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If This Sounds Like You, You Might be Undermethylated

MTHFR mutation discussions can quickly turn into Greek and the topic of overmethylated vs undermethylated MTHFR is one of the Greekest. It seems like no two resources on the internet are talking about the same thing when they talk about it and so overmethylation and undermethylation are strange, kind of meaningless words because at the end of the day it feels like nailing jello to a wall. So let’s see if we can sort some of this out.

Whose Idea Is This? I’m Following The Walsh Research Institute

The terms overmethylation and undermethylation make the most sense to me as the Walsh Research Institute uses them.  These are general physical tendencies based on the sum of your genetics, nutritional status and body burden. There isn’t one gene or genetic defect alone that can account for them – so just because you have an MTHFR C677T mutation doesn’t actually mean you’re over or under methylated (although it would be one factor that might push the balance to undermethylation).  Dr. Walsh describes one’s methylation status as being like a tug of war between opposing factors. Many of those are genetic and some are nutritional or environmental.

Undermethylation MTHFR

This is the most common state. According to Dr. Walsh’s research, 70% of the population are normal methylators, 22% are undermethylators and 8% are overmethylators. Undermethylation indicates that the methylation cycle as a whole is slowed down enough that the end product, SAMe, is typically inadequate and thus causes symptoms.

Highly competitive? You might be undermethylated




Addictive behaviour? You could be undermethylated. © Francesco Bisignani | Dreamstime Stock Photos

Is Undermethylated the Same as Under-supplemented?

No! Although it seems that in a lot of popular literature on the subject people use the term interchangeably. So often you’ll see someone say that you might still be “undermethylated” if you aren’t taking enough 5-MTHF.  I feel that these are different things entirely.  If you have a tendency to be undermethylated then certainly you will probably need to take 5-MTHF, but even once you’re taking enough you are still an undermethylator (in my opinion), you’re just taking the right protocol.  Likewise taking too much 5-MTHF, doesn’t make you suddenly “overmethylated” it just means you’re taking too much.

Okay! I’m Undermethylated. Now What?

Absolutely the best way to enhance the methylation cycle is by taking 5-MTHF, or 5-L methyltetrahydrofolate.  This is the active form of folic acid, and you can also get it from foods, especially if you have some trouble taking the supplement.  Trouble taking the supplement is surprisingly common, typically it is an adjustment reaction to actually enhancing the methylation cycle because this changes neurotransmitter levels, encourages detoxification and encourages more than 80 reactions in the body that are methylation dependent. So some adjustment reaction when you’re first taking 5-MTHF is normal and actually a good sign that things are changing in your body.   There is one BIG EXCEPTION TO THIS, and that is if you are undermethylated and have depression.

I Want to Start Taking 5-MTHF. How Do I Make This Easy?

Any time you start taking 5-MTHF, or increase your dose, there will be an adjustment period.  Here’s a whole post on it.  Just remember, start with a low dose and increase really slowly. This is changing the way your neurotransmitters work and doing some heavy detox work, so it’s vital not to overdo it because that is crazy-making. Start low and go slow.

HELP! I’m An Undermethylator and I Have Depression.

My next post is going to be all about this because UNDERMETHYLATORS WITH DEPRESSION DUE TO LOW SEROTONIN CAN’T TOLERATE 5-MTHF, FOOD SOURCES OF FOLATE OR FOLIC ACID AT ALL. That’s a really big deal! Depression is typically characterized by low serotonin states and unfortunately 5-MTHF (or any folate or folic acid). The short explanation for this is that folate, 5-MTHF and folic acid all increase the activity of the transport protein that re-uptakes serotonin into the cell. Essentially this is the opposite of a serotonin reuptake inhibitor (like prozac), it’s a serotonin reuptake promotor – meaning it makes the serotonin you have far less effective because it clears it out more quickly. There will be a whole post on this – I promise!



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