Why Is Methylation Important Anyway? Gene Regulation.

MTHFR is the rate-limiting enzyme in the methylation cycle, so the whole cycle turns into a bottle-neck at this point very easily. The methylation cycle is something we’ll talk about in greater detail later on because methylation matters. At its most basic it converts homocysteine, which is inflammatory, into methionine and ultimately SAMe. SAMe is the universal methyl donor and is necessary for almost all methylation reactions.

One simple way to illustrate the importance of methylation is to talk about gene expression. The processes in your body are essentially run by your genes. In order to turn on or off certain genes, they must be methylated. If we’re talking about the gene function of apoptosis or programmed cell death, then you really want it to be working when it should be.

Apoptosis is one of the ways your body protects itself from damage. When the gene is on (or unmethylated), the cell will self-destruct if it gets damaged. That is a good thing. If it is off (or methylated), then the cell will continue to replicate out of control even when it’s damaged. We have a word for that – it’s cancer. This could be one reason why MTHFR polymorphisms have been linked to so many different types of cancer – because your body just can’t methylate or unmethylate properly.

A methylated gene is inactive, while an unmethylated gene is active.

Outside of the methylation of genes, you also have to methylate some toxins in order to eliminate them, which means people with MTHFR mutations have differences in the way they process things like alcohol, formaldehyde, certain pharmaceutical drugs, hormones, and many other things. Methylation is also crucial when you’re building neurotransmitters like serotonin, dopamine, epinephrine, and norepinephrine.

Perhaps now it is easier to see why the internet is abuzz with news of MTHFR. A lot of this information is incredibly beneficial and helpful and accurate and some of it is a little bit crazy-making. The echo chamber of the internet does tend to amplify noise.

Why is Methylation Important? Methylation Matters For…

  • Gene Expression
  • Toxin Elimination
  • Hormone Balance (because hormones get detoxed too)
  • Neurotransmitter Formation.

That pretty much sums up why MTHFR matters so much and why methylation is important – because those four things, combined with nutrition, are literally the foundations of a healthy human. We’ll talk about the last three in seperate topics, but today I want to focus on gene expression.

What IS Methylation? Really?

Methylation is so anti-climactic when you really get down to the nitty-gritty. It’s the addition of a methyl group to whatever you’re methylating. That begs the question what is a methyl group?

The Demented, three-eared Mickey Mouse of Methylation

Um… What Am I Looking AT?

Outside of a mutant mouse head, it’s actually the chemical structure of a methyl group. One big carbon and three hydrogens bonded to it. This methyl group is the functional part of 5, L-methyltetrahydrofolate, or 5, L-MTHF, which is the valuable thing that you get out of the magic chair after the less valuable thing (folic acid) sits down. If this is all gibberish right now, read this post here or listen to the podcast from the beginning.

The mutant mouse, with labels. It’s mutant Mickey for us mutants.

If you’d like a fancier, more chemistry-looking version, it’s here. This is the entire molecule of 5, L-methyltetrahydrofolate, courtesy of PubChem, with the methyl group circled.

The Mutant Mouse Head is Causing All This Fuss?


If you picture your body like a vast, complex lego structure that moves little lego pieces around to get things done, then the mutant mouse head methyl group is one of the foundational pieces that moves around all over the place. It’s a simple on/off switch for genes, but as it happens, being able to turn genes on and off is crucial.

Why Do We Need To Turn Genes On And Off?

We have the tendency to think of our genes like a recipe out of a recipe book. The directions to follow to build (or maybe to bake) a human. This is both accurate and not complete. Your genes are the recipe to build you, but they’re filled with stretches of information that has come from outside of you, like from viruses, or information that isn’t directly used to build anything. There are also lots of bits that we don’t fully understand.

45% of your genome is composed of transposable or viral DNA. Transposable elements are called “jumping genes” and are not fully understood. They do contribute to mutations as well as a number of diseases including hemophilia, severe combined immunodeficiency, porphyria, muscular dystrophy, and Alzheimer’s disease. Viral DNA is literally leftover from viruses, and so methylating these elements well allows your body to silence them. If you aren’t methylating properly, then these genes can start to express, causing genetic errors, and potentially disease.

Some of the most critical DNA methylation happened during embryonic development, well before you were born. There is also ongoing methylation that happens as cells divide and it is especially relevant within brain cells. We don’t know a lot about it, but we do know this:

  • Methylation within brain cells can be altered by drugs like cocaine, stress, and seizures.
  • Childhood stress or abuse has a carry-over to the way adult brains methylate their DNA
  • DNA methylation changes are associated with, among other things, major psychosis.
  • Altered DNA methylation in the brain is linked to psychiatric disorders including schizophrenia and bipolar disorder.
  • DNA methylation is especially crucial when you’re making babies. Human eggs, sperm, and ultimately the embryos that they produce are all new cells, meaning that lots of DNA needs to reproduce (and methylate) for this to work out.

Can We Actually Impact This By Optimizing Methylation?

According to sperm studies, we can. Sperm seems like a bit of a random thing to analyze, but the fact is; men make sperm fresh daily. It’s a great way to measure current activity vs. what happened during growth and development.

This study, published in Human Molecular Genetics, of infertile men with a variety of MTHFR statuses (wild type, homozygous or heterozygous for C677T polymorphisms) shows high-dose folic acid changes sperm DNA methylation across the genome.

This study provides evidence that high-dose folic acid supplementation leads to genome-wide alterations in sperm DNA methylation…Homozygosity for the MTHFR C677T polymorphism was demonstrated as a factor that can modify the response to high-dose folic acid supplementation.

Aarabi M, San Gabriel MC, Chan D, et al. High-dose folic acid supplementation alters the human sperm methylome and is influenced by the MTHFR C677T polymorphism. Hum Mol Genet. 2015;24(22):6301-6313. doi:10.1093/hmg/ddv338

While I’d love to see the same study repeated with a more bioavailable form of folate than folic acid, this is still great data. I take it to mean that we can influence the methylation of our DNA by optimizing our methylation cycles. That is a really big deal.

Next week we’ll talk about methylation and detoxification because when we’re talking about optimizing methylation, you have to understand why “detoxing” and also toxin avoidance are so important for MTHFR mutants.

Share with friends:

Health Problems Linked to MTHFR mutations

Mutation Sounds So Serious and Certain – Can I Change This?

I use the term “mutations” or “mutant” mostly because I like them. MUTANT sounds so very X-men and god knows I’m a sci-fi geek. Technically, the correct term is “polymorphisms,” which is less dramatic and doesn’t imply eyeball laser beams. Polymorphisms are simply small differences – one letter substitutions – in a gene. SNP (Single Nucleotide Polymorphisms, pronounced “snip”) are part of the wonderful and astounding variability of human genetics.

SNPs or single nucleotide polymorphisms are essentially a letter substitution in your genetic story. Like the difference between “Tom is tall” and “Tom is fall”. This is why there are health problems associated with MTHFR mutations.

According to the National Institute of Health, SNPs occur in our DNA almost once per 1,000 nucleotides. Since we have over 3 billion nucleotides (or base pairs) in the human genome, this means the average person has somewhere in the neighborhood of 4-5 million SNPs. That’s a LOT of “mutations.”

The vast majority of SNPs don’t have any impact at all, but as we discussed here, some do. I am, of course, referring to the magic chair that is the MTHFR enzyme.

Health Problems Are Linked to some MTHFR SNPs Because They Change the “Magic Chair.”

If you have no idea what I’m talking about, check out last week’s post here. The basic idea is that the MTHFR polymorphisms C677T and A1298C are actually consequential because they change the shape, and therefore the function, of the MTHFR enzyme in one of the most important chemical pathways in our body, the methylation pathway.

MTHFR mutations that matter are A1298C and C677T

Quick and Dirty List of Health Problems Linked to MTHFR

These health issues have been linked to MTHFR in at least one high-quality study (a great database of relevant studies is here for C677T and here for A1298C):

  • Midline Abnormalities: neural tube defects, anencephaly, spina bifida, cleft palate, cleft lip, tongue-tie, facial asymmetries.
  • Cancer: including breast, lung, brain, stomach, head and neck, thyroid, bladder, leukemia, and kidney.
  • Cardiac disease: including thrombosis (increased tendency to clot), deep vein thrombosis, high homocysteine levels, pre-eclampsia (high blood pressure in and around pregnancy), vascular dementia, glaucoma, heart murmurs, stroke, pulmonary embolism.
  • Fertility issues: including miscarriages or multiple pregnancy loss, placental abruption, low sperm count, history of children with birth defects.
  • Neurological issues: including migraines, autism, ADD/ADHD, Parkinson’s disease, Alzheimer’s dementia.
  • Mood and Psychological issues: including anxiety, depression, obsessive-compulsive traits or tendencies, bipolar disorder, and schizophrenia. Also, reduced reactions to certain medications like SSRIs for depression, and increased tendency toward addictions.
  • Miscellaneous Conditions: including chronic fatigue, fibromyalgia, and numerous autoimmune disorders.

Symptoms That Could Be Linked to MTHFR

Outside of the slightly scary list of diagnosable illnesses and health problems linked to MTHFR, there are also a number of symptoms that are highly associated, but don’t really warrant a diagnosis (at least not until they reach an unmanageable level). These include:

  • Brain fog
  • Irritability
  • Obsessiveness
  • Workaholism
  • Sleep Issues
  • PMS
  • Difficult menopause
  • Food sensitivities
  • Chemical sensitivities
  • High levels of seasonal allergies
  • Attention issues
  • Anger and aggression
  • Gallbladder sludge and stones
  • Heart racing
  • Depression
  • Edginess
  • Headaches or migraines
  • Moodiness
  • Joint and muscle aches
  • Itching skin
  • Obesity or easy weight gain
  • Carb and sugar cravings
  • Sweating
  • Feeling “not right”
  • Addictive tendencies

Does Having MTHFR Mutations Mean I Have These Issues?

Nope. Just like having these issues doesn’t mean you have an MTHFR mutation.

So… What Does It Mean?

It means if you have any of these issues (which, honestly, most people do have at least one), then managing your MTHFR and methylation cycle in a proactive way can help you feel better, reduce your symptoms, reduce sensitivities, and hopefully prevent MTHFR-related disease in the long-term.

What IS This Witchcraft?

It’s called “epigenetics” and it is a field that has emerged in the last couple of decades as we learned how many genes really are actionable. Epigenetics is the study of the way diet, lifestyle, nutritional status, drug use, chemical exposure, self-care, and external factors influence the expression of your genes.

This video explains epigenenetics and also gives a bonus introduction to why the methylation pathway is so important to gene expression (do you see all those methyl groups?!?)

Help! I’m Drowning in MTHFR Doom!!

It can feel a little bit overwhelming – especially if you’re like me and can listen to the giant list of symptoms and find more than five that match up with issues you have in your own life. The good news is that YOU CAN TAKE CONTROL. You hav e the power, thanks to epigenetics, to change your state of health and the severity of these symptoms. Also, here’s some great news:

MTHFR Superpower – Speed and Strength!

It’s no eyeball laser beams, but it’s a start. It has been suggested that DNA undermethylation in MTHFR folks induces muscle growth. A recent study of Russian and Polish athletes found an athletic advantage in sprint-strength type activities for the A1298C polymorphs. Mutants, Unite!

Next week we’ll talk about MTHFR testing options, what the results actually mean. and who should test? Subscribe, so you don’t miss any episodes and pass it on to your grumpy, obsessive, workaholic friends because maybe they’re mutants too…

Enter Your Email Below or To The Side For A Free Downloadable .pdf of this and MUCH more MTHFR info!

Share with friends:

What is MTHFR in Simple Terms Anyone Can Understand?

Sure, you’ve heard about MTHFR on the internet, but every link you click leads to complete and utter gibberish. Yeah – I’ve been there. Chances are, I’ve written some of that gibberish. Sorry folks! So here is the simplest, easiest version of the MTHFR story and also, why it matters so much to me.

MTHFR is the name of a gene, which is like a long word in the language in which your body is written. This gene tells your body how to make the enzyme of the same name. Enzymes are essentially magic seats that turn one thing into a more valuable thing. In this case, the magic chair turns a form of folic acid into 5-LMTHF which is the active form that your body uses for everything.

MTHFR in the simplest terms possible – it’s a magic chair.

MTHFR Looks Simple. What Could Go Wrong?

Have you ever sat down in a chair that had a big lump right where your seat wants to be? Well, so has folate. Sometimes when your body copies the long word of a gene, it gets a letter wrong. Usually, that doesn’t matter so much but occasionally, it does. In the case of MTHFR mutations, the ones that matter actually change the shape of the chair.

MTHFR mutations that matter are A1298C and C677T

In Short, MTHFR Mutations Mean A Lumpy Magic Chair.

If your folate can’t sit in the chair very easily, then it is much slower for your body to get any of the party guy, active folate. There’s a long line to get into the chair, but everyone has to wait.

The MTHFR Bottleneck

So Again: What Is MTHFR In Simple Terms?

MTHFR, when you think of it like this, is kind of a glorified folate deficiency, but with plenty of dull boring old folate hanging around. The dull, boring folate just can’t get any time in the chair to turn into party-guy active folate. You’ll notice the absence of crowns and confetti in the above pictures.

Does It Matter That You Can’t Make Party-Guy Active Folate?

The short answer is that it does. We all need active folate for lots of things, including :

  • Gene expression – this is how you turn on or off the genes for other important things, like the gene that kills off cells that could become cancerous.
  • Toxin elimination – your body needs to clean its house regularly and it needs active folate to do it.
  • Neurotransmitter production – to make your serotonin, dopamine, and the other molecules that keep you happy, your body needs active folate.
  • Building babies – if you happen to be making a baby, you need lots of active folates to do it, or there could be problems with the pregnancy or the baby.

Do MTHFR Mutants Make ANY Active Folate?

Yes – thank goodness we do. There are a number of different mutations (we’ll get into that later), and each one has a different impact on how well the magic chair works. But EVERY MTHFR mutant makes some active folate, or they wouldn’t be living.

You Can’t Change Your Genes, So Why Talk About MTHFR?

The BEST thing about the MTHFR mutation is that it’s actionable. With our current technology we can’t change this gene, but by taking simple steps with nutrition, supplementation or prescriptions, and lifestyle you can change the way it affects your health. That is why we’re talking about it – because you have the MTHFR mutation, you have the power to do have a huge impact on your own health.

The BEST thing about the MTHFR mutation is that it’s actionable. By taking simple steps with nutrition, supplementation, and lifestyle you can change the way it affects your health.

– Amy Nuezil, tohealthwiththat.com

Why Does MTHFR Mutation Matter To Me? (Amy – the author)

I’m a mutant too. MTHFR has impacted me in so many ways. MTHFR certainly has had an impact on my resting mental health, my personality, my ability to have babies, and the way I look – I have a facial asymmetry that is likely linked to MTHFR. It also changes some of the conditions that I have to be concerned about in the future – like Alzheimer’s dementia. We’ll talk about all of this in much greater detail in future episodes, but for now, thanks for listening and subscribe if you want to know more. Next week we’ll talk about some of the health consequences that are linked to the MTHFR mutation. Also, for show notes and juvenile drawings of the magic chair, visit me at to health with that dot com. If you happen to have an MTHFR question, you can leave me a message by clicking the link in the show notes.

Share with friends: