Sarcosine
Summary
Sarcosine (N-methylglycine) blocks glycine reuptake and boosts NMDA receptor signalling. In schizophrenia, two meta-analyses of 2 g/day added to antipsychotics disagree: one found a moderate benefit, the other no overall effect, with gains limited to chronic, non-clozapine patients. Two small depression trials reported benefit. All trials were in psychiatric patients under medical care.
Key facts
- N-methylglycine, a natural amino acid derivative that inhibits the type 1 glycine transporter (GlyT1)[1][2]
- 2 g/day in every schizophrenia trial in the 2021 meta-analysis[1]
- Beat citalopram in a 6-week trial of 40 patients and improved results when added to SSRIs in 60 patients[3][4]
- Studied only as an add-on in diagnosed psychiatric illness, never as a general wellness supplement[1][4]
- 4 graded human outcomes on this page
- October 13, 2026
How it works
ProposedSarcosine inhibits the type 1 glycine transporter, raising glycine around NMDA glutamate receptors and enhancing their function. Reduced NMDA signalling is a proposed contributor to schizophrenia and depression. In the 2024 depression trial, serum glycine and BDNF rose more with sarcosine.[2][3][4]
What the human research says
Human trials only, one row per outcome. The form column shows what each trial actually tested. Grades follow our evidence-grading policy.
At a glance: strongest evidence per outcome
| Outcome | Grade | Effect | Strongest evidence | Rows |
|---|---|---|---|---|
| Schizophrenia | Grade C | Improved | Meta-analysis · n = 326 · 2020 | 2 rows |
| Depression | Grade D | Improved | RCT · n = 60 · 2024 | 2 rows |
Every graded row
| Outcome | Effect | Grade | Best evidence | PMID |
|---|---|---|---|---|
| Overall symptoms and cognition in schizophrenia | Improved | Grade C | Meta-analysis · n = 326 · 2020 Adults with schizophrenia in 7 double-blind RCTs Form: Sarcosine added to antipsychotics · Dose: Mostly 2 g/day · Duration: Varied (weeks) Sarcosine improved overall symptoms more than comparators (SMD 0.51, 95% CI 0.26 to 0.76), with larger effects in patients with stable symptoms. | 32122256 (opens PubMed)Source [2] |
| Symptom severity in schizophrenia | Mixed | Grade C | Meta-analysis · n = 234 · 2021 Adults with schizophrenia in 6 RCTs Form: Sarcosine added to antipsychotics · Dose: 2 g/day · Duration: 2 to more than 6 weeks No significant overall effect at any time point because of marked heterogeneity; in chronic schizophrenia and patients not on clozapine, symptom severity fell modestly after 6 weeks (SMD −0.36 and −0.31). | 33538213 (opens PubMed)Source [1] |
| Depression score (MADRS) when added to an SSRI | Improved | Grade D | RCT · n = 60 · 2024 Adults with major depressive disorder on SSRIs Form: Sarcosine added to an SSRI · Dose: Not stated in the abstract · Duration: 8 weeks MADRS fell by 13.3 points with sarcosine versus 8.7 with placebo (difference −4.6, 95% CI −7.5 to −1.7); response and remission rates were higher. | 39180989 (opens PubMed)Source [4] |
| Depression scores versus citalopram | Improved | Grade D | RCT · n = 40 · 2013 Adults with major depressive disorder Form: Sarcosine · Dose: Not stated in the abstract · Duration: 6 weeks Sarcosine improved Hamilton depression, clinical global impression and functioning scores more than citalopram, with faster remission and fewer dropouts; no significant side effects. | 23562005 (opens PubMed)Source [3] |
Forms
| Form | Elemental % | Absorption (human data) | GI tolerance | Studied for |
|---|---|---|---|---|
| Sarcosine (N-methylglycine) powder or capsules | Varies[1][3][4] | No human absorption data in the cited trials; serum glycine rose in the 2024 trial.[4] | Described as well tolerated in the schizophrenia trials and without significant side effects in the depression trials.[1][3][4] | Schizophrenia and depression add-on trials |
Studied doses
Doses studied in human trials ranged from 2,000 mg/day, the dose used in all six schizophrenia trials of the 2021 meta-analysis; the two depression trials (6 and 8 weeks) do not state their dose in the abstract.[1][3][4]
Interactions
Published interactions only: each row cites a source. No row means none was found in our sources, not that a combination is safe.
Medicines
- ClozapineReviewIn the 2021 meta-analysis, sarcosine reduced symptoms only in patients not taking clozapine; clozapine-treated patients did not benefit.[1]
- SSRI antidepressantsRCTSarcosine was given alongside SSRIs for 8 weeks in a trial that reported it as safe; long-term combination data are lacking.[4]
Who should be careful
- Schizophrenia, bipolar disorder or depression
- Every trial used sarcosine as an add-on under psychiatric supervision; it has not been tested as a replacement for prescribed treatment.[1][3][4]
- Prostate cancer
- A 2009 tissue and cell study found sarcosine rose as prostate cancer progressed, and adding sarcosine made benign prostate cells invasive in the lab. Whether sarcosine supplements affect prostate cancer has not been studied.[5]
Talk to your pharmacist or clinician before starting a supplement, especially if you take prescription medicines.
How to read the label
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Frequently asked questions
What is sarcosine?
N-methylglycine, a small amino acid derivative that raises glycine levels at NMDA receptors by blocking glycine reuptake.[2]
Does sarcosine help schizophrenia?
The evidence conflicts. One meta-analysis of 326 patients found a moderate benefit when added to antipsychotics; another of 234 found no overall effect, except in chronic patients not on clozapine.[1][2]
Does sarcosine help depression?
Two small trials (40 and 60 patients) reported benefit, one versus citalopram and one added to SSRIs. Larger trials are needed.[3][4]
Sources
- [1]Sarcosine as an add-on treatment to antipsychotic medication for people with schizophrenia: a systematic review and meta-analysis of randomized controlled trials.. Expert Opin Drug Metab Toxicol, 2021. meta-analysis
- [2]Efficacy and cognitive effect of sarcosine (N-methylglycine) in patients with schizophrenia: A systematic review and meta-analysis of double-blind randomised controlled trials.. J Psychopharmacol, 2020. meta-analysis
- [3]Inhibition of glycine transporter-I as a novel mechanism for the treatment of depression.. Biol Psychiatry, 2013. RCT
- [4]Efficacy and safety of add-on sarcosine in patients with major depressive disorder: A randomized controlled trial.. J Psychiatr Res, 2024. RCT
- [5]Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression.. Nature, 2009. animal-study
What changed
- Independent adversarial review: added a prostate-cancer caution (2009 tissue/cell study linking sarcosine to invasiveness), repaired the studied-dose sentence and noted that the 2020 meta-analysis comes from the group behind several included trials. All PMIDs re-verified.
- Adversarial second pass: every PMID re-checked against NCBI esummary (title, year, no retraction, erratum or expression-of-concern flags) and every number in each evidence row re-read against its PubMed abstract (PMC full text where the abstract lacked dose or duration). Countries and funding notes kept only where the abstract or full text states them; interactions listed only where a source supports them, otherwise stated as unstudied.
- First draft. Every PMID checked against NCBI E-utilities esummary (title and year taken from the record) and abstracts read for the cited rows.