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Selective Androgen Receptor Modulators (SARMs)

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Introduction:

A class of therapeutic compounds is called Selective Androgen Receptor Modulators (SARMs) which has very similar characteristics as the anabolic steroids have. They have reduced androgenic properties with selectively binding abilities with androgen receptors. SARMs bind to androgen receptors which is dependent on chemical structure of each SARM. Ultimately SARMs affect the anabolic cellular activity while avoid s lot of the side effects of presently and easily available anabolic steroids. Selective androgen receptor modulators (SARMs) have their applications in performance enhancing drugs used by doping athletes to fuel their anabolism. SARMs also escalate muscle mass, strength & recovery from excessive exercise trainings. SARMs are proposed to have the same effects as androgenic anabolic drugs such as steroids and hormones such as testosterone. SARMs support the belief of physiological and performance development and boost in animals.
Steroid based SARMs that are founded to modify the testosterone molecule have background for over 60 years but during last decade the discovery of a number of non-steroidal SARMs has been reported and witnessed their importance in muscle strength enhancement and health of gym going persons. The first group and production of non-steroidal SARMs are used for the treatment of followings:

  • Feebleness
  • Functional restrictions associated with aging
  • Cancer cachexia and osteoporosis

Non-steroidal SARMs are also categorized on the basis of their structure as under:

There is a great potential in SARMs to increase muscle mass and enhance physical functionality in numerous populations and age groups. They work without any undesirable effects on the prostate, skin and hair that are commonly related with testosterone or other non-selective anabolic steroids. During the last decade selective androgen receptor modulators (SARMs) are developed to recover physical functions, body mass and bone health without harmful effects of the prostate and cardiovascular issues.
Conclusively selective androgen receptor modulators (SARMs) grasp a potential as a new group of function stimulating compounds and anabolic therapies for the improvement in a number of clinical symptoms, including functional limitations linked with aging and chronic disease, frailty, cancer cachexia and osteoporosis. They are an attractive choice for gym going youngsters and people who want to enhance their muscles’ strength without any side effects.

Historical background:

Very initial developments of steroidal SARMs were based on modifications of the testosterone molecule, date back to the 1940s. It was suggested and recommended in the 1940s that 17-alpha alkyl substitution can stop the pre-systemic metabolism of testosterone, ultimately extending its half-life and proving it orally active. The recent period of non-steroidal SARMs was unrestricted by independent work at different pharmaceutical and research institutes. A novel class of androgen receptor ligands called Selective Androgen Receptor Modulators or SARMs were successfully founded by researchers in the late 1990s as a non-steroid SARM. It was discovered as an analog to bicalutamide. They are proposed to have the similar kind of properties as androgenic drugs, such as anabolic androgenic steroids but remain more selective in their action. There are certain unknown clinical benefits and applications associated with SARMs. They can be used to treat different diseases. In 1990s Dalton and Miller discovered that aryl propionamides with structural resemblances to bicalutamide and hydroxyflutamide might stimulate AR-dependent transcriptional activity. From that decade of 1990s all the major pharmaceutical companies are not only producing a large number of non-steroidal SARMs but also some witness based research is going on to get benefits from SARMs.
Historically there are two approaches that are being used to attain tissue selectivity of androgen action. The first approach is to develop SARMs with the chosen activity profile and tissue selectivity. The next approach is to clarify the mechanisms of androgen action on the skeletal muscle and the prostate & to identify signaling molecules that are down-stream of androgen receptor and which stimulate pathways involved in skeletal muscle hypertrophy, excluding the prostate.

Functions and benefits of Selective Androgen Receptor Modulators (SARMs):

SARMs might be very beneficial for stimulating specific tissue growth like muscles and bones, whereas they avoid undesirable side effects in other tissues like the liver or skin. SARMs are proved and evaluated as a clinical cure of muscle wasting or leaning caused by some diseases such as osteoporosis, cancer, heart failure, and chronic obstructive pulmonary disease. Whereas the muscle damage due to last stage of liver disease and last stage of renal disease and HIV might also be cured by SARMs.
A critical link is developed between healthcare professionals and patients, so the pharmaceutical manufacturers must be aware of this link and must produce such beneficial agents. Selective androgen receptor modulators (SARMs) which are suitable and getting increasing popularity due to following benefits and applications;

  • Performance enhancing supplements
  • Lean muscle mass building
  • Fat cutting
  • Endurance
  • Recovery properties

People who take SARMs or SARMs containing products may include:

  • Fitness fans
  • Bodybuilders
  • Physically difficult job holders

Basic mechanism and functional examples:

SARMs play an important role in male reproductive system and sex characteristics. Androgens perform a necessary role in: 1. Variation and growth of the male reproductive zone; 2. pubertal maturation; 3. Development of secondary male sex properties; 4. Initiation and regulation of spermatogenesis; 5. Male sexual performance. Steroidal androgens escalate the muscle mass, bone mass, and strength, stimulate male pattern baldness; and they also change serum lipid profiles and fat distribution.
Testosterone is synthesized and secreted by the testes and its stronger 5α-reduced metabolite, dihydrotestosterone (DHT), is the major biologically active endogenous androgens. Both of these androgens use tissue specific biological effects. For example, testosterone plays its role to stimulate muscle mass and strength, sexual development and spermatogenesis; however dihydrotestosterone (DHT) plays serious role in facial and body hair growth, acne and prostatic expansion.
Non-steroidal anti-androgens have been applied clinically for many years while the non-steroidal androgens have only newly been abstracted. A better receptor selectivity of non-steroidal ligands has been reached from the variations. This flexibility of ligands in which structural changes are done, can be used to enhance their physic-chemical, pharmacokinetic and pharmacological characteristics.

Health risks and limitations associated with SARMs:

SARMs were banned from sports applications by the World Anti-Doping Agency in 2008. While FDA issued a public recommendation stating that SARMs were being incorporated in bodybuilding products and supplements; these compounds might pose a bigger risk for heart attack, stroke and liver damages. After the FDA’s public caution the Council for Responsible Nutrition and the trade organization for the dietary supplement industry introduced some professional guidelines that advised SARMs not be incorporated in dietary supplements. Armed services personnel and healthcare providers are also warned by the Department of Defense’s (DOD) “Operation Supplement Safety” that the SARMs may artificially lower endogenous testosterone and have harmful effects on liver function and cholesterol level.
Under the section S1.2 of the WADA (World Anti-Doping Agency) all the SARMs are strictly prohibited for all athletes of every level. SARMs are listed in the category of “Other Anabolic Agents”. Following are the examples of SARMs:

  • Ostarine (Enobosarm, MK 2866)
  • Andarine, LGD-4033 (ligandrol)
  • RAD140

SARMs have great potential to be misused for strength and performance enhancement in sports and athletics due to their anabolic properties and their abilities to stimulate androgen receptors in muscles and bones leading towards bone and muscle growth.
Following points must be kept in mind before using SARMs in supplements and diets.

  • Selective Androgen Receptor Modulators (SARMs) are possibly dangerous and unlawful to be used in performance enhancing products for athletes. SARMs have been found in a number of adulterated products masked as “dietary supplements.” SARMs are unlawful and unapproved drugs, not dietary supplements.
  • Without the consultancy and suggestion of healthcare professional or physician, SARMs can pose a risk when taken for strength enrichment and performance enhancement. SARMs should be avoided, as they can result in potentially life-threatening consequences.
  • SARMs containing supplements must be labeled and listed into the ingredients. Moreover SARMs containing products must be purchased from trusted companies only.
  • SARMs are used in the dietary supplements with the names like ostarine and andarine and they can pose serious threat to consumer safety, particularly in the bodybuilding and fitness conscious people. SARMs have no business as dietary supplement anymore.

The following are examples of SARMs that are often and illegally marketed and incorporated in dietary supplements or as research chemicals:

The following banned materials are also sometime sold as SARMs:

SARMs are authorized when sold as research chemicals. They are not authorized when sold as dietary supplements. Since their manufacture goes largely unregulated so it’s a personal choice about whether or not you want to munch them.

Different types and examples of SARMs:

Revealed in the 1990s, SARMs are performance enhancing mediators that stimulate anabolism because they increase muscle build, strength and facilitate recovery from exercise. SARMs are not anabolic steroids; but they are artificial ligands that bind to androgen receptors. Different SARMs produce different results, which is why bodybuilders and other fitness fans commonly use them in combination.

  • Ostarine/Enobosarm/GTx-024/MK-2866/S-22:

Ostarine is an orally bioavailable and non-steroidal SARM that was made by Gtx, Inc. in the late 1990s mainly for the treatment of muscle wasting and osteoporosis. Ostarine is the top clinically described SARM. It is examined that it has potential for handling skeletal muscle deficiencies, urinary stress, breast cancer, lung cancer and cancer related cachexia. In clinical trials it was showed that it had an extra decrease in total fat mass with no difference in total body weight. Common low rating side effects included headache, nausea, fatigue and back pain.

  • Ligandrol/LGD-4033/VK5211:

Ligandrol is a new orally bioavailable SARM. It was developed by Ligand Pharmaceuticals and there has been only one clinical trial related to the drug. It is well tolerable with no serious adverse effects. Body mass increment is dose dependent but there might be no significant change in fat or skeletal muscle mass. Strength enhancement and stair climbing speeds may also be dose dependent. Unreliable side effects relevant with the fitness and bodybuilding grounds include nausea, fatigue, headaches and low libido.

  • Testolone/RAD-140:

Testolone is an SARM used mainly for the treatment of muscle deteriorating and breast cancer. It was developed by Radius Health; Inc. Testolone is apparently still in first stage clinical trials and very little is still known about its safety and benefits. RAD-140 is used to gain muscle strength and it has wide applications in gym going boys and athletes. Some side effects include sleeplessness and tiredness.

  • Andarine/GTx-007/S-4:

Currently there are no approved human clinical studies about andarine. Athletes and fitness community use this SARM as muscle boosting supplement that causes weight loss and speeds up muscle building and repairs. Andarine is comparatively a weaker SARM. Dosing andarine at 25 mg per day supposedly recovers mood and general wellness, while increasing the dose to 50 mg per day only humbly boosts strength, leans mass and fat burning. For body re-composition it is recommended to take andarine loaded with both ostarine and cardarine. The main side effects testified with andarine are altered vision and destruction of testosterone.

Ongoing research and conclusion:

Selective Androgen Receptor Modulators (SARMs) might be termed as investigational drugs which have been studied and researched for more than 25 years. There are certain health benefits associated with them including strength and muscle enhancement; body mass increment and many wellness issues maintenance. Their better functionality is based on their dose and target application. SARMs also have certain side effects and regulatory limitations which are necessarily followed by their consumers. FDA and other health regulating bodies have banned the use of SARMs as dietary supplements but they can be purchased or consumed as research chemical. The key research are regarding the SARMs is to identify their specific functionality and to elaborate the clinical benefits of using more than one SARMs in a combination. With minute side effects the SARMs have a great potential to be entertained for bodybuilders and wellness requiring people.
Disclaimer: “This product is intended for medical research purposes only. This product is not for human consumption. You must be a licensed and qualified healthcare practitioner to work with this product.”