The AtlasAmino acidsPolar, uncharged
SerineSer · S
A small amino acid made from glucose that feeds the folate cycle, builds the brain’s fats and, when it runs short, lets the nervous system poison itself with the wrong lipid.
Molecule · Ser · 7 heavy atoms
Serine
C3H7NO3105.09 g/mol
A small amino acid made from glucose that feeds the folate cycle, builds the brain’s fats and, when it runs short, lets the nervous system poison itself with the wrong lipid.
Built fromthe charted ones open their own entry
- Codes
- Ser · S
- Formula
- C3H7NO3
- Molar mass
- 105.09 g/mol
- Systematic name
- (2S)-2-amino-3-hydroxypropanoic acid
- Side chain
- Hydroxymethyl: one carbon and a hydroxyl; small, polar and uncharged.
- Class
- Polar, uncharged
- In the diet
- Dispensable
- Carbon skeleton
- Glucogenic
- pKa
- α-COOH 2.21 · α-NH3+ 9.15
- Isoelectric point
- pH 5.68
- Hydropathy
- -0.8 (Kyte–Doolittle)
- Codons
UCUUCCUCAUCGAGUAGC- Main transporters
- SLC1A4 (ASCT1)
pKa and isoelectric point: Nelson and Cox, Lehninger Principles of Biochemistry, table of amino acid properties (free amino acid, 25 °C). Hydropathy: Kyte and Doolittle, J Mol Biol 1982. Essentiality: Reeds, J Nutr 2000. Formula and mass computed from the structure.
In brief
What it is
An amino acid with a single carbon carrying a hydroxyl group: small, polar and uncharged. The body makes it from 3-phosphoglycerate, an intermediate of glycolysis, in three steps 1,2.
Why it matters
Serine is the main source of one-carbon units for folate metabolism, and so of nucleotides and methylation 3; the precursor of glycine, cysteine, D-serine and the sphingolipids and phospholipids of membranes 1; and, as a target for kinases, one of the cell’s main phosphorylation sites 4.
Where it runs short
Inherited defects in serine synthesis cause microcephaly, seizures and developmental delay in children, and polyneuropathy in adults 2. In diabetic mice, low serine drove peripheral neuropathy through the build-up of toxic 1-deoxysphingolipids 5.
Where it turns
There is no known toxicity of excess dietary serine at food levels; in cancer, though, many tumors depend on serine, and in mice restricting dietary serine and glycine slowed some of them 6.
When serine runs short, the enzyme that should use it takes alanine instead, and makes a lipid the body cannot break down.
The molecule
Serine is alanine with a hydroxyl on its side chain. That hydroxyl is the business end: it is where kinases attach phosphate, so serine is one of the three amino acids, with threonine and tyrosine, through which much of cell signaling runs 4. In serine proteases a serine hydroxyl, activated by a neighboring histidine, is what cuts the target protein 7.
Move across the chart to read the charge at any pH.
Computed from its pKa values (α-carboxyl 2.21, α-amino 9.15) by the Henderson–Hasselbalch equation, for the free amino acid in water at 25 °C. Inside a folded protein the same groups can shift by a unit or more. The faint lines are the other amino acids.
Kyte–Doolittle hydropathy index: positive values avoid water and tend to be buried inside a folded protein, negative values sit on its surface. Each letter is an amino acid; choose one to open it.
| 1st ↓ 2nd → | U | C | A | G | 3rd |
|---|---|---|---|---|---|
| U | UUUPhe | UCUSer | UAUTyr | UGUCys | U |
| UUCPhe | UCCSer | UACTyr | UGCCys | C | |
| UUALeu | UCASer | UAAStop | UGAStop | A | |
| UUGLeu | UCGSer | UAGStop | UGGTrp | G | |
| C | CUULeu | CCUPro | CAUHis | CGUArg | U |
| CUCLeu | CCCPro | CACHis | CGCArg | C | |
| CUALeu | CCAPro | CAAGln | CGAArg | A | |
| CUGLeu | CCGPro | CAGGln | CGGArg | G | |
| A | AUUIle | ACUThr | AAUAsn | AGUSer | U |
| AUCIle | ACCThr | AACAsn | AGCSer | C | |
| AUAIle | ACAThr | AAALys | AGAArg | A | |
| AUGMet | ACGThr | AAGLys | AGGArg | G | |
| G | GUUVal | GCUAla | GAUAsp | GGUGly | U |
| GUCVal | GCCAla | GACAsp | GGCGly | C | |
| GUAVal | GCAAla | GAAGlu | GGAGly | A | |
| GUGVal | GCGAla | GAGGlu | GGGGly | G |
Where it comes from
The body makes serine from 3-phosphoglycerate, a product of glycolysis, by three enzymes: phosphoglycerate dehydrogenase, the first and rate-limiting step, phosphoserine aminotransferase and phosphoserine phosphatase 2,8. PHGDH's best-documented role in human disease, though, has nothing to do with making serine. Altered expression of PHGDH — a biomarker of late-onset Alzheimer's disease — modulates amyloid pathology in mice and in human brain organoids INDEPENDENTLY of its enzymatic activity: it also acts as a transcriptional regulator, promoting transcription of IKKα and HMGB1 in astrocytes, which suppress autophagy and accelerate amyloid pathology, and a brain-penetrant small molecule aimed at that transcriptional function reduced amyloid and improved behavior 9. A year later the same laboratory added a third function and revised its own mechanism: PHGDH binds a 3'UTR, which lets it bring EIF2AK1 to EIF2α, driving EIF2α phosphorylation and selectively promoting translation of BACE1, the rate-limiting enzyme of amyloid-β production — again independent of both the enzymatic and the transcriptional roles 10. Meanwhile the dietary end of the same story works on a different readout: in 3xTg-AD mice an L-serine-enriched diet raised plasma L- and D-serine and partially rescued the hippocampal neurogenesis deficit WITHOUT affecting amyloid pathology 11. Three papers, two of them from one group, and none of the amyloid effects running through serine itself.
The brain cannot rely on blood serine, which crosses the blood–brain barrier poorly, so astrocytes make it and hand it to neurons through ASCT1 12.
DispensableMade from glucose through 3-phosphoglycerate, so not needed in the diet; the brain depends on making its own 1,12,13.
How much
None set; the body makes it from glucose 13.
Where it is in food
- All protein; but blood serine reaches the brain poorly 12.
In the bottle · enzymatic or extractedIndustrial serine has come mainly from extraction and enzymatic catalysis; direct fermentation from sugar with engineered Corynebacterium glutamicum or Escherichia coli is being developed 14,15.
What the body does with it
Serine is the main entry to one-carbon metabolism. Serine hydroxymethyltransferase converts it to glycine while loading a carbon onto tetrahydrofolate, and those carbons build purines and thymidine for DNA and regenerate methionine for methylation; much of this happens in mitochondria 3.
Serine is also the backbone of membrane lipids. Serine palmitoyltransferase joins it to palmitate to begin every sphingolipid, and it forms the head group of phosphatidylserine 1,16. A racemase converts L-serine into D-serine, a co-agonist of NMDA receptors at synapses 17,18. That co-agonist role has now had its cleanest pharmacological test in people, and it failed. Luvadaxistat is a selective D-amino acid oxidase inhibitor, designed to raise synaptic D-serine by blocking the enzyme that destroys it. In the phase 2 ERUDITE trial, 203 adults with schizophrenia on background antipsychotics were randomized 2:1:1 to placebo or luvadaxistat at 20 or 50 mg daily for 12 weeks: the change in the Brief Assessment of Cognition in Schizophrenia composite score did not differ from placebo at either dose (least-squares mean differences −0.7, p = 0.75 and −0.5, p = 0.69), with adverse events in about a third of participants in every group and no safety concerns 19. The mechanism is not in doubt; what raising D-serine does for cognition in schizophrenia is.
Many cancers lean on serine. In 2011 the first enzyme of serine synthesis, PHGDH, was found to be raised in 70% of estrogen-receptor-negative breast cancers and required by those cells to grow 20. In mouse models of intestinal cancer and lymphoma, a diet without serine and glycine extended survival, though tumors driven by KRAS responded less 6. The diet has now been tried in people, and it brings its own resistance with it. In colorectal cancer models a serine- and glycine-free diet slowed growth and drew in cytotoxic T cells — and the same work identified LACTYLATION of PD-L1 on tumor cells as an immune-evasion mechanism arising during that T cell response, with PD-1/PD-L1 blockade able to revive the recruited CD8 T cells. The authors also ran a single-arm phase I study whose primary outcome suggests the diet is feasible and safe for regulating systemic immunity, with tolerability and possible antitumor effect as secondary outcomes 21. Starving a tumor of serine provokes the brake that immunotherapy exists to release, which is an argument for combining them rather than for the diet alone.
Serine is also something a pathogen eats, and that turns out to matter for cancer. Colibactin-producing Escherichia coli, which abnormally colonizes colonic tissue in colorectal cancer, reprogrammes colonic epithelial cells in a colibactin-dependent way — a Warburg-like shift, altered redox balance, disrupted amino acid metabolism — and among those changes both extracellular and intracellular serine FALL. The bacterium activates its own L-serine-utilization operon during colonization, which maximizes its competitive advantage over a commensal strain; an L-serine-depleted diet produced an early transient drop in colonization along with less DNA damage and less tumor development; and deleting the bacterial gene for serine-operon use reduced its fitness, its adhesion and persistence inside epithelial cells, and its carcinogenic activity in mouse models 22. A 2026 review sets out the wider position: serine supports intestinal mucosal homeostasis through protein synthesis, redox balance, immune function, lipid metabolism, mucus production, barrier integrity and microbiota composition — and prokaryotes including E. coli have mechanisms to exploit it for growth, virulence, inflammation and carcinogenesis 23. Dietary serine is not metabolically neutral by the time it reaches the colon.
In three sentences each
The one-carbon donor
Serine hydroxymethyltransferase splits serine into glycine and a one-carbon unit carried by folate, the main source of the carbons used to build purines and thymidine and to make methionine 3.
How it is made, moved and broken down
When serine runs short, serine palmitoyltransferase starts using alanine. The products, 1-deoxysphingolipids, lack the hydroxyl that cells need to break sphingolipids down, so they accumulate. Variants in the enzyme that favor alanine cause hereditary sensory and autonomic neuropathy type 1, and lowering serine in cells shifted their lipid profile towards that pattern 16.
There is an effect of oral serine that has nothing to do with any of this page's pathways. In healthy mice, a single oral dose of either L-serine or D-serine given with a glucose load significantly suppressed the rise in blood sugar — with no change in serum insulin after the load and none in insulin sensitivity, and no effect at all when the glucose was given intraperitoneally instead. In everted intestine both suppressed glucose absorption: L-serine by lowering brush-border GLUT2, D-serine by lowering both SGLT1 and GLUT2 25. The apparent blood-sugar benefit is gut absorption, the two enantiomers do it differently, and it is mice.
Carbon skeleton · glucogenicSerine is converted to glycine and one-carbon units, and its carbon skeleton counts as glucogenic 3.
- 3-Phosphoglycerate
- Phosphoglycerate dehydrogenasePHGDH · NAD⁺
- 3-Phosphohydroxypyruvate
- Phosphoserine aminotransferasePSAT1 · vitamin B6
- Phosphoserine
- Phosphoserine phosphatasePSPH
- Serine
- Serine + THF
- Serine hydroxymethyltransferaseSHMT1, SHMT2 · vitamin B6
- Glycine + methylene-THF
- Serine racemaseSRR · vitamin B6
- D-Serine
- Serine palmitoyltransferaseSPTLC1, SPTLC2 · vitamin B6
- Sphingolipids (or, with alanine, 1-deoxysphingolipids)
How it crosses membranes
- SLC1A4 · ASCT1astrocytes and neurons — carries serine from astrocytes to neurons; recessive mutations cause microcephaly and hypomyelination 12
Where it matters most
When it goes wrong
Inherited
Serine deficiency disorders
PHGDH, PSAT1, PSPH · autosomal recessive
Microcephaly, psychomotor delay and seizures in children, or a progressive polyneuropathy in adults, with low serine in CSF and plasma; they are treatable, so prompt recognition matters 2. Milder cases can present in adolescence as ichthyosis and neuropathy, where high-dose serine and glycine cleared the skin but barely helped the nerves 27.
How it is foundFasting plasma and CSF serine; gene sequencing 2.
Inherited
Neu–Laxova syndrome
PHGDH, PSAT1, PSPH · autosomal recessive
The most severe end of the serine synthesis disorders, with multiple malformations and death before or soon after birth 8,28.
How it is foundPrenatal ultrasound and sequencing 8.
Inherited
ASCT1 deficiency
SLC1A4 · autosomal recessive
Developmental delay, microcephaly and poor myelination, sometimes with seizures, from failure to move serine from astrocytes into neurons 12.
How it is foundExome sequencing 12.
Inherited
HSAN1 and SPTLC1-related ALS
SPTLC1, SPTLC2 · autosomal dominant
Variants that make serine palmitoyltransferase use alanine cause a sensory and autonomic neuropathy through 1-deoxysphingolipids; variants that free it from its regulators cause juvenile ALS through excess sphingolipid 16,29.
How it is foundPlasma sphingolipid profiling and sequencing 16.
Association
Diabetic neuropathy
Serine and glycine are consistently low in the metabolic syndrome. In mice, diabetes lowered serine, and low serine drove neuropathy through deoxysphingolipids 5. These are animal findings 30.
How it is foundResearch only.
Inherited
SARS1 deficiency
SARS1 · autosomal recessive
A rare disorder of seryl-tRNA synthetase 1 — the enzyme that loads serine onto its tRNA — with neurodevelopmental delay, deafness, cardiomyopathy and metabolic decompensation set off by fever. Chronic amino acid supplementation is established; for the acute crisis there are no guidelines. In a 9-year-old boy whose three siblings had died in similar febrile episodes untreated, tripling his L-serine dose alongside standard supportive care carried him through a crisis with a left ventricular ejection fraction of 20%, with cardiac biomarkers normal within 20 days and the myocardial edema resolved at a month — the first documented survival of such a crisis on high-dose L-serine. A year later he had another febrile crisis and, despite an emergency protocol, died of cardiogenic shock 31. One child, rescued once and not twice, which is how n-of-1 evidence should be read.
How it is foundPlasma amino acids and SARS1 sequencing 31.
How it is measured
Serine is measured in plasma and CSF in the standard amino acid analysis, compared with age-related reference values 2,32. In research, a serine tolerance test, giving serine and measuring how fast it is cleared, revealed abnormal serine handling in diabetic mice 5.
- Plasma and CSF serineThe biochemical hallmark of the serine synthesis disorders is low serine in CSF and plasma 2.Needs age-specific reference values, since normal levels change with age 2.Late-onset, milder forms are easily missed 27.
- 1-DeoxysphingolipidsThe abnormal lipids made when serine palmitoyltransferase uses alanine; raised in HSAN1 and in macular telangiectasia type 2 16,24.Research and specialist laboratories.
Food, supplements and the evidence
Establishedreplicated in people, for a named outcome
Uncertainsmall, short, mixed, surrogate or preclinical
- Serine for diabetic neuropathy or macular telangiectasia, based on the deoxysphingolipid mechanism: shown in mice, untested in trials in people 5,24,30.
- Dietary serine and glycine restriction against cancer: effective in some mouse models, not others 6. The first human study of it is a single-arm phase I, reported alongside mouse work showing the diet both recruits cytotoxic T cells and triggers PD-L1 lactylation as an escape route 21. Feasible and safe is what that trial was designed to say, and all it says.
- L-serine for GRIN2B-related neurodevelopmental disorder, which is already given off-label on the strength of a mechanism. The first double-blind, randomized, placebo-controlled n-of-1 trials — four children, two six-month cycles each over a year — found a significant improvement in ONE of 15 measures on the primary assessment (Performance Mastery at 1.5 months), with 11 of the other 14 numerically in the same favorable direction but not significant, and no significant differences on the secondary outcomes that had group analysis. Two of the four children improved and no responder characteristics could be identified 34. The authors' own next step is better patient selection and pooled data, not wider use.
- L-serine for autism, where the current paper has no comparison group. Across 12 weeks of daily oral L-serine the authors report improved behavioral measures and more favorable Clinical Global Impression scores, with plasma extracellular-vesicle proteomic changes in immune pathways and naive CD4 T cell signatures shifting toward a more typical state 35. The abstract reports no control arm, no sample size and no effect sizes, which makes it a mechanism paper with a before-and-after attached rather than a test of whether the supplement works.
Sold asthe claim on the label, against the evidence
- “Phosphatidylserine for memory.” This is the serine product actually sold to consumers, and the trial in the population it is most marketed to is null. 100 mg a day of sunflower-derived phosphatidylserine in gummies, for 12 weeks, in healthy neurotypical children aged 8 to 12, randomized against placebo: no differences in the primary or secondary outcomes in the whole cohort. A pre-defined subgroup of children selected for consistently below-median baseline performance did better on one visuospatial memory task, and the product was safe and well tolerated 36. The trial was registered retrospectively, and company employees are among its authors.
- In dementia the pooled evidence carries its own refutation. A network meta-analysis of 29 trials in about 2,000 people with Alzheimer's disease or mild cognitive impairment found several supplements — phosphatidylserine 100 mg among them — associated with better scores on the Mini-Mental State Examination, and NO supplement producing a significant improvement on the Alzheimer's Disease Assessment Scale-Cognitive Subscale, the instrument built to measure cognition in dementia. The authors themselves say the absence of ADAS-Cog effects underscores how much the choice of assessment tool matters 37. The abstract's effect signs are internally inconsistent, so the pattern across the two instruments is the only part worth quoting from it.
- “Phosphatidylserine for mental fatigue in sport,” where the trial says in advance what a label will do with it. 97 professional male footballers took placebo, taurine with caffeine, or taurine and caffeine with 300 or 600 mg a day of phosphatidylserine for 14 days: after correction there were treatment-group effects on 30 m sprint time, Stroop reaction time, visual reaction time and perceived mental fatigue, but not auditory reaction time. The authors state that phosphatidylserine was NOT tested independently, that the 300 and 600 mg arms differed only modestly and inconsistently, that the study was not powered for a dose-response, and that because baseline decline indices were unavailable the fatigue-resistance findings do not show an intervention effect 38. The caffeine dose in every active arm was 200 mg.
What is strange about it
A deficiency treated before birth. In 2004 a fetus found to have PHGDH deficiency showed a falling head circumference by 26 weeks; serine given to the mother restored head growth, and the child was developing normally at four years 33.
Macular telangiectasia type 2, a slow loss of central vision, is linked to low serine and toxic deoxysphingolipids, and is more common in people with type 2 diabetes 24,26. Its first approved treatment, in March 2025, was not a metabolic one but an implant of cells releasing a nerve growth factor into the eye 39. The pivotal trials behind that approval are worth reading rather than the approval notice. Two identically designed phase 3 sham-controlled trials of the encapsulated-cell implant both met the primary ANATOMICAL endpoint — ellipsoid zone area loss over 24 months slowed by 0.091 mm² in one trial (p < 0.001) and 0.049 mm² in the other (p = 0.02). Changes in retinal sensitivity and reading speed were inconsistent between the two trials; vision-function questionnaire scores, loss of 15 or more letters of acuity, and serious adverse events did not differ from sham; and miosis (17% and 14%) and delayed dark adaptation (17% and 24%) occurred in the treated arms and almost not at all in the sham arms 40. An approval won on structure, with the functional benefit not yet consistent, in a disease whose metabolic cause this page describes.
Serine supplements treat one disorder of serine palmitoyltransferase and should be avoided in the other. In HSAN1 they help by giving the enzyme its proper substrate; in the childhood ALS caused by variants in the same enzyme, which already makes too much sphingolipid, serine is expected to make things worse 16,29. The biochemistry behind that warning has been measured. In two Chinese children with childhood-onset ALS carrying different SPTLC2 variants, specific sphingolipids were elevated against controls and the profiles differed from those of HSAN1 cases — and functional work showed the novel p.T66R variant REDUCES the inhibitory regulation of serine palmitoyltransferase by ORMDL proteins, leaving the enzyme unrestrained and producing excess sphingolipid 41. Same enzyme, opposite defect, opposite advice about the same supplement.
Where it connects
In the Atlas
Topics on the map
On the map
A star in Conditional amino acids, one of 14. Made from glycolysis, and the entry point to the one-carbon cycle that folate runs — which makes it the link between eating sugar and methylating DNA.
Sources
41 sources, numbered as they are cited. Every one was checked against PubMed or its publisher before it was cited here; the note under each says what it shows and what it does not.
- 1Tabatabaie L, Klomp LW, Berger R, et al. L-serine synthesis in the central nervous system: a review on serine deficiency disorders.doi:10.1016/j.ymgme.2009.10.012 · PMID 19963421
Review of the pathway and its disorders.
- 2van der Crabben SN, Verhoeven-Duif NM, et al. An update on serine deficiency disorders.doi:10.1007/s10545-013-9592-4 · PMID 23463425
Three defects; low CSF and plasma serine; treatable.
- 3Ducker GS, Rabinowitz JD. One-carbon metabolism in health and disease.doi:10.1016/j.cmet.2016.08.009 · PMID 27641100
Serine as the main source of one-carbon units.
- 4Olsen JV, Blagoev B, Gnad F, et al. Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.doi:10.1016/j.cell.2006.09.026 · PMID 17081983
6,600 phosphorylation sites.
- 5Handzlik MK, Gengatharan JM, Frizzi KE, et al. Insulin-regulated serine and lipid metabolism drive peripheral neuropathy.doi:10.1038/s41586-022-05637-6 · PMID 36697822
Mice; serine deficiency, deoxysphingolipids and neuropathy.
- 6Maddocks ODK, Athineos D, Cheung EC, et al. Modulating the therapeutic response of tumours to dietary serine and glycine starvation.doi:10.1038/nature22056 · PMID 28425994
Mouse cancer models.
- 7Brosnan ME, Brosnan JT. Histidine metabolism and function.doi:10.1093/jn/nxaa079 · PMID 33000155
The serine protease catalytic triad.
- 8Acuna-Hidalgo R, Schanze D, Kariminejad A, et al. Neu-Laxova syndrome is a heterogeneous metabolic disorder caused by defects in enzymes of the L-serine biosynthesis pathway.doi:10.1016/j.ajhg.2014.07.012 · PMID 25152457
12 families; all three enzymes.
- 9Chen J, Hadi F, Wen X, et al. Transcriptional regulation by PHGDH drives amyloid pathology in Alzheimer's disease.doi:10.1016/j.cell.2025.03.045 · PMID 40273909
Mice and human brain organoids, with the effect shown to be independent of the enzyme's enzymatic activity.
- 10Chen J, Xu M, Liu Y, Hadi F, Xue S, Chien S, Zhong S. RNA-binding activity of PHGDH drives amyloid-beta production in a human brain organoid model of sporadic Alzheimer's disease.doi:10.1073/pnas.2532234123 · PMID 41701839
The same laboratory, a year later, adding a third function and saying it is independent of the other two.
- 11Than-Trong E, Torres L, Gaudin-Guérif M, et al. L-serine-enriched diet restores impaired adult neurogenesis in the hippocampus of 3xTg-AD mice.doi:10.1177/13872877261487394 · PMID 42746964
The other pole of the same story: dietary serine helping a brain readout while leaving the plaques alone. Mice.
- 12Damseh N, Simonin A, Jalas C, et al. Mutations in SLC1A4, encoding the brain serine transporter, are associated with developmental delay, microcephaly and hypomyelination.doi:10.1136/jmedgenet-2015-103104 · PMID 26041762
ASCT1 deficiency; serine crosses the barrier poorly.
- 13Reeds PJ. Dispensable and indispensable amino acids for humans.doi:10.1093/jn/130.7.1835S · PMID 10867060
Serine as dispensable.
- 14Zhang X, Xu G, Shi J, et al. Microbial production of L-serine from renewable feedstocks.doi:10.1016/j.tibtech.2018.02.001 · PMID 29500004
Extraction and enzymatic catalysis as current routes.
- 15Xu G, Zhang X, Xiao W, et al. Production of L-serine and its derivative L-cysteine from renewable feedstocks using Corynebacterium glutamicum: advances and perspectives.doi:10.1080/07388551.2023.2170863 · PMID 36944486
Fermentation in development.
- 16Lone MA, Aaltonen MJ, Zidell A, et al. SPTLC1 variants associated with ALS produce distinct sphingolipid signatures through impaired interaction with ORMDL proteins.doi:10.1172/JCI161908 · PMID 35900868
HSAN1 and ALS variants; serine limitation shifts the profile.
- 17Wolosker H, Sheth KN, Takahashi M, et al. Purification of serine racemase: biosynthesis of the neuromodulator D-serine.doi:10.1073/pnas.96.2.721 · PMID 9892700
Rat brain enzyme; PLP-dependent.
- 18Papouin T, Ladépêche L, Ruel J, et al. Synaptic and extrasynaptic NMDA receptors are gated by different endogenous coagonists.doi:10.1016/j.cell.2012.06.029 · PMID 22863013
D-serine at synapses.
- 19Khin NA, Fan RH, Ge T, et al. A phase 2 randomized controlled trial of luvadaxistat in treatment of adults with cognitive impairment associated with schizophrenia: results from the ERUDITE study.doi:10.1038/s41386-026-02410-5 · PMID 42032293
203 participants, two doses, a 12-week treatment period and a clean primary endpoint. The cleanest test the D-serine hypothesis has had in people.
- 20Possemato R, Marks KM, Shaul YD, et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer.doi:10.1038/nature10350 · PMID 21760589
PHGDH raised in 70% of ER-negative breast cancers.
- 21Tong H, Jiang Z, Song L, et al. Dual impacts of serine/glycine-free diet in enhancing antitumor immunity and promoting evasion via PD-L1 lactylation.doi:10.1016/j.cmet.2024.10.019 · PMID 39577415
A single-arm phase I study alongside the mouse work. The starvation strategy generating its own resistance is the useful half.
- 22Devaux A, Villéger R, Roche G, et al. L-serine promotes pro-carcinogenic effects of colibactin-producing Escherichia coli.doi:10.1080/19490976.2025.2515480 · PMID 40471070
The bacterium's own serine-utilization operon, deleted, with carcinogenicity measured afterwards. Mice.
- 23Devaux A, Boucher D, Villéger R, Bonnet M. L-serine at the crossroads of microbiota, intestinal health, and disorders.doi:10.1038/s42003-026-10133-y · PMID 42050164
A current frame for the gut as a serine organ, including what the bacteria do with it.
- 24Wu L, Chen-Li G, Sanabria MDM. Macular telangiectasia type 2: an update.doi:10.1177/03000605261473180 · PMID 42551495
Serine deficiency and deoxysphingolipids in the retina.
- 25Toda A, Mohri S, Ueda K, Daido K, Fuchisawa D, Furuya F, Mukai E. Oral L-serine and D-serine acutely suppress postprandial hyperglycemia through inhibition of intestinal glucose absorption in healthy mice.doi:10.1016/j.bbrc.2026.154174 · PMID 42361737
A blood-sugar effect that is not about insulin at all, with the two enantiomers hitting different transporters. Mice.
- 26Jung M, Bucher F. Type 2 macular telangiectasia: pathogenesis — the interplay between neurodegeneration and metabolic changes.doi:10.1055/a-2936-0118 · PMID 42660511
Fewer than 5% have a serine-pathway mutation; diabetes more common. In German.
- 27Shen Y, Peng Y, Huang P, et al. Juvenile-onset PSAT1-related neuropathy: a milder phenotype of serine deficiency disorder.doi:10.3389/fgene.2022.949038 · PMID 36061210
Two adolescents with PSAT1 variants; serine and glycine cleared the skin, not the neuropathy.
- 28Abdelfattah F, Kariminejad A, Kahlert AK, et al. Expanding the genotypic and phenotypic spectrum of severe serine biosynthesis disorders.doi:10.1002/humu.24067 · PMID 32579715
15 families; a continuum.
- 29Syeda SB, Lone MA, Mohassel P, et al. Recurrent de novo SPTLC2 variant causes childhood-onset amyotrophic lateral sclerosis (ALS) by excess sphingolipid synthesis.doi:10.1136/jnnp-2023-332132 · PMID 38041679
Six patients; serine supplementation should be avoided in SPT-associated ALS.
- 30Hornemann T. Serine deficiency causes complications in diabetes.doi:10.1038/d41586-023-00054-9 · PMID 36697725
Commentary on the mouse findings.
- 31Valle VA, Wiedemnan A, Feigerlova E, et al. High-dose L-serine supplementation during febrile decompensation in SARS1 deficiency: a case report and review of the literature.doi:10.1002/jmd2.70090 · PMID 42158840
One child. It worked once and then it did not, and the paper says both.
- 32Sharer JD, De Biase I, Matern D, et al. Laboratory analysis of amino acids, 2018 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG).doi:10.1038/s41436-018-0328-6 · PMID 30459394
Amino acid analysis methods.
- 33de Koning TJ, Klomp LW, van Oppen AC, et al. Prenatal and early postnatal treatment in 3-phosphoglycerate-dehydrogenase deficiency.doi:10.1016/S0140-6736(04)17596-X · PMID 15610810
One case.
- 34den Hollander B, Rothuizen-Lindenschot M, Le HL, et al. Potential benefits of l-serine in children with GRIN2B loss-of-function variants: randomized n-of-1 trials.doi:10.1016/j.ymgme.2025.109268 · PMID 41265180
Four children, double-blind, placebo-controlled, a year each. The first randomized test of something already given off-label.
- 35Jang J, Yeo S, Kim JP, et al. Integrated proteomic and single-cell transcriptomic profiling elucidates immunomodulatory effects of L-serine in autism spectrum disorder.doi:10.1038/s41598-026-43467-y · PMID 41857206
Mechanism in place of a comparison group: the abstract reports no control arm, no sample size and no effect sizes.
- 36Friling M, Jackson PA, Kennedy D, et al. The cognitive effects of supplementation with sunflower phosphatidyl serine in healthy children aged 8 to 12 years: a randomized controlled trial.doi:10.1186/s12937-025-01264-9 · PMID 41318468
Randomized and placebo-controlled, registered retrospectively, and funded by a company whose employees are among the authors.
- 37Li Y, Leng Q, Wang Y. The impact of supplements on cognitive function for Alzheimer's disease or mild cognitive impairment: a systematic review and network meta-analysis.doi:10.1080/1028415X.2026.2703619 · PMID 42494057
29 trials, about 2,000 people. The abstract's signs are internally inconsistent, so only the pattern across instruments is quotable from it.
- 38Mizera K, Mazurek D, Martínez-Rodríguez A, Kęska A. Football-specific performance and cognitive fatigue resistance following supplementation with two phosphatidylserine doses combined with taurine and caffeine in professional male football players: a randomized, triple-masked, placebo-controlled trial.doi:10.3390/nu18162588 · PMID 42654170
97 players, four arms, and an abstract that dismantles in advance the attribution a label would make from it.
- 39Hoy SM. Revakinagene taroretcel: first approval.doi:10.1007/s40291-025-00787-5 · PMID 40540142
First FDA-approved treatment for MacTel type 2, March 2025.
- 40Chew EY, Gillies M, Jaffe GJ, et al. Cell-based ciliary neurotrophic factor therapy for macular telangiectasia type 2.doi:10.1056/EVIDoa2400481 · PMID 40693847
Two identically designed phase 3 trials, both hitting the anatomical endpoint. Funded by the manufacturer.
- 41Fu X, Gable K, Gupta SD, et al. Characterization of novel and recurrent SPTLC2 variants in childhood-onset amyotrophic lateral sclerosis: insights into sphingolipid dysregulation.doi:10.1177/22143602251370586 · PMID 40849231
Two children, with the lipids measured and the regulatory mechanism tested in cells.
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