Lysine for Herpes Simplex Virus: Limited Evidence Does Not Support Routine Clinical Use
Lysine supplementation is not recommended for the prevention or treatment of herpes simplex virus infections based on current medical guidelines and inconsistent research evidence. The established standard of care for HSV prophylaxis and treatment relies on antiviral medications such as acyclovir, valacyclovir, or famciclovir, not amino acid supplementation 1.
Why Lysine Is Not Part of Standard HSV Management
Guideline-Based Recommendations Favor Antivirals
For HSV prophylaxis in immunocompromised patients, the NCCN 2024 guidelines recommend acyclovir, valacyclovir, or famciclovir as the initial agents of choice during periods of neutropenia and immunosuppression 1.
For active HSV infections, the CDC recommends acyclovir as first-line therapy: 200 mg orally 5 times daily for 7-10 days for first episodes, or 200-800 mg orally for 5 days for recurrent episodes 1.
For pediatric HSV infections, the CDC recommends oral acyclovir 20 mg/kg per dose (maximum 400 mg/dose) three times daily for 5-10 days 2.
No major clinical practice guidelines from NCCN, CDC, or other authoritative bodies recommend lysine for HSV management 1.
The Research Evidence on Lysine Is Contradictory and Weak
Studies Showing Potential Benefit
An older 1987 double-blind trial found that 3 grams daily of L-lysine reduced HSV recurrence frequency, severity, and healing time compared to placebo 3.
A 1978 multicentered study suggested lysine (312-1,200 mg daily) accelerated recovery and suppressed recurrence, based on the theory that lysine-to-arginine ratios affect viral replication 4.
Studies Showing No Benefit
A 1984 double-blind, placebo-controlled trial found no substantial benefit of lysine therapy (400 mg three times daily) for either treatment or prophylaxis of frequently recurrent HSV infections 5.
A 2017 systematic review concluded that lysine supplementation appears ineffective at doses less than 1 gram daily, and that doses exceeding 3 grams daily only improved subjective patient experience without clear objective benefit 6.
Critical Limitations
The positive studies used varying doses (ranging from 312 mg to 3 grams daily), making it impossible to establish an effective therapeutic dose 4, 6, 3.
The 2017 review explicitly stated that longer controlled studies with doses exceeding 1.2 grams daily are required to definitively test lysine's role in HSV prophylaxis 6.
Most lysine studies are decades old and have not been replicated with modern methodology 4, 5, 3.
Safety Concerns With Lysine Supplementation
Patients with cardiovascular or gallbladder disease should be cautioned about theoretical risks of lysine supplementation 6.
High-dose lysine supplementation (3+ grams daily) has not been adequately studied for long-term safety 6.
The Proven Alternative: Antiviral Prophylaxis
For Immunocompromised Patients
Acyclovir, valacyclovir, or famciclovir are the agents of choice for HSV prophylaxis during neutropenia in patients with hematologic malignancies, stem cell transplant recipients, and those on immunosuppressive therapy 1.
Prophylaxis should continue throughout the period of immunosuppression, and longer in patients with GVHD or frequent HSV reactivations 1.
For Patients With Frequent Recurrences
Daily suppressive therapy with oral acyclovir reduces HSV recurrence frequency by at least 75% in patients with six or more recurrences per year 1.
The recommendations for preventing recurrence in adults apply to children as well 1, 2.
For Acyclovir-Resistant HSV
Common Pitfalls to Avoid
Do not recommend lysine as a substitute for proven antiviral therapy, particularly in immunocompromised patients where HSV can cause severe morbidity 1.
Do not use topical antivirals alone as they cannot reach the site of viral reactivation or impact the host immune response 2.
Do not stop antiviral treatment early when symptoms improve; continue until complete healing occurs 2.
Be aware that patients may self-treat with lysine based on internet recommendations, but this should not replace evidence-based antiviral therapy 6.