For Bibliography and Research Abstracts regarding Sarcosine and Schizophrenia

Sarcosine is currently the only available Glycine Transporter Type 1 Inhibitor and studies have show substantial benefits in treatment of schizophrenia.

For more on Sarcosine research and outcomes in schizophrenia please consider viewing the archived presentation:

“New Options in the Treatment of Negative and Cognitive Symptoms in Schizophrenia – PART 1” 

Sarcosine is a natural molecule that participates in critically important methylation cycles of human metabolism.  It is involved in glycine and choline metabolism and is found naturally in the food we eat.  Already considered a safe food-additive, Sarcosine is in many common household products.  It is highly non-toxic, even in significant concentrations.  Its safety profile, efficacy and lack of side effects make it a viable natural option for the treatment of schizophrenia.

Sarcosine – A Glycine Transporter Type 1 Inhibitor.

Sarcosine – a Glycine Transporter Type 1 Inhibitor used as a Natural Treatment for Schizophrenia

Benefits to Negative and Cognitive Symptoms

The potential benefits of Sarcosine in schizophrenia have been confirmed in three small but convincing double-blind placebo-controlled studies.  It was highly tolerable and significantly improved both the positive and negative symptoms of this illness.

Natural Glycine Enhancement

In addition to its role in methylation, Sarcosine acts as a Glycine Transporter Type 1 Inhibitor.  It likely helps to increase the availability of glycine at the synapse and extracellular space between neurons.  In combination with the neurotransmitter Glutamate, Glycine helps activate NMDA Receptors.  It is this effect that is believed to provide the benefits seen in schizophrenia research.

Please see NMDA Receptor Overview for more details on this receptor.

Glycine related treatments in schizophrenia have consistently shown benefits.  Sarcosine also breaks down into glycine, which may further increase concentrations of this amino acid and neurotransmitter in the brain.

A Note Regarding Clozapine

It is important to note that no significant benefits were shown when Sarcosine was given to patients taking Clozapine.  This consistent with other research on Glycine related treatment options in schizophrenia.  Clozapine is a distinct antipsychotic medication previously shown to erase the benefits of glycine treatments.  Clozapine may directly affect the glycine site on NMDA receptors, perhaps contributing to clozapine’s renowned efficacy in schizophrenia.

Research Studies

Sarcosine or D-Serine Add-on Treatment for Acute Exacerbation of Schizophrenia: a randomized, double-blind, placebo-controlled study.

Lane HY, Chang YC, Liu YC, Chiu CC, Tsai GE.  Arch Gen Psychiatry. 2005 Nov;62(11):1196-204

          Description:    Compared Sarcosine to both Placebo and D-Serine when added to Risperidone in patients with acute exacerbation of schizophrenia

          Design:  Six-week trial with 65 inpatients.  Double Blinded and Placebo Controlled.  Outcomes measure on PANSS, SANS-17 and SANS-20 schedules

          Considerations:  This study examined an NMDA Receptor modulation treatment in patients with acute symptom exacerbation by comparing the benefits of adding Sarcosine, D-Serine or Placebo to Risperidone in patients admitted to the hospital.  D-Serine had already shown benefits in treatment of schizophrenia.

           Results:  Sarcosine added to Risperidone significantly reduced symptom severity in many different arenas compared to placebo.  D-Serine was not effective in this study.  No significant side effects were seen.


A randomized, double-blind, placebo-controlled comparison study of sarcosine (N-methylglycine) and D-serine add-on treatment for schizophrenia.

Lane HY, Lin CH, Huang YJ, Liao CH, Chang YC, Tsai GE. Int J Neuropsychopharmacol. 2010 May;13(4):451-60.

          Description: Follow-up study compared symptomatic improvements with Sarcosine, D-serine or Placebo in patients with schizophrenia stable on Olanzipine, Risperidone or Quetiapine.

          Design:  Six-week trial with 60 stable patients on one of three atypical antipsychotics.  Study was Placebo-Controlled and Double Blinded.

          Considerations:  This was in many ways a follow-up study to the 2005 study by Lane et al., but included patients on Olanzipine and Quetiapine, as well as Risperidone.

          Results:   Sarcosine produced significant and substantial symptoms improvements compared to placebo.  Overall PANSS improvement with Sarcosine was 16.9%  (p<0.0052), over 4 times the improvement with placebo.  Results were significant for the Postive, Negative, Cognitive and Depressive symptom subscales.  Overall SANS improvement with Sarcosine was 18.6%  (p<0.021), over 3 times the improvement with placebo.  Results were significant for the Affect, Alogia, Apathy and Anhedonia symptom subscales.  Overall Quality of Life Questionnaire (QOL) improved by 26.4% (p<0.025), over 3 times the improvement with placebo.  This is a subjective survey filled out by patients.  Overall Global Assessment of Functioning (GAF) improved by 15.7% (p<0.042), almost 3 times the improvement with placebo.  This measures overall impression of improvement by the clinicians seeing the patients in the study.


Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to antipsychotics for the treatment of schizophrenia.

Tsai G, Lane HY, Yang P, Chong MY, Lange N. Biol Psychiatry. 2004 Mar 1;55(5):452-6.

          Description:  Compared reductions in symptoms due to Sarcosine vs Placebo when added to the antipsychotic regimen of stable outpatients.

          Design:  Six-week trial with 38 stable patients.  Double Blinded and Placebo Controlled.  Outcomes measure on PANNS, SANS and BPRS scales

          Considerations:  Patients were stable on antipsychotics for at least three months and were maintained through the study.  Approximately 1/3 of patients were using first generation antipsychotics (e.g., haloperidal, fluphenazine).  The rest were on Risperidone or Sulpiride (a second generation antipsychotic).  Positive outcomes were confirmed for Risperidone independently.

          Results:  Compared to placebo, Sarcosine significantly reduced symptoms in multiple categories when added to patient’s current neuroleptics.  No significant side effects were seen.

Researcher’s Words:  “Since there is no other neurotransmission site at which Sarcosine acts except the known GlyT-1 site, the effect of Sarcosine is likely due to its action on the GlyT-1.

“Superior to the other NMDA Glycine site agents, Sarcosine extends its therapeutic effects beyond the core symptoms of Schizophrenia.”

Schizophrenia and Sarcosine – Bibliography and Research Abstracts

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