L-Lysine Dosing for Recurrent Herpes Labialis
L-lysine is not recommended as first-line therapy for cold sores because current CDC guidelines prioritize proven oral antivirals (valacyclovir, famciclovir, or acyclovir), which have high-quality evidence for efficacy, while lysine has inconsistent and low-quality supporting data. 1
First-Line Treatment: Proven Oral Antivirals
For acute treatment at prodrome or within 24 hours of lesion onset:
- Valacyclovir 2 g twice daily for 1 day is the preferred first-line regimen, reducing median episode duration by 1.0 day compared to placebo 1
- Famciclovir 1500 mg as a single dose is an equally effective alternative with convenient single-day dosing 1
- Acyclovir 400 mg five times daily for 5 days is effective but requires more frequent dosing 1
Critical timing: Treatment must be initiated during the prodromal phase or within 24 hours of symptom onset, as peak viral titers occur in the first 24 hours after lesion onset 1
Suppressive Therapy for Frequent Recurrences (≥6 per year)
For patients with ≥6 recurrences annually:
- Valacyclovir 500 mg once daily (can increase to 1000 mg once daily for very frequent recurrences) 1
- Famciclovir 250 mg twice daily 1
- Acyclovir 400 mg twice daily 1
Daily suppressive therapy reduces recurrence frequency by ≥75% among patients with frequent recurrences 1
L-Lysine: Evidence Summary and Dosing (If Considered)
Why Lysine Is Not First-Line
The evidence for lysine is mixed and of lower quality compared to prescription antivirals:
- One study (1984) showed benefit: 1000 mg daily lysine reduced lesion frequency when serum lysine exceeded 165 nmol/mL 2
- Two controlled trials showed no benefit: Studies using 1000 mg daily 3 and 1200 mg daily (400 mg three times daily) 4 found no substantial effect on recurrence rate, duration, or severity
- A 2017 systematic review concluded: Doses <1 g/day appear ineffective; doses >3 g/day may improve subjective symptoms, but high-quality evidence is lacking 5
If Lysine Is Used Despite Limited Evidence
For prophylaxis (based on available research):
- Minimum effective dose appears to be 1000–1200 mg daily 2, 3, 4
- Doses exceeding 3 g/day may provide greater subjective benefit according to the 2017 review 5
- One uncontrolled study used 312–1200 mg daily in single or multiple doses 6
For acute treatment:
- No high-quality evidence supports lysine for acute episode treatment 4, 5
- The 1984 trial showing no benefit used 400 mg three times daily (1200 mg/day total) 4
Important Caveats for Lysine Use
- Patients with cardiovascular or gallbladder disease should be cautioned about theoretical risks of lysine supplementation 5
- Lysine does not replace antiviral therapy and should not delay initiation of proven treatments 1
- Arginine restriction may be necessary for lysine to be effective, as the arginine-to-lysine ratio affects viral replication 6, 5
- Longer-duration controlled studies of doses >1.2 g/day are needed to definitively establish efficacy 5
Clinical Algorithm
For a patient with ≥3 recurrences per year:
- Acute episodes: Initiate valacyclovir 2 g twice daily for 1 day at first prodromal symptom 1
- If ≥6 recurrences per year: Start daily suppressive therapy with valacyclovir 500 mg once daily 1
- After 1 year of suppression: Consider discontinuation to reassess recurrence frequency, as it decreases over time in many patients 1
- Lysine supplementation: May be considered as adjunctive therapy (not replacement) at doses ≥1000 mg daily, with realistic counseling that evidence is inconsistent 2, 3, 4, 5
Common Pitfalls to Avoid
- Relying solely on lysine instead of proven antivirals delays effective treatment and prolongs episodes 1
- Starting antiviral treatment too late (after 24 hours) significantly decreases efficacy 1
- Using topical antivirals alone, which provide only modest benefit compared to oral therapy 1
- Failing to counsel patients about trigger avoidance (UV light, stress, fever, menstruation), which can reduce recurrence frequency even without medication 1