Know About Hormones

Without a doubt the revelation of the supplement industry these past few years have been the advancement in technology where legal steroidal nutrients are concerned. Through an act, the DSHEA, some steroidal nutrients are now considered legal supplements when they meet three criteria. The first being that they have to be naturally occurring, the second being that they are currently not classified as Schedule III drugs and the last being that they have not been previously pursued as a pharmaceutical prior to their production as a supplement. This has brought us a series of steroidal nutrients we call prohormones. Substances that are largely inactive, but convert to known steroids in the body by way of enzymatic interference. So far precursors to the steroids boldenone, testosterone, nandrolone and DHT have been successfully marketed. It seemed like a ray of light towards making supplementation compete with illegal steroids, a road many are not willing to take. But prohormones had two very distinct problems to overcome.

One was the fact that they are only partially active through conversion to another compound. That meant only a small percentage (ranging from 0.08 to 30%) of what was used was finally converted to an active muscle-building substance. The second problem was that of maximal delivery. When ingested, steroidal nutrients (prohormones and steroids alike) are broken down to a large degree in the body because the liver identifies them as toxins (since they are not usually absorbed by the body, but made by the body from cholesterol). This meant that most of them were only absorbed for 4-6% in the body, with the exception of 1AD (14%) and 1,4-andro (45%). And even those last two were a far cry from what steroids usually deliver.

The World's First Legal Active Steroid.

Speaking of 1AD. It was a novel prohormone, the first marketed since the classic testosterone and nandrolone precursors, invented by the chemist Patrick Arnold. Among those in the supplement industry, it's now a household name. For those of you not so familiar, he is also the owner of LPJ research and Ergopharm, a leading company in the prohormone industry. It converted to something Patrick had dubbed 1-testosterone. A more befitting name would have been dihydro-boldenone. Structurally it's very much like boldenone (equipoise) with that difference that its 4,5-double bond has been broken and two hydrogen atoms attached at those locations. This is the same thing that occurs when testosterone is altered by the 5-alpha-reductase enzyme to form Dihydrotestosterone (DHT). 5-alpha-reduced forms of hormones have two distinct qualities. They are not capable of interacting with the enzyme aromatase, a structure that is responsible for the majority of estrogen in the male body. Even though most of them bind to the enzyme with great affinity, it cannot be structurally altered to form estrogen. In a way this lends them certain anti-estrogenic properties as whatever aromatase enzymes they do take up, cannot be used by testosterone or another aromatizing steroid to form estrogen either, lessening the risk of potential estrogen formation. But most importantly, a lack of estrogenic action makes for smaller, but much leaner results since estrogen is a major culprit in the accumulation of water and body-fat. Another major plus that a 5-alpha-reduced hormone has is that it has higher androgen binding, meaning its more potent in regards to strength and androgenic properties than the base hormone.

So why am I telling you all this? Well shortly after the appearance of 1AD, suddenly some people realized that its conversion product 1-testosterone (or dihydroboldenone) has in fact never been used pharmaceutically and is not a classified Schedule III drug, and with that... completely legal. This meant the answer to the prayers of everyone in this industry as we now possessed a legal steroid to help us bridge the gap between illicit drugs and legal supplementation. To determine what sort of drug we are dealing with here, we look at its closed compound in relation, namely methenolone (as in Primobolan). This is basically the same drug but with a single alteration. It has a 1-methyl group attached to increase its oral bio-availability. The 1-methyl structure does very little otherwise, apart from possibly increase its affinity for serum-binding proteins. One can therefore liken the effects of 1-testosterone to those of Primobolan. In fact they should be almost identical.

The attachment of a methyl group is a common practice to make steroids more orally available, which is our second concern after all in bridging the gap. But its also an alteration to the base nucleus of the steroids and forms a different steroid so to speak, even though the actions may very well be identical. Nonetheless, this difference is the only reason 1-testosterone is a legal supplement. The downside was we are now left with a full-fledged steroid, but only capable of delivering about 14% if ingested.

Solving Delivery:

Oral delivery has always been the method most preferred. But orally meant that most of what you took would ultimately be destroyed by the liver unless protected in some way. The most effective way was to attach a methyl group at the 17-alpha position. This greatly improved uptake, well over 80% in most cases. Unfortunately it was highly liver toxic. 17-alpha-methylation is basically illegal anyway, but even if it hadn't been, few would risk marketing an over the counter supplement that could damage the liver. The liability is too great. In some cases they attempted to attach the methyl structure to the 1 position, as with primobolan and proviron. This had less success and required rather large doses be taken for proper effect. And in this case it was excluded either way, because that would make 1-testosterone into methenolone, which is a Schedule III drug.

Injecting is of course the means of preference among pharmaceuticals. Its delivered into the muscle and released into the blood and doesn't reach the liver until its already traversed your entire circulation at least once. As such it can easily deliver 98-100%. Injecting is, you guessed it, illegal. The danger of promoting intramuscular injection was too great (if a blood vessel was hit and injected into the consequences can be catastrophical). Nonetheless that has not kept some companies from making a few lesser prohormones into an injectable form. Do not be fooled by such things. There is nothing to take care of conversion, requiring large doses be taken, its illegal to attach an ester for prolonged action, which insinuates daily injections and lastly there is no real quality control among supplements, meaning an infection is easily obtained and a company cannot be held responsible, as they will never market it as an injectable.

For those willing to take the risk and looking to cook up a 1-testosterone injection, think again. It turns out this stuff is quite irritating and makes for very, very painful injections. This may very well be why methenolone is preferred over 1-test, and an ester is attached, to make interaction with surrounding structures and thus irritation less of a factor. Needles, I mean needless to say injection was not an option and could invoke any number of legal problems that could easily render the world's first legal steroid, illegal.

Another way of delivery that comes highly praised from the research, is rectal administration. For those of you who have not yet burst out in laughter, it is quite effective and for the first time the idea of lymphatic absorption pops up here. Lots of pharmaceuticals have been made into suppositories and used with great success for a speedy delivery. This includes common pain and discomfort medication. However, two problems arose here as well. The first being that, considering the irritative properties of 1-test on skin and stomach, it may not have been a pleasant thing to shove this stuff where the sun doesn't shine. The other reason clearly being that there is a very small market for a supplement called Rectabol, and that it would not be easy to sell.

Lastly transdermal delivery was an option. It consists of making an alcohol suspension of the steroid and applying it to the skin. The skin can absorb substances that are below 500 in molecular weight and are lipophillic (since skin protects us from the elements, hydrophilic substances pass with great difficulty). On the one hand transdermal delivery is our savior because a good transdermal can deliver 20-25% easily which is a more than noteworthy improvement over the classic prohormones that only provide 4-6% orally, and even 1AD and the subject at hand, 1-testosterone, that deliver roughly 14% (increased resistance to hepatic breakdown due to the structural 1,2-double bond). On the other hand its our enemy, as we already know that the dermis, a layer of the skin has a rate limiting factor. That means even with the best means in the world we can only get about 30% through, maximum. Which leaves us stranded quite distant from actual steroid efficacy.

Nonetheless it's the greatest triumph to date and transdermal 1-test products such as ONE and ONE+ by Avant Labs and Higher Power's Trenabol-X are the most effective supplements currently available over the counter, hormone wise. For the record, transdermal delivery is frowned upon by the FDA as well, stamped as being a pharmaceutical delivery technique not suited for supplementation, which is why all transdermals are marketed as cosmetics. Again 1-test seems to deliver a slight problem with this type of delivery. Its irritative properties can cause rashes and such if the user starts to sweat heavily or body temperature goes up. Its occurrence is not wide-spread, but it does happen.

A Legal Alternative.

The answer was to actually be found in esters. Esters are carbon chains attached to a steroid at the 17-alpha position to make them more lipophillic. When injected intramuscularly that means they will remain in the adipose layers for some period of time (largely dependent on the size of the ester and the time it takes to break it down) and released into the blood stream slowly. This makes for less frequent injections, often only once per week. Obviously this is not where I'm headed. Injecting is illegal, and so are esters.

But the lipophillic property of esters have been put to test in another way. A more recent steroid, called andriol, tried to address oral availability issues with the use of an ester. Namely through lymphatic absorption. To understand this, you need a small notion of what the lymphatic system is and how it works more or less. First of all there is the cardiovascular system which apports nutrients and oxygen to tissues in the body, but also water. It delivers these to the interstitial fluid of tissue, the fluid that is in between different cells. The problem is that eventhough the blood will deliver about 24 liters of water to the cells through its arterial system, only about 20 liters of that is resorbed by the venous system. That means daily 4 liters are left behind. If that fluid were to remain there, we would swell up and explode.

Well, the lymphatic system is the answer to this problem. It's a fine system of capillaries located inside interstitial space that reabsorbs water. It channels all this water through a wide network of filters and delivers it to a place called the angulus venosus, where the vena jugularis interna and the vena subclavia meet, prior to going to the heart. What is of note here is that what passes through the lymphatic system is delivered straight up near the heart and bypasses the liver. Interesting, but it only carries water right ? Wrong. The lymphatic system is very well protected with more filters than anything. Almost nothing passes through. This is absolutely necessary or else any toxin or virus that entered would be delivered to the heart and be spread through the body immediately, often with death as a result. Lymphatic fluid is clear because its basically nothing other than water. Except when it comes from the gastrointestinal tract, then it has a dirty, troubled look to it. That's because in this part of the lymphatic system, fats too are absorbed. This is where it becomes interesting. An ester, as mentioned, increases the lipophillicity of a steroid which is already lipophillic. So you create a superlipophillic substance. So who cares if nothing but fat is absorbed ? Well, making it superlipophillic means it will interact with any type of fat it comes in contact with and bond. Meaning when the fat is absorbed lymphatically, so is the steroid attached to the ester.

This is the way in which the steroid andriol works. It's a form of testosterone, with an extremely long ester attached to it, then submerged in a type of oil (since the fat is what actually gets absorbed) and sealed in a cap. While it showed some clear problems, it was novel, it worked and it did not have toxicity problems like a 17-alpha-alkylated steroid would. And eventhough its rate of delivery showed it to be very inconstant not only from person to person, but even day to day, its average of success was much much higher than any legal system that had been devised to date, including transdermals.

But what does it mean to us? Well one could attempt to attach an ester and wipe his ass with the law, as one company has done, but this is not extremely interesting. And moreover the ester they selected was short and quite useless. This was a first failed attempt. The breakthrough came when a more suited compound was found. Even though they would not ultimately solve the problem, it was the company Syntrax that clearly led the way to breakthrough. They were the first to toy with the idea of lymphatic absorption and came across an ether (tetrahydropyranyl), which would lend similar lipophillic increasing properties to the steroid if attached the steroid. But Syntrax's entire line contained a main flaw. It was not readily absorbed lymphatically.

First of all, the problem was the lack of a fat to serve as a carrier. Without it the steroid would not be absorbed lymphatically. And secondly a number of extremely hydrophilic cap fillers such as barley. This made it so most of the stuff was ultimately passed on to the liver at some time. Case and point is their product Pentabol Extreme, a 5-diol THP ether. If the 5-diol had increased its potency somewhat it would begin to show properties similar to its illegal 17-alpha-alkylated form methandriol, a well-known steroid. Yet the results stayed out. At 3 doses of 225 mg each and per day, Pentabol delivered no mentionable results. That's well over 10 times the dose one would take of methandriol. So what hope did it have to make 1-testosterone more like legal Primo? None, but it did not stop them from trying. The product SAUCE showed no real increase in delivery and provided no better results than the cheaper and more effective transdermals. But Syntrax no doubt laid the foundation for the breakthrough that will follow.

Molecular Nutrition, a small company owned by Bill Llewellyn, known to most of us as the author of Anabolics 2002, was the first to chance it and invest in a properly designed carrier. Molecular took the same THP form of 1-testosterone as a base but mixed it in a fatty environment, in this case sesame oil. The oil would serve as a carrier for the steroid when absorbed lymphatically, effectively by-passing the liver and delivering the steroid through the ductus thoracicus (the main artery in the lymphatic system) to a point of insertion near the heart, from where it would spread quickly throughout the body. They then sealed it in a gel-cap of 1/2 ml, providing us with a legal form of Primobolan at 25 mg per cap. On the one hand the delivery is not as good as 17-alpha methylation, but then neither is 1-methylation, requiring high doses be used of Primo, 150 mg per day. Therefore, for most people an equal dose of this product, dubbed 1T-ethergel should do the trick in giving the same benefits as Primobolan.