Lysozyme

Every second, the healthy human mouth produces saliva containing several micrograms of lysozyme. This enzyme — over three billion years old, present even in bacteriophages — remains one of the most effective antibacterial agents ever shaped by evolution. When saliva production declines — due to stress, chemotherapy, or diuretics — the risk of caries and periodontitis rises sharply. In those conditions, lysozyme in a toothpaste is not a cosmetic addition; it becomes a functional necessity.

What It Is

Lysozyme (EC 3.2.1.17) is a muramidase-class hydrolase, a protein of 14.4 kDa and 129 amino acid residues. It was discovered by Alexander Fleming in 1922 — eight years before penicillin. In human saliva, it is secreted primarily by the submandibular and sublingual glands, as well as by neutrophils in the gingival sulcus.

Two sources are used in cosmetic and medical products:

• Hen egg white lysozyme (HEWL) — the industry standard, most studied, 94% homology to human lysozyme
• Recombinant human lysozyme (rhLYZ) — from rice or yeast expression systems, identical to the endogenous form, higher cost

How It Works

Enzymatic mechanism — peptidoglycan hydrolysis. Lysozyme catalyses the hydrolysis of β-1,4-glycosidic bonds between N-acetylmuramic acid (MurNAc) and N-acetylglucosamine (GlcNAc) — the structural elements of bacterial cell wall peptidoglycan. Disruption of this polymer triggers osmotic lysis of the bacterial cell.

Primary targets are gram-positive bacteria with a thick peptidoglycan layer: Streptococcus mutans, S. sobrinus, Staphylococcus aureus, Micrococcus lysodeikticus. Gram-negative bacteria (P. gingivalis, F. nucleatum) are less sensitive due to their outer membrane, but their susceptibility increases dramatically in the presence of lactoferrin (which permeabilises the outer membrane) — the lysozyme + lactoferrin synergy is critically important.

Cationic mechanism — non-enzymatic action. Lysozyme carries a strong positive charge (pI ~11), enabling it to insert into the negatively charged membranes of bacteria independently of its enzymatic activity. This explains its action on species in which the peptidoglycan is "shielded" by teichoic acids.

Immune mechanism. The products of peptidoglycan hydrolysis (muramyl dipeptide, MDP) are potent activators of the NOD2 receptor — an intracellular pattern-recognition receptor of gingival epithelium. This triggers an antibacterial immune response independent of TLR signaling.

Efficacy

Reduction of cariogenic flora

Studies show that lower salivary lysozyme levels correlate with increased caries risk in children and adults (Siqueira et al., 2012, PMID 22214917). Laible & Germaine (1985) demonstrated that lysozyme at 50–200 µg/mL (0.005–0.02%) killed S. sanguis and S. faecalis in vitro within 60 minutes. Crucially, muramidase-inactive lysozyme retained activity — confirming the cationic mechanism's independent contribution.

Treatment of xerostomia (PMID: 11999007)

Tenovuo (2002) systematically reviewed clinical data on the triple complex lysozyme + lactoferrin + lactoperoxidase in xerostomia. Toothpastes with this complex significantly reduced subjective complaints of dry mouth, improved mucosal condition, and decreased caries activity in patients with Sjögren's Syndrome and after radiotherapy. Lysozyme concentration in these formulations: 0.05–0.1%.

Antibacterial profile in vitro (PMID: 34659660)

Garg & Naidoo (2021) summarize that lysozyme demonstrates activity against 30+ oral bacterial species, including key cariogenic species (S. mutans, S. sobrinus) and periodontopathogens. Activity is enhanced at neutral pH (7.0), corresponding to healthy saliva conditions.

Safety

Lysozyme is a native component of human saliva, belonging to the endogenous defence proteins. Safety profile:

• Listed in EU CosIng and FDA GRAS without concentration restrictions for cosmetic use
• The sole clinically significant limitation: egg white allergy. Hen egg white lysozyme is a known allergen, and individuals with confirmed egg allergy should use products based on recombinant lysozyme or avoid it entirely
• Thermolabile at temperatures above 60°C — an important manufacturing constraint

Role in the QDRO Formula

Lysozyme is an essential component of the QDRO enzyme system: in the triad of lysozyme + lactoferrin + lactoperoxidase, each element acts through its own pathway, covering the others' weaknesses. Lysozyme provides direct cell wall disruption, lactoferrin permeabilises gram-negative outer membranes, and lactoperoxidase generates antibacterial radicals.

Concentration in toothpaste: 0.05–0.1% (total enzyme system load should not exceed 0.3% to avoid manufacturing difficulties). Especially justified in sensitive-gum pastes and for patients with reduced salivary flow.

Brand verdict: we use it — one of three enzymatic pillars of QDRO, a direct reproduction of the saliva defence system.

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Sources:

• Laible NJ, Germaine GR. (1985). Bactericidal activity of human lysozyme against Streptococcus sanguis and S. faecalis. Infect Immun. PMID: 3967927
• Siqueira WL et al. (2012). Salivary proteomics: hyperglycemia and dental caries risk. Caries Res. PMID: 22214917
• Veerman EC et al. (1996). Secretory immunoglobulin A and lysozyme in glandular and whole saliva. J Dent Res. PMID: 8901093
• Tenovuo J. (2002). Clinical applications of antimicrobial host proteins lactoperoxidase, lysozyme and lactoferrin in xerostomia. Oral Dis. PMID: 11999007
• Garg S, Naidoo A. (2021). Anticaries and antibacterial properties of lysozyme: a review. J Oral Maxillofac Res. PMID: 34659660