It’s … Complicated. (A.K.A. “MTHFR Deficiency, Sequel”)

Paper Quilt: SciMaps, Completed, Back View

This whole deal with MTHFR has ended up being so much more important than I first thought it would be. Pretty amazing to me. I’ve been meaning to talk about it here, but I’ve been so swamped with writing for work, and the information I’ve been collecting and developing has been a real up and down experience. Kind of confusing, at first glance.

It’s actually rather ironic. I started out learning about the MTHFR mutations last June, with a post that said, “I dug around a bit online and found out this is, shall we say, not a bit deal.” Then I heard things that made me think maybe it was a little more complicated, and worth a second look. I learned more. And more. And saw a trend toward this topic building in awareness among researchers. This lead to the point where I was saying, “I was tempted to run out and just buy pregnancy vitamins or folic acid vitamins.” The next step was talking this over with my doc (“I have the docs OK to start folate supplementation once I have my labs drawn.”).

Shall I warn you that the learning new things didn’t stop there? Briefly, with the changes the doc and I agreed to in my appointment, I should be off all prescription meds within six months. Pretty amazing, after the way things have gone the last ten, twelve years. We’ll reassess at that point, but I’m still heartened.

I received the lab results, with a note from the doctor that everything was fine. There was no reason not to go ahead and start the folic acid supplementation. I did wait a while, because the lab results I received gave NO indication of a normal range. I spent a couple weeks trying to find one, without any luck whatsoever. I ended up asking the wonderful folk at LabTestsOnline, who told me there is no universal normal, that it differs from lab to lab, and that the lab should have supplied that info. Darn them! They did for everything else, just not for the one piece which was the most important test result for me.

While I was looking, I did find a lot of research talking about the dangers of over-supplementation with folic acid leading to a variety of common cancers in folk with MTHFR. Oh. I also found that MTHFR protects against some cancers (mostly leukemias), while it predisposes to others. You figure with this being as widespread as it is in the general population, there almost had to be a benefit to it!

The piece about over-supplementation with folic acid being potentially dangerous to folk with two copies of the MTHFR mutations was VERY interesting! You see, folic acid is in most of our food supply, added in the manufacturing process with the encouragement of our government. This is logical, given what we knew about folic acid at the time the decision was made.

1. Folic acid is known to strongly help prevent birth defects of many sorts.
2. It is water soluble, and it is almost impossible to overdose with it. Extra folic acid just washes through the body.
3. Since it is difficult to get young women who might get pregnant to take extra folic acid when they aren’t planning to get pregnant, just in case, supplementing widely with folic acid is a great way to help get them just enough of the stuff to help prevent birth defects in the first few months of the pregnancy, when they might not yet know they are pregnant.
4. And it won’t hurt anyone else who doesn’t need it, because it is water soluble and the body will just get rid of what it doesn’t need.

Except it turns out that, while this is true for almost everyone, it is not true for those with two copies of the MTHFR mutation. In them, it looks as if the folic acid may not be properly processed by the body and doesn’t actually wash through. Instead it might be building up, and then predisposing this relatively small group of people to various new health problems they might not have had without the folic acid. However, this same group of people are the ones who need folate supplementation more than anyone else. They just can’t digest the most common way to treat that need. It’s complicated. Really complicated. And I didn’t figure this part out until later.

I’ve read things from a few different people suggesting that perhaps folic acid supplementation combined with what we are learning recently about the MTHFR mutations might explain some of the rise in certain chronic diseases, such as certain common cancers and autism and others. As far as I know, this hasn’t been examined closely, but I haven’t gone looking for it either. Something else to explore.

Learning what to do about MTHFR didn’t get easier at that point either. I started supplementing with folic acid when I received the test results, while I kept researching and reading and downloading articles. I was taking the smallest dose I could find, and felt better immediately. A week or so later, it didn’t seem to be working as well, so I upped the dose. Then I started to experience some of the signs of too much, mostly being jittery and having trouble sleeping. I started taking it in the morning instead of at night, with a second dose at lunch, none in the evening, and that fixed the sleeping problems. And then I started to feel worse again, as if I wasn’t taking anything. Around the same time, I was poisoned with trace amounts of gluten a couple times, so I wasn’t certain whether feeling worse was as a results of celiac+gluten or something related to the MTHFR.

Time for more digging. It took a little time, since I wasn’t feeling great. I did keep supplementing with the folic acid, however, because when I didn’t, I felt even WORSE. Also, I had noticed this incredibly surprising thing. When I was “glutenized” while taking the folic acid, I didn’t get as many gluten-symptoms. Briefly, I’ve noticed that I still get the hives (dermatitis herpetiformis), the joint aches, the generalized pain, and the intra-oral swelling. What I am NOT getting the severe debilitating fatigue, confusion, memory impairment, and other cognitive issues that normally accompany the other gluten symptoms. Very, VERY interesting! Unfortunately, this probably won’t work for other celiacs unless they also have two copies of the mutated MTHFR gene, so don’t go running out to try it. Certainly, not without talking to your doctor first!

This was about the time that I learned I should NOT be taking the folic acid, because of the problems and risks described above. There is another formulation that I should be taking. Oh, what is that, you ask? Good question. I’ve found quite a few different names for this. Ten. Ten different names for the folic acid alternative.

5-MTHF
L-5-MTHF
L-methylfolate
bioactive folic acid
Levomefolic acid
metafolin
metafolate
methylfolate
methylfolin
optimized folate

Now, try walking into a vitamin store and asking for help finding this. Really, I mean it. It’s awfully entertaining, unless you actually want to find it. Pick one of those names and ask. It won’t work. Trying listing all of them, and watch their eyes glaze over. Yeah. I did finally find some in town, at Whole Foods, but while they realized that the bottle labeled FOLATE said in fine print “metafolin”, they still had no clue what it was for, why anyone would want it, or the difference between “metafolin” and folic acid.

Another part of the question was how much to take. I couldn’t find much that was useful in the way of official recommendations. In the research literature, what I kept seeing were new articles from the last few years, in which the last few lines of the paper would say something like, “For patients with two copies of the MTHFR mutation, they might require more folate than other patients.” But I couldn’t find anything to give me any advice about what I should be doing, except this one naturopathic web site. Normally, naturopathic web sites are not my first choice, but I was looking for the best available evidence, and this was the best I could find. I liked that he was very conservative in his approach, starting small and titrating up as needed, and including dietary sources in the evaluation.

I eat a lot of high folate foods, and always have. Even as a child, I’d spend my allowance on fruits and vegetables instead of candy, and these days eat a lot of green leafy vegetables, tons of quinoa, and liver. Like I said before, I have cravings for high folate foods. So, I started on a low dose of the metafolin. So far, so good. The stuff I found at Whole Foods was awfully expensive. I bought more online.

The MTHFR.Net site said to take the methylfolate with methylcobalamin. I don’t know why. I wasn’t doing it yet, so bought some of that online at the same time. When the vitamins arrived in the mail a few days later, I took a tab of the methylcobalamin. The next morning, my brain felt more clear than it has in a very long time. The two together seemed to genuinely make a difference. The methylfolate alone was a huge help, but the addition of the methylcobalamin made everything just … click. It felt like something shifted into the right place.

Then I broke out in hives. That’s odd, I wonder where the gluten came from? After taking a second tab of the methylcobalamin (which turns out to be a formulation of B12), the hives got much worse. Oh. The vitamins have gluten in them. And I have four bottles of them. Jolly. I am hoping the store will take back the unopened ones. I found some without gluten at the People’s Food Co-op.

What has happened for me? I feel pretty awesome. I mean, actually, I feel NORMAL. Like I used to feel before I had kids. Well, not completely, but at least I can remember what that felt like. I am hoping that now I’ll be able to start doing some of the other things to reassemble my brain and body.

Typically, for me, when I find a solution that helps me feel better, it works for a while, then the benefits start to wear off as my body adjusts. I am really hoping that doesn’t happen this time, but I am expecting it. I am wondering how long I’ll feel good this time. We’ll see. In the meantime, I’m grateful.

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22 thoughts on “It’s … Complicated. (A.K.A. “MTHFR Deficiency, Sequel”)

  1. Pingback: What Works for Me. So Far. Right Now. | PGen Participant

  2. JHG, hope you are having a Happy Holiday Season. So glad to hear that your new vitamins are helping you feel better! I hope the Deplin vitamins I just started taking give me a clear mind again, as well. I am very curious to see if my vitamins have your vitamins in it. I’ll let you know when I find out!!!

  3. Did you ever figure outhow to get rid of your hives and manage to keep taking your supplements? I am feeling excellent on my methylfolate and active b12, but the hives are driving me wild. It feels like something finally works, but this set back makes me sad. Any advice?

    • Hey, Crys, there might be a second issue. I had huge issues for a while because the vitamins I was taking turned out to have wheat cellulose in them. When I bought gluten-free versions of the vitamins (via Swanson Vitamins) that got better. Celiac & gluten sensitivity are often associated with MTHFR deficiency. Perhaps you, like me, have both? GOOD LUCK! I’ve been having issues with gluten again. So hard sometimes to find where it comes from.

  4. I started taking Deplin 15mg only 3 days ago and I am getting my anxiety and agitation back! My doc ordered it to help along with my antidepressant Effexor Xr. I had just started feeling better and she added the Deplin and I feel awful again!!!!

    • That’s amazingly fast for a drug interaction to show up for the components in Deplin, which are all vitamins. I haven’t tried Deplin myself, but am instead taking the components over the counter and finetuning the levels to what works for me. The dose I am taking is MUCH smaller – 1 mg, instead of 15, and I started smaller yet (0.4mg) and worked up. There is a smaller dose of the Deplin that you could try (7.5), but that would still be a lot for me. Are you taking it in the morning? I found L-methylfolate keeps me up at night if I take it later in the day. I assume that the docs did do the test first to determine if you have an MTHFR deficiency? There is a patient forum at MTHFR.net where folk share info and ask questions. Perhaps that would be helpful also?

      • It’s not a drug interaction. It’s simply too much methylfolate. 15 mg., or even the 7.5 mg dose of Deplin is way too much for many people. The 1 mg. dose is often a reasonable starting dose, but many people must start on even smaller doses of methylfolate.

        Plus anyone taking methylfolate should also be taking methylcobalamin or hydroxycobalamin. Our bodies require B12 in order to process methylfolate, otherwise something called methyltrapping occurs, where the methylfolate gets wasted. If you think of the folate cycle and the methionine cycle as two gears, turning in opposite directions, the part where they interact, where MTHF gets metabolized by the MTR and MTRR genes, that particular interaction point requires B12 for the cycles to move on, for THF to be created in the folate cycle and methionine to be created in the methionine cycle.

        If anyone feels anxious, irritable, anxious or worse after taking methylfolate, they can take niacin as an antidote. As it gets metabolized, niacin uses up methyl groups and stops overmethylation.

      • Yep, I agree with this. I started with 400mg, and have been gradually increasing over time. When I was injured, I needed more to help my body heal. I like your gear analogy!

    • I should have also said, of COURSE, please tell your doc or their nurse about your reaction! The MTHFR.net forums have suggested that there might be some other vitamins that help when taken in combination with the L-methylfolate. That’s what I’m doing – a vitamin cocktail. But the doc needs to know so that they might be able to adjust your dose or switch you to another approach for this. Good luck!

  5. Hi there, enjoyed reading about your journey — I have a similar one. Anyway, to keep it brief I wanted to mention Thorne Vitamins (they have amazing formulations and know their biochem stuff). They make a Methyl Guard complex with just the right stuff, and none of the wrong stuff (like unmethylated forms of B vitamins, gluten, soy, corn, etc.). I buy mine online at Drvita.com. Cheapest place I’ve found. Best of luck!

      • There are two forms of methylfolate which are recommended. One is the form of methylfolate called L-5-Methylfolate, such as Metafolin, which is calcium-salt based. The L in the name is important; it is the biologically active geometric form. The forms for methylfolate that don’t specify the L are racemized, which means they include L and D forms, and the D are not a form the body recognizes.

        The other recommended form is 6-s-quatrefolic, which is (6S)-5-methyltetrahydrofolic acid glucosamine salt . The quatrefolic is the latest generation of methylfolate and reported to be the most stable form.

      • This is very exciting! I’ve been taking the L-5-methylfolate, but hadn’t heard about the new formulation, and have no idea how on earth to find it! I just looked it up, and it looks like the 5-methylfolate being sold by Jarrow is the 6s version. So I guess I’ve been mixing it up and taking both. Interesting!

  6. That’s exactly what happened to me! I was trying to get pregnant and taking tons of folic acid and cyanocobalamin. My health deteriorated rapidly…once I switched to the right form of vitamins things turned around. But it left me with small fiber neuropathy and who knows what other long-term consequences from my year of accidentally poisoning myself. Things have to change. People need to know about this and put pressure on the government health agencies.

    • Yes, folic acid doesn’t really work for people with MTHFR deficiency – we can’t break it down into folate! I recently heard that for folks who have both two defective polymorphisms for MTHFR *and* for COMT, that it is better to take the cyanocobalamin rather than the methylcobalamin. I’m not convinced, but I really don’t know enough about it. I’ve also heard that the MTHFR deficiency can mean trouble breaking down the cyanocobalamin into a usable form, but that with the COMT you may need to avoid extra methyl groups that come from methylcobalamin. Frankly, I’m just parroting things I’ve heard, I don’t have enough biochemistry background to understand the methylation cycle. Reading about it, watching videos, these just don’t equal actually understanding the chemistry!

      • Cyanocobalamin is a lousy form of B12 for anyone to take. It’s more stable and cheaper, but studies have show that even in the general population it’s not as beneficial. Plus if someone takes a lot there are cyanide issues to deal with.

        If someone has COMT SNPs and wants to avoid extra methyl groups, they should take hydroxycobalamin. That is what Dr. Amy Yasko recommends. However, I’m homozygous for MTHFR A1298C, plus a great many other MTHFR genes (but not C677T), and also heterozygous for 2 COMT genes, and I’ve never had any issue with sublingual or transdermal oil methylcobalamin.

      • This area is pretty confusing to me. I’ve heard opposing views on this. I’m homozygous for a couple COMTs. One “MTHFR-advisor-for-hire” said to avoid methyls, others say they aren’t that critical.

      • Yes, there is some controversy over COMT mutated peopled needing to avoid methyls. I think rather than following a blanket rule, people need to pay attention to their symptoms and lab tests as an indicator. For instance, I do a Genova 24 hr. urine hormone test that measures how well metabolites of estrogens have been methylated. Before I started on a program of methylfolate and transdermoil B12, my metabolites unfortunately were very poorly methylated, which is a risk factor for breast cancer.

        However, hydroxycobalamin doesn’t have any methyls in it. So if someone is wanting to avoid methyls, there’s no reason to take cyanocobalamin, other than it’s cheaper.

      • Yes, cyanocobalamin doesn’t appeal to me. I was not aware of the test you mention. My doctor isn’t either, but she’s willing to learn! I’ll take a look for the hydroxycobalamin. Thanks for the tip!

      • This is the Complete Hormones test I referred to: http://www.gdx.net/product/10049. Two of the analytes are 1) 2-Methoxyestrone, which is transformed from 4-hydroxyestrone via COMT and 2) 4-Methoxyestrone, which is transformed from 2-hydroxyestrone via COMT. They also give a Methylation Activity ratio, which is 2-Methoxyestrone/2-Hydroxyestrone.

        Dr. Eleanor Rogan at the University of Nebraska Medical and her research group have written extensively about the importance of the ability of the body to methylate estrone as a risk factor for breast cancer.

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