MTHFR vs Methylation?

They are not the same thing but they are related. 

MTHFR (Methylenetetrahydrofolate-reductase) is an enzyme (by the genetic snp of the same name) that is essentially responsible for taking all the folate you eat and turning it into 5-methyltetrahydrofolate (Methylfolate for short). 

Why do you care?

Methylfolate is very important for the Methionine Cycle which is often called the Methylation Cycle. The Methionine Cycle takes homocysteine, converts it into methionine (using several co-nutrients such as methylfolate) which then makes SAM (S-Adenosylmethionine). 

SAM is a potent methyl donor that helps “methylate” things like some of your estrogens to help with phase 2 detoxification. Once SAM donates its methyl group, it returns to the cycle as SAH (S-adenosylhomocysteine) and the process starts over again with homocysteine.

Phew! That’s a lot of information around the word “methyl” or “methylate.” 

Basically, if you have a "dirty" MTHFR (as referenced by Dr. Ben Lynch's book, Dirty Genes, that I highly recommend) you will have methylation problems with things ALL OVER your whole body, not just with folate. 

In fact, you’ve maybe had your MTHFR tested and told you had a variant (sometimes called a mutation - but you’re not a mutant - so I prefer variant). Having a variant in the MTHFR family affects the way you do or don’t handle folate and those cycles!

Let's take estrogen as an example.

While MTHFR is important for the Methionine/Homocysteine/Methylation cycle, the end product, SAM,  is so important for estrogens.

A different enzyme made by the COMT (Catechol-O-Methyltransferase) snp uses SAM (which required methylfolate) to detox estrogen.

When your body is done with your two main estrogens (E1 and E2), it pushes them into phase 1 detoxification and they are known as the metabolites, 2-OH or 4-OH. Typically, 2-OH is the preferred pathway.

The 4-OH pathway is considered the 'naughtier' pathway. If 4-OH does not get methylated as part of phase 2 detoxification there is an increased risk for DNA damage. (We don’t like DNA damage, btw). During the act of methylation, SAM donates its methyl group which gets transfered onto 2-OH and 4-OH by COMT. This turns them into way better neutral forms known as 2-methoxy and 4-methoxy. 

The act of methylation here turns estrogens that could be harmful into a neutral option in the body that won’t wreak havoc.  

Therefore, your estrogen detox relies on both MTHFR and COMT. 

If you have a broken MTHFR (or COMT), there is a much higher chance that you could have estrogen detoxification issues. This may be the cause of your PMS, heavy periods, clots, tender breasts, and moodiness. It may also increase your risk for estrogen based cancers. 

Does this mean you should take the nutrient, methylfolate if you have mutations in your MTHFR gene? Not necessarily. It depends on a whole lot of other factors and symptoms. Work with your functional health care practitioner to guide you appropriately!