I Have MTHFR C677T Mutation – What Does That Actually 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 C677T? 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 C677T 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).
  • 677 is the marker for one particular MTHFR gene.
  • The official genetics labeling of this gene is Rs1801133. 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 C677T”
  • If you inherited two bad copies (one from each parent) that’s called “homozygous C677T”
  • C…T stand for the bases that you actually have.  C = cytosine, T = thymine.  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” it looks like MTHFR C677C.
  • Heterozygous mutations are MTHFR C677T because there is one normal C and one abnormal T. Also occasionally written 677CT.
  • Homozygous C677T can also be written as T677T (because there are two abnormal copies with T instead of C). Occasionally you’ll also see it written 677TT




Phew! So the take-away there is MTHFR C677T means you have at least one bad copy of this gene, and if it’s called homozygous, or T677T then you have two bad copies.

How Much of a Problem Is This?

This can be a significant problem If you don’t have a good diet or you don’t take supplements. 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 C677T have about 65% normal MTHFR activity (so 35% compromise) and homozygous MTHFR C677T (T677T) have about 30% normal activity (so 70% compromise). Normal activity refers to the way your body activates your folic acid so that it can be used, so compromise usually looks like a functional folate deficiency.

What Are The Health Risks of C677T Mutation?

According to SNPedia, which compiles research on genetics, C677T 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.

What Do You Do About This?

Compromise with the MTHFR C677T gene can have severe consequences so it’s important to work on getting good sources of natural folate, 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 forms of folate very much in their lives it feels really strange when those active forms start showing up and there is a whole lot of adjusting by your body.  This 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. If it isn’t there then your body does what it can, but what it can’t do starts to pile up. Any time you start supplementation then your body starts 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 - even for MTHFR C677T mutants. Thanks to exhibithealth.com for the great image.

Is folate in foods safe in MTHFR mutants? In these foods YES, even for MTHFR C677T 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 then the mutation doesn’t have to matter.  If you aren’t, then it matters a lot.

The bottom line is MTHFR C677T mutations don’t have to mean anything at all as long as you supplement and have a good diet (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?



18 thoughts on “I Have MTHFR C677T Mutation – What Does That Actually Mean?

  1. ayşe

    merhaba mthfr677t homozigot genini taşıdıgımı ögrendim ama herhangibir tedavi başlanmadı bu genin fazla risk oluşturmayacagı söylendi dogrumu

    Reply
    1. amyneuzil Post author

      Hello,
      Sorry I cannot reply in your native language, but if google translate has done it’s job, then I believe you’re asking about a homozygous C677T mutation. This does have some serious health risks associated with it, and talking more with your doctor would be a good idea. The risks involve clotting, cardiovascular risk, risk of conditions such as anxiety and depression and also fertility complications.

      Reply
  2. Marcy

    Despite having a strong body, embracing a healthy lifestyle of a balanced diet high in whole foods (and natural folates!), and regular moderate activity, I have steadily gained weight my entire adult life (I am 40) and am now at an unhealthy weight that I fear makes me susceptible to illness and injury, and makes enjoying physical activity increasingly more difficult and unpleasant. Listening particularly closely to my body starting about 3 years ago, I started to feel like I was somehow getting in my own way, like something was inherently wrong no matter what I ate or how much I exercised. I took synthroid and antidepressants for years and have worked with doctors and lifestyle changes to take those out of my system; I feel good and healthy now without those added chemicals, but my body is still gaining weight at a steady rate (10-12 lbs a year?) and nothing I try reverses the trend for any meaningful period of time. Doctors don’t have anything to suggest at this point since all my labs are healthy and my body seems otherwise strong and healthy, except to imply that I must be misrepresenting my diet/exercise to them. A few months ago, exasperated, I took the DNA Fit health-centric genetic test (partner of 23 & me) to see if there was something there, and learned I have the heterozygous 677C/T version of the MTHFR gene. After some research, I started taking the Pure Encapsulations O.N.E. Multivitamin with Metafolin L-5-MTHF about 1.5 weeks ago and have experienced a lot of the side effects, good and bad, but have not seen any change in weight.
    I’m hoping you can help me understand what to expect with the detox / weight loss process, if anything – its my understanding from your article and others that my body has likely been storing what it couldn’t process (which tracks with how my body feels), and the methylfolate will help my system to start “digging in that pile to clear up high priority items”… If so, are there specific things I can be eating/doing to further aid my body in that process, like with other detoxes? Am I taking enough methylfolate to kickstart that digging/detox? What can I expect, timing-wise, for this process, and is weight loss too much to expect in that process? I’ve seen some articles suggest that the added methylfolate will kickstart the metabolism and thus lead to shedding weight that couldn’t be shed before, and some say that the methylfolate will increase energy to motivate the body to exercise more, thus leading to weight loss via exercise. Please understand I’m not in a rush to lose weight, per se… I’m just anxious to understand, listen to and take care of my body, and to get back to playing tennis and doing all the fun activities I enjoy but without the added struggle – for me, understanding what’s happening and what to reasonably expect in this process helps so much! Thank you!

    Reply
    1. amyneuzil Post author

      Hi Marcy,
      Great questions! I have seen so many people in the same position – they’re taking better care of their bodies than average, but still, they hold weight and can’t drop it easily. I have seen weight holding within the MTHFR community, and part of it is the detox issue you mentioned. I also think there is a “starvation” aspect to MTHFR issues – lots of us get stuck somewhere in the methylation cycle and our bodies are starved for whatever nutrients are necessary for that stuck-ness. This does lead to different metabolic states than you might see in a more genetically typical person. The third factor that matters is food sensitivities. The MTHFR community tends more towards food sensitivities than average and a lot of time those foods actually cause weight gain and weight holding because they increase the level of resting inflammation. I would STRONGLY suggest that you eliminate and challenge some of the big foods at home. Here’s a post on it, but let me know if you have questions. I can say for me that there is an 8-10 pound difference between me eating wheat (it’s my biggie) and me not eating wheat. I have a tiny frame, so 8-10 pounds is actually about 7% of my body weight.

      In terms of the detox – it will happen slowly over time. Stay on the O.N.E. Multi for a few weeks until you are stable and the side effects have disappeared, then see if you can add in an additional low-dose methylfolate supplement. Stay at that dose for a few weeks until things are stable and then see if you can increase again. The goal is to open that pathway up as wide as you can without making yourself ill. Too wide and you feel awful from detox and often the pathway gets stuck somewhere else and that’s no good. Too narrow and you just don’t get to the good detoxing place. Estrogen detox is one of the big issues because sex hormones need methylation to detoxify properly. I think it is reasonable to expect weight loss as part of the detox process, but it’s slow. You can always support your body with lots of water, fiber, saunas or anything else you can do to sweat, epsom salts baths, and that sort of thing. I wouldn’t use detox supplements at this point just because sometimes they push your body more quickly than it is ready for and too-fast detox is miserable. If you’re detoxing too fast then you’ll see symptoms like headaches, irritability, constipation, diarrhea, body aches, etc… If you’re seeing something like that then slow down with the methylfolate and support your body as much as you can with fiber, water, rest, gentle exercise, epsom salts baths, etc…

      The other thing you may want to look into is your thyroid. It sounds like you’re doing well and no longer need synthroid, but often the nutrients that your thyroid needs have never been addressed. These are things like iodine and selenium that will help to optimize your thyroid function.

      I’m not sure if I addressed all of your questions because you’re touching the tip of a huge issue (which is how MTHFR and detoxification are related), but I hope this is a start. Good luck and keep me posted!

      Reply
  3. Nora

    Hi, thanks so much for posting this. I am pregnant and was just told I have a C677T mutation and advised to take one aspirin a day for the rest of my life because of the increased clotting factor. This doesn’t sit well with me. Am I understanding correctly that changing my diet to increase folate would decrease the risk of clots? I was also told to add 1000 mg of folate supplement but side effects weren’t mentioned… is this dosage typically enough to cause the detox symptoms? Thank you for any feedback you can provide!

    Reply
    1. amyneuzil Post author

      Hi Nora,
      Congratulations on your pregnancy! That is so exciting. There is an increased risk of clotting with the C677T mutation, but there’s been a lot of debate about the one aspirin daily routine. Certainly for people without a mutation it has the potential to become too much, to inhibit clotting to a too great degree. Unfortunately, the problem with all of this is that we don’t have good clinical research specifically with MTHFR mutants. I do know a lot of MTHFR folks who swear by the one aspirin daily routine and in my household, we take around two weekly. With the methylfolate – we think, but don’t know for sure, that adding methylfolate would reduce the risk of clotting. Until the research is done, all we have are theories. 1000 mg methylfolate is certainly enough to cause detox symptoms in some people, but not all. The chance would be higher if you have a homozygous mutation (2 bad copies) rather than a heterozygous mutation (1 bad copy). During your pregnancy it is important to follow your doctor’s instructions and if you’re choosing not to, to talk with him or her about that. Your doctor knows far more about you than any internet or blog post ever will, so take everything I say with a grain of salt, please.

      Reply
  4. Brian

    Not to open an entirely separate can of worms, but I recently had a doctor tell me that she believes this mutation links to children having increased problems with adverse reactions to vaccines. Have you read anything on this?

    Reply
    1. amyneuzil Post author

      Hi Brian,
      I have never seen any published research on the subject, but we were very careful with vaccines for our daughter because of this same concern. We need healthy methylation to detoxify heavy metals and a variety of other toxins, many of which are in vaccines. It’s obviously such a difficult decision for parents. Also, our daughter didn’t start speaking until she was 2, and so we didn’t want to give a whole bunch of vaccines when her language development was in full swing. It just didn’t seem prudent. I know this doesn’t really answer your question, and I don’t think anyone really knows the answer. I can say, I share your concern.

      Reply
    1. amyneuzil Post author

      Hi Sandy,
      I’m so very glad to hear it! Thanks for reading and if you run into a question, just post it because I’m sure there are plenty of others who have the same question. 🙂

      Reply
  5. Amanda

    Are you saying that my 677 T/T and 1298 A/A is actually referred to as Homozygous C677T? I can find almost nothing online that says anything about 677 T/T and 1298 A/A

    Reply
    1. amyneuzil Post author

      Hi Amanda,
      Yes! The “677” gene is supposed to be C/C. If you have T/T then that is called homozygous C677T. Because that’s not confusing at all. 🙂 The 1298 A/A is the normal/wild-type gene so that one isn’t a problem for you, but the C677T most likely is.

      Reply
  6. Pingback: If This Is You, You Might be Undermethylated | To Health With That!

  7. Sarah

    Hi, I just recently learned I carry this gene (homozygous C677T). You stated the importance of supplementing slowly due to symptoms. What symptoms should I be looking out for? Just anxiety and irritability as mentioned in the linked article? I’ve been on an active B complex with 400 mg quadrafolate and my doctor has added MTHFR support with an additional 2000. I already experience generalized achiness in my arms and legs (I believe this to be lymph system back up because it always improves after massage) and wonder if this is a detox reaction. My doctor did not discuss any possible intolerance reactions.

    Reply
    1. amyneuzil Post author

      Hi Sarah,
      Honestly the side effects will show up wherever your body is the weakest and they’re different for every person, so it could be the ashiness is part of the symptom picture for you. Did it start after adding the additional 2000 or was it there before? It also could be just part of the inflammation caused by having an MTHFR mutation in general. The things I see most frequently in terms of symptoms starting 5-MTHF are anxiety, agitation, sleep disturbance, depression, brain fog, body pain of some kind (either new pain or worsening of some pre-existing pain), headaches, fatigue, irritability. Basically it’s the “something is wrong generally” type symptoms. Does that help?

      Reply
      1. Sarah

        The achiness started at the beginning of a long string of symptoms several years ago before I was diagnosed with an intestinal parasite that led to malabsorption. The achiness had actually improved for some time during treatment but returned recently which is when, after additional lab, I learned I carried MTHFR. I do have additional brainfog after adding the supplement and now wonder if I need to have my dose adjusted but also an increase in achiness since starting..my doctor told me I may feel a bit off at first and might feel bad but that was all I was told

        Reply
  8. Linda R.

    Please tell me how this makes any sense —–
    I have been supplementing with active B-12 (6 mg) and methylfolate (3 mg) for the past two years for my MTHFR defect (677)
    The doctor recently ran new labs and a SprectraCell analysis –
    Vitamin B-12 – 1463 pg/mL (high); B-12 – 19% (Adequate)
    RBCFolate – 1432 ng/ML (high); Folate – 36% (Borderline)
    Homocysteine, serum – 5 (sort of low)
    Looks like blah, blah, blah to me but I think it’s telling me that I’m over-methylating and that while I have lots of folate and methylcobalamin in my blood, somehow it’s not getting into my cells. What does someone have to do to actually get the active vitamins from the blood into the cells? Any suggestions from you and your readers would be greatly appreciated?

    Reply
    1. amyneuzil Post author

      Hi Linda,
      Yeah – it can be really discouraging when you see something like that, but honestly I wouldn’t jump to the overmethylation conclusion unless you are having symptoms. For whatever reason it seems like a lot of MTHFR folks feel best when their blood (RBC) folate and B12 look higher than average so I would go more by how you actually feel as a human than what the lab test says. Remember the “normal” levels don’t really represent optimal, they simply represent averages – that the average person based on how ever many thousands of tests falls between this and this number. And the B-12 and Folate levels within the cells (I believe spectra cell tests white blood cell levels for this) is probably more accurate for your actual body levels, so possibly you could even try increasing your dose of the methylfolate to see if that feels better for you. With MTHFR I typically go by symptoms more than lab tests. Does this make sense?

      Reply

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