Peroxidase

Other Names

acidic peroxidaseanionic peroxidaseArthromyces ramosus peroxidaseascorbate peroxidasebasic peroxidaseblack radish peroxidasebromoperoxidasecationic peroxidasechloroperoxidaseclass III plant peroxidaseconstitutive peroxidaseCoprinus cinereus peroxidasecytochrome-c peroxidasedehaloperoxidasedonor: H2O2 oxidoreductasedonor:hydrogen-peroxide oxidoreductaseEC 1.11.1.7eosinophil peroxidaseEPOextensin peroxidaseextracellular peroxidaseguaiacol peroxidaseH2O2 oxidoreductasehaloperoxidaseheme peroxidasehemoglobin peroxidasehorseradish peroxidasehorseradish peroxidase (HRP)horseradish peroxidase CHRPHRP-CHRPCHRPOhydrogen donor oxidoreductaseJapanese radish peroxidaselactoperoxidaselignin peroxidaseLPLPOmanganese peroxidasemanganese-dependent peroxidasemicroperoxidaseMPOmyeloperoxidaseNADH peroxidaseoxyperoxidaseplant peroxidasePODprotoheme peroxidasepyrocatechol peroxidasesalivary peroxidasescopoletin peroxidasesoybean peroxidasesoybean peroxidase (SBP)thiol peroxidasethyroid peroxidaseTPOuterine peroxidase

Synopsis

Peroxidase: A Comprehensive Reference

1. Identity: Nomenclature, Natural Sources, and Common Forms

1.1 Chemical and Biochemical Identity

Peroxidase is an enzyme in the group of oxidoreductases that is widely distributed in nature. It can catalyze the oxidation of various organic and inorganic substrates by reacting with hydrogen peroxide and similar molecules. The peroxidases are enzymes whose primary function is to oxidize hydrogen donors at the expense of peroxides. They are highly specific for hydrogen peroxide, but they accept a wide range of hydrogen donors, including polyphenols.

Peroxidases (EC number 1.11.1.x) are a large family of enzymes that typically catalyze a reaction of the form: ROOR' + electron donor (2 e⁻) + 2H⁺ → ROH + R'OH. For many of these enzymes the optimal substrate is hydrogen peroxide, but others are more active with organic hydroperoxides such as lipid peroxides. Peroxidases can contain a heme cofactor in their active sites, or alternately redox-active cysteine or selenocysteine residues.

Peroxidases are glycoproteins with a hematin compound as cofactor. Their molecular weights range between 30 and 55 kDa. Depending on the enzyme source, the isoenzyme considered, and the hydrogen donor substrate, the optimum activity is between pH 4 and 7. In many, but not all cases, the peroxidase isoenzymes are activated by calcium ions.

These proteins can be classified as haem or non-haem enzymes. According to the RedOxiBase database, haem peroxidases are approximately 84% of all known peroxidase enzymes.

1.2 Classification by Structural Superfamily

Peroxidases comprise multiple evolutionarily distinct families. These enzymes are classified into three classes: class I, class II, and class III. Among these, Class III peroxidases (also referred to as PRX, PER, POD, or POX) are plant-specific secreted enzymes that play crucial roles in plant growth, development, signal transduction, metabolic regulation, and responses to both biotic and abiotic stresses.

In mammals, a distinct subfamily predominates. The members of the Chordata peroxidase protein subfamily include myeloperoxidase (MPO), eosinophil peroxidase (EPO), lactoperoxidase (LPO), and thyroid peroxidase (TPO), and each catalyzes physiologically important reactions. They share critical structural features but are expressed differently, both with respect to intracellular and tissue location.

Among non-heme peroxidases, peroxiredoxins (Prxs) evolved as a relationship among antioxidant enzymes in all life domains. Initially identified at the end of the 1990s as "thiol-specific antioxidant proteins," peroxiredoxins are now widely known as multifunctional proteins that exert profound control over many cellular processes. Peroxiredoxin is defined by its ability to scavenge hydrogen peroxide (H₂O₂) and other organic peroxides to neutralize the effects of peroxides in cells.

1.3 Major Peroxidase Types and Their Primary Natural Sources

Horseradish peroxidase (HRP; EC 1.11.1.7): Horseradish peroxidase (donor:hydrogen-peroxide oxidoreductase, EC 1.11.1.7) belongs to a family of proteins with ferriprotoporphyrin IX as a prosthetic group. Horseradish peroxidase (HRP) is one of the most widely used enzymes in food colloid applications. It is derived from horseradish, the roots of which contain many peroxidase isoenzymes. The most abundant is C isoenzyme (HRP C).
Plant peroxidases (class III; EC 1.11.1.7): Peroxidase is found widely distributed in higher plants including horseradish, turnip, fig sap, tobacco, and potato, as well as microorganisms such as yeast cytochrome c.
Soybean peroxidase (SBP): SBP has been neglected until recently, despite offering a real alternative to HRP: SBP actually outperforms HRP in terms of stability and is now used in numerous biotechnological applications, including biosensors.
Glutathione peroxidases (GPx; EC 1.11.1.9/1.11.1.12): GPXs are an antioxidant enzyme family with peroxidase activity to catalyze the reduction of H₂O₂ and lipid hydroperoxides by converting glutathione (GSH) to oxidized glutathione (GSSG), thereby protecting the organism against oxidative damage. Human GPXs are composed of eight isozymes (GPX1–8), of which five members (GPX1–4 and 6) are selenocysteine-containing proteins (SecGPX), and three members (GPX5, 7, and 8) are cysteine-containing proteins (CysGPX) with the active site Sec replaced by cysteine.
Myeloperoxidase (MPO; EC 1.11.1.7): Myeloperoxidase (MPO) is a member of the subfamily of peroxidases. It is most abundantly expressed in immune cells, such as neutrophilic polymorphonuclear leukocytes (neutrophils) and lymphocytes, monocytes, and macrophages, and is also produced in other body cells.
Lactoperoxidase (LPO): Lactoperoxidase is found in milk, tears, saliva, and mucous of the respiratory tract. Lactoperoxidase (both human and bovine) is a single chain, monomeric glycopeptide of approximate mass of 80,000 Da (human) or 78,000 Da (bovine).
Thyroid peroxidase (TPO): MPO is a soluble protein in the matrix of azurophil granules of neutrophils and to a much lesser extent monocytes, whereas TPO is a transmembrane protein in the plasma membrane.
Peroxiredoxins (Prxs): They fulfill their peroxide-scavenging function using the conserved cysteine residues at their active sites, through which they are involved in redox cycles that are vital for their antioxidant capacity. The family of peroxiredoxins encompasses six distinct classes based on the number and arrangement of conserved cysteine residues involved in their catalytic mechanisms.

1.4 Common Forms and Preparations

As a natural ingredient and supplement context, peroxidases are encountered in several forms:

Endogenous enzymatic activity: All mammals express peroxidases constitutively. Nutritional strategies (particularly selenium supplementation) are used to support endogenous glutathione peroxidase activity.
Lactoperoxidase-based oral hygiene products: One of them is lactoperoxidase—an enzyme that can oxidise (pseudo)halide ions to reactive products with antimicrobial activity. Currently, commercially available products utilise thiocyanate as a substrate.
Plant-derived enzyme preparations: Two reagents were prepared to carry out enzymatic glucose determination: the first consisted of the commercial clinical glucose diagnostic kit and the second was prepared from peroxidases extracted from turnip roots. Although peroxidases were not completely purified, it maintained good stability in the glucose kit for up to one year.

2. Traditional and Historical Use

The peroxidase enzyme itself — as a defined, isolated molecule — is a product of modern biochemistry and was not known as a discrete substance to pre-modern cultures. However, the plants and animal-derived foods richest in peroxidase activity have extensive traditional use histories in multiple cultures, and the observed biological effects of these materials are now understood in part through the lens of their endogenous peroxidase content.

2.1 Horseradish (Armoracia rusticana)

Horseradish root is the canonical plant source of peroxidase in biochemical research. Horseradish peroxidase (HRP) is one of the most widely used enzymes in food colloid applications. It is derived from horseradish, the roots of which contain many peroxidase isoenzymes. Horseradish has been used in European folk medicine since at least the early Middle Ages as a digestive stimulant, for respiratory complaints, and as a topical rubefacient; the modern biochemical identification of HRP as the primary active enzyme of its root traces to its isolation and purification in the late nineteenth and early twentieth centuries.

2.2 Lactoperoxidase in Milk and Traditional Fermented Foods

Lactoperoxidase (LPO) is a member of the mammalian heme peroxidase family and is a component of saliva, milk, tears, and other exocrine secretions. LPO catalyzes the hydrogen peroxide-dependent oxidation of thiocyanate to hypothiocyanate, exhibiting antimicrobial properties. The antimicrobial properties of fresh milk and human saliva — long recognized empirically in traditional preservation and healing practices across cultures — are now attributed in significant part to the native lactoperoxidase-thiocyanate-hydrogen peroxide system. The use of raw milk to inhibit bacterial growth during transport and storage was effectively, if unknowingly, exploiting endogenous LPO activity.

2.3 Peroxidase in Traditional Plant Medicines

The non-animal plant peroxidases (class III peroxidase) are involved in various essential physiological processes of plant growth and development throughout their life cycle. In view of the capability of peroxidases to catalyze the redox reaction for a wide range of substrates, they are considered as one of the important enzymes from the point of view of their various medicinal, biochemical, immunological, biotechnological, and industrial applications. Many plants with high peroxidase activity — such as turnip, soybean, fig, and tobacco — have long traditions of use in different cultures. The biochemical significance of their peroxidase content as a mediator of their biological effects is a modern interpretation; historical uses were not framed in enzymatic terms.

2.4 The Selenium–Glutathione Peroxidase Connection in Traditional Nutrition

Many of the nutritional effects of selenium can be explained by its role in glutathione peroxidase. Populations with selenium-rich diets (e.g., certain regions of Japan, parts of North America, and Brazil) historically consumed foods — seleniferous grains, fish, and Brazil nuts — that supported robust GPx activity. The concept of selenium as an essential dietary trace element was not formally established until 1957, but the antioxidant protection it conferred through GPx was implicit in traditional diets rich in diverse, unprocessed foods.

3. Key Constituents and Active Compounds: Mechanisms of Action

3.1 The Heme Prosthetic Group and the Peroxidase Catalytic Cycle

All heme peroxidases (EC 1.11.1.7) have a ferriprotoporphyrin IX prosthetic group located at the active site. The mechanism of action of the heme peroxidases proceeds through the oxidation of the enzyme by the peroxide, leading to the formation of a ferryl (Fe^IV) heme moiety and the removal of an electron from either the porphyrin ring or an amino acid residue of the protein. This intermediate is commonly referred to as compound I.

These heme enzymes function to either activate dioxygen for incorporation into the substrate (oxygenase activity) or use peroxides for oxidation of the substrate (peroxidase activity).

Most peroxidases are able to oxidize a variety of substrates of widely different structures, varying from halide ions to hydroquinones to aromatic azo compounds. A binding site for the substrate to be oxidized is therefore virtually absent in most of these enzymes. Simple molecules consisting of 8–12 amino acids and a covalently linked heme moiety, with a histidine residue forming the proximal ligand, have considerable peroxidase activity. These compounds are known as microperoxidases.

3.2 Glutathione Peroxidases: Selenium-Dependent Antioxidant Mechanism

Selenium, an essential trace element, is involved in the complex system of defense against oxidative stress through selenium-dependent glutathione peroxidases (GPx) and other selenoproteins. Glutathione peroxidase (GSH-Px) has a selenium-dependent form that contains four moles of selenium per mole of enzyme. The oxidative role of this enzyme is similar to catalase in that it converts hydrogen peroxide to water and oxygen. Whenever catalase or glutathione peroxidase activity is impaired there can be a toxic build-up of peroxides. This, in turn, can lead to a build-up of the hydroxide radical.

GPX4 is a widely studied phospholipid hydroperoxidase, with a high preference for lipid hydroperoxides. GPX1 utilizes glutathione as a substrate to catalyze hydrogen peroxide, lipid peroxide, and peroxynitrite, thereby reducing intracellular oxidative stress.

Among the eight human glutathione peroxidase isoforms, glutathione peroxidase 4 (GPX4) is the only enzyme capable of reducing complex lipid peroxides to the corresponding alcohols. Unlike other glutathione peroxidase family members, GPX4 has the unique ability to reduce hydroperoxides in complex lipids such as phospholipid, cholesterol, and cholesterolester hydroperoxides.

3.3 Myeloperoxidase: Halogenation and Innate Immunity

Myeloperoxidase (MPO), a member of the haem peroxidase-cyclooxygenase superfamily, is abundantly expressed in neutrophils and to a lesser extent in monocytes and certain types of macrophages. MPO participates in innate immune defence mechanisms through formation of microbicidal reactive oxidants and diffusible radical species. A unique activity of MPO is its ability to use chloride as a cosubstrate with hydrogen peroxide to generate chlorinating oxidants such as hypochlorous acid, a potent antimicrobial agent.

Among the antimicrobial agents in neutrophils, MPO is the most abundant and constitutes 5% dry weight of neutrophils and 25% of the azurophilic granular proteins.

3.4 Lactoperoxidase: Thiocyanate Oxidation and Mucosal Defense

LPO catalyzes the hydrogen peroxide-dependent oxidation of thiocyanate to hypothiocyanate, exhibiting antimicrobial properties. The LPO system plays an important role in the defence against microorganisms within mucous membranes, mainly in the oral cavity, respiratory tract, gastrointestinal tract, and female reproductive system.

Each LPO molecule contains one molecule of modified autocatalytic heme B in its active center. Like in many peroxidases, the calcium atom associated with Asp227 plays an important role in maintaining structure, thermal stability, and enzyme activity.

3.5 Thyroid Peroxidase: Hormone Synthesis

Peroxidase-mediated post-translational modifications underlie a diverse set of biological phenomena, from thyroid hormone synthesis to pathophysiologic processes. Thyroid peroxidase (TPO) catalyzes the iodination and coupling of tyrosine residues in thyroglobulin to produce the thyroid hormones thyroxine (T4) and triiodothyronine (T3), making it essential for normal thyroid function and metabolic regulation.

3.6 Peroxiredoxins: Cysteine-Based Peroxide Reduction

The primary role of the Prxs is the peroxidase activity, which comprises the reduction of hydrogen peroxide and other organic hydroperoxides and decreases the risk of oxidative damage in the cells. The above enzymatic activity occurs through the reversible oxidation-reduction catalyzed by conserved cysteine residues. This peroxidase activity is essential for metabolism, protection against oxidative stress, and regulating redox signaling processes within human cells. The involvement of Prxs does not end with such enzymes' action; it is proven by the fact that they also have other roles that are biologically important. Prxs are involved in numerous cellular processes, including cell death, cell division, and immune reactions.

3.7 Class III Plant Peroxidases: ROS Homeostasis and Cell Wall Biosynthesis

Class III plant peroxidases are haem-enzymes that share similar three-dimensional structures and a common catalytic mechanism for hydrogen peroxide degradation. They exist as large multigene families and are involved in metabolizing reactive oxygen species (ROS), hormone synthesis and decomposition, fruit growth, defense, and cell wall synthesis and maintenance.

Potentially, Class III peroxidases are involved in generation and detoxification of hydrogen peroxide (H₂O₂), and their subcellular localization reflects through three different cycles, namely peroxidative cycle, oxidative and hydroxylic cycles to maintain the ROS level inside the cell.

4. Scientific Evidence by Area of Health Relevance

4.1 Antioxidant Defense and Oxidative Stress

Biological plausibility: Although ROS are required for numerous essential functions, such as signaling cascade and redox-governing activities, an excess of ROS can cause severe diseases, such as neurodegenerative diseases, digestive diseases, respiratory diseases, and cancer. To balance the level of ROS, organisms build an antioxidant system comprised of antioxidant enzymes that can neutralize or degrade the excessive ROS.

Selenium and GPx in humans: Analyses of patients' red blood cell (RBC) glutathione system revealed low levels of reduced glutathione and decreased activities of RBC glutathione peroxidase and glutathione reductase by 23%, 18%, and 20%, respectively, in comparison to normal RBC. Selenium treatment resulted in a significant elevation of RBC glutathione peroxidase and glutathione reductase activities and in reduced glutathione content by 64%, 57%, and 11%, respectively. On termination of the selenium treatment, and after 3 months on placebo, all of these values of the glutathione system elements returned toward baseline levels. The study concluded that dietary selenium, which activates the glutathione system, is a potent antioxidant against plasma and LDL lipid peroxidation in renal transplant recipients, and may thus be considered antiatherogenic.

Evidence strength: The role of selenium in supporting glutathione peroxidase activity is robustly established in human biochemical research. Evidence for peroxidase enzymes per se as orally administered supplements modifying systemic antioxidant capacity in humans is more limited and indirect.

4.2 Cardiovascular Disease

GPx and cardiac risk: Selenium (Se) is part of the enzyme glutathione peroxidase (GSH-Px) that plays an important role in the antioxidant defence of the body, including the myocardium, against the deleterious actions of free radicals and lipid peroxides. In a clinical study, plasma, erythrocyte and urinary Se concentrations together with plasma and erythrocyte GSH-Px activities were determined in 27 patients diagnosed with acute myocardial infarction (AMI), compared to a control group of 24 age-matched healthy individuals. Mean plasma, erythrocyte, and urine Se concentrations were significantly lower in the patient groups compared to controls.

MPO as a cardiovascular biomarker: Myeloperoxidase (MPO) is a well-known enzyme, mainly released by activated neutrophils, characterised by powerful pro-oxidative and proinflammatory properties. Recently, myeloperoxidase has been proposed as a useful risk marker and diagnostic tool in acute coronary syndromes and in patients admitted to emergency room for chest pain.

The phagocytic enzyme myeloperoxidase (MPO) acts as a front-line defender against microorganisms. However, increased MPO levels have been found to be associated with complex and calcified atherosclerotic lesions and incident cardiovascular disease. MPO plasma concentrations along with eight MPO polymorphisms were determined in 3,036 participants of the Ludwigshafen Risk and Cardiovascular Health study (median follow-up 7.75 years).

Any uncontrolled degranulation exaggerates the inflammation and can also lead to tissue damage even in the absence of inflammation. Several types of tissue injuries and the pathogenesis of several other major chronic diseases such as rheumatoid arthritis, cardiovascular diseases, liver diseases, diabetes, and cancer have been reported to be linked with MPO-derived oxidants.

Mechanistic pathway: Since MPO and its oxidative products are involved in all stages of atherosclerosis, atherosclerosis is highlighted among cardiovascular diseases. HOCl has been shown to inhibit one of the isoforms of the enzyme that counteracts MMPs, tissue inhibitor of matrix metalloproteinase-1, by oxidizing cysteine residues at the N-terminal, resulting in unopposed MMPs, which further weakens the fibrous cap, and promotes subsequent plaque rupture.

Evidence strength: The association between elevated endogenous MPO and adverse cardiovascular outcomes is supported by multiple clinical observational studies and prospective cohorts in humans. Evidence that supplementing or inhibiting exogenous peroxidase preparations alters cardiovascular outcomes in humans is not yet established. Current evidence positions MPO primarily as a biomarker and a pharmacological target, not a supplement ingredient.

4.3 Chronic Obstructive Pulmonary Disease (COPD) and Respiratory Health

The presence of oxidative stress in COPD is the result of an imbalance between pro-oxidant and antioxidant mechanisms. The aim of a systematic review was to investigate a possible association between glutathione peroxidase (GPx), a key component of antioxidant defense mechanisms, and COPD. Twenty-four studies were identified. In 15 studies assessing whole blood/erythrocytes (GPx isoform 1), the pooled results showed that GPx concentrations were significantly lower in patients with COPD (SMD = −1.91, 95% CI −2.55 to −1.28, p < 0.001; moderate certainty of evidence).

Evidence strength: This systematic review and meta-analysis demonstrates a consistent association between reduced erythrocyte GPx activity and COPD. This is observational evidence; it does not establish that GPx supplementation would improve COPD outcomes. Evidence is classified as moderate certainty.

4.4 Oral and Dental Health

Lactoperoxidase system: A significant amount of research conducted on the LPO system focuses on its role in anticariogenic defence consisting of the inhibition of metabolism or killing Streptococcus mutans—a causative organism used in research on dental caries. Some of these studies have focused on the possibilities of using an exogenous LPO system as a way to treat and prevent caries.

The exogenous administration of a LPO system consisting of an industrially isolated lactoperoxidase from cow's milk, thiocyanate ions, and a glucose oxidase-based system to generate hydrogen peroxide has shown good results in limiting caries development by eliminating cariogenic microorganisms from the oral microbiome.

Periodontal evidence: A double-blinded, randomized, controlled trial in periodontitis patients was conducted to evaluate the efficacy of lactoferrin (LF) and LPO-containing tablets on periodontal parameters, and levels of subgingival plaque bacteria, and bovine and human LF, and endotoxin in gingival crevicular fluid (GCF). However, clinical and bacteriological parameter values proved comparable between the two groups at 1 week to 12 weeks. Therefore, the effect of oral administration of LF and LPO-containing tablets might be weak on periodontal and bacteriological profile in this study.

Peroxidase systems present a paradox: although they have been shown to be active in vitro for a long time, the definitive evidence of their effects in vivo is still lacking.

Certain studies have suggested considering peroxidases as ecological selectors directing the oral microflora towards a Gram-positive cocci microflora poor in cariogenic or periodontopathogenic germs, thereby preserving the mucosa and protecting it from yeast overgrowth, among others. Thus, the administration of an efficient lactoperoxidase system in a toothpaste also containing lactoferrin and lysozyme may prevent oral dysbiosis.

Evidence strength: In vitro and some in vivo evidence supports the antimicrobial activity of the LPO-thiocyanate system in the oral environment. Human clinical trial evidence for definitive clinical benefit (reduction in caries or periodontal disease) is preliminary and limited.

4.5 Skin Disorders and Dermatological Applications

Blood glutathione-peroxidase (GSH-Px) was determined in 61 healthy subjects and 506 patients with various skin disorders. Depressed levels were observed in patients with psoriasis, eczema, atopic dermatitis, vasculitis, mycosis fungoides, and dermatitis herpetiformis. Low values of GSH-Px were also found in some patients with pemphigoid, acne conglobata, polymyositis, rheumatoid arthritis, scleroderma, and systemic lupus erythematosus.

Fifty patients with low GSH-Px levels were treated with tablets containing 0.2 mg selenium as Na₂SeO₃ and 10 mg tocopheryl succinate. The GSH-Px levels increased slowly within 6–8 weeks of treatment. The clinical effect was encouraging and calls for controlled studies.

Evidence strength: This early observational and open-label treatment study (not placebo-controlled) links depressed GPx activity to multiple dermatological conditions and suggests benefit from selenium plus vitamin E. Controlled trials are needed; evidence remains preliminary.

4.6 Cancer and GPx Genetic Polymorphisms

Numerous case-control studies and meta-analyses have assessed the association between a functional genetic polymorphism of the GPX1 gene, named Pro198Leu (rs1050450 C>T), and cancer susceptibility in different populations.

Data from 21 articles were included in a systematic review. Diseases were clustered according to the physiological system affected to understand better the role of GPX4 (rs713041) SNP in developing different diseases. Carriers of the GPX4 (rs713041) T allele were associated with an increased risk of developing colorectal cancer in additive and dominant models (p = 0.02 and p = 0.004, respectively). In addition, carriers of the T allele were associated with an increased risk of developing stroke and hypertension. On the other hand, the GPX4 (rs713041) T allele was associated with a decreased risk of developing pre-eclampsia.

Moreover, selenium levels presented lower mean values in cancer patients relative to control groups (SMD = −0.39 µg/L; 95% CI: −0.64, −0.14; p = 0.002, I² = 85%).

Severe selenium deficiency, in combination with virus infection, was found to cause myocarditis in China, but more recently, various studies have indicated that a sub-optimal intake can increase the risk of diseases such as cancer.

Evidence strength: Population-level genetic and epidemiological evidence links GPx4 polymorphisms and low selenium status to cancer susceptibility. This is associative evidence from systematic review and meta-analysis. Direct interventional evidence that exogenous peroxidase supplementation reduces cancer incidence is not established.

4.7 Renal Disease and Dialysis

Patients with chronic renal failure (CRF) often have reduced concentrations of selenium (Se) and lowered activities of glutathione peroxidase (GSH-Px) in blood components. The kidney is a major source of plasma GSH-Px.

Se and glutathione levels in blood components and red cell and plasma GSH-Px activities were measured in 58 uremic patients on regular hemodialysis (HD). The dialyzed patients were divided in 4 subgroups and were supplemented for 3 months with: 1) placebo (bakers yeast), 2) erythropoietin (EPO), 3) Se-rich yeast (300 µg 3 times a week after each HD session), and 4) Se-rich yeast plus EPO. The Se concentrations and GSH-Px activities in the blood components of dialyzed uremic patients were significantly lower compared with the control group.

Evidence strength: This clinical trial demonstrates that selenium-rich yeast supplementation (300 µg three times weekly) restores depressed GPx activity in hemodialysis patients. Sample size is modest; larger trials would strengthen conclusions.

4.8 Mycotoxin Degradation and Food Safety (Emerging Research)

Due to its wide catalytic activity, peroxidases can act in the removal of both phenolic compounds and peroxides, in chemical synthesis and, according to recent studies, in mycotoxin degradation. This area has been identified as a potential application in the food industry.

Evidence strength: This is an area of emerging preclinical and applied food science research. Human clinical evidence is absent; application is currently conceptual and laboratory-based.

5. Body Systems and Health Areas Associated with Peroxidase Activity

Immune System / Innate Immunity: The four mammalian peroxidases (myeloperoxidase, eosinophil peroxidase, lactoperoxidase, and thyroid peroxidase) catalyze the formation of antimicrobial compounds and participate in innate immunity.
Cardiovascular System: Several types of tissue injuries and the pathogenesis of major chronic diseases such as rheumatoid arthritis, cardiovascular diseases, liver diseases, diabetes, and cancer have been reported to be linked with MPO-derived oxidants.
Thyroid / Endocrine System: Thyroid peroxidase is the essential enzyme for biosynthesis of thyroid hormones T3 and T4; autoantibodies against TPO are a hallmark of autoimmune thyroid disease (Hashimoto's thyroiditis).
Oral Cavity / Mucosal Immunity: The LPO system plays an important role in the defence against microorganisms within mucous membranes, mainly in the oral cavity, respiratory tract, gastrointestinal tract, and female reproductive system.
Respiratory System: Peroxidase is an important enzyme that utilizes oxidative radicals to produce hypochlorous acid to kill pathogens. During oxidative respiratory burst, it is mostly released by the azurophilic granules of neutrophils.
Skin: Depressed GPx activity is documented in multiple inflammatory skin conditions including psoriasis, atopic dermatitis, and eczema.
Reproductive System: GPX4 is an important cofactor, which regulates ferroptosis by catalyzing the reduction of lipid hydroperoxides to lipid alcohols. The role of GPX4 is important in handling the accumulation of lipid peroxides, thereby preventing oxidative damage and ferroptotic cell death.
Nervous System: Oxidative stress is a central feature of neurodegeneration; GPx and peroxiredoxin activity is implicated in neuroprotection.
Kidneys: The kidney is a major source of plasma GPx, and its activity is markedly depressed in chronic renal failure and dialysis patients.

6. Dosage Forms and Dosages Reported in Studies

The following dosages are reported as they appeared in specific published studies; they are not recommendations.

6.1 Selenium Supplementation to Support Glutathione Peroxidase Activity

Fifty patients with low GSH-Px levels were treated with tablets containing 0.2 mg selenium as Na₂SeO₃ and 10 mg tocopheryl succinate, with GPx levels increasing within 6–8 weeks.
In a study of hemodialysis patients, one supplementation group received selenium-rich yeast at 300 µg, three times per week after each hemodialysis session for 3 months.
In the renal transplant recipient study, dietary selenium supplementation (dose not specified in the extracted data) resulted in significant elevation of RBC GPx activity by 64%.

6.2 Lactoperoxidase in Oral Hygiene Products

The lactoperoxidase-thiocyanate-hydrogen peroxide system (LPO-system) is a highly effective antimicrobial system. Randomized study with a four-replicate cross-over design evaluated the effectiveness of two oral hygiene lozenges containing LPO-system in oral hygiene.
Specific concentrations used in published lozenge research included thiocyanate at final concentrations of 10 mM and hydrogen peroxide at 700 µM in plaque acid inhibition studies.

6.3 Oral Administration of LPO-Containing Tablets

A double-blinded, randomized, controlled trial enrolled subjects who had been referred to a dental clinic, where lactoferrin and LPO-containing tablets were tested for 12 weeks in periodontitis patients. The specific LPO dose per tablet was not reported in the extracted data.

Note: No well-characterized therapeutic dosage ranges for orally administered isolated peroxidase preparations have been established in high-quality human clinical trials to date. The dosage information above pertains almost entirely to selenium (as a cofactor supporting endogenous GPx) or topical/local oral applications of LPO.

7. Safety Considerations and Interactions

7.1 Lactoperoxidase System: Cytotoxicity Findings

In a cytotoxicity study, toxicity against human gingival fibroblasts of the lactoperoxidase system was evaluated using four different (pseudo)halide substrate systems — thiocyanate, iodide, selenocyanate, and a mixture of thiocyanate and iodide. Cells were treated with the systems and then apoptosis, cell cycle, intracellular glutathione concentration, and mitochondrial superoxide production were assessed. The results showed that each system, after generating 250 µM of the product, inhibited cell divisions, increased apoptosis, and increased the percentage of dead cells. It was concluded that the mechanism of the observed phenomena was not related to increased superoxide production or the depletion of glutathione concentration. These findings emphasized the need for the further in vitro and in vivo toxicity investigation of the modified lactoperoxidase system to assess its safety and the possibility of use in oral hygiene products.

7.2 Enzyme Stability and Inactivation

Horseradish peroxidase is reversibly inhibited by cyanide and sulfide at a concentration of 10⁻⁵ M. Even though hydrogen peroxide is the natural substrate for peroxidases, its presence affects the stability of the enzyme. High concentrations of substrate hydrogen peroxide can lead to suicide inactivation of peroxidases, a recognized biochemical phenomenon relevant to any application involving exogenous peroxidase preparations.

7.3 Oral Bioavailability of Exogenous Enzyme Proteins

Peroxidases are proteins; like most enzymes administered orally, they face degradation by gastric acid and digestive proteases before systemic absorption could occur. Direct systemic effects of orally consumed isolated peroxidase preparations have not been demonstrated in well-controlled human studies. The beneficial effects of the oral LPO system are therefore understood to act locally in the oral cavity, not systemically, as consistent with the reviewed clinical literature.

7.4 Thyroid Peroxidase Interactions: Antithyroid Drugs

The antithyroid drug methimazole (2-mercapto-1-methylimidazole) and its selenium analogue have been shown to be irreversible mechanism-based inhibitors of human peroxidases. Methimazole is oxidized by thyroid peroxidase, lactoperoxidase, and MPO, because no inactivation occurred in the absence of H₂O₂. This highlights the pharmacological interaction between compounds metabolized by peroxidase enzymes and those enzymes' function — particularly relevant for individuals on antithyroid drug therapy.

7.5 Myeloperoxidase: Dual Role in Disease

While MPO is essential for innate immunity, its overactivation is associated with tissue damage. Any uncontrolled degranulation exaggerates the inflammation and can also lead to tissue damage even in the absence of inflammation. This dual nature means that strategies to boost MPO activity could theoretically exacerbate inflammatory tissue injury, while strategies to inhibit MPO (currently under pharmaceutical investigation) carry the risk of immunosuppression.

7.6 Selenium Toxicity: Upper Limits

Since dietary selenium is the primary means of modulating endogenous GPx activity, selenosis (selenium toxicity) is a recognized risk at supraphysiological intakes. Selenium deficiency markedly decreases GPx activity: selenium deficiency decreased mRNA levels by 60%, but glutathione peroxidase enzyme activity decreased by 93%, suggesting a co- and/or post-translational control mechanism. Both deficiency and excess must be considered when selenium is used to modulate GPx function.

References

Health Conditions

Health conditions that Peroxidase may help support.

No conditions available.

Body Systems

Body systems that Peroxidase may help support.

No body systems available.