You’re entitled to a good night’s sleep. Getting your “beauty sleep” isn’t vain if the alternative is puffy eyes, brain fog, and a lack of motivation. In order to relieve yourself of that under-eye baggage, you may need some assistance. Introducing glycine: an amino acid and neurotransmitter that could help you achieve a fairytale-like ending to your day.
Once upon a time—in 1820 to be precise—European chemist Henri Braconnot discovered glycine through the acid hydrolysis of gelatin.1 He boiled gelatin with sulfuric acid to break the gel down into its simpler components. The discovery was sweet, not just because of glycine’s potential, but also because of its properties.
Glycine, also known as glycocoll, is a crystalline solid as sweet as glucose, thus both names share the Greek word meaning “sweet”: glykys.1 Take a look at the ingredients in your favorite sweetener. Is glycine present?
Colorless and odorless, glycine (or aminoacetic acid) is the simplest amino acid found in nature because of its single hydrogen side chain. But its functions are anything but simple: glycine is an essential component of protein synthesis, proper enzyme function, and lipid digestion and absorption.1
Glycine is the primary amino acid in the most abundant protein in our bodies: collagen. You’ve probably heard of collagen; it’s referred to as the magical plumping agent to keep skin looking firm and healthy.
Collagen supports your bones, skin, hair, nails, and more, boosting recovery for sore joints and promoting a healthy gut.
That's why HVMN developed Keto Collagen+, made with grass-fed bovine collagen protein, plus three co-factors to support natural collagen production (vitamin C, copper, and zinc). The blend is keto-friendly with pure C8 MCT Oil Powder and prebiotic acacia fiber.
Named after the Greek “kólla” meaning “glue,” collagen’s main function is to hold everything together.2
Every third amino acid in collagen must be represented by a strong glycine molecule. If not, the tissue will be unstable. Imagine substituting the leg of a wooden chair with a piece of rolled up paper; the chair will probably collapse. Or maybe it’ll hold until you can trick your friend into trying it out. Either way, mutations resulting in a substitution of the strong glycine molecule can cause connective tissue disorders collectively referred to as brittle bone disease.3
In addition to strength, glycine provides flexibility at enzymes’ active sites, allowing them to alter their conformation in order to bind with substrates.4
Glycine’s connections are particularly important for synthesizing essential compounds. Kind of like a recipe book. Combine glycine with arginine and a dash of methionine and you get the delicious creatine.5 It may not be food, but it is a form of fuel.
Most of your body’s creatine is stored in the muscles as phosphocreatine. Phosphocreatine assists with the production of the body’s stored energy, also known as ATP.6 Creatine is a popular supplement choice among athletes because of its potential to increase energy production during high-intensity exercise7 or heavy lifting.8
Glycine is one of the main ingredients in glutathione as well. Pair the amino acid with two others, cysteine and glutamate, and you get the non-protein tripeptide known for defending against oxidative stress.9 Glutathione is a powerful antioxidant your body makes to keep your free radical levels in check. Free radicals are basically free loaders—they take electrons from your cell membranes without your permission (called lipid peroxidation), which can weaken them. Weak cells from oxidative stress can weaken the immune system and contribute to diseases such as heart disease, diabetes, and cancer.10
Glycine modulates both inhibitory neurotransmitters and excitatory neurotransmitters in the brain and the spinal cord, regulating reflex coordination, the processing of sensory information, and modulating the pain sensation.11
The inhibitory functions of glycine are owed to the glycine-specific receptors in regions of the central nervous system,12 while the excitatory effects are facilitated by glutamate and the N-methyl-D-aspartate receptor.13
Humans synthesize about 2.5g of glycine every day via serine hydroxymethyltransefrase. Despite being a great vocal warm up, this process doesn’t satisfy our daily 15g metabolic requirement for glycine.
Glycine is a conditionally-essential amino acid; we can survive on the small amount we create, but ideally, we’ll make up the deficit through our dietary choices or supplements. To be considered a non-essential amino acid, our ability to synthesize it would not be related to our dietary intake.
But why would we have such an imbalance between our glycine synthesis and our actual requirements? It may not be very efficient, but you can thank an evolutionary hiccup for this one.
When collagen first appeared as the most abundant protein in small animals, it was only required in amounts relative to size. Smaller animals, smaller needs.14 At that point, glycine synthesis was balanced.
As larger animals evolved, however, they inherited a regulatory system poorly suited to their higher collagen needs. Larger animals, larger needs, and an inability to synthesize enough glycine to satisfy them.
Let’s talk about those needs. Even though glycine is classified as only conditionally-essential, your joints might disagree. According to a meta-analyses of research studies identifying the relationship between collagen and bone health, the glycine-rich glue may increase bone mineral density and have a protective effect on cartilage around the joints.15 This posits collagen as playing a positive therapeutic role in osteoarthritis and osteoporosis. Best of all? The possibility to provide symptomatic relief from joint pain.15
Humans aren’t alone with their stunted synthesis of this (non)essential compound. Rhinos, elephants, fellow primates,16 and even our robust Neanderthal ancestors17 share a common constraint: a proclivity toward developing osteoarthritis and other skeletal and joint diseases as we age.18 These developments may be a primary example of the Bruce Ames Triage Theory, which says that when access to nutrients is restricted, immediate survival is always prioritized over long-term health.19 It’s a sacrifice your body is willing to make.
According to this theory, micronutrient deficiencies could trigger responses that accelerate cancer and neural decay in exchange for maintaining immediate metabolic processes, like production of ATP.19 It’s kind of like choosing to eat that donut over a salad. Definitely a delicious choice in the moment, but the long-term effects are less sugar-coated. Eliminating a glycine constraint may have been a low-pressure evolutionary consideration compared to survival and reproduction processes. This was fine for your survival-driven ancestors, but modern humans are left with a chronic glycine deficit that may reduce collagen turnover and nonessential metabolic processes. Thanks, great-great-great-great-great grandparents.
Collagenous proteins are the primary dietary source of glycine: bone broths, chicken and pork skins, egg whites, milk, and the aforementioned gelatin.2 But loading up on all that protein won’t necessarily stimulate additional glycine synthesis.
Studies have found that the amino acid composition of the diet is more closely related to glycine production than protein intake. For example, a controlled dietary study of healthy participants found that reducing total protein intake didn’t have an effect on glycine synthesis. However, reducing the amounts of protein exclusively from the essential amino acids (such as histidine and lysine) led to significant reductions in glycine synthesis—a whopping 66%.20
Not in love with glycine yet? This amino acid may already have your heart. Or at least the possibility of protecting it.
Mounting evidence suggests that one of the benefits of glycine is assisting with your battle against heart disease. It has been studied to have numerous inverse associations with coronary risk factors relating to hypertension21 and decreasing free fatty acids in animal models of disease.22
Glycine may break down excess compounds associated with low-density lipoprotein formation.23
Low-density lipoproteins (LDLs) are the ones that float through your bloodstream and grab onto your arteries for dear life.
Over time, these LDLs accumulate, leaving your arteries clogged and struggling to function normally. Glycine availability may be able to modulate these LDLs to help protect against coronary artery disease.23
In a follow-up study of subjects with chest pains, higher glycine levels were associated with a lower risk of both heart disease and heart attacks. While this study does not suggest causality, it does motivate promising research into the mechanism by which glycine may positively affect heart health.23
If the potential for protection against heart disease doesn’t get your blood pumping, glycine won’t either. Or at least not in excess—glycine has been investigated for its ability to reduce blood pressure.22
But the real pressure is figuring out how glycine is able to do this. It may be through glycine’s neurotransmitter activity, suggesting a reduction of heart rate when the sympathetic nervous system is activated.24 Or the reduction may be owed to glycine’s stimulation of fatty acid oxidation, which can reduce fat tissue accumulation.22
Either way, lowering blood pressure is another powerful tool to protect against developing heart disease.
Glycine has other business in your blood with its modulation of blood glucose levels. Despite being a sweetener, glycine has been researched for its ability to reduce blood sugar levels.
Post-meal blood sugar levels (also known as postprandial) may experience a reduction because of greater insulin secretion. Glycine has been observed for its ability to increase the release of a peptide that potentiates glucose-mediated insulin secretion when taken with meals.25 While more research in this area is needed, glycine treatment for type 2 diabetes is gaining momentum.
Fixing your sleeping habits shouldn’t be just a fairytale. A good dose of glycine may transform hours of tossing and turning into a restful night’s sleep.
Glycine can have a cooling effect on your brain and body. Literally cooling—glycine ingestion has been associated with a decrease in your body’s core temperature, which is a natural accompaniment on its voyage to dreamland.26
As body temperature declines, so does your heat production, followed by an increase in your heat loss. All three of these thermoregulation techniques are your body’s way of promoting sleep onset and slow brain wave activity. Conversely, your body’s core temperature begins to increase a few hours prior to waking.27
Glycine’s potential to assist with this thermoregulation may explain its link to a quickened ability to fall asleep.
In a study of subjects experiencing problems with falling asleep and dissatisfaction with sleep quality, ingesting a mere 3mg of glycine prior to bedtime was correlated with faster rates of sleep onset.28 In addition to this rapid REM reception, subjects also experienced shortened latency to reaching the deepest sleep stage without changing their sleep architecture.28
Your body is a skillful sleep architect—it plans and builds the ideal night of rest to rejuvenate you for the morning. The plan involves cycles of rapid eye movement (REM) sleep and (NREM) sleep correlated with different brain wave patterns and physiology, culminating in your unique slumber skyline.27
There are four stages of NREM sleep leading to REM sleep. REM sleep is the deepest stage of sleep you can thank for dreams. There’s no body movement during REM sleep. That’s because your body is protecting itself from physically reacting to your dreams.27 Imagine trying to actually fight off that hoard of zombies while you’re dreaming about them. It may not end well for you, the zombies, or the innocent lamp on your bedside table.
Unlike a real building, our unique cityscape snoozing is rather fragile. Disruptions in sleep architecture or irregular cycling is associated with sleep disorders.27
In a study on levels of glycine and sleep efficacy, researchers observed that glycine plays a significant role in alleviating symptoms of fatigue in people with poor sleep.29 Subjects reported positive effects on feelings of clear-headedness, liveliness, and self-assessed quality of sleep.29
A 2012 study echoed the findings, adding that glycine may be able to improve psychomotor vigilance the morning after ingestion.30 In this study, participants without sleep disturbances had their nightly naps cut by 25% to induce fatigue.
Fatigue met its match in glycine—participants reported significant decreases in sleepiness compared to the placebo while their testing performances soared.
This indicates that glycine may have practical implications for those with only occasional sleep restrictions in addition to those with sleep disorders.30
Those occasional nights of poor sleep deserve just as much attention as chronic disorders. That’s why we at HVMN developed non-habit forming sleep aid, Yawn. Yawn combines the natural sleep hormone melatonin with stress-reducing31 L-theanine and morning-motivator glycine29 to induce a high quality night of rest. In addition to falling asleep faster,32 Yawn can help you get going the next day feeling fatigue-free30 and ready to go.
Yawn is a great solution for glycine supplementation, combining the sleep-inducing effects of melatonin and glycine to help get the body and brain in recharge mode.
If you’re ready to find a happily ever after with glycine, ensure you seek medical advice from your doctor before adding it as a daily supplement.
Clinical trials have dosed glycine up to 0.8g per kilograms of body weight in a healthy adult. For an adult weighing around 175 pounds, that’d be about 64 grams of glycine. Lower daily doses of 15g - 25g have been used in most studies,33 but glycine is generally well tolerated at relatively high doses (up to 90g).33
While no major adverse effects of glycine supplementation have been reported, mild side effects have been reported. Mild side effects include abdominal pain and soft stools, with abdominal pain generally reported when taking glycine on an empty stomach. Ingesting glycine during meals is not associated with causing daytime sleepiness.33
Whether you’re looking for a better night’s sleep to fuel long workdays or want to ensure you’re hitting your evolutionarily-stunted metabolic needs, glycine may be able to help you achieve your goals.
Along the way, this powerhouse amino acid may be able to offer protection against the atherosclerotic process to boost heart health. Another heart helper? Glycine’s promising modulations of blood glucose levels in normal adults and those with blood glucose sensitivity problems.
Even if you’re not a fan of love stories, rest assured that you and glycine could live happily ever after.
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|1.||Wang W, Wu Z, Dai Z, Yang Y, Wang J, Wu G. Glycine metabolism in animals and humans: implications for nutrition and health. Amino Acids. 2013;45(3):463-77.|
|2.||Lodish H, Berk A, Zipursky SL, et al. Molecular Cell Biology. 4th edition. New York: W. H. Freeman; 2000. Section 22.3, Collagen: The Fibrous Proteins of the Matrix. Available from: https://www.ncbi.nlm.nih.gov/books/NBK21582/|
|3.||Gajko-galicka A. Mutations in type I collagen genes resulting in osteogenesis imperfecta in humans. Acta Biochim Pol. 2002;49(2):433-41.|
|4.||Yan BX, Sun YQ. Glycine residues provide flexibility for enzyme active sites. J Biol Chem. 1997;272(6):3190-4.|
|5.||Brosnan JT, Da silva RP, Brosnan ME. The metabolic burden of creatine synthesis. Amino Acids. 2011;40(5):1325-31.|
|6.||Wyss M, Kaddurah-daouk R. Creatine and creatinine metabolism. Physiol Rev. 2000;80(3):1107-213.|
|7.||Persky AM, Brazeau GA. Clinical pharmacology of the dietary supplement creatine monohydrate. Pharmacol Rev. 2001;53(2):161-76.|
|8.||Buford TW, Kreider RB, Stout JR, et al. International Society of Sports Nutrition position stand: creatine supplementation and exercise. J Int Soc Sports Nutr. 2007;4:6. Published 2007 Aug 30. doi:10.1186/1550-2783-4-6|
|9.||Lu SC. Glutathione synthesis. Biochim Biophys Acta. 2013;1830(5):3143-53.|
|10.||Masella R, Di benedetto R, Varì R, Filesi C, Giovannini C. Novel mechanisms of natural antioxidant compounds in biological systems: involvement of glutathione and glutathione-related enzymes. J Nutr Biochem. 2005;16(10):577-86.|
|11.||Zafra F, Giménez C. Glycine transporters and synaptic function. IUBMB Life. 2008;60(12):810-7.|
|12.||Betz H, Laube B. Glycine receptors: recent insights into their structural organization and functional diversity. J Neurochem. 2006;97(6):1600-10.|
|13.||Johnson JW, Ascher P. Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature. 1987;325(6104):529-31.|
|14.||Cornish-bowden A, Pereto J, Cardenas ML. Biochemistry and evolutionary biology: two disciplines that need each other?. J Biosci. 2014;39(1):13-27.|
|15.||Porfírio E, Fanaro G. Collagen supplementation as a complementary therapy for the prevention and treatment of osteoporosis and osteoarthritis: a systematic review. Revista Brasileira de Geriatria e Gerontologia. 2016;19;153-164. 10.1590/1809-9823.2016.14145.|
|16.||Jurmain R. Degenerative joint disease in African great apes: an evolutionary perspective. J Hum Evol. 2000;39(2):185-203.|
|17.||Straus WL, Cave JE. Pathology and the posture of Neanderthal man. Q Rev Biol. 1957;32(4):348-63.|
|18.||Greer M, K Greer J, Gillingham J. Osteoarthritis in selected wild mammals. Proceedings of the Oklahoma Academy of Sciences1977: 57.|
|19.||Ames BN. Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage. Proc Natl Acad Sci USA. 2006;103(47):17589-94.|
|20.||Yu YM, Yang RD, Matthews DE, et al. Quantitative aspects of glycine and alanine nitrogen metabolism in postabsorptive young men: effects of level of nitrogen and dispensable amino acid intake. J Nutr. 1985;115(3):399-410.|
|21.||El hafidi M, Pérez I, Baños G. Is glycine effective against elevated blood pressure?. Curr Opin Clin Nutr Metab Care. 2006;9(1):26-31.|
|22.||El hafidi M, Pérez I, Zamora J, Soto V, Carvajal-sandoval G, Baños G. Glycine intake decreases plasma free fatty acids, adipose cell size, and blood pressure in sucrose-fed rats. Am J Physiol Regul Integr Comp Physiol. 2004;287(6):R1387-93.|
|23.||Ding Y, Svingen GF, Pedersen ER, et al. Plasma Glycine and Risk of Acute Myocardial Infarction in Patients With Suspected Stable Angina Pectoris. J Am Heart Assoc. 2015;5(1)|
|24.||Talman WT, Robertson SC. Glycine, like glutamate, microinjected into the nucleus tractus solitarii of rat decreases arterial pressure and heart rate. Brain Res. 1989;477(1-2):7-13.|
|25.||Gameiro A, Reimann F, Habib AM, et al. The neurotransmitters glycine and GABA stimulate glucagon-like peptide-1 release from the GLUTag cell line. J Physiol (Lond). 2005;569(Pt 3):761-72.|
|26.||Bannai M, Kawai N. New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep. J Pharmacol Sci. 2012;118(2):145-8.|
|27.||Institute of Medicine (US) Committee on Sleep Medicine and Research; Colten HR, Altevogt BM, editors. Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem. Washington (DC): National Academies Press (US); 2006. 2, Sleep Physiology. Available from: https://www.ncbi.nlm.nih.gov/books/NBK19956/|
|28.||Yamadera W, Inagawa K, Chiba S, et al. Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes. Sleep and Biological Rhythms. 2007; 5 (2), 126-131|
|29.||Inagawa K, Hiraoka T, Kohda T, Yamadera W, Takahashi M. Subjective effects of glycine ingestion before bedtime on sleep quality. Sleep and Biological Rhythms. 2006; 4 (1), 75-77|
|30.||Bannai M, Kawai N, Ono K, Nakahara K, Murakami N. The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers. Front Neurol. 2012;3:61. Published 2012 Apr 18. doi:10.3389/fneur.2012.00061|
|31.||Kimura K, Ozeki M, Juneja LR, Ohira H. L-Theanine reduces psychological and physiological stress responses. Biol Psychol. 2007;74(1):39-45.|
|32.||Ferracioli-oda E, Qawasmi A, Bloch MH. Meta-analysis: melatonin for the treatment of primary sleep disorders. PLoS ONE. 2013;8(5):e63773.|
|33.||Inagawa K, Kawai N, Ono K, Sukegawa E, Tsubuku S, Takahashi M. Assessment of Acute Adverse Events of Glycine Ingestion at a High Dose in Human Volunteers. SEIKATSU EISEI (Journal of Urban Living and Health Association) 2006; 50; 27-32|
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