Herpes simplex (both oral – HSV-1, and genital – HSV-2) is an extremely common viral infection. It is estimated that up to 90% of adults are carriers of the HSV virus [1], which remains dormant in nerve cells and can reactivate in response to factors such as stress or weakened immunity. Standard treatment for cold sore recurrences relies on antiviral medications (such as acyclovir, valacyclovir, etc.), but many people seek alternative, natural remedies for herpes. One of the most popular supplements used for this purpose is L-lysine – an amino acid known for its potential to prevent and alleviate cold sore symptoms. But does L-lysine truly work against cold sores? Below, we present a detailed, science-based review of L-lysine’s mechanisms of action, its effectiveness, optimal dosage for cold sores, safety, and practical tips for its use.
Mechanism of Action of L-Lysine in Cold Sores (HSV-1 and HSV-2)
L-lysine is an essential amino acid that our body cannot produce and must be obtained through diet or supplements. Biochemically, its interaction with another amino acid – L-arginine – is particularly important. The herpes virus requires arginine for replication, using it primarily to build viral proteins. L-lysine acts as an arginine antagonist on several levels: it inhibits the absorption of arginine and competes with it during protein synthesis, thereby disrupting the virus’s life cycle [1, 2]. In other words, a high intracellular lysine level creates a state of “arginine starvation” for HSV, making viral replication more difficult. In vitro studies have shown that increasing intracellular lysine concentrations inhibits HSV replication [2], while in arginine-depleted cultures, the herpes virus was completely incapable of replicating [2].
It is important to note that arginine and lysine share the same transporters in the body, meaning that an excess or deficiency of one affects the levels of the other [3]. Dietary arginine (found abundantly in foods such as chocolate, nuts, and seeds) may lower lysine levels in tissues, thus facilitating viral replication [3]. Conversely, a diet high in lysine and low in arginine theoretically creates less favourable conditions for HSV. Some clinical observations have even suggested a link between high arginine intake and cold sore recurrences – for example, outbreaks were reported to occur within approximately 36 hours of consuming arginine-rich foods [1]. This observation led to the recognition of the lysine-arginine balance as a key factor in modulating dormant herpes viruses [1]. This is why L-lysine is considered a preventative agent – by maintaining lysine dominance over arginine in the body, it makes cellular environments less conducive to HSV replication.
It is also worth noting that L-lysine plays other roles in the body (e.g., it supports calcium absorption and is involved in the production of carnitine and collagen [3]). However, in the context of cold sores, its antiviral activity is mainly attributed to the described antagonism against arginine. Unlike conventional antiviral drugs, lysine does not inhibit viral enzymes or directly affect viral DNA but rather modifies the host cell’s metabolic environment, making it less hospitable for HSV reproduction.
The Effectiveness of L-Lysine Supplementation in the Treatment and Prevention of Herpes
The question of whether L-lysine works against herpes has intrigued researchers for several decades. Numerous studies (especially in the 1970s and 1980s) have evaluated the impact of lysine supplementation on the frequency of recurrences and the course of oral and genital herpes. The results are mixed and sometimes contradictory, partly due to varying lysine dosages used across studies, differences in methodology, and dietary influences.
Early Studies and Promising Results
Early studies suggested promising effects. For instance, in an uncontrolled observation from 1978, patients taking at least 500 mg of L-lysine daily experienced no herpes recurrences during supplementation, whereas discontinuation of lysine intake resulted in recurrences within 1–4 weeks [1]. Although this study lacked a placebo group, it indicated potential effectiveness of lysine in preventing recurrences.
In contrast, Milman’s controlled study (1980) involving 65 participants with recurrent oral herpes found that supplementation with 1 g of lysine per day led to more than twice the proportion of individuals free from recurrences compared to placebo (27.7% vs 12.3%, p < 0.05) [1]. Nevertheless, the average recurrence frequency during the study period was similar in both groups (91 recurrences during lysine supplementation vs 104 during placebo), and lysine did not significantly shorten healing time or reduce symptom severity [1].
Later Placebo-Controlled Studies
Further placebo-controlled studies emerged in subsequent years. Some failed to confirm significant efficacy of lysine, particularly when lower doses were used. For example, daily doses of 500–624 mg proved insufficient—studies found no differences in recurrence rates compared to placebo [1].
Higher doses, however, showed more noticeable effects. McCune et al. (1984) conducted a trial with a daily dose of 1248 mg of lysine, which demonstrated a significant reduction in recurrences (mean 0.89 during supplementation vs 1.56 during placebo; p < 0.05), whereas the lower dose of 624 mg was ineffective [1].
Thein and Hurt (1984) also observed fewer recurrences in individuals whose supplementation with 1 g of lysine per day achieved sufficiently high blood levels (>165 nmol/ml) [1]. Interestingly, the prophylactic effect in their study became apparent only during the second half of the trial, suggesting that longer use of lysine may be necessary to observe full benefits [1].
High-Dose Lysine and Stronger Outcomes
The most compelling results come from studies using doses of around 3 g per day. Griffith et al. (1987) conducted a six-month, multicentre, double-blind, placebo-controlled study with a daily dose of 3 g of L-lysine. Patients in the lysine group experienced, on average, 2.4 times fewer herpes recurrences than those in the placebo group, and 74% of supplemented individuals had milder symptoms compared to 28% in the control group [1].
The reduction in recurrence frequency was statistically significant (p < 0.01) [1]. However, no significant difference was observed in the healing time of existing lesions, suggesting lysine's primary role was to prevent recurrences or reduce their severity rather than to accelerate healing [1].
Studies Showing No Benefit
Some studies found no benefits from supplementation. For example, DiGiovanna & Blank (1984) found no differences between treatment and placebo groups when administering 1.2 g of lysine daily for 4–5 months [1]. Notably, some participants in the placebo group withdrew due to severe, persistent lesions [1], which may have weakened the study's statistical power.
Factors Influencing the Effectiveness of Lysine Supplementation
The effectiveness of L-lysine supplementation heavily depends on dosage and individual circumstances (such as a low-arginine diet, therapy duration, and individual susceptibility). Studies suggest that low doses (<1 g/day) are usually ineffective, doses around 1–1.25 g/day yield inconsistent results, while higher doses (2–3 g/day) are more consistently associated with reduced recurrence frequency and milder symptoms [1, 2].
A 2017 literature review concluded that supplementation appears ineffective at doses below 1 g/day (unless accompanied by a low-arginine diet) but that doses exceeding 3 g/day may improve subjective patient experiences and reduce recurrence rates [1].
However, it also noted a lack of long-term, well-controlled studies confirming the efficacy of lysine, particularly at doses >1.2 g/day [1]. Furthermore, there is no convincing evidence that lysine can treat active herpes lesions; its role appears mainly preventative [1].
Meta-Analyses and Systematic Reviews
The Cochrane Review (2015) covering randomised studies on cold sore prevention found no evidence supporting lysine's efficacy in preventing recurrences [4]. Only long-term oral antiviral therapies were confirmed effective, while lysine and other methods (such as herbal preparations or vaccines) did not show significant preventative effects [4].
However, Cochrane primarily analysed studies using doses of about 1000 mg or less, which may have influenced the lack of observed benefits.
Recent Evidence and High-Dose Recommendations
More recent publications emphasise the potential of higher lysine doses. A 2023 narrative review indicated that lysine is an effective prophylactic agent for reducing HSV recurrences and may also help in reducing severity and healing time of active lesions [2]. Doses below 1 g/day were considered ineffective [2].
The review suggested that daily supplementation with 3–5 g of lysine could offer substantial benefits [2].
This approach is reflected in practical recommendations from some integrative medicine practitioners. Patients with recurrent herpes are often advised to try high-dose lysine alongside conventional therapy [5]. Popular guidelines recommend taking at least 1000 mg of lysine daily for those prone to herpes outbreaks [5].
Conclusion: A Mixed Picture
Scientific evidence regarding the effectiveness of L-lysine is mixed. Some studies, especially older ones with lower doses, found no significant effects. However, others using higher doses or longer supplementation periods suggest a real reduction in recurrence frequency and symptom severity.
Most experts agree that lysine does not replace antiviral drugs in acute treatment (it does not accelerate healing of existing lesions) [3]. However, it may be helpful as part of long-term preventative strategies, particularly for individuals preferring a natural approach or those who would require chronic antiviral use.
Given individual variability, the effectiveness of L-lysine supplementation is often evaluated through a trial-and-error approach, observing whether herpes recurrence rates decline after a few months of regular intake.
L-Lysine Dosage for Cold Sores
The optimal dosage of L-lysine for the prevention or treatment of cold sores is not definitively established, but based on studies, certain recommendations and observations can be made.
Prophylactic doses
Literature suggests that effective prevention starts from around 1 g per day and upwards. A dosage of 500 mg per day is likely too low – such amounts did not bring benefits in controlled studies [1]. The aforementioned analysis indicated that <1 g/day generally does not prevent recurrences [1].
In practice, many natural medicine practitioners recommend 1,000 mg (1 g) of L-lysine daily as the minimum dose for individuals with frequent cold sore outbreaks [5]. This is a dosage that can generally be taken safely long-term.
Some sources suggest a specific calculation: approximately 50 mg of lysine per kilogram of body weight per day [1]. For a person weighing 70 kg, this amounts to 3500 mg (3.5 g) per day, which approaches the doses found to be effective in some clinical studies (2–3 g).
Historically, recommendations of about 1000–1500 mg of lysine three times daily have been made, resulting in a total of 3–4.5 g per day. Recent publications propose a range of 3–5 g daily as potentially the most effective in preventing recurrences [5, 2].
Such high doses should be introduced gradually and preferably under medical supervision to monitor for possible side effects.
Intervention doses (during an outbreak)
Some individuals also use L-lysine acutely, taking it as soon as they feel the first signs of an impending cold sore (e.g., tingling of the lip, known as prodromal symptoms). The goal is to saturate the body with lysine to halt the outbreak.
Various regimens have been tested in studies – for instance, Wright et al. described an approach where patients took about 4 g of L-lysine as a single dose at the first signs of an outbreak [1].
Such an intervention shortened the healing time in about 25% of patients [1]. In the remaining 75%, high-dose lysine at the onset of symptoms did not provide significant relief [1].
This aligns with the general consensus that lysine is not particularly effective in shortening individual episodes of cold sores – it cannot replace acyclovir, which directly inhibits viral replication.
Nevertheless, some doctors suggest that if a patient wishes to try, they may temporarily increase the dose to about 3 g daily (e.g., 1000 mg three times a day) during the few days of the outbreak.
Such short-term increases in lysine intake are sometimes used empirically, although scientific evidence for the effectiveness of this strategy is limited.
Diet vs supplements
Regarding dosage, it is worth mentioning lysine sources. A diet rich in lysine (meat, fish, dairy, legumes) typically provides about 2–3 g of lysine daily for a person consuming a balanced diet.
Individuals on plant-based diets low in legumes or athletes (with higher demands) may have slightly lower levels of this amino acid.
L-lysine supplementation usually involves taking tablets or capsules containing 500 mg or 1000 mg of pure L-lysine. They are available over the counter.
In the prevention of cold sores, a maintenance dose (e.g., 1 g once daily) is often recommended, and in the case of cold sore triggers (such as severe stress, infection, menstruation in women, or a diet rich in arginine) – temporarily increasing the dose or more rigorously avoiding arginine-rich foods is suggested.
In one clinical study, participants took 1260 mg of lysine daily regularly, and if prodromal symptoms appeared, they increased the dose to 2520 mg/day; this approach led to a significant reduction in the frequency of recurrences and the number of lesions compared to placebo [1].
This strategy suggests that lysine dosage can be adjusted flexibly: maintaining a moderate preventive dose daily, but being prepared to increase it when the body signals an approaching problem.
Summary of L-lysine Dosage
The minimum dosage is around 1 g per day, whereas the maximum doses used in studies were 3 g daily on a continuous basis (and even temporarily up to 6 g/day, still considered safe [2]).
Some experts recommend doses of 3–5 g daily for optimal protection against recurrences [5].
It is always important to tailor the dosage individually – if smaller doses are effective, there is no need to immediately opt for the highest ones. If no effects are observed at 1–2 g per day, the dosage can be cautiously increased while monitoring the body's response.
The pharmacological maximum is not precisely defined – there have been cases of doses as high as 6–8 g per day without serious side effects, although doses above 10–15 g may cause gastrointestinal complaints [5].
Most recommendations suggest not exceeding 3 g per day long-term, unless there is a particular need, as this amount is considered safe and usually sufficient [1].
Potential Side Effects, Interactions, and Contraindications
The safety of L-lysine as a supplement is generally considered to be very high. Lysine is a natural component of proteins found in food, so the body is accustomed to it. Studies show that doses of up to 3 g per day are well tolerated and do not cause significant adverse effects [5]. No cases of acute lysine toxicity have been reported in humans, even with long-term administration [1]. However, like any supplement, particularly when used at higher doses, lysine may cause certain side effects and should be used cautiously in individuals with specific medical conditions.
The most common side effects associated with excessive lysine intake involve gastrointestinal discomfort. At doses significantly exceeding typical amounts (e.g., 10–15 g per day), some patients have reported diarrhoea, nausea, stomach cramps, or general digestive upset [5]. These symptoms are typical of amino acid overdosing and result from the intestines’ limited capacity to absorb such large quantities at once. The occurrence of these symptoms is a signal to reduce the dose. At moderate amounts (1–3 g), such problems usually do not occur.
Long-term use of high doses of lysine theoretically carries some metabolic risks. There are reports suggesting that chronic intake of very large amounts of lysine may promote the formation of gallstones [3]. The mechanism is not fully understood, but it is likely related to cholesterol metabolism disturbances in the liver caused by an excess of certain amino acids. Isolated cases of kidney dysfunction (Fanconi syndrome, renal failure) associated with lysine overuse have also been reported [3]. It is important to emphasise that these are rare events – overall, lysine is considered to be safe and well tolerated. Nevertheless, individuals planning to take high doses of lysine for months should be monitored by a doctor and undergo periodic kidney function tests and possibly lipid profile checks (as a precaution, considering the potential risk of gallstones).
Interactions with Medications and Supplements
Regarding interactions with medications and other supplements, the most important relationship is with arginine. Supplementing both arginine and lysine simultaneously makes little sense, as these amino acids counteract each other’s effects regarding herpes management – high arginine levels negate the benefits of lysine, and vice versa [3].
Individuals taking arginine supplements (for other reasons such as pulmonary hypertension, sports supplementation, or improving erectile function) should consult a doctor before adding lysine. Generally, it is not recommended to combine high doses of lysine with high doses of arginine – it is better to prioritise one amino acid depending on the case. It is also worth noting that lysine can increase calcium absorption, so combining it with high calcium doses could theoretically raise blood calcium levels; this is not a typical negative “interaction” but a biological fact worth knowing (for instance, individuals prone to hypercalcaemia should be cautious when supplementing both simultaneously).
An important potential interaction to consider is with aminoglycoside antibiotics (such as gentamicin, streptomycin, and neomycin). Studies have shown that taking large doses of lysine concurrently may enhance the nephrotoxicity (kidney-damaging effects) of these antibiotics [3]. The mechanism probably involves lysine altering the excretion of aminoglycosides through the kidneys or increasing their accumulation in renal tubules. In practice, this means that if a patient is being treated with an aminoglycoside (usually in a hospital setting for severe infections), they should not take lysine supplements simultaneously without explicit doctor approval.
Contraindications and Precautions
Due to lysine’s influence on arginine metabolism, there are certain patient groups where caution is advised. Arginine is a precursor for important compounds, such as nitric oxide (NO) – crucial for blood vessel dilation and normal blood pressure, and it also plays a role in wound healing and immune function. Chronic arginine deficiency can negatively impact health, so individuals with conditions where arginine is important should be cautious.
Thus, the literature recommends exercising caution when supplementing lysine in patients with:
- Cardiovascular diseases – such as coronary artery disease or atherosclerosis. These individuals may already have reduced NO production, and additional depletion of arginine (through excess lysine) could pose a theoretical risk of endothelial dysfunction [1]. Although no direct harm from lysine to the heart has been proven, it is stressed that arginine is "essential for endothelial function," so disturbing its balance is not advisable [1].
- Erectile dysfunction (impotence) – nitric oxide (NO) also plays a role in the mechanism of erection. Arginine is often supplemented to improve blood flow. High doses of lysine could "displace" arginine, potentially negating its benefits or even worsening sexual performance in men with erectile dysfunction [1]. Therefore, men using arginine to support potency should not add large doses of lysine without medical advice.
- Asthma – although not obvious, severe asthma is sometimes associated with metabolic disturbances, and arginine is needed for NO production, which also helps dilate the bronchi. Theoretically, excess lysine could interfere with these mechanisms, so individuals with severe, poorly controlled asthma should be cautious [1].
- Gallstones – as mentioned, there is a risk that excess lysine could promote the formation of cholesterol stones in the gallbladder [3]. Anyone with existing gallstones or who has undergone a cholecystectomy (gallbladder removal) should consult a doctor before undertaking prolonged lysine supplementation.
- Immunocompromised individuals – arginine is sometimes used therapeutically in severely ill patients (e.g., after surgeries, burns, or in sepsis) to support healing and immune function because it becomes conditionally essential during metabolic stress [1]. Lysine in such patients, if considered at all, should be used cautiously to avoid worsening potential arginine deficiencies.
- Children, pregnant, and breastfeeding women – there is insufficient scientific data regarding the safety of high-dose lysine in these groups; therefore, aggressive supplementation (beyond normal dietary intake) is generally not recommended unless under strict medical supervision.
It is important to stress that these contraindications are based mainly on theoretical considerations and precautionary principles, rather than frequent real-world complications. In practice, many individuals (including those with heart disease or asthma) have taken moderate lysine doses without any issues. Nonetheless, one should always inform a doctor about plans to supplement L-lysine, especially when taking other medications or having serious health conditions. In general, the rule is: lysine from food is safe, but excessive supplemental doses should be used with caution.
Practical Insights and Tips for Using L-Lysine for Cold Sores
L-lysine as a "natural treatment for cold sores" enjoys considerable popularity, and despite mixed research results, many individuals report its positive effects. So, how should lysine be used in practice? Here are some tips:
Consider Lysine as a Supplement, Not a Replacement for Treatment
If you suffer from frequent cold sore recurrences (whether oral or genital), you may wish to try L-lysine supplementation as a preventative measure. However, remember that standard antiviral treatments have proven efficacy in reducing outbreaks and managing symptoms — lysine will not fully replace, for instance, aciclovir in cases of severe infection. It may, however, allow for less frequent medication use or help ease symptoms between treatments.
Start with a Moderate Dose and Observe the Effects
Begin supplementation with approximately 1 g per day (e.g., 2×500 mg or 1×1000 mg). Allow a few weeks to a month for your body to adapt and observe whether the frequency of outbreaks decreases. If cold sores still occur often, you may gradually increase the dose to 2 g (e.g., 2×1000 mg). Some individuals prophylactically take up to 3 g daily in divided doses (e.g., 3×1000 mg). Higher doses should ideally be discussed with a doctor. Consistency is key — lysine is effective as long as its levels are maintained in the body, so skipping doses or taking it sporadically may yield no noticeable benefit.
Combine Supplementation with Dietary Adjustments
To enhance effectiveness, aim to include more lysine-rich foods in your diet while reducing foods exceptionally high in arginine. For example, dairy products, fish, meat, legumes, and vegetables are good sources of lysine, whereas you might want to moderately limit chocolate, nuts, seeds, and gelatine — foods known for their high arginine content. This doesn't mean you must completely avoid nuts or cocoa (they are healthy for other reasons), but be aware that excessive consumption may counteract lysine's benefits. Balancing amino acids in your diet will support supplementation efforts. Some patients even keep a food diary to see if certain foods correlate with triggering cold sores.
Intervene at the First Sign of Symptoms
If you feel an outbreak coming — such as the familiar tingling sensation on your lips — you can try increasing your lysine dose at that moment (e.g., an additional 1000 mg or 2000 mg during the day). Although, as mentioned, this will not always stop lesion development, many people find that early support with lysine can ease symptoms. It is worth experimenting, while also remembering over-the-counter creams for cold sores and the option of promptly taking an antiviral medication if the sore is large or painful.
Monitor Your Health Carefully
During long-term lysine supplementation, pay attention to signals from your body. If you experience digestive issues or diarrhoea, consider lowering the dose or dividing it into smaller portions throughout the day. Drink plenty of water, which is always recommended when increasing protein or amino acid intake, to ease the burden on the kidneys. From time to time (e.g., every six months), it is advisable to perform basic health checks — such as kidney function tests (creatinine, urea) and a general metabolic profile. This is particularly important if you are using doses above 3 g daily.
Consult Your Doctor
Especially if you have chronic illnesses or are taking other medications. Your doctor can help assess whether there are any contraindications. As discussed, caution may be necessary in conditions involving the heart, kidneys, or liver. Supplementing with L-lysine is generally safe, but any additional substance in your diet should be introduced thoughtfully.
Integrated Approach to Cold Sore Management
In conclusion, approaching cold sore treatment should be integrated and comprehensive. L-lysine can be one piece of the puzzle. Equally important is avoiding known triggers (e.g., excessive sun exposure on unprotected lips, chronic stress — as much as possible, or a diet overloaded with arginine). Supporting your overall immunity (through a healthy lifestyle, good sleep, and perhaps supplementation with B vitamins, vitamin C, vitamin D, and zinc — all of which have also been studied in relation to cold sores) may work synergistically with lysine supplementation.
Summary: Can L-Lysine Help Manage Cold Sores?
In conclusion, L-lysine is a promising and generally well-tolerated supplement that operates by competing with arginine — an amino acid essential for viral replication. Although scientific research offers mixed results, evidence suggests that while lysine may not significantly speed up the healing of an existing cold sore, it could lower the frequency of future outbreaks — particularly when taken in appropriate doses and combined with a balanced diet [1, 3]. Proper dosing is crucial: lower amounts (e.g., 500 mg daily) are unlikely to be effective, whereas daily intake of approximately 1–3 grams may provide noticeable benefits [1].
Using L-lysine as a preventive strategy appears most beneficial for individuals prone to frequent outbreaks, especially for those seeking to complement traditional treatments or reduce their dependency on them. With mindful use and careful monitoring, L-lysine supplementation for cold sores can be adjusted individually to help minimise recurrences without causing adverse effects. If you frequently experience cold sores, it may be worthwhile to consult your healthcare provider about incorporating L-lysine into your management plan. This simple option from the field of natural therapies could potentially enhance your quality of life and lessen the need for topical treatments.
Scientific Sources
This article is based on key studies and systematic reviews concerning L-lysine’s role in cold sore management, drawing from respected medical journals and the Cochrane Database [1, 2, 4]. While we encourage critical thinking regarding new scientific findings — as research into cold sore prevention and treatment continues to evolve — the available evidence already offers cautious optimism about lysine’s potential benefits. Nevertheless, understanding its limitations remains important. L-lysine for cold sores represents an area where natural and conventional approaches can complement each other, with the patient’s wellbeing at the centre. If supplementing with lysine helps you experience fewer recurrences without side effects, it may become a valuable element of your broader strategy for HSV management (L-lysine as HSV prevention) [1, 3, 4].
Sources
[1] Mailoo V.J., Rampes S. Lysine for Herpes Simplex Prophylaxis: A Review of the Evidence. Integrative Medicine (Encinitas). 2017;16(3):42–46. PMID: 30881246; PMCID: PMC6419779.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419779/
[2] Chang J.Y., Balch C., Puccio J., Oh H.S. A Narrative Review of Alternative Symptomatic Treatments for Herpes Simplex Virus. Viruses. 2023;15(6):1314. DOI: 10.3390/v15061314.
https://www.mdpi.com/1999-4915/15/6/1314
[3] Mount Sinai Health Library. Lysine. Mount Sinai, 2025. Accessed: 27 April 2025.
https://www.mountsinai.org/health-library/supplement/lysine
[4] Chi C., Wang S., Delamere F.M., Wojnarowska F., Peters M.C., Kanjirath P.P. Interventions for prevention of herpes simplex labialis (cold sores on the lips). Cochrane Database of Systematic Reviews. 2015; Issue 8: CD010095. DOI: 10.1002/14651858.CD010095.pub2.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010095.pub2/full
[5] Dresden D. Lysine health benefits: Evidence and food sources. Medical News Today; updated 25 March 2025. Accessed: 27 April 2025.
https://www.medicalnewstoday.com/articles/324019
