Glycine and Leucine - Actions on Muscle Growth

Glycine and Leucine - Back in 1964, an exploratory party went to Easter Island in the magical South Pacific. They were looking for innovative anti-microbial agents as even in the '60s microbial resistance to antibiotics was on the rise. A chemical was discovered in one of the bacterial samples, and this agent had remarkable properties. This unique chemical was called Rapamycin (Easter Island is also known as Rapa Nui).

Thirty years pass since its discovery, and Rapamycin, which is clinically referred to as 'sirolimus', is used to coat stents (the un-blocking tubes inserted into coronary arteries to treat and prevent heart disease). In contrast, its potent immune-suppressive effects are used to avoid rejection kidneys during a kidney transplant[1].

But no one going to a gym cares about bacteria, stents, kidneys, or even Easter Island! They care about growing muscle, and mammalian/mechanistic Target of Rapamycin Complex (mTORC) grows muscle big time. There are two mTORCs, but for this article, we will only focus on the one that makes us huge (which is mTORC1).

Leucine drives mTORC1

Most serious gym goers know all about the BCAAs because they are essential amino acids that 'grow muscles'. Well, that assumption is correct! The chief of the BCAAs is leucine, and it is a good driver of mTORC1. Leucine, when taken on its own, will stimulate mTORC1 signal transduction[3]. This well-known effect has been studied for over a decade, which has led some people in the industry to believe this is the ONLY stimulator of mTORC, and growing muscle is as simple as the more leucine eaten = the more muscle produced. Of course, if that were the case, I would have a big bowl of leucine for breakfast and be done with it.

Leucine - Is more of it better?

Let's find out! Just last year, scientists took a group of resistance-trained young men (in other words, were already going to the gym) and gave them 2 x 5g of leucine extra on top of an already protein-rich diet (where these men consumed 1.8 ± 0.4 g protein/kg/d). This protein consumption level is typical for 27-year-old men, so the extra leucine would be a tremendous real-life test to see how the extra leucine would perform in a real-world situation.

The participants were strictly monitored to ensure the only difference was the leucine consumption. Their diets and exercise levels were identical to see whether the leucine itself, the only variable, would drive mTORC and put extra muscle on. After 12 weeks, the men's muscles were accurately measured for size and strength. Interestingly, adding an additional 10 g daily of leucine made no difference in muscle strength or muscle mass in these men[5].

What we can conclude from this study is that while leucine is good, an adequate, typical protein-rich diet contains enough leucine to stimulate mTORC to the maximum level, and adding extra leucine may not provide any additional benefit.

The new kid on the block - Glycine

Glycine is often considered biochemically small, and the smallest of all the amino acids. But don't let its size fool you! Glycine is required to make many biochemically essential molecules. Glycine is needed to make the vital detoxifying, and the antioxidant king called glutathione. Glycine has a broad-spectrum anti-inflammatory action, while it also modulates the immune system beneficially[6].

Glycine has become famous lately because it has been found that the commonly used herbicide, Glyphosate actually screws with glycine metabolism in the body, which has far-reaching consequences for human health[7].

Glycine boosts mTORC

Glycine is found in super high amounts in collagen, which may explain why a recent (2021) double-blind, placebo-controlled study showed that only 15g of collagen boosted muscle mass in well-fed men in as little as 12 weeks[8]. While collagen has the BCAAs in it, it has vastly high amounts of glycine, which has been recently found to boost mTORC independently of the BCAAs[9]. This is news to most people who believed that only leucine is the player in boosting mTORC however; we now know different.

Glycine has other incredible benefits.

As you can see in Figure 4 (below), glycine is an excellent booster on mTORC, but it is much more than that. Glycine-dependent transporters allow chlorine ions into cells, which regulate calcium entry into cells. If too much calcium is allowed to enter muscle cells, inflammation is generated (IL-6 and TNF-a), which in turn increases oxidative stress. This oxidative stress leads to cellular damage, which catabolises muscle tissue[10]. Thus, glycine also plays a role in not only growing muscle but reducing cellular damage.

Glycine makes energy (ATP)

Yet another extraordinary role for glycine is generating the unit of energy in the body, which is adenosine tripolyphosphate (ATP). When glycine enters a cell, it is converted into another amino acid (serine). This process liberates energy in the form of ATP [11]. And we all want more energy!

The take-home message

Leucine is good for boosting muscle mass and mTORC. No question. However, if you are on a high protein diet, taking extra leucine won't help. On the other hand, Glycine is superb for boosting mTORC, but it is more than that. Glycine acts as an antioxidant and is involved in energy production. That is a pretty good resume to increase muscle mass and energy.

References

1.Seto B. Rapamycin and mTOR: a serendipitous discovery and implications for breast cancer. Clin Transl Med. 2012;1(1):29. Published 2012 Nov 15. doi:10.1186/2001-1326-1-29

2.Saxton RA, Sabatini DM. mTOR Signaling in Growth, Metabolism, and Disease . Cell. 2017;168(6):960-976. doi:10.1016/j.cell.2017.02.004

3.Dodd KM, Tee AR. Leucine and mTORC1: a complex relationship. Am J Physiol Endocrinol Metab. 2012 Jun 1;302(11):E1329-42. DOI: 10.1152/ajpendo.00525.2011. Epub 2012 Feb 21. PMID: 22354780.

4.Li, Fengna & Yin, Yulong & Kong, Xiangfeng & Wu, Guoyao. (2011). Leucine nutrition in animals and humans: mTOR signalling and beyond. Amino acids. 41. 1185-93. 10.1007/s00726-011-0983-2.

5.DE Andrade IT, Gualano B, Hevia-LarraÍn V, Neves-Junior J, Cajueiro M, Jardim F, Gomes RL, Artioli GG, Phillips SM, Campos-Ferraz P, Roschel H. Leucine Supplementation Has No Further Effect on Training-induced Muscle Adaptations. Med Sci Sports Exerc. 2020 Aug;52(8):1809-1814. DOI:

6.Pérez-Torres I, Zuniga-Munoz AM, Guarner-Lans V. Beneficial Effects of the Amino Acid Glycine. Mini Rev Med Chem. 2017;17(1):15-32. doi: 10.2174/1389557516666160609081602. PMID: 27292783.

7.Pérez-Torres I, Zuniga-Munoz AM, Guarner-Lans V. Beneficial Effects of the Amino Acid Glycine. Mini Rev Med Chem. 2017;17(1):15-32. doi: 10.2174/1389557516666160609081602. PMID: 27292783.

8.Zdzieblik D, Jendricke P, Oesser S, Gollhofer A, König D. The Influence of Specific Bioactive Collagen Peptides on Body Composition and Muscle Strength in Middle-Aged, Untrained Men: A Randomized Controlled Trial. Int J Environ Res Public Health. 2021 Apr 30;18(9):4837. DOI: 10.3390/ijerph18094837. PMID: 33946565.

9.Koopman R, Caldow MK, Ham DJ, Lynch GS. Glycine metabolism in skeletal muscle: implications for metabolic homeostasis. Curr Opin Clin Nutr Metab Care. 2017 Jul;20(4):237-242. DOI: 10.1097/MCO.0000000000000383. PMID: 28375879.

10.Koopman R, Caldow MK, Ham DJ, Lynch GS. Glycine metabolism in skeletal muscle: implications for metabolic homeostasis. Curr Opin Clin Nutr Metab Care. 2017 Jul;20(4):237-242. DOI: 10.1097/MCO.0000000000000383. PMID: 28375879.

11.Koopman R, Caldow MK, Ham DJ, Lynch GS. Glycine metabolism in skeletal muscle: implications for metabolic homeostasis. Curr Opin Clin Nutr Metab Care. 2017 Jul;20(4):237-242. DOI: 10.1097/MCO.0000000000000383. PMID: 28375879.

12.Koopman R, Caldow MK, Ham DJ, Lynch GS. Glycine metabolism in skeletal muscle: implications for metabolic homeostasis. Curr Opin Clin Nutr Metab Care. 2017 Jul;20(4):237-242. DOI: 10.1097/MCO.0000000000000383. PMID: 28375879.