If you’re confused about the benefits of prohormones, don’t feel alone. When the United States Congress passed the Food Supplement act of 1994, it opened the door for formerly esoteric food supplements, including prohormones. The term “prohormones” doesn’t refer to any secret drugs used by professional athletes. Instead, it refers to steroidal compounds that can be converted into hormones in the body, including both testosterone and estrogen, as well as various hormonal byproducts and metabolites.
In the beginning, the prohormone market was simple. You had Mexican yam supplements that were wrongly thought to convert into active hormones (they do, but only with the assistance of certain enzymes not found in the human body); and dehydroepiandrosterone (DHEA). DHEA, still a popular supplement, acts as a precursor for both testosterone and estrogen, as well as a formerly little known intermediate in the steroid biosynthesis pathway called “androstenedione.”
DHEA may provide health benefits related to antiaging properties, but as a testosterone precursor, it left much to be desired. For example, in women, it nearly always converts into testosterone, but in men it’s fate isn’t as certain. In most cases, males convert DHEA into androstenedione, and from there it can take numerous pathways--including the undesirable estrogen route. While it would appear that androstenedione, which has a far more direct conversion into testosterone is a better choice than DHEA, only one man initially recognized this fact.
That man was Patrick Arnold, 33, a Seymour, Illinois-based chemist with an extensive knowledge of both chemistry and particularly, prohormones. Arnold has a bachelors degree in chemistry and 3 years of graduate study in chemistry from the University of Connecticut. When the public furor over baseball slugger Mark McGwire’s use of androstenedione peaked, Arnold was a sought-after expert on the effects of androstenedione. To provide a pure source of this prohormone, and subsequently others, Arnold formed a company called LPJ, with which he continues to pursue both prohormone sales and development.
But recent negative studies published about the effects of androstenedione have cast a pall over the use of prohormones for bodybuilding purposes. Add to this the ever increasing roster of various prohormones introduced since androstenedione hit the market a few years ago, and you can’t help getting confused about both the effects and benefits of these supplements.
The latest types of prohormones even feature allegedly superior delivery systems, such as cyclodextrins and liposomes--words familiar to some scientists, but likely to draw a blank with the hoi polloi of bodybuilding. Both refer to special delivery systems designed to optimize prohormone absorption. Cyclodextrins use a carbohydrate-enveloping effect with prohormones, while liposomes act in a similar manner using a fat-envelope. The effect is somewhat like a “Trojan horse,” allowing prohormones to bypass initial near-complete destruction in the liver. But this isn’t as simple as it appears. Are some cyclodextrin products better than others? How does liposome delivery compare with cyclos? Let’s clear up the confusion here and now by going to the guru of prohormones himself--Pat Arnold.
Q: A new type of delivery system for prohormones is about to emerge called “liposomes,” what are they, and how does this type of prohormone supplement compare with cyclodextrin prohormone delivery?
A: Liposomes are bi-layered shells made from certain kinds of lipids. These particular kinds of lipids, i.e., fatty acids, phospholipids, have a fattylike or non-polar end to them, combined with a more waterlike or polar end, and a long-chain structure. What these lipids can do in water under the right conditions is line-up in such as fashion that all the polar ends are sticking out from a center in which the non-polar ends are anchored.
The whole thing folds upon itself, giving a shell with a water-soluble exterior and a oil soluble interior (somewhat similarly to cyclodextrins). Non-polar drugs, such as steroids, can be trapped in the non-polar tails of the lipid chains in the interior of the liposome. These shells can also be formulated to have many layers, like an onion. The non-polar drugs, including steroid prohormones, can be trapped in the non-polar portions in each layer.
Some manufacturers have made prohormone liposome products, mainly for oral consumption. When a prohormone liposome is ingested, it passes through the stomach into the small intestine. In the small intestine, the liposomes come into contact with the non-polar intestinal cell lining, merging with it. Picture two soap bubbles merging together. When this happens, the prohormone trapped in the interior of the liposome is efficiently transferred into the intestinal lining. From there, it travels into the portal circulation to the liver.
Multi-layered liposomes take longer to completely merge with the intestinal lining cells and deliver their contents. So these are used to provide a more sustained delivery compared to single-layered liposomes. A product that contains different sized liposomes of various layer amounts should theoretically provide a time-released delivery of prohormones.
A single-layered liposome encapsulated prohormone should work similarly to a cyclodextrin (hydroxypropyl-beta-cyclodextrin) complexed prohormone. In other words, put the steroid in a water-soluble shell, then deposit it in the lipidlike surface of the oral or intestinal mucosa. However, the flux between the cavity of the cyclodextrin molecule and the mucosa is far more efficient and faster than liposomes. A liposome must first merge and dissolve into the mucosal cell membrane before its contents are delivered. In contrast, the cyclodextrin molecule undergoes no such interaction at the mucosal membrane, and does not disintegrate; it simply instantaneously delivers its prohormone payload.
A possible advantage of liposome delivery over cyclodextrins is that liposomes may provide a time-released delivery effect through using multilayered liposomes. However, I don’t believe that prohormones should be given in a time-released fashion, because doing is relatively ineffective.
My conclusion about liposome products is that single-layered liposomes featuring good manufacturing standards are a great oral product, and may also be effective sublingually (under the tongue). But I see little or no promise in the multi-layered, controlled release liposome products. In addition, I don’t think even the single-layered liposome products work as well as the cyclodextrin-complexed products.
Q: What happens to standard prohormones in the liver, and could they be toxic to that organ in a manner similar to anabolic steroid drugs?
A: Prohormones in the liver are for the most part metabolized into inactive end products, such as androsterone and etiocholanone. These end products are then usually conjugated with glucuronic acid, which renders them water soluble. They can then be excreted in the urine.
These processes used to metabolize natural steroid hormones are not significantly stressful to the liver. The medical literature shows that non-ankylated steroids such as these do not cause any toxic effects in the liver, even at relatively high doses.
Many doctors and uniformed scientists are lumping all androgenic steroids in with ankylated oral androgens (such as the anabolic steroids methyltestosterone and oxymetholone or Anadrol). Such synthetic ankylated oral steroids feature chemical alterations enabling them to resist certain metabolic deactivations in the liver. As a result of these alterations, a toxic burden is imposed on the liver. Prohormones, which don’t have such alterations, are therefore nontoxic to the liver.
Q) What advantages do cyclodextrin prohormones have over standard prohormones?
A: Cyclodextrin-complexed prohormones, and we are speaking here of the highly soluble hydroxypropyl-beta-cyclodextrin complexed products--not the inferior, poorly soluble beta-cyclodextrins, render prohormones water soluble and are efficiently absorbed into mucosal tissues (mouth, nasal, intestinal lining). This delivery is far more efficient compared to simple prohormone powders in capsules.
A major advantage offered by cyclodextrins is that they have good delivery efficacy through non-gastrointestinal routes, such as under the tongue, thus preventing the usual extensive first-pass liver destruction that happens with most standard prohormones. The result is a far higher blood androgen response per each milligram of prohormone administered. Cyclos will be much less bioavailable when taken orally, but they are still superior to simple encapsulated powdered prohormones.
Q: Are cyclodextrin prohormones (CPH) harmful from a health perspective in any way? For example, can they adversely affect blood lipid levels in manner similar to oral anabolic steroids?
A: Cyclodextrin prohormones, in fact all prohormones, share the same potential health risks associated with prescription testosterone and other steroid drugs. These include possible negative effects on cholesterol (lowered HDL levels); male pattern baldness; acne; gynecomastia (male breast development); prostate gland enlargement; depression of endogenous testosterone production, among others.
On the other hand, cyclodextrin prohormones may present far lower risk of certain side effects. For example, the liver is the site of cholesterol synthesis and lipoprotein production, as well as being quite rich in aromatase enzyme activity (aromatase converts testosterone into estrogen). Since cyclo products avoid first-pass metabolism in the liver, and require lower dosages, I would think that side effects such as HDL depression and gyno should be minimized by this dosage form. In fact, cyclodextrins have been shown to reduce cholesterol when taken orally. They can complex with ingested food cholesterol and inhibit the absorption of such food-contained cholesterol.
Q: What’s the optimal way to take CPH in regard to dosage, timing, with or without meals and so on?
A: CPH are only available in sublingual form now, so I’ll only comment on that. In a study conducted by researchers at East Michigan University, 25 milligrams of cyclo-diol gave similar blood responses to 50 milligrams. However, we never tested anything less than 25 milligrams, so we still don’t know if lower milligram amounts are just as effective as 25 milligram doses.
CPH should probably be taken an hour before meals, since some prohormone may still be unabsorbed in the mouth for some time after the lozenge is dissolved. You should not drink anything for perhaps 10 to 15 minutes after the lozenge is fully dissolved. I think for most young men, these cyclos should be taken at least three times a day. You can take more, but it doesn’t make sense to take more than has been found effective.
Q: Can women use CPH safely, and if so, at what doses?
A: Women can probably take a cyclo-nor-diol prohormone. I know that many fitness competitors love nor-prohormones, and cyclos are the best way to take them.
I won’t make up things just to impress you. I really have not investigated the use of prohormones by women that much, and as such, aren’t secure enough to suggest recommended dosages for them. I plan on doing some interview-type research with women nor users to determine what they are using and finding to be safe. Also, what, if any, side effects they may be experiencing. I have to do this because I think few women would volunteer for a dose-response study on an androgenic product [produces male pattern side effects, including facial hair growth, and so on].
I hope to learn a lot more on the use of nors by women, and then write an article in one of the women’s fitness magazines discussing my findings. I may even decide to market a lower dosage type of prohormone specifically for women. Any female athletes who are reading this and now using prohormones should contact me by mail at parnold8@ix.netcom.com, and discuss their results with me. I would be very appreciative for this feedback, and will certainly respect their anonymity if they wish.
Q:Are slow-release and absorption a desirable aspect of prohormone supplements?
A: I believe that sustained release oral prohormones are probably ineffective for the most part, and that the whole idea of sustained release runs counter to what science has demonstrated concerning the liver metabolism and oral bioavailability of these compounds.
The reasoning behind this assertion is based on bona-fide research showing that compounds easily deactivated in the liver require large amounts to increase blood levels. The reason for this is that large amounts will overwhelm the liver’s degradation capacity and allow undestroyed compound (prohormone) to pass through into the general circulation. In contrast, a time-released product will provide a trickle of prohormone to the liver over a longer time period. As a result, the small trickle is easily metabolized and not much will get into the blood.
I believe that oral prohormones should be taken in three relatively massive divided doses throughout the day. I’ve found this technique to be extremely effective, leading to significantly elevated blood androgen levels during most of the day. These oral doses can be given as single layered liposomes or cyclo complexes (the most orally bioavailable), or as micronized (next best, but expensive) formulations or as simple prohormone capsules (best bang for the buck as far as orals).
Q: Besides the recent adverse studies related to androstenedione, one as yet unpublished study showed some good effects related to prohormones--can you tell us about that study and what it found?
A: This study was different, in that the featured prohormone wasn’t androstenedione, but 4-androstenediol (4-AD or Androdiol). The study was done at Eastern Michigan University, and examined the effects of a dose of 450 milligrams a day of 4-AD for 4 weeks. The results showed significant lean mass gains in the study subjects, and also significant strength gains. There were no significant effects on beneficial high density lipoprotein cholesterol (HDL), although this type of “good” cholesterol carrier actually increased in the 4-AD group. In addition, the study found no adverse effects on estrogen levels, luteinizing hormone level (a pituitary hormone that controls testosterone levels in the body), and blood markers for liver toxicity.
I’m starting to sound like a broken record lately, as I have constantly tried to beat into the public mind that there’s a huge difference between 4-AD and androstenedione. 4-AD does not convert directly into estrogens like androstenedione, and is a far more efficient precursor for testosterone. This study could help further my cause, but the study author has experienced difficulty getting it published. Not because of any inherent flaws in the study, but merely for reasons of prejudice against these prohormones.
My company, LPJ, and other companies are co-funding an even more comprehensive safety and efficacy study on 4-AD next year, and I hope the sheer weight of available evidence from these studies finally forces someone to publish the data.
Q: Did the East Michigan Study use the cyclodextrin form of 4-AD?
A: No, I believe they used a simple chewable formulation, which of course involved oral intake.
Q: Would larger doses than what is usually suggested lead to better results with prohormones?
A: Undoubtedly. Dosages under 500 milligrams a day lead to so-so results. Many people have tried this, became disappointed, and then simple wrote off prohormones as ineffective. I am confident enough now, from what I’ve seen in athletes and in myself, to say that oral doses of 1,000 milligrams or even 2,000 milligrams a day of 4-diols (Androdiol or norandrodiol in a stack) lead to impressive results--even dramatic results--with no great increase of side effects. The lack of gyno seen with even mega-doses of 4-diols amazes me, leading me to wonder if the diols themselves in the unconverted form might not impart some kind of antiestrogenic activity. This is a long shot, I guess.
Larger doses produce not only greater blood androgen concentrations at peak, but a far more protracted time in which significant elevations are present in the blood. Three daily doses of 400 milligrams or so should elevate testosterone to the extent that daily blood levels are either far above normal or at least significantly elevated. This kind of cycle, however, should not be done for more than 6 to 8 weeks, and at least that much time should be taken off in between. Remember, you are elevating your androgen levels nearly all the time, so some LH shutdown due to negative feedback inhibition is an unavoidable consequence. As a result, you need to allow your endocrine system time to get going again. The same is true for androgenic/anabolic steroid drugs.
Q: Which is more expensive to produce and sell: hydroxy or beta cyclodextrins?
A: They aren’t too different as far as production costs, but the raw materials for hydroxy complexes are far more expensive.
Q: Since the hydroxypropyl-beta-cyclodextrins (HBC) is more water-soluble compared to the beta-cyclodextrins and is far superior, to your knowledge are there any commercial prohormone products currently marketed that contain the more desirable HBC form?
A: I believe Supertech, OSMO, Kaizen, Sportpharma, and my company, Ergopharm, sell HBC complexed prohormones.
Q: Do you think that the recent adverse publicity related to androstenedione will turn-off consumers considering the use of any type of prohormone supplement?
A: I don’t think, I know. I sometimes end up talking to strangers in gyms and health food stores around the country, and when the subject of prohormones comes up, the general response is “I’m scared of that shit” or “I’ve heard it makes you grow tits” [an objection presumably voiced by males only], or something like “I’ve tried that Andro-6 stuff and it didn’t do anything for me.” The media succeeded in imparting a big scare into consumers regarding prohormones following the publication of those adverse andro studies. That, coupled with the fact that many people tried the stuff at the old recommended dosages that I know to be suboptimal and ineffective, led such people to conclude that prohormones are just a ripoff. This has hurt the industry somewhat. Because of all these misconceptions, I’ve been trying to re-educate people about the differences between diones and diols, and what dosage patterns and forms should be used to see the promised results.
Q:Do you think the Food and Drug Administration (FDA) is trying to remove all prohormone supplements from the market? How would they accomplish this?
A: I don’t think the FDA is trying to get rid of prohormones, but the Drug Enforcement Agency (DEA) is certainly zealous in this regard. The FDA has limited power, and can’t remove prohormones from the market unless they prove clearly toxic in some way. Since, thus far, this toxicity hasn’t emerged, the FDA can’t act yet.
But the DEA, which also monitors illicit anabolic steroid usage, has their sights set on prohormones. Now, the target is just androstenedione; however, if the DEA can get rid of androstenedione, the other prohormones will also go like dominos. Federal drug czar, Barry McCaffrey, has publicly stated that he has an agenda to remove that “dangerous andro” from the market for the sake of our children’s lives.
The plan, as I know it--and this isn’t a secret--is for the government to fund a test (probably on animals) that provides massive amounts of androstenedione, possibly by injection, to prove there is some anabolic activity. Without a doubt, androstenedione is anabolic at megadoses, and when they find this, they can then say that androstenedione fits all the classifications of being an anabolic steroid under the 1990 Anabolic Steroid Control Act. Androstenedione would then be categorized as a class-3 controlled substance, meaning that possession of it will constitute a felony.
Since no one can show that prohormones are overtly dangerous, I can only deduce that our government considers muscle building to be a threat to society. What other explanation can there be?
Q: Considering the recent studies showing adverse effects associated with androstenedione, do you now consider this prohormone ineffective, or still useful for some purpose?
A: I consider androstenedione too weak and too much of an estrogen precursor for chronic bodybuilding use. However, I think it may be quite effective as a libido booster, since both androgens and estrogens are responsible for sex drive.
Q: In terms of anabolic effects, how do prohormone supplements compare to actual anabolic steroid drugs?
A: Anabolic steroid drugs have varied abilities to pack on muscle weight and different propensities for water retention. Regarding prohormones, the 4-diols at high dosages seem to produce gains similar to moderate doses of testosterone and nandrolone. I’m speaking here of doses equal to 1,000 to 2,000 milligrams of 4-AD, nor-4-AD, or a daily combination of both. I realize that people are likely to roll their eyes upon reading this and say,”Here goes the bullshit again,” but I say let them go out and give it a try for a few weeks.
Q: Would the side effects, if any, for CPH be similar to that of anabolic steroid drugs?
A: On a qualitative basis, the side effects from 4-AD are similar to testosterone as far as water retention and androgenic effects go, but the gynecomastia risk seems to be substantially lower. The side effects from nor-4-AD are qualitatively similar to nandrolone.
Q: Should certain people avoid taking any type of prohormone supplement?
A: Anyone who has a medical contraindication to avoid androgen drugs, such as testosterone or nandrolone esters, should not use prohormones. This includes people with prostate cancer, breast cancer, and those who have not yet reached full linear growth (final height, as in teenagers). To find out other examples of people who should avoid using prohormones and associated precautions, as well as possible side effects, check the entry for “testosterone” in the Physician’s Desk Reference.
Q: Since testosterone appears to play a role in prostate gland enlargement, should men with this condition avoid using prohormones?
A: Not necessarily. They may be able to use a 5-alpha-reductase inhibitor [such as finisteride or Proscar] with their 4-AD and still be okay. Or better yet, they may find that a nor-prohormone like nor-4-AD actually helps their prostate by competing with testosterone (more specifically, norDHT competing with dihydrotestosterone, the testosterone metabolite responsible for prostate enlargement) in the prostate, resulting in far less androgenic stimulation and growth. However, I must advise anyone to check with their doctor first--even though their doctor is likely to be clueless about the subject, and too scared to suggest anything but staying away from all prohormones.
Q: Some people have suggested that 19-nor prohormones may cause impotence due to a progestinlike structure--is this possible?
A: This is sheer baloney. Nandrolone does have a weak progestogenic activity, but even so, progestins have never been implicated in reducing libido. The only exception to this is when the progestin in question also had antiandrogenic qualities, due either to cell receptor antagonism or indirectly by suppressing luteinizing hormone from the pituitary gland.
But it’s true that 19-nors may decrease libido or sex drive by competing with testosterone at the level of the central nervous system, i.e., in the brain. This results in less androgenic stimulation in brain centers controlling sex drive.
Q: Are there any specific food supplements or nutrients synergistic with prohormones?
A: I hate that word “synergistic,” because it’s so often misused and abused in the supplement industry. I would say there’s nothing synergistic out there, but a high protein diet that also supplies other ergogens can only help increase gains during a prohormone cycle.
Q: Should people concerned about androgenic side effects, such as male pattern baldness, acne, and prostate enlargement, stick with only 19-nor prohormones?
A: For the most part, yes, if they want to play it smart.
Q: What are the maximum and minimum effective doses for CPH?
A: I have to admit that at this time, I don’t know. What I do know, based in the results of the East Michigan University study discussed earlier, is that taking more than 25 milligrams at one time won’t do any good. The optimal dosage lies somewhere between 5 and 25 milligrams, and I will someday find the precise dose.
Q: Can taking CPH 3 times a day or more lead to a feedback suppression of endogenous testosterone synthesis?
A: Used 3 times a day, I don’t think so. At least I know that cyclodextrin testosterone taken 3 times daily resulted in suppression only while the testosterone levels were elevated, and when they returned to normal, so did LH. I would expect the same to be true for CPH. I don’t know at which level over 3 times a day that you would reach a level of suppression that would not fully return readily to normal testosterone output.
Q: Would using any of the CPH forms of prohormones increase aggression?
A: My view on the entire ‘roid rage thing is that people who are assholes tend to be worse assholes when they build muscles. People with normal temperaments just get more confident for the most part.
Q:Are there any currently available natural estrogen antagonists that are effective?
A: I think indole-3-carbinol and its derivative, diindolymethane, are potentially effective compounds. However, I don’t know how well they are working in the real world at this time. I introduced a flavone called chrysin in 1996. But I always demanded that in-vivo testing be done before it was marketed. Despite the lack of such “in the body” tests, various companies marketed it based solely on hype.
Last year, my company, for a measly $350, funded a simple test on chrysin using rats as subjects. We had several groups, such as those receiving the chrysin as injections, orally, or other rats given a placebo for each of these. The results showed no effects of chrysin on estrogen, but the rats did get fatter after using chrysin.
Q: Regarding DHT, the “bad byproduct” of testosterone linked to male pattern baldness, acne, and prostate enlargement, some people suggest that the herb saw palmetto may reduce DHT synthesis. Would it be a good idea to take saw palmetto concurrently with CPH?
A: No, unless you are taking the herb for some health reason. The problem with saw palmetto is that it may potentially reduce the effectiveness of prohormones.
Q: To your knowledge, are there still untapped possible prohormones that have yet to be marketed?
A: As far as androgenic prohormones, I know of at least one that still isn’t marketed. But it has no advantages over the current best types of prohormones that are available, so there isn’t any actual reason to market this particular substance. I believe the androgen prohormone possibilities have been exhausted as far the best ones go. Someone may place a synthetic (perhaps unknowingly) on the market and call it a prohormone, but that’s breaking the law, and not what we’re talking about.
I do know of a steroidal prohormone that isn’t androgenic, yet may have some valuable athletic benefits. I don’t want to discuss anything more about it now, but this will definitely be a future product of my company.
Q: What type of future effective delivery systems for prohormones do you anticipate; in fact, what do you view as the future of prohormones in general?
A: I think an aqueous solution of cyclo prohormones, taken intranasally, would be quite effective, especially prior to a workout. The nasal passages go high up into the head, right next to the base of the brain. Absorption through these membranes should promote an amplified central nervous system effect. I have, in fact, made these for my own use and found them to be potent enough to feel right away.
I have developed a sustained-release cyclo product made to stick in a particular part of the mouth and dissolve very slowly. This product will provide both the high bioavailability of cyclo prohormones taken through a route that bypasses the liver, as well as a sustained release into the blood. On top of that, with this product there is virtually no bitter taste problem as is the case with sublinguals. I said earlier that sustained release delivery of orals is a bad concept because of liver degradation. However, this new product, being better absorbed through the lining of the mouth, doesn’t undergo first-pass liver metabolism, and thus is very suitable for sustained release. This stuff required extensive research and formulation work to get right, so I would expect that anyone who tries to produce a knock-off product would probably create a crappy and obvious counterfeit.
©,2013 Jerry Brainum. Any reprinting in any type of media, including electronic and foreign is expressly prohibited.
