Bodybuilding Pharmacology: Invisible Steroids

Invisible Steroids
Athletes and sports organizations have engaged in a cat-and-mouse game concerning various banned drugs. Despite ever-increasing sophistication of tests designed to detect athlete drug use, athletes somehow find ways to circumvent them. One favored method of beating drug tests was to take so-called masking agents that would disguise drug use. They included diuretics, to dilute urine volume, and probenecid, which is normally used to treat gout. When officials realized what those masking agents did, they were added to banned-drug lists.

Even so, the hot rumor in the athletic world is the reputed existence of 'designer steroids.' They aren't ordinary steroids that come in fancy packaging, as the name might imply, but are specially structured to pass undetected by the drug test. The tests currently used to detect anabolic steroids and other drugs count on established drug signatures, or breakdown products, that show up in tests. Without such signatures a drug cannot be detected.

A new study highlights another type of designer steroid that recently turned up.1 An Olympic drug-testing lab at UCLA evaluated some anonymous urine samples obtained from athletes. One sample from a female athlete showed the presence of a compound that didn't match other drug signatures. Scientists working at the lab figured out that the mysterious drug was norbolethone, also known as Genabol, norboletone and WY3475.

Norbolethone is in the 19-nor category, as are familiar drugs such as Durabolin and Deca-durabolin, as well as over-the-counter 19-nor pro-hormone supplements. The curious thing is that the drug, first synthesized in 1966, was never marketed. Early tests showed that its anabolic activity exceeded the androgenic activity by a factor of 20, making it highly anabolic. Why it was never marketed remains unknown but may have been due to negative animal toxicity studies or because it caused menstrual problems.

That last bit of information shows that the drug may have been intended for use by women. Many female athletes prefer using 19-nor steroids because they have less androgenic activity and thus are less likely to produce masculinizing side effects than, say, testosterone. On the other hand, 19-nor drugs tend to leave long-term metabolites in the body, making them an easy target for drug tests.

If the drug signature isn't available, however, it makes no difference how long it stays in the body; it's still invisible on drug tests. The drug had never been detected in any previous test by any Olympics-recognized lab procedure. That makes it a true designer steroid, probably used by many female athletes all over the world.

Since it hasn't been manufactured in more than 30 years, that leaves just one likely source: a renegade chemist with extensive knowledge of steroid chemistry. Another likelihood is that many similar drugs are also in circulation, used by countless athletes with impunity. Think about that next time you view any athletic competition in which the athletes look to be on drugs yet have passed all drug tests. In this cat-and-mouse game the mouse is truly mighty.

The Other Fat Burner
Ephedrine and caffeine deserve their reputation as a superior fat-burning combination. The term 'fat burning' is a misnomer in this case, however, since fat is only actually burned with exercise, especially aerobic exercise. A more correct term is 'fat mobilizer.' Despite numerous dire warnings in the media about using ephedrine or mahuang and caffeine, most of the problems that occur with ephedrine and caffeine arise either from preexisting conditions or from using too high a dose.

Ephedrine works because it has a structure similar to epinephrine, a catecholamine hormone that directly interacts with special cellular receptors called beta-adrenergic receptors. When they're activated, a chemical cascade is initiated in fat cells that results in a release of fat into the blood. Because of its structural similarity to catecholamine hormones, a certain level of fight-or-flight stress also occurs with ephedrine use, which manifests itself as a slight increase in heart rate and blood pressure. In people with heart disease or high blood pressure, that slight rise could be a problem, and they should avoid using ephedrine or mahuang products.

But other adrenergic cell receptors also affect fat loss'alpha-adrenergic cell receptors. Unlike the beta-adrenergic receptors, alpha receptors block the release of fat from fat cells, or lipocytes. Most scientists believe that women have such recalcitrant fat deposits in their hips, buttocks and legs because of a preponderance of alpha-adrenergic cell receptors in those areas.

What can be done about alpha-adrenergic fat-cell receptors? It turns out that one supplement works to block them, thereby allowing the body to mobilize and burn fat at a normal rate. That supplement is yohimbine, which is derived from an African tree and is found in an herbal extract called yohimbe. Most over-the-counter yohimbe supplements contain an average of 3 percent yohimbine.

An interesting'though unproven'thing about yohimbine is that many bodybuilders believe it's a testosterone booster. In pre-Viagra days a pharmaceutical drug called Yocon was often used to treat male impotence, and it had 5.4 milligrams of yohimbine per pill. It appeared to work by increasing blood circulation in the sexual organs. That led to an erection in males, with an associated increase in sexual activity. Since testosterone is reputed to do the same thing, it's not hard to see how yohimbine earned its reputation.

But while the testosterone-boosting effects of yohimbine may be apocryphal, the fat-mobilizing effect is genuine. Yohimbine, by blocking alpha-adrenergic fat-cell receptors, promotes the release of norepinephrine, a catecholamine hormone that not only offers a fat-mobilizing effect but also promotes thermogenesis, or the conversion of fat calories into heat. Unlike ephedrine, yohimbine doesn't promote epinephrine release and does not cause either the cardiac or the blood pressure effects linked to ephedrine. When taken before exercise, yohimbine promotes a greater release of norepinephrine than would naturally occur during exercise. Studies show a doubling of the level of free fatty acids in the blood during exercise after subjects used yohimbine.

The main problem with yohimbine is that when it's taken with food, particularly carbohydrates, it potentiates the release of insulin, and too much insulin tends to promote an increase in fat storage while blocking fat release. In fact, studies examining the fat-loss effects of yohimbine clearly indicate that taking it either close to or with a meal completely negates its fat-mobilizing effects. One recent review suggested that for best results, you should eat no food for at least four hours after taking a dose of yohimbine.2

The best time to take yohimbine is probably in the morning, on an empty stomach before aerobic exercise. The usual suggested effective dose is 0.2 milligrams per kilogram, or 2.2 pounds, of bodyweight. A man weighing 200 pounds would need 18 milligrams, which is a far greater amount than is found in most fat-burning supplements. The supplement may work even better for women because of their preponderance of lower-body alpha-adrenergic fat cell receptors.

While you shouldn't eat or drink anything other than water when taking yohimbine before exercise, taking caffeine may potentiate its fat-loss effects. Caffeine also promotes the release of norepinephrine. Don't drink coffee, however. Instead use a pharmaceutical preparation of caffeine, such as caffeine pills, in a dose of about 200 milligrams.

While it might appear beneficial to include ephedrine in that fat-mobilizing combination, it could lead to problems. A study of obese women found that the women experienced no problems when using ephedrine and caffeine before exercise but that when yohimbine was added to the mix, they showed signs of increased heart workload.3 That probably resulted from the abundance of both epinephrine and norepinephrine released by using the combination.

Yohimbine alone can increase heart rate, especially during aerobics, due to its potent norepinephrine-releasing effects. As noted above, however, troublesome cardiovascular effects rarely occur with yohimbine use, especially when taken in the suggested dose of 0.2 milligrams per kilogram of bodyweight.

Studies of people who have taken gross overdoses of yohimbine, ranging from 200 to 350 milligrams, show that those cases resolved themselves with no permanent effects. On the other hand, people with tendencies to either mania or anxiety should avoid using yohimbine. Norepinephrine plays a significant role in both conditions, and the greater release of norepinephrine makes matters far worse.4

If you're taking antidepressant drugs that work by blocking norepinephrine uptake, you should not use yohimbine supplements. Using yohimbine with alcohol also makes you drunker than drinking alcohol alone. Some men report spontaneous erections after using yohimbine, which may or may not be desirable, depending on existing conditions.

Another thing to keep in mind is that most yohimbe herbal supplements contain 3 percent yohimbine, so a 100-milligram dose would contain only 3 milligrams of yohimbine. That's if you're lucky enough to actually find such a supplement, since many yohimbe supplements contain no actual yohimbine.

References
1 Catlin, D., et al. (2002). Detection of norbolethone, an anabolic steroid never marketed, in athlete's urine. Rapid Commun Mass Spectrometry. 16:1273-1275. 2 McCarty, M. (2002). Preexercise administration of yohimbine may enhance the efficacy of exercise training as a fat-loss strategy by boosting lipolysis. Medical Hypotheses. 58:491-495. 3 Waluga, M., et al. (1998). Cardiovascular effects of ephedrine, caffeine and yohimbine measured by thoracic electrical bioimpedance in obese women. Clin Physiol. 18:69-76. 4 Price, L.H., et al. (1984). Three cases of manic symptoms following yohimbine adminstration. Am J Psychiatry. 141:1267-68.