Deficiency, Folic Acid VS Methylfolate, & Methylation


Methylfolate or folic acid, they are very different. We will talk about that a little bit later.

Did you know that these have links to alcohol use neural tube defects; you may know neural tube defects as spina bifida, a serious condition of birth. Over 80 countries mandate use of it to prevent that. It also has to do with megaloblastic anemia, which again we would mention it below in a few minutes. But it also has to do with that thing called methylation and anxiety and depression. So let’s get a little bit deeper.

Neural Tube Defects

So first of all, I mentioned neural tube defects. That’s what doctors learn in medical school. Folic acid is a big deal for prevention. For that, 80 countries mandate supplementation with folate. Sometimes folic acid, they are okay with that. But those of us who are little bit deeper into things like methylation would say methylfolate is better. It’s better absorbed. But the big deal is permanent spinal injury associated with inadequate development of the spinal cord.

Large immature Red Blood cells (Megaloblastic Anemia)

Then you have large immature red blood cells with what we call megalo (meaning large and immature red blood cell), megaloblastic anemia. This can be associated with fatigue, shortness of breath, glossitis or tongue inflammation, weakness, diarrhoea. Again you can see that with deficiency of folate.

What are the causes of folate deficiency?

That’s where alcohol comes in. it’s one of the more common causes of folate deficiency because it interferes with absorption of folate.

Pregnancy, it is a problem for folate deficiency because of the increased need. You have got the baby making a lot of DNA folate like cobalamin (vitamin B12). Both of these are used a lot in terms of making DNA. And when you have got a baby on board, that baby is making a lot of DNA, also dietary insufficiency.

Now we have mentioned that folate and folic acid are different.

Folate is the naturally occurring essential vitamin. It’s easily absorbed and metabolized.

Folic acid, on the other hand is synthetic. It’s used in supplements. A lot of foods are fortified with it, like cereals. It requires the enzyme dihydrofolate reductase, which methylfolate doesn’t require.

Side Effects for Some Folic Acid

Side effects for some folic acid can be some endocrine side effects, sleep, mood disorders, and things like that.

Again, folic acid is the one that’s on the mandatory for mandatory fortification list. It’s far less expensive. And again, it will prevent neural tube defects or spina bifida.

Methylation – Variation in MTHFR Enzyme

Why an Issue? Major Anti-Oxidant Activity

Methyl Group VS Hydrogen Group

Now let’s talk about methylation for just a second. Methylation is a variation in the MTHFR enzyme. Methylation is what the body tends to use for antioxidants. You must hear about the mitochondrial theory of aging. You must hear that basically there’s oxidation, there’s oxidation products lying around the mitochondria. And the mitochondria are like the powerhouse or the furnaces of the cell, and these oxidation products are like burning embers and coals lying around the fireplace. The body uses methylation to tend to put those embers out. Well, we have significant variation, over 40% of us have a variation up to 70, 75 percent of our ability to methylate, so that’s why this is an issue.

Niacin- Increased Methyl Spill

Niacin can cause the increased methyl spill of methylation methyl groups.

TMG or (Tri Methyl Glycine) Or Betaine

TMG or (Tri Methyl Glycine) or some people call it betaine. This is a chemical. It’s a supplement for methyl groups that you can take again re-supplement pill methyl groups.

Here’s a brief visual of how the methylation products process works.

Formation Of Methionine

Methionine is formed from homocysteine. Methionine is an amino acid that’s needed for DNA and protein syntheses. And it requires methylation of homocysteine to get there. So you remember that concept. You may remember that homocysteinemia or increase homocysteine in the blood is a risk factor for heart attack and stroke. Yes, it is. And one of the reasons appears to be that it’s a signal for methylation problems.


I have mentioned above the difference between folic acid and folate and their side effects and their problems in detailed. I hope it would help you with folate and folic acid.


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