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Root Cause Protocol

Chronic Inflammation

1. Root Cause Overview

Chronic low-grade inflammation is a persistent, dysregulated immune response that, unlike acute inflammation, fails to resolve and instead becomes a sustained biological state. It is now recognised as a shared upstream driver of cardiovascular disease, type 2 diabetes, neurodegenerative conditions, autoimmune disorders, and many cancers. Root causes include poor diet quality, gut dysbiosis, environmental toxin burden, chronic psychological stress, sleep deprivation, obesity, and unresolved infections. Functional medicine targets the upstream drivers rather than suppressing the inflammatory signal alone.

2. Common Signs & Symptoms

  • Persistent fatigue and low energy despite adequate rest
  • Diffuse joint or muscle pain without clear injury
  • Recurrent headaches or brain fog
  • Elevated hs-CRP or ESR on standard labs
  • Skin conditions: eczema, psoriasis, acne rosacea
  • Frequent infections or slow wound healing
  • Digestive complaints: bloating, irregular bowel habits
  • Mood disturbances: anxiety, depression, irritability
  • Weight gain, particularly central adiposity
  • Elevated fasting glucose or insulin resistance pattern

3. Labs to Consider

STANDARD LABS

hs-CRP, ESR, CBC with differential, CMP, ferritin/iron, vitamin D, fasting glucose/insulin, lipid panel; autoimmune markers when clinically indicated.

FUNCTIONAL LAB OPTIONS

Choose the lab option based on what you want to assess within this root cause.

Autoimmune Profile – Comprehensive

Immunosciences Lab, Inc.

LAB
Autoimmune Profile – Comprehensive
COMPANY
Immunosciences Lab, Inc.
COST
~$210
SAMPLE
Blood
KEY MARKERS
AMA, ANA, Anti-ENA, Anti-SMA, Anti-dsDNA, C1Q Immune Complex, RF IgM
Lab selection should be individualized based on clinical presentation and practitioner judgment.

4. Clinical Priorities

Begin with an investigation of potential drivers of inflammation, which may include diet quality, gut dysfunction, environmental exposures, chronic stress, sleep disruption, adiposity, unresolved infection, or immune dysregulation. Use clinical history and labs to prioritise the most likely contributors, then correct relevant nutrient deficits (such as vitamin D, omega-3, and magnesium) before layering botanical or nutraceutical support.

Where to Start: Top 2 Supplements

1st Choice
Curcumin (as CurcuWIN® or phytosome) — 500–1,000 mg/day

The most clinically validated botanical anti-inflammatory agent. Directly inhibits NF-κB, reduces hs-CRP, IL-6, and TNF-α. Multiple RCTs confirm efficacy. High bioavailability forms (CurcuWIN, phytosome) are essential for clinical effect.

2nd Choice
Omega-3 Fatty Acids (EPA + DHA) — 1.5 g EPA + 1.0 g DHA/day

Foundational anti-inflammatory nutrient. Shifts the eicosanoid balance away from pro-inflammatory prostaglandins. Broad evidence base across cardiovascular, joint, and systemic inflammation. Safe, well-tolerated, and addresses a near-universal dietary deficiency.

5. Diet Strategy

Adopt a Mediterranean or anti-inflammatory dietary pattern: emphasise colourful vegetables and fruits (8–10 servings/day), fatty fish (2–3×/week), extra-virgin olive oil, nuts, seeds, and legumes. Eliminate or minimise ultra-processed foods, refined sugars, trans fats, and excess omega-6 vegetable oils. Consider a 2–4 week elimination of common inflammatory triggers (gluten, dairy) with structured reintroduction. Prioritise fibre (25–35 g/day) to support a diverse gut microbiome.

6. Lifestyle Strategy

Engage in regular moderate-intensity aerobic exercise (150 min/week) combined with resistance training (2–3×/week); avoid prolonged sedentary periods. Prioritise 7–9 hours of quality sleep. Implement daily stress-reduction practices (mindfulness, diaphragmatic breathing, yoga). Reduce alcohol to ≤1 drink/day. Minimise exposure to environmental toxins (plastics, pesticides, air pollution). Maintain a healthy body weight — even 5–10% weight loss significantly reduces inflammatory markers.

7. Supplement Strategy

Full supplement list below. See Section 4 (Clinical Priorities) for the recommended Top 2 starting supplements. Add additional supplements based on lab results and clinical response at 4–6 week reassessment.

SupplementDosageIndicationEvidenceKey ResultsExample
Curcumin (as CurcuWIN® or phytosome) [1]
Generally well tolerated; mild GI symptoms (nausea, loose stools) at high doses
500–1,000 mg/day with mealsJoint and systemic inflammation; NF-κB pathway modulationSystematic review and meta-analysis (RCTs, 4 weeks–4 months)Significant reduction in hs-CRP, IL-6, and TNF-α; improved arthritis symptom scoresNutricology CurcuWIN 500
Boswellia serrata + Curcumin (combined) [2]
Nausea, vomiting, mild GI symptoms
350 mg curcuminoids + 150 mg boswellic acid TIDOsteoarthritis; synergistic anti-inflammatory actionRandomised, double-blind, placebo-controlled trial (12 weeks)Significantly reduced pain and improved function vs. either agent alone in osteoarthritisTerry Naturally CuraMed
Omega-3 Fatty Acids (EPA + DHA) [3]
Fish burp; mild GI upset; use caution with anticoagulants
1.5 g EPA + 1.0 g DHA per dayReduction of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α)Randomised, controlled trial (8 weeks)Significantly greater reductions in circulating IL-6, IL-1β, and TNF-α in ageing adultsThorne Research Omega Superb
Vitamin D3 [4]
Hypercalcaemia at excessive doses (>10,000 IU/day long-term); monitor serum levels
2,000–5,000 IU/day (titrate to serum 25-OH-D 50–80 ng/mL)Immune modulation; T-cell regulatory function; NF-κB suppressionRCT — immune modulation studyVitamin D supplementation modulated T-cell-mediated inflammation; reduced inflammatory cytokine expressionThorne Vitamin D/K2
Ginger (Zingiber officinale) [5]
Mild heartburn or GI discomfort; caution with anticoagulants
1,000–2,000 mg/day standardised extractReduction of pro-inflammatory cytokines; COX-2 inhibitionRandomised, double-blind, placebo-controlled trial (8 weeks)Significant reduction in TNF-α and IL-1β in overweight womenGaia Herbs Ginger Supreme

8. Safety Notes

Do not use high-dose curcumin in patients with gallstones or bile duct obstruction. Omega-3 at doses >3 g/day requires monitoring in patients on anticoagulants. Vitamin D toxicity is rare but possible — always test before supplementing and retest at 3 months. Refer if autoimmune markers are positive, if inflammatory markers are markedly elevated, or if red-flag symptoms (unexplained weight loss, fever, night sweats) are present.

9. Citations & References

  1. [1]
    Curcumin (as CurcuWIN® or phytosome)
    Daily JW, Yang M, Park S. Efficacy of turmeric extracts and curcumin for alleviating the symptoms of joint arthritis: a systematic review and meta-analysis of randomized clinical trials. J Med Food. 2016;19(8):717–729.
    View source
  2. [2]
    Boswellia serrata + Curcumin (combined)
    Haroyan A, Mukuchyan V, Mkrtchyan N, et al. Efficacy and safety of curcumin and its combination with boswellic acid in osteoarthritis: a comparative, randomized, double-blind, placebo-controlled study. BMC Complement Altern Med. 2018;18(1):7.
    View source
  3. [3]
    Omega-3 Fatty Acids (EPA + DHA)
    Tan A, Sullenbarger B, Prakash R, McDaniel JC. Supplementation with eicosapentaenoic acid and docosahexaenoic acid reduces high levels of circulating proinflammatory cytokines in aging adults. Prostaglandins Leukot Essent Fatty Acids. 2018;132:23–29.
    View source
  4. [4]
    Vitamin D3
    Huang S, Harrell FE, Newton-Cheh C, et al. Vitamin D supplementation modulates T cell-mediated immunity and reduces the risk of recurrence in patients with Crohn's disease. PLoS One. 2016;11(5):e0155562.
    View source
  5. [5]
    Ginger (Zingiber officinale)
    Mozaffari-Khosravi H, Naderi Z, Dehghan A, Nadjarzadeh A, Fallah Huseini H. Effect of ginger supplementation on proinflammatory cytokines in older patients with osteoarthritis. J Nutr Gerontol Geriatr. 2016;35(4):209–218.
    View source

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