Chronic Inflammation: How To Identify It Before Disease Develops

Most chronic diseases do not appear overnight. They develop quietly over time, often years before a formal diagnosis is made. Beneath the surface, subtle biological changes are already underway. One of the most important—and frequently overlooked—of these processes is chronic, low-grade inflammation.

Feeling off but cannot quite explain why? Is there a struggle with fatigue, brain fog, joint pain, weight gain, or mood changes, yet labs are considered “normal?” For many individuals, those lingering symptoms are early warning signs of inflammatory imbalance that have not yet reached the level of diagnosable disease.

What Do We Mean by Chronic Inflammation?

Inflammation itself is not a problem. In fact, it is a vital part of the immune system. Acute inflammation helps us heal after injury or fight infection, and then it resolves.

Chronic inflammation, however, is different. It lingers. Instead of shutting off, the immune system remains quietly activated, leading to:

• Persistent immune signaling
• Ongoing cytokine release
• Increased oxidative stress
• Gradual tissue damage

Over time, this low-grade inflammatory state contributes to the development of many common conditions, including:

• Cardiovascular disease
• Type 2 diabetes
• Autoimmune disorders
• Neurodegenerative disease
• Metabolic dysfunction
• Certain cancers

Importantly, inflammation often precedes these diagnoses by many years.

Why “Normal” Labs Don’t Always Tell the Full Story

In conventional medicine, inflammation is usually evaluated once disease is already suspected. Many patients never reach that threshold, even though dysfunction is present.

Standard lab work can miss early inflammation because:

• Reference ranges are designed to detect disease, not early imbalance
• Inflammatory markers fluctuate and aren’t always ordered routinely
• Subclinical inflammation doesn’t reliably alter basic labs like a CBC or CMP

With precision medicine we take a more preventive and pattern-based approach, looking for early signals that suggest inflammation before irreversible damage occurs.

Inflammatory Markers That Can Be Used for Evaluation

There is no single lab test that diagnoses chronic inflammation. Instead, the story emerges by looking at patterns across multiple markers and correlating them with symptoms.

Brain and Neuroinflammatory Markers

When cognitive symptoms, mood changes, headaches, or neurologic risk factors are present, additional markers may help assess neuroinflammation and blood–brain barrier integrity.

• Neurofilament light chain (NfL)
  A marker of neuronal injury and axonal damage; elevations may be seen in neurodegenerative disease, traumatic brain injury, and chronic neuroinflammation.
• Glial fibrillary acidic protein (GFAP)
  Reflects astrocyte activation and neuroinflammatory signaling; increasingly used in research and early clinical applications.
• Plasma amyloid beta ratios (Aβ42/40)
  Used as a risk stratification tool in cognitive decline; abnormal ratios may reflect impaired clearance and inflammatory processes.
• Homocysteine
  A modifiable neurotoxic and pro-inflammatory marker associated with cognitive decline, vascular inflammation, and impaired methylation.
• HS-CRP correlated with neurologic symptoms
  While not brain-specific, elevated systemic inflammation often parallels neuroinflammatory activity. (Note: this is also used in cardiac evaluations)
• Reflects systemic inflammation
• Even mild elevations (≥1.0 mg/L) are associated with increased cardiovascular and metabolic risk
• Helpful for tracking response to interventions

Ferritin

• Acts as an acute-phase reactant, not just an iron storage marker
• Elevated levels may indicate inflammation even when iron stores are adequate
• Low ferritin can also contribute to fatigue, hair loss, and impaired thyroid function

Erythrocyte Sedimentation Rate (ESR)

• A nonspecific but useful marker when interpreted alongside symptoms
• Elevations may suggest autoimmune or chronic inflammatory activity

Fibrinogen

• Often overlooked in routine care
• Associated with inflammatory burden and cardiovascular risk

Metabolic Markers

• TSH, Free T3, Free T4 and Reverse T3
• Fasting insulin
• Triglyceride-to-HDL ratio, cholesterol
• Hemoglobin A1c trends over time

Metabolic dysfunction and inflammation are deeply interconnected and should never be evaluated in isolation.

Specialty and Advanced Inflammatory Testing

In select cases, standard labs do not fully capture the complexity of inflammatory signaling. Specialty testing can provide deeper insight into upstream drivers and individualized risk.

Cytokine panels (e.g., IL-6, TNF-α, IL-1β)

• Helpful in complex inflammatory, autoimmune, or neuroinflammatory presentations.

Oxidative stress markers (e.g., oxidized LDL)
Assess the burden of free radical damage and its contribution to vascular and cellular dysfunction.

Advanced lipid and cardiovascular inflammation markers (e.g., LpPLA2, ApoB, LDL particle number, myeloperoxidase)

• Provide a more precise assessment of inflammatory cardiovascular risk than standard lipid panels alone.

inflammation and permeability markers (e.g., calprotectin, zonulin, secretory IgA)

• Help evaluate intestinal drivers of systemic inflammation.

Food immune reactivity testing (IgG/IgA patterns)

• It is used selectively to identify dietary contributors to chronic immune activation.

Hormonal and stress markers (e.g., salivary or urinary cortisol patterns)

• Offer insight into HPAaxis dysregulation and stressdriven inflammation.

Please note that this list of labs is not intended to be used as a checklist, nor does it represent a comprehensive evaluation. It is provided for educational purposes only. These advanced tools are not necessary for every patient; however, when used thoughtfully and selectively, they can help clarify root causes and support more precise, personalized treatment strategies.

Common Drivers of Chronic Inflammation

Identifying inflammation is only the first step. The more important clinical question is why it’s happening.

Common contributors include:

• Insulin resistance and blood sugar variability
• Poor sleep quality or untreated sleep apnea
• Chronic psychological stress and HPA-axis dysregulation
• Nutrient deficiencies (iron, magnesium, omega-3 fatty acids, vitamin D)
• Gut permeability and microbiome imbalance
• Environmental toxin exposure
• Sedentary lifestyle

Addressing inflammation without identifying its root causes may provide temporary relief, but lasting improvement requires a deeper understanding of what’s driving the process.

Approach to Calming Inflammation

Reducing inflammation is not about suppressing the immune system, it is however about restoring balance and resilience.

Targeted Nutrition

• Emphasis on whole, anti-inflammatory foods
• Adequate protein intake to support immune regulation
• Strategic reduction of ultra-processed carbohydrates and industrial seed oils when appropriate

Metabolic Optimization

• Stabilizing blood sugar
• Improving insulin sensitivity
• Supporting mitochondrial health

Sleep and Stress Regulation

• Treating sleep as a core therapeutic intervention
• Addressing cortisol dysregulation
• Incorporating nervous system support strategies

Therapeutic Interventions That Can Support Inflammation Reduction

In addition to foundational lifestyle strategies, certain targeted therapies may be appropriate depending on the individual’s clinical picture, drivers of inflammation, and response to care.

Hyperbaric Oxygen Therapy (HBOT)

• Increase tissue oxygenation and mitochondrial efficiency
• Shown to modulate inflammatory cytokines and reduce oxidative stress in select populations
• Supports reduction of neuroinflammation, wound healing, post-surgical recovery, and chronic inflammatory states when used appropriately

Inhaled Molecular Hydrogen (H₂)

• Acts as a selective antioxidant, neutralizing harmful free radicals without suppressing beneficial immune signaling
• Emerging evidence suggests benefit in reducing oxidative stress, neuroinflammation, and metabolic inflammation

Targeted Dietary Interventions

Diet is one of the most powerful tools for influencing inflammation, but no single diet is right for everyone.

• Gluten elimination may reduce inflammatory burden in individuals with celiac disease, non-celiac gluten sensitivity, or autoimmune conditions
• Low-carbohydrate or ketogenic approaches may improve insulin resistance, glycemic variability, and inflammation in metabolically compromised patients
• Anti-inflammatory whole-food plans emphasize nutrient density, fiber, phytonutrients, and healthy fats to support immune regulation

Dietary strategies are individualized, time-bound when appropriate, and guided by symptoms, labs, and sustainability.

Movement and Physical Conditioning

• Regular, appropriate exercise reduces inflammatory signaling and improves insulin sensitivity
• Overtraining, however, can worsen inflammation, highlighting the need for individualized exercise prescriptions
• These therapies are not universally indicated, but when selected thoughtfully, they can accelerate healing, improve symptom burden, and enhance long-term resilience.

Ongoing Monitoring

Repeating inflammatory markers to assess progress

Adjusting interventions based on objective data and symptom response

Why Early Intervention Matters

Chronic inflammation does not have to progress to disease. When identified early, it is often modifiable—and in many cases, reversible.

By addressing inflammation proactively, we can:

• Improve daily symptoms
• Reduce long-term disease risk
• Protect cognitive and metabolic health
• Enhance overall quality of life

This approach represents the intersection of conventional and functional medicine—using evidence-based diagnostics to guide truly personalized care.

When to Consider a Deeper Evaluation

If you’re experiencing persistent symptoms despite “normal” lab results, or if you have a strong family history of metabolic, autoimmune, or cardiovascular disease, a deeper evaluation may be appropriate.

References

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Donath, M. Y., & Shoelson, S. E. (2011). Type 2 diabetes as an inflammatory disease. Nature Reviews Immunology, 11(2), 98–107. https://doi.org/10.1038/nri2925

Katzdobler, S., Nübling, G., Klietz, M., et al. GFAP and NfL as fluid biomarkers for clinical disease severity and progression (J. Neurol., 2024).

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Valkanova, V., Ebmeier, K. P., & Allan, C. L. (2013). CRP, IL-6 and depression: A systematic review and meta-analysis of longitudinal studies. Journal of Affective Disorders, 150(3), 736–744. https://doi.org/10.1016/j.jad.2013.06.004