Understanding What Causes Glycine Deficiency?

October 6, 2025 •

5 min read

While our bodies can produce glycine, a non-essential amino acid, studies show that endogenous production may not always be sufficient to meet metabolic needs, especially during certain health conditions. A variety of factors can contribute to glycine deficiency, from metabolic issues and high body demand to dietary imbalances.

Quick Summary

Glycine deficiency stems from a combination of metabolic conditions such as diabetes and obesity, low dietary intake, heightened bodily demand, and underlying genetic factors that impair the body's production or increase its consumption of this amino acid.

Key Points

Conditionally Essential: Glycine, while endogenously produced, can become conditionally essential during metabolic stress, pregnancy, and other high-demand states when the body's synthesis is insufficient.
Metabolic Links: Conditions like obesity, type 2 diabetes, and insulin resistance are consistently associated with lower circulating glycine levels, often due to impaired synthesis and increased catabolism.
Dietary Factors: Inadequate protein intake, such as that found in some low-protein or vegan diets, can reduce the precursors needed for glycine synthesis. Conversely, higher meat intake might increase dietary glycine but not always plasma levels, indicating complex metabolic interactions.
Genetic and High-Demand Causes: Glycine deficiency can result from genetic mutations affecting its metabolic pathways or periods of high physiological demand, such as late-stage pregnancy, rapid growth in childhood, and increased detoxification processes.
Broad Symptoms: A glycine deficit can manifest as sleep problems, weakened muscle strength, slow wound healing, 'brain fog,' and digestive issues due to impaired production of collagen, antioxidants, and neurotransmitters.

The Crucial Role of Glycine

Glycine, the smallest and simplest amino acid, plays a multifaceted and vital role in numerous biological processes. Despite being non-essential because the body can synthesize it, research suggests that during certain physiological states and diseases, glycine becomes conditionally essential, meaning the body's requirements outpace its production.

Its key functions include acting as a building block for proteins, particularly collagen, which constitutes a large portion of the body’s total protein. Glycine is also critical for the synthesis of other important molecules like glutathione, a powerful antioxidant, and creatine, which provides energy to muscles. Furthermore, it serves as an inhibitory neurotransmitter in the central nervous system, calming the brain and promoting restful sleep. Impaired production or increased consumption of this essential amino acid can thus have far-reaching effects on overall health.

What causes glycine deficiency?

Several distinct but often interconnected factors can lead to inadequate glycine levels in the body. These can be broadly categorized into dietary factors, metabolic conditions, periods of high demand, and genetic variations.

Dietary Influences

While dietary intake only accounts for a fraction of the body's total glycine flux, it is a key determinant, especially when other factors come into play.

Low Protein Intake: A diet low in protein, such as some vegetarian or vegan diets, can reduce the intake of non-essential amino acids, including those needed for glycine synthesis. Studies have observed lower plasma glycine concentrations in meat-eaters compared to vegans, but the overall intake of glycine may be higher in meat-eaters due to higher total protein. However, the lower circulating levels in meat-eaters may point to a more complex interplay between protein sources and metabolic pathways.
Collagen-Poor Diet: Foods containing collagen and gelatin, such as bone broth and organ meats, are rich sources of glycine. A diet lacking these items can contribute to lower overall glycine intake. The average daily intake from food is typically 2-4 grams.

Metabolic and Pathophysiological Conditions

Metabolic diseases often involve altered amino acid metabolism, which can lead to lower circulating glycine levels.

Diabetes and Insulin Resistance: Consistently lower plasma glycine levels have been reported in individuals with type 2 diabetes and insulin resistance, including those with obesity and non-alcoholic fatty liver disease (NAFLD). This is partly due to impaired endogenous synthesis of glycine, which may be a result of a deficit in l-serine, a primary precursor for glycine production. Elevated glucagon can also increase glycine catabolism in these conditions.
Obesity: Studies show a strong inverse association between plasma glycine concentration and insulin resistance, common in obesity. This may be driven by reduced glycine synthesis, altered gut microbiota composition, or increased glycine consumption due to systemic inflammation.
Increased Detoxification Needs: The body uses glycine to conjugate and detoxify certain substances, including benzoic acid and other xenobiotics. High exposure to these substances, either through food additives or environmental toxins, can significantly deplete the body's glycine pool.

Increased Physiological Demand

In some life stages, the body's demand for glycine dramatically increases, which can outstrip the rate of synthesis.

Pregnancy: During late gestation, the fetus requires large amounts of glycine for growth, and pregnant individuals may experience a drop in plasma glycine concentration as their bodies struggle to keep up with the demand. Studies in pregnant adolescent girls have shown impaired endogenous glycine synthesis, potentially affecting infant growth.
Childhood Malnutrition: Growing children and preterm infants have significantly higher requirements for glycine for normal growth and metabolism. Inadequate nutritional intake in these stages can quickly lead to deficiency.

Genetic Variations

Certain genetic disorders can directly affect glycine metabolism, causing deficiency even with adequate dietary intake.

PHGDH Deficiency: A defect in the 3-phosphoglycerate dehydrogenase (PHGDH) enzyme, which is crucial for the synthesis of l-serine from glucose, can lead to decreased levels of both l-serine and glycine.
Glycine Transporter (GlyT1) Defects: Mutations in the SLC6A9 gene, which codes for the Glycine Transporter 1 (GlyT1) protein, can disrupt the transport and shuffling of glycine, potentially triggering glycine encephalopathy. This highlights the importance of proper glycine transport alongside production.

Symptoms and Implications of Glycine Deficiency

When glycine levels fall too low, the body redirects its limited supply to the most critical functions, such as brain activity and neurotransmission. This can impact less urgent but still important functions, leading to noticeable symptoms.

Common symptoms can include:

Sleep Problems: Glycine promotes restful sleep. Insufficient levels can cause insomnia, daytime fatigue, or a general feeling of being unrefreshed after waking.
Impaired Collagen Synthesis: As a key component of collagen, a glycine deficiency can lead to weakened connective tissues, affecting skin elasticity, joint health, and slow wound healing.
Muscle Weakness and Fatigue: Glycine is involved in protein synthesis and muscle repair. Low levels can manifest as muscle weakness, reduced endurance, and slower recovery after exercise.
Brain Fog and Cognitive Issues: As a neurotransmitter, glycine supports cognitive function. Inadequate levels can lead to difficulty concentrating, memory lapses, or general mental sluggishness.
Digestive Issues: Glycine helps maintain the gut lining. A deficiency may contribute to problems like indigestion, bloating, or leaky gut syndrome.

Dietary Strategies and Supplementation

For many, addressing glycine deficiency involves a combination of dietary modifications and, in some cases, supplementation. For metabolic and genetic conditions, medical supervision is essential.


Feature	Animal-Based Sources	Plant-Based Sources	Commentary
Typical Glycine Levels	High, especially in collagen-rich cuts like beef, chicken skin, and gelatin.	Lower overall compared to animal sources, but still present.	Vegan and vegetarian diets require careful planning to ensure sufficient intake, potentially through supplements.
Example Foods	Meat, poultry, fish, bone broth, dairy products.	Beans, lentils, soy products, nuts, seeds, spinach, cabbage.	While many plant foods contain glycine, the concentration is lower, and some, like rice, are richer than others.
Collagen Content	Excellent source, as glycine is a major component of collagen.	No dietary collagen. The body must synthesize all required collagen from amino acids.	Vegans rely on precursors and cofactors like vitamin C to produce their own collagen.
Supplement Options	Collagen peptides, gelatin supplements.	Synthetic or fermented glycine powders and capsules.	Most supplements provide a readily available and concentrated source of pure glycine.

Conclusion

Glycine deficiency is a multifaceted issue that can arise from inadequate dietary intake, various metabolic diseases, periods of high physiological demand, or genetic predispositions. While often regarded as non-essential, a sufficient supply is critical for numerous bodily functions, including collagen synthesis, antioxidant protection, and neurological health. For individuals with conditions like diabetes, obesity, or in late gestation, the body's production may be outpaced by demand, necessitating dietary or supplemental intervention. A balanced, protein-rich diet that incorporates a variety of glycine sources, particularly bone broth, meat, and legumes, is key to maintaining adequate levels. In cases of diagnosed deficiency, supplementation may be recommended by a healthcare provider. Ultimately, understanding the causes behind insufficient glycine levels is the first step toward effective management and improving overall metabolic health.

Authoritative Reference

Review Glycine as a conditionally essential amino acid and its relation with metabolic diseases: A comprehensive review on the conditional essentiality of glycine and its association with metabolic disorders like diabetes, insulin resistance, and NAFLD.

Frequently Asked Questions

A vegan or vegetarian diet can contribute to a lower intake of glycine, as it is found in high concentrations in animal products like collagen and meat. While plant-based foods contain some glycine, they are typically less concentrated, and vegans may consume less overall. However, the body can adapt, and a well-planned vegan diet can provide sufficient precursors for glycine production.

Lower plasma glycine levels are consistently observed in individuals with insulin resistance, obesity, and type 2 diabetes. The deficiency is linked to impaired glycine synthesis, often due to a lack of the precursor l-serine, and increased breakdown stimulated by elevated hormones like glucagon.

Glycine is a major component of collagen, which is vital for skin elasticity. If your body's glycine production is insufficient, your collagen synthesis can be compromised. Supplementation may help, especially if you have insufficient dietary intake, but consulting a healthcare provider is recommended to determine the best course of action.

The body uses glycine in conjugation, a key detoxification process that makes certain substances easier to excrete. High exposure to xenobiotics or dietary polyphenols can increase the demand for glycine for detoxification, potentially depleting the body's metabolic pool.

Yes, during late gestation, the fetal demand for glycine increases substantially for growth and development. This can cause a decrease in maternal plasma glycine concentrations, and impaired endogenous production has been observed in some cases.

Common symptoms of low glycine levels include sleep problems (difficulty falling or staying asleep), muscle weakness, slower wound healing, mental sluggishness or 'brain fog,' and digestive discomfort.

Yes, genetic factors can cause glycine deficiency. For example, mutations in enzymes responsible for synthesizing glycine from precursors like l-serine can lead to low levels. Other genetic conditions can also affect glycine transport and metabolism.