Lysine
Summary
Lysine is best known for cold sores, but trials disagree: doses of about 1 g/day or less showed little benefit, one 6-month trial of 3 g/day reported fewer outbreaks, and a Cochrane review found no evidence of efficacy for prevention (grade D). Lysine with arginine lowered anxiety scores in a short trial run by a lysine maker. Gut upset is the main side effect.
Key facts
- An essential amino acid supplied by dietary protein; added to foods and supplements as L-lysine or its monohydrochloride[1]
- Recurrent herpes simplex (D, conflicting trials), anxiety with lysine plus arginine (D)[4][5][6][7][8]
- No evidence of efficacy for lysine in cold sore prevention[2]
- Trials at 1.2 g/day or less found little or no overall effect; benefits were reported at 1.25–3 g/day[5][6][7][4]
- A 44-year-old woman developed Fanconi syndrome and progressive kidney failure in association with lysine use[11]
- 5 graded human outcomes on this page
- October 10, 2026
How it works
ProposedLysine inhibits herpes simplex virus multiplication in cell cultures; whether this happens at supplement doses in people is unproven. In a short human study it also increased calcium absorption.[6][3][12]
What the human research says
Human trials only, one row per outcome. The form column shows what each trial actually tested. Grades follow our evidence-grading policy.
At a glance: strongest evidence per outcome
| Outcome | Grade | Effect | Strongest evidence | Rows |
|---|---|---|---|---|
| Anxiety | Grade D | Improved | RCT · n = 108 · 2007 | 1 row |
| Cold sores | Grade D | Mixed | Crossover RCT · n = 65 · 1980 | 4 rows |
Every graded row
| Outcome | Effect | Grade | Best evidence | PMID |
|---|---|---|---|---|
| Trait and stress-induced anxiety | Improved | Grade D | RCT · n = 108 · 2007 Healthy Japanese adults Form: L-lysine plus L-arginine · Dose: 2.64 g/day lysine + 2.64 g/day arginine · Duration: 1 week Trait anxiety and stress-induced state anxiety fell versus placebo; salivary cortisol and chromogranin A fell in men. | 17510493 (opens PubMed)Source [8] |
| Recurrent cold sores (herpes labialis) | Mixed | Grade D | Crossover RCT · n = 65 · 1980 Adults with recurrent herpes simplex labialis Form: L-lysine monohydrochloride · Dose: 1,000 mg/day · Duration: 12 weeks lysine, 12 weeks placebo No overall effect on recurrence rate, healing or lesion appearance, though more people were recurrence-free on lysine than on placebo (p = 0.05). | 6153847 (opens PubMed)Source [6] |
| Recurrent herpes simplex: outbreaks, severity and time to clear | Improved | Grade D | RCT · n = 52 · 1987 Adults with frequently recurrent herpes simplex Form: L-lysine monohydrochloride tablets · Dose: 1,000 mg L-lysine three times daily (3 g/day) · Duration: 6 months The lysine group had an average of 2.4 fewer outbreaks, milder symptoms and faster healing than placebo. | 3115841 (opens PubMed)Source [4] |
| Recurrent herpes simplex: recurrence rate | Mixed | Grade D | Crossover RCT · n = 41 · 1984 Non-immunocompromised adults with recurrent herpes simplex Form: L-lysine monohydrochloride · Dose: 624 or 1,248 mg/day · Duration: Crossover periods (length not stated in the abstract) 1,248 mg/day showed evidence of fewer recurrences; 624 mg/day did not. Neither dose shortened healing time. | 6435961 (opens PubMed)Source [7] |
| Recurrent herpes simplex: frequency, duration and severity | No effect | Grade D | RCT · n = 21 · 1984 Healthy adults with frequently recurring herpes simplex Form: Lysine hydrochloride · Dose: 400 mg three times daily (1.2 g/day) · Duration: Not stated in the abstract No substantial benefit for outbreaks in progress or for preventing recurrences. | 6419679 (opens PubMed)Source [5] |
Forms
| Form | Elemental % | Absorption (human data) | GI tolerance | Studied for |
|---|---|---|---|---|
| L-lysine monohydrochloride | Varies[1][4] | No human absorption data in our sources; lysine increased intestinal calcium absorption in a short study.[12] | Gut symptoms (nausea, stomachache, diarrhea) were the main adverse events across 71 studies, without a significant overall increase in risk.[9] | Recurrent herpes simplex (1–3 g/day) |
| Lysine + arginine combination | Varies[8] | No human absorption data in our sources.[8] | No adverse effects reported in the abstract.[8] | Anxiety and stress hormones (1 week) |
Studied doses
Doses studied in human trials ranged from 1,000 to 3,000 mg/day of L-lysine for 12 weeks to 6 months in recurrent herpes simplex (lower doses of 400–624 mg showed no effect), and 2.64 g/day with arginine for 1 week for anxiety.[4][6][7][8]
Interactions
Published interactions only: each row cites a source. No row means none was found in our sources, not that a combination is safe.
Other supplements
- CalciumPK studyLysine increased intestinal calcium absorption and reduced urinary calcium loss in short human studies.[12]
Who should be careful
- Kidney disease
- A case report links lysine use to Fanconi syndrome and tubulointerstitial nephritis that progressed to chronic kidney failure.[11]
- Cardiovascular or gallbladder disease
- A 2017 review advises warning people with these conditions about theoretical risks of lysine supplements.[3]
- Doses above 6 g/day
- A systematic review set a provisional no-observed-adverse-effect level of 6 g/day; 7.5 g/day was the lowest level with adverse effects.[9][10]
- Expecting antiviral-level protection
- Cochrane found no evidence of efficacy for lysine in cold sore prevention, while long-term oral antivirals had a small benefit.[2]
Talk to your pharmacist or clinician before starting a supplement, especially if you take prescription medicines.
Safety
Generally well tolerated up to about 6 g/day.
- Gut symptoms
- Across 71 human studies (17 mg to 17.5 g/day), the main adverse events were nausea, stomachache and diarrhea; overall risk was not significantly raised.[9]
- Upper level
- NOAEL 6 g/day and LOAEL 7.5 g/day in recent dose-response studies.[10]
- Kidney
- One case report of Fanconi syndrome and progressive kidney failure associated with lysine use.[11]
How to read the label
- Label dose vs clinical dosePositive herpes trials used about 1.25–3 g/day of L-lysine, while trials at or below 1.2 g/day showed little benefit.[7][4][5][3]
- Lysine vs lysine HClMost trials used L-lysine monohydrochloride; one positive trial stated 1,000 mg of L-lysine per dose.[4][1]
- Upper safety levelNo official upper limit exists; amino acid researchers propose a no-observed-adverse-effect level of 6 g/day.[10]
Cost per studied dose, without the sales pitch
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Cost per studied dose
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Frequently asked questions
Does lysine help cold sores?
Trials disagree. A 6-month trial of 3 g/day reported fewer outbreaks, but trials at about 1 g/day or less found little benefit, and Cochrane found no evidence of efficacy for prevention.[4][6][5][2]
How much lysine was used in cold sore studies?
Positive trials used about 1.25 to 3 g/day; 400–624 mg and 1 g/day were largely ineffective.[7][4][5][6]
Does lysine reduce anxiety?
One week of lysine plus arginine lowered anxiety scores in 108 healthy adults, in a trial led by an amino acid company researcher.[8]
Is lysine safe?
Gut upset is the main side effect; a provisional no-observed-adverse-effect level is 6 g/day. One case report links lysine to serious kidney injury.[9][11]
Does lysine affect calcium?
In short studies, lysine increased calcium absorption and reduced urinary calcium loss.[12]
Sources
- [1]21 CFR 172.320: Amino acids permitted as nutrients added to foods (includes L-lysine and L-lysine monohydrochloride). U.S. Food and Drug Administration (Electronic Code of Federal Regulations), 2026. guideline
- [2]Interventions for prevention of herpes simplex labialis (cold sores on the lips).. Cochrane Database Syst Rev, 2015. meta-analysis
- [3]Lysine for Herpes Simplex Prophylaxis: A Review of the Evidence.. Integr Med (Encinitas), 2017. review
- [4]Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis.. Dermatologica, 1987. RCT
- [5]Failure of lysine in frequently recurrent herpes simplex infection. Treatment and prophylaxis.. Arch Dermatol, 1984. RCT
- [6]Lysine prophylaxis in recurrent herpes simplex labialis: a double-blind, controlled crossover study.. Acta Derm Venereol, 1980. crossover-RCT
- [7]Treatment of recurrent herpes simplex infections with L-lysine monohydrochloride.. Cutis, 1984. crossover-RCT
- [8]Oral treatment with L-lysine and L-arginine reduces anxiety and basal cortisol levels in healthy humans.. Biomed Res, 2007. RCT
- [9]Safety assessment of L-lysine oral intake: a systematic review.. Amino Acids, 2019. systematic-review
- [10]Tolerable Upper Intake Level for Individual Amino Acids in Humans: A Narrative Review of Recent Clinical Studies.. Adv Nutr, 2023. review
- [11]Fanconi's syndrome and tubulointerstitial nephritis in association with L-lysine ingestion.. Am J Kidney Dis, 1996. observational
- [12]Dietary L-lysine and calcium metabolism in humans.. Nutrition, 1992. open-label
- [13]Lysine fortification reduces anxiety and lessens stress in family members in economically weak communities in Northwest Syria.. Proc Natl Acad Sci U S A, 2004. RCT
What changed
- First draft. Every PMID checked against NCBI E-utilities esummary (title and year taken from the record) and abstracts read for the cited rows.
- Adversarial review pass: every evidence row re-read against its PubMed abstract; the Cochrane conclusion on lysine read in the full abstract. Official source opened before citing: eCFR 21 CFR 172.320 (L-lysine and L-lysine monohydrochloride as permitted food-additive nutrients). No ODS fact sheet, NCCIH page or EMA monograph exists for lysine (NCCIH A–Z checked). Industry ties: first authors of the 2004 Syrian fortification trial (PMC420386) and the 2007 lysine-arginine trial are Ajinomoto Co. researchers; the 2019 safety systematic review was funded by the International Council on Amino Acid Science (PubMed grants); funding for the herpes trials is not stated in PubMed. Retraction, expression-of-concern, erratum and withdrawn checks on all 12 PMIDs: none flagged. Page set indexable. Independent browser review (4 parallel reviewers, every evidence row checked against its abstract and official sources on the Vercel preview) found: no factual errors; dose-pattern key fact re-cited to the individual trials instead of the 2017 review.