Sarcosine, also known as N-methylglycine, is a naturally occurring compound studied for its role in human biochemistry and its potential influence on brain function. It is classified as a non-proteinogenic amino acid derivative, meaning it is not a building block for proteins but an intermediate molecule in metabolic processes. Understanding sarcosine involves examining its chemical structure, how the body manages it, and its specific interactions with the brain’s signaling systems. This article details what sarcosine is, its metabolic journey, its mechanism of action, and the current state of clinical investigation.
Defining Sarcosine and its Natural Presence
Sarcosine is chemically a methylated derivative of the amino acid glycine, formed when a methyl group is attached to the nitrogen atom. This structural difference allows it to participate in biological roles distinct from glycine. It is an endogenous molecule, meaning the human body produces it internally, primarily as an intermediate in several metabolic pathways.
Trace amounts are present in human tissues, particularly skeletal muscles and the prostate. Sarcosine is also found in foods such as egg yolks, legumes, meats (turkey and ham), and various vegetables. However, the majority of sarcosine in the body results from internal metabolism.
The Metabolic Pathway of Sarcosine
Sarcosine acts as a transitional molecule in the body’s one-carbon metabolism. It is involved in the biochemical processes of choline and methionine, specifically serving as an intermediate in the pathway that converts choline into glycine. Sarcosine levels are regulated through enzymatic reactions that both create and break it down.
The enzyme glycine N-methyltransferase (GNMT) generates sarcosine by adding a methyl group to glycine. Conversely, sarcosine dehydrogenase (SARDH) degrades it back into glycine. This interconversion primarily occurs in the liver and kidneys. Sarcosine functions as a temporary storage form of glycine, helping to manage the flow of methyl groups and the balance of these amino acids.
Sarcosine’s Influence on Brain Signaling
Sarcosine influences the central nervous system primarily by inhibiting the Glycine Transporter 1 (GlyT-1). GlyT-1 is a protein located on glial cells near synapses, and its normal function is to regulate glycine concentration by removing it from the synaptic cleft. By blocking GlyT-1, sarcosine increases the concentration of glycine available in the space between neurons.
NMDA Receptor Modulation
This accumulation of glycine is important because glycine is a co-agonist for the N-methyl-D-aspartate (NMDA) receptor, a major type of glutamate receptor. The NMDA receptor requires both glutamate and a co-agonist (glycine or D-serine) to become fully activated. Increasing synaptic glycine availability enhances NMDA receptor function, promoting stronger glutamatergic transmission.
This enhancement of NMDA receptor signaling is the core biological mechanism underlying sarcosine’s effects on cognitive function and mood. The NMDA receptor system is implicated in processes like learning, memory, and synaptic plasticity, making its modulation a target for neurological and psychiatric conditions.
Clinical Investigation and Supplementation
The mechanism of boosting NMDA receptor function has made sarcosine a subject of clinical investigation. Research focuses on its potential as an adjunctive treatment for conditions characterized by NMDA receptor hypofunction. The most prominent area of study is schizophrenia, where NMDA receptor deficits are hypothesized to contribute to negative symptoms and cognitive impairment. Clinical trials have also explored sarcosine’s use in major depressive disorder, leveraging its ability to modulate glutamatergic signaling.
Dosage and Regulatory Status
Although many studies, particularly those concerning schizophrenia, have shown promising results, sarcosine is not currently approved as a medical treatment by regulatory bodies like the FDA. It is typically sold and used as a dietary supplement. Clinical trials investigating its effect in psychiatric conditions commonly use a standard dosage of 2 grams per day, often divided into two doses. Some studies explore a lower dose of 1 gram per day, especially if side effects like agitation or irritability are reported. Research remains ongoing to determine its long-term efficacy, safety profile, and optimal clinical application.