Sarcosine

Optimal Result: 3670 - 6743 nanomol/L.

Sarcosine is an amino acid made when SAM is conjugated with glycine by the glycine-N- methyltransferase (GNMT) enzyme. It can also be made by catabolism of DMG. There are many dietary sources of sarcosine including eggs, legumes, nuts, and meats. [L]

Sarcosine is also available as an over-the-counter supplement, and it is widely used in cosmetic formulations (toothpaste, creams, and soaps) and detergents. [L]

In the methylation cycle, sarcosine is created by the GNMT enzyme, which functions to control SAM excess. Disposal of excess SAM is seen in excess methyl donor supplementation, or SAM elevation due to adiposity/ obesity. Some clinicians use sarcosine elevation as a marker of ‘excess methyl supplementation’ or ‘over- methylation.’ Currently, there is no literature to support this hypothesis, but rather it is based on physiology. [L]

Sarcosine can also be produced through the breakdown of DMG. Both sarcosine and dimethylglycine have pharmacological actions in the central nervous system. [L]

Sarcosine is a natural glycine transport inhibitor in the CNS, enhancing N-methyl-D-aspartate (NMDA) receptors. NMDA synaptic receptors are not only important for basic CNS functions (breathing, motor function), but also learning, memory, and neuroplasticity.

Decreased NMDA function results in cognitive defects, and overstimulation causes excitotoxicity. [L]

Abnormalities in these receptors are implicated in many diseases and targeted for pharmacologic therapy. [L] Sarcosine has been shown to be a co-agonist for NMDA receptors. For this reason, there are many studies evaluating sarcosine as an adjunct treatment for psychiatric diseases, such as schizophrenia, which is characterized by decreased NMDA function. In addition, using sarcosine to enhance NMDA function can improve depression-like behaviors. [L] Since DMG is essentially sarcosine with an extra methyl group, research shows that they have similar effects. [L]

Some studies have evaluated urinary and serum sarcosine’s use as a prostate cancer progression marker; however, the data is mixed. [L], [L], [L] These studies are based on nonspecific metabolomic profiling, which followed random metabolite elevation patterns. But, as noted, literature is mixed regarding whether this translates to clinical practice.

Sarcosine has no known toxicity, as evidenced by the lack of phenotypic expression of inborn errors of sarcosine metabolism. [L]

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References:

- Strzelecki D, Podgorski M, Kaluzynska O, et al. Supplementation of Antipsychotic Treatment with the Amino Acid Sarcosine Influences Proton Magnetic Resonance Spectroscopy Parameters in Left Frontal White Matter in Patients with Schizophrenia. Nutrients. 2015;7(10):8767-8782. [L]

- Luka Z, Mudd SH, Wagner C. Glycine N-methyltransferase and regulation of S-adenosylmethionine levels. J Biol Chem. 2009:jbc. R109. 019273. [L]

- Lee M-Y, Lin Y-R, Tu Y-S, Tseng YJ, Chan M-H, Chen H-H. Effects of sarcosine and N, N-dimethylglycine on NMDA receptor-mediated excitatory field potentials. J Biomed Sci. 2017;24(1):18. [L]

- Frontiers in Neuroscience. In: Van Dongen AM, ed. Biology of the NMDA Receptor. Boca Raton (FL): CRC Press/Taylor & Francis Taylor & Francis Group, LLC.; 2009. [L]

- Kemp JA, McKernan RM. NMDA receptor pathways as drug targets. Nat Neurosci. 2002;5:1039. [L]

- Hashimoto K. Glycine transporter inhibitors as therapeutic agents for schizophrenia. Recent Pat CNS Drug Discov. 2006;1(1):43-53. [L]

- Lucarelli G, Fanelli M, Larocca AMV, et al. Serum sarcosine increases the accuracy of prostate cancer detection in patients with total serum PSA less than 4.0 ng/ml. Prostate. 2012;72(15):1611-1621. [L]

- Jentzmik F, Stephan C, Miller K, et al. Sarcosine in Urine after Digital Rectal Examination Fails as a Marker in Prostate Cancer Detection and Identification of Aggressive Tumours. Eur Urol. 2010;58(1):12-18. [L]

- Sreekumar A, Poisson LM, Rajendiran TM, et al. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009;457(7231):910. [L]

- Scriver CR, Beaudet AL, Sly WS, et al. Metabolic and Molecular Bases of Inherited Disease, 4 Volume Set. McGraw-Hill Professional Publishing; 2000. [L]

- Allen RH, Stabler SP, Lindenbaum J. Serum betaine, N, N-dimethylglycine and N-methylglycine levels in patients with cobalamin and folate deficiency and related inborn errors of metabolism. Metabolism. 1993;42(11):1448-1460. [L]

What does it mean if your Sarcosine result is too high?

- Betaine, DMG supplementation [L], [L]

- Dietary intake (i.e. eggs, legumes, nuts, and meats) and environmental sources (i.e. toothpaste, creams, and soaps) [L]

- Folate deficiency (increases use of betaine backup pathway and needed as cofactor in the mitochondrial enzyme sarcosine dehydrogenase used to convert sarcosine to glycine) [L]

- SAM-e supplementation [L]

- Consider over-methylation

What does it mean if your Sarcosine result is too low?

Unknown clinical significance

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