The Master Anti-Inflammation Protocol

Fire — The Dual Nature

Inflammation is fire. And like fire, it has two faces.

Acute inflammation is a controlled burn. You cut your finger — within seconds, mast cells release histamine, blood vessels dilate, neutrophils swarm, platelets seal the breach. Redness, swelling, heat, pain: the four cardinal signs described by Celsus two thousand years ago. This is inflammation doing its job. Without it, a paper cut could kill you. A broken bone would never heal. An invading bacterium would multiply unchecked.

Chronic inflammation is a house fire that nobody called the fire department for. The alarm keeps ringing. The flames keep burning. But now the fire is destroying the house itself. Low-grade, systemic, silent — chronic inflammation simmers beneath the surface for years and decades, eroding tissue, driving disease, and accelerating aging. You do not feel it as a single symptom. You feel it as everything going slightly wrong at once.

The Inflammatory Cascade

The molecular chain reaction follows a predictable pattern:

1. A trigger (infection, toxin, damaged tissue, dietary antigen, stress) activates NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) — the master transcription factor of inflammation.
2. NF-kB translocates to the nucleus and turns on genes for pro-inflammatory cytokines: TNF-alpha (tumor necrosis factor), IL-1-beta (interleukin-1 beta), IL-6 (interleukin-6).
3. These cytokines activate COX-2 (cyclooxygenase-2) and 5-LOX (5-lipoxygenase) enzymes.
4. COX-2 converts arachidonic acid (an omega-6 fatty acid) into prostaglandin E2 — a potent inflammatory mediator that causes pain, fever, and tissue damage.
5. 5-LOX produces leukotrienes — drivers of bronchoconstriction (asthma), vascular permeability, and neutrophil recruitment.
6. Tissue damage from these mediators releases more DAMPs (damage-associated molecular patterns), which activate more NF-kB.

The vicious cycle spins. Inflammation begets damage. Damage begets inflammation. Without active resolution, it never stops.

Chronic Inflammation as the Root of Disease

The research is now overwhelming. Chronic low-grade inflammation is the common soil of the major diseases of civilization:

• Cardiovascular disease: Atherosclerosis is an inflammatory disease (not just a cholesterol disease). Paul Ridker’s JUPITER and CANTOS trials proved this — reducing inflammation (with statins in JUPITER, with the IL-1beta antibody canakinumab in CANTOS) reduced cardiovascular events independent of LDL changes.
• Cancer: NF-kB activation drives tumor survival, angiogenesis, metastasis, and resistance to apoptosis. Chronic inflammation creates the micro-environment in which cancer thrives.
• Alzheimer’s disease: Neuroinflammation (microglial activation, elevated TNF-alpha and IL-6 in the brain) precedes amyloid plaque formation. Dale Bredesen’s ReCODE protocol addresses inflammation as one of the primary subtypes of cognitive decline.
• Autoimmune disease: The inflammatory cascade attacks self-tissue. NF-kB is constitutively activated in RA, lupus, MS, and IBD.
• Type 2 Diabetes: Adipose tissue inflammation (IL-6, TNF-alpha from visceral fat) drives insulin resistance. Inflammation is both a cause and a consequence of metabolic dysfunction.
• Depression: The cytokine theory of depression — elevated IL-6, TNF-alpha, and CRP correlate with depressive symptoms. Inflammation reduces tryptophan conversion to serotonin (shunting it toward the kynurenine pathway instead). Anti-inflammatory interventions improve depression scores.
• Obesity: Fat tissue is not inert storage. Visceral adipose tissue is an endocrine organ that secretes inflammatory cytokines. Obesity is a state of chronic inflammation.
• Chronic pain: Central sensitization (the nervous system amplifying pain signals) is driven by neuroinflammation — activated microglia and astrocytes releasing pro-inflammatory mediators.

The Inflammation Dashboard — Testing

You cannot manage what you do not measure. These markers create a comprehensive inflammation profile:

Core Markers

• hs-CRP (high-sensitivity C-reactive protein): Produced by the liver in response to IL-6. The most validated and accessible inflammatory marker. Standard “normal”: <3.0 mg/L. Functional optimal: <0.5 mg/L. Between 1.0-3.0 is moderate chronic inflammation. Above 3.0 (without acute infection) is significant systemic inflammation. Above 10.0 suggests acute infection or autoimmune flare.
• Homocysteine: Not just a methylation marker — homocysteine itself is directly inflammatory and atherogenic. Damages endothelial lining, activates NF-kB, promotes oxidative stress. Optimal: 6-8 μmol/L.
• ESR (erythrocyte sedimentation rate): How fast red blood cells settle in a tube. Inflammatory proteins (fibrinogen, immunoglobulins) make RBCs clump and settle faster. Optimal: <10 mm/hr. Non-specific but useful for tracking inflammation trends over time.
• Ferritin: Iron storage protein — but also an acute-phase reactant. Elevated ferritin (>200 ng/mL in men, >150 in women) without iron overload suggests inflammation. Optimal functional range: 40-100 ng/mL. Context matters: check with serum iron, TIBC, and transferrin saturation.

Advanced Markers

• Fibrinogen: Clotting factor that rises with inflammation (acute-phase reactant). Elevated fibrinogen increases blood viscosity and cardiovascular risk. Optimal: <350 mg/dL.
• LDH (lactate dehydrogenase): Released from damaged cells — a tissue destruction marker. Elevated in hemolysis, liver damage, muscle injury, and active inflammation.
• Uric acid: A paradox. Too high (>7 mg/dL) drives gout, kidney stones, and activates the NLRP3 inflammasome. Too low (<3 mg/dL) means insufficient antioxidant defense (uric acid is the body’s most abundant endogenous antioxidant). Optimal sweet spot: 4-6 mg/dL.
• Omega-3 Index: Measures EPA + DHA as a percentage of red blood cell membrane fatty acids. Target: >8%. Below 4% is associated with a 10-fold increase in sudden cardiac death risk compared to >8% (Harris, 2004). This test measures your inflammatory set point at the cellular membrane level.
• Cytokine panels: Direct measurement of TNF-alpha, IL-6, IL-1-beta, IL-10 (anti-inflammatory), IL-17 (Th17 autoimmune pathway). Expensive, not widely available, but informative in complex autoimmune, neurological, or treatment-resistant cases.
• GlycanAge or TruDiagnostic: Epigenetic clocks that measure biological age — heavily influenced by chronic inflammation. Your chronological age is a number. Your biological age reflects accumulated inflammatory damage and can be modifiable.

Dietary Anti-Inflammatory Protocol

Remove — The Inflammatory Drivers

• Seed oils (industrial vegetable oils): Soybean, canola (rapeseed), corn, sunflower, safflower, cottonseed, grapeseed. These are 50-70% linoleic acid (omega-6) that integrates into cell membranes, displacing omega-3s, and provides substrate for pro-inflammatory prostaglandin E2 and leukotriene synthesis via COX-2 and 5-LOX. Linoleic acid consumption has increased from 2% of calories in 1900 to 8-10% today. This single dietary shift may be the most inflammatory change in human nutritional history.
• Sugar and refined carbohydrates: Glucose spikes activate NF-kB directly. Fructose (especially high-fructose corn syrup) generates uric acid, activates the NLRP3 inflammasome, drives hepatic lipogenesis, and increases intestinal permeability.
• Alcohol: Directly damages intestinal epithelium (leaky gut), burdens liver detoxification (depleting glutathione), and increases systemic LPS (lipopolysaccharide from gut bacteria entering circulation — “metabolic endotoxemia”).
• Trans fats: Partially hydrogenated oils (largely banned but still present in some processed foods). Directly inflammatory, carcinogenic, and atherogenic. Zero safe threshold.
• Processed meats: Nitrites, advanced glycation end products (AGEs), heterocyclic amines from high-heat cooking — all pro-inflammatory and carcinogenic (IARC Group 1 for processed meat).

Emphasize — The Anti-Inflammatory Arsenal

• Wild fatty fish: 3-4 servings/week. Salmon, sardines, mackerel, anchovies, herring (SMASH fish). Rich in EPA and DHA — the precursors to resolvins, protectins, and maresins (the pro-resolving mediators that actively turn off inflammation).
• Extra virgin olive oil: 2-4 tablespoons/day. Contains oleocanthal — a natural COX-2 inhibitor pharmacologically similar to ibuprofen. 50mL of EVOO provides the anti-inflammatory equivalent of approximately 10% of an adult ibuprofen dose. Also rich in oleuropein and hydroxytyrosol (potent polyphenol antioxidants).
• Turmeric and ginger: Use liberally in cooking. Curcumin (from turmeric) and gingerols inhibit NF-kB, COX-2, and 5-LOX. Add black pepper (piperine increases curcumin absorption 2,000%) and fat (curcumin is lipophilic).
• Berries: Blueberries, blackberries, raspberries, strawberries — anthocyanins are potent NF-kB inhibitors and Nrf2 activators. 1 cup daily.
• Dark leafy greens: Spinach, kale, Swiss chard, collards — rich in magnesium, folate, vitamin K, and phytonutrients that modulate inflammation.
• Cruciferous vegetables: Broccoli, cauliflower, Brussels sprouts, cabbage — sulforaphane activates Nrf2, the master antioxidant switch.
• Green tea: EGCG (epigallocatechin gallate) inhibits NF-kB and modulates Th1/Th2 balance. 3-4 cups daily or matcha (10x the EGCG of regular green tea).
• Bone broth: Glycine (inhibitory neurotransmitter, anti-inflammatory amino acid), proline, glutamine (gut barrier repair), collagen peptides.
• Fermented foods: Sauerkraut, kimchi, kefir, miso — support microbial diversity. Gut dysbiosis drives systemic inflammation via LPS translocation.
• Mediterranean diet as the template: validated in the PREDIMED trial (7,447 participants) — 30% reduction in cardiovascular events with Mediterranean diet supplemented with EVOO or nuts. This is the most evidence-backed anti-inflammatory dietary pattern.

Supplement Protocol

Omega-3 Fatty Acids

EPA/DHA: 3-4g/day pharmaceutical grade (tested for heavy metals, PCBs, oxidation). For inflammation specifically, use a 2:1 EPA-to-DHA ratio — EPA is the more potent anti-inflammatory (drives resolvin E series), while DHA is more neuroprotective (drives resolvin D series and neuroprotectin D1). Brands: Nordic Naturals, Carlson, OmegaQuant-tested products. Take with a fat-containing meal for absorption. Triglyceride form absorbs better than ethyl ester form.

Curcumin

1000-2000mg/day of a bioavailable form. Standard turmeric powder is <5% curcumin, and curcumin itself has poor oral bioavailability. Choose formulations designed to overcome this:

• Meriva (curcumin phytosome — complexed with phosphatidylcholine): 29x improved absorption
• Theracurmin (nanoparticle colloidal dispersion): 27x improved absorption
• Longvida (lipidated SLCP): crosses the blood-brain barrier (important for neuroinflammation)

Curcumin inhibits NF-kB at multiple points in the cascade. A 2004 study by Aggarwal showed it blocks over 100 different inflammatory pathways. Comparable to ibuprofen for COX-2 inhibition without gastrointestinal damage — curcumin actually protects the GI mucosa.

SPMs (Specialized Pro-Resolving Mediators)

Resolvins, protectins, and maresins — these are the molecules that actively resolve inflammation rather than merely suppressing it. This distinction matters. NSAIDs and corticosteroids suppress — they block prostaglandin production but do not clean up the inflammatory debris. SPMs recruit macrophages to clear dead cells (efferocytosis), restore tissue to pre-inflammatory homeostasis, and signal the immune system to stand down. Derived from EPA and DHA. Supplemental forms: Metagenics SPM Active, Nordic Naturals ProResolve. Dose: 2-4 softgels/day during active inflammation, 1-2/day for maintenance.

Additional Anti-Inflammatory Supplements

• Boswellia (AKBA — acetyl-11-keto-beta-boswellic acid): 500mg 2-3x/day. Specific 5-LOX inhibitor — blocks leukotriene synthesis. Studied in osteoarthritis, rheumatoid arthritis, asthma, and IBD. The Ayurvedic anti-inflammatory that Western research is validating.
• Quercetin: 500-1000mg/day. Mast cell stabilizer (reduces histamine release), NF-kB modulator, zinc ionophore (helps zinc enter cells — relevant for immune function). Found in onions, apples, and capers. Supplemental forms: quercetin phytosome or quercetin with bromelain for enhanced absorption.
• Glutathione: 500mg liposomal form. The master intracellular antioxidant — directly neutralizes ROS, supports T-regulatory cells, recycles vitamins C and E. Depleted by toxins, infections, chronic inflammation, and aging. Liposomal delivery bypasses GI degradation.
• NAC (N-acetyl cysteine): 600-1200mg/day. The rate-limiting precursor for glutathione synthesis. Also a direct NF-kB inhibitor, mucolytic (thins mucus in respiratory conditions), and chelator of heavy metals. Take on an empty stomach, away from food.
• Ginger extract: 1-2g/day. Inhibits both COX-2 and 5-LOX (dual inhibition — most pharmaceuticals only target one). Contains gingerols and shogaols. A 2015 meta-analysis showed ginger reduced CRP by an average of 0.84 mg/L.
• Resveratrol: 200-500mg/day (trans-resveratrol). Activates SIRT1 (sirtuin 1), which deacetylates NF-kB, reducing its transcriptional activity. Also activates AMPK and Nrf2. Take with fat-containing food. Synergistic with quercetin.
• Vitamin D: 5,000 IU/day with K2 (MK-7, 200mcg). Target serum 25-OH-D: 50-70 ng/mL. Vitamin D modulates over 200 genes, many in immune regulation. Deficiency (<30 ng/mL) is associated with elevated CRP, increased autoimmune risk, and poor immune response. Vitamin D is not an anti-inflammatory supplement — it is an immune-programming hormone that reduces inappropriate inflammation while preserving appropriate immune defense.
• Probiotics: Multi-strain, emphasizing Lactobacillus rhamnosus GG (LGG) and Bifidobacterium infantis 35624 (studied in IBS, shown to reduce systemic IL-6 and TNF-alpha). The gut-inflammation axis: 70% of the immune system resides in gut-associated lymphoid tissue (GALT). Dysbiosis → increased intestinal permeability → LPS translocation → systemic NF-kB activation. Fix the gut, reduce the fire.

Lifestyle — The Non-Supplementable Foundations

Sleep

7-9 hours of quality sleep. One night of sleep deprivation (4 hours) increases CRP, IL-6, and TNF-alpha measurably the next day. Chronic short sleep (<6 hours) is associated with elevated inflammatory markers equivalent to metabolic syndrome. Sleep is not recovery from inflammation — it is the primary anti-inflammatory state. During deep sleep, the glymphatic system clears inflammatory waste from the brain. During REM, immune memory consolidation occurs. Shortchange sleep and you shortchange every anti-inflammatory mechanism the body possesses.

Exercise

Moderate, consistent exercise is profoundly anti-inflammatory. Skeletal muscle contraction releases myokines (IL-6 from muscle — paradoxically anti-inflammatory in this context, unlike IL-6 from adipose tissue) that suppress TNF-alpha and activate IL-10 (the master anti-inflammatory cytokine). However, excessive exercise (overtraining) increases cortisol, intestinal permeability, and systemic inflammation. The dose makes the medicine: 150-300 minutes/week of moderate activity, or 75-150 minutes of vigorous activity. Walking counts. Walking is the most underrated anti-inflammatory intervention.

Stress Management

Chronic psychological stress activates NF-kB. This is not metaphor — it is measured molecular biology. A landmark UCLA study by Steve Cole showed that loneliness and chronic stress activate a “conserved transcriptional response to adversity” (CTRA) — upregulating NF-kB-driven inflammatory genes while downregulating antiviral and antibody genes. Meditation (mindfulness-based stress reduction) has been shown to reverse CTRA gene expression in as few as 8 weeks. Breathwork (4-7-8 breathing, box breathing, coherence breathing at 5.5 breaths/minute) activates the vagus nerve — the parasympathetic “brake” on inflammation via the cholinergic anti-inflammatory pathway.

Cold Exposure

Cold water immersion (50-59°F for 2-5 minutes) or cold showers activate norepinephrine release (2-3x increase), which suppresses TNF-alpha, IL-6, and NF-kB. Wim Hof’s method, studied in controlled trials at Radboud University, demonstrated that trained practitioners could voluntarily reduce their inflammatory response to endotoxin injection.

Sauna

Regular sauna use (4-7x/week, 20 minutes at 174°F) reduces CRP, activates heat shock proteins (HSP70, HSP90) which have anti-inflammatory and protein-repair functions, and is associated with 40% reduction in all-cause mortality in the Finnish KIHD study (2,315 men followed for 20 years).

Nature and Connection

Forest bathing (shinrin-yoku) increases NK cell activity for up to 30 days after a single session. Nature exposure reduces cortisol, blood pressure, and inflammatory markers. Social connection reduces NF-kB activation — loneliness is as inflammatory as smoking 15 cigarettes per day (Holt-Lunstad meta-analysis). Community is an anti-inflammatory intervention.

The Resolution Revolution

The old model: inflammation is bad, suppress it. NSAIDs, corticosteroids, immunosuppressants — all suppress the inflammatory response.

The new model (pioneered by Charles Serhan at Harvard): inflammation is a program with a beginning, a middle, and a resolution phase. Chronic inflammatory disease is not a failure of suppression — it is a failure of resolution. The body cannot turn off the fire because it lacks the molecular tools to do so (SPMs, resolvins, protectins, maresins — all derived from omega-3 fatty acids that most people are deficient in).

The anti-inflammatory protocol is not about suppression. It is about removing the fuel (seed oils, sugar, toxins, dysbiosis), supporting the extinguishers (omega-3s, curcumin, glutathione, sleep, exercise), and activating the resolution machinery (SPMs, vagal tone, stress management).

Chronic inflammation is not inevitable. It is a fire that can be resolved — if you stop feeding it and start providing the tools to put it out.