What Are SARMs?

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SARMs have gained a lot of traction over the past few decades, and recently, their use has exploded in the fitness world. Gone are the days of approaching the gym steroid dealer in the locker room and just asking for Dianabol, Winstrol, or Trenbolone. Today, many gym rats are buying their PEDs from research chemical company websites.

But, what are SARMs? How do SARMs work? And what are the downsides of using SARMs while training for bigger, stronger, and more powerful muscles? We’re going to break all that down today.

What Are SARMs?

SARM stands for Selective Androgen Receptor Modulators. They’re the androgen counterpart of what many gym rats would call PCT, or post-cycle therapy. If you’ve ever used gear, and been told you needed to use PCT you would have used something like tamoxifen for that. Tamoxifen is an example of a Selective Estrogen Receptor Modulator, or SERM. While SARMs and SERMs function relatively similarly, they have different biological targets and lead to very different outcomes.

SARMs are not anabolic androgenic steroids (AAS), but they are anabolic in nature since they target androgen receptors, the same receptors that anabolic androgenic steroids target. SARMs tend to amplify the anabolic while minimizing the typically unwanted androgenic side effects of steroid use. More on that later.

SARMs were discovered in 1998 when scientists came across an anabolic compound that selectively stimulated androgen receptors in muscle and bone, while sparing reproductive organs/tissue. These operated much differently than androgens (like testosterone and anabolic androgenic steroids) since they could target specific tissues.

Androgens target all tissues, while SARMs can target specific tissues. You can see the chemical makeup of typical SARMs vs the chemical makeup of testosterone in this photo to the side.

You can think of SARMs more like a tactical nuclear bunker buster, whereas anabolic androgenic steroids are more like the bombs dropped on Hiroshima and Nagasaki. It’s also fairly similar to using broad-spectrum antibiotics vs using narrow-spectrum antibiotics. Using broad-spectrum antibiotics can be beneficial, but they can also create antibiotic-resistant bacteria when not needed. Much like broad-spectrum antibiotics, AAS can also lead to unwanted side effects over time, and SARMs can mitigate many of those side effects.

Mechanisms - How They Work

There’s actually some debate as to the exact mechanisms for the function of SARMs. There are really three different pathways that are debated and they are:

• 5alpha-reductase

• Androgen receptor coregulation

• Non-genomic signaling

While the exact mechanism isn’t 100% understood yet, the overall outcome doesn’t really change. We’ll go over these mechanisms now.

5alpha-reductase

5alpha-reductase is an enzyme involved in steroid metabolism. They’re involved in androgen and estrogen metabolism, as well as bile acid biosynthesis. Testosterone is active in non-reproductive tissue without activation, and when 5alpha-reductase “activates” testosterone to its more active form of DHT, it becomes much more active in the reproductive tissues. Because of this, both Test and DHT are not very tissue-selective.

SARMs are not products/substrates of 5alpha-reductase, therefore they’re not activated in tissue like the prostate and other reproductive tissue. Scientists believe that the lack of activation by 5alpha-reductase allows for SARMs to not be activated within reproductive tissue.

In layman’s terms, SARMs aren’t given a suit jacket (not activated), so they can’t get into the nice country club (reproductive tissue).

Androgen Receptor Coregulators

So, this explanation is going to sound like Greek if you don’t have a legitimate degree in one of the Brosciences (and even then it might still). I’m going to try to do my best to make this as understandable as possible.

In your body, there are agonist and antagonist relationships. Agonists cause structures to behave a certain way, while antagonists prohibit something from behaving a certain way. You have this same relationship in your musculoskeletal system where agonist muscles cause an action, while antagonists cause the opposite action. Like your biceps and triceps function to flex and extend the elbow respectively.

In your body, you also have coregulators that are called coactivators and corepressors. Coactivators help with the upregulation of gene expression, while corepressors assist with the downregulation of gene expression. Agonists tend to recruit coactivators, while antagonists tend to recruit corepressors. They work together to accomplish the task.

SARMs have mixed functions, sometimes acting as an agonist and other times acting as an antagonist. SARMs display agonist actions in bone and muscle androgen receptors, while also acting as either an agonist or antagonist in other reproductive tissues in the body like the prostate.

Testosterone is able to recruit coactivators when bound to androgen receptors, but is not able to recruit corepressors. This makes testosterone an agonist in all tissues. Because SARMs act as both an antagonist at times and an antagonist at other times, SARMs can recruit corepressors when abundant, and coactivators when abundant. Corepressors are in excess in reproductive tissues like the prostate, while coactivators are in excess in muscle and bone tissue. Because of this, SARMs are selective in their activation of anabolism in these tissues. They function as agonists in bone and muscle tissue, while acting as an antagonist in reproductive tissue. Side note but important when it comes to the next possible mechanism, this all is said to take place within the androgen receptors located inside the nucleus of the cells.

In layman’s terms, SARMS are like Kamala Harris’ accent. SARMs will change their accent (function of agonist or antagonist) to whatever is more popular (more corepressors vs more coactivators) given their geographic environment (reproductive tissue vs muscle/bone tissue).

Non-Genomic Signaling

We also have androgen receptors in the cell membrane. The androgen receptors in the cell membrane have what are called non-genomic effects on the cells via signal transduction cascades. A transduction cascade is just a cascade of events that occur within the cell, and they’re signaled by something binding to that cell. In this case, it’s hypothesized that the SARM binds to the androgen receptors in the cell membranes and signals the cell to behave in a certain way. This process would ultimately function differently in muscle and bone tissue vs in reproductive tissue since testosterone and SARMs affect the androgen receptors in a different way.

In layman’s terms, SARMS and testosterone are like coaches telling their teams what to do. Different coaches are going to coach in different ways. Although the gameplay (transduction cascades) looks different, the coaches (testosterone and SARMs) are still doing the same job.

What Are the Benefits of SARMs?

Now we’re going to move on to what the functions of SARMs are. SARMs help to increase anabolism. Anabolism is the part of your metabolism that is responsible for growth, and there are a ton of benefits to increasing anabolism within your muscle and bone cells. Some of the possible benefits of SARM use are:

• Increased muscle mass

• Better recovery

  • Both inter and Intra-workout

• Increased strength

I know that doesn’t seem like a long list, but to most gym rats and athletes that’s the complete list of things they want in a supplement/performance enhancer. If I can simultaneously increase my output, increase my muscle size, increase my strength, and decrease my time to recover I’m a happy camper.

Now, there’s no direct mechanism for increased strength when it comes to SARM usage, but the increased muscle mass, increased work capacity, and increased ability to recover sets the table to be able to get stronger, faster. This increased strength can also have a positive impact on your power production and speed. At first glance, SARMs seem to have all the positives of steroid use without any of the negatives. We’ll go over the potential negative side effects next.

What Are the Negative Side Effects of SARMs?

The purpose of using SARMs instead of using anabolic androgenic steroids is to avoid the androgenic side effects. Since SARMs don’t target reproductive tissue, the androgenic side effects are low but for some reason, they still exist.

There was a study published in The International Journal of Impotence Research in September of 2021, where they looked at the positives and negatives of SARM usage. In this study, over 50% of SARM users reported mood swings, testicular atrophy, and acne. All of these outcomes are traditionally associated with AAS use, due to their androgenic nature. It should be noted that in this study, the product (the actual SARMs) wasn’t controlled by the researchers. Instead, they were purchased through research chemical internet=based companies by the individual subjects. These “SARMs” could have contained anything in them, including anabolic androgenic steroids. So take that study with a grain of salt.

In another study published by US Pharmacist, they found that SARMs can reduce endogenous testosterone (your body’s own testosterone production), increase cholesterol levels, and decrease liver function.

The FDA states that SARM use can cause the following:

• Increased risk of heart attack or stroke

• Psychosis and/or hallucinations

• Sleep disturbances

• Sexual dysfunction

• Liver injury and failure

• Infertility

• Miscarriage in women (or “uterus havers” if you’re one of those people)

• Testicular shrinkage

Now, the government has lost a ton of its credibility over the years, and for good reason. Side note, if you want to read about how the government helped make everyone fat, give this a read. I have a hard time believing much of what comes out of government agencies, no matter how good-intentioned it may be. With that, I’ll say that I’m a skeptic of what the government-led FDA says about SARMS. The reason is that there aren’t any good controlled studies on SARMs. Where are they getting their information? They seem hell-bent on ridding the country and culture of masculinity, and this feels like an extension of that.

There is some evidence that SARMs can decrease your endogenous testosterone production, which is a bad thing. While we want to limit the androgenic side effects of AAS use in our quest to get bigger, faster, stronger, and leaner, we don’t want zero androgenic side effects. When taking AAS, your body will also slow down/shut off endogenous testosterone production, but the steroid/testosterone will be converted to estrogen via the aromatase enzyme. With less testosterone and none being pumped into the body through AAS use, you’ll run dangerously low on estrogen. I know we want to limit estrogen, but we can’t have none. Too low estrogen in men is also dangerous and can cause many of the same issues too much testosterone can cause.

Honestly, I think as of right now with the information we have, the biggest reason you should avoid SARMs is because there are no standard manufacturing practices for the SARMs most people are buying. Much of what you’re buying is being made in someone’s basement or garage. You might be getting Osterine, you might be getting Dianabol, you might be getting flavored piss water. No one really knows. These products are often labeled “not for human consumption” and they’re produced by research chemical companies, aka basement PED operations.

While there are studies finding some androgenic side effects, there’s no real reason for SARMs to produce these side effects if their pathways and functions are truly what we’ve been told. I guess just proceed at your own risk, you don’t really know what you’re getting unless it’s prescribed by your physician for your muscle-wasting diseases or conditions.

Let’s Wrap This Up

SARMs can be a great tool for people with muscle-wasting diseases and recreational bodybuilders alike. They provide all of the anabolic benefits of AAS use while limiting much of the unwanted androgenic side effects. They’re also great for amplifying the anabolic effects of AAS, while simultaneously limiting the negative side effects of that same AAS usage.

The downside? There are some unwanted side effects, there are possible androgenic side effects, and you just don’t know what is in your product when you purchase it from these research chemical labs.

I think we need more time to study the long-term effects of SARMs before I would recommend them to anyone. This is also something kids need to stay away from, much like AAS. I believe the reasons for this are obvious, but we don’t really know the long-term effects, and you don’t really know that you’re getting the drug that is on the label that says “not for human consumption.”

Also, most people who reach for these supplements have no business dabbling in steroids and SARMs. They haven’t spent the time getting all they can from their bodies before reaching for the shortcut. If you’re getting tested, you’ll also want to avoid SARMs as they test directly for these compounds in sport now.

If you’re thinking about using SARMs, make sure you’re a grown adult, you have a training age of at least 7-8 years, and you’re buying them from a reputable lab and not a research chemical lab.