Scientific data

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Where can I find scientific data backing your products?
 
nattydisaster

nattydisaster

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We do not own the rights to any of the studies used to formulate our products. We purchased the studies. You are free to do so as well. If you have a specific question on a specific ingredient, feel free to ask

http://scholar.google.com/scholar?q=rauwolscine&hl=en&btnG=Search&as_sdt=1,10&as_sdtp=on

http://scholar.google.com/scholar?hl=en&q=alpha-yohimbine&btnG=Search&as_sdt=0,10&as_ylo=&as_vis=0

http://scholar.google.com/scholar?hl=en&q=methyl-synephrine&btnG=Search&as_sdt=0,10&as_ylo=&as_vis=0

http://scholar.google.com/scholar?hl=en&as_sdt=0,10&q=diiodo-l-thyronine

http://scholar.google.com/scholar?hl=en&q="androsta-3,5-diene-7,17-dione"&btnG=Search&as_sdt=0,10&as_ylo=&as_vis=0


Here is some data on Methyl-synephrine for example:


[size=+3]Methylsynephrine[/size]​

Methylsynephrine
Methylsynephrine (Oxilofrine, Hydroxyephrine, Oxyephrine) is a mixed-adrenergic agonist with an ephedrine-like pharmacological profile. It is used as a dietary supplement in various products and is marketed as a weight-loss compound. Here, I will explore the nature of this compound in the literature.

Synephrine
Synephrine is an adrenergic agonist similar to phenylephrine [1] . Due to its secondary terminal-amine structure, it possesses a stronger affinity for alpha-receptors than norepinephrine and has been used clinically as a vasoconstrictor and pressor (Figure 1). Synephrine is a positional-isomer of phenylephrine and its metabolism is likely similar with extensive MAO elimination in the GI tract and in the liver. Synephrine may also play a role in vesicular exchange-diffusion within synapses with norepinephrine, although this appears weak at therapeutic concentrations.


Figure 1.



Physiological effects
A study using a bitter orange extract standardized for 27 mg synephrine failed to induce any changes in hemodynamics [2]. Conversely, in another study using twice the amount, significant effects were observed for heart rate, systolic pressure, and diastolic pressures, in which all values increased [3]. This would indicate that the minimum threshold dose to elicit adrenergic activity to be somewhere between 27 mg and 54 mg for adult males.

Pharmacodynamics
Beta-receptor affinity for phenylethylamine derivatives increases as the nonpolar bulkiness on the terminal amine gets larger (Figure 2). Compared with phenylethylamine, norepinephrine, or other primary amines, synephrine should have greater affinity for beta-receptors due to its secondary amine structure. Similarly, beta-receptor affinity also increases with the addition of nonpolar substituents on the alpha-carbon, which synephrine does not possess. The fact that diastolic pressure also increased in the above study is evidence for very little beta-receptor activation. Although synephrine has demonstrated an ability to induce lipolysis by activating beta-3 receptors en vitro, its efficiency in doing so en vivo is greatly limited because of its inherent affinity for alpha receptors [4]. The dose required to sufficiently trigger lipolysis within adipocytes would be intolerable due to its effects on hemodynamics [5].

Figure 2.



Synephrines downsides
Increasing peripheral vascular resistance is a negative characteristic of a lot of stimulants and is especially exacerbated in compounds which primarily activate alpha-receptors like synephrine. Not only is the incidence of stroke and hemorrhage higher with these agents, but the work-load put on the heart can trigger ventricular fibrillations or other arrhythmias [6, 7, 8]. Using caffeine in conjunction with synephrine will potentiate the peripheral vasoconstriction by synergizing with the transduction mechanism induced by alpha-adrenergic agonism [9, 10]. Adrenergic agonists with high affinity to alpha-receptors also have the unfortunate capacity to induce platelet aggregation by agonizing alpha-2 receptors on platelets which can lead to intravascular clotting [11, 12].

Methylsynephrine vs. Synephrine
The primary difference between synephrine and methylsynephrine is the addition of a methyl group on the alpha carbon (Figure 3). As mentioned previously, this has extensive pharmacodynamic implications as it increases the affinity of the compound for beta-receptors.


Figure 3.



Pharmacokinetics
The half-life for phenylephrine is an adequate gauge for the half-life and elimination statistics for synephrine due to its similar structure and chemical characteristics. Similarly, ephedrine and pseudoephedrine can be used to make an educated guess regarding the pharmacokinetics of methylsynephrine. Phenylephrine, a positional isomer of synephrine, has a half-life of 2.1 -3 hours. The half-life of ephedrine is from 3-6 hours, depending on urine pH. Pseudoephedrine enjoys an even longer half-life due to increased steric-hindrance of MAO. The mean half-life of methylsynephrine, as compared to synephrine, would be roughly twice the duration. Neither synephrine, ephedrine, nor methylsynephrine, possess notable central effects due to the common beta-hydroxyl which prevents substantial blood-brain-barrier permeability (Appendix A).

Pharmacodyamics
Although the exact pharmacology of methylsynephrine has not been studied in great detail, its pharmacodynamics can be inferred through its effects on systolic blood pressure, diastolic blood pressure, and heart rate. Differing from synephrine, methylsynephrines effects on the heart are mostly beneficial in that it increases the pulse pressure and is a positive inotrope (Appendix B). Diastolic pressure is used clinically as a diagnostic marker for peripheral vascular resistance, especially in relation to the arterial system [13]. Activating beta-2 receptors in the periphery induces vasodilation in vascular beds in the liver and skeletal muscle, which decreases the work-load on the heart. Since it also has some alpha-adrenergic activity, reflexive tachycardia would be avoided. Similarly, activating beta-receptors would increase venous tone, which will increase the amount of blood returning to the heart, and subsequently increase cardiac output, as illustrated by Starling’s Law [14, 15]. The beta-3 receptor, as noted above, directly mediates lipolysis. The genetic homology of the ligand-binding-domain between the beta-3 receptor and the beta-2 receptor is greater than that of the beta-1 receptor. This explains why norepinephrine, which possesses a primary terminal amine, has sufficient affinity for beta-1 receptors, but very little beta-2 or beta-3 affinity, and therefore limited ability to induce lipolysis. This means that compounds which significantly activate beta-2 receptors will also have great predilection to also activate beta-3 receptors.

Physiological effects
Methylsynephrine has been used clinically for orthostatic hypotension due to its effects on stroke volume, ejection fraction, and cardiac index [16, 17]. It has been used in doses of up to 120mg in healthy adults with no adverse effects [18, 19]. Even at this dose, diastolic pressure decreased, which is evidence for very little alpha-adrenergic activity. Furthermore, it had no effect on heart rate or mean arterial pressure. Some of methylsynephrines therapeutic efficacy is mediated by acting as a norepinephrine-releasing agent, and also by inhibiting its uptake [20]. The majority of methylsynephrines pharmacological appeal resides in its ability to activate beta receptors, which is exemplified through its effects on the heart and haemodynamics as described above. This also implies significant beta-3 activity and an ability to induce lipolysis which is consistent with some of its marketing claims [21]. Another deviation from synephrine is methylsynephrines limited propensity to activate alpha-2 receptors on platelets. This would avoid the complications of intravascular clotting, which has resulted in myocardial infarction mortality associated with synephrine, although allow for the possibility of cerebral hemorrhage [22].

Summary
Methylsynephrine is a unique compound which has not been used frequently in clinical practice. Due to its ephedrine-like pharmacology, and its surprisingly clean safety record, it will likely become a more common ingredient in fat loss supplements in the future. It is currently uncontrolled in the United States [23].

Appendix A:


Appendix B:
Pulse Pressure (Pp) = Systolic pressure – Diastolic pressure

Relevant links:
PubMed Compound: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=9701&loc=ec_rcs
Methylsynephrine wikipedia entry: http://en.wikipedia.org/wiki/Oxilofrine
Mirrored site: http://www.recomp.com/wiki/index.php5?title=Methylsynephrine&redirect=no


References:
1. http://www.ncbi.nlm.nih.gov/pubmed/19721332
2. http://www.ncbi.nlm.nih.gov/pubmed/16305290
3. http://www.ncbi.nlm.nih.gov/pubmed/16317106
4. http://www.springerlink.com/content/uemq7ml1lcee6a3c/
5. http://www.ncbi.nlm.nih.gov/pubmed/15337824
6. http://www.ncbi.nlm.nih.gov/pubmed/20055074
7. http://www.ncbi.nlm.nih.gov/pubmed/18700609
8. http://www.ncbi.nlm.nih.gov/pubmed/16610576
9. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1175678/
10. http://www.ncbi.nlm.nih.gov/pubmed/18341680
11. http://www.ncbi.nlm.nih.gov/pubmed/18637307
12. http://www.ncbi.nlm.nih.gov/pubmed/20069086
13. http://www.ncbi.nlm.nih.gov/pubmed/3229871
14. http://www.ncbi.nlm.nih.gov/pubmed/3119915
15. http://www.springerlink.com/content/vmw352074216g871/
16. http://www.ncbi.nlm.nih.gov/pubmed/1530677
17. http://www.ncbi.nlm.nih.gov/pubmed/3119915
18. http://www.ncbi.nlm.nih.gov/pubmed/3229871?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_SingleItemSupl.Pubmed_Discovery_RA&linkpos=2&log$=relatedarticles&logdbfrom=pubmed
19. http://www.ncbi.nlm.nih.gov/pubmed/3403107?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_SingleItemSupl.Pubmed_Discovery_RA&linkpos=1&log$=relatedarticles&logdbfrom=pubmed
20. http://www.ncbi.nlm.nih.gov/pubmed/7191269
21. http://www.ncbi.nlm.nih.gov/pubmed/12439645
22. http://www.ncbi.nlm.nih.gov/pubmed/20179577
[23] Wikipedia contributors. "Oxilofrine." Wikipedia, The Free Encyclopedia. Wikipedia, The Free Encyclopedia, 17 Feb. 2010. Web. 14 Mar. 2010.
 
nattydisaster

nattydisaster

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For example, data on the Rauwolscine and the mechanism in which it burns fat:

Berlan M, Galitzky J, Riviere D, et al. Plasma catecholamine levels and lipid mobilization induced by yohimbine in obese and non-obese women. Int J Obes. 1991 May;15(5):305-315

Galitzky J, Taouis M, Berlan M, et al. Alpha 2-antagonist compounds and lipid mobilization: evidence for a lipid mobilizing effect of oral yohimbine in healthy male volunteers. Eur J Clin Invest. 1988 Dec;18(6):587-594

Flechtner-Mors M, Jenkinson CP, Alt A, et al. In vivo alpha(1)-adrenergic lipolytic activity in subcutaneous adipose tissue of obese subjects. J Pharmacol Exp Ther. 2002 Apr;301(1):229-233

Sax L. Yohimbine does not affect fat distribution in men. Int J Obes. 1991 Sep;15(9):561-565

Kucio C, Jonderko K, Piskorska D. Does yohimbine act as a slimming drug? Isr J Med Sci. 1991 Oct;27(10):550-556

Berlan M, Le Verge R, Galitzky J, et al. Alpha 2-adrenoceptor antagonist potencies of two hydroxylated metabolites of yohimbine. Br J Pharmacol. 1993 Apr;108(4):927-932

Berlin I, Stalla-Bourdillon A, Thuillier Y, et al. Lack of efficacy of yohimbine in the treatment of obesity. J Pharmacol. 1986 Jul-Sep;17(3):343-347

Zahorska-Markiewicz B, Kucio C, et al. Adrenergic control of lipolysis and metabolic responses in obesity. Horm Metab Res. 1986 Oct;18(10):693-697

Perry BD, U'Prichard DC. [3H]rauwolscine (alpha-yohimbine): a specific antagonist radioligand for brain alpha 2-adrenergic receptors. Eur J Pharmacol. 1981 Dec 17;76(4):461-464
 
nattydisaster

nattydisaster

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For example, studies on the active ingredient of Erase. More studies on how these mechanisms are useful in bodybuilding can be found all over

Numazawa M, Mutsumi A, Tachibana M, Hoshi K; Synthesis of androst-5-en-7-ones and androsta-3,5-dien-7-ones and their related 7-deoxy analogs as conformational and catalytic probes for the active site of aromatase; J Med Chem. 1994 Jul 8;37(14):2198-205

Schubert K, Wehrberger K, Hobe G; Androsta-3,5-diene-7,17-dione: isolation from urine and formation from 7-keto-dehydro-epiandrosterone sulphate under various conditions of hydrolysis; Endocrinol Exp. 1971 Dec;5(4):205-10
 
nattydisaster

nattydisaster

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Understand that the majority of these studies you have to read the entire full text of the study to get the proper information. Not just the abstract.
 
BBB

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Is the product in Erase the same as 3, 7-Keto DHEA used in other products?

I have been on the PES trifecta stack for a little over a week. I must admit I am somewhat skeptical but I like small companies with few product options. These companies must bring good products to the market to survive. What I can say thus far is that I wake-up with morning wood everyday. This is not norm for me. As far a recomp is concerned, only time will tell.
 
nattydisaster

nattydisaster

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Is the product in Erase the same as 3, 7-Keto DHEA used in other products?

I have been on the PES trifecta stack for a little over a week. I must admit I am somewhat skeptical but I like small companies with few product options. These companies must bring good products to the market to survive. What I can say thus far is that I wake-up with morning wood everyday. This is not norm for me. As far a recomp is concerned, only time will tell.
Yes Erase is the same ingredient as 3,7-keto DHEA used in other products. 3,7-keto DHEA is a terrible name though IMO.

3-deoxy-7-oxo-DHEA makes more sense
 

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