How to Reduce Glycine Levels Safely and Effectively

November 21, 2025 •

4 min read

High glycine levels, a condition known as hyperglycinemia, is a hallmark symptom of the rare genetic disorder nonketotic hyperglycinemia (NKH). While this specific metabolic disorder is serious and requires professional medical management, other factors can also influence glycine levels, necessitating various approaches to address them effectively.

Quick Summary

This article explores strategies for lowering glycine levels, focusing on the rare genetic disorder nonketotic hyperglycinemia (NKH). It covers medical therapies like sodium benzoate, dietary adjustments such as low-protein and ketogenic diets, and lifestyle considerations, highlighting the importance of professional medical guidance.

Key Points

Medical Supervision is Key: Treatment for high glycine levels, especially due to genetic conditions like Nonketotic Hyperglycinemia (NKH), must be managed by a qualified healthcare provider.
Sodium Benzoate Therapy: This medication is a primary treatment that helps reduce glycine levels by facilitating its excretion through the kidneys.
Ketogenic Diet's Role: The ketogenic diet is an effective therapeutic strategy for some patients with NKH, as it can help lower plasma and brain glycine levels.
Dietary Protein Restriction: Limiting high-protein foods, particularly those rich in glycine like gelatin and bone broth, can help manage intake, but should be professionally supervised to avoid malnutrition.
Check Vitamin B6 Levels: A deficiency in Vitamin B6 can impair glycine metabolism, so ensuring adequate levels is important, though supplementation is not a primary treatment for genetic disorders.
Address Underlying Conditions: Issues like liver failure or metabolic disorders can influence glycine levels and must be addressed for effective management.

Understanding High Glycine Levels

Glycine is a non-essential amino acid that plays a critical role in numerous bodily functions, including protein synthesis and neurotransmission. However, excessive accumulation of glycine, particularly in the brain, can cause serious neurological problems. The most common cause is a deficient activity of the glycine cleavage enzyme system, often due to genetic mutations in the GLDC or AMT genes. In addition to genetic disorders, other factors like certain medications (such as valproate), liver failure, or excessive intake of glycine-containing solutions can lead to elevated levels. The severity and underlying cause dictate the treatment approach, emphasizing the importance of a proper diagnosis from a healthcare provider.

Symptoms of Elevated Glycine

Symptoms of high glycine levels can vary depending on the severity of the underlying condition and the individual's age. For infants with severe nonketotic hyperglycinemia (NKH), symptoms can be life-threatening and include profound lethargy, weak muscle tone, seizures, and breathing problems shortly after birth. In contrast, those with attenuated forms or other causes may experience milder or later-onset issues.

Neonatal Onset: Lethargy, coma, weak muscle tone (hypotonia), and seizures.
Infantile Onset: Developmental delay and seizures.
Later Onset (Attenuated NKH): Variable developmental progress, hyperactivity, or mild seizures.
Other Potential Symptoms (not exclusive to NKH): Nausea, dizziness, visual disturbances, and confusion have been reported, especially in cases of rapid or high-dose glycine administration.

Medical Interventions

Medical treatment for high glycine levels is typically managed by a team of specialists and depends on the specific cause. For inherited conditions like NKH, therapies are aimed at managing symptoms and reducing glycine concentrations.

Medications to Reduce Glycine

The most common medication used to lower glycine levels is sodium benzoate. It works by combining with glycine to form hippurate, which is then excreted by the kidneys. The dosage is carefully titrated to achieve target glycine levels, and effectiveness can be improved when combined with other therapies. For non-ketotic hyperglycinemia, medications like dextromethorphan or ketamine may also be used to mitigate the effects of excess glycine on neurotransmission. These are not over-the-counter solutions and require strict medical supervision.

Dietary Strategies

Dietary interventions play a significant role, particularly when addressing metabolic disorders like NKH, though they are not a standalone solution.

Low-Protein Diet

Since glycine intake is directly linked to protein consumption, a low-protein diet can help manage glycine levels in some cases. Foods particularly high in glycine, such as meat, gelatin, and bone broth, should be limited. In studies with healthy adults, a low-protein diet has been shown to reduce whole-body glycine flux and synthesis. However, this must be done under the guidance of a nutritionist or physician to prevent malnutrition and ensure a balanced intake of other essential nutrients.

The Ketogenic Diet

The ketogenic diet (KD) has been explored as a successful alternative or supplementary treatment for lowering glycine levels in patients with nonketotic hyperglycinemia. In this therapeutic approach, carbohydrate restriction forces the body to use endogenous glycine pools for gluconeogenesis, effectively reducing circulating glycine. Studies have shown that a ketogenic diet can lower plasma glycine levels more consistently than high-dose benzoate therapy alone. However, the ketogenic diet is complex and requires close medical and dietary supervision, especially for infants and children, to prevent nutritional deficiencies.

Comparison of Glycine Reduction Strategies

Different strategies exist for lowering glycine, with varying mechanisms, effectiveness, and risks. The choice depends heavily on the root cause and severity of the condition.


Feature	Low-Protein Diet	Ketogenic Diet (KD)	Sodium Benzoate Therapy
Mechanism	Limits dietary glycine intake.	Utilizes endogenous glycine for gluconeogenesis.	Binds glycine, forming hippurate for excretion.
Primary Use	Management of chronic conditions; supplementary therapy for NKH.	Effective adjunctive therapy for NKH, particularly for seizure control.	Standard therapy for NKH; effective at lowering plasma glycine.
Primary Risks	Nutritional deficiencies, particularly if not monitored by a professional.	Requires strict monitoring to prevent complications; can cause feeding intolerance.	Repugnant taste, gastric irritation, risk of accidental overdose.
Effect on Brain Glycine	Marginal benefit, as dietary glycine has a small contribution.	Shown to reduce brain glycine levels.	Also shown to reduce brain glycine levels.
Level of Supervision	Requires professional dietary and medical monitoring to prevent malnutrition.	High level of medical and dietary oversight is essential.	Requires close medical supervision, especially for dosage titration.

Lifestyle and Complementary Approaches

While not primary treatments for serious conditions, other factors can support overall metabolic health.

The Role of Vitamin B6

Vitamin B6 is a crucial cofactor for enzymes involved in one-carbon metabolism, which includes the glycine cleavage system. Studies have found that a vitamin B6 deficiency can lead to increased plasma glycine concentrations by impairing the activity of key enzymes. Therefore, ensuring adequate vitamin B6 status is important for normal glycine metabolism. However, B6 supplementation is not a treatment for inherited disorders, and excessive B6 can be toxic.

Managing Underlying Health

Addressing any underlying health conditions, such as liver or kidney issues, is vital for managing glycine levels. For metabolic syndrome and diabetes, which can impact glycine levels, maintaining a healthy lifestyle is key. A balanced diet, regular exercise, and stress management can help support overall metabolic function.

Conclusion

While a definitive cure for conditions like nonketotic hyperglycinemia does not exist, effective strategies for managing and reducing high glycine levels are available. The cornerstone of treatment for serious metabolic disorders involves medical therapies like sodium benzoate and, in some cases, the ketogenic diet, all under stringent medical supervision. For less severe cases or as part of a broader health strategy, dietary adjustments such as limiting high-protein foods can be beneficial. It is crucial to remember that any effort to lower glycine levels must be guided by a qualified healthcare provider to ensure safety and effectiveness.

For more detailed information on NKH and its management, you may consult authoritative sources such as the GeneReviews® publication from the National Center for Biotechnology Information.

Frequently Asked Questions

The most common cause of sustained, abnormally high glycine levels (hyperglycinemia) is a genetic defect in the glycine cleavage enzyme system, leading to a condition called nonketotic hyperglycinemia (NKH). Other less common causes include liver failure, certain medications like valproate, or transient issues in newborns.

A low-protein diet primarily works by limiting the amount of glycine ingested from food sources. A ketogenic diet, by restricting carbohydrates, forces the body to use stored energy sources, including endogenous glycine, for gluconeogenesis, which helps reduce overall levels more consistently.

No, you should not use supplements to lower glycine levels. In fact, high-dose glycine supplementation or other supplements could be harmful and worsen the condition. Management of high glycine is a serious medical issue that requires prescription medication and medical supervision.

Sodium benzoate works by conjugating with glycine, meaning it binds with it to form a new compound called hippurate. This hippurate is then excreted in the urine, helping to clear excess glycine from the body.

For genetic conditions like NKH, medical intervention is essential. While adjusting dietary intake by limiting high-glycine foods can be a supporting measure, it is not a standalone treatment. Any dietary changes should be made under medical supervision to ensure safety and prevent nutritional deficiencies.

The ketogenic diet, when used for metabolic disorders, carries risks such as nutritional deficiencies and can be difficult to manage, potentially causing feeding intolerance. It requires close monitoring by a specialized medical team to ensure proper nutrition and safety.

While persistently high glycine levels, especially with neurological symptoms, are a hallmark of serious metabolic disorders like NKH, temporary elevations can occur from other causes, such as transient hyperglycinemia in newborns or certain medications. A medical diagnosis is necessary to determine the cause and appropriate action.