What Happens If Glycine Is Too High? Causes, Symptoms, and Risks

November 18, 2025 •

3 min read

Affecting at least 1 in 76,000 newborns worldwide, nonketotic hyperglycinemia is a rare but severe genetic disorder where abnormally high glycine levels accumulate in the body. Here, we detail exactly what happens if glycine is too high, the serious health implications, and distinguish these from less severe issues caused by excess supplementation.

Quick Summary

Excessive glycine levels most often stem from a rare genetic disorder known as Nonketotic Hyperglycinemia, leading to severe neurological issues, especially in infants. Extremely high acute intake, typically from medical procedures, can cause temporary neurological and visual problems. Mild gastrointestinal side effects are possible with high supplemental doses.

Key Points

High Glycine Can Indicate Rare Genetic Disorders: The most serious cases of excess glycine are caused by inherited defects in the glycine cleavage system, leading to Nonketotic Hyperglycinemia (NKH).
Neurological Dysfunction Is a Primary Risk: Pathologically high glycine is neurotoxic, especially to the developing brain, causing severe symptoms like seizures, coma, and developmental delays.
High Supplemental Doses Cause Acute Toxicity: While not comparable to genetic disorders, very high acute intake (e.g., in medical settings) can lead to temporary side effects like nausea, confusion, and visual disturbances.
Medical Supervision is Crucial: Accurate diagnosis of conditions like NKH requires specialized testing of blood and cerebrospinal fluid, and management often involves medication and dietary changes.
Common Side Effects are Mild and Transient: For healthy individuals, moderate glycine supplementation is generally safe, with mild digestive issues or drowsiness being the most reported side effects from excessive intake.
Cause Determines Severity: The risk and symptoms of high glycine depend heavily on whether the cause is a severe genetic disorder, an acute medical event, or moderate supplementation.

What Is Glycine and Its Normal Function?

Glycine is the simplest amino acid, considered non-essential as the body can produce it. It is vital for various functions, including acting as an inhibitory neurotransmitter, contributing to protein and collagen synthesis, and supporting liver function. The body typically regulates glycine levels through the glycine cleavage system (GCS). Problems with this system or overwhelming its capacity can lead to high glycine.

The Serious Implications: Nonketotic Hyperglycinemia (NKH)

The most significant issue with pathologically high glycine is Nonketotic Hyperglycinemia (NKH), a rare genetic disorder caused by GCS enzyme deficiencies due to mutations in GLDC or AMT genes. This causes glycine to build up, particularly in the brain and cerebrospinal fluid.

Neonatal (Severe) Form This form appears shortly after birth with symptoms such as progressive lethargy, hypotonia, breathing difficulties, severe seizures, profound developmental delays, and feeding issues. The prognosis is often poor.

Attenuated (Milder) Form With some remaining GCS activity, this form presents later and is milder, though symptoms vary. Individuals may experience developmental delays, learning difficulties, hyperactivity, and potentially easier-to-control seizures. Some can develop walking and communication skills.

Other Causes of Elevated Glycine

Beyond NKH, other situations can cause high glycine, including very high doses during certain medical procedures (leading to glycine toxicity syndrome), acute liver failure impacting metabolic pathways, and side effects from medications like valproate.

Acute vs. Chronic High Glycine Symptoms

The symptoms of high glycine depend on the cause and how long levels are elevated:

Symptoms of Chronic Genetic Hyperglycinemia (NKH)

Severe lethargy and coma
Weak muscle tone and spasticity
Difficult-to-control seizures
Significant intellectual and developmental delays
Breathing pauses and respiratory failure
Problems with feeding

Symptoms of Acute High-Dose Glycine Toxicity

Nausea and vomiting
Dizziness and confusion
Temporary blindness or other vision issues
High blood ammonia leading to reduced consciousness
Weakness and unusual skin sensations

What About Glycine Supplementation?

For most healthy individuals, the body effectively manages and clears glycine from supplements. Doses up to 9 grams daily are generally well-tolerated with only mild, temporary side effects like stomach upset, mild nausea, diarrhea, or drowsiness.

Comparison: Genetic Hyperglycinemia vs. Supplemental Excess


Feature	Nonketotic Hyperglycinemia (NKH)	High-Dose Supplementation
Underlying Cause	Inherited genetic mutation in the glycine cleavage system	Exogenous intake overwhelming metabolic capacity
Severity	Often severe and life-threatening, especially in neonates	Generally mild and transient; severe effects are rare and typically associated with medical procedures
Accumulation Site	Builds up systemically, especially in the central nervous system (brain, CSF)	Primarily in the bloodstream; cleared efficiently by the body in most cases
Primary Symptoms	Severe neurological damage, developmental delays, seizures, apnea	Gastrointestinal upset, drowsiness, transient visual disturbances
Treatment	Glycine-lowering drugs (e.g., sodium benzoate), special diet, symptomatic control	Reduce dosage or discontinue supplement; severe toxicity requires immediate medical intervention

Diagnosis and Management

Diagnosing glycine metabolism disorders like NKH involves medical evaluation and tests such as blood and CSF analysis for glycine levels and ratio, genetic testing for GLDC or AMT mutations, and brain imaging. Management of NKH includes therapies to lower glycine and manage symptoms, often involving a multidisciplinary team. A ketogenic diet has shown promise in reducing plasma glycine in infants with NKH.

Conclusion

Elevated glycine is most concerning in the context of rare genetic disorders like Nonketotic Hyperglycinemia, leading to severe neurological issues. The term "too high" typically refers to this inherited condition rather than routine supplementation. For most healthy people, glycine supplements are safe, with potential mild digestive or drowsiness side effects at very high doses. Always consult a healthcare provider before starting supplements, particularly with suspected metabolic conditions or high dosages.

Nonketotic Hyperglycinemia - StatPearls - NCBI Bookshelf

Frequently Asked Questions

High doses of supplemental glycine are generally well-tolerated but can cause mild, transient side effects such as nausea, upset stomach, diarrhea, and drowsiness.

Dangerous glycine levels are typically not caused by diet alone, but rather by underlying genetic metabolic disorders like Nonketotic Hyperglycinemia (NKH). The body is efficient at processing dietary amino acids.

No. NKH is a rare, severe genetic disorder where the body cannot properly break down glycine, causing it to accumulate dangerously, especially in the brain. High glycine from supplements is usually transient and causes only mild side effects.

Diagnosis of pathological hyperglycinemia involves clinical evaluation, blood tests, cerebrospinal fluid (CSF) analysis to measure glycine levels, and often genetic testing to confirm underlying mutations in genes like GLDC or AMT.

When used in large quantities as an irrigating fluid during surgery, rapid absorption of glycine can lead to toxicity symptoms like confusion, dizziness, nausea, and, in severe cases, transient blindness.

In cases of Nonketotic Hyperglycinemia, neurological symptoms include severe lethargy, seizures, developmental delay, hypotonia (weak muscle tone), and breathing difficulties. Acute toxicity from high doses can cause confusion, dizziness, and visual disturbances.

Yes, research shows that a ketogenic diet can be an effective method for lowering plasma glycine levels in infants with Nonketotic Hyperglycinemia, though brain glycine levels may not fully normalize.