I Have MTHFR A1298C Mutation – What Does That Really Mean?

MTHFR mutations are just starting to be recognized as an issue and so more and more doctors are testing, but what happens if your doctor tells you that you’re homozygous for MTHFR A1298C? They might as well be speaking Greek! So here’s the skinny on what that really means. Also here’s a post about MTHFR mutation basic in general.

MTHFR A1298C Terminology Basics (or as basic as we’re going to get with genetics).

The simplest level of information here is just the plain genetics.  Here are some quick factoids to get us started:

  • MTHFR is the short name for the genes that code for the enzyme that changes folic acid to the active form that your body uses (the long name is methylfolate reductace).
  • 1298 is the marker for one particular MTHFR gene.
  • The official genetics labeling of this gene is Rs1801131. Sigh.
  • You get one copy of this gene from your mother and one from your father, so there are two possible copies that can be either “normal” or “mutant”
  • If you inherited one good copy and one bad copy that’s called “heterozygous A1298C”
  • If you inherited two bad copies (one from each parent) that’s called “homozygous A1298C”
  • A…C stand for the bases that you actually have.  A = adenine C = cytosine.  Bases are essentially the letters that spell out your genetic code.  There are four of them commonly (C, T, A and G).
  • When this gene is “normal”or “wild type” (I love that name) it looks like MTHFR A1298A.
  • Heterozygous mutations (one good copy and one bad) are MTHFR A1298C because there is one normal A and one abnormal C Also occasionally written 1298AC.
  • Homozygous A1298C (two bad copies) can also be written as C1298C (because there are two abnormal copies with C instead of A). Occasionally you’ll also see it written 1298CC

Phew! So the take-away there is MTHFR A1298C means you have at least one bad copy of this gene, and if it’s called homozygous, or C1298C then you have two bad copies.

How Much of a Problem Is This?

The MTHFR A1298C mutation is considered less serious than the C677T mutation because it seems to cause less impairment to actual methylation function than C677T.  That doesn’t in any way mean that it isn’t an issue. This mutation can still be a significant problem If you don’t have a good diet, don’t take supplements or burden your body with a lot of stressors like smoking, alcohol, drugs, sedentary lifestyle or high stress. If you get lots of dark green leafy veggies, legumes and other food sources of natural folate – see this post – then you’re probably already getting good methylfolate. If your diet isn’t up to scratch, then supplementation can be useful and here’s a whole post about that.

Heterozygous MTHFR A1298C is thought to have mostly normal MTHFR activity  and homozygous MTHFR A1298C (C1298C) have about 65% normal activity (so 35% compromise). Normal activity refers to the way your body converts folic acid to 5-L-methyltetrahydrafolate (the active form) so that it can be used. Compromise in this case looks like a folate deficiency.

What Are The Health Risks of MTHFR A1298C Mutation?

According to SNPedia, which compiles research on genetics, A1298C mutants have been shown in at least one research study to have an increased risk for:

  • Midline defects such as:
    • Cleft lip
    • Cleft palate
    • Neural tube defects
    • Facial asymmetries
  • Cancers including:
    • Breast
    • Lung
    • Brain
    • Stomach
    • Head and neck
    • Kidney
  • Cardiac-related issues including:
    • Thrombosis (increased tendency to clot inappropriately)
    • High homocysteine levels (a heart risk)
    • Pre-eclampsia (dangerous high blood pressure in pregnancy)
    • Vascular dementia
  • Fertility issues including:
    • Multiple pregnancy loss
    • Low sperm count
    • Birth defects such as down syndrome
  • Neurological issues including:
    • Migraines
    • Autism
    • Alzheimer’s dementia
  • Mood and psychological issues including:
    • Depression
    • Anxiety
    • Schizophrenia

You’ll notice that this is quite a list, and it can be a little daunting to think about when you’re just learning about this. Most research doesn’t differentiate between the A1298C genetic variance and the C677T genetic variance so the list is the same for both mutations.  We assume the risk is lower with A1298C because the folate metabolism is less strongly impaired, but that might not be correct.

What Do You Do About This?

Compromise with the MTHFR A1298C gene can have severe consequences so it’s important to work on getting good sources of natural folate from foods, which is generally useable by mutants, or 5-MTHF (5-methyltetrahydrofolate) which is already methylated so the genetic compromise doesn’t matter.  As discussed in this article, I feel supplementation should be started slowly because for many mutants who haven’t had active folate very much in their lives it feels really strange when those active forms start showing up.  There can be quite an adjustment reaction  by your body.

Activated folate is used by your body to run enzyme pathways, to aid in some parts of normal metabolism, to help your body detoxify and even to methylate your DNA. The methylation cycle is also a big part of neurotransmitter manufacture, which explains the strong link to depression, anxiety, and mental disorders including addictions and even schizophrenia. If 5-Methylfolate  isn’t there then your body does maintains those functions as best it can, but the things your body can’t do start to pile up. Starting supplementation means your body can start digging in that pile to clear up high priority items.  This is exactly what we want, but if you start with high doses of a supplement then it’s a little like drinking from the firehose.  Kind of out of control and not very pleasant.

A great way to start if you’re unsure, is with a folate-rich diet.  I love this image because it kind of covers what we’re looking for.  Hint – think dark greens and beans. 🙂




Is folate in foods safe in MTHFR mutants? In these foods YES! For MTHFR C677T or MTHFR A1298C mutants. Thanks to exhibithealth.com for the great image.

Is folate in foods safe in MTHFR mutants? In these foods YES! For MTHFR C677T or MTHFR A1298C mutants. Thanks to exhibithealth.com for the great image.

Can Mutants Become “Normal”?

If you’re a mutant (like me) then you’ll always be a mutant, but it doesn’t have to matter. Essentially as long as you’re getting enough of the active form of folate and taking care of yourself for the other consequences of the MTHFR mutation then the mutation doesn’t have to matter.  If you aren’t taking care of yourself, then it matters a lot.

The bottom line is MTHFR A1298C mutations don’t have to mean anything at all as long as you supplement and have a good diet and lifestyle (here’s an article about a folate-rich diet for MTHFR mutants) I always suggest taking a little more care with yourself too.  There are known health risks for things like clotting, fertility and cancers so it makes sense to take some precautions.  Eat your fiber, do your exercises, get your sleep and generally treat yourself with high regard – shouldn’t we all anyway?



17 thoughts on “I Have MTHFR A1298C Mutation – What Does That Really Mean?

  1. Rebecca

    I have recently gone through a whole bunch of testing after finding out I have blood clots on my left retina. So far, the only thing they have found of relevance is one copy of this gene mutation. The hematologist seemed skeptical that one copy of this gene was enough to cause my problem, but said that if they didn’t find anything else, then this might be the cause, and so far, they haven’t found anything else. The doctor didn’t tell me much about it and only said that I should keep taking my aspirin. I am wondering, with one copy, how much do I need to worry about supplements? My doctor also tested my folic acid levels, and said they were normal. Does this mean I don’t need supplements?
    Also, you recommend not eating foods that are fortified with folic acid. I understand that this mutation makes it hard for the body to use that folic acid, but why is eating these foods bad? How much of an issue is that for people like me with only one copy?
    On another note, I was looking over the list of conditions associated with this mutation, and saw that autism is on the list. I happen to have two autistic nephews, and now I wonder if they might have this gene. If they did, would diet change of supplements really make a difference for their autism?

    Reply
    1. amyneuzil Post author

      Hi Rebecca,
      Great questions! It’s really hard to say how much you need to worry with one copy. I’ve seen clients with seemingly minor mutations have some major clinical issues, but that is probably because we’re looking at one gene out of the 20,000 protein coding genes that are estimated. We don’t test for the rest of them, so chances are in a situation with one known minor mutation there are other unknown mutations that also affect the same issue (in your case, clotting). I would say you should supplement just to cover your bases. It’s not terribly expensive and as far as we know it’s a no-harm situation.
      Blood folic acid levels being normal doesn’t actually mean that you can use that folic acid effectively – that test shows only the synthetic form of folic acid and only what is in your blood – not what is actually being used by your cells. The test assumes that you can use it effectively, but for MTHFR mutants that isn’t always the case.
      Eating foods or taking supplements that have folic acid in them (this is the synthetic form) essentially clogs up all the receptors for folate so that any of the active form you’re getting doesn’t have as much opportunity to bond or be utilized. If you can’t avoid completely, then at least minimize and supplement with an active form. Again, no telling how much of an issue it is with only one copy, that depth of research isn’t really being done yet.
      Autism can certainly be linked and for your nephews it is certainly something to discuss with their practitioner. Because there can be symptoms when you’re starting supplementation (and everything is amplified in autism) you’ll want to have them working with someone.
      This is a lot of information – let me know if it doesn’t make sense!

      Reply
      1. Rebecca

        I appreciate your reply. I am still trying to figure this all out. I guess my next question is where do I get a supplement that is natural? Is is possible to get a multi vitamin with the natural form. I hate to give up my multi, but I’m sure the folic acid in it is probably synthetic.
        My next question is how do you figure out getting the natural form and not the synthetic form in your food. For example, I read that several kinds of nuts are good natural sources, but when I look at the can of mixed nuts in my house, it doesn’t say anything about folate or folic acid. Then there’s the other side of things. I have been trying to buy organic wheat products since I read about wheat farmers being allowed to spray their crops with round-up before harvest. The packaging doesn’t say enriched, but on one that I looked at, it did say there was folic acid in it. Does that mean it still has the synthetic kind? Is there ever natural folate in a wheat product? Are the ones that don’t mention folic acid okay? I don’t think I would be able to give up all the foods that are enriched, even if I could figure out which ones they are, but I am trying to reduce the synthetic, and increase the natural. It is really hard when labeling is so poor.
        I guess my last question is this, (and I know you might not have an answer. I just want to put it out there.) if they are figuring out that this synthetic stuff is bad for a lot of people who wouldn’t have a problem otherwise, why don’t they just stop messing with the food and start teaching people (especially pregnant women) how to get more of the natural kind?

        Reply
        1. amyneuzil Post author

          Hi Rebecca,
          Great questions! With vitamins and multis it’s really hard to find one with natural folate in it because it generally occurs in small amounts in foods. If it says folic acid on the label then it’s the bad kind. If it’s a good kind they’ll say 5-LMTHF or quatrifolate or methylfolate. In terms of foods – as far as I know grains area always enriched (so the bad folic acid) – they aren’t a good natural source of folate. The best foods for natural folate are things like dark green leafy veggies, beans, lentils, nuts and that sort of thing. Here’s a post on good vs. bad foods for MTHFR folks. As for educating pregnant women – hopefully that will be the next step, although even with MTHFR mutations adding folic acid to basic foods has helped to prevent hundreds of thousands of birth defects, so it is still a good thing even if it’s not a great thing for MTHFR mutants. I think it helps mostly the population who doesn’t have great financial resources to spend on nutrition anyway, and education won’t help if those women can’t afford fresh spinach etc… Such a complex problem. Happy holidays!

          Reply
      2. di

        Hi
        I have mthfr c128c double mutant I have was always been health conscious take supplements eat right exercise but I think I might be overdoing my methyl b12 I have a symptom of ringing in the ears. Detoxing is a big issue with mthfr right ? What b12 works best.
        Thanks

        Reply
        1. amyneuzil Post author

          Hi di,
          Yes – B12 can be a huge issue for MTHFR folk. And detoxing is at the heart of everything. I’d suggest you read this post about B12 and see if it points you in the right direction. Thanks for reading!

          Reply
  2. Ash

    Hey Amy,
    Thank you for this, explains quite a bit SPECIFICALLY on the a1298c homozygous mutation I have been tested on.
    Im 23, and suffered Anxiety and Depression my entire life, found this, tested positive for a1298c, started with methyl b12 and included natural folate rich foods in my diets.
    3 days ago added a methylfolate supplement, and started with 200mcg. And predictably enough like what I had read on all the articles, my anxiety has increased (which is supposed to be the initial stage until body gets adjusted.) However, there’s no doctor in my area who deals with MTHFR, and I would like to do this under guidance, would you happen to know anyone who I can correspond with online? I live in India.

    Reply
    1. amyneuzil Post author

      Hi Ash,
      I see a limited number of clients online if it interests you. Here’s some info for new clients. I’m so glad you found out about your mutation – having information really helps. Hang in there with the methylfolate. 🙂

      Reply
  3. patricia

    I get very sleepy/tired every time I try to up my dose of methyl folate. Also I use 15 minutes in a dry sauna and now come home with a headache and again very sleepy/tired. What’s going on?

    Reply
    1. amyneuzil Post author

      Hi Patricia,
      Methylfolate is very involved in detoxification (just like dry sauna). Honestly my gut feeling is that probably when you increase your methylfolate dose you’re pushing your body to detoxify a little bit more quickly than it can cope with and so you get tired. Likewise with the dry sauna. Headache and low energy can both be symptoms that your body is just a little bit too toxic at that moment (like a hangover). Make sure you’re doing the simple things to help your body get rid of toxins every day like high dose fiber, lots of water and good sleep. If you’re already doing those things then check out some extra ways to take care of your liver here.

      Reply
  4. Martha

    Hi! I just got my 1year olds blood results back and she has two copies of the same mutation (A1298C).
    Is there something I need to be extra careful of since she is still a baby? What does she need to stay away from?
    Since she has 2 copies of the same mutation does that mean that she got if from both my husband and I ?

    Thanks!

    Reply
    1. amyneuzil Post author

      Hi Martha,
      Great questions! For little kiddos there aren’t many supplements and doing it through food is probably the best way anyway. I would try to minimize food fortified with folic acid (lots of cereals, bread, pasta that sort of thing) and increase foods that are naturally high in folate. My daughter is just about to be two and we haven’t had her tested yet but I’m assuming she has some mutation since both my husband and I do, so this is the approach we’re using. And yes – you’re right. If she has two mutant copies of the same gene then she got one from you and one from your husband.

      Reply
  5. Jennifer

    Hi, I just found out I have a homozygous A1298C mutation. I also have elevated blood levels of B12 and folate. Could these issues be correlated and might taking methylfolate (in addition to avoiding folic acid) lower my levels? Thanks!

    Reply
    1. amyneuzil Post author

      Hi Jennifer,
      I have seen MTHFR mutations often go hand-in-hand with elevated blood levels of B12 and folate (although often symptoms of LOW B12 and folate). Typically supplementation with a good methylfolate and either methyl or hydroxy B12 (see this post) will change the symptoms, but it’s really variable whether or not the blood values will change. It seems like in some people they do normalize and in some they don’t and I haven’t been able to figure out why or who will be in each group. I hope this helps!

      Reply
      1. Jennifer

        Thank you so much for your reply! I would definitely say I have the low symptoms. I haven’t been able to find much information on the high levels/MTHFR connection, so I appreciate your incite. I have seen some information suggesting high blood levels being related to intestinal pathogenic overgrowth. This is interesting as I took a food based multi for years (saccharomyces cerevisiae/cultured). I recently had a food IgG test and my highest reactivity, besides most dairy, was brewers/bakers yeast and malt. So, besides previously taking the wrong forms of b vitamins, perhaps I also have an overgrowth of some sort. Trying to figure this all out, as I am thinking about having another baby and worried about the potential associated autism risk with high levels of b12/folate. Grateful for the information I’ve learned from your site, thanks for sharing your knowledge!

        Reply
  6. Dorka Tarsoly

    Hi Amy,
    I was tested for for both MTHFR gene mutations and as it turned out i have a homozygous A1298C mutation. My question after having read the articles on your site on this topic is: should i supplement with the above mentioned methylated b vitamin complex and a plus dosage of methylfolate? I’m asking this as i maintain a really healthy vegetarian diet. I include nuts, legumes and dark leafy greens in my diet. Basically i consume the above mentioned vegetables on a daily bases.
    Thanks for your answer in advance!
    Dorka

    Reply
    1. amyneuzil Post author

      Hi Dorka,
      With a homozygous mutation it is certain that you need some sources of methylfolate. For some people food sources are enough, so the question is – are you having trouble? If you’re having symptoms or problems that could be related to MTHFR then I would say adding a supplement on top of your good diet is a good idea. I’m guessing the testing was done for a reason, so chances are you’re not getting enough. Remember to start supplementation slowly – there can be unpleasant reactions if you start with too high a dose. Here’s a post about it to get you started and I hope this is helpful!

      Reply

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