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Glycine
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Glycine

Glycine is a simple, nonessential amino acid vital to human health and many mammals. Synthesized from compounds like choline, serine, hydroxyproline, and threonine, glycine often needs to be supplemented through diet to meet the body's demands. 

Glycine serves as a precursor for crucial metabolites including glutathione. 

Glycine is essential for protein synthesis, notably stabilizing collagen's structure, and acts as a neurotransmitter in the central nervous system, influencing food intake, behavior, and homeostasis. 

It also supports immune function, lipid digestion, and absorption, playing a significant role in maintaining overall metabolic health.

What is Glycine?  [14.]

Glycine is a simple, nonessential amino acid vital to the health and function of humans and many mammals.  

It is synthesized from compounds such as choline, serine, hydroxyproline, and threonine in the kidneys and liver. 

Although classified as nonessential, glycine is not always produced in sufficient quantities, necessitating dietary intake to meet the body's needs. 

Glycine is a precursor for several critical metabolites including creatine, glutathione, haem, purines, and porphyrins.

Physiological Functions and Synthesis of Glycine

Glycine constitutes 11.5% of the amino acid content in the human body and plays essential roles in various metabolic pathways. 

It is crucial for protein synthesis, particularly in collagen, where it stabilizes the triple helix structure. 

Glycine also acts as a neurotransmitter in the central nervous system, influencing food intake, behavior, and overall homeostasis. 

It supports immune function by regulating cytokine synthesis and intracellular calcium levels and aids in lipid digestion and absorption through bile acid conjugation.

Glycine synthesis involves several pathways, including conversion from choline, threonine, and serine.

For instance, choline is converted to glycine through sarcosine, and threonine is degraded by threonine dehydrogenase. 

Serine hydroxymethyltransferase (SHMT) catalyzes the conversion of serine to glycine in both mitochondria and cytoplasm. 

This synthesis is critical for maintaining adequate glycine levels, particularly during growth and in metabolic stress conditions.

Glycine’s Role in the Nervous System  [5., 13., 14., 17.] 

In the central nervous system, glycine acts as an inhibitory neurotransmitter, regulating food intake, behavior, and body homeostasis.

It binds to glycine receptors (GlyRs), which are chloride ion channels.  When activated, GlyRs allow chloride influx, resulting in neuronal hyperpolarization and inhibition.

Glycine decreases the release of both inhibitory and excitatory neurotransmitters through the "shunting" effect, reducing membrane resistance and postsynaptic voltage.

In addition to its neurotransmitter role, glycine also acts as a co-agonist of the NMDA receptor, allowing for depolarization and calcium influx when bound along with glutamate

Glycine’s Role in Protein Synthesis  [1., 14.] 

Despite its simplicity, glycine is an essential component of many proteins, contributing to their structure and function.  

It is particularly abundant in structural proteins like collagen, elastin, and silk fibroin, where its small size and flexibility allow it to fit into tight spaces and facilitate the formation of triple helices. 

Glycine also plays a role in the synthesis of other non-protein compounds such as glutathione, creatine, and porphyrins.

Glycine’s Antioxidant Properties and Role in Glutathione Production  [11.] 

Glycine plays a crucial role in the biosynthesis of glutathione, a potent antioxidant that protects cells from oxidative stress and damage.  

Glutathione is a tripeptide composed of glycine, cysteine, and glutamic acid, and its production is dependent on the availability of these amino acids. 

By contributing to glutathione synthesis, glycine helps neutralize free radicals, detoxify harmful compounds, and maintain cellular integrity.

Health Benefits of Glycine

Glycine has multiple health benefits including enhanced sleep quality and improved neurological function.  [14.] 

Its health benefits also include hepatoprotection, as it can mitigate alcohol-induced liver damage.  [2.] 

Glycine also shows promise in treating gastrointestinal disorders, protecting against gastric ulcers and inflammation.  [3.] 

Low plasma glycine levels associated with obesity, T2DM, and NAFLD.  [2.] 

Additionally, glycine has anticancer properties, inhibiting tumor growth and supporting vascular health.  [20.] 

Glycine Deficiency Symptoms: How Do I Know If I Have Low Glycine?

While glycine is a non-essential amino acid, meaning it can be synthesized by the body, deficiencies can still occur, leading to various adverse effects. 

Fatigue and Weakness  [4., 10., 11., 18.] 

Glycine plays a crucial role in the production of creatine, a compound essential for energy production in muscle cells. 

When glycine levels are insufficient, creatine synthesis may be impaired, leading to reduced energy availability and increased fatigue. 

Additionally, glycine deficiency can disrupt the body's ability to produce glutathione, an antioxidant that protects cells from oxidative stress, further contributing to feelings of weakness and exhaustion.

Impaired Cognitive Function  [19.] 

Glycine is an inhibitory neurotransmitter in the central nervous system, and its deficiency has been linked to cognitive impairments. 

Studies have suggested that glycine deficiency may contribute to the development of neurodegenerative diseases, such as Alzheimer's and Parkinson's, by disrupting neurotransmitter balance and exacerbating oxidative stress in the brain.  [19.] 

Mood Changes  [8.]

Glycine plays a role in regulating the activity of the N-methyl-D-aspartate (NMDA) receptor, which is involved in mood regulation and emotional processing. 

Glycine deficiency has been associated with mood disorders, such as depression and anxiety, as well as sleep disturbances.  Maintaining adequate glycine levels may help support a balanced mood and promote better sleep quality.

Muscle Loss and Impaired Growth/Repair  [9., 10.] 

As a component of collagen and a precursor for creatine synthesis, glycine is essential for muscle growth, repair, and maintenance. 

Glycine deficiency can lead to muscle wasting, impaired recovery from exercise, and stunted growth in children and adolescents.  Adequate glycine intake is crucial for supporting muscle health and development.

Glycine as a Biomarker

Glycine has gained significant attention as a potential biomarker for various health conditions, particularly in the context of metabolic disorders and cancer. 

Association with Obesity, Diabetes, and Liver Disease

Several studies have reported an inverse relationship between glycine levels and the risk of obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD).   [2.] 

Lower glycine concentrations in blood and urine have been observed in individuals with these metabolic disorders, suggesting that glycine deficiency may contribute to their development or progression.

Glycine testing may also be used to assess risk of developing these conditions.  

Lab Testing for Glycine

Test Information, Sample Collection and Preparation

Glutamine levels are commonly tested in blood or urine as part of a comprehensive amino acids panel.  Occasionally it is tested in the cerebrospinal fluid (CSF).  

Blood testing typically requires a venipuncture, and urine samples can be collected from the comfort of home.  

Fasting is often required prior to sample collection.  

Interpretation of Glycine Lab Test Results

Optimal Levels of Glycine

Glycine levels should be assessed within the context of an individual’s symptom picture and medical history.  

It is essential to consult with the laboratory company used for their recommended glycine levels.  

One laboratory company reports optimal levels of glycine in plasma as: 5-23 μmoles/dL  [15.] 

One laboratory company reports optimal levels of glutamine in urine as: 95-683 μM/g creatinine.  [16.] 

Clinical Significance of Elevated Levels of Glycine

Elevated glycine levels are often associated with glycine encephalopathy, which is characterized by abnormally high levels of the amino acid glycine in the plasma, cerebrospinal fluid (CSF), and other tissues.  [12.]

Significantly increased CSF-to-plasma glycine ratios are a hallmark finding.  

Clinical Significance of Decreased Levels of Glycine

Common causes of low glycine levels include:

Diabetes and Obesity:  [2.] 

Low glycine levels are observed in diabetes, NAFLD, and obesity.  This may be related to glycine's role in regulating glucose metabolism and insulin sensitivity.  

Hypothyroidism:  [6.] 

Glycine levels tend to be low in hypothyroidism, suggesting a potential link between glycine and thyroid function.

Depression: [7.] 

Clinically, low glycine levels are suspected in cases of depression.  This is likely due to glycine's role as an inhibitory neurotransmitter in the brain and its involvement in regulating mood and emotional processing.

Glycine Supplementation

Glycine Supplement Forms and Dosages

Glycine supplements are available in various forms including capsules, tablets, and powders. Typical dosages range from 3 to 10 grams per day, depending on the intended use and individual needs. 

It is essential to follow the recommended dosages and consult with a healthcare professional, especially for individuals with underlying medical conditions or taking medications.

Collagen Supplements as a Glycine Source

Collagen supplements, which are rich in glycine, can serve as an alternative source of this amino acid. Collagen peptides, hydrolyzed collagen, and bone broth are popular forms of collagen supplements that can provide glycine and other beneficial compounds for skin, joint, and bone health.

Safety and Potential Side Effects

Glycine is generally considered safe when consumed in recommended amounts. However, high doses or long-term use may cause side effects such as digestive discomfort, nausea, or headaches in some individuals. 

It is essential to consult with a healthcare professional before starting any supplement regimen, especially for individuals with pre-existing medical conditions or taking medications, as glycine may interact with certain drugs or treatments.

Frequently Asked Questions (FAQs) on Glycine

What Is Glycine?

Glycine is a non-essential amino acid, meaning the body can produce it naturally. It is the smallest amino acid with the simplest structure, consisting of a single hydrogen atom as its side chain.

What Is the Structure of Glycine?

Glycine has the chemical formula C2H5NO2. Its structure consists of an amino group (NH2), a carboxyl group (COOH), and a hydrogen atom attached to a central carbon atom, making it the simplest of all amino acids.

What Are the Benefits of Glycine?

Glycine offers several health benefits, including supporting protein synthesis, promoting healthy sleep patterns, enhancing cognitive function, and aiding in the production of collagen. It also has anti-inflammatory and antioxidant properties, contributing to overall health and well-being.

What Are Glycine Supplement Benefits?

Glycine supplements can help improve sleep quality, enhance cognitive function, support muscle growth and repair, and promote healthy skin and joints by aiding collagen production. 

They may also support liver health and help in the management of metabolic disorders.

What Are Glycine Deficiency Symptoms?

Although glycine is a non-essential amino acid, deficiency can occur in certain situations. Symptoms of glycine deficiency may include fatigue, cognitive impairment, poor wound healing, muscle weakness, and digestive issues. 

Severe deficiencies can impact collagen production and overall protein synthesis.

How Can Glycine Help with Sleep?

Glycine can improve sleep quality by lowering body temperature and promoting relaxation. It acts as an inhibitory neurotransmitter in the central nervous system, which can help induce sleep and improve sleep efficiency. 

Taking glycine before bedtime can enhance sleep quality and reduce daytime sleepiness.

What Is Glycine Used For?

Glycine is used for various purposes, including supporting cognitive function, improving sleep quality, aiding in muscle growth and repair, promoting healthy skin and joints, and supporting liver function. 

It is also used in medical settings for the treatment of certain metabolic disorders and as a component of intravenous nutrition.

How Should I Take Glycine Supplements?

Glycine supplements are available in various forms, including powders, capsules, and tablets. The typical dosage ranges from 1 to 3 grams per day, depending on individual needs and health goals. 

It is best to follow the dosage recommendations on the supplement label or consult with a healthcare provider for personalized advice.

Are There Any Side Effects of Glycine Supplements?

Glycine supplements are generally considered safe when taken at recommended doses. However, some individuals may experience mild side effects such as gastrointestinal discomfort, nausea, or drowsiness. 

It is important to start with a lower dose and gradually increase it to assess tolerance.

Can I Get Glycine from Food?

Yes, glycine is naturally found in high-protein foods such as meat, fish, dairy products, and legumes. Bone broth is an especially rich source of glycine due to the collagen content. 

Consuming a balanced diet with adequate protein can help maintain sufficient glycine levels.

Is Glycine Safe for Long-Term Use?

Glycine is generally considered safe for long-term use when taken at appropriate dosages. 

However, as with any supplement, it is important to consult with a healthcare provider, especially if you have underlying health conditions or are taking other medications.

Order Glycine Testing

Click here to compare testing options and order glycine testing as part of an amino acid panel.  

What's 
Glycine
?
Glycine is a simple, yet incredibly important amino acid that your body uses to build proteins, which are essential for virtually every function in your body. It's like the building block for your body's construction project! Glycine is also a key player in maintaining a healthy nervous system, as it helps transmit signals that control your brain's activities and mood. It's even involved in the production of DNA, the genetic material that makes you uniquely you. Plus, it supports your body's internal antioxidant system, helping to protect your cells from damage. In short, Glycine is a versatile little worker that plays a big role in keeping your body running smoothly.
If Your Levels Are High
High levels of glycine in your body could indicate a variety of things. For instance, it could mean that your body is working overtime to repair tissue or build new proteins, which is a normal response to things like intense exercise or injury. It could also suggest that your body is trying to protect itself from damage, perhaps due to exposure to toxins or stress. Certain medications, like antacids or antibiotics, can also increase glycine levels. On the other hand, high glycine could be a sign of a genetic condition called nonketotic hyperglycinemia, where the body can't break down glycine properly. This condition is rare, but it can lead to serious neurological problems. In any case, high glycine levels are a sign that something is affecting your body's normal processes.
Symptoms of High Levels
Symptoms of high levels of Glycine could include fatigue, difficulty concentrating, and muscle weakness. In severe cases, it may cause seizures, breathing difficulties, and developmental delays in children.
If Your Levels are Low
Low levels of glycine might mean your body isn't making enough proteins, which are crucial for pretty much everything your body does. This could affect your nervous system, which relies on glycine to help send important messages that regulate your brain's activities and mood. It could also impact the production of your DNA, which is what makes you, you. Additionally, glycine helps your body's internal defense system that protects your cells from harm. So, if you're not getting enough glycine, it could be due to factors like a poor diet, certain medications, or specific health conditions that affect your body's ability to produce or absorb this important amino acid.
Symptoms of Low Levels
Symptoms of low levels of Glycine could include fatigue, difficulty concentrating, mood changes, and issues with muscle growth or repair.

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See References

[1.] Aguayo-Cerón KA, Sánchez-Muñoz F, Gutierrez-Rojas RA, Acevedo-Villavicencio LN, Flores-Zarate AV, Huang F, Giacoman-Martinez A, Villafaña S, Romero-Nava R. Glycine: The Smallest Anti-Inflammatory Micronutrient. Int J Mol Sci. 2023 Jul 8;24(14):11236. doi: 10.3390/ijms241411236. PMID: 37510995; PMCID: PMC10379184.

[2.] Alves A, Bassot A, Bulteau AL, Pirola L, Morio B. Glycine Metabolism and Its Alterations in Obesity and Metabolic Diseases. Nutrients. 2019;11(6):1356. doi:https://doi.org/10.3390/nu11061356

[3.] Chen J, Yang Y, Yang Y, et al. Dietary Supplementation with Glycine Enhances Intestinal Mucosal Integrity and Ameliorates Inflammation in C57BL/6J Mice with High-Fat Diet-Induced Obesity. The Journal of Nutrition. 2021;151(7):1769-1778. doi:https://doi.org/10.1093/jn/nxab058

[4.] da Silva RP, Nissim I, Brosnan ME, Brosnan JT. Creatine synthesis: hepatic metabolism of guanidinoacetate and creatine in the rat in vitro and in vivo. Am J Physiol Endocrinol Metab. 2009 Feb;296(2):E256-61. doi: 10.1152/ajpendo.90547.2008. Epub 2008 Nov 18. PMID: 19017728; PMCID: PMC2645018.

[5.] de Bartolomeis A, Manchia M, Marmo F, Vellucci L, Iasevoli F, Barone A. Glycine Signaling in the Framework of Dopamine-Glutamate Interaction and Postsynaptic Density. Implications for Treatment-Resistant Schizophrenia. Frontiers in Psychiatry. 2020;11. doi:https://doi.org/10.3389/fpsyt.2020.00369

[6.] Friedrich N, Pietzner M, Cannet C, Thuesen BH, Hansen T, Wallaschofski H, Grarup N, Skaaby T, Budde K, Pedersen O, Nauck M, Linneberg A. Urinary metabolomics reveals glycemic and coffee associated signatures of thyroid function in two population-based cohorts. PLoS One. 2017 Mar 2;12(3):e0173078. doi: 10.1371/journal.pone.0173078. PMID: 28253303; PMCID: PMC5333857.

[7.] Gammoh O, Aljabali AAA, Tambuwala MM. Plasma amino acids in major depressive disorder: between pathology to pharmacology. EXCLI J. 2024 Jan 4;23:62-78. doi: 10.17179/excli2023-6767. PMID: 38357097; PMCID: PMC10864705.

[8.] Hoekstra R, Fekkes D, Loonen AJ, Pepplinkhuizen L, Tuinier S, Verhoeven WM. Bipolar mania and plasma amino acids: increased levels of glycine. Eur Neuropsychopharmacol. 2006 Jan;16(1):71-7. doi: 10.1016/j.euroneuro.2005.06.003. Epub 2005 Jul 15. PMID: 16023835.

[9.] Lizzo G, Migliavacca E, Lamers D, et al. A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. Frontiers in Aging. 2022;3. doi:https://doi.org/10.3389/fragi.2022.852569

[10.] Lizzo G, Muller K, Thevenet J, et al. Effects of Glycine Supplementation on Mitochondrial Function and Protein Degradation in Skeletal Muscle of Old Mice. Innovation in Aging. 2021;5(Supplement_1):1001-1001. doi:https://doi.org/10.1093/geroni/igab046.3592

[11.] McCarty MF, O'Keefe JH, DiNicolantonio JJ. Dietary Glycine Is Rate-Limiting for Glutathione Synthesis and May Have Broad Potential for Health Protection. Ochsner J. 2018 Spring;18(1):81-87. PMID: 29559876; PMCID: PMC5855430.

[12.] Orphanet: Glycine encephalopathy. www.orpha.net. Accessed June 13, 2024. https://www.orpha.net/en/disease/detail/407

[13.] Rajendra S, Lynch JW, Schofield PR. The glycine receptor. Pharmacol Ther. 1997;73(2):121-46. doi: 10.1016/s0163-7258(96)00163-5. PMID: 9131721.

[14.] Razak MA, Begum PS, Viswanath B, Rajagopal S. Multifarious Beneficial Effect of Nonessential Amino Acid, Glycine: A Review. Oxid Med Cell Longev. 2017;2017:1716701. doi: 10.1155/2017/1716701. Epub 2017 Mar 1. Erratum in: Oxid Med Cell Longev. 2022 Feb 23;2022:9857645. doi: 10.1155/2022/9857645. PMID: 28337245; PMCID: PMC5350494.

[15.] Rupa Health.  Amino Acids Plasma Sample Report.pdf. Google Docs. Accessed June 13, 2024. https://drive.google.com/file/d/1oiUyp-9bEoPjTeuu2z19S94ALcqU4clm/view

[16.] Rupa Health.  Amino Acids Urine Sample Report.pdf. Google Docs. Accessed June 13, 2024. https://drive.google.com/file/d/1yMBkuBV2PUDH5D-S4al7bSLgK6UzoYMZ/view

[17.] Salceda R. Glycine neurotransmission: Its role in development. Front Neurosci. 2022 Sep 16;16:947563. doi: 10.3389/fnins.2022.947563. PMID: 36188468; PMCID: PMC9525178.

[18.] Schirinzi E, Ricci G, Torri F, Mancuso M, Siciliano G. Biomolecules of Muscle Fatigue in Metabolic Myopathies. Biomolecules. 2023 Dec 30;14(1):50. doi: 10.3390/biom14010050. PMID: 38254650; PMCID: PMC10812926.

[19.] Ullah R, Jo MH, Riaz M, Alam SI, Saeed K, Ali W, Rehman IU, Ikram M, Kim MO. Glycine, the smallest amino acid, confers neuroprotection against D-galactose-induced neurodegeneration and memory impairment by regulating c-Jun N-terminal kinase in the mouse brain. J Neuroinflammation. 2020 Oct 15;17(1):303. doi: 10.1186/s12974-020-01989-w. PMID: 33059700; PMCID: PMC7566050.

[20.] Yamashina, S., Kenichi Ikejima, Rusyn I, Sato N. Glycine as a potent anti‐angiogenic nutrient for tumor growth. Journal of gastroenterology and hepatology. 2007;22(s1). doi:https://doi.org/10.1111/j.1440-1746.2006.04655.x

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