Note: Andarine and other SARMs alike are considered research chemicals and are not approved for public consumption. Use of andarine and similar research chemicals should be restricted to a clinical setting.
Often referred to as S-4, andarine is a research chemical classed as a SARM, touted to potentially improve bone density and strength while favorably adjusting body composition.
Since SARMs are selective in the tissues they activate, this makes S-4 an attractive option for selectively improving bone and muscle strength for populations that can't necessarily use hormone therapy such as the aging or sick (1, 2, 3).
But with a lack of oversight and very little research only in animals, both short and long term effects of this substance have not been established in either animals or humans.
As we'll dive into, due to lack of research and unknown effects in humans, the use of andarine is discouraged.
Andarine (S-4) Is a SARM
Andarine is one of the newest research chemicals to attract the eye of both researchers and laypersons alike for its potential influence on lean body mass, fat mass, muscular strength, and bone health.
As a Selective Androgen Receptor Modulator (SARM), andarine is researched as a potential replacement for hormone therapy, which is often the first choice for treating age-related changes in the body such as muscle and bone loss.
SARMs like andarine are attractive because they are able to activate androgen receptors selectively. Doctors then have the opportunity to specifically target tissues or areas of the body like muscle or bone, without influencing other tissues such as sex tissue like the prostate (3).
Testosterone and estrogen, for example, are hormones often prescribed for developing muscle mass, muscular strength, and bone density and strength. But unfortunately, these hormones are not tissue selective and could lead to unwanted side effects and growth of tissue like the prostate (4).
Thus, andarine as a SARM is attractive because of its potential influence on muscle mass, strength and bone density with reduced risk of developing diseases such as cancer.
The potential for building lean mass and reducing body fat while minimizing side effects makes SARMs like andarine subject for illicit use. While SARMs do seem to achieve similar results as steroids without the adverse effects, long-term use and safety in humans have not been established. Despite the potential for reducing side effects, steroids may be a better option only due to knowing their potential consequences.
It’s also important to understand that the limited research studies on this substance and many other SARMs alike are not conclusive as many are only in rat models. Further, information online wrongly assumes that different names like S-4 and S-40503 represent the same SARM, creating confusing and often misleading information that could lead to improper dosing and unknown effects (5, 6).
Studies On Andarine (S-4)
Importantly, there are very few studies regarding andarine safety and effectiveness. Further, the studies that do exist are in rat models, which mean there is no definitive information on how andarine will influence the human body.
Despite rat models being the standard for research of this sort, many times analysis reveals very different results when being tested in humans. The fact that no human studies are available for this substance should discourage use.
Andarine Treatment In Orchidectomized Male Rats
In the first animal study to test andarine, scientists performed orchidectomy surgery, (removal of testicles), on 12-week-old male rats, thus removing their natural androgen production. After, these rats were held for an additional 12 weeks to allow for clearance of androgens and to also allow for reductions in muscle size and strength, similar to what would happen if natural hormone production stops (7, 8).
After the 12-week washout period, both control and rats receiving S-4 were placed into different groups, based on substance and dosage.
For the group receiving andarine, rats were given either 3 mg/kg or 10 mg/kg of body weight for the remaining 8 weeks of the study. Other groups received only placebo as a control or the steroid hormone known as DHT.
By testing varying dosages of S-4 and comparing to placebo and its direct steroid competition (DHT), scientists can potentially learn how this research chemical influences the body compared to nothing at all and the current option available (hormones).
Before, throughout, and after the commencement of treatment with S-4, rats were tested against multiple variables such as muscular strength, muscle size, body weight, body composition and also bone density. Since these are the primary targets of hormone therapy, understanding the influence of andarine on these variables helps us appreciate its effectiveness (7).
Muscular Size & Strength
Upon completion of the andarine intervention, scientists removed the soleus (calf) muscle from tested rats and rigorously tested these muscles to understand muscular strength and functions. They do so by electrically stimulating the muscle and recording different variables of muscle contraction like how quickly it reaches peak tension, which is indicative of force development (8).
When measuring the strength ability of treated rats, those receiving 10mg of andarine showed significant improvements in peak tension over both intact and ovariectomized control rats. Muscle size, however, was a different story, with no significant improvements in soleus muscle size (7).
Although, the authors do mention that this lack of size improvement could be due to low androgen receptor activity, specifically in the soleus muscle. Importantly, this lack of size increase was consistent with DHT rats as well, suggesting that this theory of low androgen activity is plausible (7, 9).
However, it was reported that levator ani muscle weight was favorably changed. In opposition to the soleus muscle, levator ani is known to respond favorably to androgens (10).
What they found was that compared to the soleus muscle, levator ani growth significantly increased when rats were given S-4, compared to castrated control rats. The administration of S-4 completely abolished muscle loss that occurred as a result of castration (7, 8).
These findings suggest that lack of soleus growth could be due to low androgen activity rather than ineffectiveness of andarine (7, 8).
Moreover, the data here indicates that despite increasing levator ani weight, andarine had only a slight influence on prostate and seminal vesicle weight, displaying similar end weights as control rats. This suggests that S-4 is indeed selective in the tissues it functions within, meaning andarine might be a strong candidate for preventing or treating muscle wasting without side effects often associated with their steroid alternatives (7, 8).
Throughout this study, rats were regularly tested via DEXA scan to understand changes in bone density. DEXA is a full body, dual x-ray scanner, which is considered to be one of the best options for testing body composition (11).
Data indicated that S-4 might play a significant role in improving bone density or at least preventing age-related decline. In fact, this study shows that treatment with andarine maintained bone density similarly to intact rats. Even more fascinating were the findings that andarine achieved this effect whereas DHT had almost no influence at all (7).
This data is essential because it means that andarine may be a good option for improving bone health and perhaps and better alternative to hormone therapy.
In terms of adjusting body composition, S-4 worked primarily through maintaining lean mass or bringing muscle mass back to normal levels. Despite a trend for an increase in body weight, which is expected with castration, rats given andarine showed almost no reduction in lean mass, compared to castrated control rats.
Compared to DHT, however, S-4 was significantly less potent in stimulating body composition changes as DHT resulted in significant reductions of fat mass and significant increases in lean mass, with a reduction of body weight (7).
Importantly, andarine did increase levator ani muscle weight compared to the castrated control rats and did so without any significant influence on prostate and seminal vesicle weight, suggesting a selective influence (7).
Overall, andarine did prove useful for castrated rats across many different variables. Most importantly, andarine produced significant improvements in bone mineral density and did so to a greater extent than DHT (7).
Additionally, changes in levator ani weight with little influence on prostate and seminal vesicle weight suggest that andarine may selectively target androgen-dense skeletal muscle while avoiding impact on reproductive tissue (7).
Again, these findings are only within a rat model and are by no means conclusive.
Andarine Treatment In Ovariectomized Rats
In a similar study to the first, 120 female rats 23 weeks of age either had ovaries removed (ovariectomy) or were placed into control. From there, rats were placed into 1 of 12 treatment groups, including 7 different dosing protocols with andarine (12).
Rats placed into andarine experimental groups were separated based on dosage and substance received. Dosages with only andarine were provided daily in milligrams as follows:
• 0.1 mg
• 0.3 mg
• 0.5 mg
• 0.75 mg
• 1.0 mg
• 3.0 mg
Notably, there was another group that received 0.5 mg of andarine in addition to 1.0 mg of a substance known as bicalutamide, which is a known anti-androgen agent. This substance is often used for hormone therapy to limit the action of androgens (13).
By combining S-4 with bicalutamide, scientists can observe which effects afforded are androgen specific. Frankly, if an effect occurs for rats using only S-4 and for those also taking bicalutamide, we can conclude the impact is not dependent on activating the androgen receptor.
Further, some rats were also provided with the steroid hormone DHT similarly to study one. This action was, of course, to serve as a control for understanding and comparing the influence of a potent steroid hormone to that of andarine (11).
After being separated into their respective groups, rats underwent DEXA scans to observe metrics like bone density, body weight, and fat and lean mass. This test commenced on day zero and at the end of the 120-day testing period to observe any changes.
Fascinatingly, the testing didn't stop there. Upon completion of the 120-day intervention and sacrificing of rats, researchers also independently tested bone strength of the rat's femur to observe the influence of andarine on bone density, strength, and resiliency.
Unsurprisingly, andarine was indeed effective at limiting bone loss in an ovariectomized female rat model. The data indicate that in a dose-dependent manner, andarine helps prevent bone loss that could arise from age-related estrogen decline or removal of female sex organs. The researchers reveal that with the highest dose of 3.0 mg, andarine almost completely prevented bone loss (12).
In accordance with improvements in bone density, 3.0 mg of andarine was the most effective dose for maintaining bone strength and resiliency (12).
The results of strength testing show that while 3.0 mg produced the most significant effect, just 1.0 mg showed bone strength measures similar to that of intact rats (rats without ovaries being removed).
Also worth considering is that the findings of this study also showed that andarine was more potent at maintaining bone strength than DHT, suggesting that andarine may indeed be an excellent option for preventing age-related or hormone-related bone degradation without many of the adverse side effects associated with hormone therapy (12).
Body Composition Changes
Similar findings to study one were revealed in that rats responded favorably to S-4 in a dose-dependent manner. When female ovariectomized rats were given 3.0mg of S-4 per day, their body composition shifted towards that of what intact rats display. This means that andarine might help prevent adverse changes in body composition that arise from changes in hormonal status due to old age or disease.
Amazingly, all rats had gained weight by the end of the study, except for intact rats receiving only andarine. In fact, even the intact placebo group gained more weight throughout the course of the study. Better yet, intact rats receiving andarine displayed the lowest body fat percentage and the highest percentage of lean mass, surpassing even the intact DHT group (12)
This seems to suggest that S-4 may have more potent action particularly in healthy females that aren't typically used to androgenic substances compared to male counterparts (7, 12).
Despite favorable body composition changes afforded by S-4, regardless of gender, these differences allude to different action and potency depending on gender. If nothing else, these mixed findings should discourage use until more information is made available.
In female ovariectomized rats, andarine administration seems to provide positive change to body composition, muscular strength, and bone strength and density in a dose-dependent manner. Further, when supplied to intact female rats, S-4 led to the most significant changes in body composition by inhibiting weight gain, increasing lean mass and reducing body fat percentage (12).
However, these findings were slightly different from the first study conducted with orchidectomized male rats, suggesting that S-4 might have different actions based on gender and current hormonal status (7).
With unclarified gender differences and research being relatively scarce, human use of andarine is discouraged until further information is provided.
S-4 is Not S-40503, And That's A Problem For SARMs
SARMs like andarine, ostarine, and cardarine are considered research chemicals. This means they are not for human consumption and should only be used for exploratory testing, outside of the body.
Since many of these chemicals are new and relatively unstudied, confusion arises over whether or not you're receiving the correct drug, or if you've even ordered the correct one in the first place. In fact, with a lack of peer-reviewed studies, many websites mistakenly consider andarine to be known as S-40503. The problem is that andarine is not the same as S-40503 (5, 6).
A simple search of the chemical composition of S-4 and S-40503 clearly show that these substances, while similar, are not the same. In fact, researchers experimenting with S-4 go out of their way to mention other studies with S-40503 and distinguish these two substances as different (5, 6, 12, 14).
This is a problem because the majority of information available to the public about SARMs is not peer reviewed. This lack of oversight means that information could be wrong, and no one thinks twice about it. It's also indicative of the fact that SARMs are relatively new to science and that evidence if far from conclusive.
With a lack of true oversight, you must be extremely diligent in your research to ensure that you're actually purchasing and using the substance you intend to. Even so, SARMs are research chemicals, and you shouldn't use them outside of a prescription from your doctor.
Other Important Considerations
As with other SARMs, there are a few considerations to be made in addition to those previously mentioned.
No Human Studies
Currently, S-4 has not been tested in or approved for humans. This means there is no short or long term data regarding effectiveness, dosing, side effects or even primary effects. This reality should discourage use until more information is released and andarine is approved for human consumption.
Mixed Evidence For Muscle Growth
The limited amount of research regarding S-4 indicates that at the very least, there may be gender differences, especially when considering muscle growth. However, with no human studies, it’s difficult to know if andarine will produce different effects based on gender or significant effects at all (7, 12).
Black Market Impurities
Since andarine and other SARMs alike are not approved for human use, production of these substances is not regulated, meaning you could be consuming something entirely different from what you intend.
In fact, one research lab tested a black market product that was available to anyone on the Internet claiming to contain andarine. They found that due to poor purification, approximately 10% of S-4 in the product was impure, which could have harmful effects in the body (15).
Without oversight and regulation, you’re merely hoping you get what you pay for, which could lead to serious issues or complications. Caution must be practiced when considering these substances.
Currently, there is no human information regarding the use of andarine in the clinical setting. Quite frankly, short and long term effects, either positive or negative have not been established.
To date, only a few studies have been conducted testing S-4 in rats that have had sexual organs removed. This is in an attempt to closely match how age progression might adversely affect hormone production, which can lead to reduced muscle mass, strength, bone density, and weight gain (7, 12).
Based on limited rat research, andarine does indeed seem to improve bone density and strength in addition to potentially reducing body weight and fat gain while potentially improving lean mass (7, 12).
Unfortunately though, despite the lack of evidence, S-4 is still an available substance, but only through third-party online manufacturers that aren't regulated the same as traditional pharmaceuticals.
This reality is of concern because many publications that discuss andarine wrongly associate it other SARMS, such as S-40503. This creates a dangerous environment in which people could accidentally take the wrong substance or improperly dose due to misinformation.
This misinformation is confounded by the fact that andarine on the black market could contain impurities or unknown substances, which could lead to severe complications (14).
Despite the potential for andarine to improve bone density and strength while favorably enhancing body composition, use of this SARM is discouraged until further information specifically in humans is released.
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