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SARMs

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Why SARMs?

Discovered in the late 1990s, SARMs are performance-enhancing agents that stimulate anabolism (i.e., increase muscle mass and strength) and facilitate recovery from exercise.

SARMs are not anabolic steroids; instead, they are synthetic ligands that bind to androgen receptors (ARs).

Depending on their chemical structure, they function as full agonists, partial agonists, or antagonists. 

Each SARMs complex possesses a different conformation, and various tissues display a unique pattern of AR expression (e.g., skeletal muscle, bone, prostate, brain, skin, liver).

Thus, in a tissue-selective manner, SARMs mediate coregulators and transcription factors or signaling cascade proteins to promote anabolic activity.

Nonsteroidal SARMs serve as an attractive alternative to anabolic-androgenic steroids.

In contrast to steroidal androgen preparations, SARMs display high oral bioavailability.

SARMs also exhibit diminished androgenic activity because they are not metabolized to dihydrotestosterone (DHT) by five alpha-reductase, an enzyme highly expressed in androgenic tissues.

They are also not metabolized to estrogen by aromatase.

Nonsteroidal SARMs are advantageous over their steroidal counterparts.

SARMs Benefits

Indeed, SARMs have shown substantial therapeutic promise for:

  1. Male contraception
  2. Treatment of osteoporosis
  3. Prostate cancer
  4. sexual dysfunction
  5. benign prostatic hyperplasia
  6. Alzheimer's disease
  7. muscular dystrophy
  8. breast cancer
  9. muscle wasting associated with cachexia and sarcopenia.

Fueled, at least in part, by the perception that SARMs are safer than anabolic steroids, recreational users are now leveraging the various anabolic profiles of different SARMs to selectively achieve results in terms of "bulking" and "cutting."

Bulking refers to a muscle-gaining phase that combines a weight-gain diet with intense weight training.

Cutting refers to a fat-losing phase that combines adherence to a strict weight-loss diet with aerobic exercise and lighter training.

Anecdotal evidence claims that different SARMs yield different bulking versus cutting results, which is why bodybuilders and other fitness enthusiasts commonly use them in combination (or stacked) with each other.

SARMs Ostarine (Enobosarm, GTx-024, MK-2866, S-22)

Ostarine is an orally bioavailable, nonsteroidal SARM developed by Gtx, Inc. in the late 1990s primarily to treat muscle wasting and osteoporosis.

Ostarine MK-2866 is the best clinically characterized SARM.

The few published clinical trials have examined its potential for treating skeletal muscle deficits seen with stress urinary incontinence, breast cancer, non–small-cell lung cancer, and cancer-related cachexia.

In clinical trials conducted thus far, a significant increase in total lean body mass was consistently observed, including in cancer patients.

There was also an accompanying decrease in total fat mass with no difference in total body weight in some studies.

Common low-grade side effects included headache, nausea, fatigue, and back pain.

Other observed effects were transient elevation in the alanine transaminase (ALT), reductions in high-density lipoprotein (HDL), blood glucose, insulin, and insulin resistance.

These altered parameters all returned to normal upon cessation of treatment. Information provided on personal blogs and commercial websites advises fitness and bodybuilding enthusiasts to supplement with Ostarine at dose ranges from 10 mg to 30 mg for at least 12 weeks.

These doses are ten times those studied clinically.

Anecdotal evidence suggests that SARMs Ostarine at these high doses over this extended period can adversely lead to lowered testosterone levels.

The side effects of decreased testosterone include reduced sex drive, erectile dysfunction, infertility, muscle weakness, loss of bone density, weight gain accompanied by increased body fat, insomnia, and depression.

SARM Stacks are famous for enhanced and differential benefits.

SARMS LGD-4033 (Ligandrol, VK5211)

Developed by Ligand Pharmaceuticals, there has been only one clinical trial involving the drug.20 In the placebo-controlled study, 76 healthy men were randomized to placebo or 0.1 mg, 0.3 mg, or 1.0 mg LGD-4033 daily for three weeks.

LGD-4033 was well tolerated, with no serious adverse events at any dose.

At the 1.0 mg dose, there was no change in luteinizing hormone.

Hormone levels returned to normal.

Lean body mass increased dose-dependently, but there were no statistically significant changes in fat or appendicular skeletal muscle mass.

Strength and stair-climbing speed and power trended toward a dose-dependent improvement but were not statistically significant.

Total and low-density lipoprotein (LDL) cholesterol did not change significantly from baseline at any dose.

Although HDL increased at the 0.3 and 1.0 mg doses, it returned to normal upon discontinuation. Triglyceride levels decreased from baseline at all doses.

Headache and dry mouth were the most common side effects.

In a recent case report, a healthy 24-year-old man displayed signs of hepatocellular liver injury.

These symptoms developed a week after drug cessation.

The man had a history of binge drinking, was not on regular medications, and had no previous history of liver disease.

Of concern, this hepatotoxicity lies within the spectrum of liver injury associated with androgenic anabolic steroids.

Many online blogs tout Ligandrol as highly effective for enhancing performance, bulking (vs. cutting), muscle hardening, increasing vascularity, gaining size, and improving recovery.

Fitness enthusiasts take between 5 mg and 10 mg daily for 6 to 10 weeks, along with the disclosure that there is a risk of testosterone suppression at doses greater than 10 mg.

Similar to Ostarine, Ligandrol SARMs stack are popular for additional benefits.

Anecdotal side effects described in fitness and bodybuilding may be attributable to reduced testosterone.

Testolone RAD-140 SARM

Testolone is a SARM used primarily for the treatment of muscle wasting and breast cancer. Developed by Radius Health, Inc.,

Testolone is reportedly still in first-stage clinical trials, with results expected later this year.

However, one recent case report describes a significant liver injury in a 49-year-old man who had taken the drug (dose not reported).

Elevations in bilirubin, AST, ALT, and creatinine indicated mixed hepatocellular-cholestatic liver injury.

Liver histology also revealed inflammation.

However, all liver tests had normalized entirely at 12 months following his initial presentation.

For gaining lean muscle mass and strength in the gym, SARMs users anecdotally recommended that RAD-140 SARM be taken at 5 mg to 30 mg daily for 8 to 16 weeks.

There is additional anecdotal evidence of side effects, including sleeplessness and lethargy.

Andarine S4 (GTx-007)

To date, there are no human clinical studies with Andarine.

In the fitness community and online forums, as a muscle-boosting supplement that elicits weight loss and promotes muscle building and repair.

However, it is comparatively more potent than other popular SARMs, commonly stacked with other SARMs supplements.

Using Andarine by itself at 25 mg per day purportedly improves mood and general wellness, whereas increasing the dose to 50 mg per day only modestly boosts strength, lean mass, and fat burning.

For bulking, Andarine S4 (50 mg) be stacked with Testolone (10 mg) daily for 8 to 12 weeks.

For strength, Andarine (50 mg) may be stacked with Ligandrol (10 mg) daily for 2 to 3 weeks.

For cutting 25mg, be stacked with Cardarine (20 mg, a non-SARM, peroxisome proliferator-activated receptor-delta agonist) daily for 12 weeks. 

For body recomposition (i.e., simultaneously losing fat and gaining muscle), it is recommended that Andarine (50 mg) be stacked with both Ostarine (25 mg) and Cardarine (20 mg) daily for 9 to 12 weeks.

The primary side effects of Andarine are altered vision (i.e., yellow-tinged) and suppression of testosterone.

SARMs PCT (Post Cycle Therapy)

PCT is required to maintain muscle mass and strength gains, facilitate the body's recovery from any potential hormonal imbalance, and expedite testosterone levels to normal.

It is recommended on numerous nonmedical, online forums that periods of post cycle therapy (PCT) in between each SARMs cycle.

Many different PCT formulations that claim to naturally increase testosterone, reduce estrogen, stabilize cortisol, and enhance liver health are available commercially.

These formulations may include but are not limited to ingredients such as the aromatase inhibitor Armistane (an anti-estrogen supplement) and D-aspartic acid (DAA).

PCT supplements are Clomid (clomiphene citrate) and Nolvadex (tamoxifen).

These are prescription drugs in the United States but may be acquired online through foreign sources.

Clomid is a selective estrogen receptor modulator (SERM) that increases testosterone production, thereby preventing gynecomastia.

However, it also carries the most reported side effects—mood swings, headaches, and altered vision at high dosages.

Nolvadex is a less potent SERM that works similarly.

Recreational or Bodybuilding SARMs users recommend that the PCT dosage be front-loaded when testosterone levels are lowest, thereby lowering the dose required when testosterone levels are closer to or returned to normal.

Users also advise that SARMs PCT therapy begin immediately after a SARM cycle.

Until concrete clinical data, the potential adverse effects of cycling SARMs with PCT supplements will remain unknown.

Selective androgen receptor modulators SARMs have the same effects as androgens; however, they are more selective in their action, allowing them to be medically for more uses than traditional steroids.

SARMs signifies a new era of tissue-selective androgens with an unknown potential to treat (and possibly cure) several diseases.

SARMs Comparison to testosterone

Currently used androgens for male hormone replacement therapy are typically injectable or skin delivery formulations of testosterone or testosterone esters.

Injectable forms of testosterone esters (such as testosterone enanthate, propionate, or cypionate) produce undesirable fluctuations in testosterone blood levels, with overly high levels shortly after injection and extremely low afterward.

Skin patches provide a better blood level testosterone profile, but skin irritation and daily application still limit their usefulness.

SARMs provide the ability to target the androgen receptors in different tissues differently selectively.

The goal of research in this area is to allow a customized response:

Tissues that are the target of the therapy will respond as they would to testosterone; other tissues where undesirable side-effects will not.

None of the developed SARMs are genuinely selective for anabolic effects in muscle or bone tissues without producing any androgenic effects in tissues like the prostate gland.

SARMs For Men

For example, if the target is bone growth in older adults with osteopenia or osteoporosis, but with no overt signs of hypogonadism, a SARM targeting bone and muscle tissue but with lesser activity on the prostate or testes would be more desirable.

SARMs for Women

A SARM for women would ideally stimulate bone retention or libido, and other functions that androgens can influence, without negative side-effects such as the development of male gender characteristics (virilization), increased LDL/HDL ratios, liver dysfunction.

Clinical testing

MK-2866, also known as Ostarine or Enobosarm

  • Enobosarm (Ostarine MK-2866, GTx-024, S-22) – One of the most popular SARMs, affects both muscle and bone, intended mainly for osteoporosis and general treatment for andropause and reversing muscle sarcopenia in the elderly and for cachexia in cancer patients.
  • BMS-564,929 – Mainly affects muscle growth, intended as an available treatment for symptoms of andropause
  • LGD-4033 (Ligandrol) – a pharmacological profile similar to that of enobosarm.

Buy SARMs

In 2013, some supplement companies began selling various SARMs as supplements, in purported violation of the Food and Drug Administration's Dietary Supplement Health and Education Act of 1994 (DSHEA) and the patent holders' intellectual rights the compounds.

In October 2017, the Food and Drug Administration issued warning letters to three supplement companies, notifying them that SARMS are classed as unapproved drugs and can cause potential adverse side effects, including cardiovascular and liver damage.

Is SARMs Legal?

In 2015, quarterback of the Florida Gators, Will Grier, allegedly tested positive for Ligandrol (LGD-4033), a claim that the University of Florida denies.

In 2017, Joakim Noah was banned for twenty games by the NBA for testing positive for Ligandrol.

Sean O'Malley, the American mixed martial artist who competes in the Bantamweight division of Ultimate Fighting Championship, was temporarily suspended by the Nevada State Athletic Commission.

In June 2019, his sample tested positive for Ostarine MK-2866 ahead of this fight against Marlon Vera at UFC 239 on July 6 in Las Vegas. 

In July 2019, tennis player Beatriz Haddad Maia from Brazil received a provisional suspension after testing positive for selective androgen receptor modulators.

Shayna Jack, the Australian swimmer, was forced to withdraw in July 2019 from the national squad before the world championships in Gwangju, South Korea, after she tested positive for LGD-4033.