Glycine: A small amino acid with big effects on the body & brain

Rudy! Rudy! Rudy!

Remember that epic movie from 1993? Rudy's dream was to play football at Notre Dame. But, he was about a foot too short and he wasn’t seen as a star athlete. Despite all that, Rudy didn’t stop working as hard as he could to make the team. In the final scene of the movie, the coach finally puts him in the game. Rudy scrambles on the field, unsure at first exactly where to line up. As the clock ticks down, Rudy gets to work and ends up sacking the quarterback for the win.

Back in ‘93, when my sister and I watched that movie at home, we were so pumped up. After watching that final scene, we got up off the couch and jogged 3 miles around the neighborhood. That day we were unstoppable.

What is Glycine?

In the body and brain, glycine is that hard-working little engine that could. Glycine is actually the simplest, and therefore smallest, amino acid. Yet, it’s everywhere, helping out with a lot of things. Actually, all of glycine’s hard work in the body is towards the same end. Glycine is the body’s peacekeeper.

From improving detoxification, to managing methylation, to combating inflammation, to speeding up digestion, to boosting energy, to preventing achy joints and unwanted wrinkles… glycine is everywhere. Glycine works hard, day in and day out, to keep the body and brain healthy and functional.

Let’s take a quick look at all of glycine’s functions, then move on to how glycine supports our mental wellness.

Digestion

Let’s start with digestion. Glycine plays an essential role in fat digestion. It participates in the digestion of fats - one of the three main macronutrients in our diets. Glycine is needed to create bile salts. Specifically, it ‘conjugates’ with bile acids in order to form bile salts (Razak 2017). These bile salts work like soap does on dirty hands. They help water mix together with dietary fat, thus breaking fat down into much smaller particles that can then be absorbed into the body. If there is inadequate bile salts, the body will not be able to make use of nutritional fats, or the all-important fat-soluble vitamins (A, D, E, & K).

Energy

Glycine is one of the three amino acids needed to manufacture creatine. The other two are methionine and arginine (Brosnan 2011). In contributing to creatine production, glycine also supports the energy supply of cells - including brain cells. Creatine provides a helpful, short-term, as-needed energy source for neurons. Energy needs to be manufactured from glucose and oxygen. Those two ingredients are always being pumped into the brain. But, when the brain is working hard, the supply lines of glucose and oxygen run short. When we’re using our brains heavily, the body’s ability to supply glucose and oxygen can’t quite meet the brain’s needs. Luckily, creatine is there to offer a quick supply of energy to the neurons (Owen & Sunram-Lea 2011). In this way, increased energy leads to better brain function.

Detox

Glycine plays a vital, behind-the-scenes role. Glycine is one of the key building blocks for glutathione (Lu 2013). Glutathione would be our body’s ‘master antioxidant’. What’s really interesting about this particular antioxidant is that we actually can make it in our bodies. Most other antioxidants have to be obtained through foods.

Glutathione, like all antioxidants, circulates the body and scavenges free radicals. These free radicals are compounds that threaten healthy cells. Free radicals can bump up against stable molecules and tear them apart. If that happens too much, we can gain weight, be overly fatigued, feel aches and pains, and get wrinkles on our face (Rahman & Hosen 2012). So we need glutathione and other antioxidants at the ready. And, in order to have enough glutathione, we need a healthy supply of glycine. This is because glycine is one of the three amino acids needed to manufacture glutathione (Lu 2013).

Immune System

What’s more, the antioxidant effect of glutathione also helps to keep inflammation down. Inflammation is a natural response to some sort of cellular or tissue damage in the body. If a cell dies, or some infection is present, then inflammation is the body’s natural response to neutralize the threat - dead cell or infectious agent. Inflammation swoops in to clean up the mess. But, inflammation also sometimes leaves a mess. With more glycine helping to make more glutathione, less inflammation is triggered in the first place.

Beyond that, glycine has been found, in humans, to limit the circulation of inflammatory messengers (cytokines) which can easily spur on greater and greater inflammation in the body (Cruz 2014). In addition, glycine acts locally on immune cells to limit them from becoming over active (Zhong 2003). So add ‘anti-inflammatory’ to this growing list of helpful things that glycine does in the body and brain.

Blood Pressure

Glycine helps relax blood vessels (Wang 2013). When blood vessels relax, they open wider, which reduces blood pressure. Relaxed blood vessels equals a relaxed mind.

Further, glycine can help the body detoxify from a toxic amino acid called homocysteine (Razak 2017). Excess levels of homocysteine have been shown to damage blood vessels. Glycine can be used to create trimethylglycine, which can transform excess homocysteine into a safer amino acid, methionine (Razak 2017).

Skin & Joints

Glycine is one of the raw material inputs for collagen production (Murakami et. al. 2012). Collagen gives connective tissue its strength, firmness, and flexibility. In boosting collagen production, glycine helps increase the moisture content and health of skin. Collagen peptide supplements (rich in glycine) has shown to reduce eye wrinkle volume (Proksch et. al. 2014).

Glycine Supports Mental Wellness

There’s actually some published human research on glycine. These studies demonstrate the generally calming effect of glycine.

In technical terms, that calming effect is called inhibition. In the brain, excitation is the gas and inhibition is the brake. Inhibition is needed to counterbalance excitation. This is actually extremely important to maintain balanced brain activity. Receptors for glycine exist throughout the nervous system, in the brain and spinal cord (Legandre 2001).

Beyond that, glycine supplementation has been studied in human subjects.

A few small studies revealed that glycine supplementation led to reduced symptoms for subjects with OCD (Greenberg 2009, Cleveland 2010). Another study with glycine supplementation for subjects with Schizophrenia found reduced psychotic symptoms (Heresco-Levy et al. 1999). It should be noted that these studies used very high doses, upwards of 60 grams per day. Glycine actually tastes sweet, but 60 grams is still a lot to take.

Luckily there have been some other human studies that demonstrated benefits with much lower doses. A few studies observed improvements in sleep onset, sleep quality, and daytime energy levels with closer to 3 grams of glycine taken at night (Inagawa 2006, Yamadera 2007, Bannai 2012, Kawai et al. 2014). Even given during the day, glycine supplementation improved attention and working memory (File 1999).

In sum, glycine is calming, supportive, and healing… who among us doesn’t need more of that these days? If you’re stressed, less than optimally healthy, feeling your age, struggling to sleep, or just want to feel more relaxed… invite more glycine into your diet, and watch this little guy get to work!

How to get more Glycine in the diet

Just as glycine travels to our joints, skin, gut lining, and other connective tissues, the best sources of glycine are the connective tissues from animals.

Unfortunately, we tend not to get enough from our diet. Glycine is a major constituent of collagen - in both humans and animals. To get enough, we would have to eat connective tissue… like chicken skins, gristle, tripe, and a whole bunch of other uncommonly eaten parts of animals. Not really part of our typical American cuisine.

Luckily, there’s a couple easy solutions.

Powdered collagen peptides or gelatin supplements can be really easy to add into the diet. You can add the powder to your coffee, smoothies or to your oatmeal. The added bonus is that your joints will thank you later.

Beyond supplements, the best dietary source is bone broth and it’s what makes bone broth so beneficial. Bone broth is created with boiling water with bones and meat, vegetables, and herbs that are cooked on low for 24-48 hours. This releases the collagen that is found in the connective tissues along with the minerals found in the marrow. This is in contrast to stock which is made with just bones and no spices which makes bone broth more tasty and nutritionally beneficial because it contains the unappreciated amino acid glycine. Bone broth can be found in natural grocers in the freezer sections. And, Pho (Vietnamese soup made with bone broth) is always a great option.

References:

Razak, M., Begum, P., Viswanath, B., Rajagopal, S. (2017). Multifarious Beneficial Effect of Nonessential Amino Acid, Glycine: A Review Oxidative Medicine and Cellular Longevity 2017(4), 1 - 8. https://dx.doi.org/10.1155/2017/1716701

Zhong, Z., Wheeler, M., Li, X., Froh, M., Schemmer, P., Yin, M., Bunzendaul, H., Bradford, B., Lemasters, J. (2003). L-Glycine: a novel antiinflammatory, immunomodulatory, and cytoprotective agent Current Opinion in Clinical Nutrition & Metabolic Care 6(2), 229. https://pubmed.ncbi.nlm.nih.gov/12589194/

Murakami, H., Shimbo, K., Inoue, Y., Takino, Y., Kobayashi, H. (2012). Importance of amino acid composition to improve skin collagen protein synthesis rates in UV-irradiated mice Amino Acids 42(6), 2481-2489. https://dx.doi.org/10.1007/s00726-011-1059-z

Greenberg, W., Benedict, M., Doerfer, J., Perrin, M., Panek, L., Cleveland, W., Javitt, D. (2009). Adjunctive glycine in the treatment of obsessive-compulsive disorder in adults Journal of psychiatric research 43(6), 664 - 670. https://dx.doi.org/10.1016/j.jpsychires.2008.10.007

Inagawa, K., Hiraoka, T., Kohda, T., Yamadera, W., Takahashi, M. (2006). Subjective effects of glycine ingestion before bedtime on sleep quality Sleep and Biological Rhythms 4(1), 75 - 77. https://dx.doi.org/10.1111/j.1479-8425.2006.00193.x

Brosnan, J., Silva, R., Brosnan, M. (2011). The metabolic burden of creatine synthesis Amino acids 40(5), 1325 - 1331. https://dx.doi.org/10.1007/s00726-011-0853-y

Lu, S. (2013). Glutathione synthesis Biochimica et Biophysica Acta (BBA) - General Subjects 1830(5), 3143 - 3153. https://dx.doi.org/10.1016/j.bbagen.2012.09.008

Heresco-Levy, U., Javitt, D., Ermilov, M., Mordel, C., Silipo, G., Lichtenstein, M. (1999). Efficacy of High-Dose Glycine in the Treatment of Enduring Negative Symptoms of Schizophrenia Archives of General Psychiatry 56(1), 29 - 36. https://dx.doi.org/10.1001/archpsyc.56.1.29

Cleveland, W., DeLaPaz, R., Fawwaz, R., Challop, R. (2010). High-Dose Glycine Treatment of Refractory Obsessive-Compulsive Disorder and Body Dysmorphic Disorder in a 5-Year Period Neural plasticity 2009(6), 1 - 25. https://dx.doi.org/10.1155/2009/768398

Yamadera, W., Inagawa, K., Chiba, S., Bannai, M., Takahashi, M., Nakayama, K. (2007). Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes Sleep and Biological Rhythms 5(2), 126 - 131. https://dx.doi.org/10.1111/j.1479-8425.2007.00262.x

Bannai, M., Kawai, N. (2012). New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep. Journal of pharmacological sciences 118(2), 145 - 148. https://pubmed.ncbi.nlm.nih.gov/22293292/

Cruz, M., Maldonado-Bernal, C., Mondragón-Gonzalez, R., Sanchez-Barrera, R., Wacher, N., Carvajal-Sandoval, G., Kumate, J. (2014). Glycine treatment decreases proinflammatory cytokines and increases interferon-γ in patients with Type 2 diabetes Journal of Endocrinological Investigation 31(8), 694 - 699. https://dx.doi.org/10.1007/bf03346417

Baer, K., Waldvogel, H., Faull, R., Rees, M. (2009). Localisation of glycine receptors in the human forebrain, brainstem, and cervical spinal cord: an immunohistochemical review Frontiers in Molecular Neuroscience 2 https://dx.doi.org/10.3389/neuro.02.025.2009

Wang, W., Wu, Z., Dai, Z., Yang, Y., Wang, J., Wu, G. (2013). Glycine metabolism in animals and humans: implications for nutrition and health Amino acids 45(3), 463 - 477. https://dx.doi.org/10.1007/s00726-013-1493-1

File, S., Fluck, E., Fernandes, C. (1999). Beneficial Effects of Glycine (Bioglycin) on Memory and Attention in Young and Middle-Aged Adults Journal of Clinical Psychopharmacology 19(6), 506-512. https://dx.doi.org/10.1097/00004714-199912000-00004

Legendre, P. (2001). The glycinergic inhibitory synapse Cellular and Molecular Life Sciences CMLS 58(5), 760-793. https://dx.doi.org/10.1007/pl00000899

Kawai, N., Sakai, N., Okuro, M., Karakawa, S., Tsuneyoshi, Y., Kawasaki, N., Takeda, T., Bannai, M., Nishino, S. (2014). The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 40(6), 1405-16. https://dx.doi.org/10.1038/npp.2014.326

Proksch, E., Schunck, M., Zague, V., Segger, D., Degwert, J., Oesser, S. (2014). Oral Intake of Specific Bioactive Collagen Peptides Reduces Skin Wrinkles and Increases Dermal Matrix Synthesis Skin Pharmacology and Physiology 27(3), 113-119. https://dx.doi.org/10.1159/000355523

Owen, L. & Sunram-Lea, S. I. Metabolic agents that enhance ATP can improve cognitive functioning: a review of the evidence for glucose, oxygen, pyruvate, creatine, and L-carnitine. Nutrients 3, 735–755 (2011). https://www.mdpi.com/2072-6643/3/8/735

Rahman, T., Hosen, I. (2012). Oxidative stress and human health. Advances in Bioscience and Biotechnology, 3, 997-1019. http://dx.doi.org/10.4236/abb.2012.327123

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