MTHFR, Folic Acid and Folate: Should I Eat It?

MTHFR folic acid and folate

MTHFR mutations are well-known genetic variations that can impact folate metabolism.

But there is a lot of confusion whether we should eat more or less folate.

This short article explains it in human terms.

Folate vs Folic Acid

folate vs folic acid vitamin b9

It’s fundamental to differentiate between folate and folic acid to understand the concept.

Firstly, both are similar types of vitamin B9 that we eat.

Folate refers to a family of different compounds that occur naturally in foods like leafy greens and legumes. This includes (1):

  • Dihydrofolates
  • Methylfolates
  • Monoglutamyl folates
  • Polyglutamyl folates.

The name folate even comes from the latin term “folium”, or what we call “foliage”.

Folic acid is one of the folate compounds and can be found naturally in foods too, in small amounts.

However, a “synthetic” version (it’s identical to natural folic acid) is also used in dietary supplements and added to foods, such as wheat flour.

High doses of folic acid are typically used to treat folate deficiency and other conditions, such as Neural Tube Defects and high homocysteine (2, 3).

The Noticeable Difference

The difference between folate and folic acid occurs during metabolism.

In particular, the process of converting them to the active form of folate, called L-methylfolate or 5-MTHF.

In this form, folate can be transported into cells and even across the blood-brain barrier.

folic acid vs folate metabolism and methylation

Click to enlarge

The human body must do this conversion because it cannot use folic acid or folate in its basic form (chemical structure).

Folic acid we eat must always go through this entire sequence (above image), from top left corner to the bottom step, L-methylfolate. Notice the last step requires the MTHFR enzyme (blue box), produced by the MTHFR gene.

On the other hand, dietary folate can either start on the top right, corner or bypass the entire sequence completely…

This is because much of our dietary folate is already in the active form of L-methylfolate.




Summary: Most of the folate and folic acid we eat must be converted into the active form, known as L-methylfolate or 5-MTHF. However, some dietary folate is already in the active form when we eat it and therefore does not rely on MTHFR.

Some Natural Folate Is Already Methylated

Some natural folate is already methylatedAs mentioned above, natural folate we eat comes in a variety of compounds.

This includes the active form of L-methylfolate.

That means we all need to eat more natural folate, MTHFR mutation or not.

I could not find a reliable source that lists the exact ratios, but many websites suggest these are the top food sources of L-methylfolate (methylated folate):

  • Romaine (Cos) Lettuce
  • Sprouted legumes (buckwheat, mung beans, chickpeas, etc)
  • Broccoli and cauliflower
  • Asparagus
  • Kale and spinach
  • Cabbage
  • Fermented foods such as miso and kefir
  • Berries like strawberries and raspberries
  • Citrus fruits like oranges and grapefruits

Natural vs Supplemental L-Methylfolate

natural vs supplemental l-methylfolateIt’s clear that an individual with no methylation (MTHFR) issues could get adequate amounts of active folate from food alone.

Either directly as L-methylfolate or from other forms of folate (such as folic acid) that are converted during metabolism.

However, an individual with a “severe” MTHFR mutation would need to consume large quantities of these foods consistently to restore – perhaps to maintain – adequate folate levels.

For example, according to one germination study, 100 grams (almost 1 cup) of soybean sprouts contains about 0.8mg of total folate maximum. 100 grams of mungbean sprouts contained about 0.7mg total folate (4).

How much L-methylfolate was in those total folate amounts was not shown, but the average person just does not eat large amounts of those foods consistently.

The recommended starting dose of an L-methylfolate supplement is 0.5mg, but that is pure L-methylfolate. Prescription varieties start at a whopping 7mg, so there is certainly some use for supplementation.

Summary: Many foods naturally rich in folate already contain L-methylfolate. So the potentially harmful effects of an MTHFR mutation could be offset through a folate-rich diet in some scenarios. However, there is still a use for supplements.

What Is The Issue With Folic Acid?

Those with an MTHFR mutation may not produce enough MTHFR enzymes.

This means they may not consistently complete the final metabolic step that converts folic acid (and some folate) into the active form L-methylfolate.

MTHFR enzymes are necessary for this to happen (as well as vitamin B2).

mthfr-enzyme-and-vitamin-b2-for-methylation

Therefore folic acid supplementation and foods fortified with folic acid may be largely ineffective in these people.

This could be a big issue if they have a folate deficiency, high homocysteine or are in the early stages of pregnancy and rely on folic acid.

Some suggest that unmetabolized folic acid can bind to folate receptors, effectively blocking access by L-methylfolate. I couldn’t find any studies to confirm this theory though.

Others also say that unmetabolized folic acid in the blood is uniquely harmful, but there’s no evidence of that in the medical literature. The body is simply getting rid of excess (a good thing), which goes from blood to kidneys, and then out through urine.




Summary: Those with an MTHFR mutation may not benefit from folic acid supplements or fortified foods. Theoretically a build-up of unmetabolized folic acid could be harmful, but it’s yet to be proven.

Everyone Should Eat More Natural Folate

Foods high in folate contain many different compounds, including L-methylfolate (methylated folate).

For this reason we should all aim to eat more, particularly leafy greens and sprouted legumes… as though we needed additional reasons to eat more vegetables.

If you have an MTHFR mutation and do not frequently eat the folate-rich foods mentioned above, you may be at risk for issues related to low folate.

This risk may be increased if you eat single sources of folic acid, such as folic acid supplements or fortified foods.

More on MTHFR and other genetic variations

MTHFR mutations can impact folate metabolism. But there is confusion whether we should eat more or less folate. This short article explains it.

 

Comments

  1. Bill Griffin says:

    I am homozygous for the C677T variant. I have a question. What chemical is tested at the lab when one’s doctor orders a Folic Acid test? If one is taking no multivitamins and has a nuturient rich diet including many vegetables with L-15methylfolate, what would one expect the lab test to show? I consume several servings most days of folate rich foods. The lab test revealed that my Folic Acid level was just barely into the normal range. Any comments, information or advice would be greatly appreciated.

  2. If one is homozygous for the C677T variant of the MTHFR gene and the lab test for folic acid is low despite a diet replete with foods having the natural L-methlyfolate, does that mean that a supplement would be in order? What does the lab test actually test for – L-methylfolate or an inactive form of folate?

  3. I have similar questions. Also, could a normal or high result for the serum test for B12 disguise a deficiency of methylcobalamin?

  4. I’m curious about the food sources for L-methylfolate because I do want to get things from my diet instead of pills.

    I’m curious why no meat sources were mentioned? I notice you link another site, but I’m still curious as to your thoughts on it?

    From what I have found Liver is one of the foods that is just packed full of all the B vitamins. It also should be B-Vitamins that are in an active form that our body can use. Since it’s coming from an animal source, from what I understand it’s going to be the active version since the animal’s body already converted it.

    Thoughts? Information and such doesn’t have one source I can quote. It’s been something I have found/learned over the course of a few weeks and speaking with my doctor as well (she focuses on genetic mutations in relationship to depression and such)

  5. If there is a “natural” form of folic acid , as opposed to the synthetic folic acid, that occurs in food BESIDES FOLATE form…… then the synthetic should not be named “folic acid”, because for a synthetic to be patented it MUST be molecularly unique. A synthetic form is usually made by deleting an electron or “mirroring” the structure (like reversing it) which no longer is IDENTICAL to the natural one. Which is the whole purpose of developing a “copied” version to be able to patent it and own. So the synthetic can never be said to be identical or react identically because it simply is not. Otherwise millions would not be spent to turn the natural derivative to a synthetic – if it were to remain natural or original. To say it is identical then the patent is a fraud…….So….. what is the “natural” form of “folic acid” mentioned here – or was naming it folic acid a mistake? There can’t be 2 “folic acid” and each be different. My understanding is that “folate” is natural and “folic acid” is the synthetic – no 3rd one exists.

  6. My husband is just newly diagnosed. I need help in knowing what foods he can and cannot eat.

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