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Methylation and mental health are intricately related. We take a deeper look into the association and why it is important

What is methylation? 

Methylation has been a buzzword in the integrative health sphere for some time now. This is unsurprising considering its importance to our overall health and wellbeing. You may have heard of it before – or even googled it… Were you then promptly turned off by it after just one glance at its complexity?

We don’t blame you, understanding methylation is not for the faint-hearted. 

However, let us break it down for you into bite sized chunks. Hopefully you can finally make sense of it and apply this knowledge to your everyday life. 

Think of it as a biological switch

Methylation is a critical biochemical process that happens billions of times in every single cell of the human body. It’s responsible for a vast range of biological functions such as: 

  • Detoxification
  • DNA expression
  • Neurotransmitter production
  • Hormone regulation

Whilst it can be complex in nature, the process of methylation simply entails the transfer of four atoms: one carbon atom and three hydrogen atoms. These are transferred from one substance to another.  

Let’s say that methylation is a type of biological switch that turns on and off to help keep our health in check. 

How does methylation impact mental health?

Whilst we know that methylation plays an intrinsic role in so many important functions in the body, for the purpose of this article, we will narrow the information down to its role in mental wellbeing and brain health. 

Put simply, methylation helps us make neurotransmitters, such as serotonin, dopamine, adrenaline, norepinephrine and melatonin. 

Methylation does this in a number of ways. It helps:

  • Convert tryptophan (building block for serotonin) to 5-HTP (precursor to serotonin) 
  • Transport dopamine, norepinephrine and adrenaline
  • Convert norepinephrine to adrenaline (important for focus and attention)
  • Lastly, convert serotonin to melatonin (sleep neurohormone) 

So as you can see, it’s pretty vital to a balanced mood and overall brain health. 

What impacts methylation? 

Unfortunately there are many things that can negatively impact methylation, such as our diet, exposure to environmental toxins, genetic factors and lifestyle habits. 

Let’s look at this in a little more detail. 

Anything that triggers oxidative stress can have a negative effect on methylation

Oxidative stress is a natural biological process that’s usually offset by our body’s own endogenous antioxidant production. But when there’s an imbalance between the two, and factors in our environment generating oxidative stress are tipping the scale in their favour, that’s when we can see prolonged inflammation and problems with methylation. 

What specific environmental factors can impact methylation?

Our modern environment is plagued with reactive oxygen species ROS that generate oxidative stress in the body. Key examples are environmental endocrine disruptors, like PCBs, herbicides, pesticides and plastisizers, as well as air pollution. 

Whilst we can’t necessarily fully control these aspects in our environment, we can control our defence against them, as well as making wise dietary choices that will have less of these substances in them. 

But first, let’s talk about what else can impact methylation.

Dietary factors and methylation

What you eat can impact how well you methylate – especially intake of processed foods and sugars, which has been shown to play a negative role in methylation.

Perhaps unsurprisingly, research shows that eating a wholefood diet that includes wholemeal cereals, fish, legumes, fruits and vegetables can have a positive effect on methylation. 

Aside from dietary factors, there are a few nutrients that play a critical role in methylation. 


Perhaps the most important nutrient is folate or B9. Methylation is almost entirely dependent on the availability of folate in the diet. It uses this nutrient to create the methyl donors – SAMe and methionine – to spark enzymatic reactions that are required for neurotransmitter production and transport. 

A large body of research confirms that folate deficiency – something that is incredibly common – is frequently seen in those with depression, and is remediated with the supplementation of this nutrient.

When we consider the role that optimal methylation plays in producing serotonin and other neurotransmitters, it’s easy to see why folate is so important. 

Be mindful with folic acid

Many are drawn to supplementing folate in the form of folic acid – the synthetic version of this nutrient. You can often find folic acid in fortified foods such as breakfast cereals and breads. 

However, what little people realise is that this version of folate needs to be converted in the body to l-methylfolate and many people lack the ability to do this efficiently due to gene variations. 

This means the body is unable to utilise the folic acid properly. 

We go into gene variants in a little more depth further down, so hold on for more information. 

Where can we get folate in our diet? 

Green leafy vegetables and legumes are perhaps the most rich sources of folate, so be sure to be getting these in your diet frequently.  


Whereas folate is important to initiate the methylation cycle, B12 is required for the activation of folate from dietary folate to  5-methyltetrahydrofolate, so that it can go on to create the methyl groups – SAMe and methionine.  

If there isn’t enough B12 in the diet, folate can get stuck in the cycle, which halts methylation. 

Where can we get B12 in our diet? 

B12 is a nutrient that’s found in animal foods, such as meats, fishes, eggs, poultry and dairy products. This means that if you’re vegan or vegetarian, you will likely need to supplement your B12 and consider eating fortified foods, such as plant milks. 


Choline plays an important role in various junctions in the methylation cycle. It is widely known that when folate is low, the body uses choline as its back up methyl donor to help keep methylation ticking along. 

Choline helps with activation of folate, as well as the recycling of homocysteine to methionine – a critical step in methylation. 

Having high homocysteine is a key way of indicating whether your methylation is struggling and whether this recycling process isn’t functioning properly. 

What’s wrong with homocysteine?

We don’t want accumulating levels of homocysteine as it is a neurotoxin that has been linked to psychiatric disorders such as depression, schizophrenia, bipolar and Alzheimer’s disease

This is why if mental health is a concern, testing for homocysteine is a great way to find out whether you may have issues methylating. 

Here’s a little more information on testing and further ways to check your methylation.

Testing methylation

In addition to homocysteine, which is explained in further detail below, you can also take a DNA test to see whether you have any mutations on the MTHFR gene – the primary gene that is responsible for folate activation and homocysteine recycling – both of which are necessary for optimal methylation and therefore neurotransmitter production.

Testing for MTHFR

Variants or mutations on the MTHFR gene are inherited from your parents and can either be heterozygous (meaning you have one mutation) or homozygous (two mutations). 

It’s well known that having a homozygous mutation is more likely to cause health problems and having a heterozygous mutation is unlikely to cause issues

Common variants are:

  • C677T 
  • A1298C

Testing for these variants is done by a simple saliva test and is usually done privately. Here in the UK, there are various providers such as Lifecode GX, however, if you’re not based in the UK there are likely many more providers globally. 

Testing homocysteine

Testing homocysteine levels is a little more invasive, as it requires a blood draw. 

Bear in mind that levels are not static and can change based on how well you’re methylating, as well as certain dietary factors, such as caffeine and alcohol consumption, which have been shown in some cases to tax methylation.

You can test your homocysteine here at Food for the Brain. Find details in our easy-to-order and simple pin-prick test here.  

How do we optimise methylation?

As well as eating a wholefood diet that is devoid of sugar and processed foods, if you suspect methylation may be an issue for you, it’s important to take the environmental factors listed above into consideration. 

In order to avoid toxins and pollutants you can:

  • Eat organic produce
  • Drink filtered water
  • Buy toxin free cosmetics that don’t include typical endocrine disruptors such as parabens, benzophenones, bisphenols, and phthalates
  • Avoid plastics (bottled water, cling film, plastic tupperware etc)
  • If you smoke, stop 

Work with a nutritionist

Working with a registered nutritionist is crucial for supporting the right supplementation programme in accordance to individual needs. 

You can find a network of nutrition professionals on BANT, as well as Nutritionist Resource

Key takeaway: genes load the gun, but it’s the environment that pulls the trigger 

Eating a healthy, balanced diet, as well as engaging in healthy lifestyle practices will always trump and cannot be replaced by supplements. 

Your environment includes your diet, lifestyle, sleep, exposure to toxins, relationships, where you live and so on. These are, for the most part, modifiable, and all play an essential role in how genes like MTHFR are expressed.  

This is good news as it means that you are in control of your health and can start taking the right steps today to help support your methylation and overall brain health and mental wellbeing. 

Enjoyed this article? Check out our blog for other deep dives into various aspects of nutrition, lifestyle and brain health.