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Andarine (S4) Benefits, Side Effects & Safety Information

Published: 18th June 2018. Last updated: 21th July 2019.

Shaun Ward MSc ANutr

Staff Writer


Introduction

S4, also known as Andarine, is a new type of selective androgen receptor modulator (SARM).

SARMs are drugs that are potential alternatives to standard testosterone replacement therapy, as they may have androgenic effects while avoiding negative side effects.

This stems from the ability for SARMs to be “tissue-selective” towards muscle and bone, while avoiding any unintentional binding on other tissues such as the prostate and the breast tissue.

As S4 is not a substrate for 5a-reductase and aromatases, it can also avoid exhibiting estrogenic functions - commonly observed with other anabolic agents [1].

At the moment, S4’s potential anabolic activity is being studied for its ability to treat disease-related muscle wasting and muscle performance in testosterone-deficient men.

Much like other anabolic drugs, it is also being used by active individuals as an alternative to steroids to improve body composition and strength.

Does Andarine (S4) Work?

It May Increase Strength

As intended, S4 has shown to be orally bioavailable with a high affinity and selectivity for the androgen receptor [2][3].

More importantly, animal and human studies have found that S4 treatment is able to fully restore muscle strength when testosterone levels are deficient [4][5].

As muscle strength is linearly related to muscle growth, it was initially assumed increases in lean body mass were the underlying reason for training adaptations.

However, researchers of this SARM state that the S4-induced increase in muscle strength cannot be fully explained by an increase in muscle mass [6].

It seems as though the change in muscle size does not properly correlate with the change in muscle strength [7].

Only future studies can confirm what other unique S4 may be having on the body to improve performance. The current hypothesis is that the increase in muscle strength may be related to changes in myosin heavy chain expression within muscle [8].

It May Improve Bone Health

Another benefit of S4 is how it may influence bone health.

Animal studies have found that S4 can partially or completely reverse bone loss in aged rats by promoting osteoblast differentiation [9].

This suggests that it could provide a novel pharmacological intervention in the prevention of bone loss in human populations, although similar studies have failed to replicate the anti-resorptive effects in bone [10].

It would not be surprising however when considering that other SARMs and androgen treatments have been found to regulate bone remodeling by altering gene expression and other signaling pathways [11][12].

Andarine (S4) Safety And Side Effects

The high anabolic potency of S4 alongside its “absence” of androgenic effects are the main reasons that attract athletes looking for advantages of steroids without the physiological side effects.

However, despite S4 being claimed to be completely tissue selective, there is evidence that indicates it may still suppress luteinizing hormone and follicle-stimulating hormone levels due to a “negative feedback loop” [13].

This is contradictory to the claims that since S4 does not affect pituitary hormone release as it does not have cross-reactivity with any of the other steroid hormone receptors [14][15].

This being said, some studies have not found these types of changes to hormonal levels [16], which likely means it highly depends on the dose of S4 being consumed.

There is a large need for more human research which is severely lacking at the moment.

Andarine (S4) Safety And Side Effects

SARMs such as S4 are currently defined as “not for human consumption”.

S4 has also been prohibited by world anti-doping agencies in sports, and is part of the S1 class of anabolic agents.

As a side note, for those looking to avoid consuming S4, it should be noted that it is often found in widely available over-the-counter supplements. For this reason, it is advised to stick to reputable supplement brands that regularly test their products for contaminants.

The Bottom Line

S4 is a selective androgen receptor modulator that is able to increase lean body mass and muscular strength.

As it preferentially targets androgen receptors, it may be able to reduce the amount of side effects that often come with standard testosterone therapy.

However, the current research still shows that it may significantly reduce natural testosterone production.

It is also not currently recommended for human consumption and should be avoided until more human research has been conducted.

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