L-Serine for cognitive function

L-Serine

  • Vitamins & Supplements
  • Updated May 22, 2018

L-serine is an amino acid essential for the synthesis of phosphatidylserine, which is a component of the membrane of brain cells (i.e., neurons). It can be produced in the body, including the brain, but an external supply from the diet is essential in maintaining necessary levels. Although preclinical studies suggest L-serine may inhibit inflammation in the brain, levels of L-serine in humans do not appear to be associated with dementia or cognitive decline. Because L-serine is a naturally occurring amino acid, supplementation is likely safe in moderation.

Evidence

No clinical studies have tested whether L-serine can prevent age-related cognitive decline or dementia, though one trial is underway now. Our search identified:

  • 4 observational studies of L-serine levels in spinal fluid, blood, or in the brain
  • Numerous preclinical studies

Potential Benefit

No clinical studies have tested whether L-serine can improve cognitive functions or prevent age-related cognitive decline. Studies examining levels of L-serine have not reported any correlations with cognitive function [1][2].

L-serine is essential for the synthesis of lipids called phosphatidylserine that make up the cell membrane of neurons [3]. It is also essential for growth of neuronal processes. However, it is not clear whether L-serine supplements directly increase L-serine levels in the brain. In a study on traumatic brain injury in small mammals, L-serine treatment helped to protect brain tissue and improve recovery of neurological functions by inhibiting inflammation [4]. Such protective effects have not been confirmed in humans yet.

For Dementia Patients

A phase 2 clinical trial testing the effects of L-serine in early-stage Alzheimer's patients is currently underway [5]. There have been several studies examining cerebral spinal fluid and blood serum levels of L-serine in people with Alzheimer's, but no clear differences with healthy people have been found, nor any correlations between L-serine levels and cognitive functions [1][2]. Postmortem studies also showed that L-serine levels in the brain were comparable between Alzheimer's disease patients and healthy people [6][7].

Preclinical studies suggest L-serine may benefit those exposed to the neurotoxin beta-methylamino-L-alanine (BMAA) [8]. Our cells can mistake BMAA for L-serine and misincorporate it into proteins, which can lead to cell death and may increase biological markers of Alzheimer's [9]. Laboratory studies indicate that L-serine may prevent misincorporation of BMAA and cell death [9]. However, it is unclear whether L-serine affects biological markers of Alzheimer's in the absence of such neurotoxins.

Safety

No clinical studies have tested the safety of L-serine supplementation in healthy adults. In a phase 1 safety trial in 20 ALS? patients, L-serine treatment (0.5-15.0 g, twice daily) for 6 months was generally well-tolerated and appeared to be safe [10][11]. Two patients withdrew from the trial due to gastrointestinal side effects but no other adverse events or changes in routine blood tests measures were observed.

NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.

How to Use

L-serine is a naturally occurring dietary amino acid. It is abundant in soy products, sweet potatoes, eggs, meat, and some edible seaweed. L-serine is also sold as a dietary supplement in capsule and powder forms. The dose used in an ongoing Alzheimer's trial is 15 grams, twice daily, in the form of gummies [12]. Most supplements come in the form of 500 mg capsules.

Learn More

Information on the Phase 2 study testing L-serine in early Alzheimer's disease at the Dartmouth Hitchcock Medical Center on ClinicalTrials.gov.

References

  1. Biemans EA, Verhoeven-Duif NM, Gerrits J et al. (2016) CSF d-serine concentrations are similar in Alzheimer's disease, other dementias, and elderly controls. Neurobiol Aging 42, 213-216.
  2. Hashimoto K, Fukushima T, Shimizu E et al. (2004) Possible role of D-serine in the pathophysiology of Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry 28, 385-388.
  3. Hirabayashi Y, Furuya S (2008) Roles of l-serine and sphingolipid synthesis in brain development and neuronal survival. Prog Lipid Res 47, 188-203.
  4. Zhai PP, Xu LH, Yang JJ et al. (2015) Reduction of inflammatory responses by L-serine treatment leads to neuroprotection in mice after traumatic brain injury. Neuropharmacology 95, 1-11.
  5. Monahan JB, Corpus VM, Hood WF et al. (1989) Characterization of a [3H]glycine recognition site as a modulatory site of the N-methyl-D-aspartate receptor complex. J Neurochem 53, 370-375.
  6. Chouinard ML, Gaitan D, Wood PL (1993) Presence of the N-methyl-D-aspartate-associated glycine receptor agonist, D-serine, in human temporal cortex: comparison of normal, Parkinson, and Alzheimer tissues. J Neurochem 61, 1561-1564.
  7. Nagata Y, Borghi M, Fisher GH et al. (1995) Free D-serine concentration in normal and Alzheimer human brain. Brain Res Bull 38, 181-183.
  8. Cox PA, Davis DA, Mash DC et al. (2016) Dietary exposure to an environmental toxin triggers neurofibrillary tangles and amyloid deposits in the brain. Proc Biol Sci 283.
  9. Dunlop RA, Cox PA, Banack SA et al. (2013) The non-protein amino acid BMAA is misincorporated into human proteins in place of L-serine causing protein misfolding and aggregation. PLoS One 8, e75376.
  10. Bradley WG, Miller RX, Levine TD et al. (2017) Studies of Environmental Risk Factors in Amyotrophic Lateral Sclerosis (ALS) and a Phase I Clinical Trial of L-Serine. Neurotox Res.
  11. Levine TD, Miller RG, Bradley WG et al. (2017) Phase I clinical trial of safety of L-serine for ALS patients. Amyotroph Lateral Scler Frontotemporal Degener 18, 107-111.
  12. Stark AC (2017) Phase IIa L-serine Trial for eAD (LSPI-2). ClinicalTrials.gov.