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Mitochondrial Support

Overview​

Mitochondrial support is a fundamental biological target in the BRAIN Diet, focusing on enhancing cellular energy production and reducing oxidative stress in brain cells. Neurodevelopmental disorders such as ADHD, ASD, and bipolar disorder, and neurodegenerative conditions like Alzheimer's and Parkinson's disease share overlapping biological dysfunctions, including mitochondrial impairment. Vitamins and minerals function as indispensable micronutrients and enzymatic cofactors in all pivotal brain biology pathways, aiding neurotransmitter synthesis, mitochondrial energy production, DNA repair, antioxidant defense, methylation, and the regulation of neuroplasticity (paper.txt, lines 132, 235).

Recipes​

Mitochondrial Power Bowl

A nitrate-rich, polyphenol-dense bowl supporting mitochondrial function, ATP generation, and metabolic resilience

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

Coenzyme Q10 (CoQ10)

Electron transport chain cofactor and antioxidant relevant to mitochondrial function

Chemical structure

Creatine

Phosphocreatine system buffer for neuronal ATP demand; cognitive support evidence

Chemical structure

Oleuropein

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

Chemical structure

Taurine

Osmoregulator; GABA modulation; mitochondrial membrane stabilizer; anti-inflammatory

Chemical structure

Butyrate

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

Chemical structure

Urolithin A

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

Chemical structure

Magnesium

Enzymatic cofactor (>300 reactions); neurotransmitters; mitochondria; redox balance

Chemical structure

Iron

Oxygen transport; dopamine synthesis (tyrosine hydroxylase cofactor)

Chemical structure

Manganese

Cofactor for MnSOD (SOD2); mitochondrial antioxidant defense

Chemical structure

Selenium

Antioxidant enzyme cofactor (GPx); supports redox balance

Biological Implications​

Neurodevelopmental disorders such as ADHD, ASD, and bipolar disorder, and neurodegenerative conditions like Alzheimer's and Parkinson's disease have complex, multifactorial origins. Although the precise causes are not fully understood, these conditions share overlapping biological dysfunctions, including mitochondrial impairment, chronic inflammation, oxidative stress, impaired methylation, gut–brain axis disruption, glucose dysregulation, micronutrient deficiencies, and neurotransmitter imbalances (paper.txt, line 132).

Vitamins and minerals function as indispensable micronutrients and enzymatic cofactors in all pivotal brain biology pathways, aiding neurotransmitter synthesis, mitochondrial energy production, DNA repair, antioxidant defense, methylation, and the regulation of neuroplasticity. Their availability can determine whether compounds such as omega-3 fatty acids, polyphenols, or amino acid precursors exert their intended effects. This interdependence highlights the importance of viewing nutrition as an interdependent system (paper.txt, line 235).

The omnivore version of the diet also incorporates nutrient-dense animal foods such as seafood, eggs, fermented dairy, occasional offal (liver), and lean animal proteins which supply other essential key brain nutrients such as omega 3, creatine, CoQ10, and taurine (paper.txt, line 156).

Creatine supports ATP recycling in neurons and enhances working memory and cognitive processing speed. It is found in beef, lamb, pork, salmon, tuna, cod, and scallops, with minimal amounts in seaweed (e.g., nori). Vegan diets lack creatine; supplementation or fortified foods may be needed (paper.txt, line 279).

Coenzyme Q10 (CoQ10) supports mitochondrial electron transport and provides antioxidant protection for neurons. It is found in organ meats (heart, liver), oily fish (sardines, mackerel), beef, and in smaller amounts in spinach, broccoli, pistachios, and olive oil. Plant forms (ubiquinone) are less concentrated; deficiency risk is higher with age (paper.txt, line 280).

The implementation of the BRAIN diet must go beyond a standard nutrient density focus; it's about choosing foods for their specific bioactive potential: early harvest extra virgin olive oil with higher levels of CoQ10, oleuropein and polyphenols (paper.txt, line 250).

Glutathione (GSH) is one of the body's major antioxidants. Low levels may suggest oxidative stress; elevated GSH levels which have been recorded against ADHD subjects may reflect a compensatory response to increased oxidative stress. Furthermore, mitochondrial metabolism of lactate depends on GSH for ROS neutralization, optimizing mitochondrial energy use (paper.txt, line 653).

Higher polyphenol intake and microbial diversity increase urolithin A and related metabolites, supporting mitochondrial resilience and mitophagy and in turn improving cognitive endurance. Hypothesis: these effects may extend to executive function (to be tested via Stroop/task-switching/n-back) (paper.txt, line 586).

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. Boosting SCFA production enhances mitochondrial and neurotrophic support, contributing to brain energy balance and resilience (paper.txt, lines 526, 602).

Excess oxalate may disrupt mitochondrial function and redox status. Boiling spinach, kale, and other greens can reduce oxalate load, improving mineral bioavailability (paper.txt, line 207).

B6 is a cofactor in the development of all the key neurotransmitters. Only once pyridoxine (PIN), pyridoxal (PAL), pyridoxamine (PAM) cross the blood–brain barrier in their non-phosphorylated forms, can they be converted into pyridoxal-5'-phosphate (PLP or P5P), the active coenzyme form. This means that systemic supplementation with PLP does not bypass the brain's reliance on its own enzymatic machinery. Instead, they require pyridoxal kinase (PDXK) activity, which is supported by cofactors such as magnesium and ATP (paper.txt, line 359).

References​

  • Neurodevelopmental disorders such as ADHD, ASD, and bipolar disorder share overlapping biological dysfunctions, including mitochondrial impairment Tardy et al. 2020
  • Vitamins and minerals function as indispensable micronutrients and enzymatic cofactors in all pivotal brain biology pathways, aiding neurotransmitter synthesis, mitochondrial energy production, DNA repair, antioxidant defense, methylation, and the regulation of neuroplasticity Tardy et al. 2020
  • Higher polyphenol intake and microbial diversity increase urolithin A and related metabolites, supporting mitochondrial resilience and mitophagy Singh et al. 2022
  • Urolithin A supports mitochondrial resilience and mitophagy and in turn improves cognitive endurance Andreux et al. 2019
  • Urolithin A supports mitochondrial resilience and mitophagy and in turn improves cognitive endurance Hou et al. 2024
  • Butyrate supports mitochondrial function, enhancing brain energy metabolism, which may help with cognitive impairments seen in ADHD Rose et al. 2018
  • Glutathione (GSH) is one of the body's major antioxidants. Elevated GSH levels which have been recorded against ADHD subjects may reflect a compensatory response to increased oxidative stress Verlaet et al. 2019
  • Mitochondrial metabolism of lactate depends on GSH for ROS neutralization, optimizing mitochondrial energy use Verlaet et al. 2019
  • Coenzyme Q10 (CoQ10) supports mitochondrial electron transport and provides antioxidant protection for neurons Zmitek, Rodríguez-Aguilera, and Pravst 2014
  • Creatine supports ATP recycling in neurons and enhances working memory and cognitive processing speed (paper.txt, line 279)