Last Updated January 22, 2024

 January 22, 2024

MK-677 researchers planning to experiment with Ibutamoren (MK-677) may be worried about MK-677 side effects.

While this research compound appears to be generally well-tolerated by test subjects, there is a distinct lack of data from long-term studies for researchers to draw on. With this in mind, what must researchers know before working with MK-677?

This guide will provide a complete overview of the main side effects linked to MK-677 including how it has been dosed in past studies, how test subjects reacted to it, and what, if any, adverse events were observed during these studies. 

For researchers unfamiliar with MK-677, this guide will also explain the purported benefits of MK-677 and how researchers have experimented with it in the past. 

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What is MK-677?

MK-677, also called Ibutamoren, is a non-peptide research chemical that mimics Ghrelin [1] and stimulates the release of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) [2].

Both GH and IGF-1 play an essential role in a number of bodily processes. They’re used at the cellular level to help cells regenerate and synthesize new tissues [3], and they help the body regulate itself and stay healthy. They also play a strong role in the processes of building muscle, burning fat, and repairing cells [4, 5].

Most people produce sufficient amounts of GH and IGF-1 on their own when they’re young. But production slows down in old age, which is part of the reason that the body doesn’t work as well — it takes longer to heal, it’s harder to build muscle and sleep becomes more difficult [6, 7]. People with a GH deficiency naturally run low on GH from an early age and may suffer from stunted growth and other side effects.

One of the proposed treatments for low GH is to simply supplement it directly with exogenous GH. But it turns out that shocking the system with GH often produces intense side effects and GH research is highly controlled. 

Instead, it appears that stimulating the body to secrete its own GH produces fewer adverse effects than traditional GH therapy [8, 9]. One group of substances that can do this is called “growth hormone secretagogues”; they can upregulate the production, secretion, and transmission of GH and IGF-1 throughout the body.

MK-677 is one such GHS that has been consistently found to result in a significant increase in the body’s growth hormone levels.

Let’s look at some of the purported MK-677 benefits. 


MK-677 Side-Effects


MK-677 Benefits

Officially, MK-677 is classified by the US FDA as an “investigational drug”. This means that it hasn’t been approved for use in humans and is only available as a research chemical. 

However, past research involving MK-677 has shown that its primary effect is that it increases GH levels. This means that it may potentially be beneficial for individuals suffering from GH deficiency or who otherwise have low GH levels. A number of studies have found that MK-677 test subjects subsequently have statistically and clinically significant increases in their blood GH levels [10, 11, 12, 13].

But MK-677 may also offer the following benefits: 

  • Increased muscle mass. GH has been found to lead to significantly increased muscle mass in several clinical trials [4, 5]. Since MK-677 boosts GH, it’s no wonder that the early research suggests that it, too, leads to significant increases in muscle development in some populations, including obese individuals [13]. It also seems to improve muscle strength and prevent muscle wasting in elderly test subjects [14].
  • Fat burning. GH plays an important role in burning fat. While research on MK-677 has not conclusively established its fat-burning potential, some research has found that MK-677 helps increase resting metabolic rate [13].
  • Denser bones. Bone fractures from falls are actually among the most common serious injuries for the elderly. Fractures occur because bones tend to lose density with age. MK-677 has been found to help reverse bone mineral loss and lead to denser bones [14, 15, 16].
  • Improves sleep. GH has long been associated with better sleep. Research on MK-677 supports that link, finding that the substance improves the length of Stage IV and REM sleep in test subjects [17].

It’s important to note that direct research on MK-677 is still lacking, so these are only potential benefits. So while caution is warranted in interpreting the research literature, the results firmly support the ability of MK-677 to increase GH levels. 

We’ll now turn our attention to the question at hand; what MK-677 side effects should researchers know about?


MK-677 Side Effects

We should preface this section by issuing the following caveat: The research is still being done. We don’t know everything. Prescription medications available at pharmacies have undergone very comprehensive (and expensive) clinical testing to determine exactly what the side effects are. That requisite testing has yet to be completed for MK-677.

Still, what we do know appears promising.

There have been several studies of MK-677 involving up to several hundred individuals, including the elderly [10, 11, 15, 16]. In those studies, there have not been any serious adverse effects linked to MK-677.

So that’s good news.

Short-Term, Mild Side Effects

Studies have linked MK-677 to several mild and uncomfortable side effects [10, 11, 15, 16]. It appears that MK-677 can occasionally lead to:

  • Flushing of the face (lasting 3 to 5 minutes)
  • Increase in appetite
  • Headache
  • Diarrhea
  • Dry skin
  • Night sweats
  • Numbness and tingling
  • Abdominal pain
  • Edema
  • Muscle pain

Does MK-677 Produce Serious Adverse Reactions?

Those are all fairly mild side effects… but are there more serious side effects?

One particularly worrying side effect is that MK-677 — and GH itself — seems to influence blood glucose and insulin. Several studies have noted decreases in insulin sensitivity and increases in blood glucose as a result of using growth hormone secretagogues [18, 19, 20].

For most healthy test subjects, this may not be an issue. But test subjects who are diabetic, pre-diabetic, or otherwise insulin-sensitive should refrain from participating in research on MK-677.

Another concerning finding was that in one study of elderly patients with hip fractures [14], MK-677 ibutamoren appeared to elevate blood pressure for some individuals. There were even cases of heart failure. It’s not clear that these cases were caused by MK-677 (the patients were all over 80), but this should still be registered as a concerning finding.

Long-Term Side Effects

There have not been many long-term studies of the use of MK-677. So whether there are long-term side effects remains an open question.

The few longer-term MK-677 studies that do exist did not note any long-term side effects. These have studied the use of MK-677 over two years [18] and 18 months [16] respectively.

Still, even though the available evidence suggests that it appears safe over a couple of years, we need to remember that the research isn’t clear yet and so caution is warranted.

Growth Hormone and Cancer?

At this stage, there is absolutely no evidence of any link between MK-677 administration and cancer.

But there have been studies that suggest GH and IGF-1 could promote the growth of cancerous cells [21]. This makes sense: GH promotes cell growth, so it also may promote the growth of cancerous cells, too.

Researchers should bear this with extreme consideration, and refrain from administering all GH secretagogues (MK-677 included) to subjects with any history or significant risk of cancer.

Side Effects are Dose-Dependent

It’s important to note that the side effects of MK-677 appear to be dose-dependent. That means that as the dose increases, the likelihood that the test subject will experience side effects also increases.

That has an important implication for test subject safety: Smaller doses are likely safer.

In general, starting a dosing protocol with a smaller dose, and then increasing it gradually, may decrease the chance of experiencing adverse effects and side effects.


 MK-677 Dosage Guide

How have researchers dosed MK-677 for their test subjects in the past?

The specific dose varies from study to study, but the majority of published studies currently use a dosing protocol that is consistent with the following:

  • Administered orally. Virtually all MK-677 studies involving human test subjects have administered this research chemical orally.
  • Administered once per day. The MK-677 half-life is about 24 hours, so it is usually taken once daily. It can be administered during the day or before bed.
  • Most effective on an empty stomach. Many studies administer it 2 hours after eating.
  • Between 10 mg and 50 mg. 25 mg seems to be the most common dose for test subjects according to  published scientific literature.

MK-677 Research Cycle?

Have test subjects been put on an MK-677 cycle?

There is no published research showing that MK-677 has been dosed in cycles before. Some MK-677 studies have lasted as little as a week, and there is no evidence that test subjects have been exposed to repeated cycles of MK-677.

The longest duration study involving daily MK-677 administration lasted up to 24 months [22]. In this study, MK-677 appeared to be well-tolerated, although it’s not clear what the long-term effects might have been on the test subject involved. 

The typical cycle does seem to be 2 to 8 weeks for most short-term research on MK-677, but perhaps longer is also safe. More research is needed to say for sure.


MK-677 Side-Effects


Where to Buy MK-677 Online? | 2024 Edition

Procuring high-quality MK-677 is essential to running a credible study.

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Side Effects of MK-677 | Verdict

Should researchers be concerned about MK-677 side effects?

Overall, researchers should definitely be aware of them. All prudent researchers must seriously consider the potential adverse effects of the substances they work with. This is especially important since there currently isn’t enough research available for us to properly understand all the side effects — especially the long-term side effects — of MK-677.

But so far, the research suggests that MK-677 is generally well-tolerated and rarely leads to serious adverse effects.

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References

  1. Patchett, A. A., Nargund, R. P., Tata, J. R., Chen, M. H., Barakat, K. J., Johnston, D. B., … & Hickey, G. (1995). Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue. Proceedings of the National Academy of Sciences, 92(15), 7001-7005.
  2. Cassoni, P., Papotti, M., Ghè, C., Catapano, F., Sapino, A., Graziani, A., … & Muccioli, G. (2001). Identification, characterization, and biological activity of specific receptors for natural (ghrelin) and synthetic growth hormone secretagogues and analogs in human breast carcinomas and cell lines. The Journal of Clinical Endocrinology & Metabolism, 86(4), 1738-1745.
  3. Liu, H., Bravata, D. M., Olkin, I., Friedlander, A., Liu, V., Roberts, B., … & Hoffman, A. R. (2008). Systematic review: the effects of growth hormone on athletic performance. Annals of Internal Medicine, 148(10), 747-758.
  4. Welle, S., Thornton, C., Statt, M., & McHenry, B. (1996). Growth hormone increases muscle mass and strength but does not rejuvenate myofibrillar protein synthesis in healthy subjects over 60 years old. The Journal of Clinical Endocrinology & Metabolism, 81(9), 3239-3243.
  5. Kim, K. R., Nam, S. Y., Song, Y. D., Lim, S. K., Lee, H. C., & Huh, K. B. (1999). Low-dose growth hormone treatment with diet restriction accelerates body fat loss, exerts anabolic effect and improves growth hormone secretory dysfunction in obese adults. Hormone Research in Paediatrics, 51(2), 78-84.
  6. Salomon, F., Cuneo, R. C., Hesp, R., & Sönksen, P. H. (1989). The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. New England Journal of Medicine, 321(26), 1797-1803.
  7. Rudman, D., Feller, A. G., Nagraj, H. S., Gergans, G. A., Lalitha, P. Y., Goldberg, A. F., … & Mattson, D. E. (1990). Effects of human growth hormone in men over 60 years old. New England Journal of Medicine, 323(1), 1-6.
  8. Bowers, C. Y., Alster, D. K., & Frentz, J. M. (1992). The growth hormone-releasing activity of a synthetic hexapeptide in normal men and short statured children after oral administration. The Journal of Clinical Endocrinology & Metabolism, 74(2), 292-298.
  9. Penalva, A., Carballo, A., Pombo, M., Casanueva, F. F., & Dieguez, C. (1993). Effect of growth hormone (GH)-releasing hormone (GHRH), atropine, pyridostigmine, or hypoglycemia on GHRP-6-induced GH secretion in man. The Journal of Clinical Endocrinology & Metabolism, 76(1), 168-171.
  10. Chapman, I. M., Pescovitz, O. H., Murphy, G., Treep, T., Cerchio, K. A., Krupa, D., … & Thorner, M. O. (1997). Oral administration of growth hormone (GH) releasing peptide-mimetic MK-677 stimulates the GH/insulin-like growth factor-I axis in selected GH-deficient adults. The Journal of Clinical Endocrinology & Metabolism, 82(10), 3455-3463.
  11. Chapman, I. M., Bach, M. A., Van Cauter, E., Farmer, M., Krupa, D., Taylor, A. M., … & Thorner, M. O. (1996). Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretagogue (MK-677) in healthy elderly subjects. The Journal of Clinical Endocrinology & Metabolism, 81(12), 4249-4257.
  12. Chapman, I. M., Hartman, M. L., Pezzoli, S. S., & Thorner, M. O. (1996). Enhancement of pulsatile growth hormone secretion by continuous infusion of a growth hormone-releasing peptide mimetic, L-692,429, in older adults–a clinical research center study. The Journal of Clinical Endocrinology & Metabolism, 81(8), 2874-2880.
  13. Svensson, J., Lonn, L., Jansson, J. O., Murphy, G., Wyss, D., Krupa, D., … & Bengtsson, B. A. (1998). Two-month treatment of obese subjects with the oral growth hormone (GH) secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditure. The Journal of Clinical Endocrinology & Metabolism, 83(2), 362-369.
  14. Adunsky, A., Chandler, J., Heyden, N., Lutkiewicz, J., Scott, B. B., Berd, Y., … & Papanicolaou, D. A. (2011). MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study. Archives of Gerontology and Geriatrics, 53(2), 183-189.
  15. Murphy, M. G., Bach, M. A., Plotkin, D., Bolognese, J., Ng, J., Krupa, D., … & Gertz, B. J. (1999). Oral Administration of the growth hormone secretagogue MK‐677 increases markers of bone turnover in healthy and functionally impaired elderly adults. Journal of Bone and Mineral Research, 14(7), 1182-1188.
  16. Murphy, M. G., Weiss, S., McClung, M., Schnitzer, T., Cerchio, K., Connor, J., … & MK-677/Alendronate Study Group. (2001). Effect of alendronate and MK-677 (a growth hormone secretagogue), individually and in combination, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women. The Journal of Clinical Endocrinology & Metabolism, 86(3), 1116-1125.
  17. Copinschi, G., Leproult, R., Van Onderbergen, A., Caufriez, A., Cole, K. Y., Schilling, L. M., … & Van Cauter, E. (1997). Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man. Neuroendocrinology, 66(4), 278-286.
  18. Nass, R., Pezzoli, S. S., Oliveri, M. C., Patrie, J. T., Harrell Jr, F. E., Clasey, J. L., … & Thorner, M. O. (2008). Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Annals of Internal Medicine, 149(9), 601-611.
  19. Denko, C. W., & Boja, B. (2001). Growth hormone, insulin, and insulin-like growth factor-1 in hypermobility syndrome. The Journal of rheumatology, 28(7), 1666-1669.
  20. Holly, J. M. P., Amiel, S. A., Sandhu, R. R., Rees, L. H., & Wass, J. A. H. (1988). The role of growth hormone in diabetes mellitus. Journal of Endocrinology, 118(3), 353-364.
  21. Weroha, S. J., & Haluska, P. (2012). The insulin-like growth factor system in cancer. Endocrinology and Metabolism Clinics, 41(2), 335-350.
  22. Nass, R., Pezzoli, S. S., Oliveri, M. C., Patrie, J. T., Harrell Jr, F. E., Clasey, J. L., … & Thorner, M. O. (2008). Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Annals of Internal Medicine, 149(9), 601-611.

Scientifically Fact Checked by:

David Warmflash, M.D.

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