IngredientsLysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. Chemically, lysine exists as two enantiomers: L-lysine (the biologically active form used in human metabolism) and D-lysine (which has no known biological role). When supplements or food databases refer to "lysine," they mean L-lysine.
Lysine contains two amino groups and a single carboxylic acid group and can be represented by the chemical formula C₆H₁₄N₂O₂. The molecule possesses a chiral center at the two carbon position. Traditionally, amino acid stereochemistry is defined in terms of D and L configurations, as is commonly done for carbohydrates; the naturally occurring form of lysine is the L enantiomer, which corresponds to the (S) configuration. It is one of the four common α-amino acids to have a nitrogen atom in its side chain.
IUPAC name: (S)-2,6-diaminohexanoic acid. Common synonyms: L-lysine, lysine, Lys, K, lysine monohydrochloride (salt form). Molecular formula: C₆H₁₄N₂O₂. Molecular weight: 146.19 g/mol.
L-Lysine is one of the nine essential amino acids — essential because the human body cannot synthesize them, so they must therefore be included in a healthy diet.
In 1889, Edmund Drechsel at the University of Freiburg, Germany, isolated lysine by hydrolyzing casein, a protein found in milk. The molecule's structure was elucidated in 1902 by Emil Fischer and Fritz Weigert at the University of Berlin; they synthesized it and compared it with the natural product.
Lysine is abundant in a wide range of high-protein foods, including red meat, some fish, eggs, cheese, and legumes. Lysine is usually low in cereal-based food products, but rich in animal food sources such as lean beef, chicken, pork, and shellfish. It is naturally found in both animal-based and plant-based proteins, especially in legumes as well as pseudocereals like quinoa and amaranth.
Most supplemental lysine is made through fermentation by certain bacteria, and is then purified and sold as capsules, tablets, powders, or liquids. L-lysine is usually found in the free base or hydrochloride (HCl) forms; acetate and sulfate are less common forms. HCl and free base forms are not significantly different with regard to total lysine available for use by the body. However, the amino acid appears faster in blood when consumed in supplement form, rather than from intact protein in foods.
L-Lysine hydrochloride was the chemical form of L-lysine used in all intervention trials reviewed in one major 2020 systematic safety assessment. The product may be turned into capsules, tablets, powders, or liquids. Because the process used to produce it involves only plant-based compounds, most L-lysine sold as a supplement is suitable for vegans, and is bio-identical to the dietary amino acid.
L-lysine, as an isolated chemical entity, has no classical ethnobotanical tradition — it is not a plant extract or herbal remedy. Its history is that of a discovered nutrient rather than a folk medicine ingredient. The isolation of lysine dates to 1889, when Edmund Drechsel at the University of Freiburg isolated it by hydrolyzing casein. Its transition into supplement use followed the systematic identification of essential amino acids in the twentieth century.
The use of lysine as a dietary supplement grew largely from two twentieth-century observations: first, the recognition that cereal-based diets prevalent in many parts of Asia, Africa, and the Middle East were lysine-deficient; and second, the empirical observation in the 1970s and 1980s that lysine supplementation appeared to reduce recurrences of herpes simplex infections. The first studies with lysine competing with arginine date back to the 1960s, when herpes simplex viruses were cultured and placed in test tubes with culture medium enriched with 13 amino acids, and the viral expression in the culture medium with an amino acid deficiency was then analysed.
By the late 1970s, clinical use of lysine for herpes labialis was being formalized. For years, people have been using L-lysine to treat the herpes virus and recover from workouts. The supplemental use of lysine for osteoporosis management, anxiety, and athletic performance emerged primarily through clinical research conducted from the 1980s onward rather than through a pre-existing healing tradition.
Lysine fortification has also been studied in an applied public-health context; for example, one study found that lysine fortification reduced anxiety and lessened stress in family members in economically weak communities in northwest Syria. This line of research reflects the recognition that lysine deficiency — common where diets are dominated by wheat, corn, or rice — may have significant neurological and psychological effects beyond simple protein malnutrition.
L-lysine is itself the active compound when used as a supplement. The following subsections describe the biochemical pathways in which it participates.
Lysine plays several roles in humans, most importantly proteinogenesis, but also in the crosslinking of collagen polypeptides, uptake of essential mineral nutrients, and in the production of carnitine, which is key in fatty acid metabolism.
Lysine has been shown to be involved in the crosslinking between the three helical polypeptides in collagen, resulting in its stability and tensile strength. Lysine plays a key role in collagen hydroxylation, a critical step in collagen maturation and stability. Within collagen precursor molecules (procollagens), specific lysine residues are hydroxylated by lysyl hydroxylase enzymes that require vitamin C as a cofactor, generating hydroxylysine residues that are then oxidized by lysyl oxidase to form the covalent crosslinks that give mature collagen its mechanical integrity.
The biosynthesis of carnitine is a multi-step process that converts the essential amino acid lysine into L-carnitine through a series of enzymatic reactions. This pathway primarily occurs in the liver and kidney and involves four key enzymes: Trimethyllysine Hydroxylase (TMLH), Hydroxytrimethyllysine Aldolase (HTMLA), Trimethylaminobutyraldehyde Dehydrogenase (TMABA-DH), and γ-Butyrobetaine Hydroxylase (BBOX). Carnitine is essential for fatty acid metabolism, transporting long-chain fatty acids into mitochondria for β-oxidation and energy production. Lysine is converted into carnitine through a series of enzymatic reactions requiring cofactors like vitamin C and iron.
Lysine increases the intestinal absorption of calcium and eliminates its renal excretion, suggesting a potential role in the management of osteoporosis. The precise molecular mechanism by which lysine enhances intestinal calcium transport has not been fully elucidated in human studies, but is believed to involve interactions with mucosal calcium-binding proteins and facilitated transport systems.
The antagonism of lysine with arginine by competition has been discussed extensively, since during absorption in the intestine or during transport across cell membranes, both compete for the same receptors. In the renal tubules, lysine further induces arginase production, resulting in the degradation of arginine to metabolites. The proposed mechanism by which lysine affects the herpes simplex virus (HSV) is by interfering with the metabolic balance of lysine and arginine. HSV cells synthesize higher levels of arginine and lower levels of lysine than human host cells; increasing cellular lysine concentrations disrupts HSV's balance between lysine and arginine and inhibits viral replication. Lysine does not have any direct antiviral properties, but is believed to act by lowering arginine levels.
Research has investigated whether L-lysine acts like a serotonin receptor 4 (5-HT4) antagonist, and if L-lysine is beneficial in animal models of serotonin (5-HT)-induced anxiety, diarrhea, ileum contractions, and tachycardia and in stress-induced fecal excretion. L-Lysine (0.8 mmol/dl) inhibited (9.17%) binding of 5-HT to the 5-HT4 receptor, without any effect on 5-HT1A, 2A, 2B, 2C, or 3 binding. This partial 5-HT4 antagonism has been proposed as a mechanism underlying both the anxiolytic and gastrointestinal effects of lysine observed in animal research.
Lysine residues in histones undergo post-translational modifications such as acetylation and methylation, regulating gene expression. For instance, acetylation of lysine residues on histones H3 and H4 is associated with gene activation, while methylation can either activate or repress gene expression depending on the site and degree of modification. These modifications are critical for cell differentiation, proliferation, and apoptosis, directly impacting cell growth and development.
This is the area in which lysine has been most extensively studied in human clinical trials. The evidence base is, however, mixed in quality and outcome.
Human/Clinical Evidence:
A key 2017 narrative review published in Integrative Medicine (Encinitas) (PMID: 30881246) systematically searched EMBASE, Medline, AMED, and CINAHL for clinical trials of lysine in HSV. Of the 12 studies analyzed, only 8 were placebo-controlled, 7 of which were double-blind, 7 randomized, and 3 of which used cross-over methodology to minimize time effects.
L-lysine supplementation appears to be ineffective for prophylaxis or treatment of herpes simplex lesions with doses of less than 1 g/d without low-arginine diets. In contrast, two double-blind controlled trials showed no significant prophylaxis with 624 mg/day or 750 mg/day. Two double-blind placebo-controlled trials showed clinically significant reductions in recurrence rates with 1 g/day and 1,248 mg/day.
One of the more commonly cited earlier studies examined prophylactic lysine over 12 months: 26 volunteers with a history of frequently recurring herpetic lesions completed a 12-month double-blind crossover study; the experimental group received daily oral supplements of 1,000 mg of L-lysine. In most instances, members of the lysine group reported significantly fewer lesions than the control group. Similarly, those who were taken off lysine supplementation generally showed a significant increase in lesion frequency. Data from this sample population indicated that when a person's serum lysine concentration exceeded 165 nmol/ml there was a corresponding significant decrease in recurrence rate.
A large questionnaire-based study (N = 1,543) found that the average dosage used was 936 mg of lysine daily; 84% of those surveyed said that lysine supplementation prevented recurrence or decreased the frequency of herpes infection. Whereas 79% described their symptoms as severe or intolerable without lysine, only 8% used these terms when taking lysine. Without lysine, 90% indicated that healing took 6 to 15 days, but with lysine, 83% stated that lesions healed in five days or less. However, this was a questionnaire study subject to substantial reporting biases and did not constitute a controlled trial.
Two studies reported 500 mg/day to be effective for reducing lesion frequency, but neither of these were controlled or statistically tested.
Evidence Strength: Of the articles analyzed, only Thein and Hurt was selected for inclusion in a Cochrane Skin Group review of randomized controlled trials, and this was deemed to be "very low" quality evidence. Overall, the clinical evidence for lysine in HSV management is inconsistent. Higher doses (≥1 g/day) show more promise in better-designed trials, but the overall evidence base is insufficient to make a definitive recommendation. Evidence quality is generally weak to moderate.
Human/Clinical Evidence:
A clinically important study investigated the effects of L-lysine on calcium (Ca) metabolism in humans: In one study, the acute effects of an oral Ca load (3 g as CaCl₂) administered with or without 400 mg of L-lysine were compared in 15 healthy and 15 osteoporotic women. A progressive increase in urinary Ca excretion was observed, except in the L-lysine-treated healthy subjects, who exhibited a blunted calciuric response to the Ca load. In a second study, the effects of a short-term dietary supplementation with either L-lysine, L-valine, or L-tryptophan (800 mg/day) on ⁴⁷Ca fraction absorption were compared in 45 osteoporotic patients. L-lysine but not L-valine or L-tryptophan significantly increased the intestinal absorption of the mineral. Results suggest that L-lysine can both enhance intestinal Ca absorption and improve the renal conservation of the absorbed Ca; the combined effects may contribute to a positive Ca balance, thus suggesting a potential usefulness of L-lysine supplements for both preventive and therapeutic interventions in osteoporosis.
A 2022 review of research suggests that essential amino acids, including lysine, have a positive effect on bone health in aging adults.
Evidence Strength: Preliminary to moderate. The calcium metabolism studies demonstrate a specific, measurable physiological effect, but the clinical trials are small and of short duration. No large randomized controlled trials (RCTs) with fracture outcomes have been conducted.
Preclinical Evidence:
Lysine may be a partial 5-HT4 receptor antagonist and suppresses 5-HT4 receptor-mediated intestinal pathologies and anxiety in rats, and an increase in nutritional load of L-lysine might be a useful tool in treating stress-induced anxiety and 5-HT-related diarrhea-type intestinal dysfunctions. This was established in animal models using radioligand binding, in vitro ileum preparations, and an elevated plus-maze paradigm.
Human/Clinical Evidence:
A randomized controlled human study published in Biomedical Research (2007) found that treatment with L-lysine and L-arginine decreased trait anxiety as well as blunted the increase in state anxiety induced by a stress battery. Salivary cortisol and chromogranin-A levels decreased in men only.
A separate study published in Nutritional Neuroscience (2005) — Jezova et al. — found that subchronic treatment with an amino acid mixture of L-lysine and L-arginine modifies neuroendocrine activation during psychosocial stress in subjects with high trait anxiety.
It has been reported in randomized clinical trials that the combination of L-lysine and L-arginine can effectively reduce patients' score of anxiety with no obvious side effects.
Evidence Strength: Preliminary. The animal data (5-HT4 antagonism) is mechanistically interesting, but human trials are small, use a combination of lysine plus arginine rather than lysine alone, and are limited in number. Further RCTs using lysine as a monotherapy in larger populations are required before conclusions can be drawn.
Lysine has been used as a common workout supplement because of its potential roles in energy production and stimulation of muscle growth. Lysine is a precursor of carnitine that is involved in mitochondrial β-oxidation to convert fatty acids into energy in mammals. Lysine has been investigated for its effects on increasing muscle mass and improving glucose metabolism.
Evidence Strength: Limited clinical trials exist to support lysine use for any of these conditions. The rationale is biochemically sound (lysine as a carnitine precursor and substrate for muscle protein), but direct human RCT evidence for lysine supplementation improving athletic performance or muscle mass in well-nourished individuals is lacking.
The lysine requirement in healthy adults is 30 mg/kg body weight/day, and lysine intake from Western diets is about 40–180 mg/kg BW/day. The average lysine intake of Americans is 75.3 mg/kg BW/day, which is over two times the daily requirement. In populations dependent on cereal-based diets (wheat, corn, rice), lysine is the first limiting amino acid. Fortification programs and supplementation trials in such populations have demonstrated improvements in growth, immune status, and psychosocial well-being, representing an area of stronger public-health evidence.
A single-blind, placebo-controlled, crossover pilot study (N=10) evaluated L-lysine 6 g/day for 4 weeks in outpatient schizophrenic adults who had been episode free for 2 months and on a stable medication regimen for 3 months prior to study initiation. The evidence in this area is highly preliminary and based on very small studies. Broader clinical evaluation is needed before any conclusions can be drawn.
The following dosage information is drawn directly from published studies and systematic reviews, not from general recommendations.
Despite the widespread use of L-lysine in dietary supplements, the safety information pertinent to excessive L-lysine ingestion is limited. A comprehensive 2020 systematic review published in The Journal of Nutrition searched PubMed, Cochrane Library, Ichushi Web, and EBSCOhost and identified 71 articles which included 3,357 study subjects. The L-lysine doses ranged from 16.8 to 17,500 mg/day, and the dosing period ranged from 1 to 1,095 days. A 2019 systematic review in Amino Acids using the same database of 71 studies similarly found that oral lysine supplementation was generally well tolerated across the studies examined.
There are no established guidelines for the upper limit of ingestion for the safe use of amino acid supplements.
Gastrointestinal adverse reactions, such as diarrhea, nausea, and abdominal pain, have been reported with lysine ingestion. Doses as high as 15 to 40 g/day for the treatment of hypochloremic alkalosis in patients with heart disease produced only abdominal pain and diarrhea, which dissipated with dosage reduction. There was no evidence of renal or hematopoietic toxicity at these doses in that clinical series.
Long-term use can potentially cause arginine deficiency. Animal studies have shown that more than 3% oral ingestion of lysine leads to accumulation of triglycerides in the liver. Other reported side effects of lysine supplementation may include headache, neutropenia, elevated liver enzymes, nausea, abdominal pain, and malaise.
High-dose intravenous L-lysine was associated with almost complete inhibition of renal tubular protein reabsorption. A case report describes the development of Fanconi syndrome and tubulointerstitial nephritis associated with lysine supplementation. A 44-year-old female entered a nephrology clinic with symptoms of polyuria, polydipsia, and fatigue. Laboratory findings included a serum creatinine of 1.8 mg/dL and serum urea nitrogen (BUN) of 18 mg/dL. A 24-hour urine collection revealed a creatinine clearance of 54 mL/min, and urinalysis demonstrated proteinuria and hematuria. Azotemia continued to progress over 4 months, with serum creatinine fluctuating between 1.8 and 3.3 mg/dL. A renal biopsy revealed long-term vascular injury with marked interstitial fibrosis and tubular atrophy, as well as a prominence of lysosomes in the proximal tubules. This represents an isolated case report; causality has not been established in a controlled study.
Arginine has many physiological roles in the body, and as it uses the same intracellular transport routes as lysine there is the potential for adverse effects due to a relative arginine deficiency. There is also the potential for adverse effects on renal function due to increased amino acid intake. Lysine competes with arginine for reabsorption in the renal tubules, thereby increasing arginine excretion in urine; lysine also competes with arginine for transport into cells and at absorption sites in the intestines.
In lysinuric protein intolerance (LPI), intestinal absorption and renal tubular reabsorption of arginine, ornithine, and lysine are impaired due to a defective cationic amino acid transporter. Deficiency of arginine and ornithine restricts the function of the urea cycle, leading to hyperammonemia after protein load, and to strong protein aversion. Since high lysine concentrations inhibit several enzymes of the urea cycle in the liver, lysine supplementation may induce hyperammonemia in LPI patients. Standard oral supplementation is therefore contraindicated or must be used with great caution in individuals with this rare metabolic disorder.
Overall, free lysine supplementation in a lysine-sufficient diet can reduce the protein quality of the diets and modify the serum concentrations of many amino acids. Excess free lysine intake adversely affects growth and utilization of nutrients due to amino acid imbalance or antagonism. Overall, lower protein intake increases susceptibility to the adverse effects of lysine supplementation.
In a study of rats, the short-term toxic intravenous dose was determined to be 4 g/kg body weight. These animal data are not directly translatable to human oral supplementation but provide context for the relative safety margin of oral lysine in humans.
Health conditions that L-lysine may help support.
L-lysine, an essential amino acid, has RCT evidence for reducing anxiety symptoms, particularly in combination with L-arginine. Clinical trials demonstrate that L-lysine supplementation reduces trait anxiety and cortisol responses to stress, possibly by acting as a partial serotonin receptor antagonist. A systematic review identified lysine monotherapy and L-lysine + L-arginine combination among reviewed anxiolytic treatments.
L-lysine is an amino acid used to suppress HSV replication, which is strongly implicated as the causative trigger in Bell's palsy. A double-blind placebo-controlled trial showed that 3 g/day of L-lysine for 6 months significantly reduced herpes outbreak frequency, duration, and severity. Its anti-HSV activity makes it a rational adjunctive intervention for Bell's palsy, although it has not been studied directly in Bell's palsy RCTs.
L-lysine is among the most researched natural agents for cold sore prevention. Multiple double-blind RCTs demonstrate that doses ≥1 g/day significantly reduce recurrence frequency and severity of herpes simplex labialis. The mechanism involves competitive antagonism of arginine, which HSV-1 requires for replication.
L-Lysine is an essential amino acid required for collagen biosynthesis in two ways: as a structural amino acid (hydroxylysine forms cross-links in collagen) and as a substrate for lysyl oxidase, which creates the covalent cross-links that give collagen tensile strength. Vitamin C-dependent lysyl hydroxylase converts lysine to hydroxylysine in procollagen. Lysine supplementation supports connective tissue integrity throughout the body.
L-lysine (125 mg/day) was a core ingredient in the FLIES double-blind, placebo-controlled RCT (n=61, 6 months) that produced a significant reduction in floater-related visual discomfort and vitreous opacity areas versus placebo. Its mechanism is inhibition of non-enzymatic glycation of vitreous collagen, a key driver of vitreous degeneration.
L-lysine, especially when combined with L-arginine, has been shown in clinical studies to significantly increase GH secretion in resting subjects. One study of 15 healthy males found that the combination of arginine pyroglutamate and L-lysine significantly elevated GH compared to either amino acid alone. Lysine alone at lower doses (1,200 mg) did not reliably raise GH, but synergistic effects with arginine are documented.
L-lysine is an essential amino acid that plays a structural role in hair keratin and facilitates iron absorption—iron being a critical factor in follicular cycling. Studies have found that iron supplementation combined with L-lysine is more effective than iron alone in treating chronic telogen effluvium. Lysine deficiency has been documented in women with diffuse hair loss.
L-lysine competitively inhibits arginine, an amino acid required for HSV capsid assembly. Multiple controlled trials and a 2017 PMC systematic review found doses exceeding 1 g/day reduce HSV recurrence frequency and outbreak severity. Evidence is mixed at sub-1 g/day doses but consistently positive at 1.2–3 g/day for prophylaxis.
L-Lysine is an essential amino acid required for collagen cross-linking; it is hydroxylated by vitamin C-dependent lysyl hydroxylase to hydroxylysine, which forms the stable intermolecular cross-links in collagen fibrils that confer tensile strength and skin elasticity. Without adequate lysine, collagen cannot form properly cross-linked, mechanically sound fibrils.
Body systems that L-lysine may help support.
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