What Supplements Should You Take If You Have a MAT1A Mutation?

The MAT1A gene doesn’t get much attention in the methylation world. In fact, many “methylation tests” don’t even test for your MAT1A variant—instead, they just focus on five genes: MTHFR, MTR, MTRR, AHCY, and COMT.

But that’s a big loss, as the MAT1A is actually highly important to your ability to properly methylate.

In fact, MAT1A is arguably the gene with the most direct impact on methylation.

How so?

The MAT1A gene produces an enzyme (like a small molecular “machine”) that converts methionine into SAMe (S-adenosyl-methionine). SAMe (also known as SAM) is the “master methyl donor” of the body. It’s exactly what we are trying to optimize when we talk about “optimizing methylation” because it’s that SAMe that goes throughout the body and performs the various methylation functions, like

• Regulating neurotransmitters,

• Producing creatine,

• Removing histamine,

• Detoxifying harmful substances,

• Regulating gene expression,

• and much more.

If you don’t have enough SAMe, many if not all of the above processes will not function properly, and you’ll develop issues like brain fog, chronic fatigue, allergies, inflammatory issues, sleep problems, weakness, etc.

MAT1A directly produces that SAMe.

So if your MAT1A enzyme (produced by your MAT1A gene) is not functioning properly, you won’t be able to effectively produce SAMe, and you’ll get those same problems.

Not optimizing MAT1A is a common mistake made in many methylation programs and supplementation regimens.

Many methylation-focused supplement regimens are all about increasing methionine.

They load you up on methyl-folate (5-MTHF), methyl-B12 (methylcobalamin), TMG (also known as betaine), and so on, all with the goal of maximizing your levels of methionine.

Presumably, your body will be able to take that methionine and produce SAMe out of it to optimize your methylation.

But it’s not really that simple.

If you’re constantly maxing-out your methionine levels by taking a lot of methyl-folate, methyl-B12, etc. daily, then you’re putting a lot of stress on your MAT1A enzyme, because it’s that same MAT1A that is going to have to go and turn that methionine into SAMe.

That’s a problem because, over time, your MAT1A can potentially become essentially “overloaded” due to all that methionine influx and become less effective at turning it into SAMe.

I’ll refer to this as “methionine fatigue.”

And that’s especially the case of you have a MAT1A deficit (or “mutation”).

A MAT1A mutation or deficit will make you less able to turn methionine into SAMe—and more prone to that “methionine fatigue” that comes with taking a bunch of methyl-folate, et. al.—and thus more prone to undermethylation.

Studies have even correlated strong deficits in the MAT1A gene with actual, bona fide vascular problems. This is probably due to a combination of the “methionine fatigue” and the undermethylation that these MAT1A deficits bring.

Severe deficits in the MAT1A gene can even cause damage to the central nervous system—meaning the brain and the spinal cord.

This makes it highly important to optimize your MAT1A function. If you do genetic methylation testing, ideally you should make sure the methylation test includes the MAT1A gene (like our Comprehensive Methylation Panel).

What supplements should you take if you have a MAT1A mutation (or deficit)?

First of all, keep in mind that the “bad” version of the MAT1A gene corresponds to the “A” allele.

One copy of the “A” allele reduces your MAT1A function somewhat—meaning less SAMe and thus undermethylation—and two copies (i.e. from both parents) of the “A” allele greatly reduces your MAT1A function—meaning much less SAMe and undermethylation.

Having even one “A” allele is enough to make it important to supplement to optimize function. Generally speaking, having a MAT1A mutation means you need to supplement or optimize your potassium, magnesium, and ATP levels, as below:

To address a MAT1A mutation, you absolutely must optimize your magnesium levels.

Magnesium is a “cofactor” for the MAT1A enzyme, meaning it is required for its function. If you don’t have enough magnesium, your MAT1A enzyme will not function properly, and you won’t be able to make enough SAMe.

How to take magnesium is a whole discussion of its own. For that, I’d suggest you refer to my Complete Guide to Magnesium Supplementation or, alternatively, my 5-Week Plan for even more detail.

It’s also essential to optimize your potassium levels to address a MAT1A mutation.

It has long been observed the increasing methylation (by taking methyl-folate, methyl-B12, etc.) tends to deplete potassium in the body.

Exactly how it does that is still not really understood, but I personally theorize that it’s partly due to the stress put on the MAT1A enzyme.

MAT1A requires potassium to function properly (just like magnesium above). When you put a lot of stress on that enzyme through a huge methionine influx, as discussed above, that can theoretically deplete potassium by requiring large amounts for the function of this enzyme.

In any case, any mutation or deficit in the MAT1A enzyme requires potassium optimization.

I do not recommend doing this through supplementation. You need to get it mainly through diet, as I discuss in my 5-Week Plan.

ATP availability also needs to be optimized for optimal MAT1A function.

ATP is the “energy currency” of the body. It’s what the body requires to fuel basically all energy-dependent reactions. And it’s what your body produces from the fuel (i.e. the food) that you consume.

ATP is usable energy for the body. And that ATP is required for the MAT1A enzyme to do its job of converting methionine to SAMe, the master methyl donor.

Optimizing ATP availability is a whole discussion of its own, so I’m not going to attempt to breach that conversation here. But at least let it be known that this is one essential component of optimizing for your MAT1A variant.

Keep in mind that this is not official medical advice. This is purely educational information and should not substitute for your doctor’s medical advice. No doctor-patient relationship is established through this article or through any other information provided on this website.