June 7, 1999
Volume 2, Number 11

---

Research Update

by Bryan Haycock MSc., CSCS
bryan@thinkmuscle.com 

Please send us your feedback on this article.

As we approach the new millennium we find the science of building muscle progressing faster than ever before. Long gone are the days of simple trial and error when it comes to building muscle. The modern bodybuilder demands more than just "hear say" if they are to adopt a new training routine or nutritional supplement. This column was created to keep today’s bodybuilder on the cutting edge of scientific research that might benefit them in their quest for body perfection.

---

Special Update on Androstenedione!
Andro 6Ô undergoes clinical trials.

Title(s):

1) Acute effects of oral anabolic-androgenic supplements on blood androgen and estrogen levels in man.

2) Oral anabolic-androgenic supplements during resistance training: Effects on serum testosterone and estrogen concentrations.

3) Oral anabolic-androgenic supplements during resistance training: Effects on body composition and muscle strength.

4) Oral anabolic-androgenic supplements during resistance training: Effects on glucose tolerance, insulin action, and blood lipids.

---

Researchers:

1) Parsons KA, Sharp RL, FACSM, Brown GA, Reifenrath TA, Uhl NL, & King DS, FACSM

2) King DS, FACSM, Sharp RL, FACSM, Brown GA, Reifenrath TA, & Uhl NL.

3) Reifenrath TA, Sharp RL, FACSM, Brown GA, Uhl NL, & King DS, FACSM.

4) Brown GA, Reifenrath TA, Uhl NL, Sharp RL, FACSM, & King DS, FACSM.

1, 2, 3, 4) Department of Health and Human Performance, Iowa State University, Ames, IA.

Source: Medicine and Science in Sports and Exercise. 31(5 Supp): May 1999

---

Summary:

1) Acute effects of anabolic-androgenic supplement on serum androstenedione, testosterone, and estradiol: On three separate days assigned in random order, 10 college age males took a placebo (PL), 50 mg DHEA, or Andro 6Ô (AN6). AN6 contains 100 mg androstenedione, 50 mg DHEA, 250 mg Tribulus terrestris, 250 mg Chrysin, 100 mg Indole-3-carbinol, and 180 mg Saw palmetto. The results are as follows:

(* indicates statistical significance)

Serum Androstenedione, nM

Serum Testosterone, pM

2) Effects of anabolic-androgenic supplement on serum testosterone and estrogen concentrations during 8 weeks of resistance training: Subjects performed 3 workouts per week for 8 weeks. Throughout the 8 weeks period subjects consumed either placebo (PL) 150 mg DHEA, or Andro 6Ô (AN6). AN6 supplied a total of 300 mg androstenedione, 150 mg DHEA, 750 mg Tribulus terrestris, 625 mg Chrysin, 300 mg Indole-3-carbinol, and 540 mg Saw palmetto daily. The results are as follows:

Changes in Androgens and Estrogens over 8 weeks

3) Effects of anabolic-androgenic supplement on body composition and muscle strength during 8 weeks of resistance training: Subjects performed 3 workouts per week for 8 weeks. Throughout the 8 week period subjects consumed either placebo (PL) 150 mg DHEA, or Andro 6Ô (AN6). AN6 supplied a total of 300 mg androstenedione, 150 mg DHEA, 750 mg Tribulus terrestris, 625 mg Chrysin, 300 mg Indole-3-carbinol, and 540 mg Saw palmetto daily. The results are as follows:

Changes in Strength and Body Composition over 8 weeks

4) Effects of anabolic-androgenic supplement on glucose tolerance, blood lipid profile, and liver function during 8 weeks of resistance training: Subjects performed 3 workouts per week for 8 weeks. Throughout the 8 week period subjects consumed either placebo (PL) 150 mg DHEA, or Andro 6Ô (AN6). AN6 supplied a total of 300 mg androstenedione, 150 mg DHEA, 750 mg Tribulus terrestris, 625 mg Chrysin, 300 mg Indole-3-carbinol, and 540 mg Saw palmetto daily.

---

Results: The area under the glucose curve during a 75 gram OGTT was unaffected by training or supplementation. The area under the insulin curve was reduced similarly under all conditions. Serum HDL-C was reduced at 2 weeks in AN6 group and remained lowered at 5 and 8 weeks indicating increased cardiovascular risk associated with AN6 supplementation.

---

Discussion: Boy, where do I start? Let’s start with the first investigation. Initial reports of the acute effects of androstenedione (ANDRO) on serum testosterone (T) indicated that ANDRO significantly raised T levels at least for the first hour or so. An often sited study in the 60's by Mahesh and Greenblatt involved giving women a 100 mg dose of DHEA or ANDRO. The results showed that an acute oral dose of DHEA raised serum T nearly 150%. The same dose of ANDRO raised serum T nearly 300% in the first 60 minutes! This was great news to all bodybuilders with aspirations of drug-like gains from a legal substance. An important issue about the Mahesh study is that it involved women. It has been shown that women convert ANDRO to T more readily than men. It could also be that the relative scarcity of T in women’s serum (~1 tenth of that found in men) make any increases by ANDRO seem very large. Another study sited in a patent filed by German researchers involved administering oral doses of 50 mg and 100 mg of androstenedione to men. They reported that the 50 mg dose raised T levels by ~160%. The 100 mg dose raised T levels by ~220%. In the present study, funded by Experimental and Applied Sciences (EAS^®), which also produces the product Andro 6Ô which was used in the study, there was no apparent effect of 100 mg ANDRO on T levels during any time within 360 minutes. It’s difficult to explain this discrepancy.

So what’s the problem here? Why are these recently published results in contrast with earlier studies? Pat Arnold has mentioned that perhaps the DHEA in Andro 6Ô is being converted to 5-androstenediol by way of 17ß-HSD. This is the same enzyme needed for the conversion of androstenedione to T. With a limited supply of 17ß-HSD, DHEA may hinder ANDRO’s ability to be converted to T. More detailed studies are needed to determine if this is the case with products that contain both DHEA and ANDRO.

In study # 2, researchers looked to see if Andro 6Ô would have any effect on serum testosterone and estrogen concentrations during 8 weeks of resistance training. The results do not bode well for Andro 6Ô. There was no increase in T at any time during the 8 week trial. Not only that, but there was an 80% increase in DHT as well as a 60% increase in serum estrones and a 30% increase in estradiol. Ouch!

It appears that the saw palmetto in Andro 6Ô either had no effect on 5a-reductase or it simply was insufficient to compensate for the large increase in androstenedione. Remember that androstenedione can be converted directly to DHT. In case some of you haven’t been reading up on the many effects of androgens, DHT stands for dihydrotestosterone. DHT is an extremely potent androgen (probably the king of androgens) and is responsible for hair loss and prostate growth and a host of other developmental changes throughout the embryonic stages as well as puberty. The saw palmetto in Andro 6Ô is supposed to block the enzyme that converts T into DHT. In this experiment, it didn’t work, or in any case, not well enough.

Indole-3-carbinol is an ingredient that was supposed to protect against the effects of estrogens by increasing the activity of degradive pathways (the C2 pathway I believe) leading to less problematic estrogen metabolites. Specifically it decreases the formation of 16 alpha-hydroxyestrone from estrone as well as decrease the availability of some androgens like 4-androstenedione which will then not be turned into estrone. In experiment number 2 Indole-3-carbinol didn’t seem to be effective. Then again, the estrone levels may have been even higher without the Indole in there.

There is one thing I should mention about androstenedione and its conversion to estrogen and body composition. It has been shown that the more body fat you have, the greater the aromatization of androstenedione to estrone and estradiol. When normal and obese subjects were compared as groups, plasma androstenedione decreased from 1.24 +/- 0.13 to 0.93 +/- 0.15 ng/ml and plasma testosterone decreased from 5.89 +/- 0.82 to 3.29 +/- 0.92 ng/ml, while estrone increased from 28.2 +/- 3.4 to 60.0 +/- 9.4 pg/ml, and estradiol increased from 21.7 +/- 3.5 to 43.9 +/- 5.3 pg/ml. So when comparing obese and normal subjects, testosterone is cut in half while estrone and estradiol are doubled. This increased aromatization occurs as a result of increased adipose tissue. So if your already heavy (fat) androstenedione is not the way to go.

In study # 3 we find out whether Andro 6Ô is effective at increasing muscle growth and/or decreasing body fat as well as it’s effects on strength. Unfortunately, Andro 6Ô didn’t effect strength, muscle growth, or fat loss. All groups showed similar changes in body composition and strength. In fact the gains in muscle for all groups were quite impressive, if we assume the gain in lean mass consisted of contractile tissue. The increase in lean mass could alternatively be explained by expected changes in blood volume and glycogen storage which could easily add 4 pounds or so to a previously untrained subject. In summary, the Andro 6Ô group took their supplements, trained their butts off and nothing out of the ordinary happened.

In the final installment of these Andro 6Ô trials, researchers looked that effects of Andro 6Ô on cholesterol and insulin sensitivity. As you might begin to expect after the previous trials, Andro 6Ô provided all of the negative effects of androgens and none of the beneficial effects. HDLs (good cholesterol) went down within 2 weeks in the Andro 6Ô group and stayed low throughout the following 6 weeks of the trial. Look at it this way, at least the increased estrogens produced by Andro 6Ô may help protect against the increased cardiovascular risks associated with decreased HDL levels. I guess the good news is that Andro 6Ô did not negatively effect insulin sensitivity.

I have to tell you that I was surprised when I read these abstracts. I happen to be an optimist when it comes to supplements. I really wanted to see that androstenedione products had some benefit for bodybuilders. At least Mark McGuire’s agent can use these results to prove that he gained no ergogenic effect from taking his androstenedione.

So what’s left? Well, for starters we need to see some trials on 4-androstenediol (4-AD). It may be true that 4-AD is converted to T 3 times more readily than androstenedione, but the significance of this is still to be determined in human trials. There are several reasons to believe that 4-AD is a much more effective approach to increasing endogenous T levels. In light of the current evidence against androstenedione I will remain very conservative in my expectations of 4-AD or the Norandro products for that matter.

Despite being hopeful about the potential of prohormones, one issue bothers me about raising testosterone levels "only slightly" above normal. Research with animals shows that sustained delivery of androstanedione significantly reduces testicular function and mass including seminal vesicles and that Leydig cells were not only reduced in size but also in number. Your Leydig cells are responsible for testicular production of testosterone. The end result is more androstanedione and less testosterone.

I’m sure you have heard of testosterone enanthate being used for birth control in men. You may also know that this kind of very low dose of testosterone seldom leads to noticeable changes in muscle growth in men with normal testosterone levels. The reason is that only enough testosterone is given to reduce the body’s endogenous production of sperm by negative feedback at the anterior pituitary which results in lower gonadotropin secretion. Until the body responds to the additional testosterone there may be some benefit, but shortly there after your testosterone levels are actually close to normal beings that you are simply replacing the testosterone that your body used to produce with the low levels injections of test enanthate. You are simply replacing what you lose! For testosterone to be effective it has to be administered in sufficient quantities not only to replace your natural production but also to provide sufficient activity of androgen receptors in muscle cells to elicit muscle growth.

It could be that although 4-AD may lead to higher testosterone levels, this increase may only be sufficient to shut down the system leaving you right where you started (or worse). Yes, very brief cycles may be the way to go to avoid this. We also mustn’t forget that this subtle increase in testosterone still may not be sufficient to elicit noticeable anabolism. I eagerly await the publication of peer reviewed studies involving 4-AD and resistance trained males to answer these questions. For now, I’m afraid the formulation of EAS^®’s Andro 6^Ô does not offer any benefits to male resistance trained subjects under the conditions used in these recent studies.

Note: There was another study recently released, in abstract form only, indicating that sublingual administration of androstenedione does indeed result in increased blood levels of androstenedione. These researchers speculated that testosterone levels may have increased during a period beyond 60 minutes. Unfortunately, these researchers did not measure testosterone levels during the period after 60 minutes.

Please send us your feedback on this article.

by Bryan Haycock MSc., CSCS
bryan@thinkmuscle.com