What is sarcosine?
Sarcosine, is a non-protein natural amino acid present as an intermediate during the stages of glycine synthesis and degradation [1,2] and found naturally in muscles and other body tissues  – such as the prostate and skeletal tissue . Sarcosine production is carried out via an enzyme called glycine-N-methyl transferase from the amino acid glycine. It is broken down through action of sarcosine dehydrogenase, to glycine , carrying out a range of biological functions , including one-carbon metabolism, which is an ‘intermediate’ compound in the metabolism of choline. One-carbon metabolism refers to a particular set of pathways that are involved in ‘switching on’ single carbons for making proteins and also building nucleotides .
Lastly, sarcosine’s competitive inhibitor function, ‘blocking’ the type I glycine transporter  – in which the NMDA function is increased  – owes to its potential as an adjunctive antipsychotic agent  through improving both schizophrenic and depressive symptoms in patients . Sarcosine is found in many food sources that we are all familiar with. Foods such as egg yolks, ham, vegetables and legumes are all food sources which are naturally supplemented with sarcosine .
Figure 1: Sarcosine chemical structure arrangement. In normal human blood serum, sarcosine has been reported at a concentration of between 1.4 +/- 0.6 micromolar. Sarcosine is an odourless amino acid, with a white crystalline appearance. Image source: Sigma-Aldrich
Benefits & side effects
Sarcosine has many interesting benefits that include enhancing memory and learning, combating positive symptoms and negative symptoms of psychotic – schizophrenic – and mental problems –depression; along with playing a positive role in obsessive compulsive disorder.
Sarcosine and schizophrenia
Sarcosine is a naturally-occurring selective glycine transporter type 1 inhibitor
that increases N-methyl-D-aspartate (NMDA) receptor function, and heightens glycine concentration within the synaptic cleft . In a randomised, double-blind placebo-controlled trial, sarcosine was shown to benefit patients with long-term stable disease and also those individuals with schizophrenia . Sarcosine works through its enhancement of the NMDAR function, which, in patients with schizophrenia is low .
In a study assessing the effects of sarcosine on toluene-induced motor incoordination and recognition memory impairment and body temperature, results showed that sarcosine alleviated the ‘block’ that toluene exhibits on the NMDA receptor . This potentiation or ‘increased strength’ of the NMDA receptors was suggested to reverse motor incoordination, memory impairment and hypothermia .
Figure 2: NMDA receptor. Sarcosine binds to the ‘glycine site’ which also binds D-serine and glycine.
Sarcosine as a biomarker in prostate cancer
Sarcosine has been shown to be implemented in prostate cancer; as a prostate cancer metabolome analysis revealed that sarcosine was elevated in metastatic prostate cancer . These results have led to the consideration of using this as a lead to develop potential biomarkers of prostate cancer progression . Another study determined that urinary sarcosine could be a potential prostate cancer biomarker .
Research into modulating the glutamatergic system is fast becoming an approach in the treatment of depression; displacing the limited efficacy that govern current antidepressants . Sarcosine carries out its antidepressant effects through activation of a key pathway called the AMPAR-mTOR signalling pathway . AMPA, or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate glutamate receptors [12,14] play a relevant role in depression. A single dose of sarcosine injected into animals demonstrated the anti-depressant effects of sarcosine as enhancing the AMPA receptor – mTOR pathway . These glutamate receptors convey most of the excitory neurotransmissions that are found in the brain [12, 14].
Long-term, in vivo, sarcosine treatment to rats under chronic and unpredictable stress (CUS) found sarcosine to induce an antidepressant-like response after a 21-day – 560mg/kg – treatment . In a 6-week, randomised, double-blind trial in 40 patients suffering from major depressive disorder, sarcosine improved scores of the Hamilton Depression Rating scale, which is a scale used to provide an indication of depression, Clinical Global Impression, and Global Assessment of Function  – which measure the efficacy of treatments in studies of patients with mental disorders. These results were indicative of sarcosine having the ability to potentially improve NMDA function . No research has linked sarcosine to anxiety or social anxiety, and this should not be concluded from sarcosine’s role in depression. More evidence is required in order to support this claim.
Sarcosine and Obsessive-compulsive disorder (OCD)
Around 40% of OCD patients receive little benefits from currently available pharmacotherapy . As glutamatergic dysfunction has been implicated in the pathophysiology of OCD, in which growing evidence suggests the role of abnormal NMDA receptor function in OCD . Sarcosine treatment for 10 weeks in individuals with OCD found a significantly reduced Yale-Brown obsessive compulsive score [16, 17].
Sarcosine and ADHD
A six-week clinical trial pilot study of sarcosine, aimed at evaluating the efficacy of sarcosine in treating children with ADHD. 116 children were administered a sarcosine dosage of 0.03g/kg per day, and was well tolerated . Although this study investigated whether sarcosine had positive effects on ADHD, results showed that only oppositional defiant disorder (ODD) were significant when compared to placebo. This led researchers to conclude that sarcosine might possibly be an agent for treating ODD in an ADHD context . Researchers of this study suggested that long-term treatment and higher dosages might yield better treatment responses in ADHD.
Memory and Learning
Sarcosine and D-serine were documented, in a schizophrenia context, as enhancing social memory in naive rats  Another study investigating sarcosine and its reversal effects of toluene, sarcosine-induced potentiation of the NMDA receptor was found to reverse object recognition impairment, leading to a reversal in memory deficits in the male mice . Although these results suggest a potential role of sarcosine in memory, this does not give proof that sarcosine can be used as a memory enhancer, or clear brain fog. In this regard, more research is necessary to fully evaluate sarcosine’s role in memory. Several online sites brand sarcosine as a ‘brain health supplement’, along with claims such as ‘promotes brain cell function.’ These are unfounded claims, with no evaluations carried out through the FDA.
Sarcosine Vs D-Serine
Sarcosine, in the context of psychotic symptoms has been suggested as being superior to D-Serine. As enhancing the NMDA neurotransmission could be a potential strategy for treating schizophrenia, D-serine, is an agonist agent that target glycine sites of the NMDA receptor act as an additional therapy to improve negative and cognitive symptoms . Comparisons of D-serine and sarcosine  have shown that sarcosine treatment in patients with chronic schizophrenia is superior to that of D-serine. This data suggested that the glycine transporter-1 antagonist (sarcosine) can improve positive and negative symptoms of schizophrenia [20,21].
Sarcosine Vs Ketamine
Ketamine has been demonstrated to induce major antidepressant effects  in patients with depression [22, 23]; it binds to the PCP-binding site of the NMDA receptor complex  inducing hallucinatory and dissociation side effects. Sarcosine, as an inhibitor of glycine transporter 1, and through its improvement of symptoms of schizophrenia, has been compared to ketamine. Results have shown that N,N-dimethylglycine (DMG) – which is a safe and non-toxic  precursor of sarcosine reverses ketamine-induced psychomimetic behaviours. Further, sarcosine, at 300mg/kg produced similar effects as ketamine at 10mg/kg . Reviews of sarcosine and ketamine – https://www.reddit.com/r/Nootropics/comments/4ysdg6/sarcosine_maybe_as_potent_as_ketamine_for/ – sarcosine and ketamine can be found here on Reddit.
Sarcosine and/or glycine
Glycine and sarcosine share a very similar chemical structure, with sarcosine having an additional methyl group attached to it  – as its chemical name ‘N-methylglycine’ implies. Sarcosine is simply a derivative of glycine. Glycine ‘docks’ with its glycine-binding sites along the NMDA receptor just as sarcosine does, and results have shown that sarcosine is a strong ‘agonist’ candidate that also binds to the same sites of the NMDA receptor .
Sarcosine and autism
Although sarcosine has not been shown to treat autism, a structurally similar chemical, N,N-dimethylglycine (DMG) – also a dietary supplement – has been noted through anecdotal evidence by medical professionals, parents and caretakers that DMG has benefits for children with autism . In this regard, dysfunction of NMDA receptors is associated with autism spectrum disorders and sarcosine has been shown to interact with the NMDA receptor in much the same way that glycine and DMG does . More research, along with clinical trialling would be suitable in deciphering sarcosine’s possible role along the autism spectrum disorder scale.
Sarcosine and cyanamide
Sarcosine and cyanamide both work together to form creatine [26; 27]. Creatine can provide energy requirements for vigorous muscle contraction, including improving physical performance , and can also be used as a treatment for gyrate atrophy – a metabolic disease of the eye along with the potential to treat traumatic brain injury. While sarcosine can essentially be a building block for making creatine, no clinical reports have documented the use of supplemented sarcosine in creatine production for health outcomes.
Long-term sarcosine use causes minimal side effects. The rare autosomal recessive metabolic disorder, sarcosenemia, has been considered a harmless effect . No reports have indicated, or reported adverse effects from the use of sarcosine. Since the European Chemicals Agency (ECHA) has labelled sarcosine with a non-hazardous classification, the ECHA communicates that sarcosine can be used for industrial purposes; to manufacture other substances.
In support of sarcosine’s safety, dosages of 2 and 4 grams per day  been described as being tolerable. In addition, no significant events or abnormalities were observed over a week . As this study evaluated pharmacokinetic data of sarcosine, sarcosine was found to reach peak concentrations in serum after two hours, with half-life being one hour . Other work has described sarcosine at a dosage of 2 grams per day as being well tolerated . Further, in a double-blind study assessing the effects of sarcosine, as an ‘additional’ therapy for schizophrenia, daily dosages of 1 and 2 grams of sarcosine, over 6-weeks showed minimal side effects and was well tolerated .
The Therapeutics Good Administration (TGA) in Australia is approved for topical use and its concentration must not exceed 0.5%. Similarly, Canada lists sarcosine as classified as a natural and non-prescription health product (NHP). Sarcosine can be readily purchased online without any incident. Due to sarcosine’s legal status it can be readily purchased online without disrupting existing guidelines from the Australian TGA. This is exemplified by the TGA’s administration of the Therapeutic Goods Act 1989 (the Act) which ensures a robust risk assessment is applied to all of its entrant compounds. As Australia has a long history of providing quality regulations and guidelines to build trust with its public, the TGA only accepts the highest standard of quality, safety and efficacy. These high standards are constructed upon scientific and clinical expertise to decision-making to ensure consumer benefits always outweigh potential risks associated with listed medicines or compounds – such as sarcosine. Sarcosine is available for purchase without any strict regulation, besides that which is outlined in the TGA reports.
Experiments on evaluating what sarcosine can be supplemented with (stacked) have not been confirmed. Literature on ‘stacks’ has not been fully established, and one should not confuse D-serine and/or glycine – or any other structurally similar metabolites – as potential stacks with sarcosine. Until this research has been confirmed stacks shouldn’t be considered.
Reviews and social media
Customer reviews and opinions of sarcosine can be found online through platforms such as Reddit, along with other portals such as schizophrenia.com, where sarcosine’s antidepressant and schizophrenic alleviating properties have spurred its popularity. Reddit is an open-source social media platform that allows its users to disseminate information through testimonials.
Other reviews provide very little reference to peer-reviews scientific data, which these sites should be avoided when considering buying sarcosine.
Reading on sarcosine through Reddit allows a balanced and multiple perspective in which sarcosine benefits, side effects, dosages and comparisons to other nootropics can be elucidated. Similarly, Amazon – https://www.amazon.com/product-reviews/B01I42EZ7Y – showcases 5 reviews on sarcosine.