The Role of Methylation in Brain Health, Mood, and Beyond

March 14, 2025 Bec Guild

You’ve probably heard the word ‘methylation’ come up in relation to a number of areas of wellbeing. Methylation is a fundamental biochemical process that occurs trillions of times every second in every cell of our bodies. This seemingly simple process has profound implications for our health, particularly for our brain.

What is Methylation?

At its core, methylation involves the addition of a single carbon and three hydrogen atoms, known as a methyl group, to another molecule at a cellular level.

We can think of it like a ‘switch’ turning genes on and off and influencing certain metabolic pathways. Methylation (ie. the donation of methyl groups) occurs body-wide at a cellular level, and influences gene expression, protein function, and the synthesis and metabolism of numerous compounds and neurotransmitters, impacting mood, immunity, inflammation and more.

SOURCE: Open Access Text

How Methylation Influences Mood and Brain Health

Gene Expression and Neurodevelopment: Methylation patterns regulate gene expression (DNA). Proper regulation is essential for brain development and the maintenance of neural plasticity, which affects learning, memory, and other cognitive functions.

Neurotransmitter Synthesis: Methylation is a crucial step in the synthesis of neurotransmitters like serotonin, dopamine, and norepinephrine, which influence mood, cognition, and behaviour. Imbalances in the nutrients that drive methylation can lead to mood dysregulation, including depression and anxiety.

Neural Protection: Methylation influences the production of myelin, the protective sheath around neurons. This not only ensures efficient nerve message transmission but also serves to protect against neurodegenerative disorders.

How Methylation Influences Inflammation and Immunity

Inflammation is a double-edged sword. While essential for healing, chronic inflammation can contribute to various illnesses, including neurodegenerative disorders. Healthy methylation is important because it regulates genes responsible for controlling inflammation, ensuring it is kept in check, remaining beneficial and not detrimental.

Additionally, healthy methylation supports the integrity of our blood-brain barrier, the vital defensive structure that prevents harmful substances from entering the brain which would trigger the immune system to respond. The immune system's efficient functioning relies on proper methylation.

How Methylation Impacts The Gut-Brain Connection

The gut-brain axis is our bidirectional communication system linking our central nervous system with our gastrointestinal tract. The quality of our gut health can influence brain function, and vice versa.

Methylation plays a role in influencing our gut bacterial composition, toxin detoxification as well as inflammation and immunity. Dysregulated methylation can contribute to gut dysbiosis and poorer detoxification capabilities and conversely, gut dysbiosis can impact methylation capabilities, highlighting the interdependent cross-over between methylation and our digestive wellbeing.

Supporting Methylation with Key Nutrients

Methylation can be supported through diet and supplementation. Macronutrients, like the amino acids from protein are important, and so are the micronutrients, like B vitamins, that function as co-factors in the methylation cycle.

Nutrients that can actively support, or influence our methylation pathways include;

Folate (also called Vitamin B9, eg. Quatrefolic®) : Due to its role in methylation, folate is critical for DNA synthesis and repair. It helps to make sure that when cells are copied, they do not initiate errors - this is what makes folate so important for pregnancy, but also for our healing and repair processes, as well as immunity.

Vitamin B12 (Eg. Methylcobalamin): Essential for nerve function and works alongside folate in the methylation cycle as an important co-factor in the activation step to create 5-methylfolate.
Betaine (also called Trimethylglycine): Acts as an important methyl donor, supporting S-adenyslmethionine (SAMe) which positively influences mood.
Vitamin B6: Is another essential co-factor that assists in the formation of neurotransmitters and is crucial for amino acid metabolism and homocysteine balance in the methylation cycle.
Vitamin B2: Another essential co-factor in methylation. It is also important for supporting healthy blood cells and helping to meet energy production needs.
Choline: Supports methylation by providing methyl groups (particularly important in the absence of sufficient folate!) and is crucial for brain, muscle and metabolic health.

It goes without saying that methylation is intricately woven into the fabric of our physiological processes, and is paramount for brain health, mood, inflammation, gut health, and immunity.

What’s more is that modern lifestyles, toxin exposures, nutritional deficiency, poor sleep, stress and certain medications can impact these important processes, further increasing the demands on nutritional needs.

Testing, to assess methylation is becoming more commonplace, particularly as awareness grows about the MTHFR polymorphism - but this is not the only gene that influences methylation, so it’s important not to supplement based on that single test alone, but to find support to look at the full upstream and downstream impacts on methylation, and using biohacking principles, personalise your supplementation choices to reflect individual needs.