Lysine (L-Lysine): Benefits, Forms, Dosing, and Side Effects

Table of Contents

• Current evidence position
• Key safety points
• Brad's videos on this topic
• Overview
• Forms and Bioavailability
• Evidence for Health Benefits
• Recommended Dosing
• Safety and Side Effects
• Drug Interactions
• Dietary Sources
• References

Current evidence position

Brad has not made a video on this topic; this is a summary of the evidence, not his view. Lysine is mostly taken to prevent cold sores, and the trials are small, old and mixed: 1,000 mg L-lysine three times a day for 6 months cut outbreaks by an average of 2.4 compared with placebo, 1,248 mg a day of L-lysine monohydrochloride showed evidence of lowering the recurrence rate while 624 mg a day did not, and 1,000 mg a day of L-lysine monohydrochloride for 12 weeks had no overall effect on recurrence ^{[9, 10, 11]}. A 2015 Cochrane review of cold sore prevention (32 trials of 19 treatments) found no evidence that lysine prevents cold sores, while a 2017 review judged doses of less than 1 g a day without a low-arginine diet ineffective and suggested doses in excess of 3 g a day may improve how people experience the disease ^{[34, 35]}. A 2019 systematic review of 71 human studies found that the side effects reported were mainly nausea, stomach ache and diarrhoea, with no significant rise in these symptoms overall ^[36]. One woman developed kidney damage that progressed to chronic kidney failure in association with lysine ^[30]; people with kidney, heart or gallbladder disease should talk to their doctor first, and people with glutaric aciduria type 1 should avoid lysine supplements unless their metabolic team advises otherwise ^{[35, 37]}.

Brad's videos on this topic

None yet.

1. Overview

Lysine (L-lysine) is one of the essential amino acids: the body cannot make it, so it must come from food ^[31]. Its main job is building protein, and it is broken down mainly in the liver ^[31]. Recommended intakes range from 64 mg per kg of body weight a day for infants aged 6 months to 30 mg per kg a day for adults, and a typical Western diet supplies 40 to 180 mg per kg a day ^[31].

Most people who eat a varied diet get enough. Diets built on wheat are the exception, because lysine is the amino acid in shortest supply in wheat protein ^[22]. In families in Pakistan and northern China who got most of their protein from wheat, lysine-fortified flour improved children's growth and some blood markers of nutrition and immunity ^{[21, 22]}.

Lysine is also a starting material for carnitine, which carries fats into cells to be burned for energy, and for the cross-links that hold collagen fibres together.

The best-known supplemental use is preventing cold sores caused by herpes simplex virus. The idea comes from tissue culture, where arginine helped the virus grow and lysine blocked that effect ^[33]. Lysine has also been studied for calcium absorption, iron status and hair shedding, immunity in people short of protein, and anxiety ^{[16, 17, 21, 27]}.

Supplements almost always use the hydrochloride salt (L-lysine HCl), sold as tablets, capsules, powders and in some topical products.

2. Forms and Bioavailability

L-Lysine Hydrochloride (L-Lysine HCl)

L-lysine HCl (L-lysine monohydrochloride) is the hydrochloride salt of the amino acid. By weight it is about 80% L-lysine; the rest is the hydrochloride. So a label reading "1,000 mg L-lysine HCl" supplies about 800 mg L-lysine. Some labels state the L-lysine content and others the weight of the salt, which makes products and trial doses harder to compare.

Free-Form L-Lysine

A few products supply L-lysine without the salt. Compare products by their L-lysine content rather than by the total weight on the label.

Supplement Delivery Forms

L-lysine is sold in several forms:

• Tablets and caplets: the most common form.
• Capsules: gelatin and vegetarian versions are sold.
• Powders: allow flexible dosing and suit people who find pills hard to swallow.
• Topical gels and creams: sold for cold sores, usually alongside other ingredients (see Topical Lysine Products below).
• Chews: mostly sold for cats with feline herpesvirus.

Absorption and Bioavailability

Lysine shares its route into the body with the other basic amino acids, including arginine. In humans and piglets, about 30 to 42% of the lysine released from digested protein is lost to first-pass metabolism ^[31]. Cooking at high heat can make some of the lysine in food unavailable, because lysine reacts with sugars in the browning (Maillard) reaction.

In a 12-month cold sore trial, people whose serum lysine exceeded 165 nmol/ml had significantly fewer recurrences, and recurrences rose when levels fell below that ^[7].

Topical Lysine Products

Lysine appears in creams and gels sold for cold sores, usually mixed with other ingredients.

In an open-label pilot study of 30 people with cold sores on or around the lips, an ointment combining L-lysine with zinc and herbal ingredients brought full resolution in 40% by the third day and in 87% by the sixth ^[8]. The study had no placebo group and tested a combination, so it cannot show what lysine itself did. The authors noted that an untreated cold sore episode can last up to 21 days ^[8].

Label Reading Tips

Check whether the label gives L-lysine or L-lysine HCl. To convert L-lysine HCl to L-lysine, multiply by 0.8: 1,500 mg of the salt supplies about 1,200 mg of L-lysine. Older trials do not always make clear which one their dose refers to; one describes its L-lysine monohydrochloride tablets as giving 1,000 mg L-lysine per dose ^[9].

Because nearly all products use the same salt, the main differences are accurate labelling, cost per gram and the form you prefer.

3. Evidence for Health Benefits

Herpes Simplex Virus (Cold Sores and Genital Herpes)

Herpes simplex virus causes cold sores on the lips and also genital sores. In tissue culture, too little arginine held back the virus, and lysine blocked arginine's growth-promoting effect ^[33]. The authors of that 1981 work suggested that people prone to cold sores avoid excess arginine and might need extra lysine ^[33]. Whether that holds in people depends on the trials below.

An early multicentre study, which had no placebo group, gave 45 people with frequent herpes recurrences 312 to 1,200 mg a day of lysine and reported faster recovery and fewer recurrences ^[6].

In a 1987 double-blind, placebo-controlled trial, 27 people took L-lysine monohydrochloride tablets (1,000 mg L-lysine per dose) three times a day for 6 months and 25 took placebo ^[9]. On average, the lysine group had 2.4 fewer herpes infections, and their symptoms were less severe and healed faster ^[9].

In a 1984 randomized, double-blind, placebo-controlled crossover study of 41 people, L-lysine monohydrochloride at 1,248 mg a day showed evidence of lowering the recurrence rate, while 624 mg a day did not work ^[10]. Neither dose shortened healing time ^[10].

In a 12-month double-blind crossover study of 26 volunteers, the group taking L-lysine, 1,000 mg a day, reported significantly fewer lesions in most instances, and lesions became more frequent in those taken off lysine ^[7]. Recurrences fell when serum lysine exceeded 165 nmol/ml ^[7].

In a 1980 double-blind crossover study, 65 people took L-lysine monohydrochloride, 1,000 mg a day, for 12 weeks and placebo for 12 weeks ^[11]. Overall, lysine had no effect on how often cold sores came back, though significantly more people stayed free of recurrences while on lysine (p = 0.05) ^[11]. Lysine did not speed healing or change how bad the sores looked at their worst ^[11].

The reviews disagree in tone. A 2015 Cochrane review of 32 randomized trials of cold sore prevention found no evidence that lysine works ^[34]. It found that long-term antiviral tablets can prevent cold sores, with a small benefit ^[34]. A 2017 review concluded that lysine appears ineffective at doses of less than 1 g a day without a low-arginine diet, that doses in excess of 3 g a day appear to improve how people experience the disease, and that longer trials of daily doses exceeding 1.2 g a day are needed ^[35].

Taken together, the trials are small, mostly from the 1980s, and point in different directions. Results were mixed even at the same dose: 1,000 mg a day helped in one trial and had no overall effect in another ^{[7, 11]}. In the one trial that compared doses, 1,248 mg a day showed evidence of benefit and 624 mg a day did not ^[10]. Antiviral medicines have stronger evidence for prevention ^[34].

Canker Sores (Aphthous Ulcers)

Canker sores (aphthous ulcers) are shallow, painful mouth ulcers. Typical ones are small, less than 1 cm across ^[12]. They are not cold sores, and their cause is still unknown: local, immune, genetic, allergic, nutritional and microbial factors have all been proposed ^[13]. Mouth ulcers that come with eye inflammation, genital ulcers, arthritis or fever need a doctor's assessment for a more serious cause ^[12].

Evidence that lysine prevents or heals canker sores comes only from small studies, such as a 1994 report on lysine for recurrent canker sores and cold sores ^[14], and none is large enough to rely on.

Calcium Absorption and Bone Health

A 1992 study looked at lysine and calcium in women ^[16]. In the first part, 15 healthy and 15 osteoporotic women took an oral calcium load (3 g as calcium chloride) with or without L-lysine, 400 mg. Healthy women given lysine lost less calcium in their urine after the load. In the second part, 45 patients with osteoporosis took 800 mg a day of L-lysine, L-valine or L-tryptophan for a short time, and only lysine significantly increased calcium absorption from the gut ^[16].

The authors suggested lysine might help prevent and treat osteoporosis ^[16]. The study measured calcium handling, not bone density or fractures.

Collagen is the most abundant protein in animals ^[3], and lysine residues in collagen form the cross-links that give it strength. This is a reason lysine matters for bone, but it does not show that extra lysine above dietary needs builds bone.

Iron Absorption and Hair Loss

Low iron stores (measured as serum ferritin) are linked to increased hair shedding in women ^[17]. A 2002 review reported that, in an open study and in double-blind data, a significant proportion of women with increased hair shedding responded to L-lysine with iron ^[17]. The same group proposed that hair shedding in women is mainly caused by low iron stores, made worse by low lysine intake ^[18].

These reports tested lysine together with iron, so they cannot show how much lysine added. Trials that compare iron alone with iron plus lysine are needed.

Immune System Health

In two 3-month studies in wheat-eating families, one of them double-blind, lysine-fortified flour raised several immune markers ^{[21, 22]}. In northern China, flour fortified with 3 g of lysine per kg increased CD3 T cells in women and children and raised IgG, IgA, IgM and complement C3 in children ^[21]. In Pakistan, families given fortified flour had increases in CD4 and CD8 cells and complement C3 compared with controls ^[22]. These families got 58% to 67% of their protein from wheat, so the results apply to people short of lysine, not to well-fed adults ^{[21, 22]}.

LASAG (D,L-lysine-acetylsalicylate glycine) is an inhaled drug related to aspirin, not a lysine supplement. In a phase II trial in people in hospital with influenza, it shortened the mean time to symptom relief (38.3 hours versus 56.2 hours in the per-protocol group) ^[24]. That result does not apply to lysine tablets taken for colds, flu or COVID-19.

Anxiety and Stress Reduction

In rats, L-lysine acted like a partial blocker of the serotonin 5-HT4 receptor and reduced anxiety caused by a drug that stimulates that receptor ^[28].

In a double-blind, placebo-controlled trial in 108 healthy Japanese adults, a week of L-lysine (2.64 g a day) plus L-arginine (2.64 g a day) reduced trait anxiety and anxiety caused by a stress test ^[27]. In men, it also lowered basal levels of salivary cortisol and chromogranin A, a marker of the stress response ^[27]. Because the two amino acids were given together, the trial cannot show the effect of lysine alone. The authors also cite earlier work in which lysine supplements reduced chronic anxiety in people with low lysine intake ^[27].

The evidence is small and short-term, and larger trials are needed.

Sleep

Lysine is sometimes promoted for sleep because of its possible effect on cortisol. The lysine and arginine trial measured anxiety and salivary cortisol, not sleep ^[27]. Lysine cannot be recommended for sleep on this basis.

Collagen Synthesis and Wound Healing

Collagen is the most abundant protein in animals ^[3]. As collagen is made, some lysine residues are converted to hydroxylysine by an enzyme that needs vitamin C. Lysine and hydroxylysine residues then form the cross-links that give collagen fibres their strength. This is part of why severe vitamin C deficiency (scurvy) weakens connective tissue and slows wound healing.

Lysine is also used to make carnitine, which moves long-chain fats into mitochondria to be burned for energy.

People who eat too little protein may heal poorly, but supplemental lysine above dietary needs has not been shown to speed wound healing in people.

Lysine for Cats (Feline Herpesvirus)

Feline herpesvirus 1 spreads very easily between cats and causes flu-like signs and eye and nose irritation in cats. More than 90% of veterinarians in cat hospitals were reported to recommend lysine ^[29]. A 2015 systematic review found multiple lines of evidence that lysine does not prevent or treat the infection in cats; some studies even reported more frequent infection and worse disease in cats given lysine ^[29]. The authors recommended an immediate stop to lysine supplementation for this use ^[29].

4. Recommended Dosing

Dietary Requirements

Recommended intakes for lysine are about 30 mg per kg of body weight a day for adults and 64 mg per kg a day for infants aged 6 months ^[31]. Typical Western diets supply 40 to 180 mg per kg a day ^[31], so most adults who eat enough protein get plenty.

People who may fall short include:

• People who get most of their protein from wheat or other cereals ^{[21, 22]}
• Vegans whose protein comes mostly from grains; a mix of plant proteins, including legumes, can meet amino acid needs ^[5]
• People who eat little food overall, such as frail older adults

Supplemental Dosing by Indication

Cold sore prevention: the positive trials used 1,000 mg L-lysine three times a day for 6 months ^[9], 1,248 mg a day of L-lysine monohydrochloride ^[10], or 1,000 mg a day of L-lysine ^[7]. A dose of 624 mg a day did not work, and 1,000 mg a day of L-lysine monohydrochloride for 12 weeks had no overall effect on recurrence ^{[10, 11]}. Benefit, if any, comes from taking lysine every day to prevent outbreaks.

Calcium absorption: 400 mg with a calcium load, or 800 mg a day for a short period ^[16].

Anxiety and cortisol: L-lysine 2.64 g a day with L-arginine 2.64 g a day, tested for a week ^[27].

Timing and Administration

The cold sore trials gave lysine either as one daily dose or as three doses a day ^{[9, 11]}. Taking it with food may ease stomach upset.

For cold sore prevention, steady daily use matters more than timing: in one trial, recurrences fell when serum lysine exceeded 165 nmol/ml and rose when it fell below that level ^[7].

Label Interpretation

Labels may give the dose as L-lysine or as L-lysine HCl, which is about 80% L-lysine by weight. For example, 3,000 mg a day of L-lysine HCl supplies about 2,400 mg of L-lysine.

Quick conversion: L-lysine HCl dose × 0.8 = approximate L-lysine content.

5. Safety and Side Effects

Common Side Effects

A 2019 systematic review of 71 human studies, with doses from 16.8 to 17,500 mg a day for 1 to 1,095 days, found that the adverse events were mainly stomach and bowel symptoms such as nausea, stomach ache and diarrhoea ^[36]. Pooled across studies, the risk of these symptoms did not rise significantly (risk ratio 1.02, 95% CI 0.96 to 1.07) ^[36]. Taking lysine with food or lowering the dose may help.

Serious Adverse Events

Kidney damage: a 44-year-old woman developed Fanconi syndrome (a disorder of the kidney tubules) in association with oral L-lysine ^[30]. She went on to severe tubulointerstitial nephritis (kidney inflammation) and chronic kidney failure ^[30]. A single case report cannot prove that lysine caused it, but it is a reason for caution with long-term use and in people with kidney disease.

Gallbladder and heart disease: a 2017 review advised that people with cardiovascular or gallbladder disease be warned of the theoretical risks of lysine supplements ^[35]. The size of any such risk in people is unknown.

Contraindications

Glutaric aciduria type 1: this is a rare inherited disorder of lysine metabolism. Treatment includes a low-lysine diet ^[37]. People with it should avoid lysine supplements unless their metabolic team advises otherwise.

Special Populations

Pregnancy and breastfeeding: there are few safety data on lysine supplements in pregnancy or breastfeeding. Lysine from normal food is not a concern; ask your doctor before taking a supplement.

Children: supplemental doses for children have not been studied for safety. Lysine from food is essential for growth.

Kidney disease: because of the case of kidney failure linked to lysine ^[30], people with kidney disease should talk to their doctor before taking lysine supplements.

Older adults: older adults with reduced kidney function fall under the kidney caution above.

Long-Term Safety

Few studies have lasted long. The 2019 review included dosing periods of 1 to 1,095 days ^[36]. A 2007 review suggested an upper limit of 300 to 400 mg per kg of body weight a day could be considered ^[31], but the 2019 review set a lower provisional no-observed-adverse-effect level of 6,000 mg a day, based on stomach and bowel symptoms ^[36]. People taking lysine long term, especially at high doses, may want their doctor to check kidney function from time to time.

Calcium Absorption Interaction

Lysine increased calcium absorption from the gut in one study ^[16]. In theory this could add to high calcium levels in people taking high-dose calcium or who have a condition that raises calcium, such as overactive parathyroid glands. If this applies to you, ask your doctor before starting.

6. Drug Interactions

Few drug interactions with lysine have been studied. If you take prescription medicines, check with your doctor or pharmacist before starting.

Calcium Supplements and Calcium-Affecting Medications

Because lysine increased calcium absorption in one study ^[16], it could in theory add to the effect of high-dose calcium, active vitamin D drugs (calcitriol, alfacalcidol), thiazide diuretics or lithium on blood calcium. These combinations have not been studied.

Aminoglycoside Antibiotics

Aminoglycoside antibiotics (gentamicin, tobramycin, amikacin) can harm the kidneys. Given the case of kidney failure linked to lysine ^[30], an added effect is possible in theory, though it has not been studied.

Arginine

Lysine and arginine share a route into cells, and the cold sore idea rests on lysine opposing arginine ^[33]. High doses of one may reduce uptake of the other. They have also been tested together for anxiety, each at 2.64 g a day ^[27].

Medications Affecting Kidney Function

Given the case of kidney failure linked to lysine ^[30], take care when combining lysine with other medicines that can affect the kidneys:

• NSAIDs (ibuprofen, naproxen)
• ACE inhibitors and ARBs
• High-dose methotrexate

Medications for Osteoporosis

Lysine's effect on calcium absorption ^[16] could in theory matter for people on osteoporosis medicines that change calcium balance, such as bisphosphonates, denosumab or teriparatide. These combinations have not been studied; tell the doctor treating your osteoporosis if you take lysine.

General Guidance

If you take prescription medicines, especially ones that affect the kidneys or calcium, check with your doctor or pharmacist before starting.

7. Dietary Sources

Meat, fish, eggs, dairy foods, soy and other legumes supply plenty of lysine. Cereal grains are low in it: lysine is the amino acid that limits the quality of wheat protein ^[22].

Lysine Content of Common Foods

USDA FoodData Central lists the lysine content of individual foods ^[4].

Practical Notes on Dietary Lysine

• Mix plant proteins. A mix of plant proteins can supply all the amino acids people need ^[5]. Pairing grains with legumes, as in rice and beans or bread and hummus, makes up for the low lysine in grains.

• Wheat-based diets. Where most protein comes from wheat, lysine-fortified flour has improved growth and some markers of nutrition and immunity ^{[21, 22]}.

• Heat processing. Baking, toasting and frying can make some of the lysine in food unavailable through the browning (Maillard) reaction between lysine and sugars.

• Arginine-rich foods. Nuts and seeds contain both lysine and arginine. Avoiding them to prevent cold sores rests only on the tissue-culture idea ^[33].