How do SARMs work and what shall You know? Selective androgen receptor modulators (SARMs) are a subject of ongoing research for their potential use as anabolic agents in medical treatments.
Early iterations of SARMs, known as steroidal SARMs, emerged in the 1940s—derivatives of testosterone designed for tissue-specific anabolic effects while aiming to minimize androgenic activity.
With the medical sanctioning of anabolic steroids, particularly testosterone, in 1939, the attendant androgenic side effects became widely recognized (1).
Such repercussions encompassed concerns like male pattern hair loss, enlargement of the prostate, acne, and masculinization in females.
Today’s modern SARMs, however, are distinct and referred to as non-steroidal SARMs. These were developed in the 1990s and are not testosterone derivatives but rather ligands that target androgen receptors (2).
The Mechanism of How do SARMs work
SARMs have a unique affinity for androgen receptors, exhibiting tissue selectivity. This property allows them to activate certain receptors—particularly those involved in muscle development—while avoiding others that may lead to undesired androgenic effects.
Despite their benefits and recent development, current non-steroidal SARMs are not entirely selective and can still influence non-target receptors to some degree.
Therefore, compared with traditional anabolic steroids, SARMs exhibit a more favorable anabolic-to-androgenic ratio, though they are not without androgenic properties.
For instance, RAD 140 boasts an estimated anabolic to androgenic ratio of 90:1, a stark contrast to testosterone’s 1:1 ratio.
As a result, users of SARMs may experience modest gains in lean body mass and a significant reduction in fat.
Here is a catalog of known SARMs:
It is crucial to distinguish SARMs from other performance-enhancing drugs that sometimes get mistakenly grouped with SARMs due to their distinct mechanism of action.
Examples of these non-SARM substances include:
- Ibutamoren (MK-677) – promotes growth hormone secretion.
- Cardarine (GW501516) – activates PPAR.
- YK-11 – an inhibitor of myostatin.
- Stenabolic (SR9009) – activates Rev-ErbA.
The Functions of Ibutamoren
Ibutamoren mimics ghrelin, enhancing growth hormone and IGF-1 levels, which promotes muscle growth and fat loss. It is often favored in bulking phases since its fat-burning effects are comparatively milder.
The Role of Cardarine
Cardarine is frequently mistaken as a SARM but functions as a PPAR agonist, primarily enhancing fat metabolism. It is often incorporated in cutting cycles to expedite fat loss while preserving muscle.
The Mechanism Behind YK-11
YK-11 boosts follistatin levels, thereby reducing myostatin, which is a muscle growth inhibitor. This maximizes muscle-building capacity, as observed in individuals with myostatin deficiencies.
How Stenabolic Operates
Stenabolic interacts with the Rev-Erb protein, enhancing its activity, which leads to increased protein synthesis. This process is non-hormonal, avoiding testosterone suppression and eliminating the need for post-cycle therapy.
Potential Adverse Effects of SARMs
Like anabolic steroids, the potential for side effects from SARMs tends to correlate with their potency.Our evaluations indicate that among SARMs, Ostarine and Andarine (S4) have shown to have the gentlest profiles. On the other hand, the most potent and possibly adverse effects have been associated with S23 and LGD-4033, while RAD 140 presents moderate side effects.
While SARMs tend to result in fewer androgenic reactions, they are not devoid of other side effects. SARMs are argued to be less severe in side effects compared to anabolic steroids, and while the impact may be less intense, our findings imply that there’s still a risk of SARMs leading to heart and liver toxicity, as well as hormonal suppression across varying extents.
Testosterone Suppression
The stimulation of androgen receptors by SARMs often leads to a reduction in the body’s natural testosterone production. This reduction is typically less severe than with anabolic steroid use, and some individuals may not notice symptoms of lowered testosterone from SARM cycles at all.
Nonetheless, there have been reports of SARM users experiencing substantial testosterone declines (>60%), leading them to a temporary hypogonadal state. In such cases, a post-cycle therapy (PCT) regimen using Nolvadex at 20 mg/day for four weeks is recommended to expedite the restoration of endogenous testosterone levels.
Cholesterol
SARM usage has been observed to lower high-density lipoprotein cholesterol, possibly due to the activation of the hepatic lipase enzyme in the liver.
As a result, blood pressure can increase with any SARM use, although generally to a lesser degree in comparison with anabolic steroids.
To manage their blood pressure, our patients adhere to routine cardiovascular exercise, maintain a low-sodium diet, and incorporate a daily supplement of 4 g of fish oil.
Liver Toxicity
It’s been established that SARMs can be hepatotoxic, leading to increases in AST and ALT liver enzymes during a cycle. There is anecdotal evidence, corroborated by clinical research, suggesting the potential for hepatocellular-cholestatic liver injury from SARMs (5). Still, such injuries tend to be rare when moderate dosages are used and adequate breaks between cycles are taken.
The likelihood of liver injury increases if SARMs are combined with hepatotoxic substances, like certain antidepressants, or if used in very high doses for extended durations.
Users with pre-existing liver conditions should steer clear of SARMs altogether.
Tip: The concomitant use of 500 mg/day of TUDCA may reduce hepatic inflammation during a SARM cycle, optimizing user health.
What to Expect
From our vantage point, SARMs may not match anabolic steroids in terms of muscle buildup and fat reduction potential. Yet, SARMs can present a reduced risk profile.
In terms of enhancing muscular strength, SARMs are nearly as effective, if not equally or more so, than anabolic steroids.
Legally, SARMs can be acquired for ‘research purposes’, while anabolic steroids are prohibited.
Further investigation is essential for a complete understanding of SARMs’ effects, but typically gains of up to 10 pounds of lean muscle mass with significant fat reduction are common outcomes from a SARMs cycle.
REFERENCES
(1) https://www.ncbi.nlm.nih.gov/books/NBK526128/
(2) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896569/
(3) https://www.ahajournals.org/doi/full/10.1161/ATVBAHA.112.247890
Dr. Grant Fourie, a specialist in male hormones, is based in Cape Town, South Africa. He provides comprehensive treatments for conditions related to low testosterone, such as erectile dysfunction, fatigue, and mood changes. His methods include hormone replacement therapy and other modern treatment options.
Contact me via email or phone to book personal appointment in my clinic: The Village Square, Cape Town - South Africa