What Is Sarcosine?
Sarcosine (also known as N-methylglycine) is required to produce the amino acid glycine and is also a byproduct of glycine breakdown. In the body, it is produced by turning dietary choline into glycine, or by breaking down methionine to glycine .
It is also produced in the laboratory (from chloroacetic acid and methylamine) .
Sarcosine has a distinct mild, sweet flavor. An ingredient of toothpaste for decades, it prevents cavities and causes foaming .
It is also a promising biomarker for prostate cancer. Sarcosine may be able to detect the early stages of prostate cancer, unlike the currently used biomarker (prostate-specific antigen or PSA) [4, 5].
Mechanism of Action
The role of sarcosine in different mental health disorders stems from its effect on 2 important brain receptors:
- Activating NMDAR (N-methyl-D-aspartate receptor) – Sarcosine increases the activity of NMDAR in the same way as glycine. Both glycine and glutamate are required for increasing the activity of NMDAR, which is thought to bring about the therapeutic effects of sarcosine in schizophrenia and other mental health disorders [9, 10].
- Blocking the GlyT1 (type 1 glycine) transporter – GlyT1 maintains glycine levels in the brain. Sarcosine blocks this transporter leading to glycine builds up in the brain (which then may increase the activity of NMDAR). This could improve the symptoms of mental health disorders, including schizophrenia [11, 12].
Health Benefits of Sarcosine
1) Sarcosine Helps Improve Schizophrenia
Schizophrenia is one of the most serious mental health disorders in the world, and still one of the most difficult to understand. The symptoms include delusions and hallucinations (positive symptoms), flattened mood, loss of speech, and disorganized speech (negative symptoms), and difficulties with attention, memory, and decision making (cognitive symptoms) [13, 14].
Multiple studies (all DB-RCT in 20, 38, 50, 60, and 65 patients) administered sarcosine with the usual antipsychotic treatment in patients with acute or stable schizophrenia. In all studies, sarcosine greatly improved positive, negative, and cognitive symptoms of schizophrenia more than the antipsychotic drug alone [16, 17, 18, 19, 20].
In a study (open-label) of 22 patients with schizophrenia, sarcosine improved symptoms and was safe .
In a study (DB-RCT) of 49 patients, sarcosine improved overall cognitive functioning when taken with benzoate, even if their symptoms did not improve .
Two case studies further outline the role of sarcosine in schizophrenia:
- In a patient with schizophrenia treated with an antipsychotic drug (quetiapine) and an antidepressant drug (citalopram), 2 g of sarcosine daily resolved their negative symptoms in 2 weeks. The patient experienced some side effects after 4 weeks, which resolved once the sarcosine dosage was reduced back to 1 g .
- Another patient with schizophrenia with negative symptoms was treated with antipsychotics and antidepressants (olanzapine and venlafaxine), plus 2 g of sarcosine for 10 weeks. Sarcosine improved the patient’s low mood, activity, and speech (negative symptoms) .
However, in another clinical trial (DB-RCT) of 20 patients, sarcosine added to clozapine failed to improve symptoms over clozapine alone .
2) Sarcosine May Treat Depression
Although depression and schizophrenia sometimes occur together, they are distinct illnesses. Both involve malfunctioning of neurotransmitters in the brain (NMDAR [N-methyl-D-aspartate receptor]) and GlyT1 [type 1 glycine] transporter). Unlike schizophrenia, depression is caused by overactivity of NMDAR [8, 26].
Since sarcosine activates NMDAR, it would follow that those with depression should avoid it. Instead, studies report that sarcosine acts as an antidepressant .
In a study (DB-RCT) of 40 patients with depression, citalopram alone or with sarcosine was given for 6 weeks. Sarcosine improved mood, compared to citalopram alone .
Additionally, sarcosine improved mood faster and patients were more likely to stick to their treatment .
Sarcosine even improved low mood in depressed rats .
3) Sarcosine May Improve OCD
Obsessive-compulsive disorder (OCD) is another mental health disorder that causes a great deal of distress, often interfering with a person’s daily life. It is characterized by repetitive unwelcome thoughts, images, and urges until the person feels compelled to act on them to reduce feelings of anxiety and uneasiness .
In a trial (open-label) of 26 OCD patients, sarcosine was administered alone or as an add-on treatment for 10-weeks. Sarcosine rapidly reduced OCD symptoms, particularly in patients who had not received any therapeutic drug treatment before the study .
4) Sarcosine May Reduce Impulsivity in Children
Oppositional-defiant disorder (ODD) is a disorder where children or adolescents behave in a defiant and impulsive manner (particularly towards their parents and teachers), and are often angry or irritable. Symptoms of ODD often coexist with ADHD .
A 6-week study (DB-RCT) of 116 children with ADHD found that treatment with sarcosine slightly improved ODD symptoms, but not ADHD symptoms .
5) Sarcosine May Help Reduce Seizures
Seizures are caused by various factors, with treatments often specific to the cause .
In mice with induced seizures treated with sarcosine:
- Sarcosine was administered each time a seizure was caused. At high doses, it increased the threshold, making it more difficult for seizures to occur .
- Sarcosine was effective in reducing the incidence of seizures and death by up to 72% .
6) Sarcosine May Reduce Neuropathic Pain
Nerve (neuropathic) pain is difficult to address. Unlike pain from physical trauma (nociceptive pain), nerve pain often results from underlying damage to the nervous system. Long-standing diabetes, stroke, and herpes zoster are some of the common causes [37, 38, 39, 40].
In rats with neuropathic pain in one paw, oral sarcosine reduced pain in both the injured and uninjured paw with higher doses showing greater pain reduction. This effect was lost shortly after it was stopped. It also reduced pain when injected into the spinal cord and brain of the rats .
7) Sarcosine May Reduce Anxiety
In a study (DB-RCT) of 40 depressed patients, sarcosine was better at reducing symptoms of anxiety than an antidepressant (citalopram) .
In rats suffering from anxiety (mothers being separated from pups), a sarcosine derivative (ALX 5407) decreased anxious behavior. The reduction was comparable to anti-anxiety medications like diazepam and escitalopram .
Sarcosine could reduce anxiety through a novel pathway .
8) Sarcosine May Reduce Harm From Toluene
Toluene is a widely-used industrial solvent that is also abused as a recreational inhalant for its intoxicating effects in the brain. Exposure can affect behavior, movement, and brain function .
Mice exposed to toluene were pretreated with sarcosine, which reversed dangerously low body temperatures, memory loss, and lack of coordination in body movements. However, it did not change the intoxicating effects of toluene. These findings show that sarcosine may have a significant role in treating toluene exposure .
9) Sarcosine May Reduce Damage From Stroke
Cerebral ischemia occurs when there is insufficient blood flow to the brain, which then results in the death of brain tissue or stroke.
In rats, pretreatment with sarcosine increased tolerance to blood shortage and reduced cell death in a brain region (hippocampus). Hence, sarcosine protected the brain from stroke .
- Decreased need for sleep
- Hypomanic symptoms (elevated mood, libido, and hyperactivity)
- Unpleasant inner tension
A study (DB-RCT) of 59 subjects with schizophrenia over a 6-month period did not find any side effects of sarcosine on metabolism (measured by blood pressure, level of fats in the blood, weight, BMI, percentage of body fat) .
Limitations and Caveats
While there are several clinical trials in humans, they are limited in sample size. Due to ethical concerns, the ability to administer sarcosine without antipsychotic drugs is limited.
The other studies were done in animals.
Hence, larger human studies are needed to confirm the beneficial effects of sarcosine.
Administering sarcosine as an add-on treatment in patients with schizophrenia taking clozapine did not show any improvement in symptoms. This may be because clozapine may have increased the activity of NMDAR (N-methyl-D-aspartate receptor) to the maximum possible level, so the addition of sarcosine does not have any further beneficial effects .
No other drug interactions for sarcosine have been reported thus far.
Natural Sources / Forms of Supplementation
Sarcosine is readily present in a variety of food products, including: Egg yolks, legumes, nuts, certain vegetables, turkey, ham, and other meats .
As a supplement, sarcosine is available in bulk powders, capsules, and sometimes liquid form.
Sarcosine is taken daily with doses ranging from 1 g to 4 g, with 2 g being the most common and effective dose. If side effects occur at the 2 g dose, then the dosage can be decreased to 1 g [23, 24].
Users describe sarcosine as helpful for panic attacks, delusional thoughts, and depression, especially in combination with other supplements.
Patients with schizophrenia have reported a variety of experiences ranging from good symptom control, no change, or a worsening of positive symptoms, including decreased sleep and racing thoughts.
Some people reported improvement in a matter of days, while others saw improvement in a month’s time. The improvement was usually observed in negative symptoms of schizophrenia.