MTHFR and no I’m not swearing at you.

So you know what genes are right?

These are the codes for your body that makes you well you within your cells. We know that certain genes have certain actions and that genes interact with one another in complex arrangements: 1+1 doesn’t = 2 in the case of gene interaction. But whether certain genes are turned on or off is due to methylation a biochemical process involving donation of a methyl group. This turning on and off of genes is called epigenetics.

SNP

And a variation within these genes expression called a “SNP” ( pronounced snip)- single nucleotide polymorphism. Some SNPs matter others don’t, there are literally millions of SNPs. The good news is yes you might have inherited some traits from your ancestors that may or may not be serving you. But the good news is you can work with your SNPS turning them up or down in volume as you need by diet and lifestyle choices.

One SNP that gets a lot of attention is the MTHFR ( Methylenetetrahydrdofolate reductase) gene. This is the rate limiting enzyme in the conversation of folate to its bioactive form. Which is in turn used for homocysteine production and methionine. You need folate processes so it can make DNA and modify proteins. This is quite a common variation, but we aren’t exactly sure on the % in the population. It is involved in over 200 reactions in the body.

MTHFR

The MTHFR can create a whole heap of health problem (can doesn’t have to). Everything from irritability and obsessiveness to birth defects and cancer. The MTHFR is the master methylation gene. It’s your ability to methylate, a key process that affects your stress response, inflammation, brain chemistry, energy production, immune response, detoxification, antioxidant production, cell repair and genetic expression. So it is kind of important that it works well.

Strength of having a MTHFR SNP (or genetic variation):

Intensity
Alertness
Productivity
Determined to solve problems
Focus
Improved DNA repair
Decreased risk of colon cancer

Weakness

Depression
Anxiety
Autoimmunity
Migraines
Increased risk of stomach cancer
Autism
Pregnancy complications
Downs syndrome
Birth defects
Cardiovascular conditions i.e. heart attack, stroke, thrombosis

The liver helps out here

Now 85% of methylation occurs in your liver so if your liver isn’t being supported than SNP or no SNP you aren’t putting it in the best place to be working optimally.

What does that involve put simply:

Drink alcohol in moderation or avoid all together
Avoid industrial chemicals and heavy metals in the air, food and water
Avoid unnecessary medication and recreational drugs
Help your body detoxify by drinking plenty of water and adequate supportive nutrients

During pregnancy you’re methylating for 2!

It’s even more important to support your liver that’s why nausea, vomiting and gallbladder issues are common in pregnancy as the methylation requirements have increased.
We have all heard the warning s about neural tubes defects and cardiac defects and so mums are being prescribed folate tablets. But it’s not a folate deficiency it’s a methylation issue. Which will make sense as we delve into MTHFR.

Methylation is great because it:

Produces creatine which is a compound used by your brain and muscles as fuel.
Produces phosphatidylcholine, which is needed for cell wall integrity, regulates cell death, bile production.
Genetic expression- turning on and off genes.
Neurotransmitter production such as serotonin, dopamine, adrenaline and noradrenaline and this also affects your stress response.
Detoxification of external and internal chemicals ie oestrogen – methylation affects your ability to make glutathione ( a master antioxidant).
Methylation helps you immune system find its sweet spot not too aggressive (autoimmune) not too passive chronic reoccurring infections).

Well give me a Supplement to overcome this then

SNPs are important to consider but taking supplements to address a certain SNP might help but a single SNP is not usually the reason for your health problems. So, taking a supplement is not going to be enough. You need to look at everything going on in your life and body. There is “no pill to cure every ill”. We are not a machine, and it doesn’t work like that. So we are back to holism principles and please don’t think having a SNP is the answer to everything.

FOLIC ACID VS FOLATE

I hope this picture helps explain things because everyone gets very confused about folate and folic acid and what this means with a MTHFR mutation.

The natural form of B9 is called FOLATE.
The active version of that is called METHYLFOLATE- which is a key compound in methylation.
The artificial form of B9 is called FOLIC ACID.

Even if your methylation is sluggish taking lots of folate will help ensure there is sufficient around i.e. spinach, mustard greens, collard greens, turnip greens and romaine lettuce. Think greens that are leafy.

Artificial B9-Folic acid

Artificial Folate is found in vitamin pills and packaged foods. It is not useful to your body until it is processes into the active usable form. However FOLIC ACID resembles FOLATE it binds to your folate receptors and prevent natural folate from getting to where it needs to be in your cells. If the natural folate can’t get in it can’t be turned into methylfolate and you can’t get proper methylation.

A lot of MTHFR polymorphs can’t convert this artificial folate properly and we end up with this problem. Well then you say to me fine I won’t take folic acid supplements problem solved. The trouble is folic acid has been added to a lot of foods on mass a a public safety initiative- to enhance them due to the spinal defects occurring and lack of it in people’s diet.

So you will find artificial B9- folic acid in:

Bread
Cereal
Cornmeal
Flour
Pasta
Rice and other grains.

If you are methylating well and not eating huge amounts of those fortified foods, you can compensate. But if you are struggling then you will encounter problems with methylating as listed above.

So what does MTHFR do?

Your MTHFR gets the methylation process going by passing a methyl group to folate. That methylfoalte then interacts with another chemical called homocysteine. Now when homocysteine is methylated it becomes methionine. Finally, the methyl group also gets passed to SAMe (sai “SAMMY”). What can SAMe do?

It helps with creatine, phosphatidylcholine and melatonin production.
It can also donate a methyl group to arsenic, histidine and estrogen to help it be expelled from the body.

When SAMe is finished being Oprah and giving methyl groups to everyone it becomes homocysteine.

Homocystine

Think of homocysteine as the excess cookie dough. You made a sheet of cookie pastry cut out all the cookies and what is left is the homocysteine. Now your body can roll the cookie dough up and reuse it (homocysteine is re- methylated and goes back into the cycle) OR you can make something different with the left overs- that something different is glutathione.

Now if there isn’t much stress in the body and toxin levels are low, we will use that left over cookie dough to make more cookies. But if its not then we will start making more glutathione.

What’s wrong with measuring Homocystine levels to see how things are going then?

The levels determined to be “normal” by pathology labs are way too high (above 7micromoles/L)- we don’t want above 7 as it blocks the methylation cycle.
Labs only report on excessive high number and not when it is low.
You can have high homocysteine for a lot of reasons not just methylation problems and you can have normal levels and still not be methylating properly.
Elevated homocysteine, is a strong marker for increased risk of hypertension and cerebrovascular disease, possibly due to atherosclerosis.

How does methylation go wrong?

Poor diet

First you need protein, then B vitamins and a variety of other nutrients. Think of methylation as a fire you need big logs and kindling to keep it going so there are a number of nutrients needed to do this process. The basic nutrients are the logs the other cofactors are the kindling.

Folic Acid

See information above

Wrong amount of exercise

A study at the Karolinska institute in Stockholm had young healthy men and women bicycle at a moderate pace only with one leg. After 3 months they analysed the DNA in each leg. The leg that was mobile in the muscle genome showed new PATTERNS OF METHYLATION. Exercise is great for methylation as long as you don’t do too much and it then becomes a stressor on the body.

Poor sleep

When you don’t sleep properly you don’t methylate, when you don’t methylate you don’t make enough melatonin which helps you sleep. It’s a vicious cycle so break it by making sure you get good sleep.

Too much stress

Too much stress and you use your methyl groups faster. To make more methyl groups you need more nutrients (building blocks) that are methyl donors.

Exposure to harmful chemicals

Poor methylation and poor detoxification go hand in hand. SO if you have too much of a toxic burden on the body by excessive chemicals it has to process methylation will, suffer as a result.

Other barriers to good methylation:

Alcohol
Antacids
Heavy metals
Infections
Inflammation
Intestinal yeast overgrowth
Nitrous oxide
Oxidative stress
Small intestinal bacterial overgrowth (SIBO) and other gut infections

Personality profiles seen with MTHFR

Some days you are blue or depressed while others you are anxious.
On good days you focus and get stuff done and bad days you have performance anxiety a temper and or headaches or are just irritable. After eating a salad you feel great.

Prevalence and what does this mean if I have it?

There are currently a total of 34 mutations in the MTHFR gene.
The MTHFR gene sits on Chromosome 1. There are two key variants we test for (as at this stage there is little or no research on the others).
The two variants (or SNPs) that we currently test for are:
- MTHFR C677T
- MTHFR A1298C
  - Your results might look like this;
    - MTHFR C677T ++ or MTHFR C677T homozygous
    - MTHFR C677T +- or MTHFR C677T heterozygous
    - MTHFR A1298C ++ or MTHFR A1298C homozygous
    - MTHFR A1298C +- or MTHFR A1298C heterozygous
      Or finally:
      - MTHFR C677T +- or MTHFR C677T heterozygous and
      - MTHFR A1298C +- or MTHFR A1298C heterozygous
      This combination of one of each means you are compound heterozygous
      For further explanation, watch this video here
      Heterozygous = 1 copy of the gene from either parent
      Homozygous = 1 copy of the gene from each parent
      MTHFR C677T Heterozygous = 40% loss of function *
      MTHFR C677T Homozygous = 70% loss of function *
      MTHFR A1298C Heterozygous = 20% loss of function (research not known)
      MTHFR A1298C Homozygous = 40% loss of function **
      MTHFR C677T & MTHFR A1298C heterozygous = compound heterozygous = 50% loss of function
Italians for example have a high rate of the SNP to their MTHFR that makes it 30% functional. Most of them don’t supplement with B vitamins even when pregantn andh yet we don’t have a higher rate of birth defect in Italy than anywhere else in the world. Why?
Because they eat leafy green vegetables (diet), interact often with family and friends (stress relief) and live in a great climate (less stress). Their foods are not generally factory made (lower toxin exposure). Using diet and lifestyle to essentially counteract this genetic predisposing.

What do we need then?

To do its just properly and methylate we don’t just need folate as mentioned but also B12 (methylcobalamin). If either is missing the process cannot work properly, they are besties and both need to be in adequate supply. But not only this Bs don’t work in isolation B2, protein and Magnesium as well as B12 and B9 help the methylation cycle work effectively. Vitamin C is also an ally and doesn’t hurt to ensure its in sufficient levels.

This is where taking an active B complex can help if you’re struggling with diet alone or need to see a response quickly.

B2: liver, lamb, mushrooms, spinach, almonds, wild salmon, eggs
B9: (Foalte): green vegetables, beans, peas, lentils, squash
B12: red meat, salmon, clams, mussels, crab, eggs
Protein: animal sources beef, amb, fish, poultry, eggs and dairy; vegan/vegetarian sources inc. beans, peas, lentils, broccoli, nuts, seeds
Magnesium: dark leafy greens, nuts, seeds, fish, beans, avocados, whole grains.

This polymorph of MTHFR seems a problem why does it exist?

Helps store adrenaline and noradrenaline due to shutting down COMT – this means stress chemicals float around longer making you more hypervigilant and able to “escape” something.
Recycled oestrogen due to MTHFR also helped keep women fertility up when starvation was occurring.

The Choline shortcut

If your body doesn’t have methylated B9 or methylated B12 it sees the problem and uses choline. Where is choline found? Eggs, red met, poultry, fish, caviar, liver and other organ meats. Although you can get it from plant sources it just isn’t usually in sufficient amounts- spinach and beets. Vegans and Vegetarians really should be supplementing their B12 anyway even if there are no MTHFR issues due to their diet preferences. The trouble with this shortcut is its just that it’s a shortcut not along term option. It will put too much pressure on your kidneys and liver long term, so you need to make sure you are getting adequate support for your methylation pathway.