Is ADHD A Methylation Problem?

mood learning & behaviour
Methylation and ADHD

Methylation, MTHFR, methyl-donors.... heard of this? Methylation is a fundamental biochemical process that happens in our bodies and over the last 20 years there has been lots of talk about how it impacts everything from heart disease to schizophrenia.

There's now quite a buzz suggesting that methylation imbalances might play a role in some cases of ADD and ADHD. 

This could be good news for parents since we know a lot about how to help a body methylate in a consistent and predictable way! In fact, seeing ADHD as a (partially) methylation issue gives us an even better understanding of why nourishment-focused strategies can help. 

Knowing your ADHD child's methylation status might help you zero in more quickly on ways to help them feel and function better.

This post goes into why methylation matters, how to assess it and what to do about it. 


What Is Methylation?

Simply put, methylation refers to our ability to create and use methyl groups - a molecular package that contains one carbon molecule connected to 3 hydrogen molecules.

Once formed, these carbon-hydrogen packages become some of the most important workhorses of the body engaging in over a billion processes a second inside every single one of our cells.

Every instant, methyl groups are transferred here and there to make things happen. It's kind of like working a dimmer switch - some processes need a methyl donor to rev up (like serotonin transport), while some processes need a methyl donor to rev down (like histamine production).

This process of methyl group donation keeps the body in a dynamic state of balance as it's exposed to... well.... life.

Here are some of the processes that involve the donation of methyl groups:

  • Methyl groups help in the conversion of serotonin to melatonin, our sleep hormone
  • Methyl groups activate the expression of certain genes - the COMT and HNMT genes, for example, can't function well unless methylated 
  • Methyl groups attach to folate to turn it into methylfolate which we need to make and recycle serotonin and dopamine, make more methyl donors, detoxify, and carry out several hundreds of other functions 
  • Methyl groups are needed for the breakdown of histamine and the regulation of inflammation
  • Methyl groups help flush certain metals like arsenic from the body
  • Methyl groups help repair DNA damage that might be caused by environmental toxins and other stressors 
  • Methyl groups are needed for the creation of phosphatidylcholine which is a critical component of our cell membrane.

These are just a few of the thousands of functions that happen every second that require methyl groups

Bottom line: Methylation is a core process that occurs thousands of time a second and impacts just about everything


All Roads Lead Back To Nourishment, Even With Methylation

We need an ample and consistent supply of methyl groups! They're critical to your child's function. But that doesn't mean we all need more carbon and hydrogen building bocks.

Many nutrients are involved in the creation and use of methyl group donors. Some nutrients involved are: zinc, B2, B3, B6, B12, iron, folate, magnesium, potassium. We also need sufficient protein.

Exercise (which I'd argue is also a form of nourishment) has also been shown to increase the production of methyl groups.

The more stressed we are the more methyl groups we burn through so helping your child feel relaxed, safe and connected (also part of nourishment in my books) will help ease the stress on the methylation system. 

The nourishment-dependent nature of methylation is one of the many reasons I almost always start by asking the families I work with, "what kind of nourishment can we add in?"  to help their struggling kids. 

Bottom Line: Kids need premium nourishment, in all its forms, to keep this methylation system functioning well! 

(related post: Top Mistake Parents Make When Changing Their Child's Diet)


Methylation And ADHD

The process of methylation impacts the brain in many ways. Here are just a few that help explain why methylation imbalances might correlate with symptoms of ADHD... 

  • Low levels of serotonin and dopamine are associated with poor sleep, poor bowel function, poor executive function, and impulsivity that can all be part of the ADHD picture (both of these neurotransmitters require methylation).
  • Low melatonin can lead to poor sleep quality which has been shown to exacerbate ADHD symptoms (without methyl donors melatonin might become deficient)
  • Overmethylation (less common, but characterized by having too many methyl donors) can lead to high levels of dopamine and adrenaline and contribute to panic, anxiety, poor concentration (TIP: if your child had negative side effects to stimulant or SSRI medications they might be overmethylating).
  • Our capacity to detoxify things like pesticides and environmental toxins requires methyl groups. If toxins build up they add significant stress and can lead to ADHD-like symptoms such as irritability, brain fog, energy crashes, memory problems, sleep issues.
  • High histamine is implicated in things like congestion, headaches, and bowel issues that further impact a child's ability to sleep, learn and feel good. High histamine can also be a factor in poor sleep, rage, and addiction. Even appetite can be affected by high histamine (when there are insufficient methyl groups histamine can become quite high)
  • Healthy mitochondria (our production centers for energy) require methylation. This means dysregulated methylation can affect our energy, memory, mood, executive function, and sleep via its effect on mitochondria.
  • Methyl donors are used in the creation of phosphatidylcholine and acetylcholine. Acetylcholine is a chief neurotransmitter of the parasympathetic nervous system and is important for memory and cognition

Bottom Line: your ADHD child might have a methylation imbalance.


How Do You Assess Methylation Status?

There are a few different ways to assess your child's methylation status. 

Whole Blood Histamine

Dr. William Walsh spearheaded the idea of using histamine as a marker for methylation function. Since histamine production needs a methyl donor to be dimmed down, people who are undermethylating (lacking methyl donors) are likely to show high whole blood histamine. Conversely, those who are overmethylating (overproducing methyl donors) are likely to show abnormally low levels of whole blood histamine. People who are methylating well are likely to have just the right amount of histamine.

Clinically, histamine has turned out to be a very helpful marker, but it requires a blood draw, and might not be readily available to everyone outside of the US. Also, some medications like Lexapro, Cymbalta, Clozapine, Risperidone, Xanax, Klonopin, and Trazadone will raise histamine by a different mechanism. So this route might not be best if your child is already on medication.

Symtpom Questionnaires

Alongside finding new biomarkers for methylation status, Dr. Walsh has spent about 40 years cataloging and refining character traits that correlate with the biochemistry of overmethylation and undermethylation.  He describes them in his book, Nutrient Power.

For example, overmethylators have a tendency towards high anxiety and panic, while undermethylators tend to be competitive and perfectionistic, trend towards OCD type behavior and often have allergies. Both types can be prone to depression and sleep disorders. 

Using a questionnaire like this is of course not diagnostic, but it can be a useful adjunct tool as you look for clues to help understand your child.

Genetic Testing

There are some key genes involved in the process of methylation. They include (but are not limited to) MTHFR1298, MTHFR677, FOLR2, and TCN2. Factors in utero and in early childhood can create variants in these genes, impacting how they function. If there are variants in these genes alongside symptoms, there might be a methylation problem.

Genetic tests, usually done by saliva, do not tell you exactly how methylation is functioning but they do give you a blueprint outlining tendencies. When used in combination with a detailed symptom history, the questionnaires, and other functional tests listed here, genetic tests can be a useful tool to piece together the picture so you can start some methylation-support. 

Organic Acids

Looking at urinary organic acids is an indirect way of assessing methylation status. Like all functional tests, an organic acid test is a way of looking for clues about how the body is functioning so you can target areas that need support. It's not diagnostic of a condition.

In terms of methylation, Uracil and Thymine, two metabolites of folate metabolism, are helpful markers. Uracil needs to be methylated to convert into Thymine, so if your child is lacking methyl groups we might see elevated Uracil in relation to Thymine as it gets "backed up".

Other methylation clues from organic acids are high levels of 2-Hydroxybutyric acid, low levels of Pyroglutamic acid and high levels of methylmalonic acid (a metabolite of B12).

Bottom Line: There's genetic tendency and then there's real-time function when it comes to methylation. Both can be helpful to know.


Are Methylation Imbalances Genetic?

As mentioned, our baseline capacity to work the dimmer switch of methylation is thought to largely be determined in utero. If, for example, you have a variant in one of the MTHFR genes you probably are not efficiently converting folate into its usable form, methylfolate. If that's happening the whole methylation cycle (and any other process that requires methylfolate) is likely to slow down.

BUT... and it's a big but... research in Epigenetics has shown us that how you methylate can actually change over time regardless of genetics.  

How the process of methylation functions minute to minute is affected by things like what we eat, what supplements we take, our environment, what chemicals we're exposed to, and our stress load. It's in these lifestyle strategies where, as parents, we can have the greatest impact.

Another way to think of it is that getting a genetic test can be a helpful blueprint to map out a person's tendencies when it comes to methylation, but we have an awful lot of control over how those tendencies are actually expressed through the choices we make. 

Your child's methylation genetics might be great and yet they still have functional methylation imbalances; their genetics might be terrible and yet they might be perfectly healthy. Some of the factors that can interfere with methylation regardless of genetics are: nutrient poor diet, candida yeast and other gut infections, mold exposure, sedentary lifestyle, excessive stress.

So you will find it helpful to look at your child's genetic blueprint as a piece of the puzzle. But genetics are most helpful when looked at alongside functional tests like histamine or organic acid tests and symptom questionnaires so you can piece together your plan based on what's actually happening.

Bottom Line: Your child's capacity to function well is about more than their genetics


The Bottom Line (of the Bottom Line)

ADHD is a complex situation that more than likely has a multitude of contributors. But research is showing compelling evidence that many kids who have ADHD struggle to methylate well (see selected references below).

Methylation capacity can have a genetic component to it (which might help explain why ADHD also has a strong genetic component), but it is also very much affected by nutrients, stress, exercise, and lifestyle (which might explain why nutritional and lifestyle measures can be so helpful).  

So knowing your child's methylation status might be one way to more quickly land on targeted nutritional tools to help them feel and function better and be more successful.

In your older child, this information can also help them understand their tendencies so they can better grasp why you're asking them to make good choices around food, supplements, exercise, stress reduction and sleep.

Knowing your child's methylation status can be incredibly empowering!

(Related article: Nutritional Approaches to ADHD, where do you start? )


Selected References:

Folate Fact Sheet

DNA methylation profiles at birth and child ADHD symptoms

Attention, cognitive control and motivation in ADHD: Linking event-related brain potentials and DNA methylation patterns in boys at early school age

Histamine in the brain

An emerging role for epigenetic factors in relation to executive function

Dopaminergic gene methylation is associated with cognitive performance in a childhood monozygotic twin

Walsh, William. Nutrient Power: Heal Your Biochemistry and Heal Your Brain. 2014

Bergen, S. E., Gardner, C. O. & Kendler, K. S. Age-related changes in heritability of behavioral phenotypes over adolescence and young adulthood. Twin Res. Hum. Genet. 10, 423–433 (2007).   ;  

Larsson, H., Chang, Z., D’Onofrio, B. M. & Lichtenstein, P. The heritability of clinically diagnosed attention deficit hyperactivity disorder across the lifespan. Psychol. Med. 44, 2223–2229 (2014)


About Jess Sherman, FDN-P, M.Ed, R.H.N

Jess is a Functional Diagnostic Nutrition® Practitioner, Registered Holistic Nutritionist and a trauma-sensitive Family Health Educator specializing in brain health & resilience for kids. She is also a teacher, with a Master's degree in education. Her Calm & Clear Kids introductory course, her Amino Acids (with kids!) Quickstart program, and her signature Resilience Roadmap,  along with her book Raising Resilience, have helped families in at least 44 countries improve the lives of their children with learning differences, anxiety, ADHD, and mood disorders and reduce their reliance on medication. She is the 2019 recipient of the CSNNAA award for Clinical Excellence for her work with families, and she continues to bring an understanding of the 5 Core Needs For Resilient Health to the mainstream conversation about children’s mental health, learning, and overall resilience through her blog, courses, workshops and as a contributor to print and online magazines. 

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The content on this website and in the guides and courses offered here is meant to provide information so that parents can make informed decisions and discuss these issue with their health care teams. It is not intended as, nor should it be considered a substitute for professional medical advice, diagnosis, treatment, or individualized care.