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Guy doing pushupsQuestion One: What do you get when you mix 19 molecules of carbon, 28 molecules of hydrogen, and 2 molecules of oxygen? It could be a lot of things, but maybe (if you’re lucky) it could order into 17beta-Hydroxyandrost-4-en-3-one. Sound familiar? That’s right, it’s your friend and mine—testosterone.

Question Two: How can you increase your body’s natural production of testosterone? That’s a tougher one. Pro-hormones are no longer easily obtained ljegally and personal stashes will soon dwindle, making this question even timelier.

In the next few pages I will review the scientific literature through exhaustive searches of Medline, CINAHL, EBM, and SPORTDiscus with regard to some of the most popular Over-the-Counter testosterone boosters currently on the market. I will examine the possible mechanism of action for each and assess whether any of these alleged testosterone boosters have a positive effect on testosterone production, exercise performance, or both.

Tribulus Terrestris

The first on the list is of course Tribulus Terrestris, specifically the steroidal saponin protodioscin. Tribulus has long been used in various cultures as an aphrodisiac and treatment for sexual dysfunction. The theory then follows that this increase in libido is probably due to increased levels of androgens, which would also mean that Tribulus generates some type of ergogenic effect. So what does the research say?

First let’s look at several studies conducted on animals that examined the aphrodisiac properties of Tribulus. The first study investigated the response of corpus cavernosal tissue isolated from rabbits that were fed Tribulus for eight weeks [1]. After harvesting, tissues were then exposed to protodiscin, contractile agents, and relaxant agents. Tissue strips from treated rabbits showed an increased rate of relaxation when administered various relaxing agents after said tissue was constricted with norepinephrine. This indicated that Tribulus seemed to have some effect on the rabbits’ ability to get erections; however, no specific mechanism could be pinpointed.

Follow up research ensued. The next two studies, conducted on castrated rats, examined variables that essentially investigated how sexually aroused the rats were [2, 3]. The researchers found that Tribulus supplementation definitely appeared to increase the rats’ libido. Again however, an exact mechanism could not be found.

The latest study by the same researchers tried to determine the mechanism of action by which the mice and rats each appeared to experience heightened arousal levels [4]. Once again, rats were fed Tribulus for 8 weeks. Immunoreactivity studies were performed on the androgen receptor (AR), while Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) levels were taken from the rat paraventricular nucleus in order to determine activity.

The researchers found activity at both receptors increased over control; however, this muddied the waters a bit. NADPH-d neurons are the same that contain NOS. Previous research indicated these neurons were inhibited by increased androgen activity. The researchers attributed this to effects mediated through the conversion of androgens to estrogen, which would then increase the number of NADPH-d neurons. The end result was the same: Tribulus undoubtedly heightened arousal, but whether this was a result of increased androgen levels was unclear.

So, rats having sex is fun to watch, but we want to get buff, right? Well, let’s talk about primates. Primates given Tribulus intravenously showed a transient (read, 30 minutes) increase in testosterone and DHT and a longer increase in DHEAS (an increase of about 25-50% for about 120 minutes), which might be helpful with DHEA mediated effects on sexual function if your testosterone was low [5]. Otherwise, this effect probably would not be noticeable.

In my opinion, the nail in Trib’s coffin comes from the following two studies. The first study examined body weight, body composition, maximal strength, dietary intake, and mood states of subjects before and after 8 weeks of taking either a Tribulus extract or a placebo [6]. No significant change was found in any of these parameters after supplementation with Tribulus when compared with the placebo group.

The next study evaluated claims that LH and subsequently testosterone levels were increased above normal after ingesting Tribulus extracts [7]. Baseline levels of testosterone and its metabolites in urine and serum were established for all subjects. Participants were then fed a heaping gram of Tribulus daily for 4 weeks. Testosterone levels were checked routinely, and researchers found no significant increase in hormone levels beyond normal day to day variations. This research is the most significant and relevant to our discussion here today. It was conducted on humans and looked for the two variables we are most concerned with: increasing testosterone and, in turn, increasing exercise performance—and in both of these studies Tribulus failed to do either.

I just briefly want to discuss the Sopharma research. This research was not included in this review for several reasons. It has not been published in a reputable English language journal and subsequently peer reviewed; and, subsequent research has been unable to elicit the same results when conducted in a similar manner [7].

In my opinion Tribulus is not useful for increasing androgen levels in healthy males or improving exercise performance. There may be some effect on individuals with androgen deficiencies where Tribulus acts as a precursor to deficient DHEA, but at this time the only conclusion that can be definitively drawn about Tribulus is that it seems to be quite effective at making castrated rats horny [8].

ZMA

Next we’ll take a look at ZMA, a combination of Zinc Monomethionine Aspartate (30mg), Magnesium Aspartate (450 mg) and Vitamin B-6 (10.5 mg). The theory behind ZMA is simple: zinc and magnesium are important in the production of steroids and B-6 is important in energy production, two things crucial to athletes. If you become deficient in any of the ingredients in ZMA you see a subsequent decrease in androgen production and performance in general–and there is evidence that a number of diets may be deficient in all three [9-22]. In addition, high protein intake and exercise can increase daily B-6 requirements. Lastly, intake of other minerals can affect the absorption of magnesium and zinc, making supplementation attractive [23-27].

But what evidence is there to show that ZMA intake increases exercise performance or testosterone levels? In vitro research clearly illustrates how supplementation with magnesium can decrease the amount of testosterone bound to human serum albumin, thus, increasing free testosterone [28]. Another study, this time actually conducted on people, showed an increase in performance in untrained males after 7 weeks of supplementing with magnesium [29].

Another interesting effect of both zinc and magnesium is their influence on cortisol secretion. Fourteen-day supplementation with magnesium decreased cortisol secretion in male subjects during ergometer testing. A study conducted with oral dosages of zinc ranging from 25 mg to 50 mg showed an inhibitory affect on cortisol secretion over 240 minutes [30, 31]. This evidence suggests that ZMA supplementation could cause performance increases and an increase in testosterone via the decrease of the catabolic hormone cortisol.

In conclusion, ZMA supplements definitely have the potential to increase testosterone production and performance in individuals deficient in any of the constituent ingredients. The likelihood of raising testosterone production above physiological maximums seems unlikely given the nature of the effect of the product; therefore, supplementation with ZMA should be looked at as a preventative measure to make sure testosterone levels don’t fall below peak.

Androstenetrione

Now let’s look at a totally different approach to increasing testosterone production. Androstenetrione, marketed by Ergopharm under the name 6-oxo, is a proven aromatase inhibitor (AI) (aromatase is the enzyme responsible for the conversion of androgens to estrogen) and has been used extensively as a legal, over-the-counter source for post-steroid-cycle therapy in order to help restore the reduced testosterone production that results from exogenous androgen use [32-36].

Recently, an interest in androstenetrione as a standalone means to increasing testosterone has peaked. The theory is simple: decrease the amount of estrogen reaching the brain (a potent stimulus to decrease the hormones that cause androgens to be made) and see the body try and correct the drop by an increase in the production of androgen and estrogen precursors. Since you are taking a substance that is reducing the body’s ability to make estrogen from said compounds, the only other option is an increase in testosterone to maintain the same amount of estrogen.

While there is a paucity of clinical research on the effects of androstenetrione on testosterone levels (actually only one study regarding the sexual differentiation of castrated rats) there is ample research on the effects of other aromatase inhibitors and their effect on hormone production [37]. Several recent studies showed that hypogonadal elderly men showed an increase in testosterone while using an AI [38, 39]. Perhaps the most relevant and exciting research in the area shows an acute decrease in estradiol. This research also shows an increase in LH and subsequent increases in testosterone in both young and old men supplementing with an AI [40]. Theoretically, androstenetrione should largely work in the same way.

Conclusion

For those of you that just like to skip to the end, I’ll give you a quick summary of my findings regarding Tribulus, ZMA and androstenetrione. There is no published literature that indicates any benefit to supplementing with Tribulus in regards to increasing testosterone or exercise performance. ZMA shows promise as a preventative supplement, much like a multivitamin, with the goal of maintaining testosterone production at its peek. Androstenetrione shows the most promise of increasing levels of testosterone production above physiological norms by modulating the signals that tell your body to make more hormones.

References

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