What is lysine (L-lysine) for cold sores?

Lysine for Cold Sores

Lysine supplementation is not recommended for treating or preventing cold sores, as high-quality evidence shows it is ineffective, and oral antiviral medications (valacyclovir, famciclovir, or acyclovir) should be used instead. 1, 2

What is Lysine?

L-lysine is an essential amino acid that has been studied for cold sores based on the theory that it might inhibit herpes simplex virus (HSV) replication by competing with arginine, another amino acid. 3, 4 However, this theoretical mechanism has not translated into consistent clinical benefit.

Evidence Against Lysine Efficacy

Treatment of Active Cold Sores

• A rigorous double-blind, placebo-controlled trial found that lysine 400 mg three times daily showed no substantial benefit for treating active episodes or preventing recurrences in patients with frequently recurring herpes simplex infections. 5
• The study concluded it is unlikely that lysine improves frequently recurrent herpes infections in the majority of patients. 5

Prevention of Cold Sores

• A comprehensive Cochrane systematic review of 32 randomized controlled trials (2,640 participants) found no evidence supporting lysine's efficacy in preventing herpes simplex labialis. 6
• This high-quality systematic review specifically evaluated lysine among 19 different preventive interventions and failed to find supporting evidence. 6

Conflicting Older Data

• While some older studies from 1978 and 1984 suggested potential benefits, 4, 7 these findings have not been replicated in more rigorous, modern trials. 5, 6
• One older study showed that 1,248 mg daily might decrease recurrence rates, but 624 mg daily was ineffective, and neither dose shortened healing time. 7

Recommended Evidence-Based Alternatives

First-Line Treatment for Active Cold Sores

• Valacyclovir 2g twice daily for 1 day is the recommended first-line treatment, reducing episode duration by 1.0 day compared to placebo. 1, 2
• Treatment must be initiated within 24 hours of symptom onset, ideally during the prodromal stage (tingling, burning sensation). 1, 8
• Alternative options include famciclovir 1500mg as a single dose or acyclovir 400mg five times daily for 5 days. 1, 2

Suppressive Therapy for Frequent Recurrences

• For patients experiencing six or more recurrences per year, consider daily suppressive therapy with valacyclovir 500mg once daily (can increase to 1000mg for very frequent recurrences). 2
• Daily suppressive therapy reduces recurrence frequency by ≥75%. 2
• Famciclovir 250mg twice daily or acyclovir 400mg twice daily are alternative suppressive options. 2

Common Pitfalls to Avoid

• Relying on lysine or other unproven supplements when effective oral antiviral medications are available. 1, 6
• Using topical antivirals alone, which provide only modest benefit compared to oral therapy. 1, 2
• Starting treatment too late, as efficacy decreases significantly when treatment begins after lesions have fully developed. 1, 2
• Failing to consider suppressive therapy in patients with frequent recurrences who could benefit substantially. 2

Safety Considerations

• Oral antiviral medications (valacyclovir, famciclovir, acyclovir) are generally well-tolerated with minimal adverse events. 2
• Common side effects include headache (<10%), nausea (<4%), and mild gastrointestinal disturbances. 2
• Resistance to oral antivirals when used episodically in immunocompetent patients is rare (<0.5%). 2