Sarcosine

• Cognitive function support
• Neurological health
• Mental health support
• Glutamatergic system modulation

• May improve negative symptoms in schizophrenia
• Potential antidepressant effects
• May reduce symptoms of OCD
• Supports NMDA receptor function
• May help with anxiety symptoms

Sarcosine (N-methylglycine) exerts its effects primarily through modulation of the glutamatergic system, which is the main excitatory neurotransmitter system in the central nervous system. The two principal mechanisms through which sarcosine acts are: 1) Inhibition of the glycine transporter type 1 (GlyT1): Sarcosine is a potent and selective inhibitor of GlyT1, which is responsible for removing glycine from the synaptic cleft. By blocking this transporter, sarcosine increases glycine levels in the synaptic cleft, particularly at glutamatergic synapses. 2) Enhancement of NMDA receptor function: The N-methyl-D-aspartate receptor (NMDAR) requires both glutamate and glycine (as a co-agonist) for full activation.

By increasing synaptic glycine levels through GlyT1 inhibition, sarcosine enhances NMDAR function. This is particularly relevant in conditions like schizophrenia, where NMDAR hypofunction is thought to play a significant role in the pathophysiology. In schizophrenia, sarcosine’s enhancement of NMDAR activity may help ameliorate negative symptoms and cognitive deficits, which are often poorly responsive to conventional antipsychotic medications. For depression, the mechanism appears paradoxical, as both NMDAR antagonists (like ketamine) and NMDAR enhancers (like sarcosine) show antidepressant effects.

This suggests that sarcosine may normalize glutamatergic transmission rather than simply increasing or decreasing it. In obsessive-compulsive disorder (OCD), sarcosine may help by modulating glutamatergic transmission in the cortico-striatal-thalamo-cortical circuits implicated in OCD pathophysiology. Additionally, sarcosine interacts with other neurotransmitter systems: it may indirectly affect dopaminergic transmission, as NMDAR function influences dopamine release in certain brain regions. There is also evidence of interaction with the serotonergic system, which may contribute to its effects on mood and anxiety.

Sarcosine is also involved in one-carbon metabolism as an intermediate in the conversion of choline to glycine, and it serves as a methyl group donor in various biochemical processes. This role in methylation pathways may contribute to its neurological effects beyond direct neurotransmitter modulation.

Based on clinical studies, the most commonly used dose of sarcosine is 2 grams per day, typically taken in divided doses.

However , some individuals may experience side effects at

this dose, and a lower dose of 1 gram per day may be better tolerated

while still providing benefits. The optimal dose may vary depending on the individual and the condition being addressed.

It ‘s important to note that

there is no officially established dosage range for sarcosine as

it is not FDA-approved for any medical condition.

Sarcosine is generally well-absorbed when taken orally. As a small, water-soluble amino acid derivative, it is absorbed primarily in the small intestine through amino acid transporters. Specific data on the exact absorption rate is limited, but it appears to have good bioavailability based on its clinical effects. Sarcosine can cross the blood-brain barrier, which is essential for its neurological and psychiatric effects.

Taking on an empty stomach may enhance absorption by reducing competition with other amino acids from food proteins, Dividing the daily dose (e.g., taking 1 gram twice daily instead of 2 grams once) may help maintain more consistent blood levels, Liposomal formulations may potentially improve bioavailability and brain penetration, though specific studies on liposomal sarcosine are limited, Sublingual administration might bypass first-pass metabolism, though this method is not well-studied for sarcosine, Micronized powder formulations may improve dissolution rate and potentially enhance absorption

For general use, sarcosine can be taken once or twice daily. For twice-daily dosing, taking doses approximately 12 hours apart may help maintain more consistent blood levels. Some clinical studies have administered sarcosine with meals to reduce potential gastrointestinal discomfort, though there’s no strong evidence that food significantly impairs absorption. For individuals using sarcosine for mental health conditions, consistent timing from day to day may help maintain stable effects.

Some users report that taking sarcosine earlier in the day is preferable, as it may have mild stimulating effects in some individuals that could potentially interfere with sleep if taken late in the evening. When used as an adjunct to psychiatric medications, it’s advisable to maintain a consistent schedule relative to the timing of other medications.

• Decreased need for sleep
• Hypomanic symptoms (elevated mood, increased libido, hyperactivity)
• Irritability
• Unpleasant inner tension
• Headaches
• Mild gastrointestinal discomfort
• Increased drive and activity (which may be unpleasant for some individuals)
• Anxiety or agitation (particularly at higher doses)
• Insomnia or sleep disturbances

• Bipolar disorder (due to potential risk of inducing hypomania or mania)
• History of psychosis (caution advised, though it has been used as an adjunct in schizophrenia)
• Prostate cancer (sarcosine is a potential biomarker for prostate cancer and may theoretically promote cancer cell invasiveness)
• Pregnancy and breastfeeding (due to insufficient safety data)
• Severe renal or hepatic impairment (due to limited data on metabolism and excretion)
• Children and adolescents (due to limited safety data in these populations)

• Antipsychotics: Sarcosine may have different interactions with different antipsychotics. It appears to enhance the effects of many antipsychotics but may not provide additional benefits when combined with clozapine
• Selective Serotonin Reuptake Inhibitors (SSRIs): Potential for increased serotonergic effects when combined with SSRIs, which may lead to agitation or serotonin syndrome in rare cases
• Other glutamatergic agents: Potential for additive effects when combined with other substances that modulate glutamate or glycine transmission
• Stimulants: Theoretical risk of additive stimulant-like effects
• Mood stabilizers: Unknown interactions, but caution advised due to sarcosine’s potential effects on mood

The upper limit for safe sarcosine consumption has not been definitively established. Most clinical studies have used doses of 2 grams per day without serious adverse effects. However, some individuals may experience unpleasant side effects at this dose, suggesting that the maximum tolerated dose may vary between individuals. Case reports suggest that reducing the dose to 1 gram per day may alleviate side effects while maintaining benefits in sensitive individuals.

There is insufficient data on the safety of doses higher than 2 grams per day.

Sarcosine is not FDA-approved for the treatment of any medical condition. In the United States, it is available as a dietary supplement under the Dietary Supplement Health and Education Act (DSHEA) of 1994. As a dietary supplement, sarcosine cannot be marketed with claims to treat, cure, or mitigate any disease. Manufacturers can make limited structure/function claims if they have evidence to support them, but these claims must be accompanied by a disclaimer stating that they have not been evaluated by the FDA.

The FDA has not issued any specific warnings or safety alerts regarding sarcosine supplementation.

Eu: In the European Union, sarcosine is not approved as a medicine. It may be sold as a food supplement in some EU countries, though regulations vary by member state. The European Food Safety Authority (EFSA) has not approved any health claims for sarcosine. In some EU countries, it may be classified as a novel food ingredient, requiring safety assessment before marketing.

Canada: Health Canada has not approved sarcosine as a prescription drug. It may be available as a natural health product (NHP), though specific product licensing would be required. No approved health claims exist for sarcosine in Canada.

Australia: The Therapeutic Goods Administration (TGA) has not approved sarcosine as a medicine in Australia. It may be available as a complementary medicine (listed on the Australian Register of Therapeutic Goods), though specific product registration would be required.

Japan: In Japan, sarcosine is not approved as a pharmaceutical drug. It may be available as a food supplement, though it is not among the commonly recognized functional food ingredients.

China: The China Food and Drug Administration has not approved sarcosine as a medicine. Regulations regarding its use as a health food ingredient may vary.

Medium

Sarcosine typically costs between $0.50 and $2.00 per gram, depending on the brand, purity, and formulation. At the standard dose of 2 grams per day used in most clinical studies, this translates to approximately $1.00 to $4.00 per day or $30 to $120 per month. Powder forms are generally more cost-effective than capsules or tablets on a per-gram basis. Bulk purchases (e.g., 100g or more) typically offer better value, reducing the per-gram cost by 20-40% compared to smaller quantities.

Some specialized formulations, such as liposomal sarcosine, may cost significantly more, up to $5.00 per effective daily dose.

For schizophrenia (negative symptoms): When compared to the cost of second-generation antipsychotics, sarcosine is generally less expensive. However, it should be noted that sarcosine is typically used as an adjunct rather than a replacement for standard medications. The potential improvement in negative symptoms and quality of life may justify the additional cost for many patients. For depression: Compared to brand-name antidepressants, sarcosine is moderately priced, though generic SSRIs are typically less expensive.

The potential for faster onset of action (as suggested by preliminary studies) could provide additional value by reducing the duration of depressive episodes. For general cognitive support: The cost-effectiveness is less clear due to limited evidence for this use. Other cognitive enhancers and nootropics may offer better documented benefits at similar or lower costs. The relatively simple chemical structure of sarcosine suggests that manufacturing costs should be moderate, making current pricing reasonable but with potential for reduction as market competition increases.

When evaluating cost-effectiveness, it’s important to consider that sarcosine addresses symptoms (particularly negative symptoms of schizophrenia) that are often poorly responsive to standard treatments, potentially offering unique value despite its cost. For individuals who respond well to sarcosine, the improvement in functionality and quality of life may offset the financial cost through improved work performance and reduced need for other interventions.

Sarcosine is generally stable under proper storage conditions. In powder form, it typically has a shelf life of 2-3 years when stored properly. Capsule and tablet formulations usually have a shelf life of 1-2 years, depending on the specific formulation and packaging. Liquid formulations tend to have shorter shelf lives, typically 6-12 months after opening. The actual shelf life can vary based on manufacturing processes, packaging quality, and storage conditions.

Store in a cool, dry place away from direct sunlight. Optimal temperature range is 15-25°C (59-77°F). Keep the container tightly closed when not in use, as sarcosine is hygroscopic and can absorb moisture from the air. Refrigeration is not necessary but may extend shelf life in hot and humid climates.

Avoid freezing liquid formulations. Keep away from strong oxidizing agents and sources of heat. For powder forms, avoid exposure to air for extended periods to prevent moisture absorption. If the original packaging includes a desiccant packet, keep it in the container.

After opening, try to use within the recommended time frame specified by the manufacturer.

Moisture (sarcosine is hygroscopic and can clump when exposed to humidity), High temperatures (accelerates degradation), Strong oxidizing agents, Prolonged exposure to air, UV light exposure, Microbial contamination (particularly in liquid formulations), Extreme pH conditions, Enzymatic degradation (in liquid formulations without preservatives)

Synthesis Methods

Natural Sources

Quality Considerations

Sarcosine (N-methylglycine) has a relatively short history as a therapeutic agent compared to many traditional supplements and medicines. It was first isolated and identified in the mid-19th century, specifically in 1847 by German chemist Justus von Liebig, who discovered it as a component of creatine in meat extracts. For most of its history, sarcosine was primarily of interest to biochemists studying amino acid metabolism rather than being used medicinally. It was recognized as an intermediate in the metabolism of choline to glycine and as a component of the one-carbon metabolic cycle.

The therapeutic potential of sarcosine began to emerge only in the late 20th and early 21st centuries, primarily through research into the glutamatergic system and its role in psychiatric disorders. The N-methyl-D-aspartate receptor (NMDAR) hypofunction hypothesis of schizophrenia, which gained prominence in the 1990s, led researchers to investigate compounds that could enhance NMDAR function, including glycine, D-serine, and eventually glycine transporter inhibitors like sarcosine. The first significant clinical trial of sarcosine for schizophrenia was published in 2004 by Guochuan Tsai and colleagues, demonstrating its efficacy as an adjunct to antipsychotic medications for improving negative symptoms and cognitive function in schizophrenia. This was followed by several other clinical trials in the 2000s and 2010s, primarily led by researchers in Taiwan, that further explored sarcosine’s potential in schizophrenia and, later, in depression and other psychiatric conditions.

Despite promising clinical trial results, sarcosine has not yet been developed into an approved pharmaceutical drug. Instead, it has become available as a dietary supplement, particularly gaining popularity in the 2010s among individuals seeking alternative approaches for mental health conditions. The interest in sarcosine has been part of a broader trend toward targeting the glutamatergic system for psychiatric disorders, which has also included research into ketamine, memantine, and other glutamatergic agents. In recent years, sarcosine has also gained attention in the context of prostate cancer research, where it has been identified as a potential biomarker.

Paradoxically, while sarcosine supplementation may have benefits for neuropsychiatric conditions, elevated endogenous sarcosine levels have been associated with prostate cancer progression in some studies, highlighting the complex and context-dependent nature of this compound’s biological effects.

Singh SP, Singh V. Meta-analysis of the efficacy of adjunctive NMDA receptor modulators in chronic schizophrenia. CNS Drugs. 2011;25:859-885. This meta-analysis found that glycine, D-serine, and sarcosine were effective in reducing negative symptoms when added to non-clozapine antipsychotics., Tsai GE, Lin PY. Strategies to enhance N-methyl-D-aspartate receptor-mediated neurotransmission in schizophrenia, a critical review and meta-analysis. Current Pharmaceutical Design. 2010;16:522-537. This review and meta-analysis found that glycine transport inhibitors like sarcosine showed promise for treating negative and cognitive symptoms in schizophrenia.

PULSAR (PoLish SARcosine study in schizophrenia) – Evaluating the efficacy and safety of sarcosine in patients with schizophrenia, Investigation of sarcosine for treatment-resistant depression, Glycine transporter inhibitors in cognitive disorders, Sarcosine as an adjunctive treatment for obsessive-compulsive disorder