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The Case of the Mysterious T-boost

Regular readers of this column know that I’m not a big fan of the so-called testosterone-boosting supplements. None of them have any scientific data to support their effectiveness for use in humans, although there are sparse anecdotal reports of folk use and increases in testosterone of animals.

Not to say that none of the over-the-counter testosterone-boosting supplements work. The last generation of pro-hormones, which were mostly removed from market sales in 2005, were quite effective at boosting testosterone. But there was a reason for their effectiveness: they really were anabolic steroids—actual discarded anabolic steroid drugs. Originally developed by drug companies nearly 50 years ago, were never marketed because their toxicity was considered too high, especially in various oral drugs. Those same drugs were resurrected a half century later and marketed as “pro-hormones,” which was a misnomer, since they were actual synthetic hormones.

One notable example of this was popular supplement called “Superdrol.” It was said to be a milder form of the popular anabolic steroid Anadrol, an oral steroid known to be particularly hard on the liver. As it turned out, Superdrol was even more toxic to the liver than Anadrol. A number of case studies were published in medical journals documenting the serious liver-based side effects experienced by those who purchased and used Superdrol. But did it boost testosterone? You bet. It just slowly destroyed your liver at the same time.

Since the removal of most of the actual-steroid pro-hormones in 2005, companies have sought to keep the lucrative market of testosterone-boosters alive by offering supplements based on truly natural substances, such as herbs. I’ve discussed some of those products in past editions of this column. In short, some of them actually work, but there simply isn’t enough evidence to show it.

One supplement, also recently removed from the market, that did have some actual published evidence behind it was ATD. It was marketed as an “aromatase-blocker,” meaning that it blocked the activity of aromatase, the enzyme that converts testosterone into estrogen. One company sponsored studies that showed a 600 percent increase in free, or active, testosterone after subjects used the standard suggested dose of the product, but that spectacular rise turned out to be an artifact caused by breakdown products of ADT that interfered with the testosterone assay tests. Even worse: later animal-based studies showed that ATD appeared to interfere with androgen receptors in the brain, leading to a total loss of libido, or sex drive, in many of those who used the product.

A new case study examined the effects experienced by a 19-year-old man who used one of the current—and legal—testosterone-boosting supplements.1 It’s marketed mainly to bodybuilders who want to boost their testosterone but don’t want to use steroids. The guy who bought this supplement, however, purchased it mainly because of a perceived low sex drive. The sales materials suggested that it could help boost his sex drive, which would make sense, as testosterone does control libido in both sexes. Instead, the man wound up going to a doctor, complaining about fluid retention, erectile dysfunction and loss of libido. An initial test showed that he had a high testosterone level, which prompted the doctors to order more tests for his gonadotropin levels, including luteinizing hormone, which controls testosterone synthesis in the Leydig cells of the testes.

The doctors were surprised to find that his leuteinizing hormone was elevated. When you use anabolic steroids, your testosterone levels skyrocket, but the L.H. drops because of a feedback mechanism sent to the pituitary gland in the brain, where L.H. is synthesized. Since the doctors didn’t suspect steroid use, their initial diagnosis was that a tumor on his pituitary gland was causing him to secrete too much L.H.—which would explain his elevated testosterone. Still, they ran tests for estrogen; sex-hormone-binding globulin, which binds testosterone in the blood; and human chorionic gonadotropin. The doctors knew that HCG is structurally similar to L.H. and is used by bodybuilders and athletes to maintain their natural testosterone production during steroid cycles, since the steroids blunt the normal release of LH. Lack of luteinizing hormone stimulating the testes can cause shrunken testicles.

The tests showed no elevated HCG, but higher-than-normal estrogen. Since higher amounts of testosterone are subject to being converted into estrogen, that was the initial explanation for the elevated estrogen, but it still didn’t explain his high testosterone. It turned out that he was using an over-the-counter supplement touted to increase testosterone. He showed no increase in urinary androgens, no increase in the epitestosterone-to-testosterone ratio, both of which ruled out any actual anabolic steroids or testosterone. In short, the man was telling the doctors the truth.

So what was in the supplement that caused these effects? It used three different mechanisms to boost testosterone without causing negative feedback to the pituitary, which is what anabolic steroids do. The three primary ingredients were stinging nettle extract, horny goat weed and Ceylon spinach, or Basella alba.

Stinging nettle is an herbal extract that contains a substance known to bind to sex-hormone-binding globulin in the blood. In fact, it tends to bind to SHBG with greater affinity than does testosterone itself. It separates the SHBG from testosterone, leading to a rise in free, or active, testosterone.

Horny goat weed, or epimedium, as the name implies, has long been used to treat sexual dysfunction and boost libido. The effects are attributed to a flavonol found in horny goat weed called icariin, which is known to inhibit the same enzyme that Viagra does, leading to vasodilation and improvement of erectile dysfunction. But it doesn’t work unless mechanisms involved in nitric oxide synthesis are working. Icariin appears to boost local NO production. In addition, it is also independently associated with elevations in testosterone, at least in animal studies. We don’t know how it does that, but is thought to work at the level of the testes, since it doesn’t boost leuteinizing hormone.

As for the third active ingredient, Ceylon spinach, it contains indole-3-carbinol, which is also found in cruciferous vegetables, such as broccoli and cabbage. I3C works by converting active estrogen into an inactive form. For that reason, it appears to protect against cancers related to active estrogen, such as breast and prostate cancers. Studies of rats show that Ceylon spinach directly boosts testosterone, although there’s no evidence that it works that way in humans.

Although the man using the supplement had higher-than-normal estrogen, his high testosterone level was enough to counteract the elevated estrogen. The resulting low estrogen-to-testosterone ratio led to the increase in L.H., since estrogen is the primary signal that lowers L.H., but the increased L.H. also boosts testosterone synthesis. That’s also the way that aromatase-inhibiting drugs, such as Arimidex, boost testosterone in men.

The doctors who wrote this case study suggest that using the supplement causes similar side effects to using anabolic steroids. I would disagree with that statement. While the supplement did boost testosterone, the increase was modest and in no way comparable to the amounts produced by using actual anabolic steroids.

While this case study involved only one person, based on the mechanisms of the supplement, it would likely produce similar effects in other users. It doesn’t appear to produce pituitary suppression, as anabolic steroids do, so it seems to be much safer. For men with low testosterone or those seeking a moderate anabolic boost, this type of supplement might be useful. Still, the mystery of the case endures, since the doctors never did explain why the supplement would cause the same problem it was supposed to cure: erectile dysfunction. My guess is that the man’s sex problem was more related to psychological factors than to anything biochemical or hormonal.

1 McDonald, T., et al. (2011). A novel case of a raised testosterone and LH in a young man. Clin Chim Acta. 412: 1999-2001.

Editor’s note: Jerry Brainum has been an exercise and nutrition researcher and journalist for more than 25 years. He’s worked with pro bodybuilders as well as many Olympic and professional athletes. To get his new e-book, Natural Anabolics—Nutrients, Compounds and Supplements That Can Accelerate Muscle Growth Without Drugs, visit IM

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