolic waste products. Additionally, adenosine’s interactions with its receptors on the muscle cell initiates what is known as the exercise mediated stimulation of glucose uptake. The muscle cells thereby take in and process glucose rapidly directly – without the presence of insulin being required.

The effect of adenosine on muscular blood flow is well recorded and is dramatic. Infusions of adenosine have been shown to increase blood flow and glucose uptake in skeletal muscle several fold. This happens very rapidly. Adenosine however must be infused into the blood stream since it is such a rapidly metabolized compound. In fact, its half-life is less than ten seconds. This is due primarily to the action of an enzyme called adenosine deaminase. This enzyme irreversibly converts adenosine to a compound known as inosine.

Adenosine Deaminase Compound Structure
The unstable nature of adenosine is unfortunate, as it makes its administration for physique and exercise enhancement problematic. Some have tried to overcome this by offering it in the form of ATP, however this does not really solve the problem because once it is converted to adenosine (and this happens rapidly during digestion) it once again becomes susceptible to adenosine deaminase and much of it is destroyed. Very little of it reaches the muscles.

We can protect adenosine from this rapid and destructive deamination reaction. By making one of the hydroxyl groups (5’) on the ribose portion of the molecule into an ester, it has been found that the action of adenosine deaminase is blocked. The protection of this hydroxyl group allows the compound extended lifetime in the body, so that it may reach target tissues. Esterases at target tissues then regenerate the parent adenosine, where it may then interact with the appropriate adenosine receptors and impart its valuable pharmacological properties.

Epharm has chosen to use the acetate ester for protection of adenosine. For purposes of convenience all three hydroxyl groups are made into acetates, and the end product is called triacetyladenosine. Utilization of the ester form has an additional benefit, as it renders the compound soluble in organic solvent bases. This allows it to be suitable for use in a topical formula, and that is exactly what we decided to do with Pump Spray.

Triacetyladenosine Compound Structure
By optimizing the influence of adenosine on the skeletal muscle you can achieve maximum capillary vasodilation. This is manifested in what is known as exercise induced hyperemia, or more commonly referred to as “the pump”. Adenosine does more than just allow for vasodilation in the muscle however, it also is known to mediate the exercise induced secretion of vascular endothelial growth factor (VEGF). This growth factor serves the purpose to promote the formation of new capillaries, thereby augmenting the vascular network that feeds muscles for contraction as well as new growth.
Below are just a sample of references to just a few of the many articles published on the role of adenosine in muscle and exercise induced hyperemia. It is clearly apparent that adenosine plays a key role in the physical response to exercise, and with the introduction of triacetyladenosine as a component of Pump Spray you are finally able to capitalize fully on its potential!!

Acta Physiol Scand. 2001 Feb;171(2):177-85.
Role of adenosine in exercise-induced human skeletal muscle vasodilatation.
Rådegran G, Calbet JA.
Acta Biochim Pol. 2006;53(2):269-78. Epub 2006 Jun 12.
Adenosine as a metabolic regulator of tissue function: production of adenosine by cytoplasmic 5'-nucleotidases.
Borowiec A, Lechward K, Tkacz-Stachowska K, Składanowski AC.
Hypertension. 2009 Jun;53(6):993-9. Epub 2009 May 11.
Adenosine contributes to blood flow regulation in the exercising human leg by increasingprostaglandin and nitric oxide formation.
Mortensen SP, Nyberg M, Thaning P, Saltin B, Hellsten Y.

J Appl Physiol. 2006 Aug;101(2):492-9. Epub 2006 Apr 13.
Bimodal distribution of vasodilator responsiveness to adenosine due to difference in nitric oxidecontribution: implications for exercise hyperemia.
Martin EA, Nicholson WT, Eisenach JH, Charkoudian N, Joyner MJ.

J Appl Physiol. 2010 Feb;108(2):378-86. Epub 2009 Nov 25.
Comparison of exogenous adenosine and voluntary exercise on human skeletal muscle perfusionand perfusion heterogeneity.
Heinonen I, Kemppainen J, Kaskinoro K, Peltonen JE, Borra R, Lindroos MM, Oikonen V, Nuutila P, Knuuti J, Hellsten Y, Boushel R, Kalliokoski KK.
Am J Physiol Heart Circ Physiol. 2010 Sep;299(3):H857-62. Epub 2010 Jun 11.
Contraction-induced secretion of VEGF from skeletal muscle cells is mediated by adenosine.
Høier B, Olsen K, Nyberg M, Bangsbo J, Hellsten Y.
Am J Physiol Regul Integr Comp Physiol. 2012 Feb 1;302(3):R385-90. Epub 2011 Nov 30.
Effects of adenosine, exercise, and moderate acute hypoxia on energy substrate utilization of human skeletal muscle.
Heinonen I, Kemppainen J, Kaskinoro K, Peltonen JE, Sipilä HT, Nuutila P, Knuuti J, Boushel R, Kalliokoski KK.
Am J Physiol Regul Integr Comp Physiol. 2005 Aug;289(2):R283-R296.
Growth regulation of the vascular system: an emerging role for adenosine.
Adair TH.
Hypertension. 2010 Dec;56(6):1102-8. Epub 2010 Nov 1.
Interstitial and plasma adenosine stimulate nitric oxide and prostacyclin formation in humanskeletal muscle.
Nyberg M, Mortensen SP, Thaning P, Saltin B, Hellsten Y.
J Physiol. 2001 Nov 1;536(Pt 3):927-35.
Oxygen delivery and oxygen consumption in rat hindlimb during systemic hypoxia: role ofadenosine.
Edmunds NJ, Marshall JM.
J Appl Physiol. 2007 Dec;103(6):2042-8. Epub 2007 Sep 20.
Role of adenosine in regulating the heterogeneity of skeletal muscle blood flow during exercise inhumans.
Heinonen I, Nesterov SV, Kemppainen J, Nuutila P, Knuuti J, Laitio R, Kjaer M, Boushel R, Kalliokoski KK.
Adv Exp Med Biol. 1998;441:97-106.
Role of adenosine in regulation of carbohydrate metabolism in contracting muscle.
Hespel P, Richter EA.
J Physiol. 2007 Sep 15;583(Pt 3):835-45. Epub 2007 Jul 5.
The roles of adenosine and related substances in exercise hyperaemia.
Marshall JM.
Am J Physiol Heart Circ Physiol. 2010 Sep;299(3):H857-62. Epub 2010 Jun 11.
Contraction-induced secretion of VEGF from skeletal muscle cells is mediated by adenosine.
Høier B, Olsen K, Nyberg M, Bangsbo J, Hellsten Y.

Pump Spray - Neovascularization
Neovascularization (also known as angiogenesis) is the formation of new vascular pathways. In the case of skeletal muscle, neovascularization is a healthy response that is stimulated by exercise. Intense exercise stimulates reactions in the muscle which increase its size, strength, as well as endurance. To support this larger and stronger muscle tissue there must be a corresponding increase in the ability of your body to feed the new tissue. This is where neovascularization comes into play.
Many people hit plateaus in training. Their muscles grow only so big and then they find it hard to make any further gains. This can be due to limitations in many areas, including the ability to activate genes that promote protein synthesis and/or an inability to repress genes responsible for protein degradation. It may also of course be due to inadequate intake of proper protein, calories, and essential nutrients to support muscle growth. Another possibility is that the body is unable to supply the muscle with the proper oxygen and substrates needed to support growth because the network of blood vessels and capillaries feeding it have not been adequately developed.

Much like how an army can only advance so far without adequate supply lines, your muscles can only grow so large without adequate vascular infiltration. This is where Pump Spray comes to the rescue. Pump Spray's two ingredients are proven to increase the production of vascular endothelial growth factor -1 (VEGF1), which is the signal protein released by muscle when it undergoes stress due to exercise that depletes oxygen and energy substrates. VEGF1 signals the muscles to sprout new blood vessels and capillaries off of existing ones to facilitate the growth and metabolic adaptations needed to handle the exercise strain.

By supporting and enhancing your body's own natural neovascularization response, you ensure that you maintain optimal anabolic supply lines so that your muscles can continue their hypertrophic blitzkrieg offensive! Not to mention the fact that roadmap veins covering your muscles definitely make a formidable fitness statement!

For further technical reading regarding the ingredients in Pump Spray and their roles in neovascularization of muscle tissue check out the following references.

Am J Physiol Heart Circ Physiol. 2010 Sep;299(3):H857-62. Epub 2010 Jun 11.
Contraction-inducesecretion of VEGF from skeletal muscle cells is mediated by adenosine.
Høier BOlsen KNyberg MBangsbo JHellsten Y.
Am J Physiol Regul Integr Comp Physiol. 2005 Aug;289(2):R283-R296.
Growth regulation of the vascular system: an emerging role for adenosine.
Adair TH.
High Alt Med Biol. 2008 Summer;9(2):158-66.
Skeletal muscle capillarity during hypoxia: VEGF and its activation.
Breen ETang KOlfert M,  ;Knapp AWagner P.
J Appl Physiol. 1999 May;86(5):1513-8.
Effect of NO, vasodilator prostaglandins, and adenosine on skeletal muscle angiogenic growth factor gene expression.
Benoit H, Jordan M, Wagner H, Wagner PD.
Adv Exp Med Biol. 2001;502:349-63.
Roles of adenosine and nitric oxide in skeletal muscle in acute and chronic hypoxia.
Marshall JM.
Biochem Biophys Res Commun. 2008 Jul 4;371(3):556-60. Epub 2008 Apr 28.
Modulation of angiogenic factors by ursolic acid.
Kiran MSViji RISameer Kumar VBSudhakaran PR.
 J Agric Food Chem. 2010 Dec 22;58(24):12941-9. Epub 2010 Nov 12.
Ursolic acid induces allograft inflammatory factor-1 expression via a nitric oxide-related mechanism and increasesneovascularization.
Lee AWChen TLShih CMHuang CYTsao NWChang NCChen YHFong THLin FY.
Can J Cardiol. 1986 Mar-Apr;2(2):120-3.
Angiogenesis in the heart and skeletal muscle.Hudlicka OWright AJZiada AM

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