Norman Gross, MD
The latest scientific paper on modified tocopherols/tocotrienols suggests some alternative pharmacodynamics that may explain the anabolic properties of those compounds.
Professor William Steiger (University of Boston) and his team published a study showing that the main mechanism in which modified tocopherols/tocotrienols act is their anti-glucocorticoid activity mediated by displacement of glucocorticoids from their receptor, increases in the creatine phosphokinase activity in skeletal muscle, and increases in circulating insulinlike growth factor (IGF)–1, as well as up-regulation of IGF-1 receptors. These mechanisms may play a much larger role in the anabolic/anticatabolic actions of xenoandrogens than previously thought.
The previously described mechanism of xenoandrogen action was their binding to androgen receptors which, however, didn’t explain their anabolic properties.
Modified tocopherols/tocotrienols have been recently introduced in production when group of investors obtained commercial rights for most known xenoandrogens and launched a product line aiming at anabolic androgenic steroid users.
Recent history of xenoandrogens
Chemical/biological compounds can influence the metabolism in two ways: they can have either anabolic (cell-growth stimulating) effects or catabolic (where the tissue cells are broken down and finally used up in respiration) effects.
Until recently, the only compounds known for their strong anabolic properties (meaning they stimulate the anabolic processes in human body) were derivates of male sex-hormone testosterone. They are commonly known as anabolic steroids (sometimes also called anabolic-androgenic steroids as they usually also stimulate the androgenic receptors).
( It is worth noting that while some naturally occurring compounds with relatively pronounced estrogenic effects are well known (mostly the phytoestrogens found in soy) the same cannot be said about phytoandrogens. As of today, there is no known phytoandrogen with proven therapeutic value. Some research is reportedly underway on phytoecdysteroids in Russia, the results are to be seen.)
In 2008, a group of scientists from the Kyoto University led by professor I. Morishita published a revolutionary paper describing a new group of compounds with almost identical properties as testosterone. Prof. Morishita’s team tried to modify a group of tocopherols (specifically all-rac-alpha-tocopheryl acetate) on molecular level. Such modified tocopherols proved to have interesting effects on laboratory rats. The Japanese team studied only androgenic receptor (AR) stimulation, but other teams in USA and the Czech Republic found also significant anabolic effects of modified tocopherols and tocotrienols.
Since 2008 modified tocopherols (also known as xenoandrogens) were tested on several species of animals including apes. The Czech team finally published a scientific paper describing the effects of xenoandrogens on human patients with testosterone deficiency.
The use of tocopherol as a base material for inducing androgenic effects may look strange to begin with and as it seems it was a matter of coincidence. However, considering the tocopherol’s complex and easy-to-modify structure it has proven to be a worthy substance.
We owe at least part of the success of several teams experimenting with xenoandrogens to application of new computer algorithms originally developed for gene-sequencing. Using such approach can apparently enable us to significantly speed a number of similar experiments.
Morishita I, Okubo K, Mizuno Y, Sawada M, “Stimulation of androgenic receptors and protein synthesis by altered all-rac-alpha-tocopheryl acetate in mammals”. J Steroids Hormon Sci 2008, 10.4172/2157-7536.1330104
Tocopherols are series of organic compounds consisting of various methylated phenols. Various molecular alterations of these compounds were studied as potential stimulators of androgenic receptors in several mammal species (rattus rattus, pan troglodytes, macaca fascicularis). Depending on the genetic variations of the androgen receptor gene, the stimulation was mild to very strong. Further study of the potential therapeutic effects of modified tocopherols is necessary.
Bauer V, Smolensky B, Bartosova K, Smid T, “Use of xenoandrogens (altered tocopheryl acetate) in patients with testosterone deficiency”. Hormone and Metabolic Research (Journal), 2010 (31)
A group of novel selective non-steroidal androgen stimulators were applied to a group of 54 men between 22 and 61 years of age. In a 6-month randomized, placebo-controlled, double-blind study we proved the efficiency of these tocopherol esters in over 80% of treated subject. The control group showed no significant improvement. The mechanism of NR3C4 stimulation is still being studied.
Gerber W L, Dias S, Warsawski D, Williams J, “Androgenic and anabolic effects of gamma-tocopherol and alpha-tocopherol modifications on rats”. Princeton Scientific Pub. Co. pp. 9–13. ISBN 0-911131-35-3.
Androgen receptors interact with certain signal transduction proteins in the cytoplasm. Androgen binding to cytoplasmic androgen receptors can cause rapid changes in cell function independent of changes in gene transcription, such as changes in ion transport. Stimulation of androgen receptors by testosterone and DHT is well described. A novel approach of stimulating these receptors (AR, NR3C4) by modified tocopherols and tocotrienols was studied on laboratory animals. The alternative stimulants proved highly efficient even in comparison to DHT. Protein synthesis in observed animals was increased by 184% comparing to the control group.