Also known as: Serine, L-Ser, Phosphatidylserine precursor
Cognitive & NootropicEmerging evidence
A non-essential amino acid involved in phospholipid production, one-carbon metabolism and neurotransmission. Produced readily by the body, though there is an emerging clinical research interest.
Typical dose
2.0–5.0 g per day
Before bed if used for sleep; otherwise with food
What it is
L-serine is classed as non-essential, since the body synthesises it from glycine and from intermediates of glucose metabolism. It is also present in soy, eggs, dairy, meat and nuts.
Some researchers argue it is conditionally essential, on the grounds that internal synthesis may not always meet demand in the brain, which relies substantially on locally produced serine.
It is the precursor to phosphatidylserine, a phospholipid concentrated in neuronal membranes and sold as its own supplement. Note that taking L-serine is not equivalent to taking phosphatidylserine; the conversion involves additional steps and the two have separate research bases.
How it works
L-serine sits at a junction of several pathways. It is a substrate for phospholipid synthesis, including phosphatidylserine and sphingolipids, both important to nerve cell membranes and myelin.
It feeds one-carbon metabolism, donating carbon units to the folate cycle that supports DNA synthesis and methylation, and it interconverts freely with glycine.
In the brain, serine is converted to D-serine, which acts as a co-agonist at NMDA receptors alongside glutamate. This gives it a direct role in excitatory neurotransmission, synaptic plasticity and learning, and is the basis for most neurological research interest.
What the evidence shows
Evidence for L-serine supplementation in healthy people is thin. There is no established cognitive or performance benefit, and the body's own synthesis generally meets demand.
There is a small sleep literature, with a Japanese trial reporting improved subjective sleep quality with a few grams before bed, plausibly mediated through the glycine relationship given glycine's better-established sleep effects.
Most other research on L-serine takes place in supervised medical settings using doses far above supplemental levels. Those protocols are not a template for supplement use.
Dosing
Supplemental doses are typically 2-5 g daily. The sleep research used around 3 g taken before bed.
Supervised research has used substantially higher amounts, in the region of tens of grams daily. Those protocols should not be treated as a template for supplement use.
If sleep is the goal, glycine at 3 g has a better-developed evidence base and is cheaper. If phosphatidylserine is what you actually want, take phosphatidylserine, since L-serine is not a shortcut to it.
L-serine is well tolerated at supplemental doses. Research using much larger amounts has reported mainly gastrointestinal effects, with nausea and diarrhoea at the highest intakes.
Serine converts to a form that acts at receptors involved in excitatory signalling in the brain, so it is not a neutral addition for everyone.
Anyone taking regular medication, particularly anything acting on the brain or nervous system, should seek advice rather than self-supplement. Long-term data at supplemental doses is limited.
Who should avoid it
Speak to your doctor before use if you take regular medication, particularly anything acting on the brain or nervous system, or if you are under medical care. Not established for use in pregnancy or breastfeeding at supplemental doses.
This entry is provided for information only. Food supplements should not be used as a substitute for a varied and balanced diet and a healthy lifestyle. Consult a qualified healthcare professional before use if you are pregnant, breastfeeding, taking medication or under medical supervision.
