MYOSTATIN INHIBITOR SUPPLEMENTS: HYPE OR REAL?

If you missed the first article on myostatin and resistance exercise on Evidence Based Muscle, you can find it here. Briefly, the article discussed that light and heavy-weight exercises resulted in identical muscle gene responses to exercise, including myostatin. Myostatin is a class of growth factors genes that put the car breaks muscle growth. Myostatin is a class of growth differentiation factors that regulate muscle growth.

Furthermore, when scientists first discovered myostatin, they believed it was the key to treating muscle-wasting disorders. Examples include sarcopenia and Duchenne muscular dystrophy, as well as other diseases. Infact, myostatin inhibits satellite cells and upregulates pathways involved in protein breakdown. (Argilés et al., 2012; McCroskery et al., 2003)

Additionally, several diseases, such as kidney disease, diabetes, heart failure, etc., associated with pronounced muscle loss, are associated with higher levels of myostatin. (Furihata et al., 2016; Miyamoto et al., 2016)

MYOSTATIN INHIBITOR SUPPLEMENTS

About 7 years ago, one of the the first myostatin inhibitor supplements called MYO-X was supposed to reduce myostatin levels. On the box, it states, “Clinically shown to reduce myostatin in 100% of human test subjects by an average of 46% in only 12-18 hours.”

Surprisingly, this was based on an abstract in which subjects taking 10 or 30 grams of MYO-X gained 1.7 kg of muscle (3.74 lbs.) and 1.68 kg (3.6 lbs.) after 12 weeks of training. The placebo group gained only .6 kg of muscle. (Sharp et al., 2014)

However, the study lacked dietary records, making it unclear if participants consumed more protein and calories, which could lead to increased muscle growth. Personally, I, along with many others, purchased this product and found it lacking in delivering the promised results. In fact, I observed no noticeable changes. Since then, various supplements claiming to inhibit myostatin or boost follistatin, with the promise of enhancing muscle growth, have emerged on the market.

Review of Myostatin Inhibitor Supplements

An excellent review of the myostatin inhibiting supplements to date was published in the journal of Metabolites titled “The Effects of Dietary Supplements, Nutraceutical Agents, and Physical Exercise on Myostatin Levels: Hope or Hype?” The review summarizes the research on myostatin blockers such as whey protein, Vitamin D, EAAs, green tea extract, etc. Here is a short synopsis of the review.

EGG PROTEIN

For instance, a 12-week study found that whole eggs and egg whites reduced myostatin with no difference between the groups. (Bagheri et al., 2020) Furthermore, follistatin, which is an inhibitor of myostatin, was increased.

WHEY PROTEIN

On the other hand, the research on whey protein and myostatin levels is mixed. Some studies have found that whey protein results in no changes in myostatin (Hulmi et al., 2008; Hulmi et al., 2009),  decreases in myostatin (Dalbo et al., 2013), whereas others found that whey protein increases myostatin levels. (Dirks et al., 2014; Paoli et al., 2015)

Notably, the variations in outcomes stem from the differing protein consumptions across the studies. Greater protein intake correlates with increased myostatin expression, while reduced protein intake leads to a decline in myostatin. (Snijders et al., 2013) Myostatin acts as a regulator for muscle growth; when the body detects all anabolic signals being activated, it logically initiates a negative feedback mechanism, elevating myostatin levels.

HMB

Similarly, in patients with a disease condition, HMB has been found to decrease myostatin, whereas healthy adults have no changes in myostatin with HMB use. (Din et al., 2019; Olveira et al., 2016)

Creatine Monohydrate

Two studies examining creatine have found that creatine supplementation results in lower myostatin levels. (Deldicque et al., 2008; Saremi et al., 2010) Test tube studies have also shown that creatine has direct effects on muscle. (Mobley et al., 2014)

In conclusion, the article also highlighted studies on various other supplements, including brown seaweed, spirulina, cocoa, epicatechin, and Vitamin D. However, the findings were largely inconclusive. Ultimately, the author emphasized that only a few studies endorsed the impact of non-protein supplements on myostatin, and their use remains unsupported.

The author concluded, “Whereas proponents of some supplements and other nature-based interventions tout the ability to modulate myostatin levels, based on limited evidence or anecdote, the main clinical recommendations for muscle growth and strength remains an appropriate resistance training program along with a personalized dietary plan, particularly including 1.6–2.0 g/kg/d (i.e., .7-.9 g/lb/day) individually appropriate energy and nutrient intake, and sleep habits.

In essence, adhering to fundamental supplements like creatine is advisable for muscle growth. If you’re abiding by core training principles, like a structured workout regimen, consuming more calories than you burn, and ensuring adequate sleep, there’s no need to stress over your myostatin levels. additionally, the present research doesn’t back the efficacy of myostatin inhibitor supplements for enhancing muscle development.

REFERENCES

Argilés, J. M., Orpí, M., Busquets, S., & López-Soriano, F. J. (2012). Myostatin: more than just a regulator of muscle mass. Drug Discov Today, 17(13-14), 702-709. https://doi.org/10.1016/j.drudis.2012.02.001

Bagheri, R., Hooshmand Moghadam, B., Jo, E., Tinsley, G. M., Stratton, M. T., Ashtary-Larky, D., Eskandari, M., & Wong, A. (2020). Comparison of whole egg v. egg white ingestion during 12 weeks of resistance training on skeletal muscle regulatory markers in resistance-trained men. Br J Nutr, 124(10), 1035-1043. https://doi.org/10.1017/s0007114520002238

Dalbo, V. J., Roberts, M. D., Hassell, S., & Kerksick, C. M. (2013). Effects of pre-exercise feeding on serum hormone concentrations and biomarkers of myostatin and ubiquitin proteasome pathway activity. Eur J Nutr, 52(2), 477-487. https://doi.org/10.1007/s00394-012-0349-x

Deldicque, L., Atherton, P., Patel, R., Theisen, D., Nielens, H., Rennie, M. J., & Francaux, M. (2008). Effects of resistance exercise with and without creatine supplementation on gene expression and cell signaling in human skeletal muscle. J Appl Physiol (1985), 104(2), 371-378. https://doi.org/10.1152/japplphysiol.00873.2007

Din, U. S. U., Brook, M. S., Selby, A., Quinlan, J., Boereboom, C., Abdulla, H., Franchi, M., Narici, M. V., Phillips, B. E., Williams, J. W., Rathmacher, J. A., Wilkinson, D. J., Atherton, P. J., & Smith, K. (2019). A double-blind placebo controlled trial into the impacts of HMB supplementation and exercise on free-living muscle protein synthesis, muscle mass and function, in older adults. Clinical nutrition (Edinburgh, Scotland), 38(5), 2071-2078. https://doi.org/10.1016/j.clnu.2018.09.025

REFERENCES

Dirks, M. L., Wall, B. T., Nilwik, R., Weerts, D. H., Verdijk, L. B., & van Loon, L. J. (2014). Skeletal muscle disuse atrophy is not attenuated by dietary protein supplementation in healthy older men. J Nutr, 144(8), 1196-1203. https://doi.org/10.3945/jn.114.194217

Furihata, T., Kinugawa, S., Fukushima, A., Takada, S., Homma, T., Masaki, Y., Abe, T., Yokota, T., Oba, K., Okita, K., & Tsutsui, H. (2016). Serum myostatin levels are independently associated with skeletal muscle wasting in patients with heart failure. International Journal of Cardiology, 220, 483-487. https://doi.org/10.1016/j.ijcard.2016.06.231

Hulmi, J. J., Kovanen, V., Lisko, I., Selänne, H., & Mero, A. A. (2008). The effects of whey protein on myostatin and cell cycle-related gene expression responses to a single heavy resistance exercise bout in trained older men. European Journal of Applied Physiology, 102(2), 205-213. https://doi.org/10.1007/s00421-007-0579-4

Hulmi, J. J., Kovanen, V., Selänne, H., Kraemer, W. J., Häkkinen, K., & Mero, A. A. (2009). Acute and long-term effects of resistance exercise with or without protein ingestion on muscle hypertrophy and gene expression. Amino Acids, 37(2), 297-308. https://doi.org/10.1007/s00726-008-0150-6

McCroskery, S., Thomas, M., Maxwell, L., Sharma, M., & Kambadur, R. (2003). Myostatin negatively regulates satellite cell activation and self-renewal. J Cell Biol, 162(6), 1135-1147. https://doi.org/10.1083/jcb.200207056

Miyamoto, Y., Hanna, D. L., Zhang, W., Baba, H., & Lenz, H. J. (2016). Molecular Pathways: Cachexia Signaling-A Targeted Approach to Cancer Treatment. Clin Cancer Res, 22(16), 3999-4004. https://doi.org/10.1158/1078-0432.Ccr-16-0495

Mobley, C. B., Fox, C. D., Ferguson, B. S., Amin, R. H., Dalbo, V. J., Baier, S., Rathmacher, J. A., Wilson, J. M., & Roberts, M. D. (2014). L-leucine, beta-hydroxy-beta-methylbutyric acid (HMB) and creatine monohydrate prevent myostatin-induced Akirin-1/Mighty mRNA down-regulation and myotube atrophy. Journal of the International Society of Sports Nutrition, 11, 38-38. https://doi.org/10.1186/1550-2783-11-38

REFERENCES

Olveira, G., Olveira, C., Doña, E., Palenque, F. J., Porras, N., Dorado, A., Godoy, A. M., Rubio-Martínez, E., Rojo-Martínez, G., & Martín-Valero, R. (2016). Oral supplement enriched in HMB combined with pulmonary rehabilitation improves body composition and health related quality of life in patients with bronchiectasis (Prospective, Randomised Study). Clinical Nutrition, 35(5), 1015-1022. https://doi.org/10.1016/j.clnu.2015.10.001

Paoli, A., Pacelli, Q. F., Neri, M., Toniolo, L., Cancellara, P., Canato, M., Moro, T., Quadrelli, M., Morra, A., Faggian, D., Plebani, M., Bianco, A., & Reggiani, C. (2015). Protein supplementation increases postexercise plasma myostatin concentration after 8 weeks of resistance training in young physically active subjects. Journal of Medicinal Food, 18(1), 137-143. https://doi.org/10.1089/jmf.2014.0004

Saremi, A., Gharakhanloo, R., Sharghi, S., Gharaati, M. R., Larijani, B., & Omidfar, K. (2010). Effects of oral creatine and resistance training on serum myostatin and GASP-1. Mol Cell Endocrinol, 317(1-2), 25-30. https://doi.org/10.1016/j.mce.2009.12.019

Sharp, M., Lowery, R. P., Shields, K., Ormes, J., McCleary, S. A., Rauch, J., Silva, J., Arick, N., & Wilson, J. M. (2014). The effects of a myostatin inhibitor on lean body mass, strength, and power in resistance trained males. Journal of the International Society of Sports Nutrition, 11(Suppl 1), P42-P42. https://doi.org/10.1186/1550-2783-11-S1-P42

Snijders, T., Verdijk, L. B., McKay, B. R., Smeets, J. S. J., van Kranenburg, J., Groen, B. B. B., Parise, G., Greenhaff, P., & van Loon, L. J. C. (2013). Acute Dietary Protein Intake Restriction Is Associated with Changes in Myostatin Expression after a Single Bout of Resistance Exercise in Healthy Young Men. The Journal of Nutrition, 144(2), 137-145. https://doi.org/10.3945/jn.113.183996