L-Lysine | Supplementopedia

Overview

L‑Lysine is an essential, water‑soluble amino acid that humans must obtain from the diet because the body cannot synthesize it.
It is a building block for proteins.
It plays a pivotal role in tissue repair, immune function, and the synthesis of important biomolecules such as collagen, hormones, and enzymes.

Herpes simplex virus (HSV) management: Randomized trials show 1–3 g daily reduces outbreak frequency and severity.
Collagen synthesis and wound healing: Lysine‑dependent cross‑linking of collagen fibers accelerates skin, bone, and tendon repair, especially in athletes and post‑surgical patients.
Bone health: Supplementation improves calcium absorption and reduces urinary calcium loss, contributing to higher bone mineral density in older adults.
Immune modulation: Lysine augments antibody production and may lessen stress‑induced cortisol spikes, supporting overall immune resilience.
Metabolic support: As a precursor for carnitine, lysine helps transport fatty acids into mitochondria for energy production, benefiting endurance performance.
Potential anxiolytic effect: Limited human data suggest lysine may attenuate anxiety‑related physiological responses when combined with arginine.
All benefits are dose-dependent and most pronounced when baseline dietary intake is insufficient.

L‑lysine enters cells via the large neutral amino‑acid transporter (LAT1/2) and participates in several biochemical pathways.
It is a required substrate for lysyl‑tRNA synthetase, enabling incorporation into nascent polypeptides.
In the lysine–carnitine pathway, lysine is hydroxylated by lysine‑hydroxylase, then combined with malonyl‑CoA to synthesize carnitine, which shuttles long-chain fatty acids into mitochondria for β‑oxidation.
Lysine also donates its ε‑amino group for cross‑linking collagen via lysyl oxidase, strengthening extracellular matrix.
In the immune system, lysine supports protein synthesis in lymphocytes and augments production of interleukin‑2 and antibodies.
Antiviral activity is thought to arise from competitive inhibition of arginine‑dependent viral replication, reducing HSV replication.
Additionally, lysine modulates the mTOR pathway, influencing protein synthesis and muscle hypertrophy.
These combined actions explain the supplement’s impact on tissue repair, immunity, and metabolic energy.

Typical adult dosing ranges from 500 mg to 3 g daily, split into two doses for optimal absorption.
For HSV prophylaxis, 1–3 g divided into 2–3 doses per day is the most studied regimen.
Bone‑health protocols use 1 g per day, while athletic recovery often employs 2 g split pre- and post‑exercise.
To maximize carnitine synthesis, a minimum of 1 g per day is recommended, especially in low‑protein diets.
Lysine is best taken with meals to improve gastrointestinal tolerance and to enhance concurrent absorption of other amino acids.
For children, 30–50 mg/kg body weight per day is common, but pediatric supplementation should be supervised.
Individuals with renal impairment should limit intake to ≤1 g/day and monitor serum creatinine; medical guidance is essential.

L‑lysine is generally well‑tolerated.
Mild gastrointestinal complaints (cramping, nausea, diarrhea) occur in ≤5 % of users and are usually reduced when the supplement is taken with food.
High‑dose intake (>6 g/day) can cause hyper‑ammonemia, especially in individuals with compromised renal function, and may exacerbate gallstone formation.
Contraindications include severe renal impairment (eGFR < 30 mL/min/1.73 m²) and known hypersensitivity to lysine products.
Drug interactions: lysine may increase absorption of zinc and iron; conversely, high‑dose arginine may counteract lysine’s antiviral effect.
Concurrent use with antibiotics (e.g., aminoglycosides) can theoretically impair renal clearance of the drug due to altered amino-acid transport.
Pregnant and lactating women have no contraindication, but the recommended 1–3 g/day limit should be observed.
Children should only use age‑appropriate doses under medical supervision.

L‑lysine (L‑2,6‑diamino‑hexanoic acid) belongs to the α‑amino‑acid family.
Molecular formula: C₆H₁₄N₂O₂
Molar mass: 146.19 g/mol
IUPAC name: (2S)-2,6‑diamino‑hexanoic acid.
The molecule features a α‑carboxylate, an α‑amino group, and an ε‑amino side chain (CH₂)₄‑NH₂, giving it a positively charged side chain at physiological pH (pKa ≈ 10.5).
This poly‑basic nature makes lysine highly soluble in water and readily interacts with negatively charged biomolecules (DNA, phospholipids).
Its α‑carboxyl participates in peptide bond formation, while the ε‑amino group is critical for cross‑linking via lysyl‑oxidase in collagen.
The L‑configuration corresponds to the natural stereoisomer found in proteins, essential for enzyme recognition and metabolic integration.

Dietary L‑lysine is abundant in animal proteins (red meat, poultry, fish, dairy, eggs) and legumes (soy, lentils, beans).
Commercially, L‑lysine is produced either by microbial fermentation (Corynebacterium glutamicum, Bacillus subtilis) or chemical synthesis from α‑keto‑δ‑aminovaleric acid using the Strecker or hydrolysis routes.
Fermentation yields a high‑purity, food‑grade product with minimal heavy-metal contamination and is the predominant source for dietary supplements.
Quality considerations include GMP‑certified production, verification of ≥98 % purity, absence of residual solvents, and certificate of analysis confirming absence of microbial toxins.
For athletes and clinicians, selecting a product with third‑party testing (e.g., NSF, USP) ensures consistent potency and safety.