Hashimoto’s and the MTHFR Gene

Pink and purple DNA strands on black background

You’re Not Crazy, It’s Your Genes

Hashimoto’s is a complicated condition. It’s not just a thyroid problem. It’s an autoimmune disease, it’s progressive and over time it can impact many different parts of your body.

This is true on the macroscopic where it affects major organs like the thyroid, liver, adrenal glands, brain, pancreas, stomach, small intestine, gall bladder and more.

And this is also true on the microscopic level where it affects immune cells, hormones, neurotransmitters, enzymes, proteins and even DNA and specific genes.

And with many of these influences, it is not a one way street.

One thing affects another and you sometimes have the creation of vicious cycles and problems and its hard to tell where they started.

The MotherFR Gene

In this post we will examine one of these vicious cycles on the microscopic level called the MTHFR gene.

MTHFR sounds a little scary and I like to think of it as the MotherFR gene because it can cause so many problems.

MTHFR is an abbreviation for a gene with a very long name, methylenetetrahydrofolate reductase.

(MotherFR is so much easier to remember.)

The MotherFR Enzyme

Basically, what the MTHFR gene does is produce an enzyme with the same really long name (methylenetetrahydrofolate reductase).

Genes produce enzymes and these enzymes do all the heavy lifting, they do the work.

They make stuff happen in the body. Without enzymes we wouldn’t have physiological function.

The job for the MTHFR enzyme is to convert one form of folate into the most active and usable form of folate in the human body – in every cell in the body.

This type of folate is called methyltetrahydrofolate  or more commonly by it’s nickname methylfolate.

Methylfolate Does 2 Important Jobs:

Firstly, it helps make neurotransmitters in your brain.

Neurotransmitters are our molecules of emotion.

They are what enable us to think, reason, laugh, cry, be happy, sad,  love, learn, crave and have crushes.

When methylfolate levels are low, so are your neurotransmitters.

And low levels of neurotransmitters like serotonin, dopamine, GABA and acetylcholine cause all kinds of unpleasant feelings and behavior.

Like depression, anxiety, bipolar disorders, ADHD, addictive behavior, irritability, insomnia, learning disorders and more.

With Hashimoto’s we often see depletions in these neurotransmitters.

This can be caused by too little thyroid hormones (both T3 and T4) and/or MTHFR defects.

The second thing methylfolate does is it allows us to make something called s-adenosylmethionine better known by its nickname SAMe.

SAMe is important because it helps regulate 200+ enzymes in the human body, its influence is second only to ATP which is every cell’s power source.

Basically what SAMe does is to take what is called a “methyl group” and give it away to these 200+ enzymes and this is what allows them to do their jobs.

Jobs like protect DNA, reduce histamine levels, maintain T and B cell responses, produce key components of cell membranes and about 196 other things.

Low Levels of SAMe – Not Good

Because SAMe is so important, when we are deficient in it, we are at higher risk for a lot of different diseases like: autoimmune disease, cancer, infertility, autism, down’s syndrome, thrombosis, high blood pressure and more.

And with autoimmune diseases, studies demonstrate the central role of SAM-dependent methylation ( I’ll explain this in a second) associated with T cell function and it is a key factor in maintaining T and B cell immune responses.

New T cell synthesis is needed in order for T cell clones to expand and respond properly to an immune assault. T cells are needed to help to control the B cells and to balance TH1 and TH2 responses.

If there are methylation cycle problems or mutations, you may have trouble making the bases that are needed for new DNA synthesis.

If you cannot make new DNA, then you cannot make new T cells and as a result you may lack immune system regulatory cells. This is like having a weak and ineffective general who can’t control his troops.

The immune system has many arms, but the B cell “arm” that makes antibodies, known as humoral immunity. I like to think of this part of the immune system as the C.I.A. It gathers intelligence and labels the bad guys.

There is also the T cell “arm” known as cellular immunity, these are like the elite soldiers of the front line. They do the attacking and killing. These are the cells that are often overzealous in Hashimoto’s.

For an in depth discussion on this, check out this post.

If you are having trouble making new T cells, in particular, T suppressor cells, then the immune response may become more heavily weighted in the direction of B cells.

B cell skewed individual has the ability to respond by making antibodies (or autoantibodies) in high numbers to attempt to overcome the T cell deficiency that fights infection.

This is one of the factors in high antibody counts in autoimmune disease.

Methylation Pathways – Follow the Yellow Brick Road

Methylation is how we get to Oz.

It is the act of taking a single carbon and 3 hydrogens – a methyl group – and attaching itself to an enzyme.

When this happens, the enzyme can do it’s thing.

One common example of this is the breakdown of histamine.

What happens here is a methylation group is made by the methylation pathway and it hangs around until it finds a specific enzyme to bind to.

In the case of histamine, when the methyl group binds to it, the histamine falls apart and goes bye bye.

On the other hand, if your methyl pathway is not making enough methyl groups, then histamine doesn’t break apart and this causes some pretty intense allergic reactions.

For some this may mean running nose and itchy eyes, for others it is full on hives and intolerable itching.

Histamine Intolerance and Hashimoto’s

One thing I have observed clinically is that there is a sub-group of people with Hashimoto’s who have histamine intolerance.

This can really complicate recovery and make some of the solutions that help others not work for them.

For example, the Paleo and Autoimmune Paleo diets both have a number of foods that are high in histamine, like bone broth.

So these people eat these foods, thinking that they are doing the right thing (and they are in theory) and they wind up feeling really crappy and just not getting better.

And the people with the most intense reactions may have higher levels of histamine and decreased methyl groups.

Research Shows Link Between More Severe Hashimoto’s and MTHFR

What is also interesting is that research has shown some correlation between more severe Hashimoto’s and some of these methylation defects.

Which kind of makes sense, because, as we have seen, SAMe is responsible for maintaining immune responses. And with autoimmune disease, these responses are out of control.

Well, this could be one reason why.

Methylation and Your Brain

Another key area where this is a concern is brain health. We’ve already seen the impact of methylation on neurotransmitters.

They also play a key role in keeping your myelin healthy.

Myelin coating on nerves is important for proper function of those nerves. Methylation of amino acids in myelin basic protein helps to stabilize it against degradation.

When you lose myelin or it starts to break down then your nerves and brain can’t communicate as well. Myelin is like the coating on the outside of a copper wire.

If a wire isn’t coated it can short out or get major interference from other electrical impulses. In you body this can lead to poor memory or more severe losses in function like those seen in Multiple Sclerosis ( an autoimmune disease caused by the breakdown of myelin).

Methylation and Glutathione

But, wait there’s more! Methylation is also really important for glutathione production.

Glutathione is our body’s body guard. It is involved in controlling inflammation and in getting every environmental toxins you can think of out of our systems through a process known as direct conjugation.

It is a major anti-oxidant, it regulates the nitric oxide cycle, it is essential for the immune system to operate properly.

It affects how antigens present to immune cells, it can strengthen the regulator part of the immune system.

It is involved in every major biochemical activity, especially those systems most impacted by Hashimoto’s: the immune system, the nervous system and the gastrointestinal system.

It’s importance can not be overstated.

Thyroid Health and MTHFR

With Hashimoto’s and hypothyroidism, some people develop a sluggish MTHFR enzyme.

This happens because thyroxine (T4) helps produce the body’s most active form of vitamin B2, flavin adenine dinucleotide know by its nickname FAD.

Vitamin B2 must be converted into active FAD by T4 so that the body can use it.

And, the MTHFR enzyme must have enough FAD in order to do its job. If FAD levels are low due to too little T4, then the MTHFR enzyme slows down, which leads to low methylfolate which leads to low neurotransmitters, which leads to low SAMe.

No bueno!

This becomes a vicious cycle.

MTHFR and High Homocysteine

Another really common finding that I see in analyzing blood test results from Hashimoto’s patients is that they have high levels of homocysteine.

As it turns out, low activity of the MTHFR enzyme may also lead to this. High homocysteine is a major risk factor for heart disease, inflammation, difficult pregnancies, birth defects, and more.

Nutrient deficiencies in Folate B6, and B12 have been linked to high homocysteine.

To matters more complicated, people with MTHFR issues may have a difficult time processing certain types of folic acid like those found in processed food and cheap supplements.

A better source is real food: asparagus, spinach, and liver. Both B12 and B6 are found in meat. And alcohol can deplete the body of B6.

Betaine is also helpful in metabolizing homocysteine.

If you are found to have the MTHFR gene variations and/or you have high homocysteine a better way to supplement is to use the activated version of folate, B6 and B12.

These are:

Methylfolate: (also known as L-5-MTHF Folate)

Pyridoxyl-5-Phosphate (P5P): B6

Methylcobalamine: B12

The Type of B12 Matters

(Thanks to Vicki Ross for sending me an email to help clarify this very important point.) Not everyone can tolerate methylcobalamine (B12). Just like not everyone can tolerate caffeine, some people don’t do with with methyl cobalamine. And the MTHFR results provide clues to how to determine who may not respond well.

The COMT & VDR genotypes determine WHICH B12 you should take. Most people can handle Hydroxocobalamin or Adenosylcobalamin, but may have problems with methyl B12.

Here is a breakdown of the 4 types of B12:

1. Methylcobalamin

This is the most active form in the human body. It converts homocysteine into methionine, which helps protect the cardiovascular system. Methylcobalamin also offers overall protection to the nervous system. This B12 form can also cross the blood-brain barrier–without assistance–to protect brain cells. It contributes essential methyl groups needed for detoxification and to start the body’s biochemical reactions.

2. Cyanocobalamin

This synthetic version of vitamin B12 is created in a lab, which makes it the cheapest supplement option. It offers the most stable form of B12, although it does so through the presence of a cyanide molecule. While the amount of cyanide is not dangerous, it does require the body to expend energy to convert and remove it.

3. Hydroxocobalamin

Bacteria naturally creates this form of vitamin B12, making it the main type found in most foods. It easily converts into methylcobalamin in the body. Hydroxocobalamin is commonly used via injection as a treatment for B12 deficiency as well as a treatment for cyanide poisoning.

4. Adenosylcobalamin

The energy formation that occurs during the Citric Acid cycle requires this form of B12. Although naturally occurring, it is the least stable of the four types of B12 outside the human body and does not translate well into a tablet-based supplement. It can be difficult to find this one in supplement form, although some supplements, like Vegansafe™, have been able to stabilize it.

What Do We Do to Fix All This?

Well, firstly, we have to do all the other stuff we do to insure that we are thyroid healthy. And, as all of us who have Hashimoto’s know, this is sometimes easier said than done with all the different systems affected and involved.

Key nutrients for thyroid function are magnesium, iodine (no end to the controversy there – more on this in a future post), selenium, zinc and tyrosine.

Methylfolate, produced by the MTHFR enzyme is also needed to convert tyrosine into active thyroid hormone.

So you can se, we have all the ingredients of a vicious cycle.

Where hypothyroidism leads to MTHFR not working as well, which leads to thyroid hormone not being converted properly and on and on.

Here are some basic tips to correct these challenges:

1. Consider supplementing with glutathione and Vitamin D.

2. Take the active forms of B vitamins mentioned above.

3. Incorporate organic grass fed meats and good fats into your diet.

4. Avoid processed foods and environmental chemical that compete for iodine receptors like fluoride, chlorine and bromine (bromide).

5. Avoid gluten, dairy and soy 100%

6. Avoid GMO foods.

7. Consider testing for homocysteine and the MTHFR gene mutations and defects.

Testing for homocysteine and the MTHFR gene variation is available through many labs. 23andme.com offers a test for the MTHFR gene and many individuals can get the tests from their physicians covered by insurance.

However, some people may be concerned ( and with good reason) with this genetic information getting reported on insurance or to employers.

A MTHFR variation or elevated homocysteine levels may affect future insurance coverage especially with the advances in personal data mining and sharing.

To find out more information about MTHFR testing – along with the ethical considerations of it – visit: MTHFR test options


http://www.jimmunol.org/cgi/content/meeting_abstract/188/1_MeetingAbstracts/116.13 -SAMe and Autoimmune disease

http://www.ncbi.nlm.nih.gov/pubmed/23039890 – Severity of Hashimoto’s corresponds with defect


MTHFR Basics, Benjamin Lynch, ND




About the Author Marc Ryan

So now, not only is it my profession, it’s my passion, and it’s personal. I’ve been joking with people lately saying it’s a blessing and a curse. A blessing because I really get it, and a curse because I really got it! ?

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