Patrick Arnold, through his company, LPJ Research, Inc., has developed the process to manufacture this chemical and has a patent on its use. It is being produced by LPJ Research and marketed by many companies.

Androdiol is also a direct precursor to testosterone just as androstenedione is. However it converts via a different enzyme, 3beta hydroxysteroid dehydrogenase. According to Blaquier et al. in the East German journal Acta Endocrinoligica 55 (1967) p.697, this conversion is more efficient for androdiol than it is for androstenedione in human blood. Incubated in human blood, 5.61% of tritiated androstenedione converted to testosterone after a period of a few hours while 15.76% of tritiated Androdiol converted to testosterone.

Since Androdiol is synthesized into testosterone, it's supplementation likely increases testosterone production and the anabolic properties associated with testosterone that are desired by bodybuilders such as increased energy, strength, muscle development and decreased recovery time from workouts.

Androdiol has been found to be present in blood plasma and has been identified as an androgen metabolite that is formed in placental, uterine, testicular, adrenal, and hypothalamal/pituitary tissues.

As is true with all androgens, the testosterone boosting effects of Androdiol is subject to possible undesirable side effects. Some possible side effects associated with androgens are head hair loss, body hair growth, acne, gynecomastia (breast tissue growth) and increased aggression. You may not experience much or any of these side effects - especially if you stick to the recommended dosages or less - but it is possible and you should be aware of this before starting to use it. Side effects of long term use of androgens is unknown, but could possibly cause health problems. As always, consult your physician before taking any product that may alter hormone levels.

Warning: Androgenic products should only be used by healthy males 21 years of age or older. These products should not be used by women who are sensitive to androgens. People with any pre-existing hormonal dependent cancers (i.e. prostate, breast, etc.) should avoid ALL andro products until more is known regarding the relationship of the testosterone precursors and the above afflictions. We recommend all people using any andro products get hormone testing done on a regular basis. We also recommend any man over 50 years old have a prostate exam and PSA to rule out the presence of microscopic cancer.

Conversion of testosterone precursors to testosterone occurs in the liver and other areas of the body. The activity of the enzyme used to convert Androstenedione to testosterone, 17-beta hydroxysteroid dehydrogenase (17betaHSD), seems to be dependent on a lot of factors. It requires high ATP levels and therefore may require large amounts of carbohydrate intake or a supplement that maintains liver ATP levels like pyruvate and phosphates to work best.

The 17betaHSD enzyme also seems to be much more expressed in women than men, so the conversion to testosterone may be more effective for women than men.

Patrick Arnold says he sees none of these problems with 3beta hydroxysteroid dehydrogenase (3betaHSD) which is the enzyme responsible for converting Androdiol to testosterone.

Zinc is a critical mineral required for this enzymatic process, so a lack of zinc may inhibit the conversion to testosterone. Therefore, it is recommended that you get at least 30 mg. of zinc per day whether it is through whole foods or supplements.

Suggested Dosage Patrick suggests multiple dosing for Androdiol because of the limiting factor of the conversion enzymes. High one-time dosages will probably overwhelm the capacity of the body's conversion enzymes and result in wasted precursor. Lower multiple dosages will probably ensure more complete conversion.

Contrary to what others are recommending, Patrick recommends that you take Androdiol with a meal containing fat. He says that the fat helps in solubilizing the steroids in the small intestine which facilitates absorption.

It is recommended to use these products for no more than 6 weeks at a time in order to give your body at least four weeks to adjust back to normal hormone production.

From Patrick Arnold:

The king of the prohormones is a steroid known as 4-androstenediol, or Androdiol®.¹ It's a direct precursor and metabolite of testosterone. You might not have heard of 4-androstendiol (also abbreviated as 4-AD) because it's not a common androgen metabolite and, as such, isn't discussed in the literature as much as androstenedione and DHEA. However, it's formed in several tissues, such as placenta, uterus, testicles, adrenal cortex, hypothalamus, and pituitary, but it doesn't stick around very long because it quickly converts to testosterone.²

For those of you who have at least a little bit of a chemistry background (or even care), it converts via the enzyme 3beta-hydroxysteroid dehydrogenase (3beta-HSD). The conversion is rapid and much more efficient than that of other prohormones, resulting in considerably more testosterone production. Take a look at the following comparison of the conversion rates of various prohormones:

Compounds and Percent Testosterone Formed*

DHEA: 0.35%
5-Androstenediol: 0.19%
Androstenedione: 5.61%
4-Androstenediol: 15.76%

*The amount of testosterone formed upon incubation in human blood. (Source: Blaquier, J., Forchielli, E., and Dorfman, R., Acta Endocrinologica, 55, 697-704)

It's no contest. This data shows 4-AD to be far superior to androstenedione in regard to testosterone conversion. To illustrate it another way, 4-AD is 281% more efficient in T conversion than its closest competitor, androstenedione.

Nevertheless, this is in-vitro (conducted in a test tube) data and doesn't necessarily indicate what will happen when living, breathing males ingest it. To answer this question, LPJ Research, Inc. funded a study at Eastern Michigan University that was supervised by Tim Ziegenfuss, PhD. What Dr. Ziegenfuss did was give seven male subjects (average age: 28.1 years) samples of 100 mg androstenedione, 100 mg 4-androstenediol, and 100 mg placebo, all on separate days.

The subjects had a portion of blood drawn before and after ingesting the samples. They continued to have blood drawn at intervals of 30, 60, and 90 minutes. Blood samples were then analyzed for total testosterone and free (unbound) testosterone.

4-AD caused a 310% greater increase (relative to placebo) in total testosterone compared to androstenedione, and a 256% greater increase in free testosterone!

Unfortunately, due to budget constraints at the time, the study was only carried out to 90 minutes, so we don't know how fast the hormone levels declined. However, if you look at  both prohormones, it appears that they both share the same pharmacokinetic (rate of rise and fall in levels) properties. This data is scheduled to be presented at a professional conference in Finland this November, and will then be considered a totally valid, peer-reviewed study.

Other 4-Androstenediol Advantages

It's clear that 4-androstenediol raises testosterone levels much higher than any of the other prohormones. However, 4-AD has a couple of other properties that make it superior to androstenedione as well. The first involves conversion to estrogens.

I pointed out that a small percentage of androstenedione gets converted into testosterone. Fine. Trouble is, a percentage of it also gets aromatized (aromatization is the biological process that converts androgens to estrogens) into estrone (an estrogenic hormone). Not good.

To back this up, there's been a growing number of anecdotal reports of mild gynecomastia (gyno, bitch tits) associated with the usage of androstenedione. A lot of young athletes started taking androstenedione in the hopes that they could be like Mark McGwire. They didn't account for the fact that it may be difficult to find a bra that large.

The issue is a complicated one and we still don't understand the exact metabolic fate of ingested androstenedione, but it's apparent that estrogen conversion is a significant problem with this supplement.

Fortunately, 4-AD doesn't suffer from the same drawback. It can't aromatize. It lacks the structural chemical characteristics to do so. The total explanation would be a lengthy one (and a boring one), but suffice it to say that the aromatization mechanism requires a ketone group at the 3-carbon that will enolize in the last step to produce an A-ring aromatization.³ Hey, you asked for it.

Anyhow, testosterone and androstenedione have this 3-ketone, while 4-AD doesn't. All you need to know is that androstenedione (along with 19-norandrostenedione) can convert directly to estrogens while 4-androstenediol (and 19-nor-4-androstenediol) can't.

I should remind you, though, that the testosterone formed from the conversion of 4-AD can itself aromatize. That problem is inherent to testosterone. If you want to raise T levels, you're going to get some aromatization. Nevertheless, the fact that the precursor (4-AD) is unable to do so makes it greatly superior to androstenedione. You won't throw your testosterone:estrogen ratio out of balance with 4-AD.

When I first developed 4-AD, I sent a sample to the owner of a well-known supplement company. He is also one of the first steroid experts to surface in the 80s and co-wrote "The Underground Steroid Handbook." This guy was one of the first to sell androstenedione, but when he tried 4-AD, he was amazed at how effective it was. What he found particularly interesting was the fact that while large amounts of androstenedione would aggravate his pre-existing gyno considerably, equally large amounts of 4-AD didn't. In fact, 4-AD seemed to shrink his nipple lumps. Quite impressive feedback, considering the source.

4-Androstenediol and DHT

DHT is generally a bad word among bodybuilders. It, along with its derivatives (particularly 5alpha-androstan-3alpha,17beta-diol) is linked to undesirable conditions, such as male pattern baldness and prostatic hypertrophy. These compounds are known as 5-alpha reduced androgens and are formed by the enzymatic conversion of androgens such as testosterone.

Well, unlike androstenedione, which can readily convert to DHT and its derivatives (5-alpha reduced compounds), 4-AD doesn't convert to DHT. It can't.

The enzyme 5-alpha reductase is responsible for this conversion. Testosterone, along with androstenedione, can undergo direct 5-alpha reduction. However, by using 4-AD instead of androstenedione, we can once again avoid an undesirable direct metabolic risk. Scientists have shown conclusively that 4-androstenediol is unable to undergo 5-alpha reduction and must convert to testosterone in the body before such a reaction can take place.⁴

Chalk another victory up for 4-AD.

5-Androstenediol Versus 4-Androstenediol

There's also a lot of confusion about 4-AD and 5-AD. After all, they sound pretty much the same and have similar chemical structures. They do, however, have significantly different biological activities.

Let me first preface this discussion by explaining the difference between "4" and "5" steroids. There are two classes of steroid precursors being sold right now that differ chemically by the position of the chemical double bond in the steroid molecule (hence the "4" and "5" designations). First, we have the compounds which fall into the "DHEA family" of steroid precursors, and that would be the "5" compounds. They are listed below:

5-Steroids

• DHEA
• 5-androstenediol
• 19-nor-5-androstenediol
• 7-keto DHEA
• Pregnenolone

Then, there are the compounds which constitute the "androstenedione family" of precursors, and these would be the "4" compounds:

4-Steroids

• Testosterone
• 19-nortestosterone
• Progesterone
• Androstenedione
• 4-androstenediol

Now, I'm going to get pretty technical here, so bear with me. The most active/effective endogenous androgens (testosterone, nortestosterone) have the C=C double bonds in the 4 position (or have no double bond at all, and a hydrogen in the 5-alpha position). For a 5 prohormone to convert to an active androgen, in this case, for 5-androstenediol to convert to testosterone, the double bond must isomerize (switch position) to the 4-compound, and an enzyme called 5,4-isomerase brings this about.

However, in the case of 4-androstenediol, no corresponding isomerase reaction is necessary. As a result. the conversion is much more efficient. That means 4-AD "turns" to testosterone much faster and much more efficiently.

I want to be fair to 5-AD, though, and mention that it does have anabolic activity in its unconverted form.⁵ (The same could be said for 4-AD, but that is beyond the scope of this discussion). That is, 5-AD doesn't seem to require conversion to testosterone to build muscle. It also has the added advantage (or disadvantage, depending on your perspective) of being slightly less androgenic. In other words, 5-AD is less likely to cause side effects, such as hair loss, aggressiveness, and increased libido.

However, when comparing absolute anabolic activity of 4-AD to 5-AD, 4-AD is the clear winner. The only head-to-head study of the two compounds ever published showed 4-AD to be 129% as anabolic as 5-AD.⁶

Also, you're likely to "feel" the action of 4-AD more than 5-AD when you're at the gym or in the sack because of 4-AD's greater androgenic potency. Anecdotal reports definitely seem to confirm this.

Another downside to 5-AD is its estrogenic activity. Numerous studies have confirmed that, at physiological levels, 5-AD acts as an estrogen agonist.^7,8,9,10 In fact, in light of its dual activity as a mild androgen and estrogen, the accepted scientific name for this compound is now "hermaphrodiol" (from the Latin term meaning "of both sexes").

On the other hand, 4-AD has much less estrogenic activity.¹¹ I'm not saying that taking 5-AD will have you in a training bra; in fact, when taken in moderate dosages, most people probably won't notice its estrogenic action. However, I do know one unfortunate person (myself) who experimented with 5-AD at large dosages (1-2 grams a day). This same unfortunate person was trying to fight off a lingering viral infection by taking advantage of 5-AD's immunostimulating action. As a result, this person ended up with a definite, and quite uncomfortable, swelling and tenderness in both nipples.

19-Nor Compounds

The 19-nor family of androgens constitutes a group of compounds that share many of the same properties as their C-19 (andro) counterparts. That is, 19-norandrogens metabolize in an essentially analogous way to C-19.¹² In other words, norandrostenedione and 19-nor-4-androstenediol will convert to nortestosterone in the same manner that androstenedione and 4-androstenediol convert to testosterone. 19-nors and C-19s also have anabolic and androgenic activities.

However, the 19-nors have substantially less androgenic activity than the C-19s while maintaining comparable anabolic activity. This does not make 19-nors any better or any worse than C-19s, only different. They are definitely an option for those who want to avoid androgenic effects, such as possible increased head hair loss, increased body hair, increased risk of prostate enlargement, and increased risk of acne.

The low androgenic activity of 19-nors does have its drawbacks, though, the most serious of these being a marked decrease in libido (a common complaint among those who use nandrolone-based steroids as well as 19-nor prohormones).

Another disadvantage of 19-nors is their high cost compared to C-19 prohormones. Also, 19-nors will not give you the heightened focus and CNS psychomotor stimulation that the highly androgenic compounds will. For these reasons, my first recommendation is always for someone to use the C-19 prohormones, and from those I recommend 4-androstenediol because it is by far the most superior.

Now, why does it appear that I'm steering people away from the 19-nor prohormones? Is it for financial reasons? Hardly. Actually, I sell both 4-AD and nor-4-AD and, truth be told, I make more money off the latter.

In my opinion, the use of 19-nors should be confined to women and to those who, for one reason or another, find the risk (albeit slight) of androgenic side effects from prohormones to be unacceptable.

Conclusion

Let me summarize the benefits of the main prohormones:

Androstenedione

• Testosterone Conversion: Moderate
• DHT Metabolite Conversion: Yes
• Estrogen Conversion or Estrogen Agonist: Yes
• Anabolic Properties: Low

4-AD

• Testosterone Conversion: High
• DHT Metabolite Conversion: No
• Estrogen Conversion or Estrogen Agonist: No
• Anabolic Properties: Very high

5-AD

• Testosterone Conversion: Low
• DHT Metabolite Conversion: No
• Estrogen Conversion or Estrogen Agonist: Yes
• Anabolic Properties: High

19-Norandrostenedione

• Nortestosterone Conversion: Moderate
• DHT Metabolite Conversion: No
• Estrogen Conversion or Estrogen Agonist: Yes
• Anabolic Properties: Low

19-NOR-4-Androstenediol

• Nortestosterone Conversion: High
• DHT Metabolite Conversion: No
• Estrogen Conversion or Estrogen Agonist: No
• Anabolic Properties: Very high

Obviously, 4-AD and 19-Nor are, by far, the superior prohormones, and both compare favorably with each other. However, if you're looking for a legal, viable alternative to anabolic steroids-if you want to put on the most muscle in the quickest way possible-4-AD remains the superior choice.

I hope I've helped clear the issue up a little bit. I realize that, in some ways, I might have given you more chemistry than you bargained for, but I hope the intended message still comes through.

References     

1) 4-androstenediol actually refers to two chemical stereoisomers (stereoisomers are compounds with the same apparent two-dimensional structure but differ in the spatial arrangement of certain atoms in the three dimensional model). The two stereoisomers are 4-androstene-3alpha, 17beta-diol and 4-androstene-3beta, 17beta-diol and they both are naturally occurring and share similar activities. However since commercial androstenediol, although composed of both isomers, contains predominantly the latter isomer (3beta), the discussion of 4-androstenediol usually is confined to this isomer.
2) F. Ungar, M. Gut, and R. Dorfman , J. Biol. Chem., 224, 191-200
3) Shengrong, L. and Parish, EJ., JAOCS, 73, 1435
4) Kundu, N., Sandberg, A.A., and Slaunwhite, W.R., Steroids, 6, 543
5) Ruzicka, Wettstein, Helv. Chim. Acta, 18, 1264
6) Ristovic L.J., Cobanovic M., Kem Ind, 24(7), 389-92
7) Hackenburg R, Turgetto I, Filmer A, J Steroid Biochem Mol Biol, 46(5), 597-603
8) Adams JB, Seymour-Munn K, J Steroid Biochem Mol Biol, 43(6), 499-505
9) Leroy B, Maquaire E, Samperez S, Jouan P, J. Steroid Biochem Mol Biol, 31(4A), 453-8
10) Seymour-Munn K, Adams JB, Endocrinology, 112, 486-491
11) Poortman J, Mol Cell Endocrin, 8(1), 27-33
12) Engel LL, Alexander J, Wheeler M, J Biol Chem, 231, 159-65