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Ser4.5
L-Serine Research
Likely helps
26 peer-reviewed studies
What the evidence says
Likely helps
L-Serine appears to help in 6 of 6 studies with measurable effects — the evidence leans clearly favourable.
Most evidence is from high-quality meta-analyses and randomised trials published 2004–2026 with a typical study size of 46 participants.
Based on 26 studies · 1 meta-analysis · 11 RCTs · 2,505 total participants
Patients with developmental and epileptic encephalopathies1
MDD patients1
Patients with serine metabolism disorders1
Active research area
19 studies in the last 5 years · Latest meta-analysis: 2021
200420152026
1Treatable variants in hereditary peripheral neuropathiesSystematic Reviewn=2,046 · very large study2021
In plain English: The 'treatable' variants highlighted in this project will be flagged in the treatabolome database to alert clinicians at the time of the diagnosis and enable timely treatment of patients with hereditary peripheral neuropathies.
Jennings MJ et al. · Journal of neuromuscular diseases (2021)
The 'treatable' variants highlighted in this project will be flagged in the treatabolome database to alert clinicians at the time of the diagnosis and enable timely treatment of patients with hereditary peripheral neuropathies.
2Precision therapies for developmental and epileptic encephalopathiesReview2025
In plain English: Additionally, the importance of enhancing access to genetic testing, conducting robust natural history studies, and employing innovative clinical trial designs is emphasized.
Samanta D et al. · Pediatric neurology (2025)
Additionally, the importance of enhancing access to genetic testing, conducting robust natural history studies, and employing innovative clinical trial designs is emphasized.
Future directions focus on addressing the challenges in developing and implementing gene-based therapies, integrating systems biology, leveraging artificial intelligence for data analysis, and fostering collaboration among stakeholders.
The rapidly advancing field of precision therapeutics for DEEs holds promise to improve outcomes through tailored, equitable, and patient-centered care.
3Peripheral blood metabolites in major depressive disorderMeta-Analysisn=46 · small study2021
In plain English: MDD patients were characterized by ... lower levels of L-acetylcarnitine, creatinine, L-asparagine, L-glutamine, linoleic acid, pyruvic acid, palmitoleic acid, L-serine, oleic acid ... compared with controls.
Pu J et al. · Molecular psychiatry (2021)
Pathway and network analyses revealed altered amino acid metabolism and lipid metabolism, especially for the tryptophan-kynurenine pathway and fatty acid metabolism, in the peripheral system of MDD patients.
Our findings may facilitate biomarker development and the elucidation of the molecular mechanisms that underly MDD.
4L-serine homeostasis in health and diseaseReview2023
In plain English: A serine tolerance test may provide a quantitative readout of l-serine homeostasis that identifies patients who may be susceptible to neuropathy or responsive to therapy.
Handzlik MK et al. · Annual review of nutrition (2023)
Compromised regulation or activity of l-serine synthesis and disposal occurs in the context of genetic diseases as well as chronic disease states, leading to low circulating l-serine levels and pathogenesis in the nervous system, retina, heart, and aging muscle.
Dietary interventions in preclinical models modulate sensory neuropathy, retinopathy, tumor growth, and muscle regeneration.
A serine tolerance test may provide a quantitative readout of l-serine homeostasis that identifies patients who may be susceptible to neuropathy or responsive to therapy.
5SLC1A4 role in neurodevelopment and neurodegenerationReview2025
In plain English: This review examines the role of SLC1A4 in neurodevelopment and neurodegeneration and assesses the therapeutic potential of serine supplementation to treat neurodevelopmental symptoms associated with mutations in SLC1A4 , as well as schizophrenia, depression, traumatic brain injury, and Alzheimer's and Parkinson's diseases.
Elazar D, Alvarez N, Drobeck S, Gunn TM. · International journal of molecular sciences (2025)
In the brain, SLC1A4 plays an important role in transporting levo (L) and dopa (D) isomers of serine.
L-serine is required for many cellular processes, including protein and sphingolipid synthesis, while D-serine is a co-agonist required for normal neurotransmission through N -methyl-D-aspartate receptors.
Through its roles transporting L-serine across the blood-brain barrier and regulating synaptic D-serine levels, SLC1A4 helps establish and maintain brain health across the lifespan.
In plain English: This review aims to summarize the research progress of serine in diseases, propose the problems that need to be solved in the future, and provide guidance for subsequent research and development.
Li P, Wu X, Huang Y, Qin R, Xiong P, Qiu Y. · Frontiers in cellular and infection microbiology (2025)
An increasing number of studies have demonstrated that L-serine is widely used in the adjuvant therapy of many diseases (e.g., inflammation, infections, fibrosis, and tumors).
Here, we summarize the synthesis and metabolism of serine followed by its functions in health and disease.
Moreover, we delineate the potential mechanisms whereby L-serine is involved in the occurrence and progression of respiratory diseases.
7ADAS-Cog score improvementRCTn=12 · very small study2023
In plain English: Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics, metabolomics, proteomics and imaging analysis.
Yulug B et al. · Translational neurodegeneration (2023)
Large benefit
← WorseNo effectBetter →
Likely real
We showed a significant decrease of AD Assessment Scale-cognitive subscale (ADAS-Cog) score on day 84 vs day 0 (P = 0.00001, 29% improvement) in the CMA group.
Moreover, the plasma levels of proteins and metabolites associated with NAD + and glutathione metabolism were significantly improved after CMA treatment.
Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics, metabolomics, proteomics and imaging analysis.
In plain English: This study suggests the possibility of personalizing sleep-support supplementation based on personal life habits, sleep conditions, and sleep problems, in addition to the known efficacy of dietary supplements.
Imafuku F et al. · Nutrients (2023)
All the tested supplements were found to ameliorate sleep problems significantly (Analysis 1).
In Analysis 2, the PCs specific to improved subjects were found to differ depending on the dietary supplements and sleep problems.
In addition, subjects who consumed dairy products often showed improvement in their sleep problems with all the tested supplements.
11Clinical improvement in GRIN2B-NDD patientsRCT2025
In plain English: These pioneering n-of-1 trials provide insights into l-serine's potential for GRIN2B-NDD, with improvements in two of four patients, though no clear distinguishing responder-characteristics were identified.
den Hollander B et al. · Molecular genetics and metabolism (2025)
Huge benefit
← WorseNo effectBetter →
These pioneering n-of-1 trials provide insights into l-serine's potential for GRIN2B-NDD, with improvements in two of four patients, though no clear distinguishing responder-characteristics were identified.
Future trials should focus on refining patient selection, the use of multiple baseline designs, establishing a core outcome set and pooling treatment data to better understand patient-specific responses.
In plain English: In terms of intestinal metabolites, the levels of acylcarnitine18:0 (ACar.18:0), cotinine, N-arachidonoyl-L-serine, phosphatidylcholine ... changed after FMT.
Zhi W et al. · Scientific reports (2024)
Flow cytometry analysis showed the absolute count of plasma B cells decreased in subjects, and this change correlated with alterations in the intestinal microbiota and metabolites.
This study preliminarily evaluates the safety and efficacy of FMT in patients with IgAN.
No significant adverse reactions were observed, and the administration of FMT alongside ACEI/ARB therapy was effective in reducing urinary protein levels in patients with IgAN, a process that may be associated with B-cell immunity.
13Clinical improvement in GRIN-related encephalopathyOpen-Label2024
In plain English: L-serine treatment was associated with significant improvement in the median Gross Motor Function-88 total score (P = 0.002) and the mean Pediatric Quality of Life total score (P = 0.00068), regardless of severity.
Juliá-Palacios N et al. · Brain : a journal of neurology (2024)
Noticeable benefit
← WorseNo effectBetter →
Likely real
Their clinical phenotypes showed 91% had intellectual disability (61% severe), 83% had behavioural problems, 78% had movement disorders and 58% had epilepsy.
Expressive (P = 0.005), Personal (P = 0.003), Community (P = 0.009), Interpersonal (P = 0.005) and Fine Motor (P = 0.031) subdomains improved for the whole cohort, although improvement was mostly found in the mild group.
The Growth Scale Values in the Cognitive subdomain of the Bayley-III Scale showed a significant improvement in the severe group (P = 0.016), with a mean increase of 21.6 points.
The protocol called for enrollment of patients with a diagnosis of probable or definite ALS, age 18-85 years, disease duration of less than three years and forced vital capacity (FVC) ≥ 60%.
Of 20 patients enrolled, one withdrew before receiving study drug and two withdrew with gastro-intestinal problems.
16Cognition and mood in older adultsRCTn=50 · small study2016
In plain English: D-serine administration may be a strategy to improve spatial memory, learning and problem solving in healthy older adults.
Avellar M et al. · Oncotarget (2016)
Noticeable benefit
← WorseNo effectBetter →
Likely real
D-serine administration improved performance in the Groton Maze learning test of spatial memory and learning and problem solving (F(3, 38)= 4.74, p = 0.03).
Subjects that achieved higher increases in plasma D-serine levels after administration improved more in test performance (r2=-0.19 p = 0.009).
Future studies should evaluate the impact of long-term D-serine administration on cognition in older adults.
In plain English: High-dose oral l-serine supplementation appears safe in patients with HSAN1 and is potentially effective at slowing disease progression.
Fridman V et al. · Neurology (2019)
Noticeable benefit
← WorseNo effectBetter →
Likely real
After 1 year, the l-serine group experienced improvement in CMTNS relative to the placebo group (-1.5 units, 95% CI -2.8 to -0.1, p = 0.03), with evidence of continued improvement in the second year of treatment (-0.77, 95% CI -1.67 to 0.13, p = 0.09).
Concomitantly, deoxysphinganine levels dropped in l-serine-treated but not placebo-treated participants (59% decrease vs 11% increase; p < 0.001).
High-dose oral l-serine supplementation appears safe in patients with HSAN1 and is potentially effective at slowing disease progression.
In plain English: The results show that treating patients infected with COVID-19 with CMAs lead to a more rapid symptom-free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.
Altay O et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2021)
Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly improved in patients treated with CMAs as compared to placebo.
A comprehensive analysis of the plasma metabolome and proteome reveals major metabolic changes.
The results show that treating patients infected with COVID-19 with CMAs lead to a more rapid symptom-free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.
In plain English: To address the urgent issue, the review summarizes Se-contained foods (plant-based foods, animal-based foods, and Se supplements), brain selenoproteins, mechanisms of Se in cognition (improvement of synaptic plasticity, regulation of Zn 2+ level, inhibition of ferroptosis, modulation of autophagy and de novo synthesis of L-serine), and effects of Se on cognitive deficits, as well as consequently sheds light on great potentials of Se in the prevention and treatment of cognitive deficits.
Bai YZ, Zhang Y, Zhang SQ. · Metabolic brain disease (2024)
Due to the disproportionate distribution of Se in the soil, the amount of Se varies greatly in various foods, resulting in a large proportion of people with Se deficiency worldwide.
Numerous cell and animal experiments demonstrate Se deficiency-induced cognitive deficits and Se supplementation-improved cognitive performances.
However, human studies yield inconsistent results and the mechanism of Se in cognition still remains elusive, which hinder the further exploration of Se in human cognition.
In plain English: Understanding these pathways could highlight new therapeutic targets to mitigate brain injury.
Carretero VJ, Álvarez-Merz I, Hernández-Campano J, Kirov SA, Hernández-Guijo JM. · Neural regeneration research (2025)
Blocking N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during hypoxia.
Thus, previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain injury.
Understanding these pathways could highlight new therapeutic targets to mitigate brain injury.