Methylation, and MTHFR SNPs. When clients come to me, typically these days they have had several tests done already because they have been trying to address their complex health concerns. It is common that people have had their genetic analysis done through a company such as 23andme and they then approach me saying, “I’m MTHFR so certainly there’s a problem”, or “I’m MTHFR – so that explains why I’m so messed up” and they’re looking to me to ‘fix’ their methylation status and then they’ll be fine.
Unfortunately, it just isn’t as simple as that.
Firstly, anyone’s methylation status cannot easily be read from their 23andme report, despite what it likes to tell you. And the bit of information you can glean from there may not actually explain anything at all.
But for those of you whom I have already lost with lists of words and letters that have completely confused… let us backtrack.
What Is MTHFR?
Let me start by saying that you can’t actually “be” MTHFR. Nor is it clinically correct to say that you have “The MTHFR Gene”, which I have heard on more than one occasion. But these phrases have fallen into a sort of lazy lexicon which people are beginning to use now that they realise that parts of our genetics can affect our overall function, sometimes with quite alarming and far-reaching impact.
MTHFR is short for Methylenetetrahydrofolate Reductase. Reductases are enzymes which break down substances in the body – and this one is used in a process (or cycle) called “methylation”. This enzyme is encoded by (i.e. the instructions for its production are held within) the MTHFR Gene. Everyone has the MTHFR Gene, hence why using the phrase “I have the MTHFR Gene” is accurate, but tells us nothing.
What most people mean when they say they ‘are’, or ‘have’, or ‘suffer with’ MTHFR is that they have had some genetic analysis done which shows that they have single nucleotide polymorphisms within the MTHFR Gene complex which encodes for the enzyme MTHFR.
In short, when you see on your 23andme data that you have a SNP in the MTHFR Gene, that means that only one – or sometimes two – amino acids within the complex is different to that which is ‘typical’. To put that in context, however, MTHFR is a complex with more than 500 amino acids.
But What Is Methylation?
MTHFR is the “rate limiting step” in the whole cycle that is known as the methylation cycle:
If you can make it out, MTHFR is one part of this massively intricate physiological process. This whole process is happening in every single one of your 37 trillion (plus) cells, every second of every day – billions of times per second. I’m not going to go massively into what methylation is or does within this article, because that could get hugely science-y and take up reams of space. Suffice to say methylation is vital and life would not exist without it. Essentially one molecule passes one of its methyl groups (one carbon and three hydrogen atoms) to another molecule. This process is important not only to create some essential substances that our body needs to survive (including influencing ATP production, the ‘energy currency’ in cells) but also to prevent the build up of some other substances that are less than ideal. More than this, however, it also regulates gene expression and it does seem to affect some systems more than others – and I will come back to this part of things a bit later.
So How Big Of A Deal Is MTHFR?
Well, this article might seem like it’s going in a specific direction – where I minimise the importance of MTHFR…
However, think of this whole methylation process like a really good, strong golf swing – with lots of power and force. One mutation within one amino acid in one enzyme in this massively complex chain is like being a millimetre off trajectory with that powerful golf swing. Because of the immense power within this cycle (or within that golf swing) millimetres matter.
And what begins as a millimetre off (or one amino acid amidst over 500) at the point of origin turns into a wildly out of kilter and off course trajectory at the extent of the swing.
That means that yes, a single nucleotide polymorphism within the gene that encodes for this enzyme can make a difference to your capacity to methylate. This ‘difference’ can drastically impact particular systems: most notably those revolving around bodily detoxification (because of its role in the production and metabolism of glutathione, the essential antioxidant for the liver’s detoxing capacity, the breakdown of histamine in the gut, and also neurotransmitter production and re-uptake.
When MTHFR Isn’t Relevant
The balance of me saying that MTHFR is important comes by me saying that there are probably countless individuals out there with SNPs within the MTHFR gene who have no idea and are symptom free. Remember that the phrase is ‘gene expression’. That simply means that some genes are expressed and some are not. So just because something is present within the genome does not mean that it is ‘switched on’, or expressing. And more than that:
An MTHFR gene mutation – even if it is being expressed (i.e. is ‘switched on’) – isn’t always a prescription for symptoms to be present.
The complex for MTHFR contains over 500 amino acids, and current genetic technology is capable of interpreting several of the locations within this gene. However, this doesn’t actually give us full diagnostic and clinical information. We are currently not able to read the whole genome, at least not in the more affordable tests on the open market. And even if we could sequence absolutely everything of your genome, we simply don’t know what all of it means yet. There is every chance that there is a compensatory SNP somewhere else in the genome of someone with one (or even two) of the known SNPs.
We are largely reverse analysing genetics currently: we are syndicating people and understanding it in the most primitive of ways. We aren’t finding what we thought: that specific traits, characteristics and features would always emerge out of the same locations and permutations of genetics. Instead we are finding that genetics is much more nuanced and variable than that.
So How Do You Know If It’s Important – For You?
Simply speaking, if you have a reduced ability to produce the MTHFR enzyme then what you are more than likely needing is to supplement with supplements that are already methylated, because it saves you from having to do this process yourself. For example, B12 is often available in many varieties – but if methylation is an issue, you are most likely to require methylcobalamin (i.e. methylated B12).
But there are real complications with this. For example, if you have other mutations in your genetics it might not be wise to go on piling on the methyl donors because you won’t be able to break down these substances and you create more problems than you solve.
22% of people are undermethylators. 8% are overmethylators, 70% are ‘normal’. 23andme may pick up some nuances which make people undermethylators, but as yet doesn’t go anywhere near to determining the overmethylators – and by focussing so much on MTHFR some clinicians and patients have neglected to understand that methylation is phenomenally complex. It has so many factors feeding into the cycle of methylation that all of these must be assessed if we are truly understand the methylation status of our clients.
So What Can We Do In Clinic?
Here is where I prefer to treat patients and not paperwork. If methylation is part of a genetic pattern AND symptom presentation then it is definitely something that can be incorporated into a treatment or supplementation protocol. But how do you tell?
Currently there are various ways in which we can test methylation itself – which is the entire point of knowing about MTHFR: how well are you methylating? The actual process of methylating the amino acids inside the body can be measured by assessing the various levels of amino acids such as SAMe and SAH, which you may have heard of. We can also check various blood levels or serum levels of nutrients to understand much more about the functioning of anyone’s body – checking homocysteine levels is done routinely and is a key first step in understanding the processing of any clients methylation capacity.
But notice that I say knowledge of MTHFR gene mutations or methylation status “can be incorporated into a treatment or supplementation protocol”. This is because MTHFR may be a factor in illness presentation, particularly in detoxification capacity as mentioned above, but it is often that generalised inflammation, food intolerances, oxidative stress, toxin overload, emotional trauma and lifestyle imbalance all contribute to the presentation of illness. Sure, adding in a methylated version of a B vitamin might tip a balance, but often it is only part of my approach, and it typically only emerges out of addressing the person as a whole, rather than their genetic report.
And yet there is one place where methylation status is so overwhelming correlated to illness presentation that I really pay attention to the testing and the treatment whilst looking through the lens of methylation.
Whilst I am yet to be fully convinced of all the science behind this, the more that I study mental health, the more I become convinced that methylation plays a key role in the development of issues. Rather than making it difficult to get well or detoxify some toxins etc, I am beginning to recognise that methylation plays such a vital role in the synthesis of, and importantly the re-uptake of, neurotransmitters that it could be the root cause, single unifying issue in countless mental health presentations: from the mild depression and anxiety to being implicated in ADHD, autistic spectrum conditions and even severe schizophrenia, bipolar and obsessive compulsive disorders.
I spend a long time with my clients in any case modulating their mental frameworks and discussing thoughts and the mental role in health. But I spend an equal amount of time reminding my clients that the brain is a physical organ, requiring nutrients and a lack of inflammation or excess stress just as much as any other physical system.
About 70% of people with mental health disorders have been shown to have serious methylation disorders. So here, knowing the methylation status is of vital importance (note: methylation status and NOT MTHFR SNPs from 23andme).
Someone’s nutrient and methylation status can drastically impact the direction of treatment and the effect of psycho-pharmaceuticals: turning them from being beneficial with side effects, to completely useless… to utterly damaging and making the condition worse.
But, more positively speaking, methylation impairment can so directly affect neurotransmitters in the brain that personality disorders, behavioural issues and characteristics that clients have come to recognise as ‘just them’ are able to be completely transformed. This can be as wide ranging as competitive tendencies, mouth/eye dryness, libido levels, socialisation tendencies, anxiety levels and sleep abilities.
And the beauty of this is that it is sometimes a little complex to fully understand the overlapping and integrated conditions occurring within any individual patient with various methylation issues, and what neurotransmitters are being affected. It also requires a care to fully comprehend the impact of changing supplement levels, and if the patient is already taking pscyho-pharmaceuticals the effect of these must be borne in mind…
However, methylation and many other factors which affect neurotransmitter production, re-uptake and breakdown, can all be improved – and often completely rectified – using simple nutrient supplementation. Tweaking the quantity of certain obvious nutrients within an individual can radically alter the brain’s function. This shouldn’t really be too surprising, as it’s just an organ after all. But it is astounding that some patients spend years battling mental health conditions when altering zinc, B6, folate, copper etc. levels may actually completely shift their neurotransmitter balance, and therefore their psychological wellbeing.
If you have been dealing with a mental health condition this may be something that you would like to discuss with someone qualified to understand brain function in the context of nutrients and neurotransmitters. This is not someone who will see your MTHFR status and immediately start supplementation, but someone who will take your genetics, your symptoms and some further (more comprehensive) testing and understand what role methylation might play in your neurotransmitter status. If you would like to contact me to discuss your mental health or methylation concerns, please just email me here.
And if someone you know is suffering with mental health concerns – please share this with them, or repost to your social media. Sometimes the simple is often overlooked when we become aware of the complexity of the human body. If nutrients might have the power to change someone’s experience of their life then all I would like is to give them the opportunity to find that solution.