What Not to Take with Glycine: A Comprehensive Guide to Safe Supplementation

November 10, 2025 •

4 min read

While glycine is generally considered safe for most healthy adults, it can cause moderate to significant interactions with certain medications, including the antipsychotic clozapine. Knowing what not to take with glycine is crucial for preventing adverse effects and ensuring the supplement's safety and efficacy.

Quick Summary

A review of potential negative interactions between glycine and various medications. It highlights specific drugs like clozapine and discusses general classes such as sedatives, muscle relaxants, and blood pressure medication.

Key Points

Clozapine (Clozaril): Do not take glycine with this antipsychotic, as it can decrease the medication's effectiveness.
CNS Depressants: Exercise caution with sedatives, muscle relaxants, and benzodiazepines, as glycine can enhance their sedative effects.
Blood Pressure Medications: Glycine may lower blood pressure, potentially enhancing the effects of antihypertensive drugs and requiring medical monitoring.
Cardiac Glycosides: Avoid combining glycine with drugs like digoxin, as it can increase the risk of adverse effects.
Pre-Existing Conditions: Caution is necessary for individuals with liver/kidney disease, epilepsy, or a history of stroke, and for pregnant or breastfeeding women.
Consult a Doctor: Always talk to a healthcare provider before adding glycine, especially if you take other medications or have underlying health issues.
Monitor for Side Effects: Watch for increased drowsiness, nausea, stomach upset, or changes in your medication's effectiveness.

Major Drug Interactions to Avoid

Certain combinations of glycine with other substances can lead to moderate or significant interactions, impacting either the effectiveness of the medication or increasing the risk of adverse side effects. It is paramount to consult a healthcare provider before combining glycine with any of the following:

Clozapine (Clozaril)

This is one of the most well-documented and severe interactions involving glycine. Clozapine is a powerful antipsychotic medication used primarily to treat schizophrenia. Taking glycine concurrently might decrease the effectiveness of clozapine, potentially compromising treatment outcomes. The exact mechanism for this interaction is not fully understood, but because of the potential risk, healthcare professionals strongly advise against combining these two substances.

Central Nervous System (CNS) Depressants

Glycine acts as an inhibitory neurotransmitter in the central nervous system, which helps produce a calming effect. When taken alongside other CNS depressants, this effect can be enhanced, leading to excessive sedation, drowsiness, dizziness, or even respiratory depression. This category includes several medication types:

Sedatives: Medications prescribed for sleep or anxiety, such as benzodiazepines.
Muscle Relaxants: Drugs like baclofen can have their sedative effects amplified by glycine.
Antipsychotics (General): Beyond clozapine, other antipsychotics may also experience altered efficacy or side effects when combined with glycine.

Cardiac Glycosides

DrugBank lists several cardiac glycosides, which are used to treat heart failure and certain irregular heartbeats, as having an increased risk of adverse effects when combined with glycine. These include:

Acetyldigitoxin
Deslanoside
Digitoxin
Digoxin

The potential for increased adverse effects means this combination should be treated with extreme caution and only under strict medical supervision.

Cautionary Combinations and Considerations

Even with less severe interactions, exercising caution is wise to avoid unintended side effects or reduced treatment efficacy.

Antidepressants and Antiepileptics

Glycine may interact with certain antidepressants, such as fluoxetine, and antiepileptics, like valproic acid. These interactions could potentially alter the efficacy of these medications or increase the risk of side effects, such as sedation or gastrointestinal discomfort. Individuals with epilepsy should also be cautious, as glycine's influence on neurotransmitter activity could potentially trigger seizures in susceptible people.

Blood Pressure Medications

Glycine has demonstrated a blood-pressure-lowering effect in some studies. For individuals already taking antihypertensive medications, this could lead to an additive effect, causing blood pressure to drop too low. Close monitoring of blood pressure levels is recommended in this scenario.

Other Amino Acids

As an amino acid, glycine competes with other amino acids for absorption in the gastrointestinal tract. For individuals on high-protein diets or taking other amino acid supplements, this competition could potentially influence absorption rates.

Glycine Interaction Comparison Table


Interaction Category	Glycine Effect	Potential Risk	Action Required
Clozapine	Decreases medication effectiveness.	Treatment compromise, uncontrolled symptoms.	Avoid combination completely.
CNS Depressants	Enhances sedative effects.	Excessive drowsiness, dizziness, respiratory issues.	Use with extreme caution under medical supervision.
Cardiac Glycosides	Increases risk of adverse effects.	Enhanced side effects related to the heart.	Avoid combination completely.
Blood Pressure Meds	Can lower blood pressure further.	Hypotension (blood pressure dropping too low).	Monitor blood pressure closely with a doctor's guidance.
Antidepressants	May alter medication efficacy or side effects.	Reduced efficacy, increased sedation or GI issues.	Consult a healthcare provider.
Other Amino Acids	Competes for absorption.	May affect overall amino acid absorption.	Be mindful of intake, discuss with a doctor.

Who Should Exercise Extra Caution with Glycine?

Beyond specific medication interactions, certain populations should be particularly cautious or avoid glycine supplementation altogether:

Pregnancy and Breastfeeding: There is insufficient reliable information on safety for these groups. It is best to avoid use to be on the safe side.
Liver and Kidney Disease: These organs play a crucial role in metabolism and clearance. Caution is advised, especially in severe cases, and regular monitoring may be necessary for liver issues.
Stroke Patients: Individuals who have had a stroke should not take glycine without supervision from a doctor.
Epilepsy: Due to glycine's impact on neurotransmitter activity, those with epilepsy should use caution.
Allergies: Individuals with known allergies to glycine should avoid it.

How to Minimize Risk When Taking Glycine

To ensure safe supplementation and minimize risks, consider these key steps:

Consult Your Healthcare Provider: This is the most important step. Always discuss any new supplement with a doctor or qualified health professional, especially if you have pre-existing conditions or are taking other medications.
Monitor Your Body: Be aware of any changes in side effects from current medications, or the appearance of new symptoms like excessive drowsiness, stomach discomfort, or dizziness.
Follow Dosage Recommendations: Stick to the recommended dosage, typically up to 6 grams daily for short periods, unless otherwise advised. High doses can increase the risk of side effects.

For more information on supplement safety, you can consult reliable sources like the Office of Dietary Supplements at the National Institutes of Health.

Conclusion

While glycine is a valuable amino acid with potential benefits for sleep, muscle health, and metabolic support, it is not without risks when combined with certain medications. Significant interactions exist with antipsychotics, particularly clozapine, and caution is needed with CNS depressants and cardiac medications. Vulnerable populations like pregnant women and those with liver or kidney issues must also be careful. By understanding what not to take with glycine and consulting a healthcare professional, individuals can make informed decisions and supplement safely.

Frequently Asked Questions

Glycine should not be taken with the antipsychotic clozapine. It should also be used with caution alongside sedatives, muscle relaxants, some antidepressants, antiepileptics, blood pressure medications, and cardiac glycosides.

You should use caution when combining glycine with blood pressure medication. Glycine can have a blood-pressure-lowering effect, which might cause an additive effect with your medication and drop your blood pressure too low. Monitor your levels closely with your doctor's guidance.

No, it is not always safe. Because glycine has a calming effect, combining it with other sedatives, including prescription sleep medication, can lead to excessive drowsiness and other side effects. Consult your doctor before combining them.

The main risk of taking glycine with clozapine is that glycine may decrease the effectiveness of the antipsychotic medication. This could compromise the treatment for schizophrenia. This combination should be avoided completely.

Due to a lack of reliable safety information, it is generally advised to avoid using glycine during pregnancy and breastfeeding. Stay on the safe side and consult a healthcare provider.

There are no specific foods you should avoid with glycine. However, be mindful that glycine competes with other amino acids for absorption, so if you are on a very high-protein diet or take other amino acid supplements, this could affect absorption.

Besides those on interacting medications, caution is advised for individuals with severe liver or kidney disease, those who have had a stroke, and people with epilepsy. Known allergies are also a contraindication.