Methylfolate Dosage for MTHFR: How much should I take?

No doubt you just got your genetic test results back. You learned that you have a MTHFR mutation.

You’re scared and want to fix it.

Breathe.

What you’re experiencing is a natural reaction to something that is unknown and appears dangerous to your health.

There are many experts claiming that a methylfolate dosage formula exists for MTHFR variants.

Is there?

I’ve been educating health professionals and the public about MTHFR since 2011. That’s well over a decade of experience. If anyone knows about how much methylfolate to take, it’s me.

Let’s break it down.

If methylfolate dosage was indeed based on which SNPs you had in your MTHFR gene, it could look something like this:

• MTHFR A1298 heterozygous (1 copy): xx mcg
• MTHFR A1298 homozygous (2 copies): twice as much
• MTHFR C677T heterozygous (1 copy): yy mcg
• MTHFR C677T homozygous (2 copies): three times as much
• Compound Heterozygous (1 copy of A1298C and 1 copy of C677T): same as MTHFR C677T homozygous

Why would the methylfolate dosage vary like this?

Each variation of the MTHFR gene impacts how effectively your MTHFR enzyme produces methylfolate.

The job of your MTHFR gene is to make the MTHFR enzyme.

The job of the MTHFR enzyme is to produce your body’s number one form of folate called methylfolate.

Thus, it makes sense that if you inherited a less effective MTHFR gene, you would need to take more methylfolate.

Various published studies on the functional effect of MTHFR genetic mutations do exist.

A functional study looks at how a specific genetic mutation impacts the function of the enzyme.

Here’s a summary of what researchers have found in terms of functional effect of each common MTHFR SNP:

Summary of MTHFR Enzyme Activity by Genotype

There are a couple things in this table that may be alarming and confusing.

• ~ xx% of normal
• If you have inherited a MTHFR C677T (TT), you see that your MTHFR enzyme may function 70% less than a normal MTHFR enzyme.
• If you have inherited a MTHFR A1298C (CC), you see that your MTHFR enzyme may function 32% less than a normal MTHFR enzyme.
• I don’t like the word ‘normal’ here. They should use ‘typical’.
• Normal means that something is more common and not a problem.
• We immediately think abnormal if it’s not normal.
• Having a MTHFR mutation is not disease causing.
• A MTHFR mutation may increase our vulnerability to various conditions but it’s not disease causing.
• Thermolability
• This term is a fancy way of saying if something is sensitive to higher temperatures or not.
• MTHFR C677T is sensitive to higher temperatures.
• MTHFR A1298C is not sensitive to higher temperatures.

“Do I base methylfolate dosage for MTHFR on which SNP I have? If so, how much methylfolate should I take?”

No.

You do not base how much methylfolate you take based on which or how many MTHFR SNPs you have.

Let’s detail it out.

The job of your MTHFR gene is to produce the MTHFR enzyme.

The job of your MTHFR enzyme is to produce methylfolate.

What is homocysteine?

Homocysteine is a compound made by your body when it’s:<

• making creatine,
• making phosphatidylcholine,
• breaking down histamine,
• breaking down dopamine and norepinephrine
• processing protein (methionine specifically)

If methylfolate is used to process homocysteine, then the question is how much homocysteine is your body producing?

Even with the most significant MTHFR mutation of C677T homozygous, one still has 30% function left.

That 30% function produces sufficient methylfolate in people who do not produce that much homocysteine.

Now, if a person with MTHFR C677T homozygous produces a lot of homocysteine, then they will certainly need more methylfolate.^†

What increases homocysteine?

• High protein diet (carnivore, paleo)
• Exercise (the more intense and the longer it is, the more you make)
• Nutrient deficiencies
• low vitamin B6,
• low vitamin B2,
• low vitamin B12,
• low glutathione,
• low choline,
• low glycine
• Vegans and vegetarians (vegans more at risk due to nutrient deficiencies)
• Mental stress (producing more dopamine, norepinephrine which get broken down)
• Histamine (when broken down, it produces homocysteine)
• Inflammation (immune system working hard fighting infections, wounds)
• Fevers (especially those with C677T MTHFR variants as it’s thermolabile)
• Nitrous oxide (laughing gas)
• Hypothyroidism

Can you get Methylfolate from food?

Yes.

Methylfolate is found in leafy green vegetables, beans and it’s especially high in liver. (5,6)

If you’re eating these in sufficient quantities, then that’s another reason why you may not need to take more methylfolate.

How much methylfolate per day you take depends on how much demand you put on your body making homocysteine.

A MTHFR genetic variation identifies if one has a genetically reduced ability to make methylfolate.

It does not identify how much methylfolate one needs to take.

Here’s a story to bring it all together.

First Time Methylfolate Dosing for a Man with MTHFR Compound Heterozygous

In 2011, I learned from genetic testing that I have the MTHFR compound heterozygous variation.

This means I have a 50% reduced MTHFR function compared to normal. It also means that higher temperatures further reduce my MTHFR enzyme’s ability to produce methylfolate.

I immediately bought a methylfolate supplement with methylcobalamin to ‘fix my MTHFR mutation.’ It contained 800 mcg of methylfolate and 1 mg of methylcobalamin as a lozenge for better absorption.^†

The first time I took it, I felt absolutely incredible. Clear head, great energy, good mood and got a lot done that day.

The next day, I took it again. Similar results.

Since I have the MTHFR compound heterozygous mutation, I need to supplement this every day for the rest of my life, right?

I took it again the next day. Got a bit of a headache and I was a bit irritable.

The following day, I took it again. The headache became more intense as did the irritability.

Well, I have to keep taking methylfolate because ‘I have MTHFR.’

I took it again the next day. Now I got a full blown migraine and was extremely irritable.

Wait a minute.

I never ever get headaches or migraines and my moods are usually pretty good.

I stopped taking the methylfolate.

After a couple days, I got myself back again, the headache was gone and my mood was pretty good.

I learned that I need to take methylfolate based on how much I made my MTHFR enzyme work. I learned that I need to take methylfolate based on how much homocysteine my body made.

I don’t eat liver. Yuck. I eat leafy green vegetables at times but not that often. I didn’t measure my homocysteine. I was not exercising hard and I was not exposed to nitrous oxide.

Here’s another story to further drive the point home.

Meat Meat Meat. Many mg of Methylfolate Needed.

I presented at an autism conference in Texas. When in Texas, you go to a restaurant that serves great steaks. I was invited to go to a Brazilian steak house there by a group of doctors. I went. For literally 4 hours, I ate meat. The food was outstanding. I shudder to think how many pounds of meat I ate that evening.

Meat is protein. Protein contains methionine and methionine turns into homocysteine.

The next morning, my brain was all in a cloud, I was slow, stiff and could hardly think. I had to present on stage in less than two hours. Thinking about why I could be feeling this way, I realized that all the meat I ate no doubt significantly increased my homocysteine levels.

I took 800 mcg of methylfolate and 1 mg of methylcobalamin as a lozenge. In 20 seconds, I felt a little better. Then, I felt just as bad again 1 minute later. I’ve never experienced this before but I figured I needed more. Over a period of 30 minutes, I took a little more of the methylfolate and methylcobalamin at a time. I took it until I felt consistently good, clear headed and in a good mood. Then, I stopped.^†

Key Points about Methylfolate Dosage:

• The methylfolate dosage based on which MTHFR variant you have does not exist.
• The methylfolate dosage should be based on how hard you work your MTHFR enzyme.
• You vary how much methylfolate you take literally on a daily basis and momentary need.

May need to supplement with methylfolate^†:

• exercising hard
• eat a lot of protein especially meat
• stressed out and want to support a healthy response to stress
• big presentation at work so need cognitive support
• exposed to nitrous oxide at the doctor and want to support the body’s natural detoxification process
• sick and have a fever and want to support a healthy immune response
• vegan or vegetarian
• homocysteine elevated

May not need a methylfolate supplement :

• eating healthy portions, not overeating protein
• eating liver
• eating leafy green vegetables daily
• relaxing by the pool
• surrounded by great people.
• homocysteine level is good

Can a lab test show me the methylfolate dosage I need?

The short answer is no.

The longer answer is order a fasting homocysteine blood test.

If your homocysteine measures between 6 umol/L to 8 umol/L, you’re doing well.

If your homocysteine measures 9 umol/L or higher, you may need methylfolate supplementation.^†

I say may because homocysteine has a variety of reasons why it is elevated as I mentioned earlier above.

Key Points:

1. Many of us have the MTHFR mutation. Some of us have a more significant MTHFR variation than others. Methylfolate dosage does not depend on this at all.
2. Methylfolate dosage depends on how much methylfolate you need. Needs of methylfolate mainly depend on your lifestyle and food.

Be careful.

You’ve read this far which means you’ve learned a ton.

You’ve learned how to properly support your MTHFR enzyme.

You’ve learned how and when to use methylfolate.

Despite this, you’re going to be tempted to listen to whatever is the easiest.

You will find, without a doubt, somewhere on the internet, a table showing you exactly how much methylfolate you need to take based on which MTHFR genetic variation you have.

That’s easy to follow.

Frankly, it’s way easier than what I’ve explained here.

We tend to gravitate towards whatever is easiest. I get it. I want it easy, too.

Shoot, I own a supplement company. I’d absolutely love to say if you have this MTHFR variant, take this supplement each day. That’s a lot of sales!

I don’t do that.

I’ll add that the number one article I’ve ever written is called Methylfolate side effects.

Don’t get sucked into the fear, the hype and the nonsense people are feeding you on the internet - or even at your doctor’s office.

Remember, I’ve been educating health professionals about MTHFR since 2011. That’s well over a decade of experience.

I’ve also written the book on MTHFR and other key genetic variations. This book is called Dirty Genes. I highly recommend you check it out from your local library, get a copy from your local bookstore or snag a copy on Amazon.

Help your friends, family and strangers

Many people are getting hurt from taking too much methylfolate.

Please share this article far and wide.

^† These statements have not been evaluated by the Food and Drug Administration (FDA). This product is not intended to diagnose, treat, cure, or prevent any disease.

Bibliography:

1. https://www.ncbi.nlm.nih.gov/books/NBK6561/
2. https://pubmed.ncbi.nlm.nih.gov/34960114/
3. https://www.healthline.com/health/mthfr-gene
4. https://www.nature.com/articles/s41598-023-44120-8
5. https://www.healthline.com/nutrition/foods-high-in-folate-folic-acid
6. https://www.goodrx.com/well-being/diet-nutrition/foods-high-in-folate