Lysine aspartate

Other Names

(2S)-2-aminobutanedioic acid, (2S)-2,6-diaminohexanoic acid(S)-2,6-Diaminohexanoic acid (S)-2-aminosuccinic acid salt(S)-2,6-Diaminohexanoic acid compound with (S)-2-aminosuccinic acid (1:1)Aspartic acid, compd. with lysine (1:1)L-Aspartic acid, compd. with L-lysine (1:1)L-Aspartic acid, compound with L-lysine (1:1)L-Aspartic acid-L-lysine (1:1)L-LYS L-ASPL-Lysine aspartateL-LYSINE L-ASPARATEL-Lysine L-aspartate saltL-Lysine, L-aspartate (1:1)L-Lysine-L-aspartateL-Lysine-L-aspartic acidL-LYSINE1-ASPARTATEL-LysineaspartateL-Lysyl-L-aspartateLysine aspartate salt

Synopsis

Lysine Aspartate

1. Identity and Chemical Characterization

Lysine aspartate (also rendered as L-lysine L-aspartate, L-lysine-L-aspartic acid, or L-lysyl-L-aspartate) is an ionic amino acid salt formed from the two naturally occurring amino acids L-lysine and L-aspartic acid in a defined 1:1 molar ratio. It is registered under CAS number 27348-32-9, with the molecular formula C₁₀H₂₁N₃O₆, and its systematic IUPAC-style designation is L-aspartic acid, compound with L-lysine (1:1); alternative Chemical Abstracts names include L-Lysine, L-aspartate (1:1), and (2S)-2-aminobutanedioic acid compound with (2S)-2,6-diaminohexanoic acid.

Lysine aspartate is a compound formed from two amino acids, lysine and aspartic acid, both of which play significant roles in human metabolism and protein synthesis. The compound presents as a white powder that is odorless or only slightly odorous; it is soluble in water but insoluble in ethanol and ether.

L-Lysine-L-aspartate is obtained from free L-lysine derived from L-lysine hydrochloride, which is neutralized by adding an equimolar quantity of L-aspartic acid, then concentrated and crystallized. The compound is also produced in USP/EP/BP pharmaceutical grades, indicating regulatory recognition in major pharmacopeias.

The two constituent amino acids carry distinct chemical profiles. L-lysine is one of nine essential amino acids that the human body cannot synthesize and must obtain from dietary sources; it plays fundamental roles in protein synthesis, collagen formation, calcium absorption, immune function, and the production of carnitine — a molecule essential for fatty acid metabolism and energy production. L-aspartate (aspartic acid; C₄H₇NO₄; 2-aminobutanedioic acid) is a non-essential α-amino acid found ubiquitously throughout the body, including in the brain.

2. Natural Sources and Dietary Occurrence

The two amino acid components of lysine aspartate are obtained from dietary protein.

L-Lysine: Foods rich in lysine include meat, cheese, eggs, legumes, nuts, and yogurt. The adult requirement for lysine is approximately 30–35 mg per kilogram of body weight per day; the World Health Organization (WHO) sets the requirement at 30 mg/kg/day. Lysine has been extensively used to fortify foods and as a dietary supplement, particularly in poor countries where cereal-based diets are the main source of nutrients.
L-Aspartic acid: Aspartic acid, a non-essential amino acid traditionally viewed as merely a protein building block, has emerged as a critical metabolic hub in the tricarboxylic acid and urea cycles, exhibiting antioxidant, anti-inflammatory, immunomodulatory, and lipid-regulating activities. Under metabolic stress, endogenous aspartic acid may become insufficient, positioning it as a conditionally functional amino acid requiring supplementation.

As a combined salt, lysine aspartate does not occur in significant quantities pre-formed in foods; it is synthesized industrially and encountered primarily in the context of pharmaceutical preparations and dietary supplements.

3. Common Forms and Preparations

L-Lysine-L-aspartate is mainly used in food as a nutritional fortifier. The compound is often utilized in dietary supplements and therapeutic formulations aimed at improving health outcomes related to amino acid deficiencies.

Commercial forms include:

Crystalline powder: The primary bulk form used in pharmaceutical and nutraceutical manufacturing, available in nutraceutical and pharmaceutical grades (including USP/EP/BP standards).
Oral tablets and capsules: Standard solid dosage forms for dietary supplementation.
Sachets and granules: Used in effervescent or reconstitutable preparations common in European markets.
Injectables and intravenous preparations: Used historically in clinical settings, particularly for parenteral amino acid support.

The compound is produced through the direct reaction of L-lysine and L-aspartate under controlled conditions, and microbial fermentation techniques employing genetically modified strains that overproduce either or both amino acids can also be used.

4. Traditional and Historical Use

Lysine aspartate has been used in nutritional supplements, especially in Europe, based on the reputed benefits of its constituent amino acids. Historically, lysine has been valued for its role in protein synthesis, tissue repair, and immune system support, while aspartate is recognized for its involvement in cellular energy production and neurotransmitter balance.

Combined as lysine aspartate, these amino acids have been utilized to support overall well-being, particularly in Europe and Asia, where amino acid supplementation has a long tradition. Lysine aspartate has been employed as a remedy for fatigue, stress, and muscle weakness, with the belief that it enhances metabolic efficiency and physical performance.

Additionally, it has been used as a supportive treatment in cases of liver dysfunction, due to its ability to assist in ammonia detoxification and improve cognitive function in patients with hepatic encephalopathy. This application parallels other amino acid salts used in European clinical medicine—most notably L-ornithine L-aspartate (LOLA)—which share the common rationale of providing aspartate as a substrate for the hepatic urea cycle.

It is important to note that there is limited historical documentation of lysine aspartate specifically as a distinct traditional remedy, as distinct from its individual component amino acids. Much of its traditional use in Europe is embedded in broader mid-20th-century European pharmaceutical and hospital-pharmacy traditions around amino acid infusion therapy, rather than in ancient or indigenous medicinal systems.

5. Key Constituents and Established Mechanisms of Action

5.1 L-Lysine Component

The primary role of lysine in the human body is to participate in protein synthesis; it is also an essential compound for building a positive nitrogen balance in the body, and promotes overall bone health by decreasing urinary calcium content and increasing calcium absorption.

Collagen and connective tissue synthesis: Lysine is essential for the synthesis of collagen and elastin; the formation of crosslinks with glutamine resistant to mechanical influences; and the stabilization of the extracellular matrix, hemostasis, and the activation of growth factors. Hydroxylysine is an essential component of collagen, and desmosine, formed from allysine, connects tropoelastin molecules and ensures elastin's flexible and stable structure.

Carnitine biosynthesis: Lysine is a precursor of carnitine, which is a crucial molecule in fatty acid metabolism and energy production. Insufficient lysine intake can therefore impair fatty acid oxidation indirectly.

Calcium metabolism: Lysine promotes calcium balance through two mechanisms: enhancing intestinal calcium absorption and reducing renal calcium excretion. Early isotope tracing studies confirmed that lysine supplementation increases intestinal calcium transporter efficiency. Lysine also directly stimulates osteoblasts, promoting collagen matrix synthesis and crosslinking, providing a structural foundation for calcium deposition.

Antiviral mechanism (HSV): In tissue-culture studies, arginine deficiency suppressed herpes simplex virus replication; lysine, as an analog of arginine, as an antimetabolite, antagonized the viral growth-promoting action of arginine. This competition occurs because both arginine and lysine are transported across cell membranes by the same carrier system; increasing lysine intake allows it to compete with arginine for absorption and transport into cells, limiting the amount of arginine available for the virus, and reducing the production of arginine-rich capsid proteins.

Neurotransmitter and stress-axis modulation: Animal studies found worsening of stress-induced anxiety and colonic health in rats fed a lysine-deficient diet; the anxiogenic response to lysine inadequacy in rats was mediated via serotonin alterations in the central amygdala, the brain region functionally comparable in rodents and humans.

5.2 L-Aspartate Component

L-Aspartate has exceptional importance in urea synthesis, the purine-nucleotide cycle (PNC), the malate-aspartate shuttle (MAS), gluconeogenesis, and neurotransmission, and it is the substrate for the synthesis of proteins, asparagine, arginine, nucleotides, and several substances that play a role in the development of nervous tissue and neurotransmission.

Urea cycle and ammonia detoxification: Aspartic acid contributes to the urea cycle by combining with citrulline to form argininosuccinate, which is then converted into arginine and fumarate; this process helps detoxify ammonia and maintain nitrogen balance in the body.

Energy metabolism: L-Aspartic acid connects directly to cellular energy production by participating in the tricarboxylic acid (TCA) or Krebs cycle; it is readily converted into oxaloacetate, an intermediate compound within this central energy-generating pathway, thereby supporting the steady operation of the cycle and the continuous production of ATP.

Malate-aspartate shuttle: Aspartate carries reducing equivalents in the malate-aspartate shuttle, which utilizes the ready interconversion of aspartate and oxaloacetate.

Nucleotide biosynthesis: Aspartate donates one nitrogen atom in the biosynthesis of inosine, the precursor to the purine bases. It is also a precursor for the synthesis of other amino acids including asparagine, methionine, threonine, and isoleucine, and its role extends to the biosynthesis of purine and pyrimidine nucleotides — the essential building blocks of DNA and RNA.

Isomer distinction: L-aspartic acid serves as a metabolic intermediate in energy and biosynthesis pathways, while D-aspartic acid acts as a signaling molecule via N-methyl-D-aspartate receptor-mediated neuroendocrine regulation. The L-isomer present in lysine aspartate is thus metabolically oriented, distinct from the D-isomer used in some testosterone-related supplements.

6. Scientific Evidence by Area of Use

6.1 Herpes Simplex Virus (HSV) Prophylaxis and Treatment

The largest body of clinical evidence for L-lysine supplementation—the principal pharmacologically active component of lysine aspartate in this context—concerns herpes simplex virus (HSV) infections. No clinical trials to date have specifically tested lysine aspartate as the intervention; trials have been conducted with L-lysine hydrochloride or free L-lysine. Findings are therefore attributed to the lysine moiety.

Evidence summary: L-lysine supplementation appears to be ineffective for prophylaxis or treatment of herpes simplex lesions with doses of less than 1 g/day without low-arginine diets. Doses in excess of 3 g/day appear to improve patients' subjective experience of the disease.

Positive trial (1987): A clinical trial by Griffith et al. (Dermatologica, 1987; PMID 3115841) found success of L-lysine therapy in frequently recurrent herpes simplex infection, reporting reductions in recurrence.

Negative trial (1984): A double-blind, placebo-controlled trial of oral lysine hydrochloride therapy (400 mg, three times a day) in 21 patients with frequently recurring infection found that using measures of episode frequency, duration, and severity, no substantial benefit of lysine therapy was detectable either as a treatment for episodes in progress or as a prophylactic drug for the prevention of recurrences, leading to the conclusion that it is unlikely that lysine improves frequently recurrent HS infections in the majority of patients.

Observational study: Members of a lysine-treated group reported significantly fewer lesions than the control group; those taken off lysine supplementation generally showed a significant increase in lesion frequency. Data indicated that when serum lysine concentration exceeded 165 nmol/mL there was a significant decrease in recurrence rate, and frequency increased significantly as concentrations fell below this threshold, suggesting that prophylactic lysine may be useful in managing selected cases of recurrent herpes simplex labialis if adequate serum levels can be maintained.

Cochrane review assessment: Of the articles reviewed, only one 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 evidence strength: Mixed and generally weak to moderate. The clinical evidence is inconsistent across trials, with conflicting results. The biological mechanism (arginine antagonism) is well-supported in vitro, but translation to consistent clinical benefit remains unproven. The Cochrane review rated available RCT evidence as "very low" quality.

6.2 Calcium Metabolism and Bone Health

Human clinical evidence: In one study, the acute effects of an oral calcium load (3 g as CaCl₂) administered with or without 400 mg of L-lysine were compared in 15 healthy and 15 osteoporotic women; in all cases the oral calcium load determined a progressive increase in serum total calcium and ionized calcium, and — in L-lysine-treated healthy subjects — a blunted calciuric response to the calcium load was observed, indicating improved renal calcium conservation.

In a second study, the effects of short-term dietary supplementation with either L-lysine, L-valine, or L-tryptophan (800 mg/day) on ⁴⁷Ca fractional absorption were compared in 45 osteoporotic patients; L-lysine but not L-valine or L-tryptophan significantly increased the intestinal absorption of the mineral, suggesting that L-lysine can both enhance intestinal calcium absorption and improve renal conservation of the absorbed calcium, with potential usefulness for both preventive and therapeutic interventions in osteoporosis.

Limitations: Clinical studies confirming the link between lysine intake and osteoporosis protection do not exist. The studies by Civitelli et al. (1992) are small, short-term, and have not been replicated in larger randomized controlled trials. In vitro data support osteoblast stimulation, but these have not been followed by adequately powered clinical outcome trials.

Overall evidence strength: Preliminary; supported by small human studies showing biochemical (absorption) effects but lacking long-term clinical outcome data.

6.3 Stress, Anxiety, and Neuroendocrine Modulation

Population study (Syria, 2004): As part of a 3-month randomized double-blind study, lysine fortification of wheat was tested to see whether it reduces anxiety and stress response in family members in poor Syrian communities consuming wheat as a staple food; in the lysine-fortified group, the plasma cortisol response to blood drawing as a cause of stress was reduced in females, and sympathetic arousal in males (measured by skin conductance) was also reduced. Lysine fortification also significantly reduced chronic anxiety as measured by the trait anxiety inventory in males. Critically, this study was conducted in a lysine-deficient population, so the results may reflect the correction of nutritional deficiency rather than a pharmacological effect in well-nourished individuals.

RCT in Japanese adults (2007): A double-blind, placebo-controlled, randomized study was carried out in 108 healthy Japanese adults; a week-long oral treatment with L-lysine (2.64 g/day) and L-arginine (2.64 g/day) significantly reduced both trait anxiety and state anxiety induced by a cognitive stress battery, without regard to gender; in addition, the combination decreased basal levels of salivary cortisol and chromogranin-A (a salivary marker of the sympatho-adrenal system) in male subjects.

Overall evidence strength: Preliminary to moderate. Results are promising but based on a small number of studies. The Syrian study's population-level lysine deficiency confounds generalization to well-nourished populations. The Japanese RCT used a combination with L-arginine, preventing attribution of effects to L-lysine alone. Further, these studies used L-lysine (not lysine aspartate specifically), and it is not established whether the aspartate salt would produce identical outcomes.

6.4 Connective Tissue and Wound Healing

Lysine is essential for the synthesis of collagen and elastin, and has been suggested in the form of creams, gels, and sprays to support wound healing. While the biochemical role of lysine in collagen synthesis is thoroughly characterized, clinical trials directly testing lysine supplementation for wound healing outcomes in humans are lacking. Available in vitro evidence and animal studies strongly support the biochemical role of lysine in collagen crosslinking, but this has not been directly tested in adequately powered human clinical trials using lysine aspartate specifically.

6.5 Ammonia Metabolism and Hepatic Encephalopathy

The aspartate component of lysine aspartate is theoretically active in hepatic ammonia detoxification. The closely related compound L-ornithine L-aspartate (LOLA) has been more extensively studied in this context. In the urea cycle in periportal hepatocytes, L-ornithine serves as an intermediary and activates carbamoyl phosphate synthetase 1, and L-aspartate stimulates the activity of arginase, resulting in the incorporation of NH₃ into urea and glutamine; meta-analyses of randomized controlled trials conducted over the past two decades evidenced the benefit of LOLA for the mental state in both overt and minimal hepatic encephalopathy, with the oral LOLA formulation particularly effective. However, clinical evidence for lysine aspartate specifically in hepatic encephalopathy is not established in the peer-reviewed literature — the evidence base for aspartate-containing compounds in ammonia detoxification derives from LOLA, not from lysine aspartate.

6.6 Athletic Performance and Fatigue

The theoretical basis for use in athletic contexts rests on the metabolic roles of both constituent amino acids: aspartate's participation in the TCA cycle and the malate-aspartate shuttle, and lysine's role as carnitine precursor. Athletes and fitness enthusiasts often use L-aspartic acid due to its potential to combat fatigue and enhance endurance; its involvement in energy metabolism and ammonia detoxification may contribute to improved stamina and reduced feelings of exhaustion during prolonged exercise. However, no human clinical trials specifically testing lysine aspartate as an ergogenic or anti-fatigue agent have been identified in the peer-reviewed literature. This area remains speculative and evidence is based primarily on mechanistic inference from the properties of the constituent amino acids.

7. Body Systems Associated with Lysine Aspartate

Musculoskeletal system: Collagen synthesis, bone mineral density, calcium absorption (via L-lysine); structural protein formation.
Hepatic/detoxification system: Urea cycle support, ammonia clearance (via L-aspartate); analogous to LOLA mechanism.
Central nervous system and neuroendocrine axis: Modulation of serotonin and stress-axis signaling via lysine; L-aspartate's major metabolic role in the brain is recycling reducing equivalents between the cytoplasm and mitochondrial matrix as part of the malate-aspartate shuttle, and L-aspartate's actions on synaptic receptors are consistent with a possible role as an excitatory neurotransmitter.
Immune system: Antiviral activity via arginine competition (HSV); support of antibody and immunoglobulin production through protein synthesis.
Cardiovascular and metabolic system: Carnitine production (via L-lysine) supporting fatty acid oxidation and energy substrate handling.
Cellular energy metabolism: Aspartate's roles in the TCA cycle, malate-aspartate shuttle, and gluconeogenesis.

8. Dosage Forms and Reported Dosages

Dosages in peer-reviewed human studies have been reported for L-lysine (the component studied most extensively in clinical trials), not typically for lysine aspartate as a unified salt. The following dosages are as stated in identified sources:

A double-blind, placebo-controlled trial used oral lysine hydrochloride at 400 mg three times a day (1,200 mg/day total) in 21 patients with recurrent herpes simplex.
Studies by Civitelli et al. (1992) used 400 mg L-lysine co-administered with a calcium load in healthy and osteoporotic women, and 800 mg/day L-lysine supplementation for 3 days in 45 osteoporotic patients to assess calcium absorption.
A double-blind RCT in 108 healthy Japanese adults administered L-lysine 2.64 g/day combined with L-arginine 2.64 g/day for one week to assess anxiety and stress-axis outcomes.
A daily dose of 50 mg/kg body weight has previously been recommended for cold sores, and doses of up to 3 g/day are thought to be safe, as oral lysine toxicity has not occurred in humans.
A systematic review identified 71 articles including 3,357 study subjects; L-lysine doses ranged from 16.8 to 17.5 g/day and the dosing period ranged from 1 to 1,095 days.
The adult physiological requirement for lysine is approximately 30–35 mg per kilogram of body weight per day (WHO: 30 mg/kg/day), translating to roughly 2,100–2,450 mg daily for a 70 kg adult.

No specific dosing data were identified in peer-reviewed literature for lysine aspartate as a distinct formulation independent of its component amino acids.

9. Safety Considerations and Interactions

9.1 General Safety Profile of L-Lysine

A 1997 review of human clinical data concluded that L-lysine hydrochloride was a safe and well-tolerated substance in humans using doses in dietary supplements up to 3.0 g/day (3.75 g/day as L-lysine hydrochloride), and that based on animal studies and high-dose trials in humans, a dose of 6.0 g/day was also safe for long-term use.

In healthy humans, lysine supplementation is generally safe, with the main reported adverse effects being mild gastrointestinal symptoms at high doses. Serious side effects are rare, and no toxicity has been observed at typical supplemental levels. The most common adverse effects are mild and include nausea, stomachache, and diarrhea. These symptoms are generally only seen at higher doses (above 6 g/day) and are not statistically more frequent than in placebo groups at typical supplemental doses; clinical studies and systematic reviews have not found evidence of serious or long-term adverse effects from lysine supplementation in adults, adolescents, or children (over 10 years) at doses up to 3 g/day.

9.2 Pre-clinical Toxicological Data

A 13-week oral toxicity study evaluated L-lysine hydrochloride in male and female Sprague-Dawley rats at doses of 1.25%, 2.5%, and 5.0% (w/w) in a standard diet; treatment-related changes were not observed in clinical signs, body weights, diet consumption, water intake, ophthalmology, gross pathology, organ weights, or histology at any concentration. The no-observed-adverse-effect level (NOAEL) for lysine was estimated at 5.0% for both genders (male, 3.36 ± 0.12 g/kg/day; female, 3.99 ± 0.28 g/kg/day).

9.3 Upper Intake Levels

In human studies establishing tolerable upper intake levels for amino acids, the NOAEL for lysine was identified at 6 g/day, and the lowest-observed-adverse-effect level (LOAEL) at 7.5 g/day.

9.4 Systematic Review Findings

A systematic review assessing the clinical safety of L-lysine supplementation searched PubMed, the Cochrane Library, and other databases; it identified 71 articles including 3,357 study subjects with L-lysine doses ranging from 16.8 to 17.5 g/day and dosing periods from 1 to 1,095 days; observed adverse events were mainly subjective gastrointestinal tract symptoms, but the risk analysis for incidence of gastrointestinal symptoms was not statistically significant.

9.5 Amino Acid Imbalance Consideration

Lysine supplementation can reduce the protein quality of casein-based diets in animal studies. Excessive lysine can disrupt the balance of other amino acids, potentially affecting nutrient utilization and growth in animals, but these effects are not seen at typical human supplement doses. The applicability of animal toxicological data has been questioned in the case of macronutrients such as amino acids, due to differences between animal and human toxicokinetics and toxicodynamics.

9.6 Populations Requiring Caution

While lysine is generally safe when taken in recommended amounts, excessive intake can lead to side effects such as stomach pain, diarrhea, and kidney issues; individuals with kidney disease, those who are pregnant or breastfeeding, and individuals with a history of lysine metabolism disorders should exercise particular caution with supplementation.

9.7 Interaction with Arginine

Lysine acts as a direct antagonist to arginine by competing for the same membrane transport carrier; increasing lysine intake limits the amount of arginine available to cells. This competition is the proposed basis for the antiviral effect against HSV, but it also implies that very high-dose lysine supplementation could theoretically diminish arginine bioavailability — which may be relevant for individuals relying on arginine for nitric oxide-mediated vascular function, immune responses, or wound healing, though clinical evidence for adverse outcomes from this competition at typical supplemental doses in humans is not established in the reviewed literature.

9.8 Aspartate-Specific Considerations

L-aspartate plays a role in the pathogenesis of psychiatric and neurologic disorders, and alterations in branched-chain amino acid levels in diabetes and hyperammonemia; further research is needed to examine the use of L-aspartate as a dietary supplement and the risks of increased L-aspartate consumption. L-aspartate is an excitatory amino acid with activity at synaptic receptors; however, at dietary supplemental doses it has not been established to produce clinically meaningful excitotoxic effects.

10. Evidence Gaps and Research Status

A critical limitation throughout the scientific literature is that lysine aspartate as a unified salt has not been independently studied in robust human clinical trials. The evidence base described above is derived from studies on the individual component amino acids — predominantly L-lysine in various salt forms. Whether the 1:1 ionic association of L-lysine and L-aspartate in a single molecule confers additional pharmacokinetic benefits (such as improved bioavailability, altered absorption kinetics, or synergistic metabolic effects) over the separate administration of the two amino acids has not been formally evaluated in published peer-reviewed human trials. Further research is needed to examine the use of L-aspartate as a dietary supplement and the risks of increased L-aspartate consumption. Clinical studies confirming the link between lysine intake and osteoporosis protection do not exist.

References

Health Conditions

Health conditions that Lysine aspartate may help support.

No conditions available.

Body Systems

Body systems that Lysine aspartate may help support.

No body systems available.