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Side Effects and Plant-Based Supplements

7305-anabolicAs I’ve noted frequently in this column, there is a huge demand for supplements that have the ability to boost natural anabolic hormones, specifically testosterone, growth hormone and insulinlike growth factor 1. Insulin is also considered to be an anabolic hormone, in the sense that it helps prevent excessive muscle breakdown. In that way it tips the balance toward anabolic, or building, effects in muscle and away from catabolic, or breakdown, effects. No specific supplement is touted to boost insulin, since simple carbohydrate will effectively do it. The other anabolic hormones are also affected by food intake, but there is still a strong desire to boost them into the high-normal range for bodybuilding purposes.

In the early ’90s a new class of supplements came along to meet that need. The first of these “pro-hormones” to hit the market was DHEA, in the ’80s, but the early DHEA supplements were of poor quality and were eventually removed from commercial sales. In the mid-’90s the first of the true pro-hormones was introduced, androstenedione, which was an intermediary in the testosterone pathway. Specifically, it was produced from DHEA and was just an enzymatic step away from being converted into testosterone. DHEA wasn’t as effective, as it could diverge into other pathways considered less desirable; for example, it could be converted into dihydrotestosterone, or DHT, a metabolite of testosterone linked to prostate problems, acne and male-pattern baldness. Or the DHEA could wind up as estrogen, which can cause problems in both sexes.

Androstenedione, or “andro,” as it was colloquially known, was advertised as being a more direct source of testosterone than DHEA, since it was a step closer in the synthesis pathway to being converted into testosterone. Subsequent studies, however, many of which included bodybuilders, showed that andro, similarly to DHEA, could take an alternate pathway that involved conversion into estrogen. Andro did share another property with DHEA, in that both substances more reliably boosted testosterone in women than they did in men.

After andro appeared, a number of other pro-hormones were developed and marketed commercially. As expected, most were targeted for use by bodybuilders and other athletes, who ostensibly wanted the benefits of increased testosterone without the risk of using anabolic steroids or other drugs. The reports of the various pro-hormones’ effectiveness were mixed. Some users reported significant gains in muscle and strength, while others reported nothing. A few even mentioned side effects normally associated with anabolic steroids, such as acne and male-pattern baldness. The scientific studies on many of the second-generation pro-hormones also proved disappointing, with the majority showing little or no benefits but significant risk of some of the same side effects that often occurred with steroid use. So you had supplements that brought many of the same side effects as steroids but with none of the hoped-for benefits, such as muscle gains.

A lot of that changed with the introduction of the third and final generation of pro-hormone supplements. This group did prove effective, and many users reported gains in muscle size and strength. Normally, that would suggest a placebo effect: The users believed that the supplements would work, so they did. But there was more than a placebo at work. The third-generation pro-hormones worked because they contained actual anabolic steroids.

To call these supplements “pro-hormones” was inaccurate, since in many instances they were actual anabolic steroids that had been synthesized 40 years earlier but never marketed by pharmaceutical companies. Most of the formulas for those old steroids were cataloged in a 1968 book by Vida. So it didn’t take much effort for someone with a background in steroid chemistry to look up the structures of the old hormone drugs and then introduce them to the market as “new” pro-hormones.

The problem was, there was a good reason that the steroids had never been marketed commercially. Most showed too high a risk-to-benefit ratio. Simply put, while they usually did have pronounced anabolic effects, their side effects proved too common and too serious for any company to contemplate marketing them. The studies that found the effects were conducted on animals. The actual possible human side effects were never examined, since the decision not to market the drugs was already made.

In fact, it was only when the same steroid drugs were resurrected as “pro-hormone” supplements in the early 2000s that their potential toxicity became apparent. Since they were oral drugs, users often suffered from liver toxicity that was similar to or even exceeded that produced by existing oral steroids. Still, they were effective in boosting muscle size and strength, as they were actual drugs. These new category of supplements came to include drugs known as “designer steroids,” for which no research at all existed. Many were developed for the express purpose of beating athletic drug tests, as testing procedures depended on having an existing profile, or “fingerprint,” of a drug. No such profile existed for the designer steroids, since they had never been on the market.

As with the hapless animals that had been exposed to some of the formulas in the ’60s, humans who used the third-generation pro-hormones soon developed some serious side effects that were documented as case histories in various medical journals. That caught the attention of the United States Food and Drug Administration and led to an amendment being added to the Anabolic Steroid Control Act in 2005 that resulted in the removal of most of the tainted pro-hormones from the market.

Even so, you still see some of them today, often in Internet ads. Although they are clearly illegal, a few unscrupulous companies attempt to cash in on the demand for “natural testosterone boosters” by selling them in defiance of the law. Recognition of the fact that so-called designer steroids are being sold as over-the-counter supplements recently led Congress to introduce a new law, the Designer Anabolic Steroid Control Act of 2014, which lists 25 current steroid additives in supplements and makes them illegal for sale. The law is also worded to prevent new formulas from being introduced.

Perusing the labels of some of the alleged testosterone-boosting supplements that are still being peddled often reveals esoteric ingredients. Some use more common ingredients but disguise them by listing alternate names. An example is DHEA, which can still be sold legally. Many of the current pro-hormones are based on DHEA—but the labels instead list an alternate chemical name for it.

In other cases, various ingredients that almost no one has ever heard of are listed. If you research them, you’ll find that most are plant based and are entirely legal. The salient questions for potential consumers: Are they effective, and are they safe? Regarding effectiveness, the honest answer is, no one knows. The research on many of them is scant, to say the least, usually involving a couple of animal studies, with no human data whatsoever. That’s an obvious problem—what happens in animals doesn’t always translate into human physiology. Sometimes it does, however, but without any human research, it’s a shot in the dark whether these plant-based ingredients work. Another aspect to consider: Just because something is “natural” doesn’t mean it’s safe. Arsenic is natural, but it’s certainly not safe.

The safety question of various plant ingredients found in supplements was recently examined .1 The study lasted six months and featured 740 trained subjects, including 420 bodybuilders, 70 cyclists and 250 fitness athletes. All had trained for at least a year, averaging one to two hours a day, three to six days a week. Of the 740 subjects, 26 said that they regularly used some type of plant-based supplement. As expected, 45 percent admitted that they had no knowledge of what those ingredients did.

Lab tests of those using the plant-based supplements showed no signs of organ toxicity or damage. Most of the other lab values didn’t differ from what happened in control subjects, who didn’t use the supplements. Still, 15 of the 23 subjects who did use them showed marked hormonal changes—that’s 65 percent. Specifically, 10 of the men showed a significant increase in progesterone, which, although produced in both sexes, is considered primarily a female hormone. Fifteen other subjects had abnormal estrogen levels, with five (two females and three males) having dramatic increases in estrogen. Two male subjects showed increases in both estrogen and testosterone.

What caused the changes in those using the plant-based supplements? The highest estrogen readings occurred in those who ate a lot of soy protein. That isn’t surprising, since soy is rich in phytoestrogens, which are plant substances that can act as weak estrogens in the body. The men with the higher progesterone levels consumed supplements containing ecdysteroids, which are insect hormones that some studies show may influence testosterone. Those with higher testosterone ate high doses of soy protein and products that contained ecdysteroids and tribulus terrestris, a plant-based supplement long touted to boost testosterone. Some studies, however, show that it more preferentially increases estrogen when used by young men. That, along with the soy, could account for some of the higher estrogen levels seen in a few of the male subjects.

While soy may boost estrogen when eaten in larger amounts, it also to some extent inhibits 5-alpha reductase, an enzyme that converts testosterone into DHT. That would have the paradoxical effect of boosting both estrogen and testosterone when soy is used in larger quantities.

The authors suggest that the primary problem with some of the plant-based ingredients is that they boost estrogen; however, smaller doses of soy have never been shown to do that. Indeed, smaller amounts of soy phytoestrogens are known to interfere with estrogen binding to its cellular receptors, which actually blocks estrogenic effects. So, if this study shows anything, it underscores the wisdom of the old saying, “Only the dose determines the poison.”

1 Borrione, P., et al. (2012). Consumption and biochemical impact of commercially available plant-based nutritional supplements. An observational pilot-study on recreational athletes. J Int Soc Sports Nutr. 9:28.


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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