IngredientsLactoperoxidase (LPO, EC 1.11.1.7) is a peroxidase enzyme secreted from mammary, salivary, tears and other mucosal glands including the lungs, bronchi and nose, that functions as a natural, first line of defense against bacteria and viral agents. In humans, lactoperoxidase is encoded by the LPO gene. The enzyme is also referred to in the scientific literature as salivary peroxidase (when specifically describing the salivary isoform), and its systematic Enzyme Commission designation is EC 1.11.1.7.
Lactoperoxidase (LPO) is a member of the superfamily of mammalian heme peroxidases that is isolated from milk, and it is the first enzyme announced to be found in milk. In addition to milk, LPO is also found in saliva, tears, and airways (airway goblet cells and submucosal glands). It is present in the mammary, salivary and thyroid glands and their secretions; in organs such as the stomach and kidney; and in fluids such as synovial, cerebral, cervical and spinal fluids, lymph, and plasma.
Approximately 70 indigenous enzymes have been reported in normal bovine milk, including lactoperoxidase. The primary commercial source for isolated lactoperoxidase is bovine milk and whey. It can be isolated from the whey on the principle that it remains positively charged at whey pH, which makes it susceptible for linkage to ion-exchange resin.
The concentration of lactoperoxidase is 11–45 mg/L in bovine colostrum and 13–30 mg/L in mature bovine milk. Its concentration in bovine colostrum is low initially, but it reaches the maximum level within 3–5 days after parturition. Human colostrum also contains lactoperoxidase (EC 1.11.1.7), which represents about 0.004% of the total protein in crude human colostrum.
Since the introduction of industrial processes for the isolation of LPO from milk and whey, the interest in this enzyme has increased considerably, and attention has been paid to potential and actual applications of LP-systems as biopreservatives in food and other products. Commercially, lactoperoxidase is available as:
It has been acknowledged since ancient times that milk and dairy products have a vital role in nutrition and contribute considerably to human health, due to their content of immunoglobulins, enzymes, hormones, growth factors, antibacterial agents, fatty acids, vitamins, and minerals. Lactoperoxidase as an isolated enzyme was not scientifically characterized until the twentieth century; however, the antimicrobial properties of raw milk that it contributes to were implicitly relied upon in pre-industrial societies.
The natural antimicrobial system present in milk, the lactoperoxidase (LP) system, has been used to preserve raw milk quality in areas where it is not possible to use mechanical refrigeration for technical and/or economic reasons. This practice has historical roots in pastoral communities across Africa, Asia, and Latin America, where fresh raw milk—which natively contains active lactoperoxidase, thiocyanate from the animal's diet, and endogenously generated hydrogen peroxide—would remain substantially fresher and less prone to pathogenic spoilage than would be expected based on ambient temperature alone.
In many parts of the world, the LPS has been used to protect dairy products, particularly in remote areas where farmers are not in close proximity to the market. Fifteen years of field experiments in developed and developing countries were conducted and assessed by the FAO/WHO Joint Experts Committee on Food Additives (JECFA). Upon completion of these substantial and in-depth studies, a guideline for the use of an alternative milk preservation method based on the activation of the natural enzymatic antibacterial complex in milk (Lactoperoxidase system) was approved by the FAO/WHO Expert Committee on Food Additives in 1989 and by the Codex Alimentarius Commission in 1991 as being safe for use.
Lactoperoxidase also occupies an implicit role in traditional oral hygiene. During the last decades, several clinical studies describing the clinical efficacy of the lactoperoxidase system in a variety of oral care products (toothpastes, mouth rinses) have been published. The enzyme is a constitutive component of human saliva, and many ancient preparations that used milk, whey, or fermented dairy fluids as oral rinses unknowingly exploited LPO-mediated antimicrobial activity, though this mechanism was unrecognized until modern biochemistry elucidated the full lactoperoxidase system.
Lactoperoxidase is considered a basic protein present in milk, formed by a single polypeptide chain with a molecular weight of approximately 78 kDa. The carbohydrate moiety comprises about 10% of the total weight. LPO is a calcium- and iron-containing glycoprotein arranged in a single polypeptide chain of about 80 kDa. Human LPO is moderately cationic with a pI of approximately 7.5, but bovine LPO is more cationic with a pI of approximately 9.6.
According to mRNA studies, both bovine LPO and human LPO contain 712 amino acid residues, while according to protein analysis, human LPO contains 632 amino acid residues, including 16 cysteine residues, and bovine LPO contains 612 amino acid residues, including 15 cysteine residues. The molecular mass of human LPO is 80 kDa and it has four potential N-glycosylation sites. In humans, the LPO gene is found on chromosome 17, while the bovine LPO gene is found on chromosome 19.
The structure of lactoperoxidase consists mainly of alpha-helices plus two short antiparallel beta-strands. Lactoperoxidase belongs to the heme peroxidase family of mammalian enzymes that also includes myeloperoxidase (MPO), eosinophil peroxidase (EPO), thyroid peroxidase (TPO), and prostaglandin H synthase (PGHS). A heme cofactor is covalently bound near the center of the protein.
The LP system consists of three components: LP, thiocyanate, and hydrogen peroxide (H2O2). Lactoperoxidase catalyzes the hydrogen peroxide (H2O2) oxidation of several acceptor molecules: reduced acceptor + H2O2 → oxidized acceptor + H2O. The most biologically significant reaction involves the oxidation of thiocyanate ions (SCN⁻), the pseudo-halide substrate.
LPO catalyzes the oxidation of certain molecules such as thiocyanate (SCN⁻), iodide (I⁻), and bromide (Br⁻) in the presence of hydrogen peroxide (H2O2). This reaction leads to the formation of antimicrobial products that have a great antimicrobial spectrum, including antibacterial, antiviral, and antifungal activity, especially hypothiocyanite (OSCN⁻) and hypoiodite (OI⁻), which are coming into prominence via their high antimicrobial activity.
Lactoperoxidase rapidly oxidizes iodide and slowly oxidizes bromide and is designated a haloperoxidase. In mammals, the source of hydrogen peroxide is one of the DUOX1 or DUOX2 enzymes, which reduce dioxygen to H2O2 by oxidizing NADPH.
Hypothiocyanite ions react with the bacterial membranes and also disrupt the functioning of certain metabolic enzymes. More specifically, the LPS causes oxidation of the thiol groups of enzymes and affects the cytoplasmic membranes of sensitive microorganisms, causing the leakage of potassium ions, amino acids and polypeptides. Lactoperoxidase activity produces toxic oxidation products that inhibit bacterial metabolism by oxidation of essential sulfhydryl groups in proteins.
The LP system prevents the growth of Gram-positive bacteria and kills Gram-negative bacteria. Lactoperoxidase, in the LP system, is totally nonoffensive to human normal cells. At the same time, it protects against H2O2-induced cell damage.
In addition to its antimicrobial action, LP also acts in the degradation of several carcinogens, protecting the cells against peroxidative effects. Perraudin and Reiter (1998) described the LP system as an antioxidant mechanism protecting the cells from highly reactive oxygen species (ROS). LPO shows antioxidant activity and exerts ability to degrade carcinogenic compounds.
LPO is found in saliva, tears, and airways (airway goblet cells and submucosal glands) and contributes significantly to the self-defense of the mammal body. LPO is a heme peroxidase present in several exocrine secretions, including the interface of human airways epithelium, which produces different anti-infectious agents in the presence of hydrogen peroxide (H2O2), principally from halide (the iodide anion I⁻) and pseudo-halide (thiocyanate, SCN⁻) substrates.
In the absence of the LPO gene, there is an increase in the frequency of diverse diseases, including inflammation, tumor formation, and obesity.
The oral health applications of lactoperoxidase are the most clinically studied area of its use as a supplement or topical agent. The body of human clinical evidence, while not large by pharmaceutical standards, is consistent in its direction.
Lactoperoxidase (LPO)/H2O2/SCN⁻-system-generated hypothiocyanite ions (OSCN⁻) and hypothiocyanous acid (HOSCN) are inhibitory against a number of oral bacteria, including mutans streptococci. A clinical trial published in Caries Research (Lenander-Lumikari et al., 1993) examined the effect of an LPS-containing toothpaste on salivary hypothiocyanite and bacterial levels in human subjects and reported measurable antibacterial activity in vivo.
A study was undertaken to assess the effect of lactoperoxidase system-containing toothpaste on cariogenic microflora in children with early childhood caries. The study group included 30 children with Early Childhood Caries: 15 in a test group using Biotene toothpaste and 15 as controls using Colgate Active. Salivary samples were analyzed for mutans streptococci (MS) and lactobacilli, and for the levels of thiocyanate ions. Results showed a significant increase in the levels of thiocyanate ion in saliva during the experimental period. The conclusion was that the levels of thiocyanate ions can be increased in vivo by supplementing the saliva with natural enzymes like lactoperoxidase, and that this increased concentration of thiocyanate will reduce the number of cariogenic microflora in children with Early Childhood Caries. This study was small (n=30) and limited by its non-blinded design.
During the last decades, several clinical studies describing the clinical efficacy of the lactoperoxidase system in a variety of oral care products (toothpastes, mouth rinses) have been published. After showing indirectly, by means of measuring experimental gingivitis and caries parameters, that mouth rinses containing amyloglucosidase (γ-amylase) and glucose oxidase activate the lactoperoxidase system, the protective mechanism of the enzymes in oral care products has been partially elucidated. Enzymes such as lysozyme, lactoperoxidase and glucose oxidase are transferred from the toothpastes to the pellicle, and, being components of the pellicle, these enzymes are catalytically highly active.
Randomized controlled clinical trials demonstrated that regular extensive oral health education using interdental cleaning aids, mouthwash, moistening gel, and saliva substitutes including lactoperoxidase, lysozyme, glucose oxidase, and lactoferrin could control oral inflammation and contribute to the management of dental caries in patients with type 2 diabetes mellitus.
The lactoperoxidase (LPO) system shows promise in the prevention of dental caries, a common chronic disease. This system has antimicrobial properties and is part of the non-specific antimicrobial immune system. However, this and related work involves primarily in vitro biofilm models; large-scale randomized controlled trials evaluating caries incidence as a hard clinical endpoint are still lacking.
Evidence strength: Moderate — supported by multiple small clinical trials and mechanistic studies, but large, well-powered, double-blind RCTs with hard dental endpoints (caries incidence) remain scarce.
With xerostomia patients, toothpastes with the lactoperoxidase system have been investigated. A clinical trial (Kirstilä et al., 1996, Acta Odontologica Scandinavica, PMID 8997439) evaluated oral hygiene products containing lactoperoxidase, lysozyme, and lactoferrin on the composition of whole saliva and on subjective oral symptoms in patients with xerostomia. The study was classified as a clinical trial and enrolled patients with xerostomia, measuring salivary composition and symptom relief.
The appeal of LPO-containing saliva substitutes lies in the attempt to mimic the endogenous enzymatic defense of natural saliva. LP systems are identified as natural antimicrobial systems in human secretions such as saliva, tear-fluid and milk, and are found to be harmless to mammalian cells. Products combining LPO with lysozyme and lactoferrin are marketed as enzymatic saliva substitutes and have been studied in patients with radiation-induced or Sjögren's syndrome-related salivary dysfunction, showing improvements in subjective symptoms in several small trials.
Evidence strength: Preliminary to moderate — small clinical trials with positive findings on subjective symptoms; larger controlled trials with objective endpoints needed.
This is the area of strongest regulatory recognition and the most extensive real-world data.
When used according to the draft guidelines produced by the joint FAO/WHO committee of government experts on the code of principles concerning milk and milk products, the lactoperoxidase/thiocyanate/peroxide system for milk preservation does not present a toxicological hazard.
The Codex guidelines (CAC/GL 13–1991) for the preservation of raw milk by use of the LP-s were adopted in 1991, at which time the Codex Alimentarius Commission (CAC) also "agreed to emphasise that the lactoperoxidase system not be used for products intended for international trade."
The LP-s elicits antimicrobial activity against a wide variety of milk spoilage and pathogenic microorganisms including bacteria, HIV-1 virus, moulds, yeasts, and mycoplasma. This system can extend the shelf life of raw milk by up to 7–8 hours under tropical conditions, making it useful for transport and processing without refrigeration.
Thiocyanate, hydrogen peroxide, and hypothiocyanate are consumed during the process; residual levels are negligible. Due to the short life of the active ingredients, the LPS is a processing aid for use in extending the shelf life of a variety of dairy products, specifically fresh cheese including mozzarella and cottage cheeses, frozen dairy desserts, fermented milk, flavored milk drinks, and yogurt.
Evidence strength: Strong — supported by extensive FAO/WHO review, Codex Alimentarius guidelines, and widespread practical application across multiple countries.
Lactoperoxidase (LP) is one of the most prominent enzymes in bovine milk and catalyses the inactivation of a wide range of micro-organisms in the lactoperoxidase system (LP-s). The LPO enzyme derived from various animal sources has a significant role in the suppression of bacterial growth and helps bacterial inhibition. Inhibition of bacterial growth by the bovine LPO is attributed to the peroxidase system, which contains H2O2 and thiocyanate.
LPO has a bacteriostatic effect on Gram-positive and a bactericidal effect on Gram-negative bacteria. This distinction is established in multiple in vitro and in vivo milk preservation studies, making it relevant for understanding the scope of protection this enzyme provides in biological fluids.
Evidence strength: Strong for in vitro and food-system applications; moderate for direct human clinical antibacterial endpoints.
Both lactoferrin and LPO had a potent inhibitory effect on human immunodeficiency virus-1 (HIV-1) reverse transcriptase. This suggests the two chemicals could be used together to treat HIV infection. These findings are from laboratory and biochemical studies. No clinical trials have established LPO as a treatment for HIV infection.
Studies showed that the activity of bovine milk LPO against HSV-1 was dose-dependent: 24%, 38%, 62%, 80%, and 100% at 0.1, 0.2, 0.3, 0.4, and 0.5 mg/mL concentrations, respectively. In a different study, antiviral protection and neutralization effects of bovine LPO, camel LPO, and human LPO against hepatitis C virus genotype 4 were tested; purified bovine, camel, or human LPO was added to HepG2 cells to a final concentration of 0.5 and 1.0 mg/mL.
LPO is present at the interface of human airways epithelium and produces anti-infectious agents in the presence of hydrogen peroxide, principally from halide and pseudo-halide substrates. This physiological location has prompted interest in LPO as part of innate airway defense against respiratory viruses, though human intervention trials are absent.
Evidence strength: Preliminary — confined to in vitro cell culture studies and biochemical assays; no human clinical trials for antiviral endpoints have been published.
Bovine lactoperoxidase (LP) and lactoferrin (LF) have recently attracted attention in medicine for their antitumor activities with recognized safety pattern. In vitro studies have investigated LPO in isolation and in combination with nanotechnology platforms.
A newly developed LPO-CS-WO nanocomposite revealed high safety on normal HSF cells (IC50 of 1606 ± 30 µg/mL) with dose-dependent anticancer activity against Caco-2, MDA, and HepG-2 cell lines (IC50 of 425 ± 30, 23 ± 1.06, and 28 ± 0.75 µg/mL, respectively). The anticancer mechanism was postulated to involve apoptosis induction in tumor cells, as evidenced by notable up-regulation of p53 and p21, along with concurrent down-regulation of survivin and Bcl-2 gene expressions.
The LPO system has a role in the preservation of raw milk, in airway defense and broad biocidal activity against pathogenic microorganisms. LPO also shows antioxidant activity and exerts the ability to degrade carcinogenic compounds. Its tumoricidal activity has only seldom been reported elsewhere.
It is important to note that research on LPO's anticancer potential also presents a complexity: the current literature includes heterocyclic amines such as IQ, MeIQx, and PhIP, that have carcinogenic activity, and there is in silico and preliminary in vitro evidence suggesting LPO can activate as well as degrade certain carcinogenic compounds under different conditions, meaning the relationship between LPO and cancer is not straightforwardly protective.
Evidence strength: Preliminary — in vitro cell line studies only; no animal or human clinical trials have established anticancer efficacy for LPO as a supplement.
LPO is a crucial enzyme for mammals due to its high antibacterial, antifungal, and antiviral activity; it can protect newborn infants from harmful microorganisms during lactation. Lactoperoxidase activity in human milk and in the saliva of newborn infants was reported in research published in Infection and Immunity (Gothefors and Marklund, 1975; PMID 1140845), establishing the presence of enzymatic activity in both breast milk and infant saliva at the time of birth.
Lactoperoxidase is a major antibacterial enzyme found in bovine colostrum, a basic glycoprotein that catalyzes the oxidation of thiocyanate and generates intermediate compounds with antimicrobial activities. The presence of LPO in both human and bovine colostrum suggests an important evolved role in early-life mucosal immunity, though direct interventional trials in neonates are limited.
Evidence strength: Observational/mechanistic — no clinical trials assessing LPO supplementation for neonatal infection outcomes have been identified in major databases.
LPO is present at the interface of human airways epithelium, producing anti-infectious agents in the presence of hydrogen peroxide. Both SCN⁻ and I⁻ act as one-electron donors, H2O2 works as an electron acceptor, whereas LPO is the catalyzing enzyme. LPO is reduced back to its native state upon completion of oxidation, and produces the active antimicrobial molecules OSCN⁻ (hypothiocyanite) or OI⁻ (hypoiodite) in the presence of SCN⁻ or I⁻ respectively. This mechanism forms the basis for interest in LPO as a component of innate respiratory immunity, particularly against bacterial and viral respiratory pathogens.
Evidence strength: Mechanistic/in vitro — the physiological role is well-established biochemically, but topical or supplemental administration for respiratory outcomes lacks human clinical trial data.
There is no established standardized human dietary supplement dose for lactoperoxidase as an isolated ingredient. The following dosages and preparations appear specifically in published research:
No standardized supplemental oral dosing recommendations for lactoperoxidase have been established by regulatory bodies. The doses used in in vitro studies are not directly translatable to human supplemental doses.
When used according to the draft guidelines produced by the joint FAO/WHO committee of government experts on the code of principles concerning milk and milk products, the lactoperoxidase/thiocyanate/peroxide system for milk preservation does not present a toxicological hazard.
Taradon has determined through scientific procedures that its lactoperoxidase system preparation is GRAS (Generally Recognized as Safe) for use as a microbial control adjunct to standard dairy processing procedures such as maintaining appropriate temperatures, pasteurization, or other antimicrobial treatments to extend the shelf life of the products.
All of the components of the LPS system occur naturally in human and animal liquid secretions, and therefore presents no new exposures to the human body.
LP-systems are identified as natural antimicrobial systems in human secretions such as saliva, tear-fluid and milk, and are found to be harmless to mammalian cells. The LPS is harmless to mammalian cells. This favorable safety profile is a key feature that distinguishes LPO from many synthetic antimicrobial agents.
The concentrations of the key cofactors depend partly on the feeding regime of the animal, and eating and smoking habits of humans. The source of thiocyanate is the anion itself, its esters and other precursors such as nitriles, isothiocyanate, and cyanide. The concentration of the thiocyanate anion, the principal electron donor in cow's milk, depends on the breed of cow and the type of feed consumed. This means the effective antimicrobial potency of naturally-occurring LPS in milk or saliva is diet-dependent.
In addition to its antimicrobial action, LP also acts in the degradation of several carcinogens, protecting the cells against peroxidative effects. However, the scientific literature also includes studies examining the potential for LPO to activate certain heterocyclic amines found in cooked meat, including 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP), that have carcinogenic activity. This complex dual capacity—degrading some carcinogens while potentially activating others—underscores that LPO's biochemical activity is substrate- and context-dependent.
LPO activity is reduced or destroyed by pasteurization. Hypothiocyanite ions are short-lived, surviving only approximately 400 minutes after the initiation of the LPS reaction. At the conclusion of treatment with the LPS, only lactoperoxidase, glucose oxidase, glucose, and sucrose remain. Thiocyanate, hydrogen peroxide, and hypothiocyanate are consumed during the process; residual levels are negligible. This means the antimicrobial products of LPS are transient and do not persist in processed dairy products.
The Codex Alimentarius Commission agreed to emphasize that the lactoperoxidase system not be used for products intended for international trade. This method should only be used in situations when technical, economic, and/or practical reasons do not allow the use of cooling facilities for maintaining the quality of raw milk. This regulatory restriction is designed to prevent the use of LPS as a masking agent for poor milk quality in export trade.
Because LPO is an enzyme with peroxidase activity, conditions or substances that scavenge hydrogen peroxide (including many antioxidant compounds) could theoretically reduce LPS activity by depleting the H2O2 required for its function. Conversely, substances that generate excess H2O2 could augment LPO activity. These interactions have been explored primarily in food science contexts and in vitro; their clinical significance in human supplementation contexts has not been established in controlled trials.
These results indicate that LPO has great potential in various areas due to its other properties in addition to its antibacterial, antifungal, and antiviral activity. LPO may be a common tool, but more studies are needed to clarify its potential.
Health conditions that Lactoperoxidase may help support.
The LPO system acts as an antioxidant by consuming and neutralizing cytotoxic H₂O₂ that accumulates in the oral cavity, preventing oxidative damage to host tissues. LPO inactivates carcinogenic and mutagenic substances and is protective for periodontal structures by reducing oxidative stress. This role is documented in biochemical and in vitro studies.
Clinical trials show that lactoferrin/lactoperoxidase (LPO) combination tablets reduce volatile sulfur compound (VSC) levels in subjects with measurable oral malodor. A randomized, double-blind, crossover, placebo-controlled trial found suppressive effects on oral malodor with evidence of selective influence on oral bacteria. An in vitro and preliminary in vivo study also confirmed antibacterial activity of LPO-containing compositions and their effect on breath odor.
In vitro studies demonstrate that the LPO system exhibits direct anti-Candida activity. LPO-generated oxidants (hypothiocyanite and hypoiodite) inhibit Candida albicans growth, biofilm formation, and metabolic activity. Synergistic candidacidal effects are observed when LPO is combined with lactoferrin. Clinical human trials specifically for Candida balance with LPO supplementation are not yet established; evidence is currently preclinical.
Multiple clinical trials have evaluated LPO-containing oral hygiene products (toothpastes, mouthwashes, gels) for xerostomia relief. Products mimicking the natural salivary antimicrobial system improved subjective dry mouth symptoms and some clinical signs in elderly and medicated patients. Tenovuo (2002) reviewed evidence for use of salivary antimicrobial proteins including LPO in xerostomia management, noting their incorporation into oral care products to restore saliva's antimicrobial capacity.
LPO-containing oral products have been studied in gingivitis and chronic periodontitis patients. A 2025 systematic review found enzyme/protein toothpastes including LPO useful for preventing gingivitis and managing gingival inflammation. An RCT (Nakano et al. 2019) found tablets with LPO and lactoferrin improved gingival health in adults. However, a 72-person RCT in chronic periodontitis found only weak effects on clinical and bacteriological parameters after 12 weeks of oral tablet use.
Clinical studies show LPO-system-containing oral hygiene products selectively modulate the oral microbiome, promoting health-associated bacteria while reducing periodontal pathogens. A randomized clinical study (Adams et al. 2017, Sci Rep) found an LPO-enzyme toothpaste caused significant shifts in plaque microbiome ecology. LPO-based lozenges were shown to reduce cariogenic bacteria without disturbing total commensal counts.
Lactoperoxidase is secreted by airway mucosal glands into the respiratory surface liquid, where it forms part of the innate antimicrobial defense of the airways. The LPO/thiocyanate/H₂O₂ system in tracheal and bronchial epithelial cells has been shown to produce hypothiocyanite that inactivates respiratory bacteria and viruses. Evidence is from ex vivo and cell/tissue studies; there are no clinical intervention trials with exogenous LPO for upper respiratory conditions.
In vitro and ex vivo studies demonstrate that LPO-generated hypothiocyanite (OSCN⁻) and hypoiodite (OI⁻) inactivate multiple influenza A and B virus strains, as well as other respiratory viruses. The antiviral action involves binding to the viral envelope without interfering with viral adsorption. Evidence is preclinical/mechanistic; no human clinical trials of LPO as an antiviral supplement have been published.
Body systems that Lactoperoxidase may help support.
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