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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.
Note: By writing this post, we are not recommending this drug. 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 scientific literature. Please discuss your medications with your doctor. Ligandrol is specifically a drug that we at SelfHacked would recommend against.
What is LGD 4033?
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, on the other hand, are turning to them as safer, yet still unapproved, alternatives to steroids.
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.
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 clean muscle gains, unlike steroids that can cause a long list of side effects and can harm your vital organs.
As all SARMs, LGD 4033 binds to androgen receptors in the muscles and bones with high affinity and selectivity. This means 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 [R].
How Does LGD 4033 Work?
LGD 4033 raises anabolic activity in the muscles and bones while reducing muscle wasting and bone breakdown. Recent clinical trials attest to the best and safest way to use it to an extent. In clinical trials, 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 [R].
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.
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
If these also sound like your exercise goals, you’re not alone. While these effects may be great for people with frail bones, they also touch upon many of the highly desired gains among bodybuilders. We are yet to see if LGD 4033 will gain approval based on new clinical trials or not.
Despite the research still being underway, LGD 4033 entered the bodybuilding community a while ago. It was first as 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, Ligandrol was all over the news for getting the Florida Gators quarterback, Will Grier, suspended. Will Grier was caught for using Ligandrol 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).
We decided to look into the reasons behind its ongoing popularity and tease apart its effects, potential gains, 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 of LGD-4033
- Lean muscle mass gains
- Fat loss
- Increases strength
- May help heal and strengthen bones
- Few side effects reported in clinical trials
- Banned in professional sports
- Long-term effects are unknown
- May cause slight testosterone suppression
SARMs & LGD 4033 Mechanisms
SARMs are selective to muscles and bones as they [R]:
- Navigate to muscles and bones to a greater extent
- Muscles and bones may have more sensors for them (so-called coregulators)
- Activate androgen receptors but are chemically different from steroids
- Being nonsteroidal, SARMs are not substrates for 5 alpha-reductase or CYP19 aromatase, which prevents their conversion to the testosterone metabolite DHT or estrogen
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.
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 may be even more potent and selective [R].
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.
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 [R].
SARMs target the same anabolic pathways as typical steroids but without the androgenic side-effects. Within the dose range for increasing muscle mass and function, they don’t cause detrimental effects on the prostate, skin, or hair. Unlike testosterone, SARMs are orally active and don’t aromatize to estrogens. Being tissue-selective, SARMs don’t cause hoarseness of the voice and other unwanted symptoms of excess male sex hormones [R].
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 [R, R].
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 based on data from animal studies [R].
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 [R].
Before scientists realized the benefits of SARMs for cachexia, many other drugs were trialed. 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 [R].
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 [R].
Being selective, SARMs are seen as a major breakthrough for cachexia. However, not all SARMs are equally effective or safe. LGD-4033 is close to an ideal SARM that selectively and potently increases muscle mass without detrimentally affecting the prostate or hematocrit. 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) [R].
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 [R].
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 connective tissue that covers the outer surface of bones [R].
The androgen receptors (AR) SARMs act on 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 [R].
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) [R].
LGD 4033 studies by Viking Therapeutics are currently underway. This SARM may see approval in the future for 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 their effects on libido and mood enhancement [R].
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 [R].
In support of their benefits on the brain, Viking Therapeutics states 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 [R].
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 also have a positive effect on the libido, which would be crucial if they were to be used as male contraceptives [R, R].
Whether you’re for or against the concept of contraceptive pills for men, SARMs have shown good results so far [R].
LGD 4033 Results: Bodybuilding & High-performance Sports
Scientific research about LGD 4033 only provides a glimpse at its real-world use. The single proper clinical trial conducted on healthy men hints at what to expect when taking it for bodybuilding. To bridge the gap, here we summarized the vast amount of available reviews and feedback from online communities with the attempt of teasing apart the most useful information.
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. And lastly, we are far from sure about the actual content and quality of LGD 4033 in numerous products users bought online.
Reviews & Reported Gains
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.
- 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 & Cycling
Users reported taking the same dosage for cutting, bulking, and body recomposition cycles:
- 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, showing that its concentration builds up in the body over time [R].
LGD 4033 Caution & Side Effects
A pilot study first showed that LGD 4033 was safe short-term in 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. No serious adverse events were reported. None of the participants discontinued due to adverse effects [R].
The most common side effects from the clinical trial were:
- Dry mouth
- Pain related to muscle biopsy (probably unrelated to the drug)
- Upper respiratory tract infections (probably unrelated to the drug)
The frequency of adverse events was similar to the placebo. Side effects were not influenced by the dose — 0.1 mg/day and 1 mg/day caused similar side effects, suggesting that these may even be a “nocebo” effect (when people experience negative effects from an inactive pill or placebo) [R].
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 [R].
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) [R].
The fact that LGD 4033 was safe, 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 [R].
Even with higher bodybuilding doses, most users didn’t experience any side effects. Some reported the following:
- Mild gyno
- 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.
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.
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 [R, R].
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 [R].
In one 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 [R].
Caveats and Limitations
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.
Buying LGD-4033 (Ligandrol)
Although LGD-4033 is available online as a research chemical, we advise against getting this drug given that its safety has not been confirmed in humans.
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