SARMs Are This Year’s Big Muscle Drug – But Are They Safe? + Side Effects

Selective androgen receptor modulators or SARMs are familiar to many fitness enthusiasts, bodybuilders, and athletes.

However, numerous controversies surround SARMs.

SARMs are compounds that have the potential to treat diseases. It is essential to take them properly with guidance from your healthcare provider.

They have similar properties to anabolic steroids but work differently.

SARMs are investigational drugs with great potential to be alternatives in treating several diseases affected by androgens.

However, the misinformation and misuse of SARMs in the fitness industry can be detrimental to the health of individuals.

There are concerns raised regarding their use in sports and dietary supplements.

Therefore, it is essential to be well informed about these ingredients.

We will look into more details about selective androgen receptor modulators and their effects.

SARMs: What’s The Harm?

What is a Selective Androgen Receptor Modulator (SARM)

Selective androgen receptor modulators are a class of androgen receptor ligands that bind ARs and display tissue-selective activation of androgenic signaling.

They are small molecule drugs that can function as nonsteroidal androgen receptor agonists or antagonists.

SARMs can selectively elicit benefits and avoid the side effects of traditional androgen therapy.

They have few side effects if any. Moreover, SARMs have excellent oral and transdermal bioavailability.

SARMs are the potential alternatives to current androgen therapies such as anabolic steroids and testosterone therapy.

They have similar properties to anabolic steroids but with reduced androgenic properties.

However, SARMs are not dietary supplements.

The FDA warns about the deception of marketing and labeling fitness products.

The world anti-doping agency prohibits using SARMs by athletes in and out of sports competitions.

Origins of Androgen Therapy

Androgen therapy originated in 1889 when Charles Edouard Brown-Sequard performed an experiment on himself. Effects reported increased vigor and capacity for work.

Testosterone was isolated in 1935. It was reported to cause nitrogen retention, which indicated anabolic metabolism.

In the 20th century, the chemical scaffold of testosterone was modified to produce safer androgenic drugs.

Near the close of the 20th century, selective androgen receptor modulators (SARMs) were recognized as the future of androgen therapy.

Testosterone therapy has garnered negative reports on satisfaction, side effects, and preparations.

Hence, clinical trials and studies continue to investigate nonsteroidal SARMs.

These compounds were synthesized for treating osteoporosis, breast cancer, and muscle-wasting conditions.

How Do SARMs work?

Selective androgen receptor modulators bind androgen receptors (AR) and display tissue-selective activation.

SARMs have selective anabolic effects on the muscle and bone.

It has varying degrees of agonist and antagonist effects on AR.

SARMs can mimic the effects of androgenic drugs or anabolic steroids.

It promises better therapeutic benefits that facilitate tissue-specific gene regulation without the drawbacks of testosterone therapy.

The AR is activated by binding androgens. Both SARMs and steroids can influence this activity, increasing your muscle growth.

However, anabolic steroids bind to androgen receptors in many tissues all over the body, which results in higher androgenic properties.

They can produce more side effects such as hair loss and acne because of their broad therapeutic utilization.

On the other hand, SARMs have tissue selectivity.

They can bind androgen receptors to specific tissues and not affect surrounding tissues.

SARMs can tap into the therapeutic potential of ARs.

According to molecular and cellular endocrinology, androgen receptor ligands such as testosterone and dihydrotestosterone (DHT) bind to the androgen receptors to elicit androgenic signaling.

Androgens can influence the development, growth, and maintenance of male sex organs.

SARMs are not metabolized to DHT by 5-reductase, reducing the risk of androgenic effects.

The unique pharmacologic actions of SARMs are attributed to their interaction with ARs.

Ligand binding induces specific conformational changes, resulting in tissue-specific gene regulation.

This allows for selective stimulation or inhibition of the androgen receptor, requiring co-regulators and transcription factors.

Potential uses of SARMs

The selective androgen receptor modulator has several therapeutic potentials. It has been studied in treating conditions such as the following:

• Osteoporosis
• Alzheimer’s disease
• Breast cancer
• Prostate cancer
• Benign prostatic hyperplasia
• Stress urinary incontinence
• Male contraception
• Hypogonadism
• Muscular dystrophy
• Chronic obstructive pulmonary disease
• Muscle wasting or Cancer cachexia

There are health risks caused by the loss of skeletal muscle mass, bone mass, and physical function.

These risks include chronic illnesses such as end-stage renal disease, congestive heart failure, chronic obstructive pulmonary disease, osteoporosis, HIV, and some types of cancer.

Examples of SARMs

1) Ostarine

Ostarine is also known as Enobosarm, GTx-024, and MK-2866.

It has a significant anabolic activity, showing potential treatment in diseases affecting muscles and bones.

Ostarine at 1 mg significantly lowered Sex hormone-binding Globulin and serum testosterone levels.

2) VK5211

It was previously known as ligandrol or LGD-4033 and is currently known as VK5211.

This SARM was developed as a potential treatment for musculoskeletal degenerative diseases.

VK5211 has the most significant ratio in its potential anabolic activity in relation to its androgenic activity. 

In human trials thus far, this SARM has generally been considered safe with minimal side effects.

VK5211 affects lipid levels and testosterone levels by suppressing high-density lipoprotein (HDL), luteinizing hormone, and follicle-stimulating hormone.

3) GSK2881078

GlaxoSmithKline (GSK) 2881078 is a SARM under investigation by GSK for treating reduced mobility and functional limitations associated with muscle weakness.

It is generally well-tolerated in human trials in both men and women.

Results showed an increase in lean muscle mass with enhanced sensitivity in women.

However, side effects are reported, such as lower HDL levels, constipation, dyspepsia, and nausea.

4) PF-06260414

It is found to be well tolerated by men.

Like with other SARMs, human trials have shown a decrease in HDL levels and an increase in alanine transaminase levels.

Participants in the trials experienced side effects like headaches, decreased appetite, dizziness, upper respiratory infection, fatigue, and anxiety.

Studies on Selective Androgen Receptor Modulators (SARMs)

Selective androgen receptor modulators are being developed and studied for their therapeutic potential in different diseases.

Successful clinical studies have given hope to improving androgen therapy.

However, no SARM has been clinically approved yet by the Food and Drug Administration (FDA), and further studies are needed on its benefits and side effects.

It is only at its early stages of clinical evaluation, but the potential and benefits are promising and several.

SARMs are usually administered orally or transdermally. They can activate the androgen receptors in the muscle and bone.

Preclinical studies on SARMs state that they can increase muscle mass and bone mass, while clinical trials have reported an increase in fat-free mass.

Research on SARMs aims to replace testosterone supplementation and other anabolic agents in treating diseases with selective androgen receptor molecules.

It may be a potential new class of function-promoting therapies for several clinical conditions.

SARMs can provide therapeutic potential for illnesses such as muscle wasting associated with burns, cancer, end-stage renal disease, frailty, osteoporosis, and hypogonadism.

1) Osteoporosis

Partial agonists selective androgen receptor modulator, called S-4, restored soleus muscle mass, muscle strength, and levator ani muscle mass in preclinical studies.

The potential of S-4 in skeletal muscle, bone, and pituitary was proven in human trials. It provides evidence of the advantages of nonsteroidal SARMs over anabolic androgenic steroids.

Furthermore, the S-4 treatment caused a more significant increase in total bone density.

Age-related androgen depletion is a risk factor for diseases such as osteoporosis and sarcopenia.

Preclinical studies have investigated SARMs, measuring the body composition, muscle mass, and bone density of mice.

The results showed an improvement in muscle growth and bone density while decreasing body fat.

2) Alzheimer’s Disease

Another age-related disease that androgens can influence is Alzheimer’s disease.

Age-related androgen depletion can result in the accumulation of β-amyloid protein, increasing the risk of Alzheimer’s.

Hypogonadal men also show a decline in cognitive processes such as episodic memory and working memory.

A high serum testosterone index is associated with improvement of cognitive disorders associated with androgen receptor modulated brain regions.

Preclinical studies have demonstrated that androgen therapy can have protective effects.

Particularly the selective androgen receptor modulator, NEP28, exhibits high tissue selectivity.

The results indicate that SARM is effective in osteoporosis, sarcopenia, and Alzheimer’s disease.

3) Prostate Cancer

Increased risk of acquiring prostate cancer comes with age. This risk is influenced by androgens. Prostate cancer is the leading cause of cancer death in males.

Treatments such as androgen deprivation therapy can shrink prostate and prostate tumors.

However, it also causes musculoskeletal and behavioral adverse effects.

The Selective androgen receptor modulator (SARM) MK-4541 has been reported as an androgen receptor antagonist with a 5α-reductase inhibitor function.

This enzyme is highly expressed in androgenic tissues, inducing apoptosis in prostate cancer cells.

Therefore, Mk-4541 can provide potent anti-androgenic activity on the prostate with protective activity on the skeletal muscle and behavior in cancer patients.

Moreover, several SARMs have antitumor effects, encouraging further clinical trials on these compounds.

4) Breast Cancer

It has been associated with androgen synthesis. SARMs exert their effects in the breast tissue that expresses AR.

Improved survival of breast cancer is correlated with AR expression. Enobasarm has a recently completed phase II clinical trial, which exhibited slowed cancer growth.

Another phase II trial of Pembrozulimab combined with Enobasarm was well tolerated and resulted in a modest clinical benefit rate of 25%.

However, further investigation is warranted for the combination of SARMs and immune checkpoint inhibitors.

5) Male contraception & Hypogonadism

Low testosterone levels are an increasing concern for men. Testosterone supplementation that has FDA approval are testosterone topicals, injections, and pellets.

There is a demand for more convenient means of administration, fewer adverse effects, and effecacy.

Testosterone replacement therapy, including male hormonal contraception, can be replaced with the oral preparation of a nonsteroidal selective androgen receptor modulator.

Nonsteroidal SARMs can elicit testosterone’s exact effects that represent a step forward in making the “male pill.”

Studies show that SARMs maintain the same pharmacologic and endocrine effects of testosterone while maintaining oral bioavailability and tissue-selective actions.

SARMs may one day be the future in treating hypogonadism through oral preparation with convenient dosing frequency.

The selective androgen receptor modulator, LY305, is under development through transdermal treatment of hypogonadism. Moreover, preclinical studies showed that LY305 could restore skeletal muscle mass through accelerated repair.

6) Chronic obstructive pulmonary disease (COPD)

COPD is defined by impaired physical function and muscle disfunction.

There is an ongoing randomized controlled trial using SARMs on patients with COPD and muscle weakness.

7) Duchenne muscular dystrophy (DMD)

DMD is a neuromuscular disease that usually affects boys. It is characterized by skeletal muscle and cardiopulmonary complications.

This effect is due to the diminished anabolic actions of androgens in muscle.

An intervention with an androgen receptor agonist will reverse complications and extend the survival rates of patients.

Preclinical study results show increased muscle mass, function, and survival. It supports the importance of a nonsteroidal androgen receptor agonist.

8) Stress urinary incontinence (SUI)

SUI is the involuntary leakage of urine that results from weakened or damaged pelvic floor muscles. It is triggered by physical stress.

The pelvic floor is rich in androgen receptors and molecules with anabolic activity. Therefore, a selective androgen receptor modulator can serve as a therapeutic option for patients with SUI.

A preclinical study on SARMs investigated their effect on body weight and lean muscle mass.

Its results showed an increase in pelvic floor muscles and may serve as a basis for evaluating their clinical applications.

SARMs vs. Anabolic Steroids

We are now aware of selective androgen receptor modulators, but what is their difference from anabolic steroids?

Healthcare providers prescribe anabolic steroids to treat hormonal issues, muscle loss, cancer, and AIDS.

They are synthetic variations of the male sex hormone testosterone. Steroids are also known as anabolic-androgenic steroids.

A clear distinction between SARMs and classic steroids is tissue selectivity.

Steroids have a higher rate of adverse effects and lack oral formulation.

On the other hand, SARMs will target tissues specific to their beneficial effects and minimize side effects.

Anabolic means muscle-building, and androgenic refers to male sex characteristics.

Anabolic steroids are misused by taking 10 to 100 times higher doses than what is prescribed to treat medical conditions.

People who take anabolic steroids for muscle building have turned to selective androgen receptor modulators as an alternative.

SARMs have the same potential anabolic activity in relation to their androgenic activity.

However, SARMs are not recommended for recreational use and are still under clinical evaluation.

SARMs and other anabolic steroids will both have contraindication and drug interaction.

A prescription is required with anabolic steroids, while SARMs are off-label drugs that are yet to be FDA approved for any clinical indications.

The world anti-doping agency prohibits both of these compounds. 

Athletes lose their eligibility if tested positive for either.

Moreover, SARMs cannot be prescribed to you by your doctor.

Individuals who wish to undergo SARMs therapy can take these investigational drugs if they participate in clinical trials.

Adverse or Side Effects of  SARMs

Selective androgen receptor modulators (SARMs) are anabolic agents designed to mimic the effects of testosterone supplementation.

Testosterone supplementation is proven to increase fat-free mass, body mass, muscle strength, and decrease fat mass.

However, all anabolic agents such as SARMs, testosterone, and steroids have adverse effects and safety concerns.

Nevertheless, the adverse effects of SARMs are not as detrimental.

The clinical investigations on SARMs have reported side effects, including heart attack, stroke, and liver damage.

Moreover, their long-term effects remain unknown.

Common adverse effects of anabolic agents such as SARMs are significant reductions in HDL and LDL.

Clinical trials on Ostarine have reported these side effects, affecting cholesterol levels.

Different SARMs continue to be tested in human trials. Promising results have been obtained in several studies for years.

Nevertheless, further human trials are needed to identify long-term safety, tolerability, and efficacy.

Adverse effects of each SARM can be different, and despite its potential, there are health risks that need to be investigated.

SARMs in the Dietary Supplements

Selective androgen receptor modulators (SARMs) have gained popularity in the market of dietary supplements. Manufacturers have been creating performance enhancement supplements that use SARMs in their formulation.

SARMs are used for performance enhancement in several dietary supplements.

These compounds may have modest gains in lean body mass, and in some reports, they had a decrease in total fat mass.

However, the evidence for its efficacy is usually anecdotal than scientific.

Clinical studies have identified significant health risks associated with SARMs.

Therefore, individuals who use SARMs recreationally should stop taking them immediately and consult their doctor.

All SARMs remain to be investigational drugs. Several body-building products are purchased online.

Over-the-counter products labeled as SARMs can also be found at nutritional supplement stores.

The following are examples of SARMs that are illegally marketed as research chemicals on dietary supplement product labels:

• ACP-105
• Andarine (S4)
• Enobosarm (Ostarine, MK-2866, S-22)
• LGD-4033
• Ligandrol (LGD-4033)
• RAD140 (Testolone)
• S-23
• Vosilasarm (RAD-140)
• RAD-150 (TLB-150, Sustalone)
• YK-11

Other popular over-the-counter products sold in nutritional supplement stores and labeled SARMs are SARM-X and Osta-Plex.

FDA has warned individuals and companies about the dangers of dietary supplements containing SARMs.

Some products have marketed and labeled the selling of SARMs as dietary supplements.

SARMs are unapproved drugs and can be life-threatening if taken as supplements because their safety and efficacy are yet to be reviewed by the FDA.

Life-threatening adverse events, such as liver toxicity, heart attack, and stroke, have been reported symptoms in clinical trials.

In addition, the Council for Responsible Nutrition introduced voluntary guidelines for SARMs not to be included in the dietary supplement industry.

The Department of Defense’s “Operation Supplement Safety” has warned individuals that SARMs may artificially lower testosterone levels, cause liver damage, and affect cholesterol levels.

Safety Concerns on Selective Androgen Receptor Modulators (SARMs)

1) FDA Warning

The FDA issued a warning about body-building products or dietary supplements that use steroid and steroid-like ingredients.

This agency is under the US Department of Health and Human Services. It protects the public from health risks by implementing strict guidelines on human and veterinary drugs, vaccines, and other biological products.

Based on an internet survey, individuals who use a selective androgen receptor modulator are primarily males between 18-29.

90% of users obtained SARMs online and did not consult a healthcare provider.

Many reported increased muscle mass, but more than half of SARM users experienced adverse effects.

Effects experienced by individuals included mood swings, acne, and decreased testes size.

People who are at risk of abusing SARMs are bodybuilders, fitness enthusiasts, and those with physically demanding jobs.

You should always consult your healthcare provider when taking supplements that might contain unapproved drugs, such as SARMs.

Disclose all medical history and information, especially if you have preexisting conditions.

Moreover, choose supplements that have a complete list of their ingredients and inquire if it contains any drugs that may cause interactions.

Currently, you can purchase and sell SARMs that are marketed simply as research chemicals. These SARMs are usually bought online.

Nonetheless, it is illegal to purchase and sell SARMs packed in capsules and labeled as dietary supplements.

You cannot purchase and sell SARMs for human consumption. SARMs cannot be labeled or marketed to the public as dietary supplements.

2) World Anti-Doping Agency

The World Anti-Doping Agency has prohibited the use of all SARMs, both in and out of competition.

Professional and collegiate athletes will lose their eligibility if tested positive for any anabolic agents.

Doping athletes use SARMs to increase muscle growth, strength, and recovery from exercise training.

Conclusion

Selective androgen receptor modulators (SARMs) are therapeutic compounds that bind to androgen receptors.

They have strong anabolic effects, minimal side effects, better bioavailability, and convenient preparations.

It can increase bone density and body composition, improve muscle strength, shrink the prostate, prevent bone loss, etc.

These benefits usually come with lesser adverse effects than other anabolic agents.

SARMs are investigational drugs that have existed for two decades. However, there are still no FDA-approved indications for SARMs.

Nevertheless, compared to other anabolic agents such as testosterone and steroids, SARMs have fewer androgenic effects.

But, they are not safe enough to be used in dietary supplements.

There is an increased risk of heart attack, stroke, and liver damage.

It would be best to check the information about the products you take.

A healthcare provider can always answer your queries regarding the ingredients in dietary supplements.

Therefore, it is the responsibility of manufacturers to give full disclosure of their formulations.

If you are an athlete, fitness enthusiast, or bodybuilder, prioritize your health over physical results.

SARMs are still in development, and their safety and efficacy are yet to be fully understood.