L‑Serine
Non-essential amino acid and metabolic neuroprotectant; precursor of D-serine and membrane phospholipids.
Pharmacology
Contents
WHAT IS L-SERINE?
Detailed overview
L-Serine is a non-essential, glucogenic amino acid that supplies the serine backbone for phosphatidylserine, sphingolipids and cell-membrane phospholipids, while also serving as a precursor of D-serine, glycine and cysteine and as a key donor for one-carbon (folate) metabolism. In the nervous system the D-serine formed from L-serine is a co-agonist at NMDA glutamate receptors, which is required for the synaptic plasticity that underlies learning and memory. Its neuroprotective effects are shown mainly in preclinical models (BMAA toxicity, ER stress, proteostasis); in humans only small Phase I safety trials have been run in ALS, without proven efficacy. Medically it is used in a targeted way for inherited serine biosynthesis disorders and for HSAN1 neuropathy.
Mechanism
Phospholipid/sphingolipid building block + D-serine (NMDA co-agonist) source
Half-life
Short (plasma levels rise and fall within hours)
Legal status
Dietary amino acid; medical use in rare disorders
Receptor profile
- Phospholipid and sphingolipid synthesisStrong
- NMDA receptor co-agonist pool (via D-serine)Moderate
- One-carbon / folate metabolismModerate
Safety
Side effects, stop signs, contraindications
Side effects · 5
- Mild gastrointestinal upset or nausea, especially at higher intakes
- Occasional headache
- Generally well tolerated as an amino acid, but data on high-dose long-term use are limited
- Theoretically, high serine loading may shift the glycine and one-carbon metabolism balance
- Incomplete long-term safety data at therapeutic (gram-scale) doses
Contraindications · 4
- Pregnancy and breastfeeding: safety of high-dose supplementation not established, therapeutic doses only under medical supervision
- Renal impairment: amino acid load should be managed with caution
- Not a proven treatment for ALS or other neurodegenerative disease: does not replace medical care
- Inherited serine biosynthesis disorders: replacement must be titrated by a specialist
Related Nootropics
Same therapeutic category
Studies
Related research and clinical findings
Phase I clinical trial of safety of L-serine for ALS patients
Levine TD, Miller RG, Bradley WG, Moore DH, Saperstein DS, Flynn LE
Studies of Environmental Risk Factors in Amyotrophic Lateral Sclerosis (ALS) and a Phase I Clinical Trial of L-Serine
Bradley WG, Miller RX, Levine TD, Stommel EW, Cox PA
L-Serine-Mediated Neuroprotection Includes the Upregulation of the ER Stress Chaperone Protein Disulfide Isomerase (PDI)
Dunlop RA, Powell JT, Metcalf JS, Guillemin GJ, Cox PA
Mechanisms of L-Serine Neuroprotection in vitro Include ER Proteostasis Regulation
Dunlop RA, Powell J, Guillemin GJ, Cox PA
Mechanisms of L-Serine-Mediated Neuroprotection Include Selective Activation of Lysosomal Cathepsins B and L
Dunlop RA, Carney JM
BMAA, Neurodegeneration, and Neuroprotection
Cox PA
FAQ
FAQ
Non-essential amino acid and metabolic neuroprotectant; precursor of D-serine and membrane phospholipids.
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Structure & chemistry
The information here is strictly for educational and scientific purposes. It does not replace medical advice or clinical consultation, and it does not encourage illegal substance or pharmaceutical use. Data is sourced. When in doubt, consult your doctor.