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SARMs (Selective Androgen Receptor Modulators) are the next generation of muscle building. Advanced Muscle Science (AMS) is constantly in search of natural ergogenic aids to make your bodybuilding life a bit easier.
There are currently very few, if any, natural SARMs available. In addition the quality of many underground or research chem shops is questionable (1). Still it’s important we stay current on natural SARMs and understanding their use. Testosterone is an all powerful hormone as we all know. Unfortunately testosterone impacts not only muscle growth, but several other tissues in the body. It’s great for bones and building muscle, but it has negative impacts on the prostate, and side effects such as increased blood pressure (2) (3). This is where SARMs come in. SARMs are selectively activating anabolic activity in muscle and bone only, thus eliminating the negative side effects associated with testosterone (4). The referenced research review states the following:
“Therefore, therapeutic agents such as SARMs that can achieve anabolic effects on the skeletal muscle and bone without the dose-limiting adverse effects associated with testosterone would be attractive as function promoting anabolic therapies (1,2,6).”
Now that you have a basic understanding of the importance of SARMs we will tell you how to achieve a similar effect by utilizing our prohormone Decavol. Normally our goal with Decavol is to get it to convert (once inside the body) to nandrolone a powerful steroid. However a recent study suggests we can achieve SARM like effects with the prohormone 19-norandrostenedione (5). Decavol is 19-norDHEA, which is a one step prohormone to both 19-norandrosteneDIONE, and 19-norandrosteneDIOL. It is a two step prohormone to nandrolone (otherwise known as nortestosterone). A depiction of these conversions is show here:
Back to the SARM study using 19-norandrosteneDIONE. The study performed both in vitro and in vivo research to determine the biological activity of 19-norandrosteneDIONE. They researched everything from the standard Hershberger assay, to mRNA myostatin and androgen receptor expression. What they found was selective tissue activity of 19-norandrosteneDIONE. In other words it acted as a SARM. Below are the results of the Hershberger assay:
The authors also found that it did not increase the weight of the liver, and they also found no adverse effects on the heart. These are obviously both great findings of two things commonly associated with steroids. The authors go on to conclude the following (note, in the study 19-norandrostenedione is referred to as NOR):
“Summarizing these data it is obvious, that NOR has powerful SARM like properties if administrated s.c. and is a potent anabolic steroid.”
The first thing you might note from this statement is “s.c.” or subcutaneous. That means they in injected the rats with 19-norandrostenedione. Obviously we cannot do this with Decavol. But the key here is that both subcutaneous administration and Decavol’s orally disintegrating tablet bypass first pass hepatic metabolism. This is again important because the author’s of the study believe the administration of 19-norandrostenedione is critical to obtaining the SARM like effects.
“A possible mechanistically explanation for the different androgenic/anabolic profile of NOR after oral and s.c. administration could be the first pass effect. The route of administration is known to have a huge impact on the activity and side effects of androgens (Marbury et al., 2003). After oral administration, androgens are absorbed from the gut into the portal system. This allows the liver to metabolize the drug, in the case of NOR mainly to nandrolone (De **** et al., 2001; Schrader et al., 2006; Uralets and Gillette, 1999). For testosterone it has been demonstrated that after s.c. administration, metabolisation in the
liver is different compared to oral administration (Jockenh¨ovelet al., 1996). This could also be the case for NOR.”
Now that we know Decavol bypasses first pass metabolism, and converts to 19-norAndrosteneDIONE, we still need to prevent it from converting to the androgenic hormones 19-norandrosteneDIOL, and nandrolone. Otherwise it will still remain a prohormone that exerts androgenic effects and negatively impacts the prostate, liver, etc. We can accomplish this by inhibiting the following enzymes to the greatest degree possible (again please refer to the conversion image above):
- 17b-HSD Type 1
- 17b-HSD Type 3
- 17b-HSD Type 5
17b-HSD Type 1 is only expressed in human placenta and ovaries (7). As males we do not have to worry about inhibiting this enzyme.
This leaves us with 17b-HSD Type 5, a multifunction enzyme that catalyzes the transformation of androstenedione to testosterone, and DHEA to androstenediol (8) (7). In our depiction of Decavol this enzyme also converts 19-norandrosteneDIONE to nandrolone, and Decavol (19-norDHEA) to 19-norandrosteneDIOL. Thankfully there are many natural inhibitors, and even many in development. But we need the most potent natural inhibitor to avoid any of the androgenic effects of nandrolone and 19-norandrosteneDIOL.
The two most relevant pieces of research on 17b-HSD Type 5 inhibition (naturally) first appeared in 2001 out of the Czech Republic, and more recently (2009) out of Germany . Both were testing multiple dietary phytoestrogens to determine the level of 17b-HSD Type 5 inhibition. The best inhibitor for our purposes will possess the following qualities:
- A low IC50 value
- Research showing that IC50 value can be reached in vivo (specifically humans)
- Naturally found
Of these three, quercetin is easily the most readily available over the counter dietary supplement. Unfortunately due to its poor bioavailability even 500mg’s three times per day would likely only result in approximately minimal inhibition based on quercetin pharmacokinetic plasma research (9). In fact it would result in mean plasma concentrations of only 1.53µM, which is well below the plasma levels needed for even 50% inhibition. And zearalenone is a toxin found in moldy food. So that’s out as our best inhibitor. And finally there is coumestrol, which also unfortunately has evidence suggesting it negatively impacts the male hormonal system. So where does this leave us?
The German Study
The Czech study did a great job initially identifying some potential natural 17b-HSD Type 5 inhibitors. The German study expanded on this by further identifying potential powerful inhibitors. They tested several potential inhibitors and narrowed them down to the seven most potent seen in the table below.
You will notice once again quercetin appears, however as we previously discussed its poor oral bioavailability eliminates it from our search. 2’-Hydroxyflavanone, and 7-Hydroxyflavone are both very effective inhibitors. Unfortunately they are not something commonly found for purchase over the counter, and are not readily available to the consumer. That leaves us with 2 promising alternatives:
- Naringenin
- Silibinin
With the lowest IC50 value of the two this holds the most potential for our purposes. The good news is this is naturally found. And we can reach plasma concentrations necessary to create significant 17b-HSD Type 5 inhibition. If fact the authors of this German study stated the following:
“After single ingestion of grapefruit juice (8 ml/kg) the mean plasma concentration of naringenin even rose to 6µM. However, big inter-individual differences in terms of bioavailability were observed in this study, e.g. the highest concentration of naringenin observed after grapefruit juice drinking was 14µM [27]. According to the present investigation, the IC50 value of naringenin for AKR1C3 was 2.4µM in vitro, hence, we would expect that concentrations of naringenin, and probably those of other flavonoids as well, may reach sufficient levels to affect AKR1C3 and hormone metabolism in vivo.”
It’s important to note the above stated “single ingestion of grapefruit juice”, indicating chronic ingestion of grapefruit juice would significantly raise naringenin plasma levels over time. The mean plasma concentration was 6µM after approximately 3 cups or 24oz’s of grapefruit juice (based on a 200lb male). In order to inhibit approximately 72% of the enzyme we would need to reach plasma levels of 20µM.
Clearly this is attainable with daily use of grapefruit juice. It is important to note that they did see some variance, with one subject showing plasma levels of 14µM after the same amount of grapefruit juice. Below you can see the various inhibition levels for each compound tested. The red bar is naringenin.
I don’t like the taste of Grapefruite Juice AMS!
We know that everyone does not like grapefruit juice and may not want to be drinking as much as 24 oz per day for an extended period of time. Thankfully just supplementing with naringenin may be as good as or better than consuming grapefruit juice. In an acute study (one dosing), researchers gave five healthy males, and one healthy female 135mg’s of naringenin on an empty stomach (10). Based on their plasma naringenin AUC (area under the curve) findings, it suggests that we can reach plasma levels of approximately 34.61µM. This is substantially above 20µM plasma levels we are seeking with only 1 dose of supplemental naringenin. They even prohibited the subjects from consuming a diet that might contain additional naringenin. As bodybuilders we consume diets with a lot of fruits and vegetables, both of which contain additional naringenin. Together this research suggests that naringenin is our most powerful tool for inhibiting 17b-HSD Type 5.
Silibinin
The second powerful inhibitor noted in the German study was silibinin, which is a well known part of silymarin. It’s used by guys to “protect” their liver on and off cycle. More importantly for us it was found to inhibit 17b-HSD Type 5 50% at the 20µM plasma levels. Silibinin like other flavonoids does have poor bioavailability. This is why you see guys dosing upwards of several grams per day of standard milk thistle extracts. Unfortunately even using an advanced delivery system milk thistle such as Siliphos® still would not reach the appropriate plasma levels for a great degree of 17b-HSD Type 5 inhibition (11).
Other Inhibitors
As you can see in the diagram above there are several other potential inhibitors (although not as potent). We will not go into those here, but feel free to check into them further if you are interested. Its possible adding them to the below suggested cycle could result in a greater level of 17b-HSD Type 5 inhibition.
The AMS SARM Cycle
Okay so we may have bored you to death with details above, so the following easily summarized the AMS SARM Cycle. Remember to eat a lot of fruit and vegetables to further increase your naringenin plasma levels, and thus inhibit a greater degree of our target enzyme.
Keep in mind you will need to find your own naringenin supplement as we do not currently offer this supplement for sale, but many stores do carry such a supplement.
Also remember that this has not been studied in humans, we may find out that we are unable to inhibit the appropriate enzymes to a degree necessary to get the same reaction they found in the in 19-norandrostenedione study. However, we may find it creates a very successful cycle with minimal side effects and massive gains! If you try this please keep us informed. We plan to look into this further and possibly sponsor some cycles including bloodwork. We will update our findings at that time.
For more information on Decavol, please visit the Advanced Muscle Science website.
References
1. Trafficking of drug candidates relevant for sports drug testing: Detection of non-approved therapeutics categorized as anabolic and gene doping agents in products distributed via the Internet. Thevis M, Geyer H, Thomas A, Schänzer W. Cologne, Germany : Drug Test Anal., 2011, Vol. May 3. doi: 10.1002/dta.283.
2. Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on the skeletal muscle. Bhasin S, Woodhouse L, Casaburi R, Singh AB, Mac RP, Lee M, Yarasheski KE, Sinha-Hikim I, Dzekov C, Dzekov J, Magliano L, Storer TW. University of California, Los Angeles, CA : J Clin Endocrinol Metab, 2005, Vols. Feb;90(2):678-88.
3. Adverse events associated with testosterone administration. Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S, Ulloor J, Zhang A, Choong K, Lakshman KM, Mazer NA, Miciek R, Krasnoff J, Elmi A, Knapp PE, Brooks B, Appleman E, Aggarwal S, Bhasin G, Hede-Brierley L, Bhatia A, C. Boston, Massachusetts : N Engl J Med, 2010, Vols. Jul 8;363(2):109-22.
4. Selective androgen receptor modulators as function promoting therapies. Bhasin S, Jasuja R. Boston, Massachusetts : Curr Opin Clin Nutr Metab Care, 2009, Vols. May;12(3):232-40.
5. The prohormone 19-norandrostenedione displays selective androgen receptor modulator (SARM) like properties after subcutaneous administration. Diel P, Friedel A, Geyer H, Kamber M, Laudenbach-Leschowsky U, Schänzer W, Schleipen B, Thevis M, Vollmer G, Zierau O. Cologne, Germany : Toxicol Lett, 2008, Vols. Apr 1;177(3):198-204.
6. Male pseudohermaphroditism caused by mutations of testicular 17 beta-hydroxysteroid dehydrogenase 3. Geissler WM, Davis DL, Wu L, Bradshaw KD, Patel S, Mendonca BB, Elliston KO, Wilson JD, Russell DW, Andersson S. Rahway, New Jersey : Nat Genet, 1994, Vols. May;7(1):34-9.
7. The intracrine sex steroid biosynthesis pathways. Luu-The V, Labrie F. Quebec, Canada. : Prog Brain Res., 2010, Vols. 181:177-92.
8. The human kidney is a progesterone-metabolizing and androgen-producing organ. Quinkler M, Bumke-Vogt C, Meyer B, Bähr V, Oelkers W, Diederich S. Berlin, Germany : J Clin Endocrinol Metab, 2003, Vols. Jun;88(6):2803-9.
9. Quercetin pharmacokinetics in humans. Moon YJ, Wang L, DiCenzo R, Morris ME. University at Buffalo, State University of New York, Amherst, NY : Biopharm Drug Dispos., 2008, Vols. May;29(4):205-17.
10. Pharmacokinetics of the citrus flavanone aglycones hesperetin and naringenin after single oral administration in human subjects. Kanaze FI, Bounartzi MI, Georgarakis M, Niopas I. Thessaloniki, Greece : Eur J Clin Nutr., 2007, Vols. Apr;61(4):472-7.
11. A review of the bioavailability and clinical efficacy of milk thistle phytosome: a silybin-phosphatidylcholine complex (Siliphos). Kidd P, Head K. University of California, Berkeley, USA : Altern Med Rev., 2005, Vols. Sep;10(3):193-203.
