Sarcosine is an amino acid currently researched as a biomarker for prostate cancer. But did you know that it is also being researched for its potential to reduce the symptoms of mental health disorders such as schizophrenia and depression? Keep reading to learn more about the health benefits and side effects of sarcosine.
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 [1].
It is also produced in the laboratory (from chloroacetic acid and methylamine) [2].
Sarcosine has a distinct mild, sweet flavor. An ingredient of toothpaste for decades, one derivative of sarcosine appears to help prevent cavities and cause foaming [3].
Sarcosine has other surprising health benefits. Studies over the past 2 decades uncovered its role in treating mental health disorders, including schizophrenia and depression [4, 5, 6].
Mechanism of Action
Some researchers believe that sarcosine’s apparent effects in different mental health disorders stem from its effect on 2 important receptors in the brain. In cell studies, sarcosine:
- Activated the NMDAR (N-methyl-D-aspartate receptor): Sarcosine increased 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 [7, 8].
- Blocked 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 [9, 10].
Potential Benefits of Sarcosine
Sarcosine supplements have not been approved by the FDA for medical use and generally lack solid clinical research. Regulations set manufacturing standards for them but don’t guarantee that they’re safe or effective. Speak with your doctor before supplementing.
Insufficient Evidence For
The following purported benefits are only supported by limited, low-quality clinical studies. There is insufficient evidence to support the use of sarcosine for any of the below-listed uses. Remember to speak with a doctor before taking sarcosine supplements, and never use it in place of something a doctor recommends or prescribes.
1) 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) [11, 12].
About 1.5 people per 10,000 are diagnosed with schizophrenia each year. Depression, anxiety, and substance abuse often appear at the same time [13].
Multiple studies (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 [14, 15, 16, 17, 18].
In a study of 22 patients with schizophrenia, sarcosine improved symptoms and was safe [19].
In a study of 49 patients, sarcosine improved overall cognitive functioning when taken with benzoate, even if their symptoms did not improve [20].
Multiple case studies, wherein sarcosine was added to patients’ conventional therapy, have also produced promising results [21, 22].
However, in another clinical trial of 20 patients, sarcosine added to clozapine failed to improve symptoms over clozapine alone [23].
2) 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 the overactivity of NMDAR [6, 24].
Since sarcosine activates NMDAR, it would follow that those with depression should avoid it. Instead, one clinical study suggests a potential benefit in depression [25].
In a study of 40 patients with depression, citalopram alone or with sarcosine was given for 6 weeks. Sarcosine improved mood, compared to citalopram alone [26].
Additionally, sarcosine improved mood faster and patients were more likely to stick to their treatment [26].
Sarcosine even improved low mood in depressed rats [26].
3) 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 [27].
In a trial 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 [28].
4) ODD
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 [29].
A 6-week study of 116 children with ADHD found that treatment with sarcosine slightly improved ODD symptoms, but not ADHD symptoms [30].
5) Anxiety
In a study of 40 depressed patients, sarcosine reduced symptoms of anxiety more effectively than an antidepressant (citalopram) [26].
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 [31].
Some researchers have suggested that sarcosine could reduce anxiety through a novel pathway – that is, with a different mechanism than any antidepressant currently on the market [31].
Animal Research (Lacking Evidence)
No clinical evidence supports the use of sarcosine for any of the conditions listed in this section. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.
6) Seizures
Seizures are caused by various factors, with treatments often specific to the cause [32].
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 [33].
- Sarcosine was effective in reducing the incidence of seizures and death by up to 72% [34].
In another study in mice, sarcosine reduced stress-induced seizures [35].
7) 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 [36, 37, 38, 39].
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 [40].
8) 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 [41].
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 [41].
9) 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 [42].
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.
Side Effects & Precautions
Sarcosine is generally well-tolerated, but it did produce the following side effects in clinical studies [14, 15, 16, 17, 30, 21, 22, 28]:
- Decreased need for sleep
- Hypomanic symptoms (elevated mood, libido, and hyperactivity)
- Irritability
- Unpleasant inner tension
- Headaches
A study 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) [43].
Drug Interactions
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 [23].
No other drug interactions for sarcosine have been reported thus far, but future studies may identify more. The best way to avoid adverse effects and unexpected interactions is to talk to your doctor before using sarcosine.
Prostate Cancer
Sarcosine is a promising biomarker for prostate cancer. Its presence may indicate and help detect prostate cancer in the early stages, with some advantages over the currently used biomarker (prostate-specific antigen or PSA) [44, 45].
However, by the same token, sarcosine supplements may increase prostate cancer risk. Sarcosine might also make harmless prostate cancer cells become more dangerous and invasive, according to animal studies. What’s more, men with prostate cancer have much higher sarcosine levels in their prostate tissue, other healthy tissues, and urine [46].
Given the possible increase in prostate cancer risk, men may want to avoid sarcosine supplements and stick to its healthy food sources unless directed otherwise by a doctor. More information about the safety of sarcosine is needed.
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 [1].
As a supplement, sarcosine is available in bulk powders, capsules, and sometimes liquid form.
Dosage
There is no safe and effective dose of sarcosine because no sufficiently powered study has been conducted to find one. That being said, clinical studies have produced benefits at certain doses.
Clinical trials have used doses ranging from 1 g to 4 g, with 2 g being the most common [21, 22].
User Experiences
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 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.
