Pushtoday
MuscleChemistry Registered Member
Copied from a PricePlow blog: August 31, 2015
SARMs: The Controversial Muscle Builders of 2015
Prohormones were a mainstay of the bodybuilding supplement industry since Patrick Arnold first introduced the world to 4-androstenedione around 1996 until the passing of the DASCA bill in December 2014, effectively banning prohormones once and for all. Since then, extreme muscle-building consumers and companies alike have been looking for alternatives – and many of them have turned to the prohormone-like compounds, SARMs.
SARMs are non-steroidal compounds that still activate the androgen receptors, and according to user feedback typically give similar results to a light prohormone or steroid cycle.
Up front, this all sounds good – the next prohormone replacement is here… right? But as you can imagine, it’s not always that simple.
Choose your own adventure
At this point, the road forks.
Most of you are here as consumers, wondering what these SARMs are and how they work. You might not care about the laws, as they typically don’t apply to the end users who aren’t re-distributing them.
The rest of you are either with brands, media outlets, or government agencies / law enforcement. In that case, you likely want to read about the industry concerns in the LEGAL section.
It’s tough to stay objective and unemotional with these compounds, but we’ll do our best.
On one hand, consumers have made it extremely clear that they demand advanced muscle-building agents that they can discreetly purchase online, rather than deal with shady characters in the gym locker room. And a few of these compounds do indeed show serious promise, despite their still-limited research.
And on the other hand, it’s tough to dispute the illegality of the production, sales, and distribution of most (if not all) of these compounds, and we ultimately see this ending with some kind of stain on our industry.
But that gets ahead of ourselves, so let’s start with the consumer-facing section:
The History of SARMs
The introduction and discovery of SARMs into the scientific community was indeed a significant breakthrough to both medical and anti-aging organizations.[1] The most common problem with androgen therapy (ie HRT — hormone replacement therapy) is the limited availability of safe compounds to administer, without some of the detrimental side effects that exogenous administration of natural androgens cause.
The effort of most SARM researchers is to acquire an agonist of the androgen receptor without the susceptibility of binding to and serving as substrates for aromatase and 5a-reductase (or possessing androgenic activity of its own). It was hoped that this could be achieved by either steroidal or nonsteroidal means, and efforts to synthesize compounds are still underway.
By big pharma, for big pharma
Note that this is all research done in the name of better prescription drugs, not research for the muscle-building industry. Several Big Pharma companies are doing the research, and their goals are typically a bit different than our average readers.[2] For instance, they want drugs that prevent muscle-wasting in the elderly and for post-surgical patients… whereas you just want to get swole. We talk about some of that research (and the patents) below.
These compounds were developed and research was largely funded when it became apparent that chemical modifications to the antiandrogen bicalutamide forged androgens (ligands) with agonistic activity.[3] There are many different classes of SARMs and there have been extensive efforts over the years to synthesize and test them for favorable qualities.
While it’s still too early to officially say so, the good news is that the pharmaceutical companies seem to be succeeding in their early-scale efforts. Certain low-dose SARMs are showing to be effective in their case subjects (such as the elderly) with minimal side effects, which is more than you can say about a lot of prohormones or other designer steroids.
Variability in SARMs
What makes SARMs unique is the variability in structure among them. Technically, anything that binds to the androgen receptor and activates it in certain tissues more than others can be classified as a SARM, which means there is little to no structural basis behind this naming classification, unlike that seen of steroids (4-ring base).
Not a steroid
This is also what made it the “Next Big Thing™” after the prohormone ban – they are not “steroidal” in the technical sense, so the 2014 DASCA law’s verbiage did not cover them.
People often confuse SARMs with steroids: a SARM can be a steroid and a steroid can be a SARM, but when we talk about SARMs on the market, what we’re talking about is usually a Nonsteroidal Selective Androgen Receptor Modulator.
Let’s break down what this means:
Nonsteroidal meaning it does not have a 4-ring base structure or the steroid nucleus.
Selective meaning it varies where it is active (tissues).
The rest denotes ability to bind and activate or modulate the Androgen Receptor.
SARM Selectivity is Key
Tissue selectivity is imperative to the medical and therapeutic benefit of a selective androgen receptor modulator.[4] For a SARM to be considered medically useful, it must have favorable tissue selectivity, meaning very little interaction with secondary sex tissues (seminal vesicles and prostate) while demonstrating agonist activity in bone and muscle (gains).
Basically, a good SARM is one that selectively causes muscle growth, yet leaves your liver, prostate, hairline, and boobs alone. It should also ideally possess anabolic activity similar to testosterone or be more potent than this natural hormone.
Each SARM requires its own research
Since these compounds are so variable, the muscle-building industry is really doing everyone a disservice when lumping them all together under one term. After all, each one may select something completely different, and have different effects on the body.
Because of that, you need to research each one on its own grounds. They’re not all the same, and the word SARM is really pretty meaningless for your purposes.
It’s not like protein, where we can get reasonably similar results between the different types within the category (ie whey, casein, and pea aren’t that much different at the end of the day). But with the various SARMs finding their way onto the market, one may work far differently than another.
Point being, if Joe Bloggs at the gym says “SARMs are awesome, you should try them”, and he doesn’t tell you what exact SARM (or in what dose and what PCT he uses), then he’s an idiot who hasn’t done his research. Listening to people like this instead of doing your own research puts yourself at risk.
Not for drug-tested athletes… but they once were…
Note that SARMs are banned by WADA (the World Anti Doping Agency),[5] so if you’re a drug-tested athlete, don’t even think about it.
Interesting to note that certain SARMs were the doping agent du jour during the 2008 Beijing Olympics, according to certain sources.[6] Yet WADA has known about these since 2007, as reported by the MIT Technology Review,[7] and they were on the 2008 banned substances list[8] (whether they could actually detect all of them back then is another question).
SARMs were also hinted as the thing that the “smart” guys in the MLB were doing in early 2009.[9]
(Meanwhile, advanced dopers who get drug tested have likely moved on to something we’ve never heard of, and blogs like PricePlow will finally write about in 2020, but we digress…)
Anyway, the point is that the drug-testing world caught up with this long ago, but a key takeaway is that while this is “new” to our industry, they’re not necessarily that new…
Investigated by Big Pharma
A number of synthetically derived SARMs have been investigated from various pharmaceutical companies such as Ligand Pharmaceuticals (LGD-4033),[10,11,12,13,14] Merck,[15] Johnson & Johnson,[16,17] GlasoSmithKline,[18], and GTx (Ostarine / MK-2866).[19,20]
The most novel compounds, also known as lead compounds, are SARMs that display preferential partial agonist activity in prostate and seminal vesicles, but which also display anabolic activity in bone and muscle tissue. GTx developed a series of SARMs with the most notable one being Ostarine / MK-2866,[21,22,23] which will be the focus of the next article in this series.
The good news is that these are legitimate companies putting a lot of time, money, and research into these drugs. Some of the research has been promising, heading into human trials, albeit at lower doses than are being sold by some underground “supplement” companies. The bad news is that they are just as described – investigational prescription drugs – which segues into some of the legal issues discussed in the next section below.
In our next post in this series, we’ll discuss the details behind Ostarine, the most well-researched of the bunch. However, we need to continue to emphasize that users are dosing 10x more than any study, and these ultimately illegal compounds may catch up to the industry sooner or later.
We encourage you to continue reading, as the drama is just about to begin:
SARMs are not legal supplements
Update – October 21, 2015: The first SARM lawsuit has been filed!
Make no mistake – any company selling these as “supplements” is being completely deceptive. There is no possible way on earth that these are FDA / DSHEA compliant,[24] and it is seriously only a matter of time before the FDA and DEA drop a serious ban-hammer on these products and the companies importing, selling, and manufacturing them. Quite frankly, nobody is even arguing this point.
Why are we here anyway?
Realize that after the DASCA bill was passed, several prohormone companies had their lives put on the line. It was to either come up with the next thing, or go broke and out of business. Some companies got out of the gray area business once and for all, branching off into DSHEA compliant products. Yet others got into the business, clearly taking the legal risk for some quick profits.
They may not violate DASCA… but that doesn’t mean they’re legal
The reasons SARMs have been the Next Big Thing™ in terms of muscle-builders is because several of them have proven to work, and DASCA does not specifically include anabolic compounds with nonsteroidal structure. It doesn’t currently specifically list any SARMs either. However, that doesn’t mean they are legal to sell by any means.
At best, SARMs are “research chemicals”: not completely illegal, since many are not prescription drugs or scheduled drugs (or analogs of such drugs).
But when they’re being sold as supplements or at supplement stores, it is clearly a violation of the FDA’s DSHEA law. This is the first avenue where companies and their leaders are taking on risk – if the FDA or DEA wants to get involved, they easily could.
Remember that you’re watching a live game of cat and mouse here (and the cat’s move is next).
But what is a supplement?
While writing this article, we reached out to a few SARM manufacturers, and a couple of them pointed out that this isn’t the first time a non-supplement has made its way into supplement stores.
After all, the cognitive-enhancing nootropic, noopept (which we practically rave about in the article linked there) is a prescription drug in Russia and isn’t even close to being DSHEA compliant as a supplement.
Yet right here in front of me sits a bottle of Noopept with the words “DIETARY SUPPLEMENT” clearly printed on the front.
Then there’s phenibut, which we argue against in our Best Sleep Aid. This is also a Russian prescription drug, and is horribly addictive to top it off. It’s sold in various “supplements” as well.
So your favorite SARM manufacture will happily argue that a nootropic drug, which works in the brain, is potentially more hazardous than a selective androgen receptor modulator that works in muscle tissue. Meanwhile, they’ll argue that there’s precedence for this kind of behavior, which is rarely being punished or enforced by the FDA.
But if it’s not specifically illegal, does that mean it’s legal?
UPDATE: One industry veteran’s response
The day after posting this article, we received this email from an industry veteran:
Two comments:
Noopept is probably DHSEA compliant. Noopept is a known PRECURSOR to an endogenous peptide found in most mammal species. It is also NOT considered a racetam. Check DSHEA about precursors.
Phenibut is a drug, I agree.
The issue here is two wrongs do not make a right.
It’s still illegal. 100% so.
Comparing to the prohormone situation
SARM manufacturers also point out that prohormones were practically illegally sold for over ten years (depending on how you look at the Anabolic Steroid Control Act and its updates in 2004[25]), and the various prohormones and designer steroids seem to be far more dangerous than the most well-researched SARMs, given the available data.
And in the same breath of air, they’ll remind you that several of your favorite above-board supplement companies were “financed” by selling illicit prohormones. The cycle repeats.
Where is this going?
The point is, non-DSHEA compliance doesn’t seem to be a concern to many users or even several large companies. What does seem to be a bigger concern is the inherent danger, and SARM companies are quick to state that these aren’t as dangerous as previous alternatives, given what they know so far. That leads into a point we make later on, where the media has been relatively uninvolved since “if it bleeds, it leads”… and nobody’s child has ended up dead from this stuff (yet, at least).
Points all well-taken.
So where’s the FDA at then?
FDA action so far
As of right now, only one warning letter has been sent one company (BioGenix), and the FDA’s action was most likely primarily due to the fact that they put unlabeled Cialis and Levitra in the product, at a serious hazard to their customers.[26]
It’s unclear how badly the FDA specifically “cared” about the SARM situation here though, since the unlabeled prescription drugs inside of this one could pose a far more serious threat — especially with weightlifters who frequently use nitrate-based pre workouts.[27]
Research chemicals?
So what does “research chemical” mean?
Ostarine, for instance, is an investigational new prescription drug. A company named GTx has been working on whether this might have a chance at becoming a prescription drug.[15,19,20]
Yet, while it is technically their IP, it can obviously be found in various underground websites that sell such research chemicals. When these stores say that they are ‘not for human consumption’ or ‘for research only’, yet include information about oral dosing for humans… you can guess that it’s only a matter of time until someone gets taken down.
We’re not lawyers, but it seems like these practices give law enforcement all the grounds they need to go bashing doors in.
After all…
Is it a drug? Yes.
Are you the approved distributor of that drug? No.
Is it patented? Oftentimes, yes.[28,29] (note that there are countless SARM patents)
Are you introducing a counterfeit drug into interstate commerce? Yes.
Now, Ostarine has made it even further than those underground research chemical sites — it’s now plainly listed on several of the supplement stores that PricePlow works with, and rumor has it that a relatively large brick-and-mortar retailer will be carrying some SARMs soon enough as well.
The ultimate legality may come down to a compound-by-compound basis, but don’t delude yourself into thinking this is legal (or not illegal). It might be “flying under the radar”, but that is no indication of actual legality.
As if the DEA cared…
And even if you can argue some gray area technicality, do you think for one moment that the DEA even cares about legal technicalities? They’ll raid your warehouse like a band of stormtroopers, take everything they see, and lock it into a vault while you go bankrupt. You didn’t expect them to play fair, did you?
What will likely happen
So whose job is it to enforce the patents? There are several federal laws that protect patent holders,[30] but does GTx need to pursue these companies themselves, or does the government? They clearly have a case (someone else is making tons of money off of their research and IP, while they aren’t), but do they care yet? Does the DEA? Where is the line drawn, and when?
Anyway, due to the fact that DASCA contains a provision that basically any compound can be added to the ban list, it’s not hard to imagine that they might just add these compounds to the list and be done with it. That’s probably where this chapter of the industry quietly ends, in our opinions at least.
But users don’t care about legality, do they?
Nevertheless, various companies have taken to sell them both online and in small brick-and-mortar stores, despite their non-compliance, and users are buying them in droves — without doing proper research.
The end-user lack of research is where we take issue, since these users all run the risk of potentially harming themselves in the process (such as by taking too much or not running PCT). Adding to the problem, the “supplement companies” selling these drugs don’t seem to be educating their customers either.
For instance, several companies are advertising doses of Ostarine as 15mg-30mg, stating that you don’t need to run post cycle therapy. However, the research-based dose of ostarine was at 3mg,[31,32] and it dropped test production by 25%![31] What in the hell do you think is going to happen when you run it at 10x that dose?!
Should you trust someone who’s breaking the law at a profit?
The bigger issue from a consumer’s point of view is, how do you trust someone who’s openly violating the law — and profiting off of that?
Some of the “supplement companies” have popped up from out of nowhere, here to make a quick buck. How can anyone be sure of what they’re getting?
This isn’t something like DMAA, which is still being disputed in the court system and could go either way. This is flat out illegal and the companies selling them know it. What’s stopping anyone from breaking the law further by missing ‘label’ claims? It’s not like it would have been legal in the first place!
So if you’re going to step into this fold, you better hope to death that you’re getting what they’re saying they’re giving you, in the dose claimed. Third party lab tests — not tests from the manufacturer or raw material suppliers — are paramount. But do they exist?
The research is still a bit flimsy
Meanwhile, the fact is that nobody in the supplement industry has anything more than a surface level clue about these first/second generation SARMs. Big pharma might not know much more, and if they do, they currently have no obligation to share it with us.
Many of these are effectively failed prescription drugs whose research was aborted upon their failure. Still others have their research still in progress, but have yet to gain approval (the primary example being GTx and Ostarine).
GTx has even go so far to state on their SEC reports,
“We do not expect to obtain FDA or EMA approval, or any other regulatory approvals, to market any of our product candidates, including enobosarm (ostarine), for the foreseeable future, and it is possible that none of our product candidates will ever receive any regulatory approvals.[33]
— GTx Inc. SEC Report, June 30, 2014
Meanwhile, their quarterly loss was just under $48 million for 2Q 2015.[34] This does not paint a rosy picture in terms of approval or safety, and that’s for the most well-researched SARM out there!!
The dangers of some compounds: Worth risking cancer?
Even worse, one compound named GW-501516 / Cardarine was abandoned for research because it caused cancer in animal studies at all doses, at all durations of use.
Arguments on GW-501516
It’s worth noting that the response to these allegations is that it is generally unlikely that PPAR is going to stimulate cancer growth in human cell lines – a valid case – but again… is anything worth that risk?
It’s also worth noting that GW-50516 is not even a SARM. However, it’s classified as one by several websites that sell the stuff, which reaffirms our pleas for users to do their research, lest the blind lead the blind!
Have things really gone this far? Spending $55/month for something that probably increases some parameters of endurance exercise… that has literally never been given to a human in a clinical setting?
This is the kind of territory you’re getting yourself into here, folks. No man’s land. There’s no reason to be someone else’s petri dish.
This probably won’t end well.
So why do we care? Because there’s a chance that this ends up in USA Today and every other major newspaper, and the media is undoubtedly going to make all of us look like scum. Every last one of us, from consumers to brands to industry advocates, will end up far worse if that happens.
But so far, nobody seems to care much. MAXIM magazine already covered this months ago,[39] and apparently Marc Lobliner’s been questioned by a massive men’s print magazine as well. That’s just the beginning… but so far, not much fanfare.
If it bleeds, it leads…
As the phrase goes in the media industry, “If it bleeds, it leads” – but nobody has gotten seriously hurt (yet).
These compounds – at least ostarine and andarine – do seem safer than most of their predecessor alternatives, specifically prohormones. But that may not matter – all it will take is for one idiot to drink himself to death while he has some kind of SARM in his bloodstream, and you can imagine the media shitstorm that will come next. (This is also why we can’t have nice things.)
So how can any level-headed company not expect this to end poorly for the industry?
At best, nobody is hurt, and some people have some gains. Eventually, DASCA may be revised to ban them, nice and quietly.
At worst, something stupid happens, which catalyzes the next John Oliver segment on the supplement industry and the next FDA push to stifle any room for legal innovation in the industry just because a few people were greedy. Conveniently during election season, no less.
It’s one thing to have these compounds in obscure places that only well-researched steroid users know about. But selling this through popular brick and mortar stores as a dietary supplement is risky to the nth degree for everyone involved.
But in the meantime, they will sell, and they will sell well, so we just urge users to do their damned homework before proceeding. And that means to understand that SARMs aren’t supplements, they are investigational drugs that should be treated with the care of steroids.
Good luck, folks. Stay safe and do your research.
UPDATE:
Bruce Kneller’s Opinion regarding FDA legality
This was emailed to us on September 1, 2015:
FDA and various US Attorneys may very likely be inclined to view all SARMs currently sold as dietary ingredients/supplements not only as mere drugs, but as prescription drugs.
The reason is very simple even if the argument may be viewed as somewhat of a stretch.
First and foremost, all of the SARMs references in your exceptional article are going to be considered drugs by the FDA and US Attorneys – and this is a correct interpretation which is pretty straightforward. None of the SARMs meet the legal definition of a dietary ingredient under DHSEA 1994 and their appearance in any dietary supplement is an act of misbranding and product adulteration. They are by default, all misbranded drugs. It would be futile to argue this point.
However, FDA and some US Attorneys may successfully argue that SARMs have a reasonable probability of resulting in permanent impairment of a body structure or function in at risk consumers and thus can not be used except under the supervision of a practitioner licensed by law to administer such.
Certainly, by selling SARMs as misbranded drugs under the ruse that they are legal, dietary supplements at 10X the dose, or even higher, studied in any human trials would surely bolster such an assertion by FDA or a US Attorney regarding likelihood of permanent impairment of a body structure or function in at risk consumers anyhow.
While some may view this perspective as a tenuous if not specious (and certainly dose dependent) argument, it’s not beyond the pale of something FDA could try to do. In 1951, The Durham-Humphrey Amendment to the FDC became law in the USA. For the edification of you and the PricePlow readers:
“The FDC Act defines a prescription drug at FDC Act § 503(b)(1) as:
A drug intended for use by man which –
(A) because of its toxicity or other potentiality for harmful effect, or the method of its use, or the collateral measures necessary to its use, is not safe for use except under the supervision of a practitioner licensed by law to administer such drug; or
(B) is limited by an approved application under section 505 to use under the professional supervision of a practitioner licensed by law to administer such drug..
As passed into law in 1951, The FDC Act § 503(b)(1) included three categories of Rx drugs: (1) habit-forming drugs under § 502(d); (2) drugs that are unsafe for use except with a doctor’s supervision; and (3) drugs limited to Rx use under an NDA.”
[emphases added are Bruce’s]
While the thought of FDA viewing SARMS being illegally sold as dietary ingredients/supplements right now as prescription drugs may seem a bit of a stretch, a quick review of FDA’s historical enforcement actions regarding aromatase inhibitors being sold as dietary supplements should serve as a prescient and clear warning that this very type of thing surely can happen.
— Bruce Kneller, Giant Sports Products
…and there you have it.
SARMs: The Controversial Muscle Builders of 2015
Prohormones were a mainstay of the bodybuilding supplement industry since Patrick Arnold first introduced the world to 4-androstenedione around 1996 until the passing of the DASCA bill in December 2014, effectively banning prohormones once and for all. Since then, extreme muscle-building consumers and companies alike have been looking for alternatives – and many of them have turned to the prohormone-like compounds, SARMs.
SARMs are non-steroidal compounds that still activate the androgen receptors, and according to user feedback typically give similar results to a light prohormone or steroid cycle.
Up front, this all sounds good – the next prohormone replacement is here… right? But as you can imagine, it’s not always that simple.
Choose your own adventure
At this point, the road forks.
Most of you are here as consumers, wondering what these SARMs are and how they work. You might not care about the laws, as they typically don’t apply to the end users who aren’t re-distributing them.
The rest of you are either with brands, media outlets, or government agencies / law enforcement. In that case, you likely want to read about the industry concerns in the LEGAL section.
It’s tough to stay objective and unemotional with these compounds, but we’ll do our best.
On one hand, consumers have made it extremely clear that they demand advanced muscle-building agents that they can discreetly purchase online, rather than deal with shady characters in the gym locker room. And a few of these compounds do indeed show serious promise, despite their still-limited research.
And on the other hand, it’s tough to dispute the illegality of the production, sales, and distribution of most (if not all) of these compounds, and we ultimately see this ending with some kind of stain on our industry.
But that gets ahead of ourselves, so let’s start with the consumer-facing section:
The History of SARMs
The introduction and discovery of SARMs into the scientific community was indeed a significant breakthrough to both medical and anti-aging organizations.[1] The most common problem with androgen therapy (ie HRT — hormone replacement therapy) is the limited availability of safe compounds to administer, without some of the detrimental side effects that exogenous administration of natural androgens cause.
The effort of most SARM researchers is to acquire an agonist of the androgen receptor without the susceptibility of binding to and serving as substrates for aromatase and 5a-reductase (or possessing androgenic activity of its own). It was hoped that this could be achieved by either steroidal or nonsteroidal means, and efforts to synthesize compounds are still underway.
By big pharma, for big pharma
Note that this is all research done in the name of better prescription drugs, not research for the muscle-building industry. Several Big Pharma companies are doing the research, and their goals are typically a bit different than our average readers.[2] For instance, they want drugs that prevent muscle-wasting in the elderly and for post-surgical patients… whereas you just want to get swole. We talk about some of that research (and the patents) below.
These compounds were developed and research was largely funded when it became apparent that chemical modifications to the antiandrogen bicalutamide forged androgens (ligands) with agonistic activity.[3] There are many different classes of SARMs and there have been extensive efforts over the years to synthesize and test them for favorable qualities.
While it’s still too early to officially say so, the good news is that the pharmaceutical companies seem to be succeeding in their early-scale efforts. Certain low-dose SARMs are showing to be effective in their case subjects (such as the elderly) with minimal side effects, which is more than you can say about a lot of prohormones or other designer steroids.
Variability in SARMs
What makes SARMs unique is the variability in structure among them. Technically, anything that binds to the androgen receptor and activates it in certain tissues more than others can be classified as a SARM, which means there is little to no structural basis behind this naming classification, unlike that seen of steroids (4-ring base).
Not a steroid
This is also what made it the “Next Big Thing™” after the prohormone ban – they are not “steroidal” in the technical sense, so the 2014 DASCA law’s verbiage did not cover them.
People often confuse SARMs with steroids: a SARM can be a steroid and a steroid can be a SARM, but when we talk about SARMs on the market, what we’re talking about is usually a Nonsteroidal Selective Androgen Receptor Modulator.
Let’s break down what this means:
Nonsteroidal meaning it does not have a 4-ring base structure or the steroid nucleus.
Selective meaning it varies where it is active (tissues).
The rest denotes ability to bind and activate or modulate the Androgen Receptor.
SARM Selectivity is Key
Tissue selectivity is imperative to the medical and therapeutic benefit of a selective androgen receptor modulator.[4] For a SARM to be considered medically useful, it must have favorable tissue selectivity, meaning very little interaction with secondary sex tissues (seminal vesicles and prostate) while demonstrating agonist activity in bone and muscle (gains).
Basically, a good SARM is one that selectively causes muscle growth, yet leaves your liver, prostate, hairline, and boobs alone. It should also ideally possess anabolic activity similar to testosterone or be more potent than this natural hormone.
Each SARM requires its own research
Since these compounds are so variable, the muscle-building industry is really doing everyone a disservice when lumping them all together under one term. After all, each one may select something completely different, and have different effects on the body.
Because of that, you need to research each one on its own grounds. They’re not all the same, and the word SARM is really pretty meaningless for your purposes.
It’s not like protein, where we can get reasonably similar results between the different types within the category (ie whey, casein, and pea aren’t that much different at the end of the day). But with the various SARMs finding their way onto the market, one may work far differently than another.
Point being, if Joe Bloggs at the gym says “SARMs are awesome, you should try them”, and he doesn’t tell you what exact SARM (or in what dose and what PCT he uses), then he’s an idiot who hasn’t done his research. Listening to people like this instead of doing your own research puts yourself at risk.
Not for drug-tested athletes… but they once were…
Note that SARMs are banned by WADA (the World Anti Doping Agency),[5] so if you’re a drug-tested athlete, don’t even think about it.
Interesting to note that certain SARMs were the doping agent du jour during the 2008 Beijing Olympics, according to certain sources.[6] Yet WADA has known about these since 2007, as reported by the MIT Technology Review,[7] and they were on the 2008 banned substances list[8] (whether they could actually detect all of them back then is another question).
SARMs were also hinted as the thing that the “smart” guys in the MLB were doing in early 2009.[9]
(Meanwhile, advanced dopers who get drug tested have likely moved on to something we’ve never heard of, and blogs like PricePlow will finally write about in 2020, but we digress…)
Anyway, the point is that the drug-testing world caught up with this long ago, but a key takeaway is that while this is “new” to our industry, they’re not necessarily that new…
Investigated by Big Pharma
A number of synthetically derived SARMs have been investigated from various pharmaceutical companies such as Ligand Pharmaceuticals (LGD-4033),[10,11,12,13,14] Merck,[15] Johnson & Johnson,[16,17] GlasoSmithKline,[18], and GTx (Ostarine / MK-2866).[19,20]
The most novel compounds, also known as lead compounds, are SARMs that display preferential partial agonist activity in prostate and seminal vesicles, but which also display anabolic activity in bone and muscle tissue. GTx developed a series of SARMs with the most notable one being Ostarine / MK-2866,[21,22,23] which will be the focus of the next article in this series.
The good news is that these are legitimate companies putting a lot of time, money, and research into these drugs. Some of the research has been promising, heading into human trials, albeit at lower doses than are being sold by some underground “supplement” companies. The bad news is that they are just as described – investigational prescription drugs – which segues into some of the legal issues discussed in the next section below.
In our next post in this series, we’ll discuss the details behind Ostarine, the most well-researched of the bunch. However, we need to continue to emphasize that users are dosing 10x more than any study, and these ultimately illegal compounds may catch up to the industry sooner or later.
We encourage you to continue reading, as the drama is just about to begin:
SARMs are not legal supplements
Update – October 21, 2015: The first SARM lawsuit has been filed!
Make no mistake – any company selling these as “supplements” is being completely deceptive. There is no possible way on earth that these are FDA / DSHEA compliant,[24] and it is seriously only a matter of time before the FDA and DEA drop a serious ban-hammer on these products and the companies importing, selling, and manufacturing them. Quite frankly, nobody is even arguing this point.
Why are we here anyway?
Realize that after the DASCA bill was passed, several prohormone companies had their lives put on the line. It was to either come up with the next thing, or go broke and out of business. Some companies got out of the gray area business once and for all, branching off into DSHEA compliant products. Yet others got into the business, clearly taking the legal risk for some quick profits.
They may not violate DASCA… but that doesn’t mean they’re legal
The reasons SARMs have been the Next Big Thing™ in terms of muscle-builders is because several of them have proven to work, and DASCA does not specifically include anabolic compounds with nonsteroidal structure. It doesn’t currently specifically list any SARMs either. However, that doesn’t mean they are legal to sell by any means.
At best, SARMs are “research chemicals”: not completely illegal, since many are not prescription drugs or scheduled drugs (or analogs of such drugs).
But when they’re being sold as supplements or at supplement stores, it is clearly a violation of the FDA’s DSHEA law. This is the first avenue where companies and their leaders are taking on risk – if the FDA or DEA wants to get involved, they easily could.
Remember that you’re watching a live game of cat and mouse here (and the cat’s move is next).
But what is a supplement?
While writing this article, we reached out to a few SARM manufacturers, and a couple of them pointed out that this isn’t the first time a non-supplement has made its way into supplement stores.
After all, the cognitive-enhancing nootropic, noopept (which we practically rave about in the article linked there) is a prescription drug in Russia and isn’t even close to being DSHEA compliant as a supplement.
Yet right here in front of me sits a bottle of Noopept with the words “DIETARY SUPPLEMENT” clearly printed on the front.
Then there’s phenibut, which we argue against in our Best Sleep Aid. This is also a Russian prescription drug, and is horribly addictive to top it off. It’s sold in various “supplements” as well.
So your favorite SARM manufacture will happily argue that a nootropic drug, which works in the brain, is potentially more hazardous than a selective androgen receptor modulator that works in muscle tissue. Meanwhile, they’ll argue that there’s precedence for this kind of behavior, which is rarely being punished or enforced by the FDA.
But if it’s not specifically illegal, does that mean it’s legal?
UPDATE: One industry veteran’s response
The day after posting this article, we received this email from an industry veteran:
Two comments:
Noopept is probably DHSEA compliant. Noopept is a known PRECURSOR to an endogenous peptide found in most mammal species. It is also NOT considered a racetam. Check DSHEA about precursors.
Phenibut is a drug, I agree.
The issue here is two wrongs do not make a right.
It’s still illegal. 100% so.
Comparing to the prohormone situation
SARM manufacturers also point out that prohormones were practically illegally sold for over ten years (depending on how you look at the Anabolic Steroid Control Act and its updates in 2004[25]), and the various prohormones and designer steroids seem to be far more dangerous than the most well-researched SARMs, given the available data.
And in the same breath of air, they’ll remind you that several of your favorite above-board supplement companies were “financed” by selling illicit prohormones. The cycle repeats.
Where is this going?
The point is, non-DSHEA compliance doesn’t seem to be a concern to many users or even several large companies. What does seem to be a bigger concern is the inherent danger, and SARM companies are quick to state that these aren’t as dangerous as previous alternatives, given what they know so far. That leads into a point we make later on, where the media has been relatively uninvolved since “if it bleeds, it leads”… and nobody’s child has ended up dead from this stuff (yet, at least).
Points all well-taken.
So where’s the FDA at then?
FDA action so far
As of right now, only one warning letter has been sent one company (BioGenix), and the FDA’s action was most likely primarily due to the fact that they put unlabeled Cialis and Levitra in the product, at a serious hazard to their customers.[26]
It’s unclear how badly the FDA specifically “cared” about the SARM situation here though, since the unlabeled prescription drugs inside of this one could pose a far more serious threat — especially with weightlifters who frequently use nitrate-based pre workouts.[27]
Research chemicals?
So what does “research chemical” mean?
Ostarine, for instance, is an investigational new prescription drug. A company named GTx has been working on whether this might have a chance at becoming a prescription drug.[15,19,20]
Yet, while it is technically their IP, it can obviously be found in various underground websites that sell such research chemicals. When these stores say that they are ‘not for human consumption’ or ‘for research only’, yet include information about oral dosing for humans… you can guess that it’s only a matter of time until someone gets taken down.
We’re not lawyers, but it seems like these practices give law enforcement all the grounds they need to go bashing doors in.
After all…
Is it a drug? Yes.
Are you the approved distributor of that drug? No.
Is it patented? Oftentimes, yes.[28,29] (note that there are countless SARM patents)
Are you introducing a counterfeit drug into interstate commerce? Yes.
Now, Ostarine has made it even further than those underground research chemical sites — it’s now plainly listed on several of the supplement stores that PricePlow works with, and rumor has it that a relatively large brick-and-mortar retailer will be carrying some SARMs soon enough as well.
The ultimate legality may come down to a compound-by-compound basis, but don’t delude yourself into thinking this is legal (or not illegal). It might be “flying under the radar”, but that is no indication of actual legality.
As if the DEA cared…
And even if you can argue some gray area technicality, do you think for one moment that the DEA even cares about legal technicalities? They’ll raid your warehouse like a band of stormtroopers, take everything they see, and lock it into a vault while you go bankrupt. You didn’t expect them to play fair, did you?
What will likely happen
So whose job is it to enforce the patents? There are several federal laws that protect patent holders,[30] but does GTx need to pursue these companies themselves, or does the government? They clearly have a case (someone else is making tons of money off of their research and IP, while they aren’t), but do they care yet? Does the DEA? Where is the line drawn, and when?
Anyway, due to the fact that DASCA contains a provision that basically any compound can be added to the ban list, it’s not hard to imagine that they might just add these compounds to the list and be done with it. That’s probably where this chapter of the industry quietly ends, in our opinions at least.
But users don’t care about legality, do they?
Nevertheless, various companies have taken to sell them both online and in small brick-and-mortar stores, despite their non-compliance, and users are buying them in droves — without doing proper research.
The end-user lack of research is where we take issue, since these users all run the risk of potentially harming themselves in the process (such as by taking too much or not running PCT). Adding to the problem, the “supplement companies” selling these drugs don’t seem to be educating their customers either.
For instance, several companies are advertising doses of Ostarine as 15mg-30mg, stating that you don’t need to run post cycle therapy. However, the research-based dose of ostarine was at 3mg,[31,32] and it dropped test production by 25%![31] What in the hell do you think is going to happen when you run it at 10x that dose?!
Should you trust someone who’s breaking the law at a profit?
The bigger issue from a consumer’s point of view is, how do you trust someone who’s openly violating the law — and profiting off of that?
Some of the “supplement companies” have popped up from out of nowhere, here to make a quick buck. How can anyone be sure of what they’re getting?
This isn’t something like DMAA, which is still being disputed in the court system and could go either way. This is flat out illegal and the companies selling them know it. What’s stopping anyone from breaking the law further by missing ‘label’ claims? It’s not like it would have been legal in the first place!
So if you’re going to step into this fold, you better hope to death that you’re getting what they’re saying they’re giving you, in the dose claimed. Third party lab tests — not tests from the manufacturer or raw material suppliers — are paramount. But do they exist?
The research is still a bit flimsy
Meanwhile, the fact is that nobody in the supplement industry has anything more than a surface level clue about these first/second generation SARMs. Big pharma might not know much more, and if they do, they currently have no obligation to share it with us.
Many of these are effectively failed prescription drugs whose research was aborted upon their failure. Still others have their research still in progress, but have yet to gain approval (the primary example being GTx and Ostarine).
GTx has even go so far to state on their SEC reports,
“We do not expect to obtain FDA or EMA approval, or any other regulatory approvals, to market any of our product candidates, including enobosarm (ostarine), for the foreseeable future, and it is possible that none of our product candidates will ever receive any regulatory approvals.[33]
— GTx Inc. SEC Report, June 30, 2014
Meanwhile, their quarterly loss was just under $48 million for 2Q 2015.[34] This does not paint a rosy picture in terms of approval or safety, and that’s for the most well-researched SARM out there!!
The dangers of some compounds: Worth risking cancer?
Even worse, one compound named GW-501516 / Cardarine was abandoned for research because it caused cancer in animal studies at all doses, at all durations of use.
Arguments on GW-501516
It’s worth noting that the response to these allegations is that it is generally unlikely that PPAR is going to stimulate cancer growth in human cell lines – a valid case – but again… is anything worth that risk?
It’s also worth noting that GW-50516 is not even a SARM. However, it’s classified as one by several websites that sell the stuff, which reaffirms our pleas for users to do their research, lest the blind lead the blind!
Have things really gone this far? Spending $55/month for something that probably increases some parameters of endurance exercise… that has literally never been given to a human in a clinical setting?
This is the kind of territory you’re getting yourself into here, folks. No man’s land. There’s no reason to be someone else’s petri dish.
This probably won’t end well.
So why do we care? Because there’s a chance that this ends up in USA Today and every other major newspaper, and the media is undoubtedly going to make all of us look like scum. Every last one of us, from consumers to brands to industry advocates, will end up far worse if that happens.
But so far, nobody seems to care much. MAXIM magazine already covered this months ago,[39] and apparently Marc Lobliner’s been questioned by a massive men’s print magazine as well. That’s just the beginning… but so far, not much fanfare.
If it bleeds, it leads…
As the phrase goes in the media industry, “If it bleeds, it leads” – but nobody has gotten seriously hurt (yet).
These compounds – at least ostarine and andarine – do seem safer than most of their predecessor alternatives, specifically prohormones. But that may not matter – all it will take is for one idiot to drink himself to death while he has some kind of SARM in his bloodstream, and you can imagine the media shitstorm that will come next. (This is also why we can’t have nice things.)
So how can any level-headed company not expect this to end poorly for the industry?
At best, nobody is hurt, and some people have some gains. Eventually, DASCA may be revised to ban them, nice and quietly.
At worst, something stupid happens, which catalyzes the next John Oliver segment on the supplement industry and the next FDA push to stifle any room for legal innovation in the industry just because a few people were greedy. Conveniently during election season, no less.
It’s one thing to have these compounds in obscure places that only well-researched steroid users know about. But selling this through popular brick and mortar stores as a dietary supplement is risky to the nth degree for everyone involved.
But in the meantime, they will sell, and they will sell well, so we just urge users to do their damned homework before proceeding. And that means to understand that SARMs aren’t supplements, they are investigational drugs that should be treated with the care of steroids.
Good luck, folks. Stay safe and do your research.
UPDATE:
Bruce Kneller’s Opinion regarding FDA legality
This was emailed to us on September 1, 2015:
FDA and various US Attorneys may very likely be inclined to view all SARMs currently sold as dietary ingredients/supplements not only as mere drugs, but as prescription drugs.
The reason is very simple even if the argument may be viewed as somewhat of a stretch.
First and foremost, all of the SARMs references in your exceptional article are going to be considered drugs by the FDA and US Attorneys – and this is a correct interpretation which is pretty straightforward. None of the SARMs meet the legal definition of a dietary ingredient under DHSEA 1994 and their appearance in any dietary supplement is an act of misbranding and product adulteration. They are by default, all misbranded drugs. It would be futile to argue this point.
However, FDA and some US Attorneys may successfully argue that SARMs have a reasonable probability of resulting in permanent impairment of a body structure or function in at risk consumers and thus can not be used except under the supervision of a practitioner licensed by law to administer such.
Certainly, by selling SARMs as misbranded drugs under the ruse that they are legal, dietary supplements at 10X the dose, or even higher, studied in any human trials would surely bolster such an assertion by FDA or a US Attorney regarding likelihood of permanent impairment of a body structure or function in at risk consumers anyhow.
While some may view this perspective as a tenuous if not specious (and certainly dose dependent) argument, it’s not beyond the pale of something FDA could try to do. In 1951, The Durham-Humphrey Amendment to the FDC became law in the USA. For the edification of you and the PricePlow readers:
“The FDC Act defines a prescription drug at FDC Act § 503(b)(1) as:
A drug intended for use by man which –
(A) because of its toxicity or other potentiality for harmful effect, or the method of its use, or the collateral measures necessary to its use, is not safe for use except under the supervision of a practitioner licensed by law to administer such drug; or
(B) is limited by an approved application under section 505 to use under the professional supervision of a practitioner licensed by law to administer such drug..
As passed into law in 1951, The FDC Act § 503(b)(1) included three categories of Rx drugs: (1) habit-forming drugs under § 502(d); (2) drugs that are unsafe for use except with a doctor’s supervision; and (3) drugs limited to Rx use under an NDA.”
[emphases added are Bruce’s]
While the thought of FDA viewing SARMS being illegally sold as dietary ingredients/supplements right now as prescription drugs may seem a bit of a stretch, a quick review of FDA’s historical enforcement actions regarding aromatase inhibitors being sold as dietary supplements should serve as a prescient and clear warning that this very type of thing surely can happen.
— Bruce Kneller, Giant Sports Products
…and there you have it.
