What you need to know about MTHFR, methylation, and over-supplementing (which can be very dangerous)

by | Aug 11, 2017 | BLOG POST, Nutrigenomics and MTHFR

If you go to a health practitioner who sees that you have MTHFR and simply tells you to take methylated B vitamins but doesn’t address any of the fundamental factors that inhibit methylation, my advice to you would be to RUN. Find a health practitioner who’ll do the fundamentals with you, as this is the only way to optimize methylation effectively – and the safest way, too.

This is a long post so I'll give you the breakdown of it below so you can decide which bits you'd like to read. Click the below links to jump to them quickly. Having said this, if you're interested in finding out more about MTHFR and methylation, but really don't know that much, I would encourage you to grab a tea, settle on in, and take your time to read through this entire post. 

What I cover in this post (click links to jump to the section that most interests you) includes:

1. What is “MTHFR”

2. What’s methylation and why it’s a fundamental pillar of optimal health

3. Deciphering your personal DNA and methylation mutations 

4. Our genes are not our fate: a quick look at epigenetics 

5. My top tips for enhancing methylation

What is “MTHFR”

MTHFR may look like a rude word abbreviation but it’s actually a very important topic in the functional medicine space.  

The MTHFR gene is responsible for the production the MTHFR enzyme. The MTHFR enzyme in long-form is: methylenetetrahydrofolate reductase. So a mutation in this MTHFR gene will cause a reduction in the production of the MTHFR enzyme. 

The MTHFR enzyme converts folate, (or “folic acid”) into the active form of folate, which is 5-methyltetrahydrofolate, so it can be metabolized and used in multiple extremely important biochemical reactions in the body. This is done via a process called methylation. 

Mutations in your MTHFR enzyme will reduce the capacity of your MTHFR enzyme to work effectively. If a person has one mutation in their MTHFR gene this is called “heterozygous” and if a person has two mutations in their MTHFR gene this is called “homozygous”. Generally, homozygous mutations are “worse” than heterozygous mutations. For example, those who are homozygous for MTHFR C677T, (one of the most common MTHFR genetic mutations) have up to a whopping 70% reduced enzyme function, (unfortunately, this is the type of MTHFR mutation I have). 

Up to 40 – 60% of the population have a mutation in their MTHFR gene. It’s not uncommon.

Researchers believe there are about 30 different types of MTHFR mutations but the most common and most well studied are the C677T or A1298C MTHFR mutations, (these numbers represent the positions at which the gene mutations are found on the MTHFR gene). 

What’s methylation and why it’s a fundamental pillar of optimal health

Methylation is a fundamental pillar of optimal health that takes place more than a billion times per second in the body, in every cell in the body. It can affect pretty much every tissue and organ system in the body because it’s working on the most fundamental processes within the body.   

Methylation is also known as “one-carbon metabolism”. It's a metabolic process in the body that involves the transfer of active methyl groups from a donor molecule, (methyl groups are carbon atoms linked to three hydrogens) to other acceptor molecules in order to cause a knock-on effect that have benefits to our overall health. 

Don’t feel overwhelmed, we’re not going to get much more complex than this, so you don’t have to worry about the biochemistry behind one-carbon metabolism, but know this: these methyl groups are essential for the efficient working of the methylation process in the body and a deficiency (or excess) of methyl groups can wreak havoc on your health.

A system in the body that is greatly impacted by methylation is mental health. Our neurotransmitters rely on healthy methylation for their synthesis, metabolism, and excretion. Without healthy methylation we start to see neurological issues such as ADD, ADHD, anxiety, depression, dementia, and more.

A search for “methylation” in PubMed yields over 94,000 hits – proving just how important the study of methylation has become – and for good reason.

According to Keith Robertson, Nature Review Genetics: “The importance of DNA methylation is emphasized by the growing number of human diseases that are known to occur when this epigenetic formation is not properly established and/or maintained.” In layman terms: poor methylation can contribute to multiple disease states.

Here's a list of the things that methylation affects in the body: 

  • Proper gene expression. Too little methylation, (aka “hypo-methylation”) can cause a gene that causes disease to be expressed and conversely, too much methylation, (aka “hyper-methylation”) can cause a gene that inhibits disease to be suppressed. This is one of methylation's most important roles in the body. 
  • Detoxification. Methylation is required to produce glutathione, and glutathione is our main antioxidant in our body. Without enough glutathione you'll have trouble detoxing heavy metals, pesticides, herbicides, mould, and more. 
  • Hormone clearance. Those with estrogen dominance or thyroid issues in particular may have an issue with their methylation.
  • Histamine clearance. Do you get hives? Bad seasonal allergies? Reactions to histamine-containing foods? Your methylation may be to blame.
  • Neurotransmitter synthesis and metabolism. Do you have mood issues? Anxiety? Depression? ADD? ADHD? Methylation plays a vital role in neurological health. 
  • Healthy cell division and DNA and RNA synthesis. 
  • Early central nervous system development.
  • Immune cell differentiation. Poor methylation can lead to autoimmune disease, food allergies, (in fact hyper and hypo-methylation are both associated with the development of childhood IgE-mediated food allergies), and cancer.
  • Cellular energy metabolism. Methylation plays a crucial role in ATP production, which is the fundamental energy unit of the cell.
  • Phospholipid synthesis. Crucial for the health of all cell membranes.
  • Myelination of peripheral nerves.

….and more. Hopefully that gives you some idea as to the importance of this process in the body. It really can’t be overstated how important methylation is.

The regulation of gene expression is one of the most crucial roles of methylation in the body. Methylation can essentially turn genes on or off by a methyl group binding to a gene. This is known as DNA methylation. 

Because healthy methylation plays such a critical role in health, when it’s not working properly this can lead to multiple health conditions. Some of these health conditions that have been strongly linked to methylation issues include:

  • ADD/ADHD
  • Addiction
  • Allergies
  • Alzheimer’s Disease
  • Anxiety
  • Asthma
  • Atherosclerosis
  • Autism spectrum disorder
  • Autoimmune disease
  • Behavioural changes
  • Bipolar disorder
  • Cancers
  • Chemical sensitivity
  • Chronic fatigue
  • Cleft palate
  • Diabetes
  • Dementia
  • Depression
  • Downs syndrome
  • Hypertension
  • Fertility issues
  • Fibromyalgia
  • Insomnia
  • Infertility
  • Multiple sclerosis
  • Migraines
  • Midline defects in children
  • Neuropathy
  • Parkinson’s Disease
  • PCOS, endometriosis, fibrocystic breasts, and fibroids
  • Schizophrenia
  • Thyroid disease
  • Increased risk of CML, (a type of leukemia)

Deciphering your personal DNA and methylation mutations 

With the mapping of the human genome completed in 2003, we are now able to sequence our personal DNA and decipher what SNPs (Single Neucleotide Polymorphims) we might have. SNPs are essentially ‘mutations’ or ‘variants’ in a gene, and we all have SNPs or mutations in certain genes.

Mutations in our genes act essentially like little car crashes, and these car crashes prevent biochemical reactions in our body from working efficiently. This can lead to backups of various nutrients or depletions of nutrients – both which can lead to health consequences. The good news is we can bypass these “car crashes” by supplementing the correct way and eating the right diet, for those with methylation mutations, (SNPs).  

One of the most commonly talked about SNPs is MTHFR, because this is one of the most important and heavily studied SNPs.

And – side note – these SNPs are on the rise. This is thought to be due to an increase in folic acid supplementation. This increases full-term pregnancies, which increases MTHFR and other methylation SNPs (see next paragraph). This has lead to increased survival rates of infants possessing these SNPs. Having said this, there are dangers to supplementing with synthetic folic acid, (as opposed to methyl-folate. Click here to read more about this).

Methylation isn’t as simple as just MTHFR. There are many other genes that play a role in healthy methylation including: MTR, MAT, CBS, GSTM1, CYT P450’s, BHMT, PEMT, PON1, DAO, FOLR, GAD, GAMT, MAO –A AND MAO-B, MAT1A, COMT, TCN2, SUOX, AHCY, and SULT. You can have mutations on all of these, which will impact how you methylate.

So how do you figure out if you have mutations in these genes? The best way to go about determining what SNPs you have is to get a 23andMe test done. The test in and of itself won’t give you the information you’re looking for, instead you have to look at the “raw data” and have a trained professional interpret this for you. Please contact me if this is something you’re interested in finding out more about. It really isn’t possible to interpret this data yourself and effectively treat yourself unless you have extensive training in MTHFR and methylation. To say it's complicated is an understatement!

Our genes are not our fate: a quick look at epigenetics 

Before you start freaking out that you have MTHFR or other SNPs know this: our genes are not our fate. You may inherit your DNA but how well you look after it will determine how healthy you are.

The extent to which your mother, father, and grandparent’s DNA was methylated will be passed down from generation to generation. This is due to something called epigenetics: the study of changes caused by modification of gene expression rather than alteration of the genetic code itself. In other words, we used to think our DNA was set in stone: what we inherited from our parents was concrete and unable to change. We now know that – via epigenetics – we can alter the expression of our genes. 

Essentially, epigenetics gives your body a way to compensate for problems in your DNA that you have inherited. So in a nutshell: you may have some shitty genes but that doesn’t mean you’re going to suffer because of them. The diet you eat, the lifestyle you lead, and the supplements you take can potentially bypass these crappy genes to ensure you have – and maintain – optimal health. In fact, it’s epigenetics that explains why identical twins who share the same DNA may get different diseases.

Do not treat your SNP! The dangers of treating SNPs instead of “people” including the dangers of over-supplementing with B vitamins  

Oftentimes health practitioners who don’t have a lot of training in methylation may tell their clients, (and I hear this all the time) that they simply need activated or methylated B vitamins to solve their “MTHFR problem”. This is because one of the crucial methylation cycles – methionine synthase – requires folate and B12 to function correctly. However, this is not necessarily the right thing to do and can even cause harm.

A common saying in the nutrigenomics community is “don’t treat the SNP”. What this means is that just because you have a specific genetic SNP, such as MTHFR, this doesn’t mean your treatment plan is automatically, in a straight-forward manner, mapped out for you, based on those SNPs.

Blindly supplementing with B vitamins isn’t addressing your own personal current health state.

Many things alter the state of methylation including whether or not you have candida or other intestinal issues such as SIBO, dysbiosis, parasites, etc, your alcohol consumption, your sleep, your digestive function, how much you exercise, your stress levels, your diet, your toxin exposure, the levels of heavy metals in your system, your oxidative stress, and more.

If you go to a health practitioner who sees that you have MTHFR and simply tells you to take methylated B vitamins but doesn’t address any of the fundamental factors that inhibit methylation, my advice to you would be to RUN. Find a health practitioner who’ll do the fundamentals with you, as this is the only way to optimize methylation effectively – and the safest way, too.

It’s not advisable, and can sometimes even be unsafe, to treat your genetic SNP and not “you”. For example, you may have MTHFR and your sibling may have MTHFR but if you eat well, exercise, employ stress reduction techniques, eliminate candida, don’t drink too much alcohol, and so on then you may be methylating quite well, but your sibling – who doesn’t do all these healthful things – may be under-methylating and hence, in need of more methylation support than you.  

Hyper-methylation can be just as dangerous as hypo-methylation – more B vitamins and methylation support is not always better and can actually be dangerous if you don’t need them

If you are supplementing with B vitamins without taking breaks or “pulsing” them you may end up over methylating, which occurs when you have an abundance of methyl groups but they're building up and can't be used properly. And methylation follows a bell-shaped curve, meaning that both under and over-methylation can be unhealthy. Note: food-based folate however, has only ever been shown to be protective. Supplemental folate, (even in the correct form, click here to read what that is) can cause deleterious effects.

Some of the reasons we don’t want to always supplement, or supplement heavily, with B vitamins in those with methylation SNPs include that:

  • We don’t know what the impact of “pushing” our genetic reaction rates actually is. We have studied MTHFR C677T and A1298C to some degree however, there are a lot of other SNPs that haven’t been studied as much as these and therefore we don’t actually know what we’re doing by pushing the reaction rates of MTHFR C677T and A1298C.
  • We don’t know what dose to use. No studies have clarified what dose of methyl donors is safe and effective as of yet. In fact, many people don’t tolerate methylation supplementation. This is likely due to poor clearance of epinephrine and hence a worsening of symptoms can occur, such as increased anxiety. Those with impaired metabolism of catecholamines via COMT and MAOA (methylation SNPs) may struggle to utilize and benefit from high-dose methyl donors.
  • Supplementing may cause hyper-methylation states. In the scientific literature we can see cases where hyper-methylation has contributed to cancer, immune dysfunction, and Downs Syndrome. We simply do not know what the effects are of long-term, high-dose methylation supplementation, so for now it’s better to be safe than sorry. Additionally, both hyper and hypo methylation states have been shown to play a role in tumorigenesis (cancer).
  • Your methylation status depends on more than just which SNPs you have. As I mentioned above, there are many things that impact how well or how poorly you are methylating. Methyl donors can essentially be “competed” for by factors such as high catecholamine turnover, (if you’re super stressed out), your detoxification state, if you’re eating a lot of high-histamine containing foods, if you’re constantly being exposed to antigens that are producing high histamine turnover, if you’re over-exposed to xenoestrogens hence putting a strain on your COMT SNP that plays a vital role in the detoxification of your estrogen, and so on. Blindly supplementing with B vitamins isn’t addressing your own personal current health state.

An increased risk for breast cancer has been seen when a MTHFR C667T polymorphism was present in association with high plasma folate levels – showing once more that supplementing with folate when you have this SNP isn’t always the best course of action. Additionally, researchers have found a potentially harmful effect of folic acid – or even other “better” forms of folate – if there’s a prior history of cancer.

Also remember, methylated B vitamins aren’t the only nutrients required to optimize methylation. There are many different co-factors, (beyond just B vitamins) that are required for healthy methylation including methionine, cysteine, taurine, DHA, zinc, magnesium, potassium, riboflavin, niacin, pyridoxine, folate, B12, betaine, choline, and more.

(Note: when talking about MTHFR and methylation it’s important to understand the difference between synthetic folic acid and folate. Please read this post to ensure you understand this difference).

My top tips for enhancing methylation

The basic idea behind supporting methylation is to remove those things that place a drain on your methylation and deplete methyl donors. This is why we want to address more than just B vitamins in order to support healthy methylation.

Beyond simply supplementing you must, must, must address all other fundamental aspects of optimal health if you wish to enhance your methylation and give yourself the best chance possible of preventing disease.

In order to support your methylation to the nth degree you must address the following:

  • Enhance gut health. This may be the first point of call when it comes to working on your methylation. Getting your digestion working optimally is crucial because there are so many nutrients that methylation depends on to function optimally. Additionally, you want to support your microbiome so that you have microbial species that produce folate. For example, most lactobacillus species are, (in vitro, aka; in a petri dish) consumers of folate, (except for the L. plantarum strain, which can produce folate in the presence of PABA). And many bifdobacteria species are folate produces. Also, dysbiosis in the GI tract promotes inflammation, which can down-regulate methylation. Additionally, anything that’s in the gut that shouldn’t be there can negatively impact methylation such as infections like c. diff, H pylori, adenovirus, and more. Running a stool test is a good idea.
  • Run the correct tests. A good idea is to run the correct tests that will show where there might be deficiencies in your methylation cycle and then correct these with supplementation as well as diet and lifestyle. Some of these tests include folate, homocysteine, CRP, ferritin, fasting insulin, cholesterol, a full thyroid panel, methylmalonic acid, B12, and a SAM/SAH ratio test. It’s also advisable to run heavy metals testing, organic acids testing, oxidative stress testing, and stool testing – all of which give even more information as to how your methylation cycles in the body may be impacted.
  • Deal with heavy metal toxicity. Those with MTHFR have a reduced ability to detoxify heavy metals, especially arsenic because to remove arsenic from the body you must have optimal glutathione and SAMe: two methyl-donor nutrients that can be low in those with MTHFR. Also think: do you have silver mercury fillings? These should be removed by a biological dentist.
  • Address a candida overgrowth. When this type of yeast overgrows in the gut it can be a major issue for those who have SNPs in their MTHFR gene. This is because candida produces a toxic byproduct called acetylaldehyde, which inhibits methionine synthase, (an important cycle in the methylation process in the body). You can read more about candida here.
  • Reduce alcohol. This is for the same reason as to why you want to treat candida: alcohol produces acetylaldehyde in the body, which will negatively impact your methylation.
  • Treat inflammation. All areas of inflammation should be addressed including food sensitivities, (food allergies and sensitivities can increase inflammation), gum disease, being overweight, (adipose (aka “fat”) tissue is pro-inflammatory), dealing with your stress, and also getting blood sugar and insulin under control as these lead to inflammation. Going gluten and dairy-free is a good start, as a lot of people are sensitive to these proteins. You may wish to do an elimination diet to address any food sensitivities that are putting further strain on your methylation.
  • Enhance your diet. Lack of nutrients is a major factor in poor methylation. You must ensure your diet is full of various different colours from the produce you eat and ensure you’re getting enough vegetables, protein, and healthy fats. I don’t recommend a vegan or vegetarian diet for most people and this is because our methylation depends greatly on nutrients that are most typically found in animal products including taurine, methionine, DHA, and B12.
  • Consume methylation functional foods. These are foods that will supercharge your methylation and include beets, spinach, sea vegetables, daikon radish, shiitake mushrooms, salmon, fish roe, whitefish, oyster, eggs, pumpkin seeds, sesame seeds, sunflower seeds, and organ meats such a liver.
  • Enhance detoxification. Because methylation plays such a crucial role in detoxification it’s important to eliminate the strain you put on your detoxification pathways. So think about things like only choosing non-toxic personal care products, getting an air filter in your room (I’ve got the Germ Guardian), not wearing perfume or using toxic air fresheners or candles, reducing your exposure to plastics, don’t use Teflon coated pans, ensure you’re not living or working in an environment that is contaminated with mould, ensure you’re eating organic food, filter your drinking water (the Berkey water filter is my favourite), ensure you’re getting enough hydration and fibre, making sure the products you clean your clothing with and clean your house with are non-toxic, and ensure you’re regularly consuming foods that promote healthy detoxification such as cruciferous veggies, beets, parsley, ginger, artichokes, seaweed, turmeric, protein, etc. Click here to purchase my 7 Day Detox which goes into detail about the ways you can amplify your detoxification. Use the code DETOX40 to get 40% off.
  • Don’t over-cook or burn your meat. This produces AGES (Advanced Glycation End Products), which cause oxidative stress in the body. Using dry heat and moisture are the best ways to cook your meat.
  • Address stress. Too much stress can enhance the production of epinephrine and norepinephrine, which require methylation for their production, metabolism, and removal from the body. Stress plays a HUGE role in healthy methylation.
  • Exercise, but not too much. Don’t over-exercise. This can negatively alter methylation biomarkers.

But above all else, remember this: currently the safest means we have to “treat” MTHFR and deficiencies in methylation is via dietary and lifestyle strategies. Get these right, and you’re well on your way to optimal health.

I offer a methylation support package in which we go over all your tests, biomarkers, address your diet, lifestyle, stress, and more. If you want to find out about this package, please contact me.

In happiness and health,  

 

 

 

 

SOURCES

  • https://kresserinstitute.com/treating-methylation-supplementing/?utm_source=activecampaign&utm_medium=email&utm_term=new-this-week-treating-methylation&utm_content=&utm_campaign=ki-roundup
  • Dr. Ben Lynch Part 1 and Part 2 course
  • http://mthfr.net/methylation-inhibited-by-candidas-toxin/2012/09/08/
  • Dr Amy Yasko Methylation, Diet and Lifestyle 
  • https://www.mthfrsupport.com.au/
  • https://www.ncbi.nlm.nih.gov/pubmed/28520345
  • http://ajcn.nutrition.org/content/104/6/1665
  • http://onlinelibrary.wiley.com/doi/10.1002/mnfr.201500819/abstract
  • http://mthfr.net/berkey-water-filter/2016/12/15/
  • https://chriskresser.com/methylation-what-is-it-and-why-should-you-care/
  • https://www.newscientist.com/article/dn10518-you-are-what-your-grandmother-ate/
  • https://www.dietvsdisease.org/mthfr-c677t-a1298c-mutation/