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Methylation

Overview​

Methylation is a fundamental biological process that serves as a critical target in the BRAIN Diet. This biochemical process involves the addition of methyl groups to DNA, proteins, and other molecules, playing a crucial role in gene expression, neurotransmitter synthesis, and overall brain health.

Recipes​

Turkey Wing Stew

A collagen-rich, glycine-heavy slow-cooked stew made from affordable turkey wings — supporting gut, joint, sleep, and brain health.

Turmeric Lentil Dahl

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

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

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

Choline

Acetylcholine precursor; methyl donor; phospholipid synthesis for membranes

Chemical structure

Methionine

Essential AA; precursor to SAMe via methylation cycle

Omega-3 Fatty Acids

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

Chemical structure

Zinc

Cofactor in neurotransmission and antioxidant enzymes; dopamine modulation

Biological Implications​

B vitamins, particularly B6, B2, folate (5-MTHF), and B12, are essential cofactors in the remethylation of homocysteine (Hcy) to methionine, which is subsequently converted to S-adenosylmethionine (SAMe).

A precursor to the key coenzymes FMN (Flavin mononucleotide) and FAD (Flavin adenine dinucleotide). FAD acts as a critical cofactor for MTHFR, linking riboflavin to homocysteine recycling and methylation capacity. Riboflavin coenzymes facilitate the metabolism also of B12, vitamin B6, and niacin.

Elevated plasma homocysteine, a byproduct of methylation, is frequently elevated in ADHD and other neurodegenerative disorders, cognitive impairment, and psychiatric conditions. Hcy is implicated in the induction of oxidative stress, the modulation of oxygen levels, and the initiation of lipid peroxidation pathway.

Trimethylglycine (TMG), also known as betaine, is a dietary methyl donor that helps recycle Hcy to methionine via an alternative pathway. Choline, a precursor to both TMG and phosphatidylcholine (PC), is similarly involved in homocysteine clearance and membrane phospholipid biosynthesis. These pathways are vulnerable to genetic variants such as MTHFR polymorphisms, which reduce the efficiency of folate cycling and methylation, thereby increasing susceptibility to cognitive dysfunction and ADHD-related symptoms (paper.txt, line 483).

Dietary patterns can modulate gene expression and epigenetic regulation through multiple pathways. Nutrients involved in one-carbon metabolism (e.g., folate, riboflavin, B12, choline) can influence methylation dynamics relevant to MTHFR and COMT activity. Polyphenols and omega-3 fatty acids have been shown to upregulate BDNF expression, potentially offsetting functional impacts of the common Val66Met polymorphism (paper.txt, line 484).

Research indicates that deficiencies in vitamins and minerals essential for methylation, such as folate, vitamin B12, and zinc, are correlated to ADHD symptoms and that supplementing these micronutrients has shown potential in supporting methylation and reducing symptom severity (paper.txt, line 245).

References​

  • Riboflavin (B2) is a precursor to the key coenzymes FMN and FAD. FAD acts as a critical cofactor for MTHFR, linking riboflavin to homocysteine recycling and methylation capacity Aragão et al. 2024
  • A large meta-analysis shows that folic acid supplementation (0.5-5 mg/day) typically reduces plasma homocysteine by ~25%. Adding B12 gave an additional ~7% reduction over folate alone Collaboration 1998
  • Long chain ω-3 fatty acids and vitamin B12 contribute meaningfully to homocysteine reduction, and in combination more effectively. One study with vitamin B-12, fish oil, and vitamin B-12+fish oil lowered plasma Hcy concentrations by 22%, 19%, and 39%, respectively Tao Huang et al. 2015
  • B vitamin supplementation slowed cognitive decline only in participants with adequate omega-3 status, supporting a nutrient synergy model Oulhaj et al. 2016
  • Elevated plasma homocysteine is frequently elevated in ADHD and other neurodegenerative disorders, cognitive impairment, and psychiatric conditions Yu et al. 2020
  • Elevated plasma homocysteine is frequently elevated in ADHD and other neurodegenerative disorders Luzzi et al. 2022
  • Elevated plasma homocysteine is frequently elevated in ADHD and other neurodegenerative disorders, cognitive impairment, and psychiatric conditions Lukovac et al. 2024
  • Hcy is implicated in the induction of oxidative stress, the modulation of oxygen levels, and the initiation of lipid peroxidation pathway Lukovac et al. 2024
  • Deficiencies in vitamins and minerals essential for methylation, such as folate, vitamin B12, and zinc, are correlated to ADHD symptoms and supplementing these micronutrients has shown potential in supporting methylation and reducing symptom severity Razavinia et al. 2024
  • 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
  • B-vitamins play a central role in brain biology pathways Kennedy 2016
  • A lowered abundance of Bifidobacterium longum in infancy has been associated with increased risk of developing ADHD and Asperger syndrome in childhood Pärtty et al. 2015