What causes elevated myeloperoxidase?

Elevated serum MPO reflects neutrophil and monocyte activation in the vascular environment. Primary drivers include: atherosclerotic plaque inflammation (foam cells within plaque release MPO), metabolic syndrome and insulin resistance (promotes neutrophil activation), oxidative stress from poor diet, smoking, environmental toxin exposure, sleep deprivation, and chronic infection. MPO is also transiently elevated by acute infections, so testing should ideally occur during stable health.

Lab Reference Library / Myeloperoxidase (MPO) Inflammation & Cardiovascular

Myeloperoxidase (MPO)

Q: What is the optimal myeloperoxidase level?

In functional medicine, optimal myeloperoxidase is below 300 pmol/L. The standard reference defines elevated risk as above 470 pmol/L, but functional medicine targets the lower portion of the range to minimize oxidative LDL modification and vascular oxidative stress. Multiple prospective studies, including the Cleveland Clinic Cardiovascular Risk Prevention study, demonstrate that MPO above the median is associated with 2 to 3-fold elevated risk of major cardiovascular events independent of traditional risk factors.

Q: What does elevated myeloperoxidase mean?

Elevated serum MPO indicates active neutrophil and monocyte degranulation in the vascular environment, producing reactive oxidants that directly oxidize LDL cholesterol, consume nitric oxide (impairing endothelial vasodilation), destabilize atherosclerotic plaques, and promote endothelial cell apoptosis. Elevated MPO with normal LDL cholesterol identifies a patient whose LDL is being converted to highly atherogenic oxidized LDL at an accelerated rate, substantially underestimating their true atherogenic burden.

Q: Why does MPO predict cardiovascular events even when LDL is normal?

MPO converts standard LDL cholesterol to oxidized LDL (oxLDL), which is 3 to 5 times more atherogenic per particle than native LDL. In the presence of high MPO activity, the same absolute LDL cholesterol concentration produces a much greater atherogenic burden because a higher fraction of LDL particles are being converted to the highly reactive, foam-cell-promoting oxidized form. Additionally, MPO directly consumes nitric oxide, impairing endothelial vasodilation and promoting vasoconstriction independent of LDL levels.

Q: How do you lower myeloperoxidase?

Evidence-based approaches include: omega-3 fatty acids (EPA and DHA reduce neutrophil activation and MPO release; 2 to 4g daily), pomegranate extract (inhibits MPO activity through punicalagins), dark chocolate flavonoids (inhibit MPO), statins (reduce plaque macrophage and neutrophil activation), Mediterranean diet (reduces neutrophil inflammatory activation), smoking cessation (smoking directly activates neutrophils and elevates MPO), vitamin C and E (reduce MPO-generated oxidant burden), and aggressive blood pressure control (reduces vascular wall shear stress that activates MPO release).

MPO · Myeloperoxidase · Cardiac MPO

Reference range, optimal functional medicine levels, and why myeloperoxidase is the marker of neutrophil-driven vascular oxidative stress, the enzyme responsible for oxidizing LDL to its most atherogenic form, and why elevated MPO predicts cardiovascular events even when LDL is normal.

Oxidative StressVascular Marker

Standard RangeBelow 470 pmol/L

FM OptimalBelow 300 pmol/L

High RiskAbove 470 pmol/L

Unitspmol/L

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Category: Inflammation & Cardiovascular | Also known as: MPO, Cardiac MPO, Myeloperoxidase Level | Sample: Serum; draw during stable health for chronic cardiovascular risk assessment

1. What This Test Measures

Myeloperoxidase (MPO) is a heme-containing enzyme abundantly expressed in the azurophilic granules of neutrophils and in smaller amounts in monocytes and macrophages. It is a central component of the innate immune defense against pathogens: during phagocytosis or extracellular killing, neutrophils release MPO, which uses hydrogen peroxide to generate highly reactive oxidizing species including hypochlorous acid (the active ingredient in household bleach), chloramines, reactive nitrogen species, and tyrosyl radical.

These reactive oxidants are extraordinarily effective at killing bacteria and viruses. However, in chronic inflammatory states where neutrophils are continuously activated in the vascular environment, the same oxidizing chemistry that kills pathogens is directed against the arterial wall and its contents. The most clinically significant consequence is MPO-mediated LDL oxidation:

MPO generates hypochlorous acid and other reactive species that modify LDL lipids and proteins
MPO-oxidized LDL is not recognized by normal LDL receptors and cannot be cleared by the liver
MPO-oxidized LDL is taken up without limit by macrophage scavenger receptors (CD36, SR-A), converting macrophages into cholesterol-laden foam cells
MPO also directly consumes nitric oxide (NO) through a HOCl-mediated oxidation reaction, reducing NO bioavailability and impairing endothelial vasodilation
MPO activates matrix metalloproteinases (MMPs) that degrade the fibrous cap of atherosclerotic plaques, increasing plaque vulnerability to rupture

Serum MPO therefore reflects both the degree of neutrophil activation in the vascular environment and the rate of LDL oxidation occurring in the arterial wall.

2. Why This Test Matters

Predicts cardiovascular events independent of LDL: multiple large prospective studies demonstrate that elevated MPO predicts major cardiovascular events (myocardial infarction, stroke, cardiovascular death) independent of traditional risk factors including LDL cholesterol. In a 2003 NEJM study of emergency department patients with chest pain, MPO above the median was associated with 4.7-fold elevated 30-day major cardiovascular event risk. In primary prevention, elevated MPO predicts future MI and stroke in apparently healthy individuals with normal LDL.
Explains cardiovascular risk in normal-LDL patients: the clinical question of why some patients with normal LDL have heart attacks is partly answered by MPO. High MPO activity converts normal amounts of LDL cholesterol into highly atherogenic oxidized LDL at an accelerated rate. The atherogenic burden from the same absolute LDL concentration is substantially higher in a high-MPO environment.
Direct LDL oxidation mechanism: MPO is the primary enzyme driving LDL oxidation in the arterial wall. The presence of MPO-oxidized LDL adducts within human coronary atherosclerotic plaques has been confirmed histologically. MPO levels correlate with oxLDL levels, confirming that serum MPO reflects the rate of LDL oxidative modification.
Nitric oxide depletion: MPO consumes NO through a direct oxidation reaction. In the presence of elevated MPO, NO bioavailability falls proportionally, impairing endothelial-dependent vasodilation, increasing platelet aggregation, and promoting vascular smooth muscle proliferation, all without any change in LDL or traditional inflammatory markers.
Heart failure risk: MPO is elevated in acute decompensated heart failure and predicts adverse outcomes. Elevated MPO in patients with heart failure identifies those at highest risk for cardiovascular death and hospitalization.

3. Standard Lab Reference Range

MPO Level	Risk Classification
Below 470 pmol/L	Below median: lower cardiovascular risk
Above 470 pmol/L	Above median: elevated cardiovascular risk in prospective studies

MPO reference ranges vary by assay platform and laboratory. Some laboratories report in ng/mL or µg/L rather than pmol/L. The Cleveland Clinic cardiovascular risk studies used pmol/L units with 470 pmol/L as the median threshold. Confirm units with your laboratory. In functional medicine, targeting the lowest achievable MPO (below 300 pmol/L) is the goal for cardiovascular risk minimization.

4. Optimal Functional Medicine Range

MPO Level	Functional Interpretation
Below 200 pmol/L	Excellent: minimal vascular neutrophil activation; lowest LDL oxidation rate
200 to 300 pmol/L	Optimal: low vascular oxidative stress; maintain with antioxidant and anti-inflammatory support
300 to 470 pmol/L	Borderline: measurable neutrophil vascular activation; address root causes
470 to 700 pmol/L	Elevated: significant LDL oxidation and nitric oxide depletion; comprehensive intervention
Above 700 pmol/L	High: markedly elevated vascular oxidative stress; urgent cardiovascular risk management

5. What Causes Elevated MPO

Atherosclerotic plaque inflammation: macrophages and neutrophils within active plaques are a primary source of circulating MPO; larger plaque burden with higher inflammatory activity produces higher serum MPO
Metabolic syndrome and insulin resistance: promotes neutrophil activation and priming, increasing the vascular MPO burden; visceral adipose tissue generates IL-8 and other neutrophil-activating chemokines
Smoking: cigarette smoke directly activates neutrophils and primes them for enhanced MPO release; smoking is one of the most potent MPO elevators
Periodontal disease: oral bacteria chronically activate systemic neutrophils, elevating MPO; treating periodontal disease reduces systemic neutrophil activation
Chronic infections: sustained neutrophil activation from low-grade infections (H. pylori, Chlamydia pneumoniae, CMV) elevates MPO through constant immune activation
Sleep deprivation: consistently elevates neutrophil inflammatory activation and serum MPO; chronic poor sleep is an underappreciated driver of vascular oxidative stress
Hypertension: elevated blood pressure activates vascular wall endothelial cells, which recruit neutrophils that release MPO at the vessel wall
Low omega-3 index: insufficient EPA and DHA reduces neutrophil anti-inflammatory polarization and increases MPO release per activation event
Acute infections: MPO rises significantly with any bacterial or viral infection due to massive neutrophil activation; always test during stable health for cardiovascular risk assessment

6. How to Lower MPO

Primary Interventions

Smoking cessation: the most impactful single intervention for reducing neutrophil activation and MPO; cessation reduces MPO within weeks to months as sustained neutrophil priming resolves
Periodontal disease treatment: professional dental treatment of periodontitis reduces systemic neutrophil activation and MPO; dental health is integral to vascular inflammatory management
Sleep optimization: 7 to 9 hours of quality sleep reduces neutrophil inflammatory activation; one of the most underutilized anti-MPO interventions
Blood pressure control: reducing hypertension lowers vascular wall shear stress and endothelial neutrophil recruitment
Treat underlying chronic infections when identified

Nutritional Support

Omega-3 fatty acids (2 to 4g EPA and DHA daily): reduces neutrophil activation and MPO release through EPA and DHA incorporation into neutrophil membranes; shifts neutrophil function toward reduced oxidative burst; multiple studies demonstrate 15 to 30% MPO reduction with high-dose omega-3
Pomegranate extract (standardized to punicalagins, 500mg daily): directly inhibits MPO enzymatic activity; pomegranate polyphenols are among the most potent natural MPO inhibitors identified; also reduces LDL oxidation and blood pressure
Dark chocolate flavonoids (70% or above cacao, 30 to 40g daily): epicatechin and procyanidins inhibit MPO and reduce neutrophil activation; multiple clinical trials demonstrate MPO reduction
Vitamin C (1,000mg daily): regenerates oxidized antioxidants and reduces MPO-generated oxidative burden; MPO consumes vitamin C rapidly
Quercetin (500 to 1,000mg daily): flavonoid with direct MPO inhibitory activity; reduces neutrophil oxidative burst

Medical Options

Statins: reduce vascular endothelial neutrophil recruitment and MPO production from plaque macrophages; high-intensity statins produce the largest MPO reductions (15 to 25%) through plaque stabilization and anti-inflammatory effects
Colchicine (low-dose, 0.5mg daily): potent anti-neutrophil agent through NLRP3 inflammasome inhibition; the COLCOT and LoDoCo2 trials demonstrating cardiovascular benefit may partly operate through MPO and neutrophil pathway reduction
ACE inhibitors and ARBs: reduce vascular wall inflammation and neutrophil activation through angiotensin pathway inhibition
Nitric oxide support (L-arginine, L-citrulline, dietary nitrate from beet root): partially compensates for MPO-mediated NO depletion by increasing NO substrate availability

7. Related Lab Tests

Oxidized LDLDirect Product of MPO LDL Oxidation

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Lp-PLA2Complementary Vascular Plaque Marker

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hs-CRPSystemic Inflammatory Context

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Omega-3 IndexOmega-3 Status Reduces Neutrophil MPO Release

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ApoBLDL Particle Burden Available for Oxidation

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SDMABoth Deplete Nitric Oxide Through Distinct Mechanisms

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8. When Testing Is Recommended

Advanced cardiovascular risk assessment in patients with normal or borderline LDL: MPO identifies oxidative LDL modification risk invisible to standard lipid testing
Patients with cardiovascular events or family history despite "normal" cholesterol panels
Heavy smokers or recent ex-smokers: MPO quantifies residual neutrophil activation and LDL oxidation risk
Patients with metabolic syndrome: elevated MPO alongside elevated hs-CRP and ApoB defines a high-risk inflammatory metabolic phenotype
Monitoring anti-inflammatory interventions: omega-3 supplementation, statin therapy, pomegranate extract, and smoking cessation should reduce MPO within 3 to 6 months
Draw during stable health; avoid testing within 2 to 4 weeks of acute infection or significant injury
Any comprehensive advanced cardiovascular inflammation panel

9. Clinical Perspective

Clinical Perspective

Myeloperoxidase is the test I reach for when I want to understand the oxidative environment surrounding a patient's LDL particles. Two patients can have identical ApoB of 90 mg/dL, but if one has MPO of 280 pmol/L and the other has MPO of 680 pmol/L, their actual atherogenic burden is dramatically different. The first patient's LDL is largely native and being cleared normally. The second patient's LDL is being oxidized at an accelerated rate into the form that macrophages cannot stop consuming, forming foam cells at a rate that their LDL count alone does not predict. And separately, the high MPO patient is depleting nitric oxide in their vascular endothelium through a completely independent mechanism that impairs vasodilation and promotes platelet aggregation. Pomegranate extract has become a regular part of my high-MPO protocol specifically because of its direct enzymatic inhibition of MPO activity, which is a different mechanism from omega-3s or statins. When I can address MPO from multiple angles simultaneously, the response is faster and more complete.

Brian Lamkin, DO | Founder, The Lamkin Clinic | Edmond, Oklahoma

10. Frequently Asked Questions

What is the optimal myeloperoxidase level?

In functional medicine, optimal MPO is below 300 pmol/L. The standard reference defines elevated risk as above 470 pmol/L (the median in prospective cardiovascular studies), but functional medicine targets the lower portion of the range to minimize active LDL oxidation and nitric oxide depletion. Multiple studies including Cleveland Clinic data demonstrate 2 to 3-fold elevated cardiovascular event risk in patients above the MPO median.

What does elevated myeloperoxidase mean?

Elevated MPO indicates active neutrophil and monocyte degranulation in the vascular environment, generating reactive oxidants that oxidize LDL to its most atherogenic form, deplete nitric oxide, destabilize plaque fibrous caps, and activate matrix metalloproteinases. Elevated MPO with normal LDL identifies patients whose LDL is being converted to highly atherogenic oxidized LDL at an accelerated rate that their LDL cholesterol alone does not reflect.

Why does MPO predict cardiovascular events even when LDL is normal?

MPO converts native LDL into oxidized LDL, which is 3 to 5 times more atherogenic per particle because it is taken up without regulation by macrophage scavenger receptors, forming foam cells indefinitely. In high-MPO environments, the same absolute LDL particle count produces far greater atherosclerotic plaque formation than in a low-MPO environment. Additionally, MPO directly depletes nitric oxide through a separate mechanism, impairing vasodilation independent of LDL effects.

How do you lower myeloperoxidase?

The most evidence-based approaches are: omega-3 fatty acids (2 to 4g EPA and DHA daily reduces neutrophil activation and MPO release by 15 to 30%), pomegranate extract (directly inhibits MPO enzymatic activity), smoking cessation (removes the most potent neutrophil activator), periodontal disease treatment (eliminates chronic systemic neutrophil activation), sleep optimization, statin therapy, colchicine, and dietary interventions including dark chocolate flavonoids and quercetin.

Should MPO be tested during or after an acute infection?

No. MPO rises dramatically with any acute bacterial or viral infection due to massive neutrophil activation for immune defense. For cardiovascular risk assessment, MPO should be drawn during stable health, at least 2 to 4 weeks after resolution of any acute infection, injury, or significant inflammatory event. Testing during illness will produce a falsely elevated result that does not reflect chronic vascular inflammatory state.

Content authored and clinically reviewed by Brian Lamkin, DO, founder of The Lamkin Clinic in Edmond, Oklahoma. Brian Lamkin, DO has 25+ years of experience in functional and regenerative medicine. This page reflects current functional medicine practice standards and is updated as new clinical evidence becomes available.

Two patients with identical LDL can have dramatically different atherogenic burdens depending on how fast their MPO is oxidizing that LDL.

MPO is the missing link between normal LDL and unexpected cardiovascular events. Schedule a consultation for a complete advanced vascular inflammation panel.

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Medical Disclaimer: This content is provided for educational purposes only and is not intended as a substitute for professional medical advice, diagnosis, or treatment. Lab interpretation should always be performed in clinical context by a qualified healthcare provider. Reference ranges and optimal targets may vary based on individual patient history, clinical presentation, and laboratory methodology. Schedule a consultation to discuss your specific results with Dr. Lamkin.