Lysine Doses Used in Studies

Table of Contents

1. Chemical Forms of Supplemental Lysine
2. How Studies Report the Dose
3. Absorption and Transport
4. Doses Used in Herpes Prevention Trials
5. Doses Used for Outbreaks in Progress
6. Doses Used in Collagen and Calcium Studies
7. Doses Used in Anxiety and Fortification Trials
8. Combination Products: What Has Been Studied
9. Children in Lysine Studies
10. Pregnancy and Lactation
11. Requirements, Upper Limits and Kidney Reports
12. Side Effects and Interactions Reported
13. Key Research Papers
14. Connections
15. Featured Videos

Chemical Forms of Supplemental Lysine

L-lysine ((2S)-2,6-diaminohexanoic acid) is an essential amino acid with two amino groups, which is why it is grouped with arginine and ornithine as a dibasic (cationic) amino acid. Oral supplements and study products use it in a few chemical forms:

• L-lysine (free base) — the amino acid itself, C₆H₁₄N₂O₂, molecular weight 146.19 g/mol (PubChem).
• L-lysine hydrochloride (monohydrochloride) — lysine paired with hydrochloric acid as a salt, C₆H₁₅ClN₂O₂, molecular weight 182.65 g/mol (PubChem). Flodin's 1997 review describes L-lysine monohydrochloride as the form widely available to the public as a nonprescription oral supplement, mostly used against recurrent herpes simplex. Most of the herpes trials below used this form.
• L-lysine monohydrate — lysine crystallised with one molecule of water, C₆H₁₆N₂O₃, molecular weight 164.20 g/mol (PubChem).
• L-lysine acetate — lysine paired with acetic acid, C₈H₁₈N₂O₄, molecular weight 206.24 g/mol (PubChem).

Because a salt or hydrate carries extra mass, a milligram of the salt holds less lysine than a milligram of the free amino acid. No study comparing the absorption or effect of these forms in people was found for this page.

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How Studies Report the Dose

Trial reports do not all state the dose the same way, and the differences matter when doses are compared:

• Milman 1980 and McCune 1984 gave the dose as milligrams of L-lysine monohydrochloride (1,000 mg; 624 mg and 1,248 mg a day).
• Griffith 1987 gave L-lysine monohydrochloride tablets and described each dose as 1,000 mg of L-lysine.
• DiGiovanna and Blank 1984 gave 400 mg of lysine hydrochloride three times a day.
• Thein and Hurt 1984 and Griffith 1978 gave the dose as milligrams of lysine (1,000 mg; 312–1,200 mg a day).

Each dose on this page is given as the study reported it. Supplement labels likewise differ in whether a stated amount refers to lysine or to the salt.

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Absorption and Transport

Amino acids are absorbed in the small intestine and reabsorbed in the kidney by several transporters working together; across the apical membrane, transport uses sodium-dependent symporters, the proton-motive force and exchange against other amino acids, and with very few exceptions each amino acid is carried by more than one transporter (Bröer 2008). Lysine shares a renal b^0,+ transporter with cystine, ornithine and arginine; the transporter's two subunits, rBAT and b^0,+AT, are encoded by SLC3A1 and SLC7A9, the genes defective in the inherited kidney-stone disease cystinuria (Eggermann 2012).

In the Thein and Hurt trial, the recurrence rate fell significantly when a person's serum lysine exceeded 165 nmol/mL and rose when it fell below that level. Free amino acids taken as supplements raise plasma levels of that amino acid more than the same amino acid eaten as part of protein, because protein intake also stimulates protein synthesis (Pencharz 2008).

No human pharmacokinetic study (time to peak, half-life) of oral lysine supplements, and no trial comparing lysine taken with and without meals, was found for this page.

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Doses Used in Herpes Prevention Trials

The controlled and uncontrolled trials of oral lysine for recurrent herpes simplex, in date order:

• Griffith, Norins and Kagan 1978 — 45 patients with frequently recurring herpes infection, 312–1,200 mg of lysine daily in single or multiple doses. Benefit reported (faster recovery, fewer recurrences); the abstract describes no placebo or control group.
• Milman, Scheibel and Jessen 1980 — double-blind, placebo-controlled crossover in 65 patients with recurrent cold sores; 1,000 mg L-lysine monohydrochloride daily for 12 weeks, then placebo for a similar period. No overall effect on recurrence rate; significantly more patients were recurrence-free on lysine than on placebo (p = 0.05); no effect on healing.
• DiGiovanna and Blank 1984 — double-blind, placebo-controlled trial in 21 patients; 400 mg lysine hydrochloride three times a day. No substantial benefit as treatment or as prevention.
• McCune, Perry, Muller and O'Fallon 1984 — randomized, double-blind, placebo-controlled crossover in 41 patients. 1,248 mg a day of L-lysine monohydrochloride showed evidence of fewer recurrences; 624 mg a day was not effective; neither dose shortened healing time.
• Thein and Hurt 1984 — 26 volunteers completed a 12-month double-blind crossover of 1,000 mg L-lysine daily. In most instances the lysine group reported significantly fewer lesions, and lesions became more frequent when lysine was withdrawn.
• Griffith, Walsh, Myrmel, Thompson and Behforooz 1987 — double-blind, placebo-controlled, multicenter trial; L-lysine monohydrochloride tablets, 1,000 mg L-lysine three times a day for 6 months. 27 participants on lysine and 25 on placebo completed it. The lysine group had an average of 2.4 fewer HSV infections (p < 0.05), milder symptoms and shorter healing time.

Two reviews summarise this evidence. Mailoo and Rampes (2017), a literature review, concluded that lysine appears ineffective for prevention or treatment at doses below 1 g/day without a low-arginine diet, that doses above 3 g/day appear to improve patients' subjective experience, and that longer controlled studies of doses above 1.2 g/day are needed. The 2015 Cochrane review of interventions for preventing cold sores found no evidence of efficacy for lysine (Chi 2015). The trials, the arginine mechanism and the antiviral drugs are covered on the Herpes Prevention page.

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Doses Used for Outbreaks in Progress

Two of the trials above measured lysine during outbreaks as well as between them. DiGiovanna and Blank (1984, 400 mg lysine hydrochloride three times a day) found no substantial benefit for episodes in progress. Griffith 1987 (1,000 mg L-lysine three times a day for 6 months) reported milder symptoms and shorter healing time; Milman 1980 and McCune 1984 found no effect on healing time at 1,000 mg, 624 mg or 1,248 mg a day.

No trial was found that gave a short, higher “outbreak” course of oral lysine starting at the first symptoms, or that compared such a course with a lower daily dose. Outbreak schedules such as 3 g a day for 5–7 days do not come from a published trial identified for this page. No trial of lysine combined with acyclovir, valacyclovir or famciclovir was found either.

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Doses Used in Collagen and Calcium Studies

No human trial has tested lysine on its own for a collagen outcome such as wound healing or skin, so no study dose exists for that use; the related studies (collagen hydrolysate, gelatin, amino-acid mixtures) are listed on the Collagen Synthesis page.

For calcium, the human data come from one 1992 paper by Civitelli and colleagues, covered on the Calcium Absorption page:

• Acute study — 15 healthy and 15 osteoporotic women given a single 3 g oral calcium load with or without 400 mg of L-lysine; lysine blunted the rise in urinary calcium in the healthy women only.
• Absorption study — 45 osteoporotic patients given 800 mg/day of L-lysine, L-valine or L-tryptophan for a short period; intestinal absorption of a calcium tracer rose with lysine only.

No trial has measured bone density or fractures with lysine.

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Doses Used in Anxiety and Fortification Trials

• Smriga 2007 — double-blind, placebo-controlled, randomized study in 108 healthy Japanese adults: 2.64 g of L-lysine plus 2.64 g of L-arginine a day for one week. The combination reduced trait anxiety and stress-induced state anxiety, and lowered basal salivary cortisol and chromogranin-A in the men. Lysine was not tested alone.
• Ghosh 2010 (Accra, Ghana) — double-blind randomized trial of 1 g lysine/day versus placebo in men, women and children from poor peri-urban households (n = 271). Lysine reduced diarrhoeal episodes in children and respiratory illness in men.
• Smriga 2004 (northwest Syria) — 3-month randomized double-blind study of lysine-fortified wheat flour in family members of poor communities eating wheat as a staple. Fortification reduced the plasma cortisol response to blood drawing in women, sympathetic arousal in men, and trait anxiety in men. The abstract does not state the amount of lysine added.
• Ghosh 2008 (rural northwest Syria) — 16-week double-blind trial of lysine-fortified wheat flour in households, with measurements in men (n = 69), women (n = 99) and children (n = 69). Complement C3 was higher in men given lysine, and women given lysine had less diarrhoea; the abstract does not state the amount of lysine added.

The rat studies by Smriga and Torii (2002, 2003) on lysine deficiency, serotonin and anxiety are animal studies, not human results. These trials are covered on the Anxiety and Stress page.

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Combination Products: What Has Been Studied

Lysine is sold alone and in combination with zinc, vitamin C, lemon balm and other herbs. What the cited research covers:

• Oral combinations — no controlled trial of an oral lysine combination (with zinc, vitamin C, lemon balm or other herbs) for herpes was found for this page.
• A topical combination — Singh 2005 was a small open-label pilot study in 30 participants using an ointment combining L-lysine with zinc and herbal ingredients, with no placebo comparison; the contribution of lysine itself cannot be separated out.
• Lemon balm alone — in a double-blind, placebo-controlled trial in 66 patients with recurrent cold sores, a cream containing 1% dried lemon balm (Melissa officinalis) leaf extract, applied four times daily for five days, produced a lower combined symptom score on day 2 than placebo (Koytchev 1999). Lysine was not part of that trial.

Zinc, vitamin C and lemon balm are covered on their own pages (see Connections).

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Children in Lysine Studies

No trial of lysine for herpes in children was found. Children took part in the Ghana trial (1 g lysine/day versus placebo, with fewer diarrhoeal episodes and fewer days ill in the lysine-supplemented children) and in a 16-week double-blind trial of lysine-fortified wheat flour in rural Syrian households, which measured 69 children alongside men and women and found its clearest effect on diarrhoea in women (Ghosh 2010; Ghosh 2008). Herpes simplex infection itself is covered on the Herpes Simplex page.

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Pregnancy and Lactation

Lysine from food is part of a normal diet. No safety data on supplemental lysine doses in pregnancy or breastfeeding were found for this page, and no trial of lysine in pregnant or breastfeeding women was identified.

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Requirements, Upper Limits and Kidney Reports

• Requirement — the 2007 Joint WHO/FAO/UNU Expert Consultation on protein and amino acid requirements gives an adult lysine requirement of 30 mg per kilogram of body weight per day.
• Upper limit — there are no official guidelines for an upper limit of intake for amino acids such as lysine (Hayamizu 2019). Pencharz, Elango and Ball (2008) describe the existing human data on safe upper intakes as essentially observational and propose measuring each amino acid's maximal oxidation rate as one marker of an upper limit.
• Systematic reviews of safety — Hayamizu and colleagues reviewed 71 human studies of oral lysine (3,357 participants in the 2020 version): doses ranged from 16.8 mg to 17.5 g a day for 1 to 1,095 days. The adverse events observed were mainly subjective stomach and bowel symptoms (nausea, stomach ache, diarrhoea); the pooled risk ratio for these symptoms was 1.02 (95% CI 0.96–1.07), not a significant increase. They set a provisional no-observed-adverse-effect level of 6.0 g/day in healthy people, based on those symptoms (Hayamizu 2019; Hayamizu 2020).
• Kidney case report — a 1996 case report describes a 44-year-old woman who developed Fanconi's syndrome and severe tubulointerstitial nephritis, progressing to chronic kidney failure, in association with oral L-lysine; the authors describe the entity as previously unrecognised in humans (Lo 1996).
• Reduced kidney function — no safety data on lysine supplements in people with chronic kidney disease were found for this page.
• Cystinuria and lysinuric protein intolerance — inherited disorders of the transporters that carry lysine in the kidney and gut (Bröer 2008; Eggermann 2012). The shared transporter raises a theoretical concern about lysine loading in cystinuria; no trial has tested it. In lysinuric protein intolerance, lysine, arginine and ornithine intake is managed under specialist care.

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Side Effects and Interactions Reported

• Stomach and bowel symptoms — nausea, stomach ache and diarrhoea were the main adverse events in the human studies reviewed by Hayamizu, without a significant increase in risk overall.
• Calcium — in the Civitelli study, 400 mg of L-lysine taken with a calcium load blunted urinary calcium loss in healthy women, and 800 mg/day raised intestinal calcium absorption in osteoporotic patients. No study of lysine supplements in people with high blood calcium was identified; lysine and kidney stones are discussed on the Calcium Absorption page.
• Arginine — lysine and arginine share transporters (Bröer 2008). Smriga 2007 gave the two together; no study testing whether arginine supplements change lysine's effect in herpes was found.
• Antiviral drugs — no study of lysine taken with acyclovir, valacyclovir or famciclovir was found.
• Cardiovascular and gallbladder disease — the Mailoo and Rampes review states that people with these conditions face theoretical risks from lysine supplementation.

Flodin's 1997 review surveys lysine's toxicity data and the safety of chronic dosage levels, and Garlick (2004) summarises the evidence on the safety of individual amino acids taken in excess of the amounts absorbed from dietary protein. Decisions about supplements belong with a clinician.

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Key Research Papers

1. Hayamizu K, Oshima I, Fukuda Z, Kuramochi Y, Nagai Y, Izumo N, Nakano M (2019). Safety assessment of L-lysine oral intake: a systematic review. Amino Acids 51(4):647-659. — PubMed PMID: 30661148
2. Garlick PJ (2004). The nature of human hazards associated with excessive intake of amino acids. Journal of Nutrition 134(6 Suppl):1633S-1639S. — PubMed PMID: 15173443
3. Flodin NW (1997). The metabolic roles, pharmacology, and toxicology of lysine. Journal of the American College of Nutrition 16(1):7-21. — PubMed PMID: 9013429
4. Bröer S (2008). Amino acid transport across mammalian intestinal and renal epithelia. Physiological Reviews 88(1):249-86. — PubMed PMID: 18195088
5. Griffith RS, Walsh DE, Myrmel KH, Thompson RW, Behforooz A (1987). Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Dermatologica 175(4):183-90. — PubMed PMID: 3115841
6. Thein DJ, Hurt WC (1984). Lysine as a prophylactic agent in the treatment of recurrent herpes simplex labialis. Oral Surgery, Oral Medicine, Oral Pathology 58(6):659-66. — PubMed PMID: 6438572
7. Civitelli R, Villareal DT, Agnusdei D, Nardi P, Avioli LV, Gennari C (1992). Dietary L-lysine and calcium metabolism in humans. Nutrition 8(6):400-5. — PubMed PMID: 1486246
8. Smriga M, Kameishi M, Uneyama H, Torii K (2002). Dietary L-lysine deficiency increases stress-induced anxiety and fecal excretion in rats. Journal of Nutrition 132(12):3744-6. — PubMed PMID: 12468617 (Editorial note, 2026-10-14: this entry previously read “Smriga M, Kameishi M, Torii K (2002). Brief and chronic stress responses are mediated by hypothalamic 5-HT neurons in rats. Stress”; no such paper was found in PubMed. The entry now gives these authors' 2002 rat study of lysine and stress.)
9. EFSA Panel on Additives and Products or Substances used in Animal Feed (2014). Scientific Opinion on the safety and efficacy of L-Lysine. EFSA Journal. (Editorial note, 2026-10-14: EFSA published several opinions on L-lysine feed products in 2014 and the entry does not identify which one; no statement on this page rests on it. Its former search link is listed under PubMed Topic Searches.)
10. Pencharz PB, Elango R, Ball RO (2008). An approach to defining the upper safe limits of amino acid intake. Journal of Nutrition 138(10):1996S-2002S. — PubMed PMID: 18806114
11. Smriga M, Torii K (2003). L-Lysine acts like a partial serotonin receptor 4 antagonist and inhibits serotonin-mediated intestinal pathologies and anxiety in rats. Proceedings of the National Academy of Sciences 100(26):15370-5. — PubMed PMID: 14676321
12. Mailoo VJ, Rampes S (2017). Lysine for herpes simplex prophylaxis: a review of the evidence. Integrative Medicine (Encinitas) 16(3):42-46. — PubMed PMID: 30881246
13. Hayamizu K, Oshima I, Nakano M (2020). Comprehensive safety assessment of l-lysine supplementation from clinical studies: a systematic review. Journal of Nutrition 150(Suppl 1):2561S-2569S. — PubMed PMID: 33000161
14. Griffith RS, Norins AL, Kagan C (1978). A multicentered study of lysine therapy in Herpes simplex infection. Dermatologica 156(5):257-67. — PubMed PMID: 640102
15. Milman N, Scheibel J, Jessen O (1980). Lysine prophylaxis in recurrent herpes simplex labialis: a double-blind, controlled crossover study. Acta Dermato-Venereologica 60(1):85-7. — PubMed PMID: 6153847
16. DiGiovanna JJ, Blank H (1984). Failure of lysine in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Archives of Dermatology 120(1):48-51. — PubMed PMID: 6419679
17. McCune MA, Perry HO, Muller SA, O'Fallon WM (1984). Treatment of recurrent herpes simplex infections with L-lysine monohydrochloride. Cutis 34(4):366-73. — PubMed PMID: 6435961
18. Chi CC, Wang SH, Delamere FM, Wojnarowska F, Peters MC, Kanjirath PP (2015). Interventions for prevention of herpes simplex labialis (cold sores on the lips). Cochrane Database of Systematic Reviews (8):CD010095. — PubMed PMID: 26252373
19. Lo JC, Chertow GM, Rennke H, Seifter JL (1996). Fanconi's syndrome and tubulointerstitial nephritis in association with L-lysine ingestion. American Journal of Kidney Diseases 28(4):614-7. — PubMed PMID: 8840955
20. Joint WHO/FAO/UNU Expert Consultation (2007). Protein and amino acid requirements in human nutrition. World Health Organization Technical Report Series 935:1-265. — PubMed PMID: 18330140
21. Smriga M, Ando T, Akutsu M, Furukawa Y, Miwa K, Morinaga Y (2007). Oral treatment with L-lysine and L-arginine reduces anxiety and basal cortisol levels in healthy humans. Biomedical Research 28(2):85-90. — PubMed PMID: 17510493
22. Ghosh S, Smriga M, Vuvor F, Suri D, Mohammed H, Armah SM, Scrimshaw NS (2010). Effect of lysine supplementation on health and morbidity in subjects belonging to poor peri-urban households in Accra, Ghana. American Journal of Clinical Nutrition 92(4):928-39. — PubMed PMID: 20720257
23. Smriga M, Ghosh S, Mouneimne Y, Pellett PL, Scrimshaw NS (2004). Lysine fortification reduces anxiety and lessens stress in family members in economically weak communities in Northwest Syria. Proceedings of the National Academy of Sciences 101(22):8285-8. — PubMed PMID: 15159538
24. Ghosh S, Pellett PL, Aw-Hassan A, Mouneime Y, Smriga M, Scrimshaw NS (2008). Impact of lysine-fortified wheat flour on morbidity and immunologic variables among members of rural families in northwest Syria. Food and Nutrition Bulletin 29(3):163-71. — PubMed PMID: 18947029
25. Eggermann T, Venghaus A, Zerres K (2012). Cystinuria: an inborn cause of urolithiasis. Orphanet Journal of Rare Diseases 7:19. — PubMed PMID: 22480232
26. Singh BB, Udani J, Vinjamury SP, Der-Martirosian C, Gandhi S, Khorsan R, Nanjegowda D, Singh V (2005). Safety and effectiveness of an L-lysine, zinc, and herbal-based product on the treatment of facial and circumoral herpes. Alternative Medicine Review 10(2):123-7. — PubMed PMID: 15989381
27. Koytchev R, Alken RG, Dundarov S (1999). Balm mint extract (Lo-701) for topical treatment of recurring herpes labialis. Phytomedicine 6(4):225-30. — PubMed PMID: 10589440

PubMed Topic Searches

1. PubMed: Lysine dosing pharmacokinetics
2. PubMed: Lysine form bioavailability
3. PubMed: Lysine in pregnancy
4. PubMed: Cystinuria and dibasic transport
5. PubMed: Lysine renal considerations
6. PubMed: EFSA scientific opinions on L-lysine

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Connections

• All Amino Acids
• Lysine Overview
• Lysine Benefits Hub
• Herpes Simplex & Cold Sores
• Collagen Synthesis
• Lysine-Arginine Ratio
• Lysine Amino Acid
• L-Arginine (Counterpart)
• Vitamin C (Collagen Cofactor)
• Zinc
• Copper
• Calcium (Lysine Synergy)
• Lemon Balm (Combination Partner)
• Herpes Labialis
• Chronic Kidney Disease (Caution)
• Immune Boosting
• History
• Sources

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