Ligandrol, as it’s often referred, also goes under the names LGD-4033, Anabolicum, and VK5211. This research chemical is considered a SARM and is currently under investigation for its potential use of improving bone health and treating muscle wasting.
Unfortunately, very little primary research exists, meaning, we don't have a good understanding of how this SARM influences the body long term. Despite being tested as far as phase 2 clinical trials, much of this and previous research on ligandrol have yet to be released.
While ligandrol does seem to provide benefit in terms of muscle mass, strength and bone health, research is far from conclusive, and use is discouraged until more information is made available.
As mentioned in our other SARM articles, SARMs are known as selective androgen receptor modulators, which mean they interact with androgen receptors in the body, similarly to how androgenic hormones like testosterone do.
Hormones like testosterone are powerful. They interact with androgen receptors across the body and stimulate muscle growth, muscle strength and also bone strength. But, these hormones are also associated with numerous adverse side effects. Plus, they aren’t selective in the tissues they influence (1, 2, 3).
This presents different problems for many individuals. The elderly, for example, experience age-related hormone decline and thus display reductions of muscle mass, muscular strength and bone health. But the use of hormone therapy could result in adverse side effects (4, 5).
Further, imagine a cancer patient experiencing nutrition-resistant muscle wasting. While hormones would be a bad idea, SARMs present a novel, potential opportunity to maintain or grow muscle and strength without risking further progression of the disease.
Fortunately, research is beginning to reveal that SARMs might be the answer, due to their selective nature. But since these chemicals are relatively new, concrete information is scarce, and the long term ramifications of using them are unknown.
Research On LGD-4033/VK5211
Much like other SARMs, LGD-4033 is relatively new to scientists and laypeople alike. This means there is very little empirical data available for us to read about this substance. Fortunately, there is some clinical data available in both animals and humans regarding LGD-4033, but this information is far from conclusive.
Empirical research on ligandrol is limited. Thus far, there is data regarding ligandrol from a few preclinical animal trials and fewer human clinical trials. Worse, preclinical and surprisingly, much of the clinical data is available only in abstract form or in brief summaries from government websites or the manufacturer’s website.
This lack of full data and limited available research makes drawing conclusions about this controversial drug quite tricky. However, the current findings suggest that ligandrol should at least be tested in future trials.
Initial testing for substances such as ligandrol must go through extensive, preclinical trials in animal models before being tested in humans. Animal studies allow researchers to test the drug in vivo, or in a living being. From here, researchers can then estimate how the drug will influence humans.
In the first preclinical trial, ovariectomized rats, (rats with ovaries removed) were tested. By removing the rat's ovaries, natural hormone production ceases, placing the rat in a similar hormonal state as the elderly. This, of course, allows researchers to begin concluding how the drug might influence an elderly, human population.
Unfortunately, the company that manufactures VK5211 (ligandrol) for testing has only released small bits of information regarding this study. According to their official website, ligandrol was well tolerated in this pre-clinical rat model (6).
Further, the manufacturers note that VK5211 showed a “500-fold” greater selectivity for skeletal muscle as opposed to the prostate. These findings suggest that ligandrol is selective in the tissues it influences, which could be a reason to choose ligandrol over hormone therapy (6, 7, 8).
Additionally, the same data suggests that use of ligandrol significantly improved the rat’s ability to maintain bone density and strength. In fact, these rats showed greater bone strength than control rats and even rats receiving testosterone. These findings suggest that VK5211 might selectively target bone to help maintain and improve density and strength (7, 8).
However, primary research for this study is not available, which calls into question the validity of these findings.
Preclinical Trial In Cynomolgus Monkeys
In a second preclinical trial, ligandrol was given to male and female cynomolgus monkeys in ascending dosages including 0.6mg, 3.0mg, 15mg and a whopping 75mg per kilogram of body weight, per day. This dosage was provided to the monkeys daily for 13 weeks (7, 9).
The results indicated that in a dose-dependent manner, supplementation with ligandrol led to significant increases in body weight for both male and female monkeys (7, 9).
Quite interestingly, the data revealed that for males, receiving more than 15 mg/kg/day held no additional benefit. Mostly, even when consuming 75mg/kg/day, monkeys displayed no further growth. As for females, it was more of the same; only, this limit was reached around the 3mg/kg/day mark, suggesting that females might respond differently and more robustly to ligandrol than male counterparts (7).
Interestingly, these monkeys were able to maintain roughly 70% of body weight gains for at least four weeks after ceasing administration of ligandrol. In opposition to steroid hormones, this suggests that gains may be more permanent and not dependent on hormonal status. These results also indicate that ligandrol could be useful for older individuals or even younger individuals looking to build or maintain body size, without the adverse side effects so often associated with hormonal therapy (4, 5).
Importantly, however, was the fact that monkeys consuming equal to or greater than 15mg of ligandrol per day displayed “maturation” in the prostate and seminal vesicles, as the authors note. This suggests that at higher doses, influence on hormone-sensitive tissue is possible. Considering that one of the primary allures of SARMs is to avoid this from happening, this should be of concern (7).
Preclinical Findings: In both rats and monkeys, ligandrol led to significant improvements in body size and favorable tolerance. However, this data is minimal. Further, data suggest that higher doses (15 mg+) could lead to maturation of prostate and seminal vesicle tissue, which could limit the potential use of this chemical (6-9).
Phase 1 Clinical Testing
Upon successful completion of preclinical testing in animals and humans, VK5211 was pushed towards Phase 1 clinical testing. By entering into phase 1 trials, we can begin to assume a high chance of therapeutic potential for this drug. However, just as with preclinical testing, available data regarding these studies is limited.
Phase 1 Trial 1
In a similar fashion to preclinical testing, 48 healthy males were recruited for this study and were administered a single dose of ligandrol ranging from 0.1mg all the way to 22mg.
The purpose of this test was to observe the influence of a single dose on various processes, including how the drug is metabolized and also how it might influence natural androgen production.
The limited information on this study suggests that while there were no significant adverse side effects, there was a reduction in total testosterone and sex hormone binding globulin (SHBG), suggestive that this SARM could adversely influence natural hormone production (8, 10).
Unsurprisingly, this isn’t the first SARM to display this issue. Ostarine, which is a SARM tested for similar purposes, has also been implicated in adversely influencing testosterone and SHBG. Despite the potential lack of side effects afforded by these SARMS, these results at least suggest that some form of post cycle therapy may be required (11, 12).
Phase 1 Trial 2
After assessing single dose action in healthy volunteers, VK5211 was used in the second of three phase 1 clinical trials. In opposition to the initial testing, this test involved more subjects and observed the longer-duration influence of the SARM for 21 days (10).
During this time, 76, male subjects were administered 0.1mg, 0.3 mg, or 1 mg of ligandrol.
In addition to understanding the metabolism of VK5211 in humans, this study also measured changes in body weight and lean mass, muscular strength, power production and changes to natural androgen production. Since many SARMs lead to favorable changes in muscle size and strength, understanding if VK5211 provides those benefits is valuable.
Additionally, this SARM is being considered for an elderly population in current clinical trials. While these individuals are likely to experience a decline in bone health, they also often experience muscle wasting and loss of function. Thus, finding a SARM that can manage both simultaneously is highly desirable.
After completion of the 21-day study, researchers revealed a significant influence of ligandrol administration on lean body mass, but only for subjects receiving the highest dose of 1 mg per day. Notably, 0.1 mg and 0.3 mg groups did show a trend for improvement but did not reach significance (10).
These trends, however, are essential to consider because the duration of this study was quite short. Based on the observed pattern for improvement, it seems plausible that longer-term dosing of ligandrol could lead to significant increases in muscle size, even with lower doses.
Importantly, despite trends for improvement, there was little influence of ligandrol administration on changes to fat mass or muscular strength. Again, these trends might reach significance with more extended duration dosing (10).
Lastly, in a similar manner to the initial trial, subjects showed a significant decrease in free and total testosterone and SHBG with the most significant change occurring with 1 mg dosing. Fortunately, the data suggest that natural hormone production returned to normal levels 35 days after ending treatment (10).
Keep in mind though that 1.0 mg is quite low and still led to significant changes to natural androgen production. Many bodybuilders taking SARMs illicitly use dosages topping double digits, which could have unknown consequences. The data here reveals that natural hormone production didn't return to normal until almost five weeks post administration. Using progressively higher doses could lead to unknown effects, and this reality should be considered.
Phase 1 Trial 3
In a third effort to observe effectiveness, VK5211 was then administered to a group of healthy, elderly participants in an attempt to closely match a population that might experience a hip fracture and thus, utilize this SARM.
During this brief study, elderly subjects, aged 65 years or older were administered different dosages of VK5211 for seven days. It was reported there were no adverse effects of the drug (8, 13).
Again, like other trials including ligandrol, the information made available regarding this study is scarce and far from conclusive.
Phase 1 Clinical Testing: According to the limited research made available, VK5211 performed quite well in phase 1 testing. With little adverse side effects, ligandrol led to favorable changes in muscle mass and strength, despite some of these improvements only being trends. However, notable reductions in natural testosterone production suggest that this SARM may require post cycle therapy, and might produce unfavorable side effects at higher doses or both (8-13).
Phase 2 Clinical Testing with VK5211
VK5211 is one of the few SARMs to make it as far as phase 2 clinical testing. For this trial, scientists investigated ascending doses of ligandrol in elderly individuals recovering from a recent hip fracture. Subjects ingested placebo, 0.5 mg, 1.0 mg or 2.0 mg of VK5211 orally each day for 12 weeks (14, 15).
Fortunately, this study design is appropriate since VK5211 is marketed and investigated for its potential influence on bone health. Thus, testing within the drug’s primary population is preferred.
The limited data available suggests that the drug was well tolerated, with few adverse side effects. More interestingly were reports of significant improvements in total lean body mass, with the most significant change afforded by the 2.0 mg dose. However, the data suggest that more than 50% of those gains diminished within 12 weeks of stopping treatment (14, 15).
Unfortunately, this data is only made available through third-party investment research firms and in press releases via the manufacturer's website. Even the government's clinical trial database has not posted results for this Phase 2 study, which is a reason to question these findings (14, 15, 16).
Phase 2 Clinical Testing: Phase 2 testing has only just begun. Despite some information made available by the manufacturer and third-party investment research firms, this data is not currently available to the public. This lack of available data suggests that further research is necessary (14-16).
Conclusions of Benefits Based On Research
Based on the limited data available, we can draw a few conclusions about ligandrol, at least in theory.
Muscle Size and Strength
According to the few studies on VK5211, this SARM does seem to be useful for developing lean body mass and potentially for improving strength. Fortunately, the human trials that investigated ligandrol showed positive influence on muscle growth and more importantly, did so in an older population with few side effects (10, 13).
This is important because SARMs present a unique opportunity to build or at least maintain lean mass, without exercise. They are also attractive for elderly individuals, individuals that can't exercise for one reason or another, or a combination of the two.
Further, it's not a stretch to imagine that selectively targeting muscle tissue via VK5211 would be attractive for sick populations, such as those experiencing cancer-related cachexia (nutritional intervention-resistant muscle wasting).
However, there are two important considerations to be made here.
First, all trials commenced in the absence of any exercise protocol. It's very likely that the inclusion of exercise, regardless of intensity or duration, would significantly improve muscle growth and potentially even strength afforded by ligandrol.
Second, this potential makes ligandrol a target for illicit use and abuse.
This reality is a problem mostly because there isn’t any conclusive data on safety regarding this chemical. Yes, preclinical and initial clinical trials suggest few adverse side effects, but with no data testing longer than 12 weeks and a lack of public data, both long and short-term side effects are relatively unknown.
Bone Density, Strength & Health
VK5211 does seem to improve bone density and strength, at least in animal models. Unfortunately, very little data has been released regarding the influence of ligandrol on human bone.
However, based on previous results regarding muscle, it's likely that use of VK5211 will need to continue long term for maintenance of improvements, should clinical trails show significant and favorable changes to bone density and strength (14, 15)
Strong Influence On Endogenous Hormone Production
Similarly to other SARMs like ostarine, ligandrol does display a dose-dependent suppression of endogenous testosterone production that only returned to normal levels around 35 days after stopping treatment (10, 11).
This marked reduction in natural androgen production occurred after only 21 days of 1.0 mg doses, which is very low and of short duration. Many people using SARMs for body composition purposes often take much higher doses for longer durations, which is cause for concern (10).
This is without mentioning that some of the studies showing growth also showed substantial reductions of those gains in the months following the end of treatment. This suggests that a post cycle therapy routine is required or that sustained use will be necessary to maintain benefit (14, 15).
Potential Influence On Androgen Sensitive Tissue
Arguably the biggest reason to consider a SARM is to avoid the side effects of traditional steroids, including the growth of reproductive tissue like the prostate. At the very least, the preclinical data in monkeys shows there is an influence of VK5211 on these tissues. The rat study, however, showed much less but some (7, 8, 9).
Confusingly, the current information available suggests that change to prostate tissue was not intensively evaluated. According to the one full manuscript available, researchers only tested changes to prostate-specific antigen, which is a measure of the development of prostate cancer. But since the duration of the study in question was quite short, it’s unlikely any significant change would have occurred regardless (10, 17)
Perhaps, based on preclinical data, the manufacturers or researchers decided the potential risk to prostate growth was low. However, since SARMs like ligandrol are touted to avoid prostate growth selectively, this should have been a primary area of research.
This lack of information regarding the influence of ligandrol on human prostate tissue is a bit confusing and questionable.
Very Limited Public Data
Alarmingly, there is very little data available to the general population. Apart from one full manuscript (phase 1, trial 2), there is almost no primary research on ligandrol.
A majority of information available on this SARM is only available in abstract form, on conference posters, from investment reports, or short and vague blog posts from the manufacturer of VK5211 (7, 8, 13, 14).
This lack of data is not only confusing but alludes to the fact that the influence of SARMs like ligandrol is relatively unknown.
Where to Buy LGD-4033 / Ligandrol / VK5211?
There are places you can purchase Ligandrol on the internet. Seeing as Ligandrol has scarce research behind it, we cannot recommend that you use Ligandrol, and should you decide to try it anyways you should consult with your medical practitioner first.
Final Verdict On Ligandrol (LGD-4033/VK5211)
Thus far, very little scientific data has been made available to the public regarding ligandrol. Although, the information available does suggest that this SARM could potentially be useful for developing lean body mass, muscular strength, and bone density and strength (7, 8, 13, 14).
However, these potential benefits were alongside significant declines in natural hormone production post-therapy. Even more, some gains achieved diminished substantially in the weeks following the end of treatment, particularly in humans (9, 15).
Lastly, the lack of scientific information made available to the public is a reason for concern. In addition to unknown long-term effects, we also don't have much of the actual research to begin concluding. With most information available only in blogs on the manufacturer's website or through third parties, it's challenging to know not only how this drug influences the body, but also if current claims are true.
Based on the current evidence (or lack thereof) and the fact that this research chemical is still in clinical trials, use of ligandrol outside of a clinical setting is not advised.
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