Root Cause Protocol

Neuroinflammation

1. Root Cause Overview

Neuroinflammation is the activation of the brain's innate immune system — primarily microglia and astrocytes — in response to injury, infection, toxins, metabolic dysfunction, or peripheral inflammatory signals. While acute neuroinflammation is protective, chronic neuroinflammation drives neurodegeneration, mood disorders, cognitive decline, and conditions including Alzheimer's disease, Parkinson's disease, depression, anxiety, and autism spectrum disorder. Key drivers include gut dysbiosis (gut-brain axis), blood-brain barrier disruption, chronic systemic inflammation, toxin burden, and metabolic dysfunction.

2. Common Signs & Symptoms

Brain fog, cognitive slowing, poor concentration
Memory impairment (short-term > long-term)
Depression and/or anxiety
Fatigue disproportionate to activity
Headaches (often diffuse, pressure-type)
Sensory sensitivities (light, sound, smell)
Sleep disturbances (difficulty initiating or maintaining sleep)
Mood lability, irritability
Peripheral neuropathy symptoms
Elevated inflammatory markers on standard or functional labs

3. Labs to Consider

STANDARD LABS

hs-CRP, ESR, fasting glucose/insulin, B12/MMA, vitamin D, thyroid panel, iron/ferritin; neurologic referral for red-flag symptoms.

FUNCTIONAL LAB OPTIONS

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

BEST FOR

Comprehensive Neurotransmitter Profile – Random

Doctor's Data

LAB

Comprehensive Neurotransmitter Profile – Random

COMPANY

Doctor's Data

COST

~$275

SAMPLE

Urine

KEY MARKERS

20+ neurotransmitter markers: serotonin, dopamine, GABA, glutamate, norepinephrine, epinephrine, histamine, PEA

Lab selection should be individualized based on clinical presentation and practitioner judgment.

4. Clinical Priorities

Evaluate for multiple potential contributors to neuroinflammation, such as gut dysfunction, metabolic imbalance, thyroid issues, vitamin D insufficiency, neurotoxic exposures, chronic infection, sleep disruption, and unresolved psychological stress. Use the clinical picture and testing to prioritise which drivers appear most relevant, while supporting sleep and glymphatic clearance as part of the overall strategy.

Where to Start: Top 2 Supplements

1st Choice

Omega-3 Fatty Acids (DHA-dominant) — 2–4 g/day

DHA is the primary structural fatty acid of neuronal membranes and the most evidence-backed anti-neuroinflammatory nutrient. Reduces microglial activation, resolves neuroinflammation via specialised pro-resolving mediators (SPMs), and improves cognitive function. Start here for any neuroinflammatory condition.

2nd Choice

Curcumin (BCM-95 or CurcuWIN®) — 500–1,000 mg/day

The most studied botanical for neuroinflammation. Crosses the blood-brain barrier (high-bioavailability forms), inhibits NF-κB in microglia, upregulates BDNF, and has demonstrated cognitive benefit in RCTs. Synergistic with omega-3 for combined resolution of neuroinflammation.

5. Diet Strategy

Adopt a brain-protective dietary pattern: Mediterranean or MIND diet. Emphasise fatty fish (DHA/EPA), blueberries (anthocyanins), leafy greens (folate, vitamin K), nuts (vitamin E, polyphenols), olive oil (oleocanthal — natural COX inhibitor), and turmeric. Eliminate ultra-processed foods, refined sugars, trans fats, and alcohol. Consider a low-glycaemic diet to reduce neuroinflammatory insulin spikes. Ensure adequate choline (eggs, liver) for acetylcholine synthesis.

6. Lifestyle Strategy

Regular aerobic exercise is the most potent anti-neuroinflammatory intervention — increases BDNF, reduces microglial activation, and improves glymphatic clearance. Prioritise 7–9 hours of quality sleep (glymphatic system clears neuroinflammatory waste during deep sleep). Mindfulness meditation reduces neuroinflammatory markers. Minimise screen time and electromagnetic exposure. Social connection and cognitive engagement are neuroprotective.

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.

Supplement	Dosage	Indication	Evidence	Key Results	Example
Omega-3 Fatty Acids (DHA-dominant) [1] Fish burp; anticoagulant interaction at high doses	2–4 g/day (DHA:EPA ratio ≥2:1 for brain)	Neuroinflammation resolution; microglial modulation; DHA structural component of neuronal membranes	RCT and meta-analysis	Reduced neuroinflammatory markers; improved cognitive function and mood; reduced microglial activation	Nordic Naturals Ultimate Omega
Curcumin (BCM-95 or CurcuWIN® — high bioavailability) [2] Mild GI upset; avoid in gallstone disease	500–1,000 mg/day	NF-κB inhibition; microglial modulation; BDNF upregulation; amyloid inhibition	RCT and mechanistic studies	Reduced neuroinflammatory markers; improved memory and attention in older adults; BDNF upregulation	Nutricology CurcuWIN 500
Lion's Mane Mushroom (Hericium erinaceus) [3] Generally well tolerated; rare GI upset; caution in mushroom allergy	500–3,000 mg/day standardised extract	Nerve growth factor (NGF) stimulation; neuroregeneration; cognitive support	RCT (double-blind, placebo-controlled)	Significantly improved cognitive function scores in mild cognitive impairment; increased NGF expression	Host Defense Lion's Mane
Phosphatidylserine [4] Generally well tolerated; mild GI upset; anticoagulant interaction at high doses	300–400 mg/day	Neuronal membrane integrity; cortisol modulation; cognitive function	RCT	Improved memory, learning, and cognitive function in older adults with memory complaints; reduced cortisol response	Jarrow Formulas PS100
Magnesium L-Threonate [5] Loose stools at high doses; generally well tolerated	1,500–2,000 mg/day (providing ~144 mg elemental Mg)	Brain-penetrant magnesium form; synaptic plasticity; NMDA receptor modulation; anxiety and sleep	RCT	Improved cognitive function and memory in older adults; increased brain magnesium levels; reduced anxiety	Life Extension Neuro-Mag

8. Safety Notes

Neurological red flags (sudden cognitive decline, focal neurological deficits, seizures, severe headache) require immediate medical referral. Do not use supplements as a substitute for neurological evaluation. High-dose omega-3 requires monitoring in patients on anticoagulants. Lion's Mane is contraindicated in mushroom allergy. Always address the upstream drivers (gut health, metabolic dysfunction, toxin burden) concurrently with neuroinflammation support.

9. Citations & References

[1]
Omega-3 Fatty Acids (DHA-dominant)
Calder PC. Omega-3 fatty acids and inflammatory processes: from molecules to man. Biochem Soc Trans. 2017;45(5):1105–1115.
View source
[2]
Curcumin (BCM-95 or CurcuWIN® — high bioavailability)
Small GW, Siddarth P, Li Z, et al. Memory and brain amyloid and tau effects of a bioavailable form of curcumin in non-demented adults: a double-blind, placebo-controlled 18-month trial. Am J Geriatr Psychiatry. 2018;26(3):266–277.
View source
[3]
Lion's Mane Mushroom (Hericium erinaceus)
Mori K, Inatomi S, Ouchi K, Azumi Y, Tuchida T. Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial. Phytother Res. 2009;23(3):367–372.
View source
[4]
Phosphatidylserine
Kato-Kataoka A, Sakai M, Ebina R, Nonaka C, Asano T, Miyamori T. Soybean-derived phosphatidylserine improves memory function of the elderly Japanese subjects with memory complaints. J Clin Biochem Nutr. 2010;47(3):246–255.
View source
[5]
Magnesium L-Threonate
Liu G, Weinger JG, Lu ZL, Xue F, Sadeghpour S. Efficacy and safety of MMFS-01, a synapse density enhancer, for treating cognitive impairment in older adults: a randomized, double-blind, placebo-controlled trial. J Alzheimers Dis. 2016;49(4):971–990.
View source

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