Pre-workoutVasodilator and Performance Optimizer
In Pumping Iron, Arnold waxes poeticallyabout, “the pump” by saying this:
The greatestfeeling you can get in a gym, or the most satisfying feeling you can get in thegym is...the pump.
Can you really disagree? We all haveour different reasons for training, of course: overall health and well-being,the satisfaction of dedication, achieving a goal, looking great – all valid.All noble and good reasons for dedicating your life to the iron. But, let’s behonest – the rawest, most visceral, most primal satisfaction you can possiblyenjoy is the feeling of an intense pump that seems as if it will tear your skinoff.
So, when was the last time youexperienced a pump that incredible? Last workout? Maybe the one before that? AtCore, it amazes us how many struggle to answer that question – and how seldomthe industry has provided a product that delivers that kind of pump.
With Core PUMP, we can confidentlysay you will never struggle to answer that question again. We have taken ourstandard, Core approach – amazing ingredients, in clinical servings, all formulatedin a non-proprietary blend – to the issue of pumps, and we have produced aproduct whose name simply couldn’t have been anything else.
Best of all, Core PUMP is completelygimmick-ingredient free. The compounds we have chosen are verified by science,backed by clinical research, and have been shown to increased bloodflow througha number of independent mechanisms. The pump from Core PUMP is therefore notjust for vanity – though, you will likely spend more time in front of themirror – but is also of real, verifiable, and measurable physiological benefit.
Our beta testers described PUMP as, “Skin-bursting,”and “intense.” They also described it as, “The best I have ever used. Handsdown.” See why for yourself.
Physiological Properties and Effects:
Agmatine is part of a group ofcompounds known as polyamines, alphatic amines which play multiplephysiological roles in tissue growth and differentiation, body weightincrement, brain organization, molecular mechanisms of hormonal action,intracellular signaling, and extracellular communication. Agmatine itself isnaturally produced in the body by the breakdown of arginine. Paradoxically, thestudied effects of agmatine not only appear to mimic those of its parentcompound arginine, but in many cases, surpass it. These effects include anincrease in localized bloodflow (better plasma delivery), dilation of thevasculature (expanding of blood vessels), increased nutrient delivery, and ahypothesized effect on the functioning of the hypothalamic-pituitary axis.
The most recent literature suggeststhat agmatine sulfate’s positive regulation of NO (nitric oxide) levels are notfrom direct conversion to NO within the classical NO-eNOS (endothelial nitricoxide synthase) pathway. Unlike arginine, agmatine now appears to increaseplasma nitric oxide concentrations not via functioning as a substrate fornitric oxide synthase, but rather through a separate enzymatic pathway –therefore increasing the benefits of using agmatine and arginine (orcitrulline) in conjunction with one another.
Agmatine has also recently beendemonstrated to possess a potential nutrient partitioning effect through aninteresting brain-based compound known as a “neuropeptide.” This compound,b-endorphin, may be released when agmatine binds to specialized receptors onthe adrenal gland – in turn, it may acutely lower blood glucose through anumber of mechanisms. Most importantly, the effects of agmatine-catalyzedb-endorphin appear specific to skeletal muscle cells (known as myocytes), asGLUT-4 dependent glucose uptake activity did not occur in fat tissue cells(known as adipocytes) in rat trials.
Citrulline is a non-essential,non-protein amino acid that forms during the urea cycle and forms ornithinewhen combined with carbon dioxide. Citrulline is also a critical source ofendogenous (natural) arginine, as it is rapidly and efficiently converted toarginine in the vascular endothelium and other tissues.
Citrulline’s benefits have beenshown to be greater than its parent compound. While arginine undergoes directhepatic (liver) metabolism through the enzyme arginase, citrulline bypasseshepatic metabolism entirely and it is delivered straight to the bloodstream.The result is that gut absorption and plasma (blood) bioavailability studiescomparing citrulline and arginine have shown two things. First, that citrullineis less readily destroyed and has greater absorption than arginine. Second,that citrulline supplementation increases arginine levels more effectively thanarginine supplementation itself.
This translates to promisingresults. For example, animal studies show a significant increase in anaerobicperformance at a 250mg/kg/day serving of citrulline, while studies in humansimplicate citrulline in both aerobic and anaerobic performance increases. As acritical part of the urea cycle, citrulline’s performance benefits are thoughtto be a result of its role in ammonia clearance. Citrulline is implicated inreducing the oxygen cost of muscle processes, along with increasing the rate ofpost-exercise ATP and phosphocreatine replenishment. As ATP and phosphocreatineare the body’s ‘exercise fuel,’ this may result in citrulline delaying time toexhaustion in aerobic and anaerobic exercise.
In combination with the HydroMax™found in Core PUMP, citrulline’s potential endurance applications aresignificant.
Glycerol is a fascinating and highlyuseful compound that has achieved a somewhat cult status in the fitnesscommunity – while both peer-reviewed research and anecdotal reports centered onthe endurance functions of glycerol are plentiful, its bodybuildingapplications are not as widely lauded. Those who do use glycerol, however, arepersistent in their belief that it provides some of the most noticeable, andeffective, engorging (“pump”) effects possible.
Glycerol has been well-establishedas a so-called, “hyperhydrating agent” because of its ability to potently andpositively affect plasma (blood) osmolality. As an incredibly powerful osmoticagent, and when combined with large quantities of water, glycerol induces the intracellularretention of fluid (not the extracellular kind, you do not want) that wouldotherwise be renally excreted. Various research has shown that glycerol’scapacity to positively affect osmolality and expand fluid volume (an increasein total body water) has beneficial effects on performance and physiologicfunction.
Studies that administered glycerolbefore both moderate and high endurance fitness tests found that glycerolreduced increases to core temperature, caused athletes to exercisesignificantly longer before fatigue, reduced urinary elimination of water andincreased total body water content, and, in several studies, significantlyimproved intramuscular water expansion. In less complex terms, this meansglycerol has been demonstrated to keep your muscles hydrated, significantlyincrease the ever-desired, “pump effect” of muscle engorgement, and, maybe mostimportantly when it comes to a supplement formulation, deliver and keep more nutrients where they are needed (inside themuscle).
Until recently, however, most ofthese studies noted a significant drawback: the low glycerol concentration ofmarket-available glycerol products forced researchers to test glycerol loadsthat were significantly higher than average use cases. Core PUMP uses HydroMax®to overcome precisely this problem.
HydroMax® is a highly-concentrated(65%) form of glycerol that offers greater water stability, and thereforepotency, as compared to standard GMS (glycerol monostearate). Of particularinterest to bodybuilders, HydroMax®’s greater potency translates to evengreater levels of intramuscular water retention – keyword, intramuscular, andtherefore no bloat – over GMS.
Overall, supplementation withHydroMax® has been shown to:
· Keepathletes hyperhydrated for extended periods of time.
· Reducepost-workout urine volume (more efficient fluid use).
· Lowerheart rate and improve endurance time.
· Enhanceplasma and intramuscular volume expansion.
Nitrosigine®(Inositol arginine silicate)
Along with creatine, arginine isperhaps the most well-known, and most well-understood, workout supplement. Itsrole in the classical NO-synthase-pathway of nitric oxide production has beenmeticulously studied, and as a consequence, the compound enjoys wide andconstant use within the industry.
With familiarity comes complacency,however; as a consequence, legitimate breakthroughs with respect to novel and(more effective) forms of arginine have been infrequent. Though the attachmentsof various salts and/or other organic compounds to arginine have purportedlyincreased its rates of absorption and effectiveness, clinical research intothese alternatives has been relatively sparse.
Enter Nitrosigine®. Nitrosigine® isa uniquely bonded complex of arginine and silica that possesses synergisticeffects – translating to physiologic benefits that are greater than the sum ofarginine and silica alone. The secret lies in Nitrosigine®’s highly unique andhighly patented chemical structure. Nitrosigine® is produced by synthesizing potassiumsilicate and arginine together with an inositol base. The resultant complex, inositolarginine silicate, possesses significantly greater nutritional availabilitythan its parent compounds, as the inositol base increases the solubility ofboth the typically water-insoluble potassium silicate and arginine.
The positive results of this synergyhave been well-documented in both pre-clinical and human clinical trials. Forexample, a human clinical study, using healthy males ages 18-40, found thatNitrosigine® not only rapidly and substantially elevated plasma arginine (40%increase), but that plasma elevations persisted for approximately three hours.In comparison to arginine, another pre-clinical trial using animal subjectsfound that Nitrosigine®-induced blood vessel relaxation was five-fold greater,and vasodilation and localized blood flow levels were approximately double.
These acute effects are of course inaddition to what is perhaps Nitrosigine®’s greatest benefit: prolonged andchronic plasma nitric oxide level increases. These same trials found thatbaseline nitric oxide levels – as measured by salivary nitrites, byproducts inthe production of endothelial NO – were found to be increased after 14consecutive days of product consumption. In practical terms, these resultssuggest that Nitrosigine® continues to be an effective, “NO-enhancer” after theacute effects of the compound dissipate.
Overall, studies on Nitrosigine®have shown:
· Nitrosigine® to be more biologicallyeffective than arginine hydrochloride (HCl).
· Enhanced blood flow during and afterexercise, helping with muscle growth and recovery.
· Blood vessel relaxation almost 5xgreater than Arginine HCl.
· Higher nitric oxide related maximumblood flow and vessel relaxation.
Thousandsof reactions occur within the body as a result of intense physical training.Many of these cellular reactions form destructive oxygen atoms, known asradical oxygen species – or more commonly, free radicals. The cumulativeeffects of free radicals on human cells are known as oxidative stress, andhence, “anti-oxidants” have become a staple of most supplementation regimens.
Oneof the most potent and widely used anti-oxidants is vitamin C. In an exercisespecific context, Vitamin C has been demonstrated to cleave (get rid of) manyof the destructive radical oxygen species created in human skeletal muscleduring exercise, and in the production of nitric oxide (the very purpose of a “pump”product). In one human trial, seven healthy, exercise-trained males were giveneither placebo, or a mixture of antioxidants containing primarily vitamin C(1500 mg), prior to an acute exercise challenge of 90 minutes. Afterward, the vitamin C groups displayedsignificantly lower levels of exercise-induced radical oxygen species. VitaminC’s radical scavenging effects have also been demonstrated to exert a dose andtime-dependent effect on nitric oxide levels – meaning that the effectincreased, to a point, with the serving provided. Researchers believe thatVitamin C does not directly affect nitric oxide, but rather protects a compoundknown as tetrahydrobiopterin from various radical oxygen species.Tetrahydrobiopterin is, in turn, a critical component in the production of eNOS(endothelial nitric oxide).
Thinkof it like this: tetrahydrobiopterin (and therefore nitric oxide) is the popstar, and vitamin C is the bodyguard. Vitamin C itself does no singing, itsimply prevents the creeps from interrupting the pop star, allowing it to sing.
Frank, M.S.B., Nahata, M.C., Hilty,M.D. (1981). Glycerol: a review of its pharmacology, pharmacokinetics, adversereactions, and clinical use. Pharmacotherapy, 1, 147-160.
Freund, B.J., Montain, S.J., Young,A.J., Sawka, M.N., DeLuca, J.P., Pandolf, K.B., Valeri, C.R. (1995). Glycerolhyperhydration: hormonal, renal, and vascular fluid responses. Journal ofApplied Physiology, 79, 2069-2077.
Koenigsberg, P.S., Martin, K.K.,Hlava, H.R., Riedesel, M.L. (1995). Sustained hyperhydration with glycerolingestion. Life Sciences, 5, 645-653.
Latzka, W.A., Sawka, M.N., Montain,S.J., Skrinar, G.S., Fielding, R.A., Matott, R.P., and Pandolf, K.B. (1997).Thermoregulatory effects during compensable exercise-heat stress. Journal ofApplied Physiology, 83, 860-866.
Lyons, T.P., Riedesel, M.L., Meuli,L.E., Chick, T.W. (1990). Effects of glycerol-induced hyperhydration prior toexercise in the heat on sweating and core temperature. Medicine and Science inSports and Exercise, 22, 477-483.
Montner, P., Stark, D.M., Riedesel,M.L., Murata, G., Robergs, R.A., Timms, M., Chick, T.W. (1996). Pre-exerciseglycerol hydration improves cycling endurance time. International Journal ofSports Medicine, 17, 27-33.
Murray, R., Eddy, D.E., Paul, G.L.,Seifert, J.G., Halaby, G.A. (1991). Physiological responses to glycerolingestion during exercise. Journal of Applied Physiology, 71, 144-149.
Noakes, T.D. (1993). Fluidreplacement during exercise. Exercise Sport Science Review, 21, 297-330.
Riedesel, M.L., Allen, D.Y., Peake,G.T., Al-Qattan, K. (1987). Hyperhydration with glycerol solutions. Journal ofApplied Physiology, 63, 2262-2268.
Robergs, R.A. and Griffin, S.E.(accepted for publication, November, 1997). Glycerol: biochemistry,pharmacokinetics, clinical and applied applications. Sports Medicine.
Sawka, M.N., Latzka, W.A., Montain,S.J., Skrinnar, G.S., Fielding, R.A., and Pandolf, K.B. (1997). Hyperhydration:Thermal and cardiovascular effects during uncompensable exercise-heat stress.Medicine and Science in Sports and Exercise, 29, Abstract 760.
Li YF, Gong ZH, Cao JB, Wang HL, LuoZP, & Li J. (2003). Antidepressant-like effect of agmatine and its possiblemechanism. European Journal of Pharmacology. 469(1-3), 81-8.
Zhu MY, Wang WP, Cai ZW, RegunathanS, & Ordway G. (2008). Exogenous agmatine has neuroprotective effectsagainst restraint-induced structural changes in the rat brain. The EuropeanJournal of Neuroscience. 27(6), 1320-32.
Demady DR, Jianmongkol S, VuletichJL, Bender AT, & Osawa Y. (2001). Agmatine enhances the NADPH oxidaseactivity of neuronal NO synthase and leads to oxidative inactivation of theenzyme. Molecular Pharmacology. 59(1), 24-9.
Zarandi M, Serfozo P, Zsigo J,Bokser L, Janaky T, Olsen DB, Bajusz S, & Schally AV. (1992). Potentagonists of growth hormone-releasing hormone. Part I. International Journal ofPeptide and Protein Research. 39(3), 211-7. Kalra SP, Pearson E, Sahu A, &Kalra PS. (1995). Agmatine, a novel hypothalamic amine, stimulates pituitaryluteinizing hormone release in vivo and hypothalamic luteinizing hormone-releasinghormone release in vitro. Neuroscience Letters. 194(3), 165-8.
Arndt MA, Battaglia V, Parisi E, Lortie MJ,Isome M, Baskerville C, Pizzo DP, Ientile R, Colombatto S, Toninello A, &Satriano J. (2009). The arginine metabolite agmatine protects mitochondrialfunction and confers resistance to cellular apoptosis. American Journal ofPhysiology. Cell Physiology. 296(6), C1411-9.
Lu XL, et al. Marine cyclotripeptideX-13 promotes angiogenesis in zebrafish and human endothelial cells viaPI3K/Akt/eNOS signaling pathways. Mar Drugs. (2012)
Shi F, et al. Effects of simulatedmicrogravity on human umbilical vein endothelial cell angiogenesis and role ofthe PI3K-Akt-eNOS signal pathway. PLoS One. (2012)
Jung HJ, et al. Agmatine promotesthe migration of murine brain endothelial cells via multiple signalingpathways. Life Sci. (2013)
Auguet M, et al. Selectiveinhibition of inducible nitric oxide synthase by agmatine. Jpn J Pharmacol.(1995)
Jianmongkol S, et al.Aminoguanidine-mediated inactivation and alteration of neuronal nitric-oxidesynthase. J Biol Chem. (2000)
Wolff DJ, Lubeskie A. Aminoguanidineis an isoform-selective, mechanism-based inactivator of nitric oxide synthase.Arch Biochem Biophys. (1995)
Nakatsuka M, Nakatsuka K, Osawa Y.Metabolism-based inactivation of penile nitric oxide synthase activity byguanabenz. Drug Metab Dispos. (1998)
Li Q, et al. Effect of agmatine onintracellular free calcium concentration in isolated rat ventricular myocytes.Sheng Li Xue Bao. (2002)
Li Q, Yin JX, He RR. Effect ofagmatine on L-type calcium current in rat ventricular myocytes. Acta PharmacolSin. (2002)
Lortie MJ, et al. Agmatine, abioactive metabolite of arginine. Production, degradation, and functionaleffects in the kidney of the rat. J Clin Invest. (1996)
Gao Y, et al. Agmatine: a novelendogenous vasodilator substance. Life Sci. (1995)
Ishikawa T, et al. Nomega-hydroxyagmatine: a novel substance causing endothelium-dependentvasorelaxation. Biochem Biophys Res Commun. (1995)
Gill F, et al. Effects of agmatineon the survival rate in rats bled to hemorrhage. Arzneimittelforschung. (2011)
Ernsberger P, et al. Hypotensiveaction of clonidine analogues correlates with binding affinity at imidazole andnot alpha-2-adrenergic receptors in the rostral ventrolateral medulla. JHypertens Suppl. (1988).
Proctor SD, Kelly SE, Russell JC. Anovel complex of arginine-silicate improves micro- and macrovascular functionand inhibits glomerular sclerosis in insulin-resistant JCR:LA-cp rats.Diabetologia. 2005 Sep;48(9):1925-32.
Proctor SD, Kelly SE, Vine DF,Russell JC. Metabolic effects of a novel silicate inositol complex of thenitric oxide precursor arginine in the obese insulin-resistant JCR:LA-cp rat.Metabolism. 2007 Oct;56(10):1318-25.
Presented at The ExperimentalBiology (EB) 2014 meeting held at the San Diego Convention Center, April 30,2014 and in the Federation of American Societies for Experimental Biologyjournal (FASEB).