The Dangers of UMFA in Pregnancy

UMFA or unmetabolized folic acid is something that has been popping up on research radars more and more frequently in recent years. The combination of food fortifed with folic acid, multivitamin use, the popularity of B complex supplements for energy, and the standard practice of hyper-dosing women with at-risk pregnancies has led to UMFA becoming a common problem. Last week we discussed the remarkable results methyl folate produced in couples with infertility relative to the current standard of care, which is supplementing with folic acid. This week, I’d like to talk about the risks of too much unmetabolized folic acid or UMFA during pregnancy.

First, Let’s Talk Useable Folate

One very wisely designed study published in the American Journal of Clinical Nutrition, compared serum and red blood cell levels of total folate, 5-LMTHF, UMFA, and MeFox which is a methyl folate oxidation product – kind of the 5-LMTHF version of UMFA. The reason I call this study design “wise” is that it gives us a good window into what is actually happening here. Serum levels test the amounts in the fluid part of the blood, which is not yet inside the cells. This isn’t really a functional space for folate – it’s been absorbed digestively, but hasn’t reached useful cellular tissues yet. Red blood cell levels, however, measure the amount that is actually inside of the cell spaces and therefore doing something useful. This study didn’t differentiate between MTHFR or non-MTHFR, or at different forms of folate intake. It simply compares two different doses of folic acid.

One group received about 1.1 mg of folic acid in their prenatal vitamins. The other group received the prenatal vitamin amount plus an additional 4 mg to bring the total to 5.1 mg, or 5100 mcg of folic acid.

What they found in this study, was that the RBC folate level, which is the functional folate, didn’t differ significantly between the two groups. The high-dose folate group did have higher serum levels of total folate, UMFA, and even 5-LMTHF. Other parameters didn’t differ significantly.

The researchers came to the conclusion that there was some kind of tissue saturation happening, where more folate just can’t get into the cells, which makes sense. They also suggest that higher UMFA concentrations in the women receiving the high-dose folic acid indicates that these doses are “supraphysiologic.” That is a fancy way of saying the dose is just too high.

So What is All that UMFA Doing In Pregnancy?

Another study, also published in the American Journal of Clinical Nutrition, studied UMFA levels in cord blood relative to autism spectrum disorder. Cord blood is the blood that remains in the placenta and the attached umbilical cord after delivery.

This study found that babies in the highest quartile of UMFA percentages in the cord blood had the highest risks for autism spectrum disorder. This effect was highest in black babies and significantly correlated with race. This correlation did not apply to the concentrations of 5-MTH or to serum total folate.

Another study, published in the Journal of Allergy and Clinical Immunology In Practice, looked at the association between UMFA levels and food sensitivity and food allergy. This study tested total folate, 5-MTHF, and UMFA levels at birth and again in early childhood.

The researchers found that of 1394 children tested, 507 were found to have food sensitivities and 78 had food allergies. In those children who developed food allergies, the average total folate concentrations at birth were lower and the UMFA levels at birth were higher. Higher UMFA levels later on in childhood didn’t seem to have this same association.

I will quote from the conclusion of this study. “Higher concentrations of UMFA at birth were associated with the development of food allergies, which may be due to increased exposure to synthetic folic acid in utero.”

What To Make Of This?

These are just a few studies and so we really can’t, as much as we might like to, draw sweeping conclusions from them, but it certainly gives us some compelling evidence that too much of what is supposed to be a good thing, can rapidly become a bad thing.

Because we, with MTHFR polymorphisms, are more susceptible to problems associated with folic acid, I think it is important to have an informed and complete conversation with your health care practitioners about the risks of folic acid supplementation in pregnancy for us specifically, and the viable, albeit less well-researched option of supplementing with 5-LMTHF instead.

Links to the research studies I’ve talked about in this podcast are supplied in the complete show notes at tohealthwiththat.com, so if you’re planning a visit to your OB/GYN or midwife, go armed with research to show them.

Thank you so much for listening today and please make sure you’re signed up for our email list – the email list will be the first to know about new courses, programs, and freebies for MTHFR folks.

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The Harm That 5mg Folic Acid Can Do For MTHFR Fertility

This week I wanted to diverge on subjects a bit just because a very relevant question came up in the MTHFR community, This is such an important issue that I want to make sure it gets the attention it deserves.

One of our members in Genetic Rockstars is pregnant and her midwife is recommending 5000 mcg folic acid in spite of her MTHFR issue.  This is a common question because 5000 mcg folic acid is standard practice in many fertility centers and medical offices for pregnancies that are considered in any way at risk.

Like everything else involving MTHFR, research is limited but I do want to deep dive into a couple of relevant studies.

The most important piece of research to take to your midwife or fertility practitioner is a study published in the Journal of Assisted Reproduction and Genetics in 2018.

This study followed 33 couples in which one or both of the partners had an MTHR polymorphism who had fertility problems lasting at least 4 years.  This could include recurrent fetal loss, premature ovarian failure, or abnormal sperm parameters – so bear in mind this could be the mother or the father who has MTHFR issues. Two-thirds of these couples had previously failed assisted reproductive technology attempts.

Most of the women in this study had been previously treated, unsuccessfully, with 5000 mcg (or 5 mg) folic acid.

The couples in this study were given 600 mcg 5-LMTH, which is the active form of folate, for four months before attempting conception or starting another round of assisted fertility treatment. This four-month period was chosen to allow for a complete cycle of spermatogenesis, which is approximately 74 days.

The results of this one simple intervention were, in my opinion, absolutely astounding. Of the 33 couples:

  • 2 were still in treatment at the date of reporting.
  • 13 couples conceived spontaneously (this is after four years of unsuccessful reproductive attempts)
  • 14 achieved successful pregnancies using ART (assisted reproductive technology). ART typically refers to IVF or in-vitro fertilization. 
  • 3 couples did not achieve successful pregnancies.
  • 1 couple failed to report back.

I am going to read the conclusion of this research article verbatim because frankly, I couldn’t sum it up better.

“The conventional use of large doses of folic acid (5 mg/day) has become obsolete. Regular doses of folic acid (100–200 μg) can be tolerated in the general population but should be abandoned in the presence of MTHFR mutations, as the biochemical/genetic background of the patient precludes a correct supply of 5-MTHF, the active compound. A physiological dose of 5-MTHF (800 μg) bypasses the MTHFR block and is suggested to be an effective treatment for these couples. Moreover, it avoids potential adverse effects of the UMFA syndrome, which is suspected of causing immune dysfunction and other adverse pathological effects such as cancer (especially colorectal and prostate).”

Servy EJ, Jacquesson-Fournols L, Cohen M, Menezo YJR. MTHFR isoform carriers. 5-MTHF (5-methyl tetrahydrofolate) vs folic acid: a key to pregnancy outcome: a case series. J Assist Reprod Genet. 2018;35(8):1431-1435. doi:10.1007/s10815-018-1225-2

The most startling result of this research, I feel, is the tremendous number of couples who conceived spontaneously after a simple few-month intervention with 5-LMTHF. Imagine the amount of heartache, expense, and medical intervention that could be avoided if 5-LMTHF became the standard of care?

The other issue considered here is something called Unmetabolized Folic Acid Syndrome, which has been demonstrated in  “wild type” people to cause pseudo-MTHFR. In pseudo-MTHFR, people who have fully functioning MTHFR enzymes have both high levels of unmetabolized folic acid and high levels of homocysteine in their blood. In people with an MTHFR deficiency, UMFA blocks the entry of folates into the folate cycle and further impairs the capacity of their already struggling MTHFR enzymes.

Unmetabolized Folic Acid has also been implicated in promoting colorectal and prostate cancer. And folic acid itself shows poor clinical success and in some cases, it tests worse than placebo in reducing homocysteine levels or downstream measures of cardiac health.

Next week I’d like to talk about some of the issues that have been linked to high levels of unmetabolized folic acid in pregnant mothers and the problems that travel downstream to those unborn children. If you haven’t done so already, please sign up to the email list on tohealthwiththat.com, or join the MTHFR community Genetic Rockstars at community.tohealthwiththat.com. I have big plans this year for courses and I want you to be the first to know.

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S2E2: Getting the Folic Acid Out of Your Diet.

I know it’s poor planning on my part to start this season off with the hardest part of this whole process, but sadly this is the only good way to start. If you skip this step, you can create mountains of problems for future you. Keeping folic acid in sounds good to so many people, but folic acid actually blocks the other, more useful forms of folate from being utilized. I talked a lot about the technical details in this post. This basically makes all the work you’re thinking about doing to add in natural food sources of folate or to take expensive 5-LMTHF supplements, worthless. All the money you spend on those things becomes wasted as well.

Let’s start with a bang.

Folic acid also hangs out in your bloodstream as unmetabolized folic acid, or UMFA which contributes to many health problems for MTHFR folks and non-MTHFR folks alike, including increased risk of many forms of cancer.

This is step one, and ignoring it is far, far easier than actually doing it, but you’ll regret it in the long run. Honestly, it won’t even serve you in the short term because eliminating folic acid from your diet can show you a lot about how you react to folates in general. It’s a huge part of this journey and skipping it isn’t a great option. I know it’s hard but stay with me.

Folate is vital to our functioning as humans and especially to the healthy making of babies, which is a pretty big deal. Folate deficiency during pregnancy leads to major preventable complications like cleft palate, spina bifida, anencephaly, heart defects, low birth weight, and stillbirth. Because it’s so important, many governments around the world have adopted programs to fortify commonly eaten foods with the synthetic form of folate, which is our nemesis, folic acid.

This public health measure has had a tremendous impact on the rate of these birth defects, which is wonderful. It just doesn’t take into account people with the MTHFR mutation, or a culture that generally over-eats and over-supplements the way we are prone to in North America.

As a caveat to public health in general, even for MTHFR folks some folate in the worst form, folic acid, is better than none at all. This measure makes sense for society. The problems start to happen when either there is too much folic acid, which is now very common, or when there are too many compromised copies of the MTHFR gene.

So this week, if you want to follow along with this MTHFR adventure, you are ditching all of the folate fortified foods and starting with a folic-acid-free diet. Nothing else should change. Just get the folic acid out of there. This includes supplements as well so if your multivitamin, B-complex, energy-booster, or meal-replacement has folic acid in it or says “folate” on the label, then it’s out. If you’re dropping supplements, try not to add anything back in right now unless it’s absolutely necessary – we’ll look for particular things in the weeks to come and there’s no sense rushing out to buy something you might be changing shortly.

In the US, there are two foods that are fortified with folic acid. Those are wheat and corn, which are pretty much the backbone of every American meal out there. This means your bread, pasta, tortillas, corn chips, baked goods, even the doughnuts have to go. Here’s a bit more about what to eat and what not to eat for MTHFR folks.

This is the moment when people’s eyes bulge menacingly and a tic starts in one of their eyelids. Typically, spittle flies out of their mouths when they say, “But, but, then what do I eat?”

Have no fear. There is actual food left, but you might have to look around a bit. First off, you can still have wheat products as long as they are certified organic. In order to earn organic certification, they have to be unadulterated. In terms of bread, finding an organic option, or a sprouted whole-grain option is probably the best one.

For pasta, there are not so many organic options, but lots of gluten-free options that are not fortified – look for any pasta that claims to be gluten-free, or rice pasta that is made of rice and therefore not fortified.

For the baked goods, you’re going to be in a bit of trouble. There are some gluten-free options but they’re pretty limited if you’re used to the smorgasbord of wheat-based options. Sorry about that. Even baking at home has to be different because wheat flour is mostly enriched. Some whole wheat flour is safe, but some still has added folate so read your labels.

I can see that tic under your eye intensifying, so let me just reassure you that there is also every meat, veggie, fruit, and nut option under the sun. It is really just your major sources of carbs that are taking a hit. I know, that reassurance is entirely too thin for anybody’s liking.

This is the hardest part of the whole thing, so stick with me – it’s all so much simpler from here. Just keep using the symptom tracker that you started last week to see if you notice anything from the folate elimination. People are often surprised to find that something as mundane as bread can be causing them so much mental and physical pain.

It’s a bit last-minute, but I’m just offering a course starting September 15th called Methylfolate masterclass to answer the #1 question I get, which is, “How do I know when I’m taking the right dose of 5-LMTHF?” If you’re interested you can find out more at tohealthwiththat.com but register now because the cart closes at 11:59 pm Monday the 13th.

Thanks so much for listening today and if any of you are brave enough to come back next week, we’ll lighten it all up with talk about some amazing high-folate foods that you can add in to your diet to give your body good sources of natural folate. It will be great! To everyone who didn’t throw their device out the window when I started talking about not eating wheat, thanks for hanging in there!

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What To Eat For MTHFR Mutants

We’ve been talking a lot about natural folate and its food sources vs. synthetic folic acid (which is toxic in high doses.). So in theory, we’ve got it. But in reality, what does this actually look like? Let’s dive in right now.

How Much Folate Are We Talking? Do I Have To Bathe In The Stuff?

Not at all. Although MTHFR folks might need to adjust based on their own responses, generally we’re aiming for the same targets as everyone else. The units are in “dietary folate equivalents” because absorption of folate and folic acid are different. Natural folate is about 50% absorbed and folic acid about 85%. If you want to geek out on it:

1 mcg DFE = 1 mcg natural folate = 0.6 mcg artificial folic acid.

According to Harvard University School of Public Health, daily folate needs are:

  • Adults: 400 mcg
  • Pregnant women: 600 mcg
  • Lactating women: 500 mcg
  • People who regularly drink alcohol: 600 mcg (because alcohol impairs absorption).
  • Children – from 65 mcg up to 400 mcg at 14 years old.
Assuming 1 whole avocado and 1 cup of fresh-squeezed orange juice (juice from about three oranges) this breakfast has approximately 300 mcg of natural folate. BOOM. Photo by Ba Tik from pexels.

Food Sources of Natural Folate

Naturally occurring folate is present in lots of the foods you might already eat, and also in some that might be new to you. Here are the 10 foods highest in natural folate according to USDA nutrition data:

FoodFolate per 100g (3.5 oz)Folate per cupRelated foods?
Edamame311 mcg482mcgPeas, soybean sprouts
Lentils (cooked)181 mcg358 mcgRoman beans, black-eyed peas, pinto beans, chickpeas, black beans
Asparagus
(cooked)
149 mcg268 mcgArtichokes, beets, okra
Spinach146 mcg263mcgTurnip greens, pak choi, collard greens
Broccoli
(cooked)
108 mcg168 mcgBrussels sprouts, kale, cabbage, cauliflower
Marmite (yeast extract)100 mcg per 8 g servingUnhelpfully, the makers of Marmite have listed the folate as “folic acid” because the terms are used interchangeably. It is actually natural folate.
Avocados81 mcg163 mcg
Mangos43 mcg71 mcgGuavas, pomegranate, papaya, kiwi, durian
Romaine lettuce136 mcg64 mcgEndive, butterhead lettuce, garden cress
Sweet corn42 mcg61 mcg
Oranges54 mcg30 mcgStrawberries, cantaloupe, blackberries, honeydew, pineapple
So many yummy choices…

With MTHFR Mutation, If You Can Eat Your 400 mcg and Avoid Folic Acid, You’ve Pretty Much Nailed It.

Of course, there are lots of times when it isn’t quite so simple, but this is a nice easy benchmark to strive for. So – What to eat for MTHFR? Lots of beans, veg, and fruit. No problem. The much harder part is what not to eat.

Don’t make getting your natural folate harder than it has to be! Photo by alleksana from Pexels

With MTHFR mutation, if you can eat your 400 mcg of natural folate and avoid folic acid, you’ve pretty much nailed it.

– Amy Neuzil

What Not To Eat For MTHFR Folks

There is a small list of fortified foods that have added synthetic folic acid that should be avoided (also, all vitamins and supplements with folic acid). The list is short but impactful. Here it is:

  • Enriched wheat flour
  • Enriched corn flour

There – That wasn’t so hard, was it? Except it turns out it is hard because here are all the foods that are made with those two things.

  • Bread
  • Cereal
  • Pasta
  • Crackers
  • Cookies
  • Corn chips
  • Tortillas
  • Baked goods
  • Baking mixes for cakes, cookies, brownies and whatnot.

This is very much where the wheels fall off the cart because, in the West, most people don’t really know how to eat without hefty doses of bread, pasta, crackers, and cereal. It is just how we are used to eating.

What to eat for MTHFR? Yeah. It’s not doughnuts. Lovely photo by Sharon McCutcheon from Pexels

What to Eat for MTHFR – Substitutions

With every substitution, be sure to read the label. If folic acid is listed in the ingredients (or fortified or enriched flour), then it’s a no-go. Also, remember that if you’re just buying flour and making it yourself (go you!), then you still have to make sure you get un-enriched flour – usually, this is gluten-free, organic, or specialty.

Fortified FoodMTHFR-Safe Substitution (usually. Read your labels.)
BreadOrganic bread, 100% rye bread, gluten-free bread, sprouted bread, rice cakes
CerealOrganic cereals (sometimes), oatmeal (sometimes – usually not the instant ones),
PastaRice noodles, gluten-free noodles, organic pasta (don’t forget, rice and potatoes are still on the menu!)
CrackersRice crackers, rice cakes, Some rye crackers, most organic crackers
CookiesGluten-free cookies, organic cookies.
Corn chipsOrganic corn chips, bean chips,
TortillasOrganic tortillas or sprouted tortillas.
Baking flourOrganic flour, brown rice flour, gluten-free baking mix, wheat alternative flours like buckwheat or sorghum.
You’ve got options!

This Sounds Like a Big Change

It is a big change from the typical Western diet, but it’s a very doable change – especially now when there are so many products designed for people with gluten sensitivities or people looking for organics. Still, it takes some commitment, especially at first, while you’re getting used to your new normal.

Why Do This?

The payoff from this one change can be really significant. Many people report better energy, more stability in moods, reduced brain fog, increased attention, and even better hormone balance. Also, if you’re trying to get pregnant, this sets you up for a healthier pregnancy. That still doesn’t make it easy, but it does make it worth it.

This is The Foundation For a Healthy Life With MTHFR Issues

Many of us MTHFR folks can reduce or resolve any MTHFR related issues just by following this diet. There are a few exceptions.

  1. MTHFR folks with very low serotonin – sometimes these folks can’t tolerate any folate intake and have to avoid folate-rich foods along with fortified foods (although cutting out the fortified foods will make a huge positive difference). We’ll talk about this in detail next week.
  2. Some overmethylators – MTHFR folks with symptoms usually fall into one of two categories. Overmethylators or undermethylators. Undermethylators are more common and usually need higher doses of folate to manage symptoms. Overmethylators are less common and sometimes need very low doses of folate to manage their symptoms. I happen to be an overmethylator but I still eat a very high-folate diet and occasionally supplement so it’s very individual. We will talk more about over- and under- methylators in September.

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This Vitamin Could Be Hurting You

It makes sense that if your body has a difference in its ability to process folate, like the MTHFR variants, then you just flood the system so that even if the enzyme is moving slowly, you’ve still got enough. There is a problem with this logic – the form of folate that we usually see in supplements, foods, energy drinks, and everywhere else is FOLIC ACID and there is compelling evidence that it’s toxic.

First off, What is Folic Acid?

Folic acid is the first synthetic form of folate, which is a group of related compounds found in food that we group under the label Vitamin B9. There are many different forms of folate in foods, but most of them are unstable and degrade quickly and so can’t be used in vitamins or supplements.

Folic acid was first developed in 1948 – the first synthetic form of folate available and it was a revolution. Natural forms of folate, with the exception of folinic acid, are pretty unstable and certainly won’t keep if you add them to foods or vitamins. Folic acid has solved so many problems in undernourished populations and kept the rates of cleft palate, cleft lip and neural tube defects like spina bifida far lower than they would be without it, so it isn’t that it’s an entirely bad thing – when you have a choice between folate deficiency and not having that deficiency because of folic acid, then the choice is easy to make. It’s when you’re not in an undernourished situation that you have to be careful.

At high doses, folic acid is toxic.

I’m Fuzzy – Why Would Folic Acid Be Toxic? They Add It To My Vitamins!

Vitamins and food additives must be shelf-stable, and naturally occurring folates aren’t. The crystalline form of folic acid was first synthesized in 1943 by Bob Stokstad at the American Cyanid Company (!!) What a name! And researched for use in human disease by 1945. It was shown to be useful in the same anemias and diseases of pregnancy for which folate was discovered to be useful by researcher Lucy Wills in 1931. Folic acid is not toxic in small doses and it can help correct a folate deficiency, but high doses are a problem.

Risks Associated With High-Doses of Folic Acid – Not Just For MTHFR Folks!!

Many of us have a chronically high intake of folic acid (not folate) because of the combination of fortified foods, energy drinks, and supplements. In the U.S. the recommended daily intake is 400 𝝁g, but actual consumption can be much higher due to fortified foods.

 Folate has a dual effect on cancer, protecting against cancer initiation but facilitating progression and growth of preneoplastic cells and subclinical cancers, which are common in the population. Thus, a high folic acid intake may be harmful for some people.

Smith AD, Kim YI, Refsum H. Is folic acid good for everyone?. Am J Clin Nutr. 2008;87(3):517-533. doi:10.1093/ajcn/87.3.517
  • Cancer – this is a risk nobody wants to face. Many studies have shown a link between high-dose folic acid and cancer, especially, as with the above quote, in terms of promoting the growth of cancerous cells that are already in the body.
  • Cognitive Decline – like cancer, this seems to be a double-edged sword. See the quote below.
  • Diabetes and thyroid disease – two conflicting studies have shown associations between high folate status in pregnant mothers and metabolic syndrome or diabetes in the children. The results of each study are opposed to each other, and so inconclusive. (See this review article for more details).
  • Hypersensitivity like childhood allergies, eczema, and asthma – this is thought to be through the mechanism of DNA methylation.
  • Autism, twinning, heart disease, mortality (that’s death), immune issues, neurological issues, and fertility problems – these have all been shown in various small studies without larger research studies to back them up.

An observational study of data collected in the NHANES found that “In seniors with low vitamin B12 status, high serum folate was associated with anemia and cognitive impairment. When vitamin B12 status was normal, however, high serum folate was associated with protection against cognitive impairment.”

Morris MS, Jacques PF, Rosenberg IH, Selhub J. Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. Am J Clin Nutr. 2007;85(1):193-200. doi:10.1093/ajcn/85.1.193

Another Problem is The Extra Unmetabolized Folic Acid Found Hanging Out In The Blood

What with all this food fortification, many people have more folic acid than their bodies can handle. Folic acid must be converted into something else to even begin to become useful, and it uses an enzyme (just like the MTHFR magic chair, only it converts a different valueless thing (folic acid) into something more valuable), called dihydrofolate reductase. We’ll call it DHF. DHF is a little bit slow, and can’t always keep up so we see folic acid hanging around in the blood stream, being harmful. Here’s a great study showing the link between fortified foods and unmetabolized folic acid.

The problem with this unmetabolized folic acid in the bloodstream is that it is associated with reduced Natural Killer Cell cytotoxicity. Your natural killer cells (NK) are your main patrol against cancer, so we want these guys to be as potent as possible – this is another potential explanation for the tendency of high folic acid levels to cause cancer.. Here’s a full research article from the Journal of Nutrition.

So, If Folic Acid is Toxic In Normals, What About MTHFR Folks?

Great question. With MTHFR issues, the folic acid situation becomes even dicier. This specific question hasn’t actually been studied in humans yet, and there are a lot of ethical considerations that would go into that (it’s frowned-upon to give humans potentially toxic doses of something for the sake of science.) There is a really great mouse study (we’re allowed to poison them) and the name mostly sums it up.

High folic acid consumption leads to pseudo-MTHFR deficiency, altered lipid metabolism, and liver injury in mice.

My work here is done.

Let me give you the run-down of key points from this study:

  • Mice were fed either a normal diet or a high-folate diet (10x the normal level).
  • Normally fed mice worked out normally so this is the last we’ll talk of them.
  • Folic Acid-fed mice had abnormally weighty livers and spleens
  • Folic Acid-fed livers were fatty in a pattern typical of Non-Alcoholic
  • Fatty Liver Disease (often seen in MTHFR folks, BTW).
  • Folic Acid-Fed mice showed signs and symptoms of megaloblastic anemia, worse in MTHFR+/+ mice (this is usually caused by folate deficiency)
  • Folic Acid-Fed mice showed high white blood cell counts, which were even higher in these same mice with MTHFR issues.
  • MTHFR activity is inhibited by high levels of folic acid in mice, even in genetically wild-type mice.
  • The livers of Folic Acid-fed mice had reduced ability to methylate toxins as compared to the other mice.
  • The amounts of SAMe (the product of the methylation pathway) and methyl-THF (active folate) were reduced in the Folic Acid-fed mice, especially in those with MTHFR issues.
  • The expression of other genes involved in the methylation pathway was also altered in the Folic Acid-fed mice. (Mtr, Chdh, Pemt, and Mat1a)

We suggest that high folic acid consumption reduces MTHFR protein and activity levels, creating a pseudo-MTHFR deficiency. This deficiency results in hepatocyte degeneration, suggesting a 2-hit mechanism whereby mutant hepatocytes cannot accommodate the lipid disturbances and altered membrane integrity arising from changes in phospholipid/lipid metabolism. These preliminary findings may have clinical implications for individuals consuming high-dose folic acid supplements, particularly those who are MTHFR deficient.

Christensen KE, Mikael LG, Leung KY, et al. High folic acid consumption leads to pseudo-MTHFR deficiency, altered lipid metabolism, and liver injury in mice. Am J Clin Nutr. 2015;101(3):646-658. doi:10.3945/ajcn.114.086603

So For MTHFR Folks, Folic Acid is… TOXIC.

Or at least, very, very bad. The bottom line is, don’t take it and avoid it in foods. We’ll cover foods in more detail because naturally occurring folate are great and should be eaten, but fortified foods – like breads, cereals, and grain products, should be avoided.

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