posted January 25, 2000 10:40 AM            

Enjoy,
George

In this issue of EFN: An exclusive inside look at the explosive
androstenedione controversy. EFN sheds new light on the recent media
blitz and reveals flaws in the Iowa State Study.

Dear friends and fellow athletes,

The new pro-hormone supplement rage is under attack! On June 2, 1999
the Journal of the American Medical Association (JAMA) published a
controversial study funded by Bill Philips of EAS and conducted by
Douglas S. King, Ph.D., of Iowa State University. The study looked at
the effects of oral androstenedione supplementation on serum
testosterone levels and skeletal muscle fiber size and strength. As
many of you have seen the media went wild crucifying the new
supplement, claiming the study showed that the popular pro-hormone
androstenedione was ineffective at raising testosterone levels. Upon
comparing the media's claims with an analysis of the findings one will
note three major points of controversy in the Dr. King/EAS study. The
first being the determination that short- and long-term oral
supplementation does not increase serum testosterone levels in men.
The second, that androstenedione supplementation does not aid in the
increase of skeletal muscle size and strength. And the third being Dr.
King's preoccupation with common rises in estrogen levels. In this
issue of EFN, we will take an in depth look at the pro-hormone
androstendione, Dr. King's Iowa State study, and other competing
reports and evidence that clearly show androstenedione to be a
worthwhile and highly effective supplement.

THE STUDY
Before examining the results of Dr. King's study, let's look at its
design as published in JAMA. Thirty men with normal testosterone
levels were selected and screened for the entire experiment. None were
to have previously used androstenedione, nor were they to be actively
weight training. The men were then split into two groups. Group one
consisted of ten men who were selected solely to measure their
short-term post administration response to androstenedione. These
subjects received either a 100mg androstenedione capsule or a placebo
in a double blind manner. Their blood was drawn every thirty minutes
afterwards for six hours in order to measure hormonal changes. The
other twenty men (group two) were placed into an eight week exercise
and supplement program to determine long-term androstenedione effects
on testosterone levels and skeletal muscle fiber size and strength.
Group two took either 300mg androstenedione per day (3 x 100mg) or
placebo in a double blind manner for most of the study. No capsules
were given to the subjects on weeks three and six. The capsules were
given at 9:00 AM, 3:00 PM and bedtime to mimic "the standard
manufacturer recommendations" for taking androstenedione. Blood
hormone levels were measured periodically through the experiment. One
rep maximum (1-RM) lifts were calculated and measured throughout the
study to determine strength increases.8

GROUP ONE'S RESULTS
Charted results from group one's 100mg dose of androstenedione were
not dramatic, but a testosterone increase was noted in this experiment
none-the-less. For example, at the start of the procedure the average
free testosterone level for the "andro group" was about 78 pmol/L.
This value peaked at over 90pmol/L after 60-90 minutes had past, and
stayed above 80pmol/L for nearly 6 hours. The "placebo group" did not
show this increase, and in fact showed slightly declining testosterone
values during measurement. But, in the opinion of the authors this
rise seen in the "andro group" is not worthy of interest. They go on
to explain "The lack of any significant increase in serum testosterone
... suggests that any putative increase in serum testosterone with
higher doses would be associated with additional elevations in the
serum estrogen concentration...."9 This consequently fostered the
media's conclusion that androstenedione does nothing to effectively
increase testosterone levels and produced an alarming elevation in
estrogen levels. Clearly Dr. King noticed the increase, but was
obviously more interested in discussing the raise in estrogen. The
fact that any testosterone increase, however minor, was made at a
100mg dose is testament to the testosterone boosting effects of
androstenedione.

EFN contacted Dr. King regarding the increase observed in testosterone
levels at the 100mg dose. Dr, King then acknowledged the slight
testosterone increase, yet refused to comment further on the specifics
of his study. It should also be noted that one of group one's ten
subjects in Dr. King's experiment dropped out of the study.
Statistically speaking, this greatly weakens Dr. King's argument.

GROUP TWO'S RESULTS
In group two, Dr. King used a 100mg dose (three times per day), which
he referred to as a 300mg dose. The group two subjects exercised for
eight weeks. Dr. King claimed that this dose, according to industry
claims should have yielded even further gains in serum testosterone
than was shown in group one. Unfortunately Dr. King findings again
showed this not to be the case. Dr. King based the dosing schedule for
group two on what he referred to as "current industry standards and
claims,"--100mg, three times per day. This dosing schedule relies on
claims made by the 1995 German patent. In the U.S., no one really
gives credence to such extended elevation claims especially at a small
dose of only 300mg split three times a day.

In group two, researchers were looking for much longer lasting
testosterone boosting effects from a 100mg dose of androstenedione
than today's industry research and results would suggest. This was
apparent in their blood drawing schedule. The researchers were taking
blood samples from the subjects first thing in the morning (before any
androstenedione was taken). Andro has always been known as a temporary
testosterone booster, which is why today manufacturers recommend
dosing anywhere from 300-600mg prior to workout with additional mgs
supplemented throughout the day. It goes without saying that by
today's industry standards a 100mg dose is at best a modest, if not an
insufficient dose. From a single 100mg dose, we know not to expect an
elevated testosterone level for days, and certainly would anticipate
levels to be back down to normal upon waking the following morning.

It is safe to say that the bodybuilding industry recognizes that more
ambitious dosing will indeed produce a much higher testosterone peak.
It should be noted that since the 1995 German patent (the cornerstone
of Dr. Kings refute) was released we've learned a lot about the proper
dosing and diet requirements surrounding successful androstenedione
supplementation. While the use of higher dosing was discussed by Dr.
King it was never investigated in the article. Unfortunately, no more
than 300mg per day (in divided dosing) was ever used in the study.
Also, very strange, is that in a short eight-week study participants
took two weeks off from all supplementation. It is common sense that
this does nothing to help build consistent elevated testosterone
levels. We do not know if the subjects trained during these two-week
periods or not.

Dr. King also reports that in group two of his experiment there was
virtually no strength variation between the placebo and
androstenedione subjects. Both showed significant increases of muscle
size and strength, but the change was comparable in both groups. This
consequently helped foster the media's conclusion that androstenedione
does nothing as a performance enhancing agent. The main fault with
this is that none of the men who took part in this study had training
experience nor did they participate in a proper diet regiment. Only
two men studied had ever lifted weights before, and these men had
abstained from such training for over a year. The positive effects of
such a small dose of androstenedione (100mg) could easily have been
overlooked by the strong gains expected in those so new to weight
training.

Training and diet are as important to the success of androstendione
supplementation as is dosing schedule. There was no mention in Dr.
King's study of supervised high intensity training, which we know to
be the single most crucial factor to success in weight training. When
in the gym the bodybuilder wants to focus energies on only performing
work that is productive, i.e., growth producing. In good form, he
should push himself as far as he can go on every set. It has been
shown that the harder that one trains (intensity), the greater the
adaptive response. A high level of intensity is characterized by
performing an exercise to the point of concentric (positive) muscluar
failure, i.e., exhaust the muscle(s) to the extent that the weight
cannot be moved for any more repetitions. Failure to reach this level
of intensity will result in little or no gains in strength or size
regardless of supplements or drugs. There was no mention of anything
close to this kind of training routine in Dr. King's study.

Any successful bodybuilder knows the importance of food.
Androstenedione and its testosterone metabolite do not by themselves
turn into muscle. They facilitate a conversion of food, specifically
protein, into muscle. Knowing what to eat is at least as important as
knowing how to train. Making the hardcore gains expected in Dr. King's
study means eating hardcore. The body needs energy for working out and
fuel for recovery. In other words, the successful bodybuilder needs to
make an effort to eat a lot more than he may be comfortable with when
training in order to make significant gains. I received an email from
a consultation client who recently gained 20 lbs. taking pro-hormones.
When I asked him about his diet, he had these words to say...

"What I think is equally important is the fact that at a starting
weight of 180 pounds on a 6 foot tall frame, I ate between 4000 to
5000 calories a day, while downing between 250-300 grams of protein
per day (I think that many novice lifters fail to realize that if you
don't eat and sleep well it doesn't matter what supplements you take
or how hard you lift."

He concluded with this often-ignored piece of advice "You have to eat
big to get big." I did not see anything close to this type of diet in
the King study.

THE ALLEGED "ALARMING" ESTROGEN INCREASES
The Iowa study makes some alarming claims about high levels of
estrogen buildup (and the associated health risks) with the use of
androstenedione. The process of testosterone to estrogen conversion
(aromatization) is of course well known, and is the primary source of
estrogen (low levels) found naturally in the male body. With increased
levels of testosterone, estrogen levels will also rise. Higher than
normal levels can lead to fat accumulation, water retention and
gynecomastia (breast tissue development), a well known phenomena among
steroid users.

As shown in the study, androstenedione does have a path of conversion
to estrogen not seen with testosterone, namely that it can convert
directly to estrone in the body. Estrone is a very weak estrogen which
is typically formed from the breakdown of estradiol. Again, this is
not secret, and is a basic function of body processes. The authors of
the study believe this can be very detrimental, yet produced no
findings which would indicate that a major problem was evident. In
fact, the higher levels of estrogen seen with the androstenedione
group did not produce greater fat retention, which one would expect.
When examining the data, we actually see a greater loss of body fat in
the androstenedione group than in the placebo group (2.2kg average fat
loss compared to .8kg). Overall body fat percentage loss for the
androstenedione group was an average of 3.2% as compared to 1.4% in
placebo, clearly a notable difference. No signs of gynocomastia were
evident in the treated group as well, nor were there any other signs
of estrogen linked health complications. This would support the notion
that androstenedione is not a very troublesome product in terms of
estrogen until very large doses are given.

The study also did not examine the use of anti-estrogenic compounds
like chrysin, Clomid or Nolvadex (the latter two being prescription
drugs). It is safe to say estrogen is a concern with hardcore
androstenedione dosing just as it might be with many anabolic
steroids. There is little evidence to demonstrate that andro's
estrogen conversion is so serious that it would sit in a class by
itself as the King study leads one to believe.

OTHER ANDROSTENEDIONE STUDIES
While the Iowa study has been interpreted to show very poor results
from androstenedione, a number of other studies show it to have a
pronounced testosterone boosting effect. As we have mentioned before
differences in intake regiment, individual body chemistry, diet, and
training could have caused the Iowa study to wind up so uneventful
while other studies were not. Studies like the German androstenedione
patent for example, show a much higher average testosterone boost from
this hormone. In fact, the patent states that the boost from a single
100mg dose can equate to a raise in testosterone levels of over 300%,
far above what Iowa is reporting.10 The German government has spent a
lot of time and energy researching, testing, and implementing
androstenedione as a performance enhancing agent, which would not have
been justified if the hormone was worthless as a testosterone
precursor.

Michigan State University also conducted another enlightening study
using androstenedione.11 This study used a head to head comparison of
oral dosing with androstenedione and 4-androstenediol. While the
intent of this study was to compare the two pro-hormones, the data
from it clearly shows that androstenedione is a formidable
testosterone precursor. It is also interesting to note that there was
a notable amount of variation in the responses to the andro products,
with some subjects receiving a benefit many times greater than others.
Some individuals just appear to have an easier time converting andro
than others. This questions the results of other small group studies
such as the Iowa investigation. Such variations can easily skew the
final data.

Research by Victor Uralets Ph.D backs up the fact that androstenedione
can alter testosterone levels.12 In fact, Mr. Uralets' research shows
that the boost can be so pronounced, that an athlete might fail a drug
test for testosterone when taking an androstenedione product. A
steroid drug test is conducted by comparing epitestosterone and
testosterone concentrations in the body. If testosterone is given from
an outside source, the ratio would widen, indicating steroid use.
Apparently androstenedione can raise testosterone levels to a point
where the accepted ratio of 6:1 (T/E) could be quickly exceeded.
Indeed this product has caused problems for a number of professional
athletes and men in the service that failed steroid drug tests due to
androstenedione use.

ANDROSTENEDIONE IN PROFESSIONAL SPORTS
On August 21, 1998, the eyes of the world were opened wide to the use
of the performance-enhancing supplement androstenedione in
professional sports. On this day a reporter, from the Associated
Press approached the locker of St. Louis Cardinal slugger Mark McGwire
to receive a comment on McGwire's now famous Roger Maris home run
chase. The reporter noticed a brown bottle labeled androstenedione
sitting on the top shelf of McGwire's locker. The very next day, the
Associated Press published a report stating that McGwire was taking
androstenedione as a testosterone-producing supplement to increase his
strength and endurance.13 McGwire states, "Everything I've done is
natural. Everybody in the game uses the same stuff I use." The
Associated Press wrote "The drugs ability to raise levels of the male
hormone (testosterone), which builds lean muscle mass and promotes
recovery after injury, is seen outside of baseball as cheating"

Major league baseball and the NBA, ban only illegal drugs from use
during sport competitions. Athletes in other sports are often not
quite as lucky. On April 1st 1998, the 1996 Olympic gold medallist
Randy Barnes tested positive for androstenedione during an out of
competition test for the drug.14 This world class shot-putter is now
banned for life from Olympic competitions after his second positive
test for androstenedione.

On September 3rd 1998, Pittsburgh Steelers offensive lineman Paul
Wiggins was suspended by the NFL after a positive test for
androstenedione. 15 Wiggins received a 4 game suspension for his first
offense of the league substance abuse policy. Wiggins tested positive
for elevated testosterone levels during a training camp urine test.

Dr. Gary Wadler, a consultant for the U.S. Department of Justice has
some very strong view about androstenedione.16 In an interview
published in USA today Dr. Wadler says of androstenedione "[It is]...a
steroid, always was a steroid, always will be a steroid and should be
treated with the utmost respect as a drug and not as a dietary
supplement". He also believes that "androstenedione is no safer than
testosterone. Androstenedione becomes testosterone. In many ways they
are one in the same. It's just a matter of quantity. I do not believe
it should be available over the counter, period."

The relevance of these professional sports examples is to the
questions they raise. If this drug doesn't elevate testosterone
levels, then why is the Olympic committee so concerned with its use by
athletes? If the drug does not significantly raise testosterone
levels then why does its use cause a positive result on urine tests
that detect an excess of the male sex hormone? Why would an athlete
jeopardize his career by taking a banned substance if it did not
increase athletic performance? Interesting questions indeed.

THE MEDIA
So where did the media go wrong in all of this? Clearly the reporters
picking up on this story could have done a little more research into
the study and androstenedione before printing the headlines they did,
but we must remember that it is the nature of public media to cover
the "hot" story--a story that will sell papers. When the Mark
McGwire/androstenedione controversy first broke. It was all over the
news in what seemed to be minutes. A sports celebrity linked to
potential steroid use is quite a story. Likewise we would expect a
major study which could potentially shine a new light on this hot
topic to be "big news" as well. Reporters know that readers thrive on
fear, danger, controversy, and scandal and will "spin" a story
accordingly. They are not so much interested in the facts or the
ultimate legitimacy of a given study, but rather the newsworthiness of
it. They also know that the public is always interested in a consumer
health-risk related story. It sells, plain and simple. Keep in mind,
reporters are not out to analyze every study they come across. In fact
it is not their job. They usually just pass along the information they
are given with its sources cited. If they read or are given a story
from JAMA they feel confident in its legitimacy. The blame really
falls more on the JAMA for releasing what is obviously an inaccurate
study, but that's another newsletter.

IN SUMMARY
Yes, the results of the Dr. King/EAS study were disappointing.
However this study plagued with contradictions and inconsistencies to
what we all now know to be the adequate and appropriate dosing,
administration, training and diet for success androstenedione
supplementation. While the Iowa study was certainly an interesting
investigation into androstenedione, it should not be considered the
"end of discussion" regarding this supplement. Hopefully, there will
be more funding for future studies looking at andro administered at
much higher dosages by trained bodybuilders to once again back up the
use of androstenedione.

Interestingly in the past similar studies with untrained men led
researchers to conclude anabolic/androgenic steroids were worthless
for enhancing performance. Some professionals still hold this opinion
today. Athletes of course know that steroids work remarkably well, and
we are finding the same with regards to pro-hormones like
androstenedione.

Another area ignored by the Iowa study was the use of various
bioavailability-enhancing agents. Problems with poor gut absorption
and conversion percentages of oral prohormones are well known in the
sports supplement industry. This is why we need to take moderate to
high doses with water and on an empty stomach to receive optimal
results. This has led a few pioneering firms to add compounds like LPC
(lysophospatidylcholine), vitamin/mineral mixes with Zinc and Niacin,
and/or the liver protecting/stimulating agent silymarin to their
prohormones. LPC acts to expand the cell lining in your intestines and
stomach, which will allow a greater amount of nutrients, hormones etc.
to pass through. Niacin and Zinc are crucial for the conversion of
androstenedione to testosterone, as the enzyme responsible (17 Beta
hydroxysteroid dehydrogenase) is dependant on them for optimal
performance. Silymarin aids in liver conversion of prohormones, as it
is shown to protect and enhance overall liver activity. Making sure
Dr. Kings subjects ingested the andro with water and on an empty
stomach as well as any combination of the above products would
probably have altered the results of this study to a noticeable
degree.

We must also consider the source of this study. EAS, one of the world
most prominent supplement manufacturers, funded this study and has
recently dropped their androstenedione containing supplement (Andro 6)
from their web site. We are told it can only be found in health food
stores, perhaps due to a halt in new production. Some are speculating
that EAS may be losing sales revenue to the many small firms making
andro products, and would likewise like to see a switch back to the
use of "natural" products like their MyoPlex and Phosphagen brand
creatine monhydrate. Of course this is theory, and EAS may have indeed
expected a favorable study to be returned.

In the opinion of Elite Fitness, the introduction of androstenedione
to the sports supplement industry should be considered nothing short
of a giant leap forward. For the first time ever athletes can purchase
a potent hormone that will directly convert to testosterone in body
tissue. The athlete who would formerly have considered illicit steroid
purchases may now find a legal and cheap alternative in his local
health food store and on the web. If you have never used
androstenedione or other prohormones, you may certainly be missing
out. The results most athletes are obtaining from its use are most
often astounding, with gains commonly reported to be over 15lbs of
weight. The Iowa study be damned.

Yours in sport,

George Spellwin

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REFERENCES

1. Horton R, Tait JF. J. Androstenedione production and
interconversion rates. Clin Invest. 1966;45:301-313.
2. Thomas PZ Dorfman RI. C.J Metabolism in vitro androstenedione. Biol
Chem. 1964;239:762-765.
3. Van der Molen HJ, Groen D. Interconversion of progesterone. Acta
Endocrinol. 1982;93:253-266.
4. Randall VA, Ebling FJ Hargreaves G. IN vivo uptake and metabolism.
J Endocrinol. 1982;93:253-266
5. Chapdelaine A. J Sites of in vivo extraction. Clin Invest.
1969;48:2063-2073.
6. AJR Am J Roentgenol, 1998 Feb, 170:2, 423-7
7. J. Clin Endocrinol Metab, 1997 Feb, 82:2, 407-13
8. Brown Gregory, King Douglas, Parsons Kerry, Reifenrath Tracy, Sharp
Rick, Uhl Nathaniel, Vukovich Matthew. JAMA. 1999; 281: 2020-2028.
9. Brown Gregory, King Douglas, Parsons Kerry, Reifenrath Tracy, Sharp
Rick, Uhl Nathaniel, Vukovich Matthew. JAMA. 1999; 281: 2027.
10. Abramowicz, M (ed.) (1999) The Medical Letter. 40:105-106.
11. Study not yet published. Preliminary information released through
LPJ.
12. Victor Uralets, Androstenedione abuse and detection in urine.
Natural Bodybuilding, 40-41.
13. McGwire takes legal drug Androstenedione. ESPN.COM. Wilstein,
Steve. August 22, 1998.
14. Doping Cases of 1998. USA Today. Associated Press. January 30,
1999
15. Steelers' Wiggins suspended for taking Andro. ESPN.COM.
Associated Press. September 3, 1998
16. Answers about a mysterious pill. ESPN.COM. Associated Press.
November 13, 1998