LGD-4033, also known as Ligandrol, is a compound that selectively targets androgen receptors. It is often used as a legal alternative to steroids by professional athletes and bodybuilders due to its purported anabolic effects and supposed lack of androgenic side effects (compared to steroids).
Having a high affinity towards AR (androgen receptors), LGD-4033 selectively binds to the androgen receptors in the muscles. It has a lower affinity for binding to other locations where androgen receptors are present in the body. Ligandrol carries an anabolic vs. androgenic ratio of 10:1.
Comparatively, natural testosterone carries a ratio of 1 to 1. Androgenic binding is one downside of using synthetic steroids to treat men in Testosterone Replacement Therapy due to major cosmetic and health side effects.
Research has been carried out on LGD-4033 over the years. The Pharmaceutical industry is interested in SARMs due to how they target and bind to androgen receptors.
Selectivity for targeting the receptors is a major consideration that medical research is interested in. High anabolic vs. androgenic ratios is something that is important when evaluating the theoretical safety of a specific SARM.
Clinical Research & Human Investigation
LGD-4033 is under investigational research and currently in Phase II of human clinical trials. In Phase I, administration of LGD showed an increase in lean muscle mass with the administration of this SARM.
The study also demonstrated the tolerability of side effects in the group of placebo-controlled males . In the study, they tested for levels of certain substances and signaling compounds that might induce side effects like enlarged prostate but no significant increases were found. Free testosterone, FSH and a sex hormone binding compound were decreased in a dose-dependent manner.
Free testosterone production was suppressed dramatically when above 1mg dosage but returned to baseline after cessation. Ligandrol showed a dose compounding effect due to its long half-life and also showed a dose-dependent increase in lean muscle mass.
LGD Dosage in Study
- 0.1 mg daily for 21 days
- 0.3 mg daily for 21 days
- 1.0 mg daily for 21 days
Although the study does not note this, the dosage of LGD-4033 was most certainly orally since the substance is orally active and it is the easiest ROA.
Notable Results (Results Compared with Placebo Group):
No increases in hemoglobin, prostate-specific antigen, aspartate aminotransferase, alanine aminotransferase level
- Increase in Lean Muscle Mass
- No Significant decrease in fat-loss
- Hormone & lipid levels back to normal after discontinuation
- No complaints or signs of adverse effects by study group
Although this is the first real human study of LGD-4033 at this time, its results are astonishing. A measurable increase in lean muscle mass over 21 days is a major feat (the study doesn't confirm if the group was weight training).
The safety profile of this substance is likely to be high at or below the 1mg oral dosage range. Free-testosterone, FSH and other hormone levels returning to baseline after cessation is another major benefit this SARM may have over steroidal based drugs used in medicine.
Although this was just Phase I of Ligandrol, the results look promising to SARM research in the medical field.
Side Effects of Ligandrol
The human study (mentioned above) studied the safety and tolerability of LGD-4033. Based on this data, two things might be concluded with the side effect profile of this substance in humans:
- At 1 mg or less taken orally each day, Ligandrol is likely to be well tolerated and quite safe.
- Ligandrol has a long half-life, so taken daily it might have a compounding effect in the bloodstream. This build-up is dose dependent so therefore, if a human were to supplement this SARM over a long time and in high dosages, the resulting risk of adverse effects goes up.
There are some important factors to determine when looking at safety and side effects. Purity and adulterants may be an issue with vendors online so this will always be one of the highest risks to those supplementing this substance. Also, it is always possible that someone's body will not tolerate a specific substance. The most common side effect of human intolerance is an allergic reaction. It is quite possible that extremely rare cases could pop up that involve both serious or even life-threatening cases of allergic reaction to oral, topical, IV or IM usage.
Another safety concern to consider is the effects this substance may have on lipid levels such as HDL (good cholesterol). In the case of HDL, lowering it within the body may have a dose-dependent negative effect on the heart. With this in mind, most experts might agree that SARMs are much safer than steroids in general by not directly affecting the heart tissue to a significant degree.
Ligandrol does not seem to affect hormones as severely as steroids post-cycle. In the noted study, hormone levels such as free-testosterone returned to normal. Steroids are known to cause the body to reduce its production of free testosterone for many weeks after cessation. Untreated, this effect of steroids after could cause side effects such as hypogonadism (shrinking testicles), gynecomastia (man breasts), lowered libido, decrease in muscle/bone mass and low energy levels just to name a few.
The dosages used in the LGD-4033 study were more than likely safe post-cycle because they did not require any post cycle treatment (or even close). Higher dosages might possibly require post cycle therapy to reduce cessation side effects although it is not entirely clear what this human dosage would equate too.
If one were to insist on taking SARMs there is always a safety and side effect risk. Risks might be drastically reduced by lowering dosage and taking breaks every 6-12 weeks (known as cycling). The only data to really go off of is the human research and even this isn't technically medically sound advice.
There is evidence of bodybuilders taking massive high oral (and even injection) dosages of LGD-4033. Many of these users are entering the unknown and at a much higher risk for adverse results.
Other Possible Benefits
Outside of increasing lean muscle mass, this SARM might have some other interesting medical applications. It might increase energy levels and be suited not only for those looking for testosterone replacement but also for men and women with chronic fatigue syndrome. Diseases and disorders involving muscle wasting and endocrine disruptions might also benefit. It could be especially useful in cases of bone diseases like osteoporosis as well. When used for rare types of cancer involving bone and muscle tissues, LGD-4033 might possibly have a medical application.
How Does it Work?
Ligandrol works by binding itself to androgen receptors (ARs) in the body. The selective nature of how this compound and other SARMs affect these receptors might determine the appearance and likelihood of side effects. Each SARM has a different binding affinity affecting how anabolic it is versus how much androgenic activity. A perfect SARM might have a 100% binding affinity for lean muscle and bone tissue strictly.
The heart and prostate are two organs that have androgen receptors and it is well-known that steroids can negatively affect these organs both in the short term and long term . LGD-4033 is non-steroidal and differs from steroids in how it releases androgens from the receptors and which tissues these androgens target. Theoretically, LGD-4033 and other SARMs have a better safety profile than natural testosterone in terms of androgenic side effects.
It is not understood exactly how SARMs work but there is one popular hypothesis. The hypothesis suggests that steroidal and non-steroidal SARMs have a specific and distinct molecular arrangement that makes them unique. These unique compounds then bind to ARs and exert a subsequent change in the receptor. This receptor then sends out a "message" by either genetic signaling or via non-genetic processes.
LGD-4033 is legal in the United States and many other countries and continents. It appears to be legal in Canada, the UK, the EU and Australia to name a few although certain laws may prohibit SARMs importation or distribution in those areas.
Ligandrol is legal for research applications only. Using or carrying this product around in public might get some people in trouble. At this time, LGD-4033 is not in schedules 1 through 5 under The Consitution. Several companies including larger bodybuilding supplement companies are selling and marketing this and other SARMs as supplements. Many companies are selling it "for research" however, are selling in capsule form or with labels that look similar to FDA approved labels. This might get the distributor in trouble legally. For this reason, buying from a legitimate online seller of LGD-4033 for research is recommended.
1. https://www.ncbi.nlm.nih.gov/pubmed/22459616 - Placebo-controlled study in healthy males
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907129/ - SARMS - heart and prostate