L-Lysine for Cold Sores: Evidence-Based Dosing Recommendations
L-lysine supplementation is not recommended as first-line therapy for cold sores because high-quality evidence does not support its efficacy, and proven antiviral medications (valacyclovir, famciclovir, acyclovir) should be used instead. 1
Why L-Lysine Is Not Recommended
The evidence for L-lysine in treating or preventing herpes labialis is weak and contradictory:
Conflicting Clinical Trial Data
A double-blind, placebo-controlled crossover trial of 1000 mg daily L-lysine in 65 patients found no effect on recurrence rate overall, though a subset of patients remained recurrence-free during lysine treatment (p=0.05). 2
A separate double-blind, placebo-controlled trial of 1200 mg daily (400 mg three times daily) in 21 patients with frequent recurrences found no substantial benefit for either treatment of active episodes or prevention of recurrences. 3
One small study of 26 volunteers receiving 1000 mg daily suggested fewer lesions when serum lysine exceeded 165 nmol/ml, but this has not been replicated in larger, higher-quality trials. 4
A 1983 survey study (not a controlled trial) reported subjective improvement with an average dose of 936 mg daily, but this lacks the rigor of placebo-controlled evidence. 5
Why This Evidence Is Insufficient
- The positive studies are either uncontrolled surveys subject to placebo effect 5 or small trials with marginal statistical significance 2, 4
- The two most rigorous placebo-controlled trials showed no clinically meaningful benefit 2, 3
- No major clinical guidelines (CDC, AAD, IDSA) recommend L-lysine for herpes labialis 1, 6
What You Should Use Instead: Proven Antiviral Therapy
For Episodic Treatment (Active Cold Sore)
Valacyclovir 2 g twice daily for 1 day (doses separated by 12 hours) is the most convenient and effective first-line treatment, reducing episode duration by approximately 1 day when started within 24 hours of symptom onset. 1
Alternative regimens include:
- Famciclovir 1500 mg as a single dose 1
- Acyclovir 400 mg five times daily for 5 days (requires more frequent dosing, lower adherence) 1
Critical Timing
Treatment must be initiated during the prodromal phase (tingling, burning) or within 24 hours of lesion appearance because peak viral titers occur in the first 24 hours, making early intervention essential. 1
For Suppressive Therapy (≥6 Outbreaks Per Year)
If you experience six or more cold sore episodes annually, daily suppressive therapy reduces recurrence frequency by ≥75%: 1
- 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
After 1 year of continuous suppressive therapy, consider discontinuation to reassess recurrence frequency, as it decreases over time in many patients. 1
Common Pitfalls to Avoid
- Relying on topical treatments or supplements (including L-lysine) when oral antiviral therapy is proven superior 1
- Starting treatment too late—efficacy decreases significantly when treatment begins after lesions have fully developed 1
- Using inadequate dosing—short-course, high-dose therapy (e.g., valacyclovir 2 g twice in one day) is more effective and convenient than traditional longer courses 1
If You Still Want to Try L-Lysine
While not evidence-based, patients who choose to use L-lysine despite the lack of strong supporting data have used:
- 1000 mg daily for prevention (the dose used in the one marginally positive controlled trial) 2, 4
- 936 mg daily average (from the uncontrolled survey) 5
However, this approach delays or replaces proven antiviral therapy and is not recommended by any major medical guideline. 1, 6