SARMs: The Ultimate Guide (Side Effects & Benefits)

Dr George TouliatosDisclaimer: 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.


What Are SARMs?

SARMS (selective androgen receptor modulators) are a new generation of anabolic compounds, synthesized with the intention of being a superior medicine to exogenous testosterone (anabolic steroids).

Scientists’ main objective when formulating SARMs, was to achieve a high binding affinity to the androgen receptor, with tissue selectivity, thus mimicking the muscle-building effects of anabolic steroids; but without the same degree of side effects.

SARMs are currently being studied as a potential treatment for cachexia (muscle wasting), osteoporosis, cancer, sexual dysfunction, Alzheimer’s disease and multiple sclerosis.

Several anabolic-androgenic steroids (AAS) have shown to be effective in treating the above health conditions with an acceptable level of safety, specifically being: testosterone, anavar and deca durabolin. These three compounds are FDA-approved in medicine today, being prescribed to millions of people worldwide.

However, anabolic steroids are not the perfect medicine, with them having the potential to cause cholesterol fluctuations, benign prostate enlargement, erythrocytosis (excess of red blood cells), gynecomastia, low testosterone, virilization and leg edema in patients.

The objective with SARMs is to inhibit the androgenic, estrogenic and cardiovascular side effects associated with anabolic steroids, through the mechanism of tissue selectivity. However, the transcriptional activation of SARMs’ tissue selectivity is not yet fully understood. Thus, it is possible that SARMs may still cause unpleasant side effects — like anabolic steroids. Until further human trials are conducted, SARMs are only to be utilized as ‘research chemicals’.

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SARMs are very popular among the bodybuilding community, due to them being perceived as a ‘safe version of steroids‘. However, this hypothesis is yet to be confirmed and is somewhat dubious, based on existing research and vast anecdotal evidence from our doctors (presented in this article).

Are SARMs Safe?

The production of SARMs stems back to the 1940s, with these early chemicals being derivatives of testosterone, known as steroidal SARMs.

Fast forward to the late 1990s and non-steroidal SARMs arrive onto the scene (which is what bodybuilders refer to today). Due to these compounds being a recent discovery, their effects are largely unknown and consequently under investigation.

As SARMs’ safety is not yet fully understood, they are not FDA-approved for human use. In 2017, the FDA labeled SARMs as ‘potentially dangerous’ (1) and warned the public about using them.

The FDA also suggested evidence of SARMs causing liver and cardiovascular issues in users, from short-term use. They further stated that the long-term side effects of SARMs remain unknown.

A limited investigation has shown that only 52% of SARMs products being sold on the internet, actually contained the SARM listed on the label.

It was also found that 39% of SARMs products contain another unapproved substance, increasing safety concerns (2).

Dr. Thomas O’Connor has hypothesized SARMs to be more dangerous than steroids, based on 10 years worth of anecdotal evidence and analysis of 2,000 patients’ labs (who have taken SARMs).

Are SARMs Legal?

SARMs are currently legal to buy and sell as ‘research chemicals‘. This is why they are commonly sold in liquid form i.e. a suitable method of administration for rodents.

However, as bodybuilders are becoming increasingly aware of their potential anabolic effects, companies have begun selling SARMs in capsule form (a favourable administration method for humans).

Complications with the law can arise when manufacturers label SARMs as ‘dietary supplements‘ for humans, due to a lack of FDA approval. Supplement companies are also forbidden from describing their benefits, which are yet to be medically concluded.

SARMs Benefits

Muscular Size and Strength

It is already evident that SARMs can stimulate muscle hypertrophy (size) and strength. 

However, early human trials suggest SARMs may only build a fraction of the muscle compared to anabolic steroids (3).

In this study, participants on SARMs gained 1kg-1.5kg in fat free mass over a 4-6 week period. In contrast, those on testosterone enanthate gained 5-7kg in fat-free mass (on 300 and 600mg doses/week).

Fat Loss

Stimulation of the androgen receptor increases lipolysis (fat loss), enabling users to burn notable amounts of subcutaneous fat. SARMs therefore will not only add lean muscle tissue, but simultaneously increase muscle tone/definition.

More Socially Accepted

There is less social sigma attached to SARMs, as they are relatively unknown and less taboo than anabolic steroids; with the latter (ironically) routinely prescribed to bodybuilders in the 1960s, before their side effects became more obvious.

SARMs, being less demonized by the public, has caused them to overtake steroids in popularity.

68,000 people in the US search for ‘steroids’ in Google, which is surpassed by 96,000 people searching for ‘sarms’.

No Injections Required

SARMs are predominantly administered orally, as a liquid, thus eliminating the risk of contaminated needles or improper injection technique that may lead to paralysis.

Suitable for Women

SARMs do not typically cause virilization effects in women (in low to moderate dosages), due to weak levels of androgenicity via tissue selectivity. This makes them a more suitable option for women, compared to many anabolic steroids.

However, as SARMs are currently in the ‘investigational‘ stage, it may be safer for women to opt for the few female-friendly steroids that have been thoroughly researched, such as anavar, primobolan or deca durabolin — known to inhibit masculinization.

A Better Treatment for Osteoporosis?

Anabolic steroids increase bone mineral density (BMD). A lack of BMD significantly increases the risk of fractures and disability.

SARMs not only improve bone mineral density, but also bone mechanical strength; providing a potentially better treatment for those suffering from osteoporosis.

SARMs Side Effects

Gynecomastia & Hair Loss

SARMs inhibit aromatase and 5-alpha reductase enzyme activity, thus no conversion to estrogen or DHT directly occurs.

Therefore, in theory, bodybuilders on SARMs would experience lean muscle gains, without the risk of gynecomastia or hair loss.

However, in practice, SARMs users do report cases of gyno and male pattern baldness. 

The reason these side effects occur is because normally, a person’s natural testosterone levels bind to the androgen receptor (AR); however, SARMs interfere with this process, competing with your natural testosterone for binding to the AR.

SARMs have a significantly higher binding affinity vs natural testosterone and thus will win this contest, consequently leaving free testosterone more readily available for conversion to estrogen and DHT.

Thus, SARMs indirectly cause higher estrogen and DHT levels, responsible for these adverse effects.

Arimistane (Androsta-3,5-diene-7,17-dione) is a mild aromatase inhibitor that bodybuilders may utilize during SARMs cycles to prevent gynecomastia, and other estrogenic effects.

Other AI’s such as aromasin, letrozole or anastrozole, are commonly used during steroid cycles, but are likely too potent for SARMs, causing an estrogen deficiency (as opposed to preventing excessive levels).

Testosterone Suppression

SARMs lower FSH and LH, via its excessive binding to the AR receptor, causing a decrease in natural testosterone levels. Different levels of suppression may depend on the SARM used, causing some users to administer a PCT (post cycle therapy).

Of the most popular SARMs, here is how they rank from most suppressive first, to least suppressive last:

  1. LGD-4033 (Ligandrol)
  2. RAD 140 (Testolone)
  3. S4 (Andarine)
  4. MK-2866 (Ostarine)

The more potent the SARM, the more suppressive it will be.

If our readers are using SARMs, we advise to get blood work performed by your doctor, to assess the extent of damage to the HPT (hypothalamic-pituitary-testicular) axis, helping to determine whether a PCT is needed.

High dosages of less suppressive SARMs can still inhibit endogenous testosterone production. Stacking SARMs together may also exacerbate this hypogonadal effect.

In terms of a PCT, SARMs typically have short half lives due to oral administration; thus users only need to wait a few days before administering a PCT. This is drastically different to steroids, which can take a couple of weeks to clear out of the body.

Typically, bodybuilders will administer either Nolvadex or Clomid as a PCT for SARMs; with nolvadex being the more potent SERM of the two.

Increased Blood Pressure

In phase I and phase II trials, SARMs have caused significant decreases in HDL cholesterol (the good type), thus increasing the risk of hypertension.

Such cardiovascular strain may be attributed to SARMs being delivered orally, with oral steroids being notorious for their negative effect on blood lipids. Additionally, a lack of aromatization may also be a culprit for deleterious cholesterol levels, with higher estrogen levels known to increase HDL.

SARMs-users may incorporate regular cardio during their cycles, in combination with fish oil supplementation to combat reductions in HDL and prevent cardiac damage.

Liver Toxicity

Mild to severe elevations in in ALT/AST liver enzymes have been noted during SARMs research, indicating hepatic strain. To help protect the liver during cycles, it may be worth supplementing with TUDCA, which has shown to reduce inflammation and damage to the organ.

Thus, combining SARMs with hepatototoxic oral steroids, such as: dianabol, anadrol, winstrol etc. is not advised. 

Dr. Thomas O’Connor, from his experience of analyzing patients’ labs, believes SARMs are not safe and that one man under his care experienced deteriorating liver enzymes and cholesterol levels from taking Cardarine. He likened the adverse effects to taking a mega dose of anavar (50mg/day). Interestingly, the patient did not report any noticeable positive effect on body composition from this SARM.

Further research has shown two men develop hepatocellular–cholestatic liver injuries after using SARMs (4). A previously healthy 24 year old man had taken LGD-4033 (Ligandrol) for 9 weeks. And a 49 year old man had taken RAD140 (Testolone) for 4 weeks, with sporadic use thereafter.

Possibly Carcinogenic

In long-term animal studies, a popular SARM, known as cardarine (GW 50156), has caused cancerous tumors (5).

However, in this study, rats were administered cardarine in high doses (3mg/kg) for 2 years continuously, which translates to 2/3 of their lifespan.

In contrast, a shorter duration study performed on humans, administered lower doses of cardarine, found no instances of tumor formation. Interestingly, researchers observed cardarine to have anti-inflammatory effects on pancreatic cancer cells (6).

Thus, the long-term effects of SARMs in relation to cancer and humans is unknown, although it is possible that SARMs, at least when abused, may lead to cancer.

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How to Take SARMs?

SARMs can be taken orally, sublingually or intramuscularly.

Orally

SARMs generally come in liquid form, thus users are to place the correct dosage in their mouth (measured with an eye dropper or syringe) and swallow. SARMs typically have a strong odor and taste, causing some users to pinch their nose when swallowing to eradicate the taste. Keeping mints nearby may also help to maintain fresh breath after consumption.

Some bodybuilders place the liquid in food, such as a slice of bread, to subdue the taste; however this methodology may affect biological availability and thus is not recommended for optimal results.

MK-677 is known to be the strongest tasting SARM, that can linger for hours after administration. To counteract this unpleasant sensation, it can help to administer the liquid near the back of the throat (avoiding the tongue).

sarms

Sublingually

From the latin ‘sub lingua‘, meaning ‘under the tongue’.

Sublingual administration, is often preferred to oral, due to a faster and more direct entry into the bloodstream (7). This is due to the liquid coming into contact with the mucus membrane (situated beneath the tongue), which in turn allows for easy entry into venous circulation, due to the presence of capillaries beneath the epithelium.

This method of administration also increases biological availability, by avoiding presystemic metabolism, thus potentially increasing results.

Users may place the liquid under their tongue (using an eye dropper or syringe) and leave it to sit for 10-15 seconds, before proceeding to swallow.

The disadvantage with sublingual administration is users find it increasingly difficult to avoid the foul taste. However, this may not be an issue as a person gains more experience.

Intramuscularly

Injectable SARMs are much less common, however there are a few advantages with such administration, being: higher biological availability compared to oral delivery, as the compound will not be broken down by the liver (8). Thus, superior results may be experienced on the same dose compared to oral delivery.

Furthermore, SARMs taken orally negative affect HDL cholesterol (9), attributed to them passing through the liver, specifically stimulating hepatic lipase. Thus, injectable SARMs may offer better protection for cholesterol values, reducing cardiovascular strain.

FAQs

Are SARMs Banned From Sports?

Yes, the World Anti-Doping Agency (WADA) added SARMs to their prohibited list in 2008 (10). WADA tests athletes all around the world across various sports, including the Olympic Games.

Some natural bodybuilding federations even test for SARMs including the WNBF (11).

Will SARMs Cause a Failed Drug Test?

General drug tests i.e. for the police or military will not test for SARMs. However, they can utilize specific tests that detect SARMs, however these are a rare occurrence and generally only performed when there is strong suspicion of foul play.

Verdict

sarms
The recent emergence of non-steroidal SARMs presents great promise, for the medical and bodybuilding communities.

With a successful outcome, significantly more people would be healed from cachexia and osteoporosis, without toxic side effects. Equally, fewer bodybuilders would experience negative downturns in health, improving harm reduction and effectively steering people away from anabolic steroid use.

However, initial research and anecdotal evidence suggest SARMs are not safer than anabolic steroids; and may only produce a fraction of the positive effects, in terms of muscle hypertrophy. Thus, the risk-to-reward ratio of SARMs may be even less optimal than steroids.

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