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Inflammation

Overview​

Chronic inflammation is a biological dysfunction that contributes to cognitive, emotional, and behavioral dysregulation in ADHD and other neurodevelopmental conditions. Neurodevelopmental disorders such as ADHD, ASD, and bipolar disorder, and neurodegenerative conditions like Alzheimer's and Parkinson's disease, share overlapping biological dysfunctions, including chronic inflammation, oxidative stress, impaired methylation, gut–brain axis disruption, glucose dysregulation, micronutrient deficiencies, and neurotransmitter imbalances. The BRAIN Diet targets inflammatory pathways through anti-inflammatory nutrients, gut barrier support, and strategies to reduce inflammatory load (paper.txt, lines 132, 505).

Recipes​

Ginger Yogurt and Blueberries

An Anti-inflammatory polyphenol-rich breakfast bowl with high fibre. Start the day with anti-inflammatory gingerols and omega 3 nuts, blueberry polyphenols, a fibre from steel rolled oats. Great to set up dopamine for focus and attention.

Turmeric Lentil Dahl

Anti-inflammatory curcumin-rich lentil dish supporting gut health, NF-κB inhibition, and SCFA production

Turmeric Milk

A warming drink combining turmeric (curcumin) with milk/fat for enhanced curcumin absorption

Therapeutic Areas​

ADHD

Dietary strategies targeting inflammation, neurochemical balance, mitochondrial function, and gut-brain axis to support attention, focus, and executive function

Alzheimer's Disease

Dietary interventions targeting mitochondrial function, oxidative stress, inflammation, and neurochemical balance to slow cognitive decline and support neuroprotection

Anxiety & GAD

Nutritional strategies targeting HPA axis regulation, stress response, neurochemical balance, and gut-brain communication to reduce anxiety and support emotional regulation

Bipolar Disorder

Nutritional approaches to support mood stability and cognitive function through modulation of neurotransmitter balance, mitochondrial health, and inflammatory pathways

Depression & MDD

Food-first dietary interventions targeting neurochemical balance, inflammation, gut-brain axis, and metabolic health to support mood regulation and emotional resilience

Substances​

Chemical structure

Berberine

Polyphenolic alkaloid; glycemic control; antimicrobial effects; microbiome modulation

Chemical structure

β-Carotene

Neuroprotective carotenoid; vitamin A precursor; supports immune regulation and neuronal development

Chemical structure

Lutein

Neuroprotective carotenoid; accumulates in neural tissues and retina; supports cognitive performance

Chemical structure

Lycopene

Neuroprotective carotenoid; found in tomatoes; absorption enhanced by cooking and dietary fat

Chemical structure

Zeaxanthin

Neuroprotective carotenoid; accumulates in neural tissues and retina; supports cognitive performance

Chemical structure

Curcumin (Turmeric)

Anti-inflammatory, antioxidant; bioavailability enhanced with piperine and fats

Chemical structure

Genistein

Soy isoflavone; ECS modulation via FAAH inhibition; anti-inflammatory/neuroprotective

Chemical structure

Oleocanthal

Secoiridoid polyphenol in extra-virgin olive oil; NF-κB inhibition and anti-inflammatory effects

Chemical structure

Oleuropein

Major secoiridoid polyphenol in olive oil; oleuropein aglycone supports mitophagy, SIRT1, and AMPK activation

Chemical structure

Acetate

Most abundant SCFA supporting gut barrier integrity and immune regulation

Chemical structure

Butyrate

Key SCFA supporting mitochondrial function, gut barrier integrity, and neuroinflammation reduction

Chemical structure

Propionate

SCFA supporting neuroinflammation reduction, blood-brain barrier protection, and neurotransmitter regulation

Chemical structure

Urolithin A

Microbiome-derived metabolite from ellagitannins; supports mitochondrial resilience and mitophagy

Chemical structure

DHA (Docosahexaenoic Acid)

Accounts for ~10–15% of total brain fatty acids, 20–30% of neuronal phospholipids (PE, PS), and >90% of brain omega-3 PUFA; critical for membrane fluidity, synaptic vesicle fusion, neurodevelopment

Omega-3 Fatty Acids

(EPA, DHA) Anti-inflammatory, membrane, and neuromodulatory lipids central to BRAIN Diet

Chemical structure

Copper

Cofactor in redox enzymes; dopamine β-hydroxylase; iron metabolism interplay

Chemical structure

Zinc

Cofactor in neurotransmission and antioxidant enzymes; dopamine modulation

Biological Implications​

Neuroinflammation Mechanisms​

High levels of ROS can cause astrocytes and microglia to become activated; reactive astrocytes can release pro-inflammatory cytokines (e.g., ADHD associated biomarkers IL-6, IL-1β, TNF-α), exacerbating inflammation and neuronal damage creating a vicious cycle. This vicious circle may increase the risk of ADHD pathogenesis (paper.txt, lines 735-736).

Gut-Brain Axis and Inflammation​

The gut barrier is the dynamic interface between the microbiome, immune system, and brain. Its integrity is critical: when the barrier weakens, bacterial fragments such as lipopolysaccharide (LPS, a bacterial endotoxin) and dietary antigens enter circulation, sustaining chronic low-grade inflammation and altering neurotransmitter metabolism. These processes are strongly correlated with poor cognitive function, fatigue, mood instability, and ADHD symptom severity (paper.txt, line 505).

Diets rich in probiotics, prebiotics, and fibre (which help produce short-chain fatty acids like butyrate, propionate and lactate) can enhance gut health. Furthermore, a decreased microbial diversity (alpha diversity) has also been reported in ADHD and may contribute to 'leaky gut' syndrome and contribute to the low-grade systemic inflammation reported in ADHD (paper.txt, line 521).

Butyrate and Neuroinflammation Reduction​

Butyrate has anti-inflammatory effects, potentially reducing neuroinflammation associated with ADHD. Butyrate supports mitochondrial function, enhancing brain energy metabolism, which may help with cognitive impairments seen in ADHD while also aiding in reducing cholesterol and neuroinflammation (paper.txt, lines 525-526).

Propionate research suggests that increased propionate levels could help reduce neuroinflammation and enhance cognitive function while protecting the blood-brain barrier and stimulate the secretion of norepinephrine, possibly benefiting ADHD symptoms like attention and focus (paper.txt, line 527).

Omega-3 Fatty Acids and Inflammation Resolution​

In a controlled endotoxemia model, high-dose EPA+DHA (3.6 g/day) attenuated fever and downstream cytokines (IL-6, IL-10), even though TNF-α remained unchanged, suggesting that omega-3s reshape the resolution phase of acute inflammation rather than block its initiation. The endotoxemia model is discussed as an analogue of postprandial inflammation, which is highly relevant as ADHD is associated with metabolic disorders, and specifically linked to postprandial inflammation (paper.txt, line 462).

Specialized pro-resolving mediators (SPMs), derived from omega-3s (DHA and EPA), play an active role in terminating inflammation without suppressing immune surveillance. These include resolvins, protectins, and maresins, which exert effects such as inhibition of neutrophil infiltration, downregulation of COX-2, and enhancement of macrophage-mediated clearance of cellular debris. Moreover, SPMs modulate endothelial function through nitric oxide release and support neuroprotection by limiting glutamate-induced excitotoxicity and promoting regulatory T-cell differentiation (paper.txt, line 460).

Postprandial Inflammation​

ADHD is associated with metabolic disorders, and specifically linked to postprandial inflammation. This postprandial inflammation is relevant to the endotoxemia model, where omega-3s reshape the resolution phase of acute inflammation (paper.txt, line 462).

Immune Dysfunction and Allergies​

There are many scientific findings supporting dietary antioxidant treatment of ADHD which accounted for substantial alterations in the immune system, epigenetic regulation of gene expression, and oxidative stress regulation in ADHD and also how immune dysfunction results in increased IgE levels and allergies, another link between ADHD (paper.txt, line 632).

Polyphenols and Anti-Inflammatory Effects​

Quercetin has antioxidant, anti-inflammatory, and anti-neuroinflammatory and neuroprotective properties. Quercetin bound to a sugar molecule forming quercitrin has anti-inflammatory and anti-oxidative effects may be augmented by the co-ingestion of N-3 polyunsaturated fatty acids and olive oil (paper.txt, line 675).

Genistein, a soy-derived isoflavonoid, has shown potential as a modulator of several biochemical pathways, including the endocannabinoid system and neuroinflammation, potentially enhancing the activity of certain endocannabinoids like anandamide (paper.txt, line 677).

Carotenoids, particularly lutein, zeaxanthin, and β-carotene, play a neuroprotective role through their antioxidant and anti-inflammatory properties. These fat-soluble pigments accumulate selectively in neural tissues, including the retina and brain, where they help scavenge reactive oxygen species and stabilize cell membranes (paper.txt, line 647).

Integration with Other Systems​

The BRAIN Diet targets inflammatory pathways by combining polyphenol-dense foods, omega-3s, and gut-supportive nutrients to reduce inflammatory load. Dietary polyphenols, prebiotic fibres, and lactobacilli strains have been shown to reduce LPS translocation and neutralize its inflammatory signaling, underscoring the microbiome's role in inflammation control (paper.txt, line 789).

References​

  • High levels of ROS cause astrocytes and microglia activation, releasing pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) associated with ADHD Chang et al. 2020
  • The gut barrier is the dynamic interface between the microbiome, immune system, and brain. When the barrier weakens, bacterial fragments such as lipopolysaccharide (LPS) enter circulation, sustaining chronic low-grade inflammation Mohammad and Thiemermann 2021
  • A decreased microbial diversity (alpha diversity) has also been reported in ADHD Prehn-Kristensen et al. 2018
  • Butyrate has anti-inflammatory effects, potentially reducing neuroinflammation associated with ADHD Yunting Li et al. 2024
  • Butyrate aids in reducing cholesterol and neuroinflammation Cavaliere et al. 2022
  • Increased propionate levels could help reduce neuroinflammation and enhance cognitive function while protecting the blood-brain barrier Grüter et al. 2023
  • Propionate can stimulate the secretion of norepinephrine, possibly benefiting ADHD symptoms like attention and focus Hoyles et al. 2018
  • In a controlled endotoxemia model, high-dose EPA+DHA (3.6 g/day) attenuated fever and downstream cytokines (IL-6, IL-10), suggesting that omega-3s reshape the resolution phase of acute inflammation rather than block its initiation Ferguson et al. 2014
  • ADHD is associated with metabolic disorders, and specifically linked to postprandial inflammation Brown et al. 2025
  • Specialized pro-resolving mediators (SPMs), derived from omega-3s (DHA and EPA), play an active role in terminating inflammation without suppressing immune surveillance Serhan and Petasis 2011
  • Immune dysfunction results in increased IgE levels and allergies, another link between ADHD Wesselink et al. 2019
  • Quercetin has antioxidant, anti-inflammatory, and anti-neuroinflammatory and neuroprotective properties Tongjaroenbuangam et al. 2011
  • Quercetin bound to a sugar molecule forming quercitrin has anti-inflammatory and anti-oxidative effects that may be augmented by the co-ingestion of N-3 polyunsaturated fatty acids and olive oil Camuesco et al. 2006
  • Genistein has shown potential as a modulator of several biochemical pathways, including the endocannabinoid system and neuroinflammation Fuloria et al. 2022
  • Carotenoids play a neuroprotective role through their antioxidant and anti-inflammatory properties Johnson 2014