What is 11-OXO?
11-OXO is the trademark name for adrenosterone. Adrenosterone is an adrenal androgen. Adrenal androgen means it is a hormone produced by the adrenal gland that is in the same general hormonal class as testosterone (another example of an adrenal androgen is DHEA).
Adrenosterone is released by the adrenal gland in conjunction with other stress hormones, primarily cortisol and cortisone. The exact function of adrenosterone has never been fully understood, however recent research seems to indicate that it serves to modulate the actions of cortisol in the body.
Cortisol is a vital hormone made by the adrenal gland and it is considered a stress hormone. When your body is stressed it seeks to quickly liberate energy stores and cortisol assists this by stimulating the breakdown of muscle protein to amino acids and stored triglycerides (fat) to free fatty acids. It also instructs the liver to up-regulate its systems for processing these fuels - the gluconeogenesis pathway for amino acids and the beta-oxidation pathway for fats.
The catabolic consequences of elevated cortisol on muscle tissue is pretty clear-cut and well understood by most bodybuilders. The effects of cortisol on body fat content and distribution, and on vital metabolic pathways in the liver however are not. Even less understood are the tissue specific controls that activate and deactivate cortisol on a local level throughout the body. I am talking about enzymes located at places like the liver, visceral fat, brain, vascular tissue, and (yes) skeletal muscle that serve to control whether cortisol is activated or deactivated within these tissues themselves. It is these enzyme systems that scientists are now recognizing as perhaps the most significant metabolic aspect of cortisol in regards to body composition, heart disease, diabetes, and other maladies that together have come to be known as Syndrome X. And most importantly, it is this localized enzyme system that holds spectacular medical promise as a pharmacological target to greatly improve health and physical fitness
Fat and cortisol
I mentioned how cortisol release liberates fat for use as energy. Upon hearing me say that you probably thought to yourself that cortisol must have an overall effect in the body of reducing body fat. That is not the case however. Cortisol affects fat metabolism and storage in the body in a multitude of ways. To best achieve an overall understanding of cortisol’s effect on body fat we should keep mind of cortisol's overall purpose in the body, which is to help your body respond to stress. Cortisol controls both immediate and long-term adaptations to stress within the body. Of course the immediate effects on body fat are the release of energy in the form of fatty acids, but cortisol also goes to work on setting the stage within your body so that it will have an ample resource of the most easily accessible body fat stores to draw upon in the future.
What I mean by the most easily accessible body fat in the body is the kind of body fat that cortisol can most readily tap into when urgent fatty acid energy is needed. I am talking here primarily about visceral fat. Visceral fat has a direct root to the liver via the portal system so it is perfectly positioned to provide a quick supply of fatty acid fuel for immediate processing. Simply put, this is the fat located around your internal organs. It is the fat that gives you the potbelly look and it is also the fat that is most closely associated with health risks such as heart disease, diabetes, and perhaps even cancer. For me personally, as it is for many adult males, visceral fat is a constant source of disgust against which I fight a constant battle.
What cortisol does in the body over time is switch the distribution of fat away from the more stubborn areas (such as the subcutaneous fat in the extremities) to the more highly cortisol sensitive areas of the body. These areas include the viscera as I mentioned already but also include oddball areas such as the upper back and face. The classical phenotype (physical appearance) of the individual suffering from cortisol excess is the pot belly, buffalo hump, and moon face. Not a pretty sight I know.
Cortisol and the liver
Ok now what about the effects of cortisol upon liver. If you are a hopeless muscle head you may be asking why should I give a damn about my liver? Well I will explain to you why, and you will see that for several reasons the negative effects of cortisol on the liver can have a profound impact upon your ability to build muscle. The liver is the number one target of cortisol in the body and it is also the number one area where it is metabolized. Cortisol has a ton of actions in the liver but to make this short and sweet I will stick to the ones that are most relevant to bodybuilders.
First of all, cortisol affects carbohydrate metabolism. It lowers insulin sensitivity and switches on the pathways of gluconeogenesis. Gluconeogenesis is the formation of glucose from non-carbohydrate precursors, primarily amino acids. What this means is that it turns your liver into an amino acid devouring machine, turning amino acids that your muscles need to grow into sugar - sugar that will probably mostly end up later being made into fat. Cortisol also negatively influences the levels of IGF-1 in the body by a few mechanisms, most notably by decreasing the IGF-1 production response to growth hormone and increasing the production of the deactivating factor IGF-1 binding protein-1. Furthermore, cortisol down regulates the T3-deiodinase enzyme in the liver resulting in a lowering of thyroid hormone activity. Look, I can go on and on about cortisol's terrible influence on the liver but I am getting as bored with the liver as you probably are right now so I want to move on. I think you get the point
Goes on and on
Before I go on to the important part of the story here let me just wrap up the background with some mention of other tissues of relevance to the physique enthusiast. Vascular tissue suffers from excess cortisol by becoming more sensitive to hormones, which influence constriction (i.e. adrenaline, angiotensin II). Furthermore, cortisol inhibits vasodilation by decreasing the biosynthesis of nitric oxide and prostaglandin 1 as well as attenuating the actions of atrial naturietic peptide. This can result in elevated blood pressure (hypertension) and a decreased vasodilatory response to exercise (in english that translates to a decrease in the ability to get a good pump). As for the brain, it is not immune from cortisol's ravages either. Cortisol reduces the release of LH, GH, and TSH from the pituitary resulting in reductions in circulating levels of the anabolic hormones testosterone, IGF-1, and triidothyronine (T3). The testosterone producing leydig cells of the testicles also are directly adversely affected by cortisol so along with the LH suppression you get a double whammy against testosterone. Last but not least are the muscles themselves which I don't have to elaborate on. You already know that cortisol breaks down muscle protein into amino acids that then get converted to glucose for energy and fat production.
11HSD1R is the target
So now onto the main point. All of these parts of the body that are influenced by cortisol action contain the enzymes I mentioned earlier that control the local concentration of this dastardly hormone. Which means all these tissues are targets for enzyme blockers that will protect them from all of this. And that is what this is all about. It is not just theory either; the practical solutions are actually presently attainable. Now lets talk about the enzymes themselves without getting too bogged down in laborious technicalities (I hope).
Cortisol belongs to a group of hormones collectively known as glucocorticoids. Glucocorticoids are steroid hormones just like testosterone, progesterone, and estrogens are. The hallmark of an active glucocorticoid molecule is a part of the steroid structure known as the 11beta hydroxyl group. This chemical group is essential for the activity of cortisol or any other glucocorticoid. In the body, this 11beta hydroxyl group is constantly being converted into what is known as an 11-keto (or 11-oxo) group and then back again into the 11beta hydroxyl. This is what is known as an equilibrium reaction. Anyway, 11-keto's are inactive glucocorticoids and the 11-keto version of cortisol is known as cortisone.
So to summarize so far, cortisol is active and cortisone is inactive. Cortisol is an 11beta-hydroxyl and cortisone is an 11-keto.
In the blood, there is more cortisone than cortisol. So if these target tissues (fat, liver, muscle etc) want a decent shot of cortisol they have to convert some of that cortisone into cortisol themselves. And they do this with an enzyme known as 11beta-hydroxysteroid dehydrogenase type1 reductase (11HSD1R for short). In recent years a tremendous amount of research has been directed towards this enzyme and its vital role in the body. It has been recognized as a metabolic regulatory mechanism of huge significance for some of our societies most widespread and insidious health threats - cardiovascular disease, diabetes, and obesity just to name a few.
The great thing about the discovery of this enzyme and the fact that its activity can be influenced is that it offers us a method of controlling the negative actions of cortisol on the body without blocking cortisol's vital functions necessary for life. It is important to remember that although excess cortisol is undesirable, maintaining a crucial minimal supply of this hormone is essential to our health. Eliminating it or reducing it inappropriately can result in severe health consequences. In fact, this is what has been the problem with cortisol suppression approaches of the past. Non-specific approaches that reduce cortisol production (aminoglutethimide, trilostane) or cortisol receptor binding (mifepristone) basically throw the baby out with the bath water. They eliminate the problems of cortisol excess all right but in exchange they present the patient with a new set of problems - problems associated with cortisol deficiency such as weakness, loss of weight, low blood pressure, and gastrointestinal disturbances.
So what are the ways of blocking this enzyme? First of all you must be aware that there are other cortisol metabolism enzymes closely related to 11HSD1R such as 11-beta hydroxysteroid type1 dehydrogenase and 11beta-hydroxysteroid dehydrogenase typeII. You do NOT want to block these enzymes - the former will increase cortisol levels in target tissues while the latter will cause your kidneys to go nuts and raise your blood pressure through the roof. So you need a selective inhibitor. This is not easy. There are lots of non-selective inhibitors around but few selective ones.
Endogenous Inhibitors
Interestingly enough, some hormones our body make naturally are quite good selective inhibitors of 11HSD1R. Most notable are GH and IGF-1, and it is no surprise that the body recomposition powers of these hormones are not in small part due to their effect on 11HSD1R. But there are other endogenous hormone inhibitors of this enzyme, many of which are made by the same gland which makes cortisol itself and which possess many of the same key chemical structural characteristics while lacking cortisol's activity. It is these hormones that I find most fascinating and which have the potential for use by the average bodybuilder (without a prescription.) You see, in addition to cortisol, cortisone, and other similar glucocorticoids, the adrenal gland produces a strange series of steroid hormones that also possess 11beta-hydroxyl and 11-keto chemical functional groups. These include progesterone type hormones like 11-ketoprogesterone and androstene type hormones such as adrenosterone. Adrenosterone in my opinion holds the most promise for athletes a safe, effective, and selective cortisol modulating performance enhancing and body recompositioning agent and is the compound found in 11-OXO
How 11-OXO works to inhibit 11HSD1R is actually pretty straightforward. 11-OXO simply occupies the enzyme, preventing cortisone from accessing it. This is known as competitive inhibition. If cortisone cannot access 11HSD1R then it won't have the opportunity to be converted to cortisol at the target tissue. The 11HSD1R enzyme acts the same way on 11-OXO as it does on cortisone, that is it reduces the 11-keto functional group to an 11beta-hydroxyl functional group - only in this case it is converting 11-OXO into another hormone known as 11beta-hydroxyandrostenedione.
11-OXO competitive inhibition of 11b-hydroxysteroid dehydrogenase type I reductase (11beta-HSD1)
Controlling cortisol via 11HSD1R is still a new frontier but it is an area of health and physique enhancement that I feel has enormous potential and just might prove to be a godsend for a lot of health conscious individuals. For bodybuilders in particular I feel that in conjunction with other biochemical manipulations (supplements, steroids, etc.) this approach may provide an amplification of effects that are pronounced and impressive. But in my opinion all that pales in comparison to what we may see in regards to overall health, vitality, and life extension benefits. We have a real possible win-win situation here, as what we are talking about is a way to build muscle and lose fat, while extending life and overall health at the same time.
Totally natural hormone
Adrenosterone is found in the blood of both men and women. For men it is present in the blood at a concentration about 1/10 that of testosterone, and in women it is actually present in amounts roughly 33% greater than men.
In most species including humans it is produced in the adrenal gland under the influence of adrenocorticotropic hormone (ACTH). However in many fish, including salmon, tilapia, eel, trout, bass, and others it is produced in the testes along with 11-oxotestosterone (which is actually the major androgen in many fish)
*It is important to mention that being a precursor to the active androgen 11-oxotestosterone, exceeding the recommend dose and duration of use may result in increased risk of androgenic side effects and HPTA suppression. This suppression while minimal at the recommended dosage, can temporarily effect fertility and sex hormone production at higher dosages. This directed use of this product is specifically designed to selectively provide cortisol modulation while minimizing sex hormone activity. Please do not exceed recommended dosage. This product is to be used by males only.
