One of the major drawbacks of the current DSHEA compliant prohormones is the limited research. However, we can utilize the existing research on their active steroid counter parts to understand how the pharmacokinetics of the current prohormones will act once inside the biological environment of your body. In addition, more recent research is available on the now banned prohormones that is also very applicable. A summary of each will be provided in the proceeding sections.
Standard Oral Encapsulation
The standard oral encapsulation is the most common delivery form of over the counter supplements you will find. It is simple, cheap, and depending on what’s inside often times very effective. However prohormones, and specifically 1-DHEA, 4-DHEA, & 19-norDHEA and their target hormones are heavily metabolized and excreted in a standard encapsulation.
Let’s use 19-norAndrostenediol to illustrate the poor bioavailability of oral prohormones. As a brief overview, 19-norAndrostenediol is a one step precursor to 19-nortestosterone, a powerful muscle builder. Alpha Hard is 19-norDHEA a one step precursor to 19-norAndrostenediol.
Researchers found that the oral bioavailability of 300mg’s of 19-norAndrostenediol when compared to an adjusted dose of nandrolone decanoate (50mg’s) was less than 1% (not adjusted for subject weight) (1) (2). This is why we use to see doses over 1 gram per day with standard oral 19-norAndrostenediol back in the early days of prohormones. And considering the new age prohormones (19-norDHEA) requires one additional conversion step the bioavialability is likely even lower.
Orally Disintegrating Tablets
Orally disintegrating tablets were the next generation of prohormones specifically designed to improve bioavailability and make prohormones more cost effective. The power of this delivery lies in the fact that it can avoid first pass metabolism. This is obtained by utilizing a cyclodextrin complex which enables it to pass through the oral mucosa and directly into the blood stream.
Using the same example as we did for the oral encapsulation (19-norAndrostenediol), we can also determine the bioavailability of a cyclodextrin based orally disintegrating tablet.
Researchers found that the orally disintegrating tablet bioavailability of 25mg’s of 19-norAndrostenediol when compared to an adjusted dose of nandrolone decanoate (50mg’s) was approximately 69% (not adjusted for subject weight) (1) (2) (3). That is significantly better than your typical oral capsule.
Still there are some drawbacks to orally disintegrating prohormones. First, peak plasma levels fall off quickly, so dosing often is critical to a successful cycle. Second, the oral mucosa has a limited surface area, so it’s difficult to “megadose” orally disintegrating tablets. And third, prohormone users commonly feel that swallowing them is just as efficient, when in reality they will not avoid first pass metabolism unless they give each dose time to dissolve inside the mouth.
Lipid Soluble Oral Prohormones (lymphatic)
Lipid soluble prohormones are similar to orally disintegrating tablets because they also attempt to bypass first pass metabolism. They accomplish this very differently however. Fatty acid esters are attached to the prohormone molecule. In the case of ForeRunner Labs™ Ultra 1-DHEA, Ultra 4-DHEA, and Ultra 19-norDHEA we have attached the fatty acid ester known more commonly as the enanthate ester. This drastically increases the lipid solubility (how well it absorbs in fats) compared to an un-esterfied version of the same prohormone (DHEA LogP = 3.2, DHEA Enanthate LogP = 6.3).
ForRunner Labs™ then dissolves the lipid soluble prohormone into an oil based carrier that contains sesame seed oil, medium chain triglycerides, conjugated linoleic acid, and ethoxylated sorbitan monooeleate. Together this process creates what is known as a Self Emulsifying Drug Delivery System (SEDDS). SEDDS systems have been shown to significantly improve the bioavailability of many drugs and supplements. For example:
So that leaves us with a lipid soluble prohormone in a SEDDS based system. But as you know ForeRunner Labs™ didn’t stop there. Berberine, rhizoma coptidis, and cobalt were added to increase bioavailability even further. These three supplements also work to drastically inhibit enzymes that break down the prohormone and render it useless. In a recent study berberine was shown to inhibit specific cyctochrome enzymes which enabled the tested drug to increase in bioavailability by approximately 40% (7).
- Increased the bioavailability of exemestane (a.k.a. Aromasin®) 2.9 times (or a relative bioavailability increase of 287%). (4)
- Increased the Cmax and AUC of curcumin 4.6 and 7.6 times, representing a large bioavailability increase. (5)
- Increased the bioavailability of Vitamin E approximately 210 to 410% in humans. (6)
Together ForeRunner Labs™ has utilized several different pathways to increase the bioavailability of their prohormones. We do not have pharmacokinetic research on this type of formulation; however we believe the bioavailability to be similar to orally disintegrating tablets. In addition, you can use a much larger dose because it doesn’t carry the same limitations as orally disintegrating tablets. Below we have provided a price comparison chart, which includes estimated bioavailability and the cost per active milligram.
Because of the limited research that’s currently available we will continue to follow up on any research regarding the pharmacokinetics of these prohormones and related compounds. Stay tuned for more on utilizing multiple forms (sublingual/lymphatic) to create the most efficient prohormone cycle.
1. Gas chromatography-mass spectrometry method for the analysis of 19-nor-4-androstenediol and metabolites in human plasma: application to pharmacokinetic studies after oral administration of a prohormone supplement. Torrado S, Segura J, Farré M, Ventura R. Barcelona, Spain. : Steroids., 2008, Vols. Aug;73(7):751-9.
2. Pharmacokinetics of 19-nortestosterone esters in normal men. Belkien L, Schürmeyer T, Hano R, Gunnarsson PO, Nieschlag E. s.l. : J Steroid Biochem. , 1985, Vols. May;22(5):623-9.
3. Quantitative determination of metabolic products of 19-norandrostenediol in human plasma using gas chromatography/mass spectrometry. Schrader Y, Thevis M, Schänzer W. Cologne, Germany : Drug Metab Dispos., 2006, Vols. Aug;34(8):1328-35.
4. Oral bioavailability enhancement of exemestane from self-microemulsifying drug delivery system (SMEDDS). Singh AK, Chaurasiya A, Awasthi A, Mishra G, Asati D, Khar RK, Mukherjee R. Pradesh, India : AAPS PharmSciTech., 2009, Vols. 10(3):906-16.
5. Enhanced Oral Bioavailability of Curcumin via a Solid Lipid-Based Self-Emulsifying Drug Delivery System Using a Spray-Drying Technique. Yan YD, Kim JA, Kwak MK, Yoo BK, Yong CS, Choi HG. College of Pharmacy, Yeungnam University. : Biol Pharm Bull., 2011, Vols. 34(8):1179-86.
6. Improved bioavailability of vitamin E with a self emulsifying formulation. Julianto T, Yuen KH, Noor AM. University of Science Malaysia, Penang : Int J Pharm, 2000, Vols. Apr 25;200(1):53-7.
7. Repeated administration of berberine inhibits cytochromes P450 in humans. Guo Y, Chen Y, Tan ZR, Klaassen CD, Zhou HH. People's Republic of China : Eur J Clin Pharmacol, 2011, Vol. Aug 26.
8. The intracrine sex steroid biosynthesis pathways. Luu-The V, Labrie F. Laval University and Laval University Hospital Research Center (CRCHUL), Quebec, Canada : Progress in Brain Research, 2010, Vols. 181:177-92. PMID: 20478438 .
9. 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.
10. Absolute bioavailability of testosterone after oral administration of testosterone-undecanoate and testosterone. Täuber U, Schröder K, Düsterberg B, Matthes H. s.l. : Eur J Drug Metab Pharmacokinet., 1986, Vols. Apr-Jun;11(2):145-9.