Sarcosine – An Overview
Sarcosine (N-methylglycine) is a precursor and derivative of the amino acid glycine. Physicians primarily prescribe sarcosine for treating schizophrenia, although it may also have some nootropic benefits for:
Sarcosine works by activating the NMDA (N-methyl-D-aspartate) receptor. Researchers believe that it achieves most of its therapeutic effects through this mechanism.1Harsing LG Jr, et al. Glycine transporter type-1 and its inhibitors Journal or Curr Med Chem. 2006
The body produces it by turning dietary choline into glycine, or by breaking down methionine to glycine.
It is a non-toxic compound that you can find in certain foods, such as meat, eggs, and vegetables.
Sarcosine is also an additive in toothpaste because it can prevent cavities, and is responsible for its foaming action.
What Does Sarcosine Do?
This nootropic has multiple uses related to mental health.
Sarcosine For Schizophrenia
The major use for sarcosine is for treating symptoms of schizophrenia. This is most likely because schizophrenia is at least partially caused by malfunctioning NMDA and glycine receptors.
Multiple clinical trials show it can be effective in combination with other antipsychotics in treating this disorder.2Lane HY, et al. Sarcosine or D-serine add-on treatment for acute exacerbation of schizophrenia: a randomized, double-blind, placebo-controlled study Arch Gen Psychiatry. 20053Nancy C. Andreasen. The Scale for the Assessment of Negative Symptoms (SANS): Conceptual and Theoretical Foundations British Journal Of Psychiatry. 19894Singh SP, Singh V. Meta-analysis of the efficacy of adjunctive NMDA receptor modulators in chronic schizophrenia CNS Drugs. 2011
Patient who received sarcosine treatment showed significant improvements in their general psychiatric symptoms across the board.
Researchers noted that sarcosine was well-tolerated, and no significant side effects were noted.
The significant improvement with the sarcosine further supports the hypothesis of N-methyl-D-aspartate receptor malfunction in schizophrenia.
This seems to be the most promising avenue for treating this condition.5Tsai G, et al. Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to antipsychotics for the treatment of schizophrenia Biol Psychiatry. 2004
In fact, sarcosine has been widely used in clinical trials of schizophrenia and other disorders, and is considered the “gold standard” for assessing antipsychotic treatment efficacy.6Mark G.A. Opler, et al. Positive and Negative Syndrome Scale (PANSS) Training Challenges, Solutions, and Future Directions Innov Clin Neurosci. 2017
Sarcosine For Depression
Sarcosine is generally considered an antipsychotic, but there is also evidence that it can also treat depression symptoms. At least, it may help with depression in the context of schizophrenia.
There is currently not enough evidence to show its full effectiveness, but there is some preliminary evidence nonetheless.
According to recent research, the NMDA receptor, a subtype of glutamate receptors, plays an important role in the neurobiology and treatment of Major Depressive Disorder. Sarcosine has been shown to affect this receptor.7Dang YH, et al. Targeting of NMDA receptors in the treatment of major depression Curr Pharm Des. 2014
Some trials show sarcosine can improve depression-like behaviors in rodent models and in human patients. Researchers suspect that glycine transporter-I inhibition could be a novel treatment for depression, although we do need further human studies to confirm this further.8Huang CC, et al. Inhibition of glycine transporter-I as a novel mechanism for the treatment of depression Biol Psychiatry. 2013
Sarcosine For OCD
There is also some preliminary evidence that sarcosine may treat obsessive and compulsive behaviors through its action on the NMDA and glycine channels in the brain.
Current research points to the NMDA system being a major factor in how OCD manifests.9Papouin T, et al. Synaptic and extrasynaptic NMDA receptors are gated by different endogenous coagonists Cell. 2012
A study of 25 patients taking a sarcosine treatment showed that it can achieve a fast therapeutic effect in some OCD patients. This study supports the glycine transporter-1 as a novel target for developing new OCD treatment.10Wu PL, et al. Sarcosine therapy for obsessive compulsive disorder: a prospective, open-label study J Clin Psychopharmacol. 201111Chan MH, et al. Sarcosine attenuates toluene-induced motor incoordination, memory impairment, and hypothermia but not brain stimulation reward enhancement in mice Toxicol Appl Pharmacol. 2012
One study showed that sarcosine, taken in addition with a benzoate, significantly improved memory scores of people with schizophrenia.12Chun-Yuan Lin, et al. Adjunctive sarcosine plus benzoate improved cognitive function in chronic schizophrenia patients with constant clinical symptoms: A randomised, double-blind, placebo-controlled trial The World Journal of Biological Psychiatry. 2017
However, there have not been any studies regarding sarcosine’s ability to boost memory in otherwise healthy users. It is possible that it may have some nootropic benefit when taken this way, but more evidence is needed.
Sarcosine For Neuroprotection
Sarcosine may act as a neuroprotectant, being able to prevent damage from conditions such as stroke.
One study found that sarcosine could prevent damage from transient ischemic attack (stroke) in mice. Researchers suspect this could be due to its inhibitory effects on glycine receptors.13Huang B, et al. GlyT1 Inhibitor NFPS Exerts Neuroprotection via GlyR Alpha1 Subunit in the Rat Model of Transient Focal Cerebral Ischaemia and Reperfusion Physiol Biochem. 2016
There is also evidence that sarcosine can block the neurotoxicity of NMDA antagonists, such as glutamate. The buildup of excitatory transmitters such as glutamate can eventually damage neurons. Luckily, sarcosine seems to be able to modulate levels of these types of neurotransmitters.14Chaves C, et al. Glutamate-N-methyl-D-aspartate receptor modulation and minocycline for the treatment of patients with schizophrenia: an update Braz J Med Biol Res. 2009
How Sarcosine Works In The Brain
The enzyme sarcosine dehydrogenase metabolizes sarcosine into glycine. Glycine is an important inhibitory neurotransmitter that is necessary for proper cognitive functioning.15Sarcosine Wikipedia. 2019
The enzyme glycine-N-methyl transferase also generates sarcosine from glycine.
Sarcosine vs Glycine
Sarcosine is structurally similar to the naturally occurring amino acid glycine. This means it is capable of binding to the same receptor sites as glycine.16Hai Xia Zhang, et al. The glycine transport inhibitor sarcosine is an NMDA receptor co-agonist that differs from glycine J Physiol. 2009
Researchers believe that by binding to these receptors, sarcosine inhibits glycine uptake, which in turn agonizes NMDA receptors. This action seemingly improves NMDA function, and is most likely the source of sarcosine’s therapeutic effects.
According to current research “sarcosine may enhance NMDAR function by more than one mechanism and may have different effects from other NMDAR co-agonists.” This means that sarcosine’s particular benefits may be unique in some aspects.17Hai Xia Zhang, et al. The glycine transport inhibitor sarcosine is an NMDA receptor co-agonist that differs from glycine J Physiol. 2009
How Much Sarcosine Should I Take?
Most studies found that 1-2 grams a day was effective and well-tolerated in most test subjects.
Sarcosine Potential Side Effects
Sarcosine is generally well-tolerated. However, in high doses it may cause side effects like:
- Lack of sleep
There is also the potential that sarcosine can increase the possibility of prostate cancer, although the evidence on this is not conclusive.
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