Have you seen or read about the MTHFR genetic mutation? It’s the new kid on the block and a lot is being said about it. Do you have it? Does it contribute to your health condition and is it making you sick? Here’s the lowdown on MTHFR.
MTHFR is a genetic mutation or snp (single nucleotide polymorphism) that can be identified with blood or saliva testing and may or may not be contributing to conditions as diverse as cardiovascular disease, cancer, autism, infertility and probably autoimmunity.
The Methylation Cycle used to be the called the Methionine Cycle but Dr. Amy Yasko has now indicated 5 biochemical cycles that are intertwined. These are 5 major biochemical pathways in the body. When we discuss them you can refer to the image below.
Methylation Cycle is Made Up of 5 Major Biochemical Pathways
- BH4 Cycle – this involves the synthesis of the neuro-transmitters tryptophan into serotonin and tyrosine into dopamine
- Folate Cycle – this is how we process folate from the diet and it involves B12 as well
- Methionine cycle and the processing of SAMe
- Transulfuration Cycle from homocysteine
- Urea Cycle – how we process ammonia
If one cycle is not operating properly, it will affect the others. There are several critical functions of these cycles:
- Immune function – building of immune cells, NK cells and T cells
- Energy balance
- Hormonal balance and mood
- Controls inflammation
- Production, synthesis and repair of RNA and DNA and DNA protection
- Helps to metabolize histamine
They do much more but this gives you the general idea of how important it is.
The MTHFR enzyme is at a critical point in the methylation cycle right in the middle of all these gears. It transfers a different type of folate to the methyltetrahydrofolate and starts the metabolism where it donates the methyl group to homocyteine in order to keep the cycle spinning. That creates SAMe which helps with energy production and DNA protection and continues around and helps the BH4 cycle in making the neurotransmitters.
MTHFR is critical for the production of SAMe. This has a lot to do with creating the neurotransmitters serotonin and dopamine from trytophan and tyrosine. So there are 3 pathways turning here and it is all dependent on the MTHFR enzyme.
Co-factors are also necessary to move the pathways. Every step of the way includes an enzyme and most co-factors are the B vitamins – B2, B6, B12, folate as well as magnesium and zinc.
There are different types of folate. Folic acid is the synthetic form and takes an extra step to process. Methylfolate is the natural, bioactive form that keeps the gears turning.
All the factors and cofactors need to been available to keep the cycles spinning productively.
Methylfolate can be taken as a supplement. If you have a MTHFR snp you may need to take a supplement. Some people can go up to 200 mg (this may seem like a small dose but usually doses are in micrograms so 200 mg is huge). However, if you have other genetic snps such as COMT or MAO you need to be careful with these higher doses. Dosing can be tricky.
Good quality methylfolate supplements will be seen on a label as 5 methyltetrahydrofolate or 5 MTHF. It may also be listed as 5 methylenetetrahydrofolate or in a quadrafolinic form. Folinic acid may also be on the label.
You should not consume synthetic folic acid at all. It is not readily metabolized and can be causing problems. You need to check your multivitamins and other supplements for this. Avoid processed foods as these are fortified with folic acid and this causes a burden in metabolism, especially for these folks with the genetic snp.
Is the Genetic Snp Expressed?
You can have the mutations or snps (single nucleotide polymorphisms), (most of us have some) but that doesn’t necessarily mean that it is expressed. They can be turned on or kept off, usually through diet and lifestyle.
There are 61 mutations on the MTHFR gene – the two most studied are the A1298C and 677C. The A1298C has to do more with the BH4 cycle and mood disorders. However there is a lot of crossover in symptoms and diseases.
Studies are showing hypertension and cardiovascular disease via the homocysteine marker in the blood. Cancers are also involved because of inflammation and high folic acid (synthetic forms) which reduce natural killer cells. Miscarriages can also be involved. Anxiety and depression are also involved as they have to do with the neurotransmitters.
This study showed a decreased risk of colorectal cancer with the 677C snp – good news there.
Studies show the positive effects of B vitamins on mood, such as B6 for anxiety. Studies have shown B vitamins improved anxiety in celiac disease. This can be due to the methylation cycle being improved.
Pyroluria is a condition in which B6, and zinc is depleted and leads to depression and mood problems. This can all be alleviated with appropriate supplementation.
We inherit one gene from each parent so we have two. Heterozygous means you can have one mutation (one snp) from one parent and not the other. Being heterozygous means that the enzyme slows down.
Being homozygous refers to having 2 snps or mutations and that makes detoxification more difficult as methylation is reduced by a much greater percentage. Some labs say up to 70% deficiency with the homozygous mutation. That’s a lot.
What Disturbs Methylation?
Methylation can be disrupted due to the genetic mutation and the turning on or off of the snps. Diet can help. The folate from green leafy veges and eggs is helpful, but you may also have folic acid from processed foods which is not good. Choline, tyrosine, tryptophan, methionine, SAMe and other amino acids need to be in supply for methylation to occur.
Lifestyle factors are extremely important and all have an affect on methylation. These include:
- State of mind and state of adrenal stress levels
- Lack or excess of exercise
- Alcohol and caffeine intake can deplete the methylation cycle
- Lack of nutrients which are cofactors such as the B vitamins, zinc, magnesium, selenium, etc.
- Oxidative stress and inflammation can reduce methylation
- Toxic load can affect methylation
- The MTHFR snp can cause a burden from the heavy metals
- Gut health, pathogens and infections can decrease the methylation pathway
- Lack of sleep can decrease the methylation pathway
- As we age we have accumulations of stress, toxic load, etc
Interestingly, 98% of autistic children have the MTHFR gene and some other mutations that may contribute to autism.
What’s the Good News?
We can turn the expression on and off with diet and lifestyle changes.
This is the field of epigenetics, the science of how our environmental triggers influence, modify and regulate our gene activity. It can alter the way our genetic code is expressed. The genes can turn on and they can turn off. Genes are not necessarily our destiny, we can modify them through lifestyle changes.
There are studies on identical twins where one is sick and one is healthy although they have the same exact genes. This shows that it’s not just about DNA – diet and lifestyle factors can turn the genes on and off.
Genetic Testing and Interpretation
When to test – perhaps there is cardiovascular disease, miscarriage, mood disorders, or other indications.
One of the labs that does this testing is 23andme. They will test all the snps for $99.00. This will give you the raw dates and you can go to different websites to figure out the indications, or you may have a doctor that can help you interpret it.
I had my test done at Labcorp (Quest also does it), but these labs just do the MTHFR panel for the two main snps (A1298C and 677C).
Just because you may have a snp doesn’t mean that you are going to be sick from it. As with anything, you have to correlate the test with the clinical presentation.
This is an emerging field and so there is still a lot we do not know about it. However, if you do have a disease this is a good test to do as you continue on your healing journey.
If you find out that you do have MTHFR snps that may be contributing to your illness, be aware that just taking high dose supplements is not going to be the answer. In fact, you should never take high dose supplements without the guidance of a knowledgeable health care provider.
Coleen Walsh gives the advice of going low and slow in the beginning and this goes for any changes in diet, changes in supplementation or other lifestyle changes. When you have these snps, your detoxification system is not working well and if you suddenly start to detoxify with new supplements or dietary changes, you could feel worse and really make yourself sick.
Therefore, I repeat, go low and slow and work with a knowledgeable health care provider.
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As with any new change, discuss this with your personal health care provider. See my Disclaimer here.