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What is MTHFR?


Did you know that 70% of the world’s population has an MTHFR gene mutation?!

If you’re visiting us, chances are you’ve heard of MTHFR. Perhaps you or someone you love has recently discovered that an MTHFR mutation is behind longstanding health concerns.

But we can’t all be scientists, and we don’t always have the time or energy to dive into the minutiae of MTHFR.

That’s where Methyl-Life comes in!

We’ve done the research. We’ve read the books, talked to the doctors, taken the deep dive.

We’ve done it all so that we can deliver you the best-quality supplements, but also so that we can share what we’ve learned and build a community around our shared health concerns and requirements.

Here’s just a few examples of informational topic we cover on our site:

MTHFR Symptoms                    Treating MTHFR                             MTHFR and Methylation

But before we get to all that, let’s make sure we’re all on the same page…

What is MTHFR, and what does it mean to have an MTHFR mutation or MTHFR deficiency?

MTHFR stands for Methylenetetrahydrofolate Reductase. It is a key regulatory enzyme in the metabolism of folate. It also refers to a specific gene that plays a major role in the body’s methylation process. However, when people talk about “MTHFR,” they’re usually not talking about either the enzyme or the gene, precisely. They are actually referring to one of the two common MTHFR gene mutations that causes the enzyme to become imperfect and much less effective in the body.

The gene’s role is very complex, and MTHFR gene polymorphisms (or variants) have been the focus of recent discoveries uncovered by the Human Genome Project. In fact, thanks to the Human Genome Project, we now know that there are as many as 50+ variants of the MTHFR gene! MTHFR polymorphisms are often referred to as ‘mutations’ or ‘defects’ because of the problems they cause in the body.

MTHFR most often refers to a genetic mutation that inhibits the ability of the body to methylate. This means that the body has trouble converting folic acid from the food we eat into methylfolate (L-MTHF). Unfortunately, our cells cannot actually use folic acid directly. It must go through a 4-step process (called a metabolic pathway) to be converted into methylfolate, which is the “active” or usable form of folate that our body’s cells require. The MTHFR gene defect inhibits this metabolic pathway and prevents our cells from getting the methylfolate they need.

Read more about Methylation and folic acid conversion.

Although we now know that there are more than 50 possible MTHFR gene mutations, the MTHFR Blood Test used today only checks for the two defects that are considered “common”: 677 and 1298 (discovered in 1995 and 2001, respectively). Learn more about Methyl-Life’s top 3 recommendations for MTHFR testing >>

But, since we all get one copy of the MTHFR gene from each parent, a person could have many different combinations, as well as the problems that go with it. In fact, it’s very rare, but some folks can have 3 mutations (a double mutation in one gene and a single mutation on the other), or even 4 mutations (though we have not heard of any specific case of this).

With or without knowing your specific MTHFR mutation status, however, we can still help you determine what nutritional supplements can help you feel better.

Methylation Protocol >>

Dosage >>

Choosing the Right Methylfolate Products >>

Want to know more about possible MTHFR gene mutations?

For handy reference, below is a chart listing possible MTHFR gene mutation combinations and the potential health issues related to it.

 AA1298 / CC677 Normal for the two common variants, or mutations, 677 and 1298
 AA1298 / C677T Single 677 mutation – More susceptible to environmental damage, depression, central nervous system issues, etc. (referred to as Heterozygous)
 A1298C / CC677 Single 1298 mutation – More susceptible to environmental damage, depression, central nervous system issues, etc. (referred to as Heterozygous)
 1298CC / CC677 Double 1298 mutation – Much worse for the above problems (referred to as Homozygous)
 AA1298 / 677TT Double 677 mutation – Similar to 1298CC plus heart disease, blood clots, and more (referred to as Homozygous)
 C677T / A1298C Single 1298 + Single 677 – Susceptible to all of the above and worse for strokes, heart disease, blood clots, etc. (referred to as Compound Heterozygous)

What happens if the cells don’t get enough methylfolate to keep your body healthy?

LEARN MORE ABOUT MTHFR SYMPTOMS

MTHFR is a key regulatory enzyme in the metabolism of folate. It also refers to a specific gene that plays a major role in the body’s methylation process. Both the enzyme and the gene have the same name, MTHFR. The gene’s role is very complex, and recent discoveries of the Human Genome Project have been focused around the MTHFR gene polymorphisms (or variants). These polymorphisms are often referred to as ‘mutations’ or ‘defects’ because of the problems they cause in the body. Most often, when you hear someone talk about MTHFR, the person is actually referring to one of the two common MTHFR gene mutations that causes this MTHFR enzyme to become imperfect and therefore much less effective.

To put it simply, MTHFR most often refers to a genetic mutation that inhibits the ability of the body to methylate (or convert folic acid from the food we eat into the enzyme we need, L-5-Methyltetrahydrofolate  [or L-MTHF for short]). Methylfolate (L-MTHF) is most often referred to as the ‘active’ or usable form of folate that our cells require. Because the body’s cells cannot actually use folic acid, it must first go through a metabolic pathway or 4-step conversion process to become Methylfolate (L-MTHF) before the cells can directly use it (see MTHFR and Methylation). It is this metabolic pathway that the MTHFR gene defect inhibits!  See diagram on folic acid conversion steps.

Many of the learnings about this gene defect have come out of the Human Genome project and taught us that there are as many as 50+ variants of the MTHFR gene. However, only two are considered ‘common’ defects that today’s MTHFR Blood Test checks for, those  are:  677 and 1298 (discovered in 1995 and 2001 respectively). Check the FAQ to learn more about being tested for MTHFR.

Since, we all get one copy of the MTHFR gene from each parent, a person could have any one of the following combinations as well as the problems that go with it:

check_mark_gray  AA1298 / CC677 Normal for the two common variants, or mutations, 677 and 1298
check_mark_gray  AA1298 / C677T Single 677 mutation – More susceptible to environmental damage, depression, central nervous system issues, etc. (referred to as Heterozygous)
check_mark_gray  A1298C / CC677 Single 1298 mutation – More susceptible to environmental damage, depression, central nervous system issues, etc. (referred to as Heterozygous)
check_mark_gray  1298CC / CC677 Double 1298 mutation – Much worse for the above problems (referred to as Homozygous)
check_mark_gray  AA1298 / 677TT Double 677 mutation – Similar to 1298CC plus heart disease, blood clots, and more (referred to as Homozygous)
check_mark_gray  C677T / A1298C Single 1298 + Single 677 – Susceptible to all of the above and worse for strokes, heart disease, blood clots, etc. (referred to as Compound Heterozygous)

Interpreting 23 and me results

check_mark_gray  MTHFR AA1298 (rs1801131) or TT is normal (no gene mutation)
check_mark_gray  MTHFR A1298C (rs1801131) or GT is heterozygous (single gene mutation)
check_mark_gray  MTHFR 1298CC (rs1801131) or GG is homozygous (a double gene mutation)
check_mark_gray  MTHFR CC677 (rs1801133) or GG is normal (no gene mutation)
check_mark_gray  MTHFR C677T (rs1801133) or AG is heterozygous (single gene mutation)
check_mark_gray  MTHFR 677TT (rs1801133) or AA is homozygous (a double gene mutation)
check_mark_gray  MTHFR A1298C (rs1801131) or GT + MTHFR C677T (rs1801133) or AG is referred to as “compound heterozygous” (a single gene mutation of each type)

And it’s very rare, but some folks can even have 3 mutations (a double mutation in one gene and a single mutation on the other) or conceivably 4 mutations (though I’ve not heard of any specific case of this in real life) if they have:

check_mark_gray  MTHFR 1298CC (rs1801131) or GG    +    MTHFR C677T (rs1801133) or AG   –   (a triple mutation)
check_mark_gray  MTHFR A1298C (rs1801131) or GT    +    MTHFR 677TT (rs1801133) or AA   –   (a triple mutation)
check_mark_gray  MTHFR 1298CC (rs1801131) or GG    +    MTHFR 677TT (rs1801133) or AA   –   (a quadruple mutation)

Note

Normal means the MTHFR gene has neither the 677 nor the 1298 variant (defect), so it could prove to actually be ‘Normal’ or it could be one or more of the 48+ other variants there is no typical medical test for yet (though it’s worth noting that 23andme will actually test for a number of MTHFR genes, not just the 677 & 1298). If a test comes back ‘Normal’ or negative for the two well-known mutations (677 &1298), it does not necessarily mean that the body’s methylation process is working well. See MTHFR and Methylation.

Ben

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