SARM

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Selective Androgen Receptor Modulators or SARMs are 'research chemicals' (unapproved drugs) able to improve strength and muscle-building capacities. These chemicals bind with androgen receptors like anabolic steroids do but are more selective, which means they mainly bind with androgen receptors in muscles and bones, and less so the scalp, prostrate, and other areas which are associated with the androgenic side-effects of those drugs.

The appeal of SARMS over steroids to many users is the legality of the substances (albeit in a dubious 'grey market' area) in many jurisdictions, the lower potential for androgenic and estrogenic side effects (such as baldness and gynecomastia) compared to steroids, and the results of small scale clinical trials which have established the muscle-building potential of these substances in humans at very low doses compared to typical anabolics (with the dose-response curve for these drugs not yet known).[1][2]

SARMs indicate the potential for significant muscle growth but also side effects, most notably the potential for testosterone suppression and liver damage. The latter could be due to the effects of the SARMs themselves or due to the presence of toxic adulterants, as research has indicated that 48% of the products labelled as "SARMs" sold online are faked or contaminated with other substances.[3] As clinical trials into SARMs are lacking, the optimal dosage regimens, the full spectrum of side effects, and the true anabolic capacity of these drugs is unproven.

List of SARMs[edit | edit source]

The list is ordered by the most powerful according to recreational users:

  • S23: an investigational male hormonal contraceptive that positively impacts muscle growth due to its affinity for the androgen receptors in muscular tissue. It likely (like anabolic steroids) can cause typically reversible male infertility via inhibiting spermatogenesis due to its strong suppression of endogenous testosterone, as demonstrated by rodent studies.[4]
    There are anecdotal reports that S23 is less selective than other SARMs, which is supported by the rodent studies mentioned above that indicate this SARM strongly disrupts the HPGA. As such, users of this substance may expect a greater potential risk of experiencing androgen induced side effects, such as hair shedding and acne.
  • Ligandrol (VK5211, LGD-4033): is another research chemical that is currently undergoing clinical trials to examine its potential for treating muscle wasting and osteoporosis. Recreational users have reported solid muscle growth effects, albeit with a high potential for low quality weight gain (increased water weight). Several case reports have indicated a potential for hepatotoxicity, similar to that found with a 17-alpha-alkylated anabolic steroid. Several of these cases were confounded by the intake of alcohol and other drugs.[5] The patients' liver health increased with the cession of the drug. [6]
    As these individuals were not thoroughly drug-tested, it is not actually known if LGD was the culprit, as SARMs are often faked or 'spiked' with other potentially hepatotoxic substances such as oral steroids or prohormones.
    However, the results of a phase 2 clinical trial publicized in 2018 by the manufacturer of Ligandrol, Viking Pharmaceuticals, claimed the drug exhibited 'encouraging safety and tolerability in their test subjects (elderly patients recovering from hip fractures). This trial found no evidence that higher doses were associated with a significantly higher risk of side effects. This study also found that ligandrol induced an improvement in lean mass of 10% in the subjects at a dose of 2mg, making it much more potent than other SARMs like Ostarine.[7] Despite increasing lean mass much more than the anabolic steroid nandrolone (administered at a meagre dose of 25 mg every three weeks in a comparable group; a dose that would not even suffice to replace the effects of endogenous T in men), ostarine, and experimental myostatin inhibiting drugs, this study found evidence for diminishing returns in terms of muscle gain setting in even at a dosage of 2mg compared to 1mg. These doses are much lower than the dosages of around 5mg-10mg often sold (and tacitly advised) by SARM manufacturers and users. This drop off in effectiveness in even low doses indicates that LGD (and comparable substances) probably generally exhibits a more modest potential for anabolism than typical administration regimes of anabolic steroids used by bodybuilders, lining up with the anecdotal reports of SARMs users.[8]
  • RAD140: a research chemical, it is currently undergoing clinical trials to examine its potential in treating muscle wasting and breast cancer. Purportedly one of the most anabolic SARMs with a mg per mg anabolic effect much more potent than testosterone (albeit likely with lower overall anabolic potential). Recreational users have also reported a significant strength improvement.
    Some preliminary in vitro and animal model research has indicated that RAD140 may mimic the neuroprotective effects of testosterone.[9]
    A low-powered first phrase clinical trial conducted on breast cancer patients in 2021 found RAD140 exhibited an "acceptable safety profile", with elevated enzymes associated with mild hepatotoxicity, vomiting and digestive issues being the most common side-effects in this cohort.[10]
    This study used doses of RAD140 much higher than is commonly advised for recreational bodybuilders (50-100 mg ED) with no evidence of virilizing side effects in any of the female test subjects, indicating that genuinely sourced RAD140 has a low potential for inducing the androgenic adverse effects associated with anabolic steroid use.
  • YK11: a steroidal SARM, which also can increase the follistatin level in the organism. This substance has not currently been tested in humans or animals. Follistatin has been found in animal studies to have myostatin-inhibiting effects.[11]
    However, it is not known if this effect is clinically relevant in the dosage schemes typically taken by recreational users.
    This myostatin inhibition has potential implications for the effectiveness of YK-11 in inducing hypertrophy in humans, as myostatin acts to inhibit muscle growth. A tiny number of people naturally have a genetic myostatin deficiency, which results in them gaining muscle mass extremely easily, even without strength training. Some cattle breeds have even been selectively bred to develop this deficiency to increase meat yields.[12]
  • Andarine is a discontinued[13] investigational drug developed to treat muscle wasting, osteoporosis, and prostate hyperplasia. Recreational users have reported muscle growth and ocular side effects, such as yellow-tinted vision. This side effect possibly owes to this drug's potential affinity for the androgen receptors in the eyeballs, and purportedly generally goes away after cession of the drug, though this claim hasn't been clinically examined. Generally considered a weaker SARM most suitable for maintaining muscle during weight loss periods by recreational users.
  • Ostarine: anecdotally considered the weakest SARM; recreational users typically use it to prevent muscle loss during a 'cutting' (weight loss) phase.

Compounds often sold with SARMS[edit | edit source]

  • MK-677: Not a SARM, though often lumped in with SARMs and commonly sold on sites dedicated to SARM dealing. MK-677 is a human growth hormone secretagogue. It has been the subject of clinical trials in humans. These trials indicate that it is successful in increasing serum levels of IGF-1 (insulin-like growth factor I) and growth hormone. In some trials, the increases in fat-free body mass associated with the dose commonly advised by recreational users (25mg per day) are fairly substantial (roughly equivalent to a low dose of exogenous testosterone).[14]
  • SR9009, or Stenabolic, is an experimental Rev-Erb agonist. Rev-Erb alpha and beta are part of a duo of intracellular transcription factors that play crucial roles in regulating the body's internal clock (circadian rhythm) and the metabolic and immune pathways under the control of the bodies internal clock.[15] As such, SR9009 has been studied for its effects on weight loss, metabolic rate, mitochondrial function and biogenesis, inflammation and heart function in animals, among other things.
    Stenabolic has been shown to have efficiency in the treatment of obesity in rodent models,[16] and has also been examined for its potential to induce apoptosis (cell death) in cancer cells.[17] As such, many people take SR9009 in the hopes that this substance will boost their energy and exercise performance (due to its positive effects on the mitochondria, the powerhouse of the cell) and induce weight loss.
    However, it is important to note that the research into the potentially ergogenic and lipolytic (fat burning) effects of SR9009 in animal models have used injectable SR9009. This is a major issue when one takes this substance recreationally, as oral bioavailability has been found to be very low in rats (~3%),[18] with the bioavailability not known in humans. Together with the short half-life of this compound,[19] it is not known if the substances labelled 'SR9009', even if genuine, can legitimately induce clinically significant metabolic changes in the amounts and dosing regimens typically administered by recreational users.
    SR9009 has also been found to exhibit metabolic effects outside of its purported mechanism of action in rodent models.[20] This is a common principle in pharmacology, to assume that a drug will have potentially far-reaching effects outside of its theoretical mechanism of action, but it is important to note as some of the research sparking interest in SR9009 has relied on other Rev-Erb agonists or theoretical extrapolations based on the functions of the cellular transcription factors themselves, and not SR9009 per se, in vitro.

Potential effects[edit | edit source]

The FDA, case reports and, to a lesser extent, clinical trials, have indicated a potential for life-threatening reactions, including liver toxicity, among users of SARMs. SARMs also can increase the risk of heart attack and stroke, though preliminary clinical trials into RAD140, at least, have not demonstrated evidence for heart damage in the case of that drug. Just like steroids, SARMs suppress the production of endogenous testosterone, though to a lesser degree; many users attempt to counter this side effect by taking a low dose of SERMs (selective estrogen receptor modulators) or aromatase inhibitor drugs after or even during the cycle (the latter in an attempt to halt suppression altogether, the former the so-called PCT). Recreational SARMs users commonly use a low dose of SERMs such as tamoxifen owing to the weaker testosterone suppression of SARMs compared to more potent anabolics as PCT.

Indeed, some argue this is just risking side effects from those drugs for no good reason, and no PCT is needed with SARMs, as SARMS do not entirely suppress T production like anabolic steroids typically do, though it is not clear how well this applies to high doses and more suppressive SARMs. After multiple years of SARM usage, the testosterone suppression may be permanent, but this is not known as there exist no high-quality long-term human trials regarding the effects of SARMs.

Potential side effects from SERMs[edit | edit source]

If one were to juggle between SARMs and SERMs long term, it would possibly present the risk of neurological damage since estrogen is neuroprotective. Discerning the potential neurotoxic effects of SERM use is difficult due to these drugs' ability to antagonize or act as an agonist of the estrogen receptor agonist in various body tissues. In animal models, it has been found that the lower the estrogen, the more SERMS mimic the effects of estradiol on the brain. At the same time, they counteract the neurological effects of estradiol when levels are high. One would expect the estrogen levels of SARMs users to be low post-cycle as estrogen in men is produced via the aromatization of testosterone, which SARMs suppress. Therefore, studies have found these compounds can both exert potential neurotoxic and neuroprotective effects depending on ones own levels of endogenous estrogen, which determines whether SERMs mimic or block estrogen in the brain. Other research has indicated the potential for SERMs to treat psychotic diseases, such as schizophrenia and bipolar disorder.[21] Clinical trials into the most commonly used SERM, tamoxifen, have demonstrated a lowered risk of Alzheimer's disease with the use of tamoxifen in post-menopausal women.[22]

Legal status[edit | edit source]

SARMs are currently legally saleable as "research samples" in the USA. However, a bill was introduced to the US Congress in 2019 which proposes the classification of SARMS as a controlled substance, similar to anabolic steroids, with the bill in limbo as of late 2021.[23] Several other countries have proposed similar bans.[24] SARMs are scheduled substances in Australia (Class 4, prescription only).[25]

References[edit | edit source]

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4111291/
  2. https://www.tandfonline.com/doi/abs/10.1080/13543784.2020.1777275
  3. https://jamanetwork.com/journals/jama/article-abstract/2664459
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2630904/
  5. https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/hep4.1456
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304490/
  7. https://filecache.investorroom.com/mr5ir_vikingtherapeutics/118/download/Viking%20Corporate%20Presentation%20September%202018.pdf
  8. https://www.reddit.com/r/sarmsourcetalk/
  9. https://pubmed.ncbi.nlm.nih.gov/24428527/
  10. https://www.sciencedirect.com/science/article/abs/pii/S1526820921002408
  11. https://www.jstage.jst.go.jp/article/bpb/36/9/36_b13-00231/_article
  12. https://www.pnas.org/content/94/23/12457
  13. https://www.sportintegrity.gov.au/news/blog/2019-12/dont-risk-using-andarine
  14. https://academic.oup.com/jcem/article/83/2/362/2865156
  15. https://pubmed.ncbi.nlm.nih.gov/22460952/
  16. https://www.nature.com/articles/s41467-021-25674-5
  17. https://www.nature.com/articles/nrd.2018.24
  18. https://pubmed.ncbi.nlm.nih.gov/32738989/
  19. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC4347663/
  20. https://www.pnas.org/content/116/25/12147.short
  21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669724/
  22. https://www.oncologynurseadvisor.com/home/cancer-types/breast-cancer/can-hmt-reduce-risk-of-alzheimer-disease-and-dementia-in-women-with-breast-cancer/
  23. https://www.congress.gov/bill/116th-congress/senate-bill/2895
  24. https://sarms.io/sarms-ban/
  25. https://www.tga.gov.au/blogs/tga-topics/consumer-story-tim-and-selective-androgen-receptor-modulators-sarms

See also[edit | edit source]

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