How Do SARMs Work? What You Need to Know
Disclaimer: SARMs are only to be used for research purposes, as they are non-FDA approved compounds and thus may cause adverse effects. If you have any questions or concerns, Dr. Touliatos is currently available for consultations.
Selective androgen receptor modulators (SARMs) are currently being studied as a potential anabolic treatment in medicine.
Chemical modifications of testosterone, known as steroidal SARMs, were formulated in the 1940s as a means to induce anabolism (without androgenicity) in specific tissues.
When anabolic steroids (specifically testosterone) were first medicinally approved in 1939, their androgenic side effects became well known (1).
Such effects included male pattern baldness, prostate hypertrophy, acne vulgaris and virilization in women.
However, the SARMs that are referred to today are non-steroidal SARMs. These are not modifications of testosterone, but instead, androgen receptor ligands—that were formulated in the 1990s (2).
How Do SARMs Work?
SARMs bind to androgen receptors in the body with special tissue selectivity. Thus, they are capable of stimulating some receptors and not others.
This means that receptors with muscle-building potential are targeted, whilst other receptors with potential for androgenic side effects are avoided.
However, due to the recent formulation of non-steroidal SARMs, they are yet to be perfected. Thus, as of now, they are not 100% selective with zero effects on non-targeted receptors.
Therefore, we still see some androgenicity exist with SARMs, but their anabolic to androgenic ratio is highly favourable vs anabolic steroids.
For example, RAD 140’s anabolic to androgenic ratio is roughly 90:1. In contrast to Testosterone’s 1:1.
Consequently, SARMs will cause moderate increases in LBM (lean body mass), combined with notable amounts of lipolysis (fat loss).
Below is a list of SARMs:
- Ostarine (Mk-2866)
- RAD 140 (Testolone)
- LGD-4033 (Ligandrol)
- Andarine (S4)
It is important to differentiate SARMs from non-SARMs, as some PEDs get (unofficially) labeled as part of the SARM family, yet work completely differently.
Some examples of non-SARMs are:
- Ibutamoren (MK-677) – a growth hormone secretagogue.
- Cardarine (GW501516) – a PPAR (Peroxisome Proliferator Activated Receptor) agonist.
- YK-11 – a myostatin inhibitor.
- Stenabolic (SR9009) – a Rev-ErbA agonist.
How Ibutamoren Works
Growth hormone secretagogues, such as Ibutamoren, mimic the role of ghrelin; a hormone that binds to growth hormone secretagogue receptors (GSHR) in the brain.
This consequently spikes GH (growth hormone) and IGF-1 (insulin-like growth factor 1) levels, which increases muscle-building and subcutaneous fat loss. In our experience, users typically gain 6lbs of muscle when bulking on Ibutamoren. Generally, Ibutamoren is more suited for bulking cycles, with its lipolytic effects being less potent.
How Cardarine Works
Cardarine is often mistaken for a SARM, but instead is a PPAR (Peroxisome Proliferator Activated Receptor) agonist.
Cardarine is known for its exceptional fat-burning properties, and thus it is often utilized during cutting cycles, alongside other SARMs (such as Ostarine).
Peroxisome proliferator-activated receptor-delta (PPAR-δ) balances essential metabolic functions, that contribute to preserving optimal energy balance. It is particularly important for regulating β-oxidation, fatty acids and insulin sensitivity.
Therefore, Cardarine’s potent fat-burning effects are the byproduct of its positive effects on insulin sensitivity, glucose tolerance and lipid balance.
We have had users lose as much as 40lbs on Cardarine from a 12-week cycle (3). We have also observed some anabolic effects with Cardarine, with research also reporting FFM (fat-free mass) increases of 1.3kg in users (4). Thus, Cardarine appears to not only accelerate fat burning when cutting, but also increase muscle retention/gain.
How YK-11 Works
YK-11 increases follistatin, which decreases myostatin levels. Myostatin is a myokine that inhibits muscle growth, thus by taking YK-11 users will essentially maximize their muscle-building potential.
We find users typically gain 10-15lbs after their first YK-11 cycle.
It is believed that several IFBB bodybuilders, that are tremendously gifted genetically, have myostatin deficiencies.
In 1998, BALCO laboratories analysed 62 men that had previously experienced exceptional muscle growth. Of these 62 men, 9 were diagnosed with a myostatin deficiency/mutation.
Flex Wheeler, one of the all-time great bodybuilders of the 90s, was one of these 9 men. Flex actually carried one of the rarest of myostatin mutations—the ‘exon 2’ gene.
How Stenabolic Works
Stenabolic is a Rev-ErbA agonist. This means that it binds to the Rev-Erb protein, which is present in our fat cells, liver and muscles. Thus, Stenabolic significantly enhances the activity of this protein, shifting the body into an enhanced anabolic state.
As Stenabolic stimulates higher levels of protein synthesis, its effects are non-hormonal, meaning it does not suppress endogenous testosterone. Consequently, a post-cycle therapy is unnecessary after taking Stenabolic.
SARMs Side Effects
We have found that, similar to anabolic steroids, the more potent a SARM is — the harsher its side effects.
Based on our tests, Ostarine and Andarine (S4) are the mildest SARMs. The harshest SARMs are S23 and LGD-4033. RAD 140 poses moderate side effects.
Although users may experience less androgenic effects from SARMs, other side effects may still occur. One argument for SARMs is that they do not produce as harsh side effects compared to anabolic steroids. Although this may be partially true regarding intensity, we have found SARMs can still be cardiotoxic, hepatotoxic and suppressive (to different degrees).
Due to excessive stimulation of androgen receptors, endogenous testosterone will decrease on SARMs. This is not generally to the same degree as anabolic steroids, with some users not experiencing any low testosterone symptoms from SARM cycles.
However, some SARM users do experience significant drops in testosterone (>60%), causing them to become temporarily hypogonadal. In this instance, a PCT of Nolvadex at 20mg/day for 4 weeks will aid in the acceleration of endogenous testosterone recovery.
SARMs suppress high-density lipoprotein cholesterol, possibly due to a stimulation of the hepatic lipase enzyme in the liver.
Consequently, blood pressure will rise on any SARM, albeit to lesser heights than most anabolic steroids.
Our patients perform regular cardio, limit their sodium intake and supplement with 4g/day of fish oil to keep blood pressure within a normal range.
SARMs are hepatotoxic and thus AST/ALT enzymes will rise on-cycle. Anecdotally, we have found that SARMs have the potential to cause hepatocellular–cholestatic liver injury. This is also confirmed in clinical research (5). However, such an injury is uncommon when taking moderate dosages and taking rest in-between cycles.
The main risks of injury will include combining SARMs with hepatotoxic medications (such as antidepressants) or taking mega doses for excessively long periods of time.
However, if a user’s liver is not healthy before a cycle, they should avoid SARMs.
Tip: Taking 500mg/day of TUDCA will minimize hepatic inflammation during a cycle, keeping users as healthy as possible.
What to Expect
In our experience, SARMs are not as potent as anabolic steroids, regarding muscle gain and fat loss. However, there is a case that SARMs pose less risk.
SARMs are almost as potent, if not more so, for increasing muscular strength vs anabolic steroids.
SARMs are also legal to purchase if used for ‘research purposes’, whereas anabolic steroids are illegal.
More research needs to be conducted before we know the exact effects of SARMs. However, gains of up to 10lbs in lean muscle from a cycle, with notable amounts of fat loss, appear to be a common outcome.