L-Serine
Amino acid made via brain glycolysis; needed for NMDA receptor signaling and declines in the aging brain.
Summary
Debbie explains that serine is a non-essential amino acid made from glycine or glycolysis, and that astrocytes convert L-serine to D-serine, which is needed alongside glutamate to activate NMDA receptors for learning and memory. She highlights a mouse study showing that reduced brain glycolysis in Alzheimer's-prone mice lowers serine, and that serine in drinking water restored synaptic plasticity and spatial memory. In humans, L-serine was one of four 'combined metabolic activators' in a placebo-controlled Alzheimer's trial that improved cognitive scores, and a single dose improved executive function and spatial memory in healthy older adults. She concludes low serine isn't the whole problem in neurodegeneration but plays a bigger role than she had thought.
Low serine "isn't the whole problem in neurodegenerative diseases, but it plays a more important role than I had thought."From Serine for Cognitive Enhancement
The evidence
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Human trial
In a placebo-controlled randomized trial of 69 Alzheimer's patients, a combination of L-serine, nicotinamide riboside, NAC, and L-carnitine significantly improved ADAS-Cog scores at day 84, with more improvement in those with more severe symptoms (serine's individual effect not isolated).
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Human trial
In a clinical trial in healthy older adults in Brazil (average age 73), a 30 mg/kg dose of serine taken 1.5 hours before testing improved executive function and spatial memory.
Read the study Discussed in Serine for Cognitive Enhancement -
Human trial
A meta-analysis of schizophrenia trials found D-serine levels are lower and that adding serine to antipsychotic treatment helped symptoms.
Read the study Discussed in Serine for Cognitive Enhancement -
Animal
In Alzheimer's-prone mice, reduced glycolysis in astrocytes lowered brain serine by middle age, and serine added to drinking water rescued synaptic plasticity and restored spatial memory.
Read the study Discussed in Serine for Cognitive Enhancement -
Animal
In Alzheimer's and Parkinson's animal models, two combined metabolic activator stacks containing L-serine markedly enhanced metabolic and behavioral outcomes.
Read the study Discussed in Serine for Cognitive Enhancement -
Animal
In animals, D-serine supplementation reversed age-related declines in brain function.
Read the study Discussed in Serine for Cognitive Enhancement
Doses used in studies
Amounts reported in the research, not dosing recommendations.
| Dose | Context |
|---|---|
| 12.35 g L-serine (once daily for 28 days, then twice daily) | Combined metabolic activator stack in Alzheimer's phase II trial |
| 30 mg/kg single dose, 1.5 hours before testing | Healthy older adults (average age 73) in Brazil |
| 12 g/day | Trial in healthy adults with no observable adverse effects |
| up to 25 g/day | Upper range used in clinical trials |
| 3.5–8 g/day | Typical dietary intake |
Cautions
- Possible bloating or upset stomach at high doses.
- Supplemental serine may affect mood; talk with a doctor if on medications, especially psychiatric medications, since excess NMDA receptor activation can be harmful.
- Conversion of L-serine to D-serine requires vitamin B6 as a cofactor; consider whether you could be low in B6.
- The Alzheimer's trial doses are much higher than usually taken; she does not suggest high doses are needed for prevention at younger ages.