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What is Ligandrol (LGD 4033)? A Science-Based Review

Written by Puya Yazdi, MD | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:
Jonathan Ritter
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology) | Written by Puya Yazdi, MD | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:

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Ligandrol

LGD 4033 is allegedly the most potent SARM on the market. It’s currently being developed to improve recovery from hip fractures, while its unofficial use remains popular among bodybuilders and those seeking appearance enhancement. Among all the hype, read our unbiased review to understand what the actual science says about its potential uses.

Disclaimer: By writing this post, we are not recommending this drug. Ligandrol is an unapproved research chemical without a complete safety profile, and we simply don’t know enough about its adverse effects or efficacy. Some of our readers who were already taking the drug requested that we commission a post on it, and we are simply providing information that is available in the clinical and scientific literature.

We do not recommend taking ligandrol for any reason.

What is LGD 4033?

A New SARM

LGD 4033 is a fairly new oral selective androgen receptor modulator (SARM). SARMs have received a lot of attention recently, both in the medical community and among people who are seeking physical performance and appearance enhancement. Scientists are exploring the ways SARMs could be used to overcome muscle wasting and bone diseases.

Bodybuilders believe that they’re safer alternatives to steroids, but there is no data to suggest that unapproved SARMs are safe at all.

LGD 4033 is also known as Ligandrol and Anabolicum. LGD 4033 is among the two most popular SARMs when it comes to bodybuilding, MK-2866 (Ostarine) being the other.

Like all SARMs, LGD 4033 binds to androgen receptors in the muscles and bones with high affinity and selectivity. Because of this, scientists hypothesize that LGD 4033 shouldn’t affect other organs (sparing the liver, prostate, and sebaceous glands) or cause severe suppression of your natural testosterone production. Being nonsteroidal, LGD 4033 shouldn’t be converted to estrogen either; these hypotheses are purely speculative, however, and lacking in clinical data. Future human trials may very well prove them wrong [1].

Users claim that LGD-4033 is more potent than MK-2866. Others prefer MK-2866, especially when it comes to cutting cycles. Both are favored for their perceived muscle gains, unlike steroids that can cause a long list of side effects and can harm your vital organs.

Yet, this is an unapproved drug. We do not know how safe it is, or even if it works. We highly recommend against taking Ligandrol for this reason.

Ligandrol or LGD-4033 is a new SARM that’s become popular among bodybuilders but never went though proper clinical trials.

We decided to look into the reasons behind LGD 4033’s ongoing popularity and tease apart its actual effects. In this article, we review the most up-to-date research on its potential uses and provide a summary of its proposed mechanism of action.

Snapshot

Proponents:

  • Lean muscle mass gains & increased strength
  • Fat loss
  • May help heal and strengthen bones
  • Few side effects reported in clinical trials

Skeptics:

  • Insufficient human research
  • Banned in professional sports
  • Long-term effects are unknown
  • May cause slight testosterone suppression
  • Not enough data to determine side effects
  • No data to suggest correct dosage

How Does LGD 4033 Work?

SARM Action

SARMs can selectively navigate to muscles and bones. They activate androgen receptors but are chemically different from steroids. As such,they are not substrates for 5 alpha-reductase or CYP19 aromatase, which prevents their conversion to the testosterone metabolite DHT or estrogen [2]:

However, not all SARMs are equally muscle-selective. Some SARMs were abandoned due to their potential for serious side effects. On the other hand, a handful of SARMs are being developed as potential birth control pills for men since they act on the pituitary. These are all currently theoretical at this point, with research still ongoing. Some or all such substances may turn out to be ineffective or unsafe in large, high-quality studies.

The first generation SARMs (developed by Ligand Pharmaceuticals and including LGD 4033) had a modest but undeniable effect on lean body mass gains. The second generation of SARMs we are yet to see might be even more potent and selective—but, again, this is highly speculative until better-quality research is conducted [3].

Scientists are trying to understand what makes some SARMs better than others in the hopes of discovering safer and more selective drugs. Ongoing LGD 4033 research should give us additional clues in the near future.

Like all SARMs, LGD-4033 is thought to bind to androgen receptors in the muscles and bones, but its effectiveness, selectiveness, and safety remain unknown.

Anabolic Activity

LGD 4033 raises anabolic activity in the muscles and bones while reducing muscle wasting and bone breakdown. This is very early clinical work, and we will need much more research before we can be confident in this effect [1].

In one small, early clinical trial, LGD 4033 increased lean body mass and strength, decreased body fat, improved wellbeing, and enhanced the healing process. However, the doses and goals of clinical studies differ from its real-world use [1].

To rewind to the early research phases, both MK-2866 and LGD-4033 were developed with the goal of reducing muscle wasting in people with muscular dystrophy, the elderly, and in cancer patients. Realizing that these drugs may also increase bone strength and healing, scientists began looking into their potential to improve bone diseases such as osteoporosis.

Ligandrol was developed with the aim of increasing anabolic activity and reducing muscle wasting in people with serious illnesses.

Fracture Recovery

LGD 4033 was initially created by Ligand Pharmaceuticals, hence the name “Ligandrol”. Viking Therapeutics took over LGD 4033 research in the meantime, renaming it to VK5211. This small pharma company is researching LGD 4033/VK5211 for hip fracture recovery. They state that it will hopefully produce all the benefits of testosterone with improved safety, aiming to get approval for its clinical use sometime in the future.

According to their claims, the goals of SARM therapy in people with fractures are to:

  • Increase lean body mass
  • Increase muscle and bone strength
  • Improve physical performance and quality of life

We are yet to see if LGD 4033 will gain approval based on new clinical trials or not.

Some scientists have hypothesized that Ligandrol might improve fracture recovery, but this hasn’t been proven.

Bodybuilding

Despite the research still being underway, LGD 4033 entered the bodybuilding community a while ago. It was, at first, classified as a supplement and recategorized later as a research chemical, along with all other SARMs.

The World Anti-Doping Agency banned all SARMs, including Ligandrol, under the S1 Anabolic Agent category of the Prohibited List back in 2008. With this in mind, LGD 4033 can get professional athletes into serious trouble. A couple of years ago, LGD 4033 was all over the news for getting the Florida Gators quarterback, Will Grier, suspended. Will Grier was caught for using it during a routine urine test.

Despite the negative media coverage, users are claiming that LGD 4033 is the most potent SARM on the market and the only option for serious gains without steroids. It’s rivaled only by RAD-140 (Testolone). WIthout rigorous clinical studies, however, these are only anecdotal claims; we currently have no way of knowing whether ligandrol is actually effective or safe.

Ligandrol is still sold illegally, although it’s classified as a research chemical (not a supplement) and is on WADA’s prohibited list.

Potential Uses of LGD 4033

Insufficient Evidence For:

1) Muscle Wasting

Cancer patients often suffer from muscle wasting, which begins early on and can reduce the quality of life, chemotherapy tolerance, and survival. SARMs increase muscle mass and improve fitness in both healthy people and cancer patients. In light of their specificity and safety, SARMs emerged as promising new therapeutics for combating muscle breakdown [4].

According to their proponents, SARMs may target the same anabolic pathways as typical steroids but without the androgenic side-effects. Within the dose range for increasing muscle mass and function, these people say, they don’t cause detrimental effects on the prostate, skin, or hair. Again, this is currently an unproven hypothesis.

Unlike testosterone, SARMs are orally active and seem unlikely to aromatize to estrogens. Being tissue-selective, SARMs don’t cause hoarseness of the voice and other unwanted symptoms of excess male sex hormones [5].

The only clinical trial so far with LGD 4033 involved 76 healthy men, who all received escalating low doses (0.1, 0.3, and 1 mg/day). LGD 4033 was well tolerated and safe over 3 weeks and 1 mg/day was sufficient to increase lean body mass by almost 3 lbs; lower doses didn’t have an effect. LGD 4033 slightly increased leg press strength and stair climb power [1, 4].

An earlier study previously demonstrated the safety of doses up to 22 mg/day. The lower doses in the larger study, however, were estimated to maximize lean muscle gains while minimizing side effects. Note that this data came from animal studies, the purpose of which was to determine the appropriate dose for future clinical trials. Such animal studies don’t reflect the safety or effectiveness of ligandrol in humans [1].

One small trial suggested that Ligandrol might increase lean body mass, hinting at its potential to reduce muscle wasting, but this has yet to be verified.

2) Cachexia

Cachexia is a broader term than muscle wasting. It involves extreme weight loss and muscle atrophy, fatigue, and appetite loss. This wasting syndrome is common in patients with AIDS, cancer, kidney disease, sepsis, and severe burns.

The main contributors are high cytokine levels (IL-6, TNFα, IFN 1b, IFN gamma) and high levels of muscle-degrading molecules (proteolysis-inducing factor). The wasting of respiratory muscles and resulting pneumonia causes over one-third of cancer-related deaths [6].

Before scientists realized the potential benefits of SARMs for cachexia, many other drugs were studied. Anabolic steroids such as nandrolone improved cachexia, lean body mass, and bone density in some studies. However, their major drawbacks are serious side effects such as liver toxicity and masculinization in women [6].

Testosterone, on the other hand, could increase lean mass and muscle performance in HIV-infected men. On the downside, testosterone increases the risk of prostate cancer, affects the sexual organs, and causes red blood cell imbalances by raising the hematocrit [6].

Being selective, SARMs are seen as a major breakthrough for cachexia. However, not all SARMs are equally effective or safe. According to its proponents, LGD-4033 selectively and potently increases muscle mass without detrimentally affecting the prostate or hematocrit; however, no studies have yet investigated this claim [6].

By increasing muscle strength, LGD 4033 could increase survival in people with cachexia and may help them better tolerate intensive treatments (such as radio and chemotherapy) [6].

SARMs like Ligandrol are thought to have potential for improving catexia (a form of extreme muscle wasting with fatigue), but clinical data are still lacking.

3) Osteoporosis and Fractures

Preventing bone loss and increasing bone formation are key to protecting against osteoporosis. The standard therapy for osteoporosis is far from ideal and SARMs are being researched as a safer option for increasing bone strength and bone healing.

Currently, bisphosphonate drugs are the first-line, in addition to calcium and vitamin D supplements. Bisphosphonates increase bone mineral density by inhibiting bone-degrading cells called osteoclasts. They also come with side effects that are hard to tolerate for some.

Women in menopause may be prescribed hormone replacement therapy. However, synthetic hormones such as progestins that are often part of the regimen increase the risk of breast and uterine lining (endometrial) cancer, and heart disease [6].

Activating the androgen receptors can boost bone mineral density by increasing the formation of new bones in response to injury, which is called the “periosteal reaction”. The periosteum is the connective tissue that covers the outer surface of bones [6].

The androgen receptors (AR) SARMs are crucial for maintaining bone mass and allowing for the healing of fractures. For example, mice without ARs have reduced bone mineral density (osteopenia). Men undergoing androgen deprivation therapy for longer periods of time also suffer from low bone mineral density [6].

SARMs have the potential to be used for osteoporosis in both men and women, as they don’t trigger androgen excess. The SARM S-4 completely prevented bone loss In postmenopausal rats, returning their bone mass and strength to the levels of healthy controls. It was more efficient than dihydrotestosterone (DHT) [6].

LGD 4033 studies by Viking Therapeutics are currently underway. This SARM may see approval in the future for improving recovery after hip fracture surgery. However, it’s important to understand that future work could reveal ligandrol to be either unsafe or ineffective. It’s dangerous to assume that ligandrol is safer than standard treatments with known safety profiles; a lot of drugs that showed promise in early studies turned out to be downright dangerous.

Scientists hypothesize that Ligandrol might stimulate androgen receptors in the bones, potentially helping reduce bone loss. Studies will soon reveal whether it’s effective at improving recovery after hip fracture surgery.

4) The Brain & Libido

The effects of SARMs on the brain are still an active area of research. It’s well-known that testosterone has a large impact on psychosexual and cognitive behavior. SARMs are bone- and muscle-selective but they also cross into the brain, which helps explain why they are being studied for libido and mood enhancement [7].

It’s uncertain exactly how much SARMs affect the brain. On one hand, their effects on cognition could just be a consequence of increased muscle strength and stamina. On the other, they may, in fact, activate androgen brain receptors [3].

In support of their benefits on the brain, Viking Therapeutics claims that LGD 4033 has the potential to improve cognition, libido, and energy. Many users report an increased sense of wellbeing and stamina with this SARM.

Due to a lack of research, we don’t yet know how Ligandrol might affect brain health.

5) Contraception for Men

Despite some promising research, no male contraceptive pills have yet reached the market. Even with the increasing need for population control, contraceptive choices available to men are very limited [8].

Most SARMs alone couldn’t cause the hormonal changes required of a male contraceptive pill. Some SARMs are suitable candidates, as they can inhibit gonadotropins from the pituitary (FSH and LH) but spare the prostate. SARMs might also have a positive effect on libido, which would be crucial if they were to be used as male contraceptives [8, 3].

Limitations and Caveats

The only proper clinical study was supported by Ligand Pharmaceuticals, who developed LGD. The ongoing studies are funded by Viking Therapeutics, a company that bought over the rights to LGD 4033 research. It’s difficult to objectively assess the quality of studies funded by pharma companies, their conflict of interest, and bias. The company-funded studies were furthermore very limited, without much of value to say about whether Ligandrol is effective or safe or what the correct dose might be.

We at SelfHacked advise speaking to a doctor before taking any drug, especially an unscheduled drug with limited long-term safety data in humans.

Takeaway

Ligandrol is an unapproved drug that may increase muscle size and strength. Some people believe that it has fewer side effects than conventional testosterone replacement therapy, but there isn’t currently enough data to support this idea.

Talk to your doctor about lifestyle changes or other approved strategies that may help you reach your fitness and health goals, especially since we don’t know whether ligandrol is safe.

Further Reading

About the Author

Puya Yazdi

Puya Yazdi

MD
Dr. Puya Yazdi is a physician-scientist with 14+ years of experience in clinical medicine, life sciences, biotechnology, and nutraceuticals.
As a physician-scientist with expertise in genomics, biotechnology, and nutraceuticals, he has made it his mission to bring precision medicine to the bedside and help transform healthcare in the 21st century.He received his undergraduate education at the University of California at Irvine, a Medical Doctorate from the University of Southern California, and was a Resident Physician at Stanford University. He then proceeded to serve as a Clinical Fellow of The California Institute of Regenerative Medicine at The University of California at Irvine, where he conducted research of stem cells, epigenetics, and genomics. He was also a Medical Director for Cyvex Nutrition before serving as president of Systomic Health, a biotechnology consulting agency, where he served as an expert on genomics and other high-throughput technologies. His previous clients include Allergan, Caladrius Biosciences, and Omega Protein. He has a history of peer-reviewed publications, intellectual property discoveries (patents, etc.), clinical trial design, and a thorough knowledge of the regulatory landscape in biotechnology.He is leading our entire scientific and medical team in order to ensure accuracy and scientific validity of our content and products.

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