Evidence Based If you buy something through a link on this page, we may earn a small commission. How this works.
4.2 /5
8

LGD 4033 (Ligandrol): What is it? + Safety & Dangers

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:

SelfHacked has the strictest sourcing guidelines in the health industry and we almost exclusively link to medically peer-reviewed studies, usually on PubMed. We believe that the most accurate information is found directly in the scientific source.

We are dedicated to providing the most scientifically valid, unbiased, and comprehensive information on any given topic.

Our team comprises of trained MDs, PhDs, pharmacists, qualified scientists, and certified health and wellness specialists.

All of our content is written by scientists and people with a strong science background.

Our science team is put through the strictest vetting process in the health industry and we often reject applicants who have written articles for many of the largest health websites that are deemed trustworthy. Our science team must pass long technical science tests, difficult logical reasoning and reading comprehension tests. They are continually monitored by our internal peer-review process and if we see anyone making material science errors, we don't let them write for us again.

Our goal is to not have a single piece of inaccurate information on this website. If you feel that any of our content is inaccurate, out-of-date, or otherwise questionable, please leave a comment or contact us at [email protected]

Note that each number in parentheses [1, 2, 3, etc.] is a clickable link to peer-reviewed scientific studies. A plus sign next to the number “[1+, 2+, etc...]” means that the information is found within the full scientific study rather than the abstract.

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 uses and risks vs. what the users and manufacturers claim.

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.

We decided to look into the reasons behind LGD 4033’s ongoing popularity and tease apart its effects and risks. In this article, we review the most up-to-date research and provide a summary of user experiences to give you a clearer picture of what to expect from LGD 4033.

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.

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.

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.

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.

Potential Uses of LGD 4033

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].

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].

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.

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.

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].

LGD 4033 Anecdotes

Bodybuilding & High-performance Sports

The single clinical trial conducted on healthy men hints at what people who take ligandrol for bodybuilding may experience. We are providing some user experiences here, to discuss why some people take ligandrol and to explore anecdotes of possible adverse effects. None of this can replace proper clinical testing.

Note: All the information below is anecdotal and based on only on personal experiences of LGD 4033 users. We can’t attest to its accuracy. We also can’t say to what extent these experiences are affected by other SARMs or different drugs/supplements taken at the same time. We cannot be sure about the actual content and quality of LGD 4033 in numerous products users bought online.

And most importantly: 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.

Reviews

Many athletes and professionals who are seeking to build muscles and optimize body composition are turning to LGD 4033 as their SARM of choice. Its use is not limited to weightlifters and bodybuilders but also includes models, crossfitters, and exercise enthusiasts.

For a lot of people who are willing to experiment with SARMs, LGD 4033 the first drug from this class to try. While most SARMS are stacked together, a lot of users take LGD 4033 alone and claim to experience great results. Others stack it with Cardarine, Ostarine, and Testolone. Some compare it to Anavar with Dianabol.

Note that we don’t even know how safe ligandrol is, let alone ligandrol in combination with other (often illegal, unapproved) drugs. Taking ligandrol alone or in combination is a very dangerous practice, and we believe you are better off talking to your doctor about lifestyle changes and proven therapies that can achieve the same goals.

Users report:

  • Lean muscle mass gains (5-10 lbs/month)
  • Great keepable gains even with lower doses (5 mg/day)
  • Easier fat loss
  • Increased stamina and libido
  • Quicker recovery
  • Less pain
  • The best SARM for bulking
  • Good results for body recomposition
  • Combined with Cardarine for cutting cycles
  • “Amazing pumps”
  • Increased lifting and cardiovascular strength (by the 3rd week)
  • A heightened sense of wellbeing without mood swings or crashes
  • Much stronger than Ostarine
  • The closest you can get to testosterone, especially for body recomposition
  • No bloating or only slight water retention
  • No male-pattern body hair growth or hair loss
  • No liver damage
  • No changes in cholesterol or blood pressure

Although gyno (gynecomastia or breast swelling in men) was rare, men who are more estrogen-sensitive and taking higher doses did report it.

Dosage & Cycle

Users reported taking the same dosage for cutting, bulking, and body recomposition cycles. However, there is no safe, effective dosage of ligandrol because no high-quality clinical trials have determined one.

  • Up to 10 mg/day for men
  • Up to 5 mg/day for women

Some athletes reported using doses as high as 20 mg/day but most don’t recommend going above 10 mg/day. Cutting cycles were for 8-12 weeks. Users recommend shorter bulking cycles (3-6 weeks) and experiencing tolerance after 6 weeks. One user recommended limiting cycles to 4 weeks and then taking 4 weeks off to allow for the recovery of natural testosterone levels.

The half-life of LGD 4033 is 24–36 hours, so most users take the whole daily dose at once. Something to keep in mind is that blood LGD 4033 levels nearly tripled in clinical studies after 3 weeks compared to day 1, suggesting that its concentration builds up in the body over time. However, this conclusion is speculative at best [1].

LGD 4033 Side Effects & Safety

Clinical Trials

Remember: these early studies are not designed to prove whether a compound is safe—they are only designed to weed out very dangerous substances from future testing. Much larger studies with many more participants are required to determine the safety of an experimental drug.

That being said, no serious adverse events were reported in a small study of doses up to 22 mg/day. In the only proper clinical trial on 76 healthy men, low doses (0.1, 0.3, and 1.0 mg/day) were well tolerated over 3 weeks. None of the participants reported significant adverse effects [1].

The most common side effects from the clinical trial were:

  • Headaches
  • Dry mouth
  • Pain related to muscle biopsy
  • Upper respiratory tract infections

The frequency of adverse events was similar in the treatment and placebo groups. Side effects were not influenced by the dose—0.1 mg/day and 1 mg/day caused similar side effects [1].

However, this clinical study suggests that LGD 4033 can cause mild suppression even at 1 mg/day, which is 10 times lower than the typical bodybuilding doses. It suppressed testosterone, sex hormone-binding globulin (SHBG), and follicle-stimulating hormone (FSH). Luteinizing hormone (LH) levels were not affected. Hormone levels returned to normal after stopping treatment [1].

These findings seem to indicate that, even if this compound is later found to be effective, it will probably cause many of the same problems as traditional testosterone therapy. Given that people often take ligandrol in an attempt to avoid these side effects, this study undermines the purported usefulness of this drug.

LGD 4033 did prove tissue selectivity when it comes to vital organs in this trial. It didn’t alter hemoglobin levels, prostate-specific antigens, liver enzymes (AST and ALT), or heart rate (QT intervals) [9].

LGD 4033 reduced HDL cholesterol and triglyceride levels, which returned to normal after the therapy. No effects on fat mass were noted [9].

The fact that LGD 4033 appeared to be safe and bioavailable and increased lean body mass over a short span of time with low doses calls for longer trials to fully evaluate its efficacy and safety [9].

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.

Reviews

Some users reported the following:

  • Mild growth of breast tissue
  • Mild testosterone suppression, especially with higher doses (normalized 3-4 weeks after stopping it)
  • Some water retention
  • Most gains were keepable but a bit of loss post-cycle was common

We don’t know what the quality of the product was or if users were taking other drugs/supplements.

PCT

Users claim that LGD 4033 doesn’t cause aromatization but that mild testosterone suppression is not uncommon. A subset of users recommends mild PCT (Clomid or Nolvadex) cycles for ~4 weeks to stimulate natural hormone production. Some feel no need for PCT after stopping LGD 4033, while others take only testosterone boosters.

Urine Screening

Since Ligandrol earned the Florida quarterback Will Grier a suspension, professional athletes are becoming more aware that routine urine tests can easily pick up this SARM. Anti-doping agencies are well-aware that LGD 4033 is used by athletes despite the ban and are always developing new ways to screen for it. Precise screening tests make it hard for any professional athlete to get away with using LGD 4033 [10, 11].

How Long Does LGD Stay in Your System?

LGD-4033 has a long half-life of 24–36 hours, which is the time it takes the drug levels in the body to be halved. This means that your levels will be halved ~1 day after stopping it, quartered within ~2 days, 1/8th the following day, and so forth until they become undetectable [1].

In one case study, a healthy man received a single 10 mg dose of LGD-4033. With more precise instruments, the unchanged drug was detected in the urine for up to 7 days. However, its metabolites could be detected for the whole duration of the study lasting up to 21 days. The detection window is probably even longer with repeated and higher doses [12].

Remember that this is one limited study without outside data to back up its claim. Even in this single study, however, ligandrol seemed to suppress testosterone.

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. In fact, many of the limited studies available have produced the same side effects as testosterone. We recommend talking to your doctor about lifestyle changes or other strategies that may fulfill the same goal, especially given that we don’t know the correct dosage or even whether ligandrol is safe.

Buy LGD-4033 (Ligandrol)

There are vendors who sell LGD-4033 in the United States.

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

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.

Click here to subscribe

RATE THIS ARTICLE

1 Star2 Stars3 Stars4 Stars5 Stars
(14 votes, average: 4.21 out of 5)
Loading...

Leave a Reply

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.