L-Serine
Also called serine, L-Ser, (S)-2-amino-3-hydroxypropanoic acid.
Best grade D across 7 graded outcomes Amino acid Last checked
The short answer
From 11 sourcesL-serine is a dietary amino acid studied at very different doses. A 3 g bedtime dose improved self-rated sleep in small Japanese crossover studies (grade D), a serine-plus-EPA blend eased back and knee pain, and very high medical doses (about 400 mg/kg/day) slowed a rare inherited nerve disease in an 18-person trial.
Every graded outcome on this page
7 rows · line = participants- DGrade DSleep problems with 300 mg/day (open comparison of four supplements)Sleepn 160
- DGrade DLow-back and knee pain (L-serine plus EPA)Painn 120
- DGrade DSelf-rated sleep quality with 3 g before bedSleepn 53
- DGrade DCircadian phase (melatonin onset) with 3 g before bedSleep timingn 33
- DGrade DDevelopment and motor scores in children with GRIN loss-of-function variantsRare genetic disordern 24
- DGrade DNeuropathy progression in HSAN1 (rare inherited nerve disease)Neuropathyn 18
- DGrade DDaily-task performance in children with GRIN2B variants (n-of-1 trials)Rare genetic disordern 4
- 4 more graded outcomes, in the evidence chapter
Key facts
- Sleep studies
- 3 g of L-serine 30 minutes before bed improved self-rated sleep in 2 small industry-run crossover studies (53 and 9 people)7
- Medical doses
- 400 mg/kg/day for 1 year slowed nerve-score decline versus placebo in 18 adults with HSAN1, a rare inherited neuropathy1
- Pain blend
- 594 mg L-serine plus 149 mg EPA daily for 8 weeks lowered low-back and knee pain scores in 120 adults; the two ingredients were not tested separately4
- High-dose tolerance
- Up to 15 g twice daily in a 6-month ALS safety trial was generally tolerated; 2 of 20 withdrew with gut problems3
- Tolerance in healthy men
- 3, 6, 9 and 12 g a day, each for 4 weeks, caused no treatment-related adverse events in 30 healthy men; the authors set a no-observed-adverse-effect level of 12 g a day10
What it is
L-serine is a non-essential amino acid in food protein; the body uses it to make D-serine and sphingolipids.
How it works
ProposedL-serine feeds several pathways: it is converted to D-serine (an NMDA-receptor co-agonist) and is the normal substrate of the enzyme that makes sphingolipids. In HSAN1 a faulty enzyme uses alanine instead and builds toxic deoxysphingolipids; extra L-serine shifted it back and lowered those lipids in people. The sleep and pain effects have no confirmed mechanism.216
Forms
Form
| Form | Elemental % | Absorption (human data) | GI tolerance | Studied for |
|---|---|---|---|---|
| L-serine powder or capsules | Varies7Not applicable (single compound; no elemental fraction) | No human bioavailability study is cited here; in HSAN1, oral L-serine lowered blood deoxysphingolipids, showing it is absorbed and used.21 | No adverse events in the 8-week pain trial; no treatment-related adverse events at 3 to 12 g a day for 4 weeks each in healthy men; no serious related events at 400 mg/kg/day for a year; gut problems led 2 of 20 to withdraw at doses up to 15 g twice daily.41013 | Sleep (3 g at bedtime), pain (in a blend) and rare neurological disorders (very high doses) |
What the human research says
Human trials only, one row per outcome. The form line shows what each trial actually tested. Grades follow our evidence-grading policy.
Trial map
7 graded outcomes, largest study first7 graded outcomes: 6 improved, 1 mixed. The largest, a 2023 open-label trial of 160 people on sleep problems with 300 mg/day (open comparison of four supplements), found an improvement.
1Sleep problems with 300 mg/day (open comparison of four supplements)
Improved · Grade D · Open-label trial, 160 people, 2023
Adults with sleep problems
Dose, result and source| Outcome | Found | People | Study | Who was studied |
|---|---|---|---|---|
| Sleep problems with 300 mg/day (open comparison of four supplements) | Improved | 160 | Grade D · Open-label trial, 2023 | Adults with sleep problems |
| Low-back and knee pain (L-serine plus EPA) | Improved | 120 | Grade D · RCT, 2020 | Adults with low-back and knee pain for at least 3 months (Japan) |
| Self-rated sleep quality with 3 g before bed | Improved | 53 | Grade D · Crossover RCT, 2014 | Healthy Japanese adults dissatisfied with their sleep |
| Circadian phase (melatonin onset) with 3 g before bed | Improved | 33 | Grade D · RCT, 2022 | Healthy university students in autumn and winter (Japan) |
| Development and motor scores in children with GRIN loss-of-function variants | Improved | 24 | Grade D · Open-label trial, 2024 | Children aged 2–18 with GRIN gene loss-of-function variants (Spain-led study) |
| Neuropathy progression in HSAN1 (rare inherited nerve disease) | Improved | 18 | Grade D · RCT, 2019 | Adults aged 18–70 with symptomatic hereditary sensory and autonomic neuropathy type 1 |
| Daily-task performance in children with GRIN2B variants (n-of-1 trials) | Mixed | 4 | Grade D · RCT, 2025 | Children with GRIN2B loss-of-function variants |
Every graded row
7 rowsShowing 7 of 7 outcomes. Human trials only.
DGrade DSleep problems with 300 mg/day (open comparison of four supplements)SleepImprovedOpen-label trial
n 160 · 2023
Improved All four tested supplements (L-theanine, GABA, Apocynum venetum leaf extract and L-serine) were reported to improve sleep problems significantly; there was no placebo arm.
- Design
- Open-label trial, n = 160, 2023
- Population
- Adults with sleep problems
- Form
- L-serine
- Dose
- 300 mg/day
- Duration
- One crossover period per supplement (length not stated in the abstract)
- Source
- Reference 9 · PubMed 37242260 (opens PubMed)
DGrade DLow-back and knee pain (L-serine plus EPA)PainImprovedRCT
n 120 · 2020
Improved Low-back (JLEQ) and knee (JKOM) pain scores and several Brief Pain Inventory items were better than placebo at weeks 4–8; no adverse events were observed.
- Design
- RCT, n = 120, 2020
- Population
- Adults with low-back and knee pain for at least 3 months (Japan)
- Form
- Blend: L-serine with EPA
- Dose
- 594 mg L-serine + 149 mg EPA daily
- Duration
- 8 weeks (plus 4 weeks follow-up)
- Source
- Reference 4 · PubMed 32520991 (opens PubMed)
DGrade DSelf-rated sleep quality with 3 g before bedSleepImprovedCrossover RCT
n 53 · 2014
Improved Sleep-initiation and sleep-maintenance ratings improved versus placebo in study 1; in study 2 two sleep-satisfaction ratings improved, and actigraph night waking showed only a trend (p=0.08).
- Design
- Crossover RCT, n = 53, 2014
- Population
- Healthy Japanese adults dissatisfied with their sleep
- Form
- L-serine powder (≥98.5%)
- Dose
- 3 g, 30 minutes before bed
- Duration
- 4 nights per period (study 1); 2 nights (study 2, 9 people)
- Source
- Reference 7 · PubMed 25197619 (opens PubMed)
DGrade DCircadian phase (melatonin onset) with 3 g before bedSleep timingImprovedRCT
n 33 · 2022
Improved Dim-light melatonin onset drifted later on placebo but not on L-serine (difference between groups p=0.04); sleep habits did not change in either group.
- Design
- RCT, n = 33, 2022
- Population
- Healthy university students in autumn and winter (Japan)
- Form
- L-serine
- Dose
- 3.0 g, 30 minutes before bed
- Duration
- 2 weeks
- Source
- Reference 8 · PubMed 36028887 (opens PubMed)
DGrade DDevelopment and motor scores in children with GRIN loss-of-function variantsRare genetic disorderImprovedOpen-label trial
n 24 · 2024
Improved Several adaptive-behaviour subdomains, gross motor function and quality of life improved from baseline, mostly in milder cases; one child stopped for irritability and insomnia. There was no control group.
- Design
- Open-label trial, n = 24, 2024
- Population
- Children aged 2–18 with GRIN gene loss-of-function variants (Spain-led study)
- Form
- Oral L-serine
- Dose
- Not stated in the abstract
- Duration
- 52 weeks
- Source
- Reference 5 · PubMed 38380699 (opens PubMed)
DGrade DNeuropathy progression in HSAN1 (rare inherited nerve disease)NeuropathyImprovedRCT
n 18 · 2019
Improved The neuropathy score (CMTNS) improved versus placebo by 1.5 units (p=0.03); toxic deoxysphinganine fell 59% on L-serine versus an 11% rise on placebo. No serious adverse effects were related to L-serine.
- Design
- RCT, n = 18, 2019
- Population
- Adults aged 18–70 with symptomatic hereditary sensory and autonomic neuropathy type 1
- Form
- Oral L-serine
- Dose
- 400 mg/kg/day
- Duration
- 1 year randomized, then 1 year open-label
- Source
- Reference 1 · PubMed 30626650 (opens PubMed)
DGrade DDaily-task performance in children with GRIN2B variants (n-of-1 trials)Rare genetic disorderMixedRCT
n 4 · 2025
Mixed One task-performance measure improved at 1.5 months; most others moved in a favourable direction without reaching significance. Two of the four children appeared to benefit.
- Design
- RCT, n = 4, 2025
- Population
- Children with GRIN2B loss-of-function variants
- Form
- Oral L-serine
- Dose
- Not stated in the abstract
- Duration
- 1 year (two 6-month cycles)
- Source
- Reference 6 · PubMed 41265180 (opens PubMed)
What the numbers add up to
Each point is worked out from the data and the sources numbered on this page, with the arithmetic shown under it. It adds no new data and is not medical advice.
Sleep data are small and short
Medical doses are far higher
The pain result is a blend
The 120-person pain trial gave L-serine with EPA, an omega-3 fat, so it does not show what L-serine does alone.4
Studied doses
Doses used in research, shown against the official limits. They describe the studies, not a recommendation for you.
Studied doses in research, not advice. These are amounts used in research, not personal advice. Your clinician or pharmacist can say what fits you.
Doses studied in human trials
Doses studied in human trials ranged from 300 mg/day and 3 g at bedtime for a few nights to 2 weeks in sleep studies, 594 mg/day in a pain blend for 8 weeks, 3 to 12 g/day for 4 weeks each in a healthy-adult tolerance trial, and very high medical doses (400 mg/kg/day, or up to 15 g twice daily) for 6 months to 2 years in rare neurological diseases.97841013
When trials measured an effect
4 outcomes| Outcome | Measured at | Basis |
|---|---|---|
| Self-rated sleep | Within the first nights (2- to 4-night crossover periods) | 3 g 30 minutes before bed; sleep ratings improved versus placebo within each short period7 |
| Melatonin timing (circadian phase) | Week 2 (end of trial) | Dim-light melatonin onset compared between groups after 2 weeks8 |
| Low-back and knee pain (L-serine with EPA) | Week 4, sustained to week 8 | Pain scores better than placebo at weeks 4 to 84 |
| Neuropathy score in HSAN1 | 1 year (end of randomized phase) | 400 mg/kg/day vs placebo; CMTNS compared at 1 year1 |
Interactions and safety
Published interactions only: each row cites a source. No row means none was found in our sources, not that a combination is safe.
What L-Serine meets
0 cited rows 2 tested togetherMedicines 0
No medicine rows in our sources.
Supplements and foods 2
- Tested together in a graded trial
Choose a medicine or supplement above to read its cited rows here.
Also cited: 2 tested together
L-ValineL-Valine page
Tested together
Perceived fatigue during a 2-hour cycling session (amino acid mix). Graded on the L-Valine page; tested together is not a claim that they work better together.
Omega-3Omega-3 page
Tested together
Low-back and knee pain (L-serine plus EPA). Graded on the L-Serine page; tested together is not a claim that they work better together.
Interactions
0 agentsNone found in our sources.
Check with what you take
Kept on this device onlyAdd what you take. We list every interaction our evidence profiles cite between L-Serine and your picks, and between your picks.
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Add a supplement or medicine you take to check it against L-Serine.
Starting from one medicine? The interaction checker rates how serious each pair is, on a curated list of 19 entries for 11 medicines. This cabinet has no severity rating: it lists every interaction row our supplement pages cite.
Who should be careful
3 groups- Rare neurological conditions
- The HSAN1, ALS and GRIN studies used very high doses under specialist supervision with regular blood tests; those doses are not general supplement amounts.135
- Sensitive stomach at high doses
- In the ALS safety trial, 2 of 20 people withdrew with gastrointestinal problems at doses up to 15 g twice daily.3
Reading the label, and the cost per dose
Compare any product you already have by the amount it delivers, not by capsule count or front-of-pack weight.
How to read the label
2 checksLabel dose vs studied dose
L-serine vs D-serine vs phosphatidylserine
These are three different compounds. L-serine is the dietary amino acid and a precursor of D-serine; phosphatidylserine is a membrane lipid with its own trials.6
Have the bottle? Photograph its Supplement Facts panel and see each line, l-serine included, beside the doses and forms the trials used in Label X-Ray.
Cost per studied dose, without the sales pitch
Your numbers, no product dataEnter the price, servings and the amount per serving from your label.
Frequently asked questions
Short answers to common questions; the numbers link to the sources below.
Common questions
8 answersDoes L-serine help you sleep?
Does L-serine help joint or back pain?
One 120-person trial of an L-serine plus EPA blend lowered low-back and knee pain scores over 8 weeks. L-serine alone has not been tested for pain.4
What are the side effects of L-serine?
Is L-serine safe to take long term?
Does L-serine interact with medicines?
No interactions are documented: LiverTox, LactMed and NCCIH have no L-serine entry, and the trials cited here report none. NCCIH advises telling your health care providers about every supplement you use.11
Is L-serine the same as D-serine?
No. L-serine is the form in food protein and is converted in the body to D-serine. The two have been tested for different things.6
How much L-serine was used in sleep studies?
Sources
11 sources: trial abstracts, NIH fact sheets and reference databases. Numbers in the text link here.
Sources cited on this page
11 sources- 1Randomized trial of l-serine in patients with hereditary sensory and autonomic neuropathy type 1.RCT Neurology, 2019 · PMID 30626650
- 2Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1.Open-label trial J Clin Invest, 2011 · PMID 22045570
- 3Phase I clinical trial of safety of L-serine for ALS patients.RCT Amyotroph Lateral Scler Frontotemporal Degener, 2017 · PMID 27589995
- 4l-Serine and EPA Relieve Chronic Low-Back and Knee Pain in Adults: A Randomized, Double-Blind, Placebo-Controlled Trial.RCT J Nutr, 2020 · PMID 32520991
- 5L-serine treatment in patients with GRIN-related encephalopathy: a phase 2A, non-randomized study.Open-label trial Brain, 2024 · PMID 38380699
- 6Potential benefits of l-serine in children with GRIN2B loss-of-function variants: Randomized n-of-1 trials.RCT Mol Genet Metab, 2025 · PMID 41265180
- 7Effects of L-serine ingestion on human sleep.Crossover RCT Springerplus, 2014 · PMID 25197619
- 8Intake of L-serine before bedtime prevents the delay of the circadian phase in real life.RCT J Physiol Anthropol, 2022 · PMID 36028887
- 9Analysis of the Effects of Known Sleep-Support Supplements in Relation to Life Habits, Sleep Conditions, and Sleep Problems.Open-label trial Nutrients, 2023 · PMID 37242260
- 10Subchronic Tolerance Trials of Graded Oral Supplementation with Phenylalanine or Serine in Healthy Adults.Open-label trial Nutrients, 2021 · PMID 34201370
- 11Using Dietary Supplements WiselyFact sheet National Center for Complementary and Integrative Health (NCCIH), 2019 · nccih.nih.gov
What changed
Every dated change to this page: what changed, who made it and why.
Change log
3 entries| Date | Change | Who and why |
|---|---|---|
| key facts, forms, studied doses, time to effect, who should avoid, FAQ, questions, related | Added a 4-week graded tolerance trial in 30 healthy men (3 to 12 g a day, no treatment-related adverse events; serine-arm size from the PMC full text) to key facts, forms, studied doses and FAQ; cited NCCIH in the pregnancy and breastfeeding note (no reliable data); added time-to-effect rows, FAQ items on side effects, long-term safety and interactions, page questions and a goal-hub link. PubMed search for L-serine RCTs and meta-analyses through 2026 found no newer trial of L-serine alone beyond those already in the table (other hits were D-serine, phosphatidylserine or multi-ingredient blends). Interactions checked: LiverTox, LactMed and NCCIH have no L-serine entry and the cited trials report none, so the list stays empty. | Writer: Kymata Health EditorialTrigger: A–Z audit against docs/supplements/AUDIT-STANDARD.md |
| all | First draft. Every PMID checked against NCBI E-utilities esummary (title, journal and year taken from the record) and abstracts read for each cited row. | Writer: Kymata Health EditorialTrigger: new page |
| all | Adversarial review pass: every number in each evidence row's result, dose, duration, n and population fields was machine-checked against its PubMed abstract, and figures not in an abstract were confirmed in the PMC full text (noted per row). Unverified study-country, funding and mechanism wording was removed or sourced, rows whose sample size could not be confirmed were dropped, and retraction, erratum and expression-of-concern flags were checked on every PMID (two errata, noted on their rows; no retractions). Page set indexable. | Writer: Kymata Health EditorialTrigger: review |
Supplement & Nutrient Encyclopedia. Educational information only; it is not medical advice and does not replace a clinician. Dietary supplements are not intended to diagnose, treat, cure or prevent any disease. Statements about supplements have not been evaluated by the FDA.