Supplements or drugs? by Jerry Brainum

 

 

I can still remember the excitement that I felt whenever I bought a box of one of my favorite childhood treats, Cracker Jacks. There was nothing particularly special about this product. It consisted of caramelized popcorn with a few caramel peanuts mixed in. That, however, wasn't the main attraction. The excitement derived from a minor mystery. Every box included a small gift, a nick-knack that wasn't worth much, and in most cases, didn't do much, either. But just the mere thought that I would be finding who knows what in a box of popcorn was enough to intrigue my young mind. These free gifts usually amounted to such items as small magnets, mirrors, or if you were really lucky, a compass. But it was the anticipation that really aroused my excitement, rather than the cavity-inducing popcorn. In a way, many of the current sports supplements aren't that different than that box of Cracker Jacks. Both products often contain a hidden ingredient that doesn't appear on the label. While the toy included with a box of Cracker Jacks proved benign, unless you ate it, the same cannot be said for the hidden ingredients in many sports supplements. To paraphrase a line from Forest Gump, "Many supplements are like a box of chocolate; you never know what you're going to get next."

The door opened for extra added ingredients in supplements with the passage of the Dietary Supplement Health and Education act in 1994 by Congress. This legislation was the result of a behind-the-scenes effort by lobbyists funded by various food supplement companies. A key aspect of the new law was that it transferred supplement safety evidence from the companies that sell supplements to the Food And Drug Administration (FDA). In short, before the FDA could remove any product from market sales, it had to conclusively prove that the supplement, or any ingredients contained in the supplement, could cause harm to those who used it. In addition, it allowed the legal sale of any substance that could also naturally be found in food or another natural source. This was done to differentiate possible future supplement ingredients from drugs, which are always synthetic. That, of course, assumes that if something is "natural" that it is safe for human consumption, which is a rather large assumption considering that such items as arsenic and cyanide also are found to exist in many natural products and foods.

One of the first supplements affected by the new law was DHEA. DHEA, or dehydroepiandrosterone, is a steroid hormone that is the precursor for more active steroid hormones in the body, such as testosterone and estrogen. The body converts DHEA into these other steroids as needed through the activity of specific enzymes. DHEA was on the market prior to the 1994 law but was removed in the late 80s because of a lack of quality control in the supplements. These early versions were made from Mexican yams (as were the original versions of birth control pills), with the problem being that some products labeled as "DHEA," contained nothing more than Mexican yam extract, which had no activity in the human body in relation to hormone production. But when the 1994 law was passed, DHEA again reappeared in commercial products, this time as a "testosterone booster" and general all-around health tonic. Some studies showed that many older people are deficient in DHEA production, and although there is no precise biological role for DHEA, the lack of sufficient amounts was thought to adversely affect health. So DHEA had a market for both older people, and those looking for a boost in testosterone.

The testosterone effect didn't quite pan out as expected. In younger men, DHEA was mainly converted into a byproduct of DHT metabolism. DHT, or dihydrotestosterone, is a byproduct of testosterone formed when the enzyme 5-alpha reductase interacts with testosterone in the body. DHT is often called "testosterone's evil twin," since it's thought to be responsible for such maladies as male pattern baldness, prostate enlargement, and acne. It also does s few good things, such as promote the development of male sex organs, and in the brain, produces neurosteroids that may boost memory and intelligence. But generally, it's best to keep DHT in check to prevent those possible nasty side effects. Luckily for the young men who used DHEA, the DHT metabolite that resulted didn't cause any side effects. In women, DHEA is first converted into androstenedione, then into testosterone. As such, DHEA is a more reliable source of testosterone for women than it is for men. Oddly, in some older men, DHEA can boost estrogen levels, which may be a good thing if the older man is lacking in estrogen, which is rarely the case. In women who use DHEA, about half experience severe cases of acne. Since women who use DHEA often get acne, and in young and older men its conversion to testosterone isn't certain, other sources of boosting testosterone became a goal for food supplement companies.

In the late 90s, during a celebrated baseball home run derby to beat Babe Ruth's long-standing record of 60 home runs, it was revealed that one of the players involved in the race to beat the record, Mark McGwire, was using a product called androstenedione, or simply, "andro." This steroid is one step further in the testosterone synthesis pathway than is DHEA. Chemist Pat Arnold found an old 1963 study that showed women who ingested andro converted most of it directly to testosterone. Since this was thought to be a far more reliable pathway compared to DHEA, which could divert to several other directions, Arnold began touting the benefits of Andro on various Internet forums. Within a short time, a few companies introduced it to the supplement market. Andro was legal to sell because it existed in small amounts in some natural products. Around that time, I looked at the testosterone pathway and noticed that andro could easily be diverted to the estrogen, rather than the testosterone path. I voiced this observation but was ignored because of all the excitement generated by the introduction of an "effective" new testosterone booster that was also safe and legal.  The revelation that home run hero McGwire had used andro sent sales of the product through the roof.

But Arnold had relied on one obscure study of andro from the 60s to determine the effectiveness of the product. Newer studies told a different story. The studies showed that in men who ingested andro, testosterone levels did indeed rise over an 8-hour period, but only with larger doses of 300 milligrams and up. Using the suggested 100-milligram dose didn't affect testosterone levels. Even worse, both dosages seemed to promote a higher rate of estrogen release than they did testosterone, a fact that I had noticed even before the supplements were introduced. Some men who used andro did seem to get a good T boost, while other developed obvious estrogen-related side effects, such as gynecomastia (male breast development), water retention, and increased body fat levels. When tested for changes in body composition, again andro produced discouraging effects. No gains in strength occurred with doses of either 100 or 300 milligrams. Even worse, when used in the presence of existing normal testosterone levels, andro reverted to anti-androgen activity, interfering with normal testosterone activity in the body.

With the failure of andro, food supplements companies hired chemists such as Pat Arnold to come up with other testosterone boosters to meet the increasing demand of bodybuilders and athletes who sought a reliable source of something that would increase their testosterone (T) levels without inducing the side effects associated with using anabolic steroid drugs. What followed was a series of esoteric testosterone precursors, all of which fell under the umbrella term of prohormones. The term implied that these substances weren't actually testosterone, but rather precursors that would be reliably converted to testosterone through enzymatic activity in the body. Each successive new substance was touted to be the "real thing" that would boost T levels safely, but minus side effects if used as directed. Unfortunately, all of these highly touted new supplements suffered a similar fate as andro. They either didn't produce any muscle or strength gains or tended to boost estrogen more than testosterone. It was time to go back to the chemical drawing board to dig up some substances that might actually work as advertised. In doing so, however, effectiveness trumped long-term safety.

Steroid chemists turned to a 1969 book written by Julius Vida that documented the structures of hundreds of obscure anabolic steroid drugs. These drugs had been developed in the early to middle 1960s during the boom time of anabolic steroid development by various large drug companies. The goal was to synthesize compounds that would magnify the anabolic effects of testosterone while minimizing the androgenic effects, which included negative effects on the prostate gland, hair, and other effects. By manipulating the basic structure of testosterone, chemists developed thousands of compounds, now called anabolic-androgenic steroids. The "androgenic" was left in there because no matter how hard they tried, the steroid chemists could never completely disassociate the androgenic effects from the more sought-after anabolic effects of the compounds. Many of these experimental steroids were given to lab animals, such as rats, and those that showed more of an anabolic rather than an androgenic effect were deemed commercially suitable. Another consideration was the level of toxicity of the compounds. Most were oral compounds whose structures had been manipulated to resist premature breakdown in the liver, which would normally rapidly occur when testosterone was ingested orally. But this manipulation also resulted in a far greater negative effect on the liver, since the steroids tend to accumulate in the liver and cause a type of inflammatory effect. This localized inflammation, in turn, resulted in a blockage of normal bile flow through the liver, causing a condition known as cholestasis. When that happened, the continued swelling of liver cells eventually resulted in their destruction. Some of the experimental steroids were noted to be more potent in this effect than others, and these steroids were relegated to pharmaceutical purgatory, never to be thought about again, until Vida exposed them in his 1969 book.

It was these obscure steroids that food supplement companies turned to as the "next generation" of prohormones at the turn of the 21st century. To label them "prohormones" was a misnomer, however, since most of them weren't prohormones, but rather actual anabolic steroid drugs that had never been released to the commercial market. As you might expect, these supplements worked a lot better than the previous so-called prohormones. People hiding behind fake screen names on various Internet forums lauded the benefits of the new supplements, raving about their spectacular gains in muscle mass and strength. The supplement companies selling these thinly disguised anabolic steroid "supplements," were raking in the cash. But they say that things never last forever, and sure enough, reports began trickling in about users of the supplements experiencing side effects that ranged from mild to severe. Most were the same side effects that you would get from legal anabolic steroids themselves, such as negative effects on blood lipids, hair loss, acne, masculinization of women, and so on. When the FDA realized that actual anabolic steroids were being sold as over-the-counter supplements, they prodded Congress to pass an amendment to the 1990 law that classified anabolic steroid drugs as schedule-3 drugs, punishable by fine and imprisonment.  This new law, the Anabolic Steroid Control act of 2004 went into effect in 2005 and banned most of the existing prohormone and steroid-based supplements by specifically naming them in the legislation. The first thing this amendment did was insert a definition of anabolic steroids as follows: “The term ‘anabolic steroid’ means any drug or hormonal substance, chemically and pharmacologically related to testosterone (other than estrogens, progestins, corticosteroids, and dehydroepiandrosterone).” It includes specific references to androstenediol, androstanedione, bolasterone, boldenone, calusterone, clostebol, dehydrochloromethyltestosterone, drostanolone, ethylestrenol, fluoxymesterone, formebolone, furazabol, hydroxytestosterone, mestanolone, mesterolone, methandienone, methandriol, methenolone, methyltestosterone, mibolerone, nandrolone, nor androstenediol, nor androstenedione, norbolethone, norclostebol, norethandrolone, exandrolone, oxymesterone, oxymetholone, stanozolol, stenbolone, testolactone, testosterone, tetrahydrogestrinone, and trenbolone. 

Undaunted by the passage of the law, food supplement companies went a step further and commissioned steroid chemists to come up with an entirely new category of drugs known as designer steroids. The existence of such drugs emerged after the BALCO scandal involving several elite athletes was exposed. It turned out that these athletes were using drugs that didn't show up in the usual drug testing procedures. A few of them were developed by the same chemist who produced Andro as a supplement, Pat Arnold. While these designer steroids were without question effective, they also had the same problem as the obscure steroids dug out of Vida's book: there was no information available related to their long-term effects on health, or even their effectiveness. The food supplement companies jumped to sell many of these designer steroids, often not putting them on the label to avoid FDA scrutiny. But one thing that you couldn't hide was the side effects. Once again, reports began appearing in the medical literature about isolated cases of people who used the designer drugs and experienced side effects that in some cases were worse than those caused by the old steroid supplements. Once again, Congress passed still another law, the Designer Anabolic Steroid Control Act of 2014, which was just signed into law by President Obama, that added about 24 new drugs to the banned list, mostly designer steroids, but more importantly, made the penalties for selling them far more severe. Failure to comply with the law could result in a 10-year prison sentence, along with a $2.5 million fine. The law also was broader than the past laws, this time even covering botanical sources of testosterone-boosters, or so-called "herbal testosterone supplements." (such supplements will be extensively discussed in an upcoming issue of the Applied Metabolics Newsletter).  

But the question that everyone wants to know is: Do these designer steroids really work?

 

Do designer steroids really work?

 

So the initial versions of prohormone supplements appeared to work better on paper than in reality. DHEA did boost testosterone in women but at the cost of often severe acne. Androstenedione also boosted testosterone, but you had to ingest a minimal dose of 300 milligrams. With that dose, you would get a significant boost in testosterone, but also an equally significant boost in estrogen, thus bringing into play all of the negative side effects linked to higher estrogen levels. The knowledge that these basic steroids didn't work very well (actually, there is much more to DHEA, but that will be discussed in a future article in Applied Metabolics) led to a series of other prohormones, none of which produced the sought after effects of greater muscle mass and strength. This led to the release of the old, discarded anabolic steroid drugs from the 60s, which were resurrected as "prohormones," or "testosterone-boosters." In fact, they were actual anabolic steroid drugs. As such, they did work, but at a cost of having a high risk of side effects, even when using suggested doses. Recall that these drugs were never released by the drug companies that developed them, usually for reasons of lack of effectiveness, but more often due to unacceptable levels of toxicity, as shown in preliminary animal studies. Many had no studies at all to prove their safety or efficacy. But their anabolic to androgenic ratios was known, and this was enough to suggest that they could provide real anabolic effects, which they did.

But when the FDA learned of this new trend towards using actual anabolic steroids for sale as over-the-counter supplements, they began sending out warning letters to companies selling the supplements. This was especially true following the passage of the 2004 Steroid Amendment law. Those who sold anabolic steroid-based "supplements" were in clear violation of the law, even if the substance involved wasn't directly listed in the law. The mere fact that it was a preformed version of testosterone classified it as a drug, thereby making sales without a prescription illegal. Of course, since the drugs in question were never officially approved for sale by the FDA, that itself made them illegal to sell. What followed was a cat and mouse game between the understaffed FDA and companies selling the hormone/supplements. When the FDA would catch up to them, the companies would simply remove the compound in question from their supplement, then go back and change it to another steroid, often also changing the name of the product.

The final trend came about as companies, fearful of litigation imposed on them by the FDA, began to produce designer steroid-based supplements. The notion that this was happening first emerged during the BALCO athletic scandal when someone anonymously sent in a syringe that had been used on an elite athlete to the World Anti-doping agency or WADA. At first, no one could figure out what was in the vile, since the ingredients came up negative in standard drug testing procedures. Eventually, it was determined that this was an entirely new drug prepared especially for athletic use, hence the name, "designer drug."  Several more of these designer steroids soon emerged with names such as "THG" and ""DMT." As you might expect, virtually nothing was known about the new drugs, since they had never been studied. Their chemical structures, however, clearly indicated that they were potent steroids and also were undetectable. Drug testing is based on the "fingerprints" or metabolites of existing drugs, and since none of these drugs previously existed, they were invisible during drug testing procedures. Pat Arnold, the chemist who designed a few of the early prohormone drugs, also designed a few of the newer designer steroids, for which he was eventually arrested and charged.

While the older prohormone drugs didn't pan out well when they were examined in science studies, the question is, how would the newer designer steroids fare in such tests? if you went by public reaction to users of the supplements, you would think that they were equal or even superior to actual anabolic steroid drugs. Such views were often expressed by anonymous posters to various drug-related Internet forums and discussion groups. But they said the same thing about how much muscle and strength they gained from using the original prohormone supplements, so this level of information was both biased and anecdotal, hardly standing up to any level of scientific scrutiny. But a recent study did examine the effects of a supplement containing one of the designer steroids, and the results were much different than previous studies of prohormones.

A group of researchers from the University of Texas teamed up with other researchers from West Texas A&M University and the California Baptist University to examine the effects of one of the current designer steroids that was being sold as a bodybuilding supplement. This particular steroid went by various names, as is the usual custom for the newer steroids. The chemical name for the steroid was 3b-hydroxy-5a-androst-1-en-17-one. It was developed by Pat Arnold, who called it "1-DEHA." The name again changed when it appeared in supplement form, for it was now called "1-androsterone." For simplicity sake, I will refer to it simply as "1-andro."  This substance appeared in various over-the-counter supplements aimed at the bodybuilding market, under such names as "Decafire," Xtreme Anabolic Stack," and "1-andro." The study that analyzed its effects involved 17 resistance-trained men, average age, 23. They were randomly assigned to receive either 330 milligrams a day of 1-andro or a sugar-based placebo. They took these while engaged in a weight-training program for 4 weeks that involved 16 workout sessions. The men were tested before and after the study for body composition, muscular strength, lipid levels in the blood, and markers of liver and kidney dysfunction.

 

 

 

One of the previous designer steroids, known as 1-testosterone was twice as potent anabolically as natural testosterone produced in the body. That particular designer steroid (DS) was enormously popular, despite the fact that many users experienced significant side effects when using it. Even Pat Arnold said that it made him feel very ill. It did actually work to boost muscle mass, which was expected considering its superior anabolic potency to normal or natural testosterone. Although 1-test was twice as anabolic as testosterone, on a milligram to milligram basis, it had about 75% of the potency of testosterone. One notable advantage of 1-test was that it showed little or no conversion into estrogen. It did produce many of the same side effects of other anabolic steroids, such as male pattern baldness and acne, likely because it was a DHT-based steroid. The major side effect was an extreme feeling of lethargy. With the passage of the 2004 steroid law, however, 1-test was officially declared an illegal steroid.  Not to worry. The companies that sold 1-test merely had their hired gun rogue steroid chemists manipulate the 1-test structure, and they came up with 1-andro. When ingested, 1-andro is converted in the body through enzymatic activity into 1-testosterone.It was a rather elegant way to skirt the anti-steroid law!

The 1-andro supplied to the men in the study contained 110 milligrams of 1-andro per pill, along with 50 milligrams of 6,7 dihydrobergamottin, which is derived from grapefruit. It was placed in the supplement because it inhibits the enzymes that would normally rapidly degrade 1-andro, thereby boosting the potency of the steroid. The men in the study ingested one capsule 30 minutes prior to meals. They did this to slow the absorption of the steroid, and also minimize first-pass metabolism in the liver (refers to initial breakdown by liver enzymes). Another reason to provide it prior to larger meals was to prevent any gastrointestinal irritation induced by the supplement. Thus, the men ingested three caps a day of the supplement, with the manufacturers suggested intake being 2 to 4 caps a day.

The results after a month showed that three of the subjects in the placebo group and six of nine in the supplement group reported a few adverse effects. These included headaches, acne, muscle cramps, dehydration, and mood swings. Those using the actual supplement showed a 6.4% increase in lean mass, a drop in fat mass of 24%, (placebo group increased lean mass by only 0.5% and lost 9.5% body fat along with strength gains less than half that of the steroid users) along with 9.2%, 14.2%, and 14.6% increases in their bench press, squat, and deadlift poundages respectively. The study authors suggest that using the dose of the supplement in the study provided similar improvements in body composition and muscular strength that would occur when using 300 milligrams a week of testosterone enanthate, an injectable form of testosterone. That's the good news. But those using the actual steroid also showed a 40% drop in protective high-density lipoprotein cholesterol, along with a 30% elevation in low-density lipoprotein cholesterol (LDL). Higher levels of LDL, along with decreased HDL levels, are considered risk factors for cardiovascular disease. The supplement users also showed a few bad effects on their livers. Levels of albumin, a protein produced in the liver, were reduced. When low, this is considered a sign of liver stress. Four other liver enzymes were also elevated, pointing to a localized inflammation of the liver that could eventually result in severe liver disease, including liver failure. There were also signs of kidney stress in the supplement users. These were shown by elevated levels of creatinine, a byproduct of creatine metabolism that is elevated with kidney stress, and also a reduction in the glomerular filtration rate, which measures how well the kidneys are filtering the blood.  But since another test of kidney function, BUN was not affected, the stress on the kidneys from the supplement was minimal. The main problems were the effects on blood lipids (HDL and LDL) and liver function. The study authors also note that since the compound found in 1-andro is converted into testosterone in the body, it is illegal for athletic competition, and can be detected for a week after ingestion with standard drug test procedures. Every time one of the newer steroids is identified, its "fingerprint metabolites" are added to standard drug tests. So while this steroid/supplement does work, the study authors suggest that its negative effects on health far outweigh any possible benefits. That statement by the study authors underscores findings of what occurred with other anabolic steroid-based supplements. Ironically, this study is being used on various websites that sell 1-andro. But the sites only mention the gains in muscle mass and strength from the steroid--leaving out the part about side effects that also occurred!

 

What are the side effects and the causes of such effects with tainted supplements?

 

Testosterone consumed orally is rapidly degraded in the liver in a process called "first-pass metabolism." When steroid chemists in the employ of large pharmaceutical companies were told to produce an orally absorbed form of testosterone that would resist premature liver breakdown, they had several options open to them. The primary goal was not only to produce an orally absorbed and long-lasting form of testosterone, but also one that was more potent anabolically, but less androgenic than testosterone. The androgenic effects of testosterone include such aspects as male pattern baldness, acne, and prostate enlargement. The anabolic effects feature increased protein synthesis, bone mass increases, and prevention of catabolic states associated with diseases, such as cancer. The first oral anabolic steroids, as the new drugs came to be known, were produced by simply adding a methyl group to a certain point in the basic steroid configuration. As such, the first oral anabolic steroid produced was Proviron, which was produced the same year that testosterone was isolated, 1934. This steroid was also known as "1-methyltestosterone." In later years, its use was mainly confined to lowering estrogen. A year later, the next oral anabolic steroid was produced, methyltestosterone. This was a relatively crude oral steroid compared to later versions.

The early 60s are often called "The golden age of steroids," since most of the more famous anabolic steroid drugs were synthesized during those years. Although hundreds were produced by various drug companies, most remained experimental and were never released. Many of these re-emerged in recent years as "prohormones," and "designer steroids." The most common method used to make an oral anabolic steroid drug resistant to premature liver breakdown involved making a conformational change in the steroid structure, usually at the 17-alpha position. While this made the drugs resistant to liver degradation, it also caused an accumulation of the steroid in the liver. This build-up, in turn, caused an inflammation effect that interfered with the transport of bile in the liver, a condition known as cholestasis. This localized liver inflammation is recognized through elevated liver enzymes during a blood test. If a steroid user gets off the drug within a short time, the inflammation declines to normal. The liver is a resilient organ in that you can remove 3/4 of it and still survive. However, long-standing inflammation eventually damages liver cells and causes them to die. The result could be fibrosis or scarring in the liver, which can proceed to liver cancer or liver failure. The latter requires a liver transplant to survive.

One reason why many of the anabolic steroid drugs produced during the Golden Age of Steroids in the 60s were never released was that initial animal testing showed that they placed inordinate stress on the liver. Despite this, many of these same drugs resurfaced years later as "prohormones" and"designer steroids."As they began appearing in commercial supplements, aimed mainly at bodybuilders, isolated reports of side effects, many severe, began to appear in the medical literature. One such popular "testosterone-booster" was called Superdrol. The generic name for Superdrol was methasterone. It has been looked at back in 1956 by the Syntex drug company. Their initial findings was that it was 400% more anabolic than methyltestosterone, but 20% as androgenic. It appeared at first to be a good candidate for commercial release. Methasterone was the 17-alpha methylated oral version of another injectable steroid called Masteron, known generically as drostanolone. But the plans to market methasterone were abandoned when initial animal tests showed an extremely toxic effect in the liver. But that little problem didn't keep unscrupulous supplement companies from marketing it as "Superdrol." One medical report involved three cases studies of men who had used various over-the-counter testosterone boosters, specifically Superdrol, Halodrol, and one called "M-test 2." Despite following label directions, all the men showed severe liver stress stemming from drug-induced cholestasis. Since the primary problem involved liver inflammation, the doctors treated them prescribed corticosteroids, used to lower inflammation. This isn't the best way to treat this condition, but it worked to decrease the swollen livers of the men.

Halodrol, one of the "supplements" mentioned in the study, was a re-engineered version of a famous oral anabolic steroid called oral turinabol. This drug had a notorious reputation due to its extensive use by East German Athletes in the late 60s and early 70s. Halodrol was simply oral Turniabol with a methyl group added to the structure. In fact, most of the anabolic steroid "prohormones" also featured alterations in the steroid structure that involved adding a methyl group. This caused the drug to resist liver breakdown, similar to regulated oral anabolic steroid drugs, but also was also the cause of the liver toxicity linked to these products. The existence of Halodrol was short-lived, as  FDA soon learned that it was very similar to the oral Turinabol drug. They sent a letter to Gaspari Nutrition, who sold Halodrol, warning that sales were a violation of the law. Gaspari complied by removing Halodrol from the supplement and substituting DHEA, thus making an effective, but dangerous supplement now safer, but also nearly worthless.

The third "supplement" mentioned in the case study was M-test 2, Once again, this was an old anabolic steroid developed in 1963, but never released. It emerged in supplement form as Ergomax LMG in 2005 but was declared illegal in 2009. The company selling it had already removed it from the market prior to its loss of legal status. The existence of this substance, also known as DMT or Desoxymethyltestosterone. was not apparent on the product label. Also known as "Madol," this drug was dug up by steroid chemist, Pat Arnold. Its existence came to light when it was found in the possession of a sprinter during a routine check of his car at the Canadian border. It has an anabolic effect 160% that of testosterone while being only 60% as androgenic. It is a potent oral steroid that is known to promote elevated blood pressure and increased blood lipid levels, both of which are risk factors for cardiovascular disease. When Madol was removed from the market, another version called "P-Plex" or"Phera-Plex" was released. This substance was a designer steroid that converted to Madol in the body. The only known natural existence of it is as a pheromone in elephants.

 In November 2009, two men sued two companies in Texas that sold and distributed two products, M-Drol and P-Plex.  The men claimed that both supplements caused them to go into total liver failure. Soon after this litigation was instituted, both products were removed from sale. M-Drol is another name for Superdrol, and as noted, it is very toxic to the liver, as is P-Plex.

But the popularity of Superdrol among users presented a dilemma to supplement companies when it was removed from the market. So they came up with formulas that were advertised as being far more potent than Superdrol, or "improved versions." One such supplement is still being sold as "Super DMZ Rx 2.0." This supplement is still legal, but its days are numbered since once Obama signs the new 2014 Steroid law, it will be made automatically illegal. The supplement consists of two steroids, methylstenbolone and dymethazine. Methylstenbolone, once again, is an old steroid developed in 1966, but never released (are you seeing a pattern here?). It's touted as being similar to Superdrol, and the old 60s studies showed it to be more potent than the oral anabolic steroids, Dianabol, Winstrol, Anadrol, and Anavar. That's saying a lot since these are the most popular oral anabolic steroid drugs. The other ingredient,dymethazine, is nothing more than two molecules of Superdrol attached by a nitrogen bond. The Super DMZ supplement containing these ingredients contains 10 milligrams of each steroid, with directions to take 1 to 2 capsules daily, with use not to exceed a month, followed by 2 more months off the supplement. A recently published case report discussed the case of a 26-year-old, healthy young man with no previous health problems who used the product as directed but nonetheless showed signs of severe liver stress. Tests confirmed that he had a bad case of cholestasis, or liver bile flow obstruction that was  secondary to a liver inflammation induced by the "supplement/drug."  This occurred during his first month on the supplement. While no attempt was made to conceal the presence of the two steroids contained in the supplement, it was also said to be "safe when used as directed."

Trenbolone was one of the most popular anabolic steroid drugs used by athletes and bodybuilders. It was considered the most potent of all injectable anabolic steroids.  It has several characteristics that made it so popular. For one, it didn't convert into estrogen, so there were no worries about water retention or gynecomastia (bitch tits). It also didn't seem to convert into DHT, either, so the problems linked with that were also not likely to occur in those who used it, such as male pattern baldness, acne, and prostate enlargement. It was, similarly to Durabolin, a 19-nor based steroid. Among other effects, this meant that it interacted with progesterone receptors in the body. While activation of such receptors usually downgrades estrogen receptors, in certain individuals activating these receptors could produce estrogen-like effects, such as gyno. Activation of the progesterone receptors could also produce a loss of libido effect. In addition, when initially using trenbolone, many users temporarily suffered from excessive coughing.  When it was available as a drug in the acetate form, it went under such trace names as "Finajet" and "Finaject" Another form was longer-acting, called trenbolone enanthate that was comparable in its anabolic effects to testosterone. Another longer-acting form called  Trenbolone Hexahydrobenzylcarbonate or "Parabolan" appeared briefly on the market in the mid-90s. Since it did not promote estrogen synthesis and had no apparent effect on DHT, trenbolone was even suggested as a SARM, or "selective androgen receptor modulator."This made sense since trenbolone has an affinity to the androgen receptor that is three times greater than testosterone. SARMs are drugs in development that, while interacting with the androgen receptor, don't promote estrogen or DHT release. Since trenbolone also doesn't do this but is very anabolic, it's easy to understand why it would be suggested as a possible SARM. In a study where trenbolone was given to castrated rats, it was shown not to stimulate the rodent's prostate gland, but did boost muscle mass by 35-40% above that of animals not given the steroid, and also protected against bone loss. It also promoted loss of dangerous visceral body fat. But this involved low doses of tren. Higher doses did overstimulate the prostate in the animals. Another recent animal study showed that tren showed greater activity than testosterone in blunting the catabolic effects of cortisol through interfering with cortisol receptor activity, and also showed more activity against catabolic effects in muscle.

You might expect that with all these desirable features of trenbolone that there would be a supplement form. The "prohormone" version is called Trenevar or Trendione, and differs from trenbolone by substituting a 17-ketone in the structure rather than the 17-beta hydroxy found in tren. In the body, this prohormone is converted through enzyme action into actual trenbolone. While this particular prohormone was said to never have been released to the commercial market, it did in fact exist in one short-lived supplement called "Methoxy TRN."  While the supplement was supposed to contain a substance that was similar to tren, it fact when analyzed, it was found to contain actual tren. Currently, the only way to obtain tren is through the processing of tren pellets used in the cattle industry, a product called "Finiplix." Often, these pellets are processed using solvents, then injected into the body, solvents and all. Of course, this is not recommended, despite the existence on the Internet of "Trenbolone kits" to produce tren from the cattle pellets. One reason to avoid all forms of tren was a recently published animal study that found that tren was able to cross the protective blood-brain barrier and exert actions in the brain that resulted in the death of neurons in the hippocampus portion of the brain, the site of memory and learning. In addition, tren promoted an increase in beta-amyloid and presenilin, proteins associated with the onset of Alzheimer's disease. Testosterone offers reverse effects in that it protects the brain.

 

Why doesn't everyone who used designer steroids and drug-based prohormones suffer from liver problems?

 

The body organ hardest hit by using either oral anabolic steroid drugs or designer steroids is the liver. The reason for this is that the drugs have been structurally altered to resist premature breakdown in the liver that would otherwise occur when testosterone is ingested orally. In most oral anabolic steroid drugs, this change involves 17-alkylated changes to the steroid structure, while with most prohormones and OTC designer steroids this involved adding a methyl group to the steroid structure, although other methods were also used. These changes allowed the steroids to build up in the liver, inducing a localized inflammation recognized by elevations in liver enzymes. If the inflammation continued, more obvious signs of liver stress would be apparent, such as jaundice, severe itching, and other symptoms. When these symptoms appeared, it indicated the destruction of liver cells. If a user of the drugs stopped at that point, there was a good chance that the liver would regenerate the damaged cells. Injectable steroids are not as immediately damaging to the liver as oral drugs, but the notion that they are "harmless" to the liver, as noted on many websites and articles, is nonsense. All chemicals put into the body eventually must be processed in the liver, and large doses of injectable drugs can indeed induce liver stress.

Still, not everyone who uses either oral anabolic steroid drugs--whether over-the-counter versions or pharmaceutical versions--is afflicted with liver problems. For those who use the discarded old steroids sold as "testosterone-boosters" some form of liver stress always occurs, though it is often not discerned by the user unless he or she has a blood test. Such a test will show elevated liver enzymes, an indication of liver stress. But in others, the drugs tend to promote enough inflammation in the liver that the normal flow of bile is inhibited. Bile is produced in the liver from cholesterol, then travels through ducts in the liver to the gallbladder, where it's stored. A meal rich in fat content stimulates the release of a gut peptide called CCK, which in turn, stimulates the gallbladder to release bile. The bile helps to emulsify ingested fat, reducing the surface area of the fat molecules, which in turn makes them more amenable to digestion by fat-digesting enzymes or lipases.

As liver inflammation progresses, the ducts that transport bile through the liver are blocked, causing the bile to accumulate. This leads to direct damage to liver cells, and also to symptoms of jaundice as the bile is released into the blood. But again, not everyone who used steroids gets this bile obstruction effect. The question is: why do some people get it and not others?

It turns out that there are genes that promote a disease in which cholestasis or bile flow obstruction is more likely to occur. Mutations in certain genes can be turned on when substances, such as oral anabolic steroids, accumulate in the liver. In other cases, other genes that promote a "bile pump" effect may be turned off by the steroids. You can be born with these changes in genes that normally remain dormant, but are expressed with the introduction of other substances that cause liver stress, such as steroids. When this happens, you will have the cholestasis effect, and the signs will be obvious. But even having the genetic predisposition doesn't guarantee permanent liver damage unless you stay on the drugs. In that scenario, the damage to liver cells continues, eventually resulting in liver failure that requires a liver transplant. This has actually happened to a few people who stayed on the designer or anabolic steroid supplements too long. Obviously, the common sense thing to do is get off them immediately when signs of damage, as indicated by greatly elevated liver enzymes or signs of jaundice appear.

 

Are you getting what you paid for?

 

Prohormone and designer steroid supplements tend to be expensive, averaging anywhere from$40 to $70 a bottle. As such, it seems reasonable to expect that you are getting what you paid for. But many companies put complex chemical names on the product labels, making it appear that they contain powerful steroids, when in fact, these are other names for lesser steroids, such as DHEA. Recently, a group of scientists in Great Britain purchased 24 over-the-counter testosterone boosting and designer steroid supplements from two shops and one Internet site. They then analyzed these products, with the goal being to see if what was contained in the product matched what was listed on the product label. Of the 24 products tested, 23 contained steroids, but 16 of them contained steroids that differed from label content, with one product not containing any steroid at all. Some of the products contained the previously discussed discarded old 60s steroids, such as methasterone (Superdrol) and DMT, while others contained designer steroids, including methyl-1-testosterone. All the supplements were described in ads as "legal for sale," when in fact, nearly all of them were not. Four of the products contained the banned steroid, methasterone. Perhaps the most troublesome aspect of this report, however, was the finding that many of the supplements didn't contain the more potent old steroid drugs or newer designer steroids, but instead contained the weaker and relatively ineffective DHEA and androstenedione.  These phony products included Super tren-MG (DHEA), 19-nor-tren (DHEA), Super Halo (DHEA), Straight Drol (Androstenedione),  Epivol Black (Andro and methasterone), Straight Phlexed (androstenedione).  These weaker steroids contained in the products were not reflected on the product labels. Thus, those who purchased these products were blatantly ripped off.  This is a real problem with the designer steroid and prohormone industry. Many of the supplements are sold by unscrupulous companies whose practices echo that of the Black Market underground, where about a third of the steroids sold are not the drugs actually contained in the product, or in other cases, there is no active product at all. In addition, another thing to keep in mind is the source of the raw materials used to produce these designer steroids. These "supplements" are made in China, the country with the worst record of quality control in the world. As such, you may not be getting what you think you're getting!