- 01-14-2008, 11:00 AM
"Next Generation?" No thanks. With Adrenalean, Designer Supplements goes one step further and introduces the future of stimulating fatburners and carves its own niche in the weight loss industry both for competitive athletes, as well as the average individual aiming to shed some pounds. Adrenalean truly is the very best fat burning product designed to date as it is not simply a collection of stimulating compound aimed to make you 'feel' like you're losing weight, it actually helps you lose weight! Each individual component of the product has been carefully researched for effectiveness and the suitable dose, and has been combined with synergistic compounds that make Adrenalean unbeatable. Beginning with the Euphroamine formula, Designer Supplements introduces another potent fatloss ingredient to the industry in Arecoline. We then compliment this amazing ingredient with PEA and hordenine for enhanced mood and increased energy expenditure, quercetin to prolong the fat burning effect, and L-Huperzine A for its cholinergic focusing effects. The EvoSyn blend combines the tried and true caffeine with evodiamine, which naturally increases thermogenesis, and synephrine, which potently controls appetite.
Arecoline is found naturally in the Areca catechu plant and is chewed socially in many regions of Asia for its stimulating effect. This stimulating effect results in a significant dampening of appetite in man, as well as a swift increase in energy expenditure (1). While exercise clearly helps, the increased energy expenditure associated with arecoline occurs even in the resting state! Simply put, controlled appetite and more calories being burned for fuel even at rest can potentially lead to enhanced weightloss without increased activity...now imagine the effect when combined with a rigorous workout!
Arecoline exerts its effects through the muscarinic receptor system. Like the nicotinic receptor, the muscarinic receptor is a subtype of acetylcholine (Ach) receptor which is activated by the neurotransmitter Acetylcholine (Ach.) Found throughout the body, Ach is crucial for autonomic activation of the central nervous system and by binding to the muscarinic receptor, arecoline increases cholinergic activity (more acetylcholine) (2). The effects of this enhanced activity are vast and include improved muscle contractions, enhanced cognitive ability, and elevated epinephrine and norepinephrine release. It is the latter that manifests as stimulation in those that take arecoline.
In addition to the above benefits, recent research into arecoline has found an intriguing effect on the pineal gland; the gland which produces melatonin. While the pineal gland is large during childhood and releases abundant melatonin, which is thought to inhibit sexual development of children, the gland shrinks at puberty to allow proper sexual development. Arecoline has the effect of inhibiting the pineal gland, thereby stimulating testicular function by releasing the restraints of melatonin (3) and subsequently increasing testosterone levels (4). This is obviously a welcome effect for those aiming to retain muscle during dieting.
As is evident from the statements above, Arecoline alone is clearly an excellent tool for fat loss as it speeds up your metabolism, blunts your appetite and helps enhance your training, but why stop there? Arecoline is merely the first constituent in a truly synergistic blend of ingredients.
Phenylethylamine (PEA) is a naturally occurring neuroamine found in foods such as chocolate and has very recently gathered great popularity in the bodybuilding community for stimulation and fat loss. Designer Supplements was the very first company to release PEA in a fat burning product with the product BASIC CUTS.
Due to increased urinary concentrations of phenylacetic acid - a major metabolite of PEA (5) - after exercise, it has been theorized that PEA may be partly responsible for the 'runners high', or post-lifting elation experienced by most weightlifters or exercise enthusiasts (6). PEA appears to exert a stimulatory effect in the brain through its effect on the beta-adrenergic and dopamine receptors, similar to antidepressants (7). Through these mechanisms, PEA not only increases attention and activity but can also elevate mood significantly (8). As anyone can see, these effects can certainly lead to increased focus and motivation both in the gym and in daily activities.
The major stumbling block for PEA is that oral bioavailability is pitifully low. This is because PEA is quickly metabolised by the enzyme Monoamine Oxidase B (MAO-B), so that very little, if any, makes it to the brain. It has been suggested that one may get around this by taking the amino acid phenylalanine (a PEA precursor), however this does not guarantee significant concentrations of PEA will be synthesised, let alone make it to the brain. To every problem lies a solution, however, and this leads to the introduction of another ingredient for Adrenalean? - Hordenine.
The Monoamine Oxidases, MAO-A and MAO-B, are two enzymes principally involved in catalyzing the oxidation (metabolism) of the monoamines. MAO-A is commonly thought to break down the neurochemicals serotonin and norepinephrine while MAO-B generally catalyzes the break down of dopamine and PEA (as stated above). Hordenine is included in Adrenalean due to its ability to inhibit MAO-B (9) and thereby make PEA orally bioavailable thus allowing all the intriguing effects of stimulation and mood enhancement mentioned above to become a reality. As a consequence of hordenine's MAO-B inhibition, dopamine activity is also prolonged. During dieting, dopamine is of particular importance because it is generally theorized to be the body's means of communication between the brain and the anti-starvation hormone Leptin. Additionally, dopamine is also associated with nutrient partitioning (where the calories you consume go), mood, appetite and a whole host of other biochemical functions. Unfortunately, when you diet, dopamine also happens to decrease quite significantly (10), thus some means of ensuring adequate dopamine output should be paramount (hint: hordenine helps).
As if its efficacy in increasing PEA availability and dopaminergic tone weren?t enough, there is also credible evidence that hordenine not only 'liberates' norepinephrine (11), but also inhibits its metabolism (12), leading to increased stimulation. As many know, norepinephrine and epinephrine collectively form the catecholamines the means through which the popular supplement ephedrine indirectly exerts its stimulatory effect on the central nervous system and improves lipolysis (fat burning).
L-Huperzine A is a naturally occurring alkaloid found in the extracts of the Chinese herb Huperzia serrata. While it has been used for centuries in ancient Chinese medicine, it has recently came into view to the Western World for its neuroprotective effects. L-Huperzine A works by inhibiting the enzyme acetylcholinesterase (13, 14) which breaks down acetylcholine, thereby halting signal transmission. By preventing this enzyme from working, the life cycle of acetylcholine is increased, resulting in improved cognitive effects, increase muscular control and enhanced focus. Recent research has demonstrated the alkaloid to enhance memory, reduce oxidative stress and promote neural protection (15) without any negative implications or side effects (14). Due to its mechanism of action, L-Huperzine A is known as a 'nootropic', or 'smart drug' and works synergistically with Arecoline to potentiate Adrenalean's neurocognitive effect.
Quercetin is the last component of the Euphroamine blend. Quercetin is a type of flavonoid called a flavonol. Flavonoids are also called phytochemicals, and are found in all vascular plants including all the common fruits and vegetables. Quercetin serves as the backbone for most other flavonoids and tends to be the phytochemical most studied in research due to its health benefits. In fact, it is generally stated that a lot of the health benefits found in fruits and vegetables are due to their quercetin content.
Quercetin is included in Adrenalean because of its effects regarding the Cytochrome P450 (CYP450) system. CYP450 is a family of enzymes located mostly in the liver. These are drug, steroid and toxin-metabolizing enzymes that are also used to make cholesterol, steroids and other important lipids. The toxins they breakdown may be waste from metabolic processes within the body, or substances consumed by the person such as antibiotics, recreational drugs or even toxins in the air or the food we eat.
Quercetin inhibits several enzymes of the CYP450 system (16, 17, 18, 19) and also MAO-A (20) thereby prolonging the effect hepatically metabolized compounds in the body. This inhibition results in the effects of Arecoline, PEA, hordenine, caffeine, evodiamine and synephrine exerting their fat burning effects for longer periods of time. In addition to CYP450 inhibition, quercetin also inhibits p-glycoprotein (PGP) (21, 22), a protein located generally in the gut, dealing with absorption and are thus considered part of the "first-pass effect". Although not as significant as inhibition of CYP450, inhibiting PGP also helps improve oral bioavailability of the compounds in Adrenalean?, as well as prolonging their life and effectiveness.
Quercetin has also been demonstrated to inhibit an enzyme known as Catechol-O-methyl transferase (COMT) (20, 23). COMT is involved in the deactivation of the neurotransmitters epinephrine, norepinephrine and dopamine. By enhancing the signalling of these hormones, lipolysis is maintained, and the brain continues to get the dopamine it needs to continue allowing body fat to be oxidized.NSCA-CSCS and CPT - Doctor of Physical Therapy
- 01-14-2008, 11:00 AM
EvoSyn™ is a precise blend of caffeine, evodiamine and synephrine. This triad not only works synergistically together, but also beautifully compliments the ArecoLean™ blend.
Caffeine is one of the world’s most popular drugs. Caffeine acts in the brain by antagonising (blocking) adenosine A1 and A2A receptors (24, 25), thereby inhibiting the breakdown of Cyclic Adenosine Monophosphate (cAMP). Adenosine typically slows nerve cell activity, initiating a relaxed type of environment similar to the state experienced during sleep. By antagonising adenosine, this effect is in fact reversed and nerve cell activity is increased. This causes catecholamine release and central nervous stimulation that makes caffeine such a Godsend for those who find mornings difficult. Adenosine also inhibits dopamine release, thus inhibiting adenosine can help maintain dopamine signalling, which as explained earlier, is of the utmost importance.
While most users will testify that caffeine alone is a sound appetite suppressant, it appears that it has significant effects in potentiating the effect of other stimulants (26, 27). This stimulation can also aid performance by delaying fatigue and allowing one to maintain training intensity for a complete session (28). It can also assist strength training (29) and help improve endurance, making it a valuable compound to utilize for cardiovascular training which can further assist any fat loss endeavour (30).
Evodiamine is an alkaloid found in the Evodiae Fructus plant, and has been used for centuries in ancient Chinese medicine. Evodiamine exerts its fat loss effects in a similar manner to capsaicin, via agonizing the vanilloid receptor TRPV1, but does so without the risk of indigestion (31, 32.). TRPV1 is a receptor typically activated by heat or acidic conditions and is involved in pain regulation. Through activation of this receptor, Evodiamine simultaneously ramps up heat production, thereby promoting fat burning while also increasing heat loss via vasodilation.
As an added benefit, evodiamine has been shown to enhance the secretion of stimulatory neurotransmitters when induced by acetylcholine (33). This means that evodiamine works as another part of the synergistic formula with L-Huperzine-A and Arecoline to promote cAMP signalling in concert with caffeine.
The final ingredient in Adrenalean, Synephrine, is included as an added benefit for those with a big appetite. Synephrine is found naturally in the citrus tree Citrus Aurantium and when ingested acts an agonist of the alpha-1 adrenergic receptor (34, 35). While the rest of the Adrenalean formula will blunt hunger in most individuals, this activation of the alpha-1 receptor further suppresses the drive to eat in even the worst dieter (36). All variables considered, controlling food intake on your diet while using Adrenalean™ should not be a problem.
Many high calorie foods tastes good and eating is associated with a myriad of pleasurable physiological effects...face it, dieting is never “fun!” Then again, being fat, tired, and out of shape isn’t much fun either. Adrenalean is a highly effective stimulating fat burner that provides a smooth pharmaceutical grade energy that will last all day long. There’s no crash, no tremors, no shaking and NO APPETITE!
Using a complex formula of innovative ingredients, Adrenalean mimics the powerful effects of adrenaline and noradrenaline which destroy fat at an alarming rate and by boosting “feel good” chemicals in the brain, you’ll be sure to love every minute of it! Whether you want a daily fat burner to be used during your diet, a staple pre-workout stimulant to aid performance or something to enhance focus and get you through your school or work day, Adrenalean is your only choice.
1. Strickland SS, Veena GV, Houghton PJ, Stanford SC, Kurpad AV. Areca nut, energy metabolism and hunger in Asian men. Ann Hum Biol. 2003 Jan-Feb;30(1):26-52.
2. Laloux C, Derambure P, Jacquesson JM, Bordet R, Dest?e A, Monaca C. The effects of serotoninergic, noradrenergic, cholinergic and dopaminergic drugs on vigilance states in MPTP-treated mice. Brain Res. 2007 Aug 3;1161:79-87.
3. Kuş I, Sarsilmaz M, Oget?rk M, Yilmaz B, Keleştimur H, Oner H. Ultrastructural interrelationship between the pineal gland and the testis in the male rat. Arch Androl. 2000 Sep-Oct;45(2):119-24.
4. Saha I, Chatterji U, Chaudhuri-Sengupta S, Nag TC, Nag D, Banerjee S, Maiti BR. Ultrastructural and hormonal changes in the pineal-testicular axis following arecoline administration in rats. J Exp Zool Part A Ecol Genet Physiol. 2007 Apr 1;307(4):187-98.
5. Sabelli HC, Javaid JI. Phenylethylamine modulation of affect: therapeutic and diagnostic implications. J Neuropsychiatry Clin Neurosci. 1995 Winter;7(1):6-14.
6. Szabo A, Billett E, Turner J. Phenylethylamine, a possible link to the antidepressant effects of exercise? Br J Sports Med. 2001 Oct;35(5):342-3.
7. Paetsch PR, Greenshaw AJ. 2-Phenylethylamine-induced changes in catecholamine receptor density: implications for antidepressant drug action. Neurochem Res. 1993 Sep;18(9):1015-22.
8. Sabelli H, Fink P, Fawcett J, Tom C. Sustained antidepressant effect of PEA replacement. J Neuropsychiatry Clin Neurosci. 1996 Spring;8(2):168-71.
9. Barwell CJ, Basma AN, Lafi MA, Leake LD. Deamination of hordenine by monoamine oxidase and its action on vasa deferentia of the rat. J Pharm Pharmacol. 1989 Jun;41(6):421-3.
10. Ernsberger P, Koletsky RJ, Kilani A, Viswan G, Bedol D. Effects of weight cycling on urinary catecholamines: sympathoadrenal role in refeeding hypertension. J Hypertens. 1998 Dec;16(12 Pt 2):2001-5.
11. Hapke HJ, Strathmann W. [Pharmacological effects of hordenine] Dtsch Tierarztl Wochenschr. 1995 Jun;102(6):228-32.
12. Frank M, Weckman TJ, Wood T, Woods WE, Tai CL, Chang SL, Ewing A, Blake JW, Tobin T. Hordenine: pharmacology, pharmacokinetics and behavioural effects in the horse. Equine Vet J. 1990 Nov;22(6):437-41.
13. Cheng DH, Ren H, Tang XC. Huperzine A, a novel promising acetylcholinesterase inhibitor. Neuroreport. 1996 Dec 20;8(1):97-101.
14. Wang R, Yan H, Tang XC. Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine. Acta Pharmacol Sin. 2006 Jan;27(1):1-26.
15. Zhang HY, Tang XC. Neuroprotective effects of huperzine A: new therapeutic targets for neurodegenerative disease. Trends Pharmacol Sci. 2006 Dec;27(12):619-25.
16. von Moltke LL, Weemhoff JL, Bedir E, Khan IA, Harmatz JS, Goldman P, Greenblatt DJ. Inhibition of human cytochromes P450 by components of Ginkgo biloba. J Pharm Pharmacol. 2004 Aug;56(8):1039-44.
17. Kim KA, Chung J, Jung DH, Park JY. Identification of cytochrome P450 isoforms involved in the metabolism of loperamide in human liver microsomes. Eur J Clin Pharmacol. 2004 Oct;60(8):575-81. Epub 2004 Sep 8.
18. Patel J, Buddha B, Dey S, Pal D, Mitra AK. In vitro interaction of the HIV protease inhibitor ritonavir with herbal constituents: changes in P-gp and CYP3A4 activity. Am J Ther. 2004 Jul-Aug;11(4):262-77.
19. Kang IH, Kim HJ, Oh H, Park YI, Dong MS. Biphasic effects of the flavonoids quercetin and naringenin on the metabolic activation of 2-amino-3,5-dimethylimidazo[4,5-f]quinoline by Salmonella typhimurium TA1538 co-expressing human cytochrome P450 1A2, NADPH-cytochrome P450 reductase, and cytochrome b5. Mutat Res. 2004 Jan 12;545(1-2):37-47.
20. Singh A, Naidu PS, Kulkarni SK. Quercetin potentiates L-Dopa reversal of drug-induced catalepsy in rats: possible COMT/MAO inhibition. Pharmacology. 2003 Jun;68(2):81-8.
21. Limtrakul P, Khantamat O, Pintha K. Inhibition of P-glycoprotein function and expression by kaempferol and quercetin. J Chemother. 2005 Feb;17(1):86-95.
22. Yang ZG, Meng H, Zhang X, Li XD, Lv WL, Zhang Q. [Effect of quercetin on the acyclovir intestinal absorption]. Beijing Da Xue Xue Bao. 2004 Jun 18;36(3):309-12.
23. Nagai M, Conney AH, Zhu BT. Strong inhibitory effects of common tea catechins and bioflavonoids on the O-methylation of catechol estrogens catalyzed by human liver cytosolic catechol-O-methyltransferase. Drug Metab Dispos. 2004 May;32(5):497-504.
24. Justinova Z, Ferre S, Segal PN, Antoniou K, Solinas M, Pappas LA, Highkin JL, Hockemeyer J, Munzar P, Goldberg SR. Involvement of adenosine A1 and A2A receptors in the adenosinergic modulation of the discriminative-stimulus effects of cocaine and methamphetamine in rats. J Pharmacol Exp Ther. 2003 Dec;307(3):977-86.
25. Cauli O, Morelli M. Caffeine and the dopaminergic system. Behav Pharmacol. 2005 Mar;16(2):63-77.
26. Jessen A, Buemann B, Toubro S, Skovgaard IM, Astrup A. The appetite-suppressant effect of nicotine is enhanced by caffeine. Diabetes Obes Metab. 2005 Jul;7(4):327-33.
27. Shekelle PG, Hardy ML, Morton SC, Maglione M, Mojica WA, Suttorp MJ, Rhodes SL, Jungvig L, Gagne J. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis. JAMA. 2003 Mar 26;289(12):1537-45. Epub 2003 Mar 10.
28. Davis JM, Zhao Z, Stock HS, Mehl KA, Buggy J, Hand GA. Central nervous system effects of caffeine and adenosine on fatigue. Am J Physiol Regul Integr Comp Physiol. 2003 Feb;284(2):R399-404. Epub 2002 Oct 24.
29. Hespel P, Op't Eijnde B, Van Leemputte M. Opposite actions of caffeine and creatine on muscle relaxation time in humans. J Appl Physiol. 2002 Feb;92(2):513-8.
30. Cox GR, Desbrow B, Montgomery PG, Anderson ME, Bruce CR, Macrides TA, Martin DT, Moquin A, Roberts A, Hawley JA, Burke LM. Effect of different protocols of caffeine intake on metabolism and endurance performance. J Appl Physiol. 2002 Sep;93(3):990-9.
31. Kobayashi Y, Nakano Y, Kizaki M, Hoshikuma K, Yokoo Y, Kamiya T. Capsaicin-like anti-obese activities of evodiamine from fruits of Evodia rutaecarpa, a vanilloid receptor agonist. Planta Med. 2001 Oct;67(7):628-33.
32. Pearce LV, Petukhov PA, Szabo T, Kedei N, Bizik F, Kozikowski AP, Blumberg PM. Evodiamine functions as an agonist for the vanilloid receptor TRPV1. Org Biomol Chem. 2004 Aug 21;2(16):2281-6.
33. Yoshizumi M, Houchi H, Ishimura Y, Hirose M, Kitagawa T, Tsuchiya K, Minakuchi K, Tamaki T. Effect of evodiamine on catecholamine secretion from bovine adrenal medulla. J Med Invest. 1997 Aug;44(1-2):79-82.
34. Hwa J, Perez DM. The unique nature of the serine interactions for alpha 1-adrenergic receptor agonist binding and activation. J Biol Chem. 1996 Mar 15;271(11):6322-7.
35. 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.
36. Wellman PJ. Norepinephrine and the control of food intake. Nutrition. 2000 Oct;16(10):837-42.NSCA-CSCS and CPT - Doctor of Physical Therapy
01-14-2008, 05:37 PM
01-14-2008, 05:40 PM
01-14-2008, 06:29 PM
01-14-2008, 06:31 PM
01-15-2008, 10:40 AM
01-15-2008, 11:25 AM
01-15-2008, 11:26 AM
01-15-2008, 11:42 AM
01-15-2008, 01:04 PM
01-15-2008, 03:56 PM
Recommended dosing won't put you at 600, but you can always take more once you know how you react.
NSCA-CSCS and CPT - Doctor of Physical Therapy
03-11-2008, 01:32 PM
After reading the writeup, I have some questions regarding arecoline and it's effects on the pineal gland, more specifically to it's effects on melatonin.
I have been working shift work for the past 10 years, and have been taking melatonin on a daily basis, due to the fact that my melatonin production is likely messed up due to the constantly rotating sleep schedule. What kind of effect could I expect arecoline to have on me in this type of situation?
03-12-2008, 09:38 AM
03-12-2008, 09:41 AM
It'd be a good idea to start at one solitary dose per day without altering your tonin dose or the time of the dose.
03-12-2008, 04:51 PM
03-12-2008, 05:04 PM
03-12-2008, 05:57 PM
recreate is not a stim but it does have a little caff. not a high dose though, i felt like the combo took me to a whole new level the last two days
03-12-2008, 06:23 PM
04-05-2008, 06:38 PM
Well shoot, I think I'll try this as well!! Ihave 2 bottles of recreate coming, and I have a bottle of Adrenalean that I have been using for about a week now. By the way, I LOVEthe clean energy that Adrenalean gives me(NO CRASH!), and I have not noticed the appetite suppressing ascpects of it, but just realized...HOLY SH!TE, I've only had a Muscle Milk shake today, and am not hungry. In other words, the Adrenalean has definitely been suppressing my appetite, I just have not noticed it because I have not been hungry and thinking about food all the time like my fat azz usually does!
04-06-2008, 10:50 AM
In "The Anti-Estrogenic Diet", Ori Hofmekler talks about the anti-estrogenic characteristics of Quercetin: one o' y'all like to blow a riff on that theme , in context?
04-06-2008, 06:06 PM
04-15-2008, 11:31 AM
I've been taking 3 caps of Adrenalean with 2 caps of ReCreate, twice a day, as well as 4 caps of Lean Extreme 2 spread out through the day, and it's really really intense.
I made the mistake of adding some Reset-AD the other day and it rivaled one of the worst ephedrine crack outs i've ever had.
I think i'm going to have to drop the dosage of Adrenalean and/or Lean Extreme 2 in order to maintain the current stack. But it's nice to know that when I need something more intense, the option is there.
04-15-2008, 08:09 PM
04-16-2008, 01:45 AM
I think i'll also need to go down to 2x2 Adrenalean instead of 3x2.
This is all pretty crazy for me, as I'm very stimulant tolerant. I could handle 75mg ephedrine a day and just a couple weeks ago, I was doing 3 or even 4 caps of Adrenalean, twice a day, and getting a nice effect from it, but something in ReCreate is synergizing with Adrenalean and really rocking me out.