MK 677 vs LGD 4033

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Mk 677 vs LGD 4033​

MK 677 and LGD 4033 are both effective at muscle repair and bone building and have been researched in the settings of age-related frailty and muscle wasting in chronic disease. While neither compound is considered a peptide, MK 677 comes closer to being a peptide than LGD 4033 does. What unites these compounds in terms of scientific interest is that they are both of intense focus for their ability to alter body composition and affect energy homeostasis. Here is a look at how MK 677 and LGD 4033 compare with one another because you will often hear these two compounds discussed in the same conversation.

MK 677 vs LGD 4033: Structure​

MK 677:

Chemical Structure: C27H36N4O5S

Molecular Weight: 528.7 g/mol

PubChem CID: 9939050

CAS No.: 159634-47-6

Synonyms: Oratrope, Ibutamoren, L-163,191



Source: PubChem



LGD 4033:

Chemical Structure: C14H12F6N2O

Molecular Weight: 338.25 g/mol

PubChem CID: 44137686

CAS No.: 1165910-22-4

Synonyms: Ligandrol, VK-5211



Source: PubChem

MK 677 vs LGD 4033: SARMs​

LGD 4033 is a classic SARM. It binds to the androgen receptor, stimulates muscle growth, and displaces testosterone. In fact, LGD 4033 is one of several compounds initially developed to prevent testosterone from acting on the prostate gland. It was thought that SARMs could be used in certain settings to prevent or treat both benign prostatic hyperplasia (BPH) and prostate cancer. Research shows that LGD-4033 is well tolerated with few adverse effects in phase 1 safety trials. It has been shown to dose-dependently reduce total testosterone, sex hormone-binding globulin, high density lipoprotein (HDL) cholesterol, and triglyceride levels. Even in small doses it leads to increased lean body mass, primarily as a result of increased muscle growth[1].

MK 677 also increases lean body mass, but it does so by stimulating growth hormone release. MK 677 acts like a ghrelin-related peptide by binding to the growth hormone secretagogue receptor (GHS-R) but it is not actually a peptide. Neither is MK 677 a SARM. This synthetic propenamide derivative is essentially in a class of its own. Research studies show that once daily oral administration of Mk 677 increases body weight by approximately 2 kg over a short time period. It increases both bone and muscle mass, but appears to have no impact on fat mass. It also initially increases appetite, but that tends to revert to normal after several months[2].

Of note, because MK 677 works by affecting GH levels and LGD 4033 works by binding to androgen receptors and stimulating them, only the latter has an appreciable impact on testosterone levels. It is this fact that explains why holidays are required when using LGD 4033 vs MK 677. In order to prevent the side effects of long-term LGD 4033 usage, such as decreased libido, the compound needs to be cycled on and off. This is true of all SARMs. MK 677, on the other hand, can be used continuously without any increase in adverse effects.

MK 677 vs LGD 4033: Muscle Repair​

The primary usage for which SARMs have been investigated, outside of controlling symptoms associated with prostate disease, is in preventing muscle wasting. Chronic disease, such as heart disease and cancer, can lead to muscle wasting and difficulty maintaining lean body mass. These effects are often so severe as to limit the amount and duration of treatment that an individual can tolerate. Research shows that a high percentage of mortality in chronic disease is due to loss of muscle and lean body tissue rather than to the disease itself. The ability to maintain lean body mass in the setting of chronic disease can help to prolong life and increase the efficacy of other treatments. Thus, SARMs have been of active interest for their ability to counteract muscle loss and protect lean body mass.

Research shows that muscle loss is not just an issue of quantitative outcomes, but also affects quality of life as well. Cancer patients who are protected from muscle loss report better day-to-day functioning and increased quality of life despite the severity of their disease. Most experts believe that LGD-4033 and other similar SARMs should be approved by the FDA for this indication as they may substantially impact quality of life[3].

Interestingly, combining MK 677 and LGD 4033 work together to increase muscle mass and strength[4]. This is an important finding because previous research has shown that, when used alone, both compounds promote lean body mass development but do not necessarily result in increased muscle strength. It is thought that the combination of both may alter intramuscular androgenic hormone and receptor concentrations in a way that stimulates increases in strength.

MK 677 vs LGD 4033: Heart​

The heart is a muscle, but it differs from skeletal muscle in some key respects that make it unclear whether compounds that affect skeletal muscle will have the same effects on cardiac muscle. Research indicates that MK 677 is a net positive when it comes to heart health but the jury is still our regarding LGFD 4033.

The jury is out regarding net heart health benefits for all SARMs. This is because even though they appear to positively impact heart muscle itself, particularly in the setting of chronic disease, their indirect effects indicate they cause long-term problems. Namely, the lowering of HDL or good cholesterol by SARMs is viewed by some in the research community as problematic. The problem is that the exact impact of lowered HDL levels of long-term heart outcomes is not entirely clear. Further, it is not clear if the benefits of improved cardiac muscle mass offset the speculated negative effects of decreased HDL cholesterol.

While the jury remains out on SARMs, the evidence for MK 677 is that it is a net positive for heart health. By increasing growth hormone and IGF-1 levels, MK 677 increases the production of nitric oxide in blood vessels and helps to decrease blood pressure. Additionally, research indicates that MK 677 increases the growth and survival of epithelial progenitor cells that help to restore blood vessels following damage. A decline in the population of these cells is associated with the development of atherosclerosis and high blood pressure, so protecting them helps to thwart long-term problems with the heart[5], [6].

It is unclear how the combination of MK 677 and LGD 4033 will impact heart health. This area is ripe for research and may ultimately need to new therapeutic paradigms aimed at both preventing and reversing heart disease.

MK 677 vs LGD 4033: Brain​

IGF-1 plays an important role in the clearance of amyloid beta in the central nervous system. Amyloid beta is a component of the plaques that build up in conditions like Alzheimer’s disease and have long been a target for treatment of the disease. Interestingly, IGF-1 levels are known to decline with age, suggesting that at least part of the reason that Alzheimer’s disease is a “disease of the elderly” is because the body’s natural clearance mechanisms wane with age.

Research shows that MK 677 increases IGF-1 levels and thus the compound has been of intense research focus in dementia. Animal studies suggest that MK 677 may, in some cases, be both a curative and a preventative when it comes to dementia. Mice that are treated with MK 677 starting a birth, but are genetically susceptible to Alzheimer’s disease, show reduced amyloid beta plaque and less neuron and synapse loss than their untreated controls[7]. This suggests that MK 677 might offer the first real shot at treating or preventing dementia.

MK 677 vs LGD 4033: Summary​

LGD 4033 is one of the most promising but least researched SARMs in the pharmacopeia. What research has been performed suggests that LGD 4033, when used appropriately, may help to protect lean body mass, neurological tissue, muscle, and the heart. Ongoing research is needed to verify these claims and to extend the work that has already been done.

MK 677 is a more established molecule and one for which obvious benefit is present. What is interesting, however, is that recent work indicates that the combination of MK 677 and SARMs like LGD 4033 may both enhance the benefits of these compounds and mitigate some of their side effects. Further work is needed to delineate not only how these compounds might be used in tandem to produce superior outcomes, but also the dosing and administration regimens that produce the best results.