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What Are Cyclodextrin Supplements

Posted by Admin

THE NEXT STEP IN PROHORMONES: CYCLODEXTRIN COMPLEXES (SCCs)

By LPJ Research.

Prohormones (metabolic precursors to male sex hormones such as testosterone) are a relatively new product category in the nutritional supplement industry, however within a short time span their popularity has increased dramatically. This popularity is undoubtedly due to the implicit attraction of the nature of their actions (testosterone makes men stronger, more virile, more energetic) and to their ever more apparent efficacy when actually taken.

The fact remains, the existing technology of prohormone delivery, specifically the simple oral encapsulated preparations, are rather crude. In describing the actions of these oral prohormone products, one may use the military analogy of the saturation bombing of a wide area with the intent on the simple destruction of a small and specific target. This is obviously a wasteful and unnecessarily damaging practice. What would most desirable would be a prohormone "smart bomb", one that would deliver the desired effect with a minimal dosage and minimal stress on the body.

This is where the new cyclodextrin technology comes in. This technology, as it applies to steroid hormones, has been patented and written about extensively in several prestigious scientific journals. However, the intent for its usage was for active steroid hormones like testosterone, estradiol, and progesterone. What LPJ Research has done is apply this technology to prohormones, developed the production processes, and then had the final product university tested in live human subjects.

THE TROUBLE WITH REGULAR ORAL PROHORMONES

Lets examine what happens to a regular prohormone that is taken orally. In this case lets use 4-androstenediol (4-AD). 4-AD is a common precursor to testosterone similar to androstenedione (it is in fact considered to be the state of the art, next generation testosterone precursor, compared to androstenedione). The 4-AD cap is ingested and makes its way to the stomach. In the stomach, the capsule disintegrates and the 4-AD crystals disperse (they do not dissolve) in the liquid that you hopefully washed it down with. This suspension of 4-AD crystals then makes its way into the small intestine, where absorption takes place slowly. When the 4-AD is absorbed through the small intestine its first route is to the liver. There is no other way, it's an express lane that has to go to the liver immediately. In the liver, the 4-AD is for the most part chopped up and deactivated. In other words, the vast majority (probably >95%) of the 4-AD will be metabolized into inactive substances that will then be excreted. A small amount will metabolize into testosterone while in the liver, and another small amount will get through as unchanged 4-AD (which will then later metabolize to testosterone in extrahepatic (outside of the liver) tissues). To sum it up then, most of the oral prohormone a person takes is being wasted, and in the process putting a hefty burden (although not enough of one to be acutely toxic) on your liver.

CYCLODEXTRIN COMPLEXES

LPJ research has found a way to overcome this poor bioavailability / liver overload problem. Actually that is incorrect, other scientists have found a way, but LPJ recognized this technology and applied it to prohormones. What we are talking about specifically here is cyclodextrin complexation of steroids, in our case, steroid prohormones. What are cyclodextrins? Cyclodextrins are a form of carbohydrate, or sugar molecules linked together. They are formed by an enzymatic synthesis starting from starch. The enzymes, called transglycosidases, are derived from bacteria. What these enzymes do is couple the starch molecules together to form a truncated conical molecular structure with a hollow cavity inside. Picture each cyclodextrin molecule as one of those silly megaphone things that cheerleaders use at football games to rile up the crowd. That is basically what they look like.

CYCLODEXTRIN MOLECULE

What makes these cyclodextrin molecules so interesting to us, and to the drug industry in general, are certain unique properties that I will explain. The inside of this cyclodextrin "cone" is just about the perfect shape and volume to fit a steroid molecule in to. It is also of a chemical nature called non-polar (fatty or oil like) that allows it to latch on to the steroid molecule. However, while the inside of the cyclodextrin cone is non-polar (fatty like), the outside is polar (water like). What is the significance of all this? Well, when a steroid molecule and a cyclodextrin molecule hook up they form a 1:1 complex. Picture cyclodextrin as sort of a "molecular condom" for steroids. The remarkable thing about this condom complex is that it is water soluble. So while steroids themselves will not dissolve in water, a cyclodextrin/steroid complex will.

SUBLINGUAL CYCLODEXTRIN COMPLEXES (SCCs)

OK, so we know that cyclodextrins complex with steroids and render them water soluble. How does that translate into a better mouse trap for prohormones? The answer to that gets pretty complex. Basically what it does is make steroids far and away more absorbable through the oral mucosa (the surface area of your mouth). The explanation for this involves the painfully slow and tedious breakdown of plain steroid crystals in your saliva to particles small enough to aborb through cell membranes compared to the extemely fast and efficient flux of individual steroid molecules out of the cyclodextrin complex and into the cell membranes.

Why is finding a way to make steroids extremely absorbable through the mouth so important to us? It is because the mouth is rich in blood flow and that blood flow goes out the rest of your body and not straight to the liver. As a result, steroids that are absorbed in this fashion will not undergo the massive liver first pass mutilation that plain oral steroids (non 17alpha-alkylated) do, and therefore be available for conversion to testosterone in other tissues of your body. Tissues such as muscle and brain, the two that are most important to us.

Let us look now at some of the clinical research that has been published on sublingual cyclodextrin complexes (SCCs) in humans. At the forefront of this research has been Josef Pitha of the U.S. Department of Health and Human Services. Pitha has several patents on sublingual steroid cyclodextrin complexes . He also has a journal article where he details the results of a SCC of testosterone on men . Pitha found that a SCC containing 10mg testosterone per tablet raised testosterone levels astronomically high (900% over baseline at one hour .) At 2 hours, the levels were still elevated 485%. On the other hand it is known that regular oral testosterone at 20 times the dose used in this study raises testosterone only around 500% at the peak.

Another study performed by Stuenkel et.al. showed that testosterone SCCs of 2.5 and 5.0 mg raised testosterone levels in hypogonadal men 2341% and 4270% (absolute increases of 1765 ng/dL and 2406 ng/dL) respectively. The average time to maximum blood testosterone levels was around 20 to 30 minutes, however, even at 8 hours post dose, the testosterone levels were still elevated 126% for the 2.5mg dose and 195% for the 5.0 mg dose. Interestingly enough, the peak levels for estradiol were only increased 300% and 340% over baseline respectively. Remarkable considering that one usually sees estradiol levels increase proportionally with testosterone levels with other forms of administation (i.e. injectable esters and TU orals).

So it has been shown that SCC's are very effective for active steroid hormones. However how do we know if they offer any benefit for the administration of prohormones? In an effort to answer this question a clinical study was undertaken recently at Eastern Michigan University. Mind you, this study has yet to be published so I have to be very careful about how I report on the results here (cannot give absolute numbers at this time, only percent increases) otherwise the researcher may run into problems getting the study published. Once it is published however, the details can and will be released in their entirety.

This study examined the acute responses to 25mg and 50mg doses of a 4-androstenediol SCC (Cyclo-Diol) in healthy males. These males (the same seven that took part in the original EMU 4-androstenediol study recently presented in Finland) had average baseline testosterone concentrations in the high normal range. The results, expressed as average percent increases over baseline, are as follows.

Lets examine the results of this study and compare them to the results that these same seven subjects had a few months earlier with regular oral 100mg 4-androstenediol capsules.

As you can see the % increase at peak is much higher for the 25mg SCC (128%) than it is for the straight oral (49%). That translates to a 261% greater testosterone increase with the SCC over straight oral at one quarter the dosage!!

Also you may notice the difference in the times to peak blood values for the SCC versus the straight oral. The time to peak is much sooner for the SCC than it is for the straight oral; 40 minutes vs. 90 minutes.

Furthermore, the drop off in the levels for the 25mg SCC is quite gradual with testosterone increases at 2 hours still well above the peak levels seen with the straight oral 100mg.

One of the most intriguing findings from this study was that a 50mg dose was no more effective than a 25mg dose. From talking to other experts in the field, I have come to gather that this is likely due to the limited capacity for absorption through the sublingual tissues. There is only so much surface area under your tongue. We wonder then whether or not a 10mg dose of androdiol SCC (or even a 5mg dosage) might not be equally, or almost as effective, as a 25mg dose. LPJ may examine this in an upcoming study.

Another note of interest from this study was that the variablity of testosterone responses among subjects taking the androdiol SCC was extremely low. This is in contrast to the oral androdiol study where some ubjects had increases of testosterone over 100%, while others had increases of barely 25%. This leads us to believe that the biggest factor in the variable responses to prohormones may not be differing levels of conversion enzymes throughout the body as is generally assumed but rather differing absorption capabilities from the gut and/or the differing capacity of peoples livers for deactivating orally ingested prohormones upon first pass. Therefore,when taking prohormone SCCs one can be assured that they are getting the testosterone elevation response that is promised them. And at the same time saving their liver from the task of processing a megadose of prohormone.

CONCLUSION

Well, there you have it, the future of oral prohormones are SCCs., they are undoubtedly the most effective and safest way to go. And due to the low variablity in responses from person to person, the most reliable way as well.

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