Holy MTHFR!

surprise1If I say MTHFR, then Methylenetetrahydrofolate Reductase are the two words that pop into your brain, right? No? Well, hopefully after reading this, you’ll see more than that swear word that caught your attention.

If I next mention bipolar struggles, rapid mood swings, depression, anxiety, heart disease, strokes, macular degeneration, miscarriages – and any of these issues hit home for you, then read on, because you might just want to know about MethyleneTetraHydroFolate Reductase – better known by its abbreviation – MTHFR.

MTHFR is a gene and like all genes, it acts as a light switch – turning on or turning off various body processes. In this case, MTHFR takes folate (vitamin B9) and methylates (converts) it into methylfolate (5-methylTHF). Hardly seems like a big deal, does it? Yet, if you belong to an autism, Pandas, Lyme or chronic fatigue group, you’ve probably noticed a big buzz around this thing called methylation. While the past decade has seen MTHFR studied in terms of cardiovascular disease and cancer, it turns out it might also be a very big deal for those raising kids with developmental, neurological or behavioral symptoms and for those fighting chronic infections.

Methylwhat?

A lot of parents raising kids with challenges are already overwhelmed – too overwhelmed to start stuffing their brains with hard to pronounce words describing hard to understand biochemistry. But you can think of methylation as a kind of metabolism. Imagine the insides of a clock with many cogs, each cog regulating specific chemical reactions. This is an over-simplified diagram of the methylation cycle:


The cogs in this picture turn in your body billions of times per second. But quick, before your eyes glaze over, find the MTHFR in the middle of the picture. Got it? The MTHFR gene sits at a critical point. If you have a glitch that keeps this gene from doing its job, the cogs on both sides of the picture are going to get mucked up. Instead of the light switch being on or off, it’s stuck in some sort of dimmer switch mode, functioning, but not nearly as well as it should be. The proper interaction of methylfolate and Methyl-B12 is what drives your body’s ability to fuel every cell in your body with energy (this is what’s going on in the green and red cogs). Methyl-B12 regulates certain T-cells that may play a role in some autoimmune diseases. Improper methylation can also raise your levels of homocysteine (look to the bottom of the red cog on your right).  This can greatly increase your risks for heart disease, stroke, macular degeneration, dementia and some cancers (e.g. lung, colon and leukemia). It also impedes your ability to manufacture glutathione (bottom right of diagram), the body’s master antioxidant (the “sanitation engineer”) that plays a critical role in autism treatments, chronic Lyme disease and some tic disorders. While there isn’t enough research to say for certain, some MTHFR literature discusses a possible role of MTHFR mutations and increased miscarriages. Insufficient levels of methylfolate are linked to neural tube defects, which is why pregnant women are told to take supplements of folic acid. But if your body has a faulty MTHFR gene and can’t properly convert folate into methylfolate, then this advice may not be having the intended benefits.

So you can see why this one little gene is a big deal. And you can find some pretty decent articles on the web on why treating an MTHFR mutation is so important for many health issues. But there’s one more important role that MTHFR plays. One that doesn’t get nearly enough ink. Look to the left of the MTHFR circle. See the blue cog labeled “BH4 cycle”? MTHFR plays a direct role in how well the BH4 cycle works – and the BH4 cycle controls those two neurotransmitters that are so essential to people with behavioral and emotional challenges – serotonin and dopamine. This has a huge potential impact for how some kids might be helped – kids whose parents are averse to psychotropic medications as well as kids for whom medications have been ineffective or caused serious side effects.

After months of studying everything I could get my hands on, I came to realize that given my long family history of heart disease and depression, this microscopic chemical conductor, aptly named MTHFR, might be the cause of a lot of suffering along my family tree.

Testing MTHFR is actually very simple. Most commercial labs in the U.S. can test for it.  Go to your local lab’s website, find their test menu (usually under the section for doctors) and search on “mthfr” or “methylfolate” or some similar phrase. This should bring you the test code number that you can ask your physician to order. The list price for my test was $150 but my insurance negotiated rate was $50 and since we’d met our annual deductible, my 20% portion of the bill was $10. 

A note from the Easy to Love editor: a couple online labs that offer MTHFR testing are:
23 and Me and Seeking Health

The results for one of my children came back normal. So the source of his hurdles lay elsewhere. MTHFR, no matter how important, is certainly not the single root of all evil. But my other child showed one mutation (called a polymorphism) on her MTHFR gene. At least 24 mutations have been identified on the MTHFR gene. Only two are well studied at this point – mutations labeled C677T and A1298T. My daughter had one mutation of C677T, making her heterozygous. (If she had two mutations of C677T, she’d be homozygous).

In the U.S., it’s estimated that roughly 45% of the population may have at least one mutation of MTHFR, though your heritage can increase or decrease your individual risk. While exact numbers are hard to verify, one mutation on C677T means you’re probably methylating (converting) folate into methylfolate at 40-60% efficiency. If you have two mutations, that number drops to approximately 10% efficiency. In my personal experience, this is a pretty big deal when it comes to dealing with anxiety and depression. (I couldn’t find estimates for A1298C mutations and much less is written about this. It seems to play a greater role in gut health. For more details, you’ll need to watch Dr. Amy Yasko’s videos. It’s well beyond my ability to do justice to A1298C.)

By following the green cog counterclockwise to the blue cog, you can see the impact on serotonin and dopamine and why knowing about this gene can be important to those who struggle with mood and behavioral disorders.

So what to do about it?

Those who’ve studied methylation extensively have developed various protocols depending on what ailment they’ve focused on. But the common thread for those with a C677T mutation is that if your body can’t convert folate into methylfolate properly, then you can help your body around this hurdle by taking a supplement that already contains methylfolate (not regular folate) to make up for the shortage.  (Think of using instant mashed potatoes where the hard work has already been done for those of us who are cooking-challenged – except unlike potatoes, methylfolate from a store is just as good as “home-made”).

Because this is an emerging field of research, little guidance is out there regarding dosage and step by step how-to’s. There’s no vetted resource to tell you the proper dosage of 5-methylTHF to give an adult, let alone a child. I know one child who’s doing well at less than 100mcg/day (that’s micrograms) and a teen who’s on 10mg/day (that’s milligrams) of Deplin (a prescription form of methylfolate). This is an enormous range for dosage. Most sources I’ve come across discuss ranges of 100-400mcg for a child and 800mcg-1mg for an adult. But many factors are at play and it’s best to work with a physician if possible. Unfortunately, the whole field of epigenetics is so new that few clinicians have much experience in this area. So you may need to do a lot of research alongside an open-minded doctor. We started out slow – very slow, then gradually built up dosage under the guidance of my daughter’s doctor. Even with a doctor’s help, there was still an element of guesswork involved, in the same way doctors work with any patient to zero in on an ideal dosage for any medication.

Supplementing with methyfolate has made a huge difference for my daughter. Over a few months, my daughter’s anxiety, mood cycling and sadness evaporated. So we kept tweaking. At the two month mark, we unwittingly went too high and endured a period of extreme anger, serious depression, food refusal, rapid mood swings, oppositional defiance and truly ugly times – the very things that drove us to our supplementation trial to begin with. Confused, I was ready to give up. But then, almost by accident, we stumbled onto the problem when I stopped the methylfolate in order to do a lab test. Within 24 hours of being methylfolate-free, my daughter’s issues melted away. Hmmm. She became pretty stable – for about a week. Had we been on the wrong path? Then things started to head south again. That feeling of panic returned to the pit of my stomach – that feeling just before you plunge over the peak of the rollercoaster track and you start screaming for your life.

So I re-started the methylfolate at a low dose – and things got good again. It felt like the sun had come back out from behind the clouds. So we built back up once more, not as high as before but just to the point where things got a little dicey again. When warning signs of a meltdown showed on the horizon, I used the advice from one of the MTHFR researchers and gave a small dose of niacinamide(vitamin B3), which has the effect of using up methyl groups (think of it as a sponge mopping up a spill). Within the hour, things were calm again – and stayed that way. Over the course of a few weeks, we zeroed in on the dose of methylfolate that seemed to work best. It will inevitably change as my daughter grows and when her body may need extra resources, like when she’s fighting an illness. It will always be a little bit of an experiment, in the same way that dosing of an SSRI or psychotropic medication is never carved in stone. After all, what fun would parenting be if you were allowed to figure things out and then get on with your life?

Our experiment has been going on for awhile now and I’m happy to report that things have stayed pretty stable. I did find that in addition to methylfolate, my daughter also needs methyl-B12, because both are necessary to keep the methylation cycle functioning properly. If you only take one without the other, you can develop what’s called a folate trap and you can end up thinking you’re on the wrong track when you’re really not. I’ve also tried to keep my daughter away from things fortified with regular folate – things like cereals and multi-vitamins. Her body just can’t handle the regular stuff and if she consumes too much, we end up paying for it with glimpses of the bad old days. Things we once used to help with anxiety have gone by the wayside. I’ll never know if I’ve helped her avert some other ailment, such as the macular degeneration that robbed my father of his eyesight or the strokes that crippled my grandmother or the congestive heart disease that killed my uncle. But I know that my daughter has improved her own odds significantly. Best of all, as winter brings shorter days, it isn’t bringing the depression and sense of dread that has often come with it. Is this all because of a supplement? Hard to say. I’m sure having a happy child plays a role in many ways. But unless things take a dramatic change for the worse, I’m feeling like we’ve found a key piece of our behavioral and health puzzles.

MTHFR is by no means the Holy Grail. The entire field of epigenetics promises to bring even greater gifts and ideas and more than a few dead ends. But for now, this one little gene has proven to be one big deal in my family.

For additional resources, please investigate the works of

(image courtesy of flickr user Franklin Park Library)

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90 thoughts on “Holy MTHFR!

  1. Absolutely fabulous article and so well written! You’ve done it again, Queen Analogy!

  2. Thank you for this well written, easy to digest article. Finally a MTHFR! print I can understand. Yay.

  3. Great post! You really explained it well, and I especially liked how you included how the dosing can be so unique to an individual. You might be interested in reading my paper posted on my blog http://www.greensandgenes.blogspot.com. I have a pretty comprehensive post from research about MTHFR and it’s wide-ranging effects on our collective health! I especially like to point out the neurological damage that can result from using nitrous oxide in someone with MTHFR mutations, as I believe is a major factor behind my son’s challenges. You may also want to visit Facebook’s MTHFR Support page where we share and discuss all things MTHFR. That is where I saw the link to this post.

    • Wow, who knew that I would learn so much on a Sunday morning. Thanks for sharing.

  4. Great article and very well written. Thanks for making a complex topic so easy to understand.

  5. Hi- Thank you for writing this. Your story could be mine and I am just learning more as we figure out how to do this. My family shares the MTHFR mutation to different degrees and as adults we can figure out the medication that works best for us individually but my child also has the C6779 Mutation and no one knows anything about how to help a child. So at 7 years old I started giving him my Deplin. He was having mood and defiance/ control issues mainly at school. He just wasn’t a very happy kid. So the Deplin seemed to really work until it gave him a neuropathy of his foot so we cut it and cut it more until I just felt wrong even giving it to him. We stopped and didn’t know what to do…his behaviors increased and he had difficulty controlling himself and he just wasn’t happy anymore. So we started him on some 5 methylfloate from Seeking Health. It gave him headaches and made him dizzy/ nauseas. We stopped and started with Thorne Research – 5-MTHF (5-Methyltetrahydrofolate) – 1mg — I upped it slowly and it seems like 3 mg is the answer for him right now. It is amazing the difference in him. Now I just want to have a community or someone that understands this because no drs around here do and because he is a child they can’t really test out different drugs etc or believe that this could make such a difference. Anyway your story really hit home and I appreciate it so much. I am curious how you decided to start giving the B12 or is it just a given that we should supplement with that. I find it hard to differentiate know what is behavior and what is from this methylation process….so don’t know what to do. I am so curious how your daughter is doing now. I hope well and I hope your household is calm. Thank you again.

    • Paige
      I am going through the exact same thing with my 8 year old right now. I would love to talk to you about your experience with deplin. Please email me at clubbie1@aol.com if you are interested in sharing stories.
      Allison

  6. Folate and B12 work together as co-factors. Having one without the other doesn’t make the proper reactions occur and both need to be in the methylated form in order for the body to use them. “Normal” bodies can take regular forms of folate and B12 and turn them into methylated forms. Those with MTHFR alterations cannot do this efficiently. So we bypass this bottleneck by supplementing directly with the methyl forms, doing the work that the body can’t do for itself. But you need both methylfolate and methylB12, so it’s a good idea to supplement both together. To only supplement with methylfolate runs the risk of having the stuff puddle up, unused. By adding methylB12 as well, you can make sure the proper actions occur.

    Since writing this, I’ve run a full series of genetic tests using the a company that analyzes DNA for the public (I used 23andMe but there are others). I’ve learned that in addition to MTHR, there are other roadblocks in my daughter’s methylation cycle. I’ve making adjustments to diet and supplements accordingly and her moods have improved even further. For her, this is certainly a major component of her struggles and has given us a way to potentially prevent a lifetime of emotional and cardiovascular battles. (Fingers crossed).

    • Thank you. We have added the B12 and ordered the 23andMe for the whole family. It is truly amazing the differences we see in our child just with the 5-MTHF and b12. It is amazing. THANK YOU for this writing and your help. I feel like I have been looking for something online like your article for years – it is incredible to finally find it. Thanks.

    • Thanks for explaining this so well! We are battling sudden-onset ocd, extreme oppositional defiance in our 7 yr old daughter. With the help of a spec scan and countless blood tests we discovered she has pandas (rheumatic fever of the brain). We have had success reducing her symptoms and getting our daughter back and recently discovered she has 1 mthfr mutation (based on blood tests). We started her on 250mcg of L-5 methyltetrahydrofolate and 2000 mcg of methyl B-12 two weeks ago and are keeping our fingers crossed it helps.
      We are about to do the 23andme tests to see if anything else pops up and I was wondering what other methylation “roadblocks” that you specifically uncovered so I know what to look for in the results. Thanks!

      • One of my children also has Pandas, so I totally understand how the rug has been pulled out from under you. I’m glad to hear you’re having success getting her back to baseline! I’ve found the support group at Latitudes http://www.latitudes.org/forums/index.php?showforum=17 to be essential in helping me through some very rough times. For greater understanding of your 23andMe results, you can run your results through an app at http://www.geneticgenie.com where the owner requests a small donation. This gives you a report that quickly identifies other methylation roadblocks. I then used this resource by Dr James Roberts to help me understand what nutrients/supplements would be appropriate for my family’s needs http://www.heartfixer.com/AMRI-Nutrigenomics.htm (scroll down past the diagram for a very long article). Best of luck in your daughter’s recovery! (Oops- it’s geneticgenie.org ! My apologies. Thanks for pointing that out Amanda! (see comment below))

        • Thanks so much!
          The http://www.geneticgenie.com/ link just looks like one of those spammy websites that lists a bunch of ads related to your search. Do you have any more specifics regarding the app you run the 23andme results through for the methylation roadblocks?
          Cheers.

          • Leon, the site is actually geneticgenie.org and it’s helpful.

    • Thanks for your article. I have been going through this with my twelve year old daughter. She was initially diagnosed with diabetes but after weeks of up an down glucose , insulin levels, she has been stable without insulin for 3 months. She was tested positive for MTHFR and mercury toxicity. We are starting the methylation process. I was wondering how long it took you to get some results? Did your children attend school during treatment?

      • Yes, my kids have been able to stay in school. My daughter responded to the addition of methylfolate almost immediately. Within days, it was clear it was having an effect. But it did take us a few months of tweaking until we found the ‘sweet spot’ doses of methylfolate and methylb12 that were “just right” for her body. That meant going overboard in doses, realizing we’d gone too high, backing down, realizing it may not be enough, etc. But we always saw changes within a few days – for better or worse. Thankfully, she’s been very, very stable for over a year now. No one would ever suspect she once had trouble regulating her moods.

  7. Pingback: Snips about SNPs ~ MTHFR | Taking Baby{food}Steps…

  8. Thanks for your article. It explains this topic simply and well. I have had anxiety/depression issues, super-low energy and food intolerances for a long time now. I just found out I have only one copy of the C677. My husband and I have been having a great time feeling so naughty using the accronym. My kids, though of course very bright, are soooo slow at all their school work. I do know my son is a worrier. They’ve never had any diagnosis because they are very well behaved, but I’m wondering if some methylation could help them have an easier time with certain tasks that seem easy for other kids.

  9. Hiya. GREAT article! Thanks so much for this. My family has faulty MTHFR and my 5 yo daughter has kryptopyrroluria. We also use B9 and B3, and B12 (plus a whole host of other supplements) for her condition. We use ionic drops from Metabolics and her dosage is a few drops which varies day to day. Like you say, too much, and her symptoms return. I also find that magnesium is an absolute must to keep her calm and able to cope with school and other day to day challenges. The peds never mentioned that, but through trial and error I’ve found that magnesium does wonders – especially for her insomnia as well.
    Looking forward to reading more. Thanks again for putting the cogs together, really helps make it all much clearer in my mind.
    Blessings :)

  10. Thanks for writing this article in such an easy way to understand this complicated process. My daughter is taking 5-MTHF for a month (her dose is 5mg/day). Some of her behavior issue improved, but not “amazing” changes as I expect. After reading your article, I felt she may also need B12 because she has C677T mutation, high VB12 and Folate from her blood test. What brand of B12 do you use for your daughter? Did you also increase the dose of B12 gradually as you gave 5-MTHF? As for Niacinamide, did you give it to your daughter routinely with 5-MTHF or only gave to her when you saw meltdown?

    • I’ve used several brands of methylB12 and don’t have a brand preference. We use a subliungual tablet. I initially tried to split the tablet in half so we could titer up the dose but it crumbles quite a bit so after a week we moved to the whole tablet, which is 1000mcg. You don’t give your daughter’s age or weight, but 5mg of 5-MTHF is rather high for a child, so if adding the methylB12 doesn’t bring you to the level of improvement you’d hoped, you may want to discuss a decreased dose with your doctor to see if that helps. Sometimes, too much of a needed supplement can bring about the same symptoms you’re trying to eliminate. It is, unfortunately, a process of trial and error.

      As for the niacinamide, we only used it twice for meltdowns during our own trial and error phase. When she reacted positively and quickly, we reasoned that it was a sign the dose of methylfolate was too high and we adjusted downward. Once we settled on a dose, we put the niacinamide in the back of the medicine cabinet and haven’t used it since.

      Since writing this, we’ve used a commercial genetic testing service to look at all the genes involved in the methylation cycle and found additional roadblocks. Life is really, really good and my daughter is happier than I’ve seen her in years. Best of luck on your daughter’s healing!

      • Thanks for your reply. My daughter is 9 years old. Her weight is about 60 lbs. My daughter told me to give her 2 capsule (2.5mg/capsule) per day. I will talk to my doctor about reducing the dose and adding methyl-B12.
        Do you know if adjusting the methylation cycle will also improve sensory issue?
        As for the commercial genetic testing, did you mean 23andme or Dr. yasko?
        Thanks

  11. We just got the test results for neurogenetic testing for my son (10yo, ADHD, Anxiety, severe EF deficits, dysgraphia, written expression disorder, and gifted intelligence) yesterday. I have been trying to make heads or tails of many scientific articles on MTHFR and COMT for several weeks now — thanks for describing this process in a way that is easy to understand!

    So my son has
    MTHFR +/- decreased on both C677T and A1298C
    COMT +/- decreased
    GSTM1 ABSENT (explains why his heavy metals were high but never been exposed)
    GSTP1 A114V -/- and I105V +/- (decreased)
    SOD2 +/- decreased

    Holy MTHFR and other genetic polymorphisms!

    These abnormalities explain almost every single “issue” my son has.

    Your article and the success with your daughter is very encouraging. Supplements recommended by our doc are on their way in the mail. I can’t wait to get started and {fingers crossed} see some positive changes.

    If nutrigenomics were part of the “regular” treatment plan for kids like ours, so many of them would be doing better than with standard medical practices today. Incidentally, I had to pay $387 out of pocket for this test. {sigh!}

  12. Thank you for this article. Our naturopath brought up the possibility for MTHFR for my 3 year old son. Turns out he has one copy of C677T (my husband has one of each). So, he wants to start him on L Methylfolate 800 mcg. After reading your post, that seems high for a 30 pound child. Besides which, all I can find are 1000mcg capsules. I was wondering how you played around with doses? Divided capsules in something?

    • I’m not a doctor, but 800mcg is a dose I use as an adult. So for a 30 pound child, it does sound like a high starting dose to me. Mu daughter takes a liquid form of l-methylfolate and each drop of the product she uses contains 67mcg. So she’s able to take 67mcg without my needing to divide capsules or imperfectly cut pills. I can’t recommend one brand over another but here’s one product that comes in liquid form:

      When I was trying to zero in on dosing, I started low and stayed low for several weeks. I then mistakenly increased the dose and saw a return of the same mood issues I’d seen disappear in the low dose. I then gave a “small” dose (50mg) of niacinamide (most supplements come in much larger doses) and about 45 min. later, my daughter’s mood became much more stable. This told me that over/undermethylation was a big factor in her mood swings. So while she normally needs to avoid lots of niacinimide (she stays at doses less than 20mcg on average), the extra niacinamide helped mop up the excess methyl groups I’d mistakenly added to the mix when I moved to a higher than needed dose of l-methylfolate. This little experiment told me to back down on her dose of l-methylfolate and she seems to do best on 67mcg every other day. This may change as she grows. But to answer your question, I played with dose until I went too high, then backed down until we got a place where things seem stable. Another reasons using a liquid form when you start out is so helpful, even for adults.

      You’re fortunate to have a clinician who’s aware of methylation issues and is willing to consider this for a child. Sounds like a keeper! Good luck!

      • Hello. I just ordered the DNA testing through 23 and me and working with our pediatrician to start a supplement plan based on your findings. I’m wondering, do you have a spreadsheet or tracking plan that you use to document and track dosages, special events, etc?

        One of the things that I think will really help for future parents and such is tracking successes, set backs, etc…especially when it comes to getting certified approvals for reimbursements – insurance companies rely on benchmarks.

        But also, as a mother of a child with ODD, I have to track everything and if you already have a successful process in place, I would certainly love your insights!

        Lastly, anyone that is ordering these supplements – that can share websites, stores to purchase, are greatly appreciated.

        • I use an excel spreadsheet to track behaviors, events, changes in supplements or medications… Set up a bar chart that has dates on the bottom axis. Tonight, I’d rate the day’s symptoms/behaviors on a scale of 1-10. If it was a good day, it’s a 1, a bad day would be a 10. On the day I started a supplement, I’d write it – by hand or as a text box – above that day’s bar. On a day my child had a cold or stressful event or change in dosage, I’d write that in above that day’s bar. Over time, you can track patterns and recall events you might otherwise forget. My doctor loves this. In 30 seconds, he can see how my kids are doing and then get on with what we should do next, instead of wasting precious time re-capping the past. If you’re really good with excel, you can rank separate behaviors (e.g. hyperactivity, anger, fatigue) and make a stacked bar chart for each day. This would tell you that X supplement greatly helped with hyperactivity but made the anger much worse. So you could see another layer of detail instead of just a “good” or “bad” day.

          As for where to buy supplements, I personally use Amazon when I can. Sometimes I need to go directly to a supplier’s website. I find it helpful to ask others on the support forums I belong to for product recommendations. One group that’s been helpful on methylation topic is the Facebook page mthfrsupport – they often are aware of sources I hadn’t known about before. The one lesson I learned the hard way was to avoid the temptation to order large quantities to save money. The first or second time you use a product, order the smallest quantity until you know it will work well for you. I have a very large “shoebox of shame” filled with half bottles of things that didn’t work but I can’t bear to throw away. Occasionally, I’ll be able to use it for a different family member or pass along to a friend. But there’s a lot to be said for a “trial” size!

          • Thank you so much for this!

      • Laura–

        What a great article!!! You simplify it so beautifully–thank you thank you.

        I have a question: did I read correctly that one of your children has the MTHFR mutation but the other doesn’t? I thought siblings shared 99.95% of genes. I ask b/c I have the c677t mutation (homo) and was wondering if my sister will have it, too. Also, my husband doesn’t so I’m thinking my daughter will be heterozygous (she’s two).

        Thanks,

        M

        • In this document there’s a good explanation of what’s called a Punnett Square, that shows the statistical probabilities of a child’s genes based on his parents’s genes.
          When both parents are homozygous (+/+) all of their kids will be homozygous (+/+)
          When both parents are homozygous (-/-) all of their kids will be homozygous (-/-)

          When both parents are heterozygous(+/-)
          1/4 of their kids will be homozygous (-/-),
          1/2 will be heterozygous (+/-), and
          1/4 will be homozygous (+/+)

          With (+/+) and (+/-) parents,
          1/2 of their kids will be homozygous +/+), and
          1/2 of their kids will be heterozygous (+/-)

          So without knowing your parents’ genes, it’s hard to predict if your sister would carry the same mutations you do. Since you’re homozygous (+/+) for C677T and your husband is (-/-), your kids would fall into the last category. But since many other genes affect methylation in combination with MTHFR, it might be worth looking into additional testing so you can see what other genes might be playing a role in her methylation/neurotransmitter pathways.

          • Thanks again Laura–and for getting back to me so quickly!!!

            Also, from the reading, I’ve surmised that your daughter is heterozygous MTHFR677–am I correct? That would by my daughter, too. Do you have advice on dosing for a two year old, which is her age. I want to get started early for her.

            I ordered the children’s chewable multi from Seeking Health and it contains methylated Folate and B12, but I was wondering if you have direct experience or have heard about a good sweet spot ball park for a toddler.

            Thank you thank you thank you.

            M

  13. Hi there,

    Would you PLEASE be so kind as to share where you have found the liquid form. Is it by chance Amy Yasko’s? We are struggling so hard with aggressiveness with our 4 year old from under and over methylation as Im trying to slit a 1000mcg pill. I was going to order her methylmate b drops but I wasnt clear if the form was ok as it states: 6S)-5-Methyltetrahydro folic acid (as glucosamine salt). Thank you and take care!

    Michelle

    • Yes, my daughter uses Holistic Health’s (Yasko’s) Methylmate B drops. The 6(s) form is one of the “good” forms according to the article on Ben Lynch’s site and according to the folks who admin the mthfrsupport facebook site.

  14. Thank you for your very clear and informative page! I’m just getting started and am looking for some guidance.

    I am compound heterozygous MTHFR. I’ve done LiveWello and Genetic Genie and seen a few other mutations, most notably CBS. My health issues that I suppose are MTHFR-related are anxiety, migraines, IBS. I also have POTS and IgA Nephropathy and am investigating the possibility of EDS and mastocytosis, both as causes of POTS.

    We haven’t done 23andme for our 4 year-old son yet but he is autistic (more Aspbergers-like now) and has some anxiety and sensory issues. Since my husband’s results showed the A1298C mutation, we know our son has that at a minimum or is compound heterozygous like me.

    I’ve looked into the Yasko protocol as well as some others. I’m leaning towards just adding the methyl-B12 and methylfolate now, or one first then the other. Any suggestions what dosages to start with or where I can find this information? My son will only take chewable or liquid meds (no matter how bad they taste!) so for him I need to avoid capsules or sprinkles. I’ve seen some chewable multivitamins and sublingual m-B12/l-5-mthf combos but am not sure if those would be good for him or even me based on what you and others say about having to taper up the dosage.

    Thanks!
    Alison

    • We use the drops of methylfolate from Holistic Health and a sub-lingual form of B12. The drops allow you to taper up the dose in small increments.

  15. Hi,

    I have been having a similar problem to what you described. I tried 3X800 micrograms of methyfolate with no results, and when I went up to 5-6 (~4.5 mg) had huge improvement in my mood. So I figured I would go up to 15mg and get even more results, but instead my mood deteriorated signficantly.

    I was curious what dose your daughter found most effective because it seems we respond similarly, I’m wondering if I should try 7.5 Deplin. I was also really curious about the methylated b-12 and what ratio you should have between it and the l-methyfolate. Anyone know?

    • My daughter ended up doing best on 67mcg every other day – a very, very small dose. If you’ve found a sweet spot at 4.5 mg, perhaps you can try to slowly add one or two more 800mcg tablets to get to a 7.5mg dose to see how you feel, before committing to a 7.5mg dose of Deplin. As you say, more is not always better but it seems to be highly individual and something you can only figure out through trial and error until more doctors become well versed in methylation issues. Your best dose may also change if you ever discover/treat other genetic methylation issues, or in the case of a child, the dose may change as he grows.

      I don’t know what the ideal B9/B12 ratio would be. I’ve been told by my doctor that methylB12 is very poorly absorbed orally and it’s estimated that only 10% of it makes its way into your system. But I don’t have any source to confirm that. If true, you’d have to take a lot more methylB12 than methylfolate just to arrive at a 1:1 ratio once inside your body. But it’s a good question. Most people I know arrive at their optimum B12 level thru trial and error. Some also find that a blend of methyl+hydroxy B12 works better for them than straight methylB12. Perque makes a sublingual blend and SourceNaturals makes a good sublingual that’s strictly methyl form.

      One problem I ran into after supplementing these forms of B9 and B12 is that it was very difficult to find a way to supplement the other B vitamins, because it’s so hard to find a B Complex that doesn’t contain regular folate and/or some form of B12. I finally found a B Complex without B9 or B12 in Nature Made B Complex (not the Super B – just regular B Complex).

      • Thanks so much for the info! One last thing- I think you are suggesting that taking b9 and b12 in an unmethylated form is bad, I just figured it would wash out after not being absorbed, this is not the case?

      • Buy Country Life Co-enzyme B complex. All the Bs are in the correct forms.

        • I was asking for websites/brands earlier and I think this entry has a great deal of information in it. Wow – now to collect it all in one place and process…

  16. Really well written article that was so easy to follow You have a gift there. :-)
    I personally have had a lifetime (4o years) of trying to get to the bottom of seemingly intractable regular ‘episodes’ of migraine…which seem to lead into depression etc…exremely debilitating. I have recently been diagnosed with 2 x heterozygous MTHFR gene mutations (C677T & A1298C) which goes a long way to explaining it all. Now to sort out the treatment!!

  17. Hi everyone,
    I also have been diagnosed very recently with Heterozygous c667t. My kids haven’t been tested yet however based on symptoms, I’m sure they have it too. As well as the methylfolate and methyl b12, we also take P5P (active form of b6) and TMG (Trimethylglycine). You can get all these in a single supplement called Thorne Methylguard which is great for cutting the number of pills your kids have to swallow. B6 in the form of p5p is absolutely critical for methylation as well. When I started the TMG, it was like a lightbulb went on in my head and I can honestly say I haven’t felt this good in years. I actually get stuff done instead of sitting on the couch thinking about what I must do! We have had dramatic results with my son as well.

  18. Jeannine,
    I’m really glad to hear about your success! I would caution people tho, on supplementing without fully understanding or confirming their unique combination of genetics. Treating MTHFR made a world of difference for my daughter. But while I had always assumed she got it from me based on family history, it turns out I don’t have this mutation and should not treat myself for it. Likewise, those with a mutation on their CBS gene should restrict the amount of B6 and/or P-5-P, even if they have an MTHFR mutation. You’re right – it is essential. But not everyone will do well on the same doses. As tempting as it is to use a supplement that combines several vitamins and minerals, I’ve found personally that I need different doses of various things and haven’t been happy with combo supplements because they either have too high or too low a dose of one of the ingredients I need. So you really need to understand your unique set of issues before jumping into treatment plans. I’m a huge believer in the power of treating methylation road blocks. But I have to strongly encourage people to wait until they have test results before treating. It’s your combination of genetic mutations that determine the right doses for you. Still, I’m very happy to hear this has worked so well for you and I hope you have similar success with your kids!

  19. Wow! Thank you for an article well written and easy (well as easy as possible!) to understand! I was recently diagnosed compound heterozygous with one copy each of the C677T & A1298C mutations after losing my 4th baby @ 17 1/2 weeks. There doesn’t seem to be *nearly* enough information ou there about this problem considing how many people have it, how MANY aspects of your life it can affect, and how simple it is to test for it!! It sure sounds like this seemingly “small” problem could be the root of a whole list of health issues I’ve dealt with over the years! Thanks, again!

    • I’m so sorry for your loss! One miscarriage is painful enough. I can’t imagine enduring four. I’ve “met” many parents who’ve found that treating MTHFR has really helped with mood issues in their kids. But a few have said it wasn’t their golden ticket. In addition, there are several other genes involved in methylation that can also influence neurotransmitters, heart health and other disease risks. So this is only the tip of the iceberg and I reall yrecommend doing all you can to understand your whole genetic picture. But there are privacy and insurance factors to consider, so there’s no single “right” answer for everyone.

      You might also want to browse all the information on http://www.mthfr.net where you’ll find a fair amount of discussion on miscarriages. I do hope treating your MTHFR issues helps with your personal struggles. It’s heartbreaking and I’ll really be pulling for you!

  20. Also, how long did you take methyl folate before seeing a drop in bp? That’s another issue I’ve been battling for years now!

    • After seeing such amazing results with my daughter, we tested the whole family. It turns out, despite my family history with heart disease, that she doesn’t get her MTHFR issues from me after all. I have different genetic issues that contribute to my blood pressure problems. So methylfolate did not, in the end, allow me to stop my BP medication as I’d hoped when I first wrote this. But I did find other issues I’ve been able to address with great success. It sounds like understanding your genetic profile and how methylation supplements can help you detour roadblocks could be very helpful to you. It’s been a big help to my entire family. Good luck on your path to recovery!

  21. Thank you for sharing all of your experiences – they are invaluable to people who are just learning of this mutation. My son is 11 years old and for the past 6 years has had persistent migraine aura and lots of headaches and migraines. When he was about 12 months old, he stopped growing and gaining weight. Doctors did numerous tests and found nothing. He started growing again 15 months later and now is about 2 years behind his friends in growth and development. Allergy tests showed nothing, but we noticed milk products affected him, so we took him off milk for a few years, between the ages of 1 and 3. Dealing with the persistent aura has, by far, been are biggest obstacle yet. In searching the Internet I came across a woman’s blog who also had migraines and persistent aura and was under the care of a migraine specialist/ neurologist. She was tested for MTHFR and showed up with a mutation, for which she started taking Methyl Protect and is now symptom free. My son’s pediatrician agreed to test him for MTHFR mutations and we found out he has the c677t. I am hopeful that getting him on methyl folate and methyl b12 will help get him on track. I was a little concerned that his doctor prescribed folic acid, as I read that will hinder instead of help him. I have ordered Methyl Protect and we are waiting for it to be shipped. Now after reading all of these posts, I feel like I should do all of the supplements separately. Thank you for all of your information — have any of you had relief from migraines or persistent aura after starting the vitamin supplements after finding out about having a mutation?

    • I don’t know of any first hand stories of aura and migraine relief from treating MTHFR snps. But it would make sense that in some people, addressing individual methylation issues (MTHFR or the 30+ other genes involved) could make dramatic improvements in all sorts of health issues. My focus has always been on the impact methylation has on neurotransmitter levels. But you could probably get input from members of the various online methylation support groups. I know there’s at least one group that follows Amy Yasko’s protocols and several methylation groups on Facebook.

      As for supplements like MethylProtect – in general I think it’s better to fist use single “ingredient” supplements first until you figure out the best dose of each ingredient, and then look for a combo supplement that matches your needs. I personally think too many kids are put on doses of methylfolate that are too high for them. These supplements can have a “paradoxical” effect where too high a dose can cause the same issues that too low a dose can cause. So dosing each one individually I think sets you up for a better outcome. Later, when you’re stable, you can look at other options. That’s been my experience anyway.

  22. This information is very encouraging. I have an 8 year old daughter who last year was diagnosed with anxiety and ODD. She has been on a SSRI for the last year but we are still struggling. I just recently found out about MTHFR through a friend. We are currently in the process of finding a naturopathic doctor where I am hoping we can get some testing and some answers! It has been such a long hard road, but I know there are reasons for her behaviors. Feeling hopeful after seeing this might be the cause. So interesting !
    Thanks for the info!

  23. Thank you so much for this blog, it has really helped my understanding of what can be a very complicated topic. I have C677T mutation – Homozygote. I will be seeing a specialist soon for a genetic consultation however in the meantime i am going to do as much research as possible so i am armed with as much information as possible. In my research i stumbled across this product –

    Dr’s Best Fully Active B Complex

    Supplement Facts
    Serving Size: 1 capsule
    Servings Per Container: 30 servings
    Amount Per Serving %DV

    Vitamin C (as ascorbic acid) 40 mg 67%
    Thiamin (Vit. B1) (as hydrochloride) 60 mg 4000%
    Vitamin B2 (as riboflavin and 75 mg 4412%
    riboflavin-5-phosphate)
    Vitamin B3 (as niacin and niacinamide) 50 mg 250%
    Vitamin B6 (as pyridoxine hydrochloride 50 mg 2500%
    and pyridoxal-5-phosphate)
    (6S)-5-methyltetrahydrofolate (MTHF) 400 mcg 100 %
    (elemental, as 800 mcg (6S)-5-methyltetrahydrofolic acid,
    glucosamine salt (vegetarian source))
    Vitamin B12 (as methylcobalamin) 1000 mcg 16667%
    Biotin 600 mcg 200%
    Pantothenic acid (as calcium pantothenate) 100 mg 1000%

    Other Ingredients: Modified cellulose (vegetarian capsule),
    cellulose, ascorbyl palmitate, medium chain triglycerides,
    silicon dioxide.

    Contains nothing other than listed ingredients.

    Do you think this would be suitable for someone like myself whom has had no previous treatment? I realise that not one supplement would be suitable for everyone and each individual needs are different. I was thinking of it more as a benchmark supplement? As i live in Australia it seems most supplements i will need to source oversea’s as i cant seem to find anyone here who sell’s the active supplements.

    • As you said, everyone’s needs are different, but this product does contain the correct form of methylfolate and fir an adult, it seems to be in a reasonable dose. The problem you may run into is that you may need a higher dose, yet taking two capsules of this product would give you high doses of the other B’s that you may not need. The other issue is that my personal experience is that B12 taken orally doesn’t get absorbed well. My doctor has said it doesn’t survive the trip through the stomach acids very well. So most people who need B12 take it sublingually, letting it dissolve under the tongue where supposedly it’s better absorbed.

      But if access to supplements is limited, I can understand the appeal of this one. Understanding your full health picture is really important when looking at methylation. Hopefully, the specialist you’re going to see will be able to give you personalized suggestions and get you on the road to good health!

  24. This is a great article for understanding MTHFR. I really love the “over simplified” diagram of the methylation cycle. Very well put together!

  25. Would you mind posting what your excel spreadsheet of behaviors/supplements looks like? I’d love to make one, but have a hard time visualizing it (without actually seeing it)! Thank you for the informative article.

    • I’m sorry – I can’t post a file or image in the comments section.

  26. I’m struggling to find a dr who is well informed on MTHFR. My 6 year old daughter and myself both have one copy of the c677t gene mutation.
    Her dr prescribed 5mg methalfolate as a starting dose which seems high. She never mentioned anything about starting on the active form of b12.
    This page has helped a ton. Starting low and working up slowly seems like a smart plan until they have a better way to gauge how much the individual needs.
    When my daughter had her blood work done her b12 was high but not nearly as high as her b6. Her homocysteine was high and her ferritin was low.
    A brief history about my daughter. She is a very active 6 year old (probably adhd but I have never pursued a diagnosis) she is very bright but has extreme mood swings and emotional melt downs. She also has had sleep problems her entire life but is doing much better now (gluten free, dairy free, plus removing fortified b vitamins and supplements) she has celiac disease and is allergic to basically everything. She has reoccurring symtoms of candida.
    Can anyone tell me how iron is connected to mthfr? Has anyone else had their blood work show extremely high b6? Is high b6 a common problem with mthfr or should I be looking at testing her for another gene mutation? I was going to order the health test through 23andme but the FDA shut them down.
    I can’t seem to find a source of Niacinamide that is in the form of mcg. Everything is 100 mg or higher. I want to have something on hand incase she starts having symptoms of over methylation. Where do you get the 50mcg of niacinamide?

    • I agree that 5mg of methylfolate is a very high starting dose for anyone, especially a child. If you can start low and build up, I think you have a better chance of finding her “sweet spot”. I don’t know the relationship between iron and MTHFR but you can post this question on the FB page MTHFRSupport (and there are others on FB as well).

      In my own experience (again, I’m not a doctor), when people have very high levels of something like B12 or B6, it’s been due to a methylation blockage. In other words, her B12 intake may be adequate but without sufficient methylfolate as a dance partner, the B12 puddles up, unused. I’d expect that with adequate intake of methylfolate, the B12 should become better utilized and the levels should come down as the roadblock is cleared and the backup clears. The same for B6 – which I suppose could be “puddling up” due to an MTHFR roadblock, but could also be from a genetic roadblock elsewhere in the methylation cycle.

      The best way to figure out your daughter’s unique issues is to do the 23andMe test. The FDA has not shut them down. They are still operating and you can still order a test kit for $99. The FDA didn’t object to the validity of 23andMe’s raw data (the test is processed through a CLIA certified lab). What they objected to was the 240 “health reports” that 23andMe provided to its customers – reports that said “based on your data, you have an xx% higher risk for abc disease and an xx% lower risk for xyz disease”. The FDA questions the accuracy of these % risk assessments. It’s not the accuracy of the raw data that’s being questioned but rather the interpretation of what the raw data means.

      Personally, I never found the 23andMe health reports very informative and they certainly didn’t tell you what to do about the identified risks. But I’ve found the raw data invaluable. By taking the status of the 30+ genes involved in methylation and using the resources I’ve linked to above, I think you can get a great roadmap for what supplement and dietary changes you can make to improve neurotransmitter balance and mental health. If you’re at all interested in pursuing testing, you can still do the 23andMe test. You just don’t get their reports anymore. But it’s the raw data that holds the real value, so to me, the test is still very helpful.

      As for the niacinamide, I mis-typed the dose I use for my daughter – I use 50mg in an emergency, not 50mcg. I’ve gone back to my previous comment and corrected it. Thanks for pointing that out!! You can get 100mg capsules and break them open, dividing the dose in half.

  27. Thank you so much for the information. Can you please tell me the dosage of sublingual B12 you give your daughter? My son is only 2 and has 2 mutated copies of C677T.

    • My doctor tells me that it’s estimated that only 10% of B12 taken sublingually actually gets absorbed. So my daughter takes 1000mcg methylB12 sublingually, which would be roughly 100mcg getting into her body. B12 swallowed apparently doesn’t survive the stomach acids very well, so sublingual or B12 shots are the preferred methods. I used to dissolve the B12 tablet in water and have my daughter drink it, because she wouldn’t/couldn’t keep the tablet under her tongue. She still tested B12 deficient. So drinking it was ineffective. It was only after she learned to keep it under her tongue that she stopped complaining of fatigue. For a toddler, you may want to speak with a pediatrician. I’m not sure how to advise you on the best way to get the B12 into him effectively.

      • Thank you. At what age was your daughter able to keep the tablet under her tongue? My son has an appointment with his hematologist on Monday, we’ll what they say. I saw in your bio that you are from Connecticut. We live in NYC and I was wondering if there are any integrative doctors or naturopaths whom you could recommend.

        • Also, I was looking for something that has 1000mcg and only see 5mg. If you could tell me brands that have a lower dose, I would really appreciate it. Thank you!

  28. I have just stumbled across your article. This has shed a great deal of light on MTHFR for me. After multiple miscarriages in the last year, I found out I have MTHFR both C677T & A1298C. I have spoken with both my GYN/OB and GP and the most informatin they have given my is take and aspirin and day and continue with pre natals. When pregnant , they will start me on anticoagulants. I have asked for more information and booked numerous appts where they have told me there is nothing to be done and just to keep taking aspirin.
    After reaserching a bit more myself this weekend. I find out the prenatals are doing nothing as my body can;t absorb them anyway. I have been depressed for so long and had so many other issues that reading this has given me hope that I can maybe start the right path myself. Unfortunately, I live on an island that does not have any form of a specialist here and as is my current experiance, no one here knows what to do with MTHFR other then pat you on the head and send you home. I am still crying of releif reading this.
    Thanks you so much for posting this and I am so happy to find this article amongst my searches. I have today bought L-Methylfolate and tomorrow will go on the hunts for Methyl-B12.

    • I’m so glad this has given you some hope and some things to research! Please check out the links at the end of the article, particularly Dr Lynch’s http://www.mthfr.net as he’s written a lot about MTHFR and miscarriages. Also read the comments, as they have some good thoughts too. I know how tempting it is to dive in when something resonates and after so much frustration. But please, when starting methylfolate and/or methylB12, start with low doses and go slow. The ideal dose for one person can be very different than the ideal dose for another. And nearly everyone I know who’s gone down this path has crossed an “invisible line” as they build up dose or frequency. Initially, they feel great as they build up. And then suddenly, BAM – they can start to feel angry, emotional, and re-visit all the symptoms they thought they were fixing. Whatever dose provokes this negative “reversal” where you go back to the bad old days seems to be that upper limit for you personally. Stop for a few days and re-start at a lower dose. The trick is finding out the dose and frequency (every day, every other day, etc) where your body feels best. Good luck!!

  29. Hi. Thanks for this information. I am compound heterozygous (677&1298) with normal homocysteine, normal b12, folate and histamine. But my b6 is very high at 96! My symptoms for years have been anxiety, panic attacks, moodiness with PMS, acne, and most recently, reflux lpr symptoms and throat spasms. I’ve had increased congestion for years but more in recent months and allergy tests are all negative. I just sent away for 23andme and am considering yasko’s SNP test although my doctor is not a fan of hers. I don’t see him till next month. Can someone tell me the significance of the high b6? (And I do realize just because my b12 is normal doesn’t mean I’m using it). I’ve been on Vitaprime with methylfolate and methylcobalmin for a few years. Doc recently put me on higher doses and I am working my way up. Also on DGH.

    • It’s possible that your high B6 is related to a variation on your CBS gene, but your best bet is to do either 23andMe or Yasko’s testing to confirm. All of the 30+ genes involved in the methylation cycle work in concert, so you can’t really base your treatment plans on just the results of one gene. You may find that other genes, like COMT, VDR, MAO, CBS, SUOX – all play a role in your symptoms. It can take many months of tweaking but unraveling methylation issues and finding the right balance of nutrients has really helped my family. I hope the testing puts you on the road to recovery! It’s by far the best $99 I ever spent.

  30. So you said your daughter has to stay away from foods fortified with folate. Does that mean she can still eat foods that have plenty of natural folate like leafy greens or do those also affect her? Thanks so much for the article!!

    • My daughter thinks “leafy greens” are disgusting, so staying away is something that happens naturally for her. I don’t know how this might apply to a child who actually enjoys vegetables.

  31. I am homozygous for the t677c mutation which I found out several years ago due to multiple miscarriages and genetic testing from my fertility dr. I not have 7 year old twins and an 18 month old. I would live to start supplements for myself my dr advised 1 mg methyl folate. My one son has as of late become extremely temperamental and the other has tics (they last for about a month) and difficulty focusing and staying on task at school. I make almost all our food from scratch thankfully as did my mother as I was growing up. I would like to try supplements for my boys starting at a low level. They weigh 43 and 47 lbs. can you please provide a link to the supplements that you but and have been pleased with. Do you have any doseage recommendations as the drs have all told me I would need to use trial and error. With no specifics as to where to start. Any help would be so appreciated

    • If your sons are struggling with intermittent tics, focus and behavioral issues, I strongly suggest looking into PANDAS. There’s a introductory e-book that goes into testing, treatment, etc (I’m a co-author) There are also PANDAS and Tic support forums on the same site.

      As for supplements, there are several discussed in the comments above. For my daughter, I use Holistic Health’s liquid Methylmate B so that I can give her a very small dose without trying to split capsules or cut tablets. One drop = 67mcg of methylfolate. I then couple this with a Source Naturals methylcobalamin sublingual 1000mcg (cherry flavored – the orange flavored uses adenocobalamin and tastes awful). Most things I’ve read say cobalamin (B12) is poorly absorbed when taken orally and only about 10% of what you take gets absorbed and survives its journey thru the stomach. So taking 1000mcg would deliver approx. 100mcg into the body. Some people take B12 shots instead, which would be more effective but not that practical for kids who have needle phobias. You can do a blood test to check for B12 serum levels, but high levels don’t necessarily mean good things. It could mean you have a block and aren’t processing the B12 properly. The links at the end of my blog should help but your doctor is right – it does take trial and error to find the sweet spot of what your body needs. Start low and build up. If/when you see improvement but then see a decline as you continue to increase dose, then back down. Sometimes you have to cross the line to find out where that line is. For my daughter (60lbs) she takes 67mcg methylfolate every other day and 1000mcg methylB12 daily. But it’s highly individual. Good luck!

      • Hi Laura,
        Thank for this primer, which helped so much! Where can I find your e-book on PANDAS?

        • The book can be purchased here:
          Glad this helped a little.

  32. Curious of a protocol/med options for a child under 2? My 15 month old daughter has 2 copies of the c677t mutation. I myself am compound heterozygous (a and t) and am currently pregnant with our 2nd child.
    We had our daughter tested at 3 months of age as it was a concern of mine but outside of diet we have yet to start her supplementation. I’m in the Chicagoland area and finding it hard to locate a doctor that can help guide us in the right direction to achieve optimal health.
    I have AI disease myself (unclassified inflammatory arthritis) and am still struggling with getting well myself. I really don’t want my daughter to end up like me, and with her having 2 copies of the t mutation, I fear for her future health. Any advice is appreciated. Thanks.

    • I don’t know about supplementing a child so young. It’s important to remember that having a genetic variant doesn’t necessarily mean that the variant is expressing itself. Genes can stay “off” for many years or even for a lifetime, or can be switched “on” and start expressing sometime during your lifetime. So it’s great that you know about your daughter’s risks but I’d probably hold off on “treating” until you had signs that this was an active issue for her. At her age, you’d need to be using very small doses of supplements and you’re probably better off just being aware of diet and limiting the amount of regular folate she ingests (e.g. fortified cereals). For yourself, you might find help from MTHFRsupport.com or their Facebook page of the same name. They have a list of doctors who treat methylation issues and some do phone consults.

  33. Hi. I am homozygous C677T, had one early miscarriage and now I am trying to conceive. I just started taking l-methylfolate in pills of 1000 mcg. I am thinking that I should increase it to 2000 mcg per day, what is your opinion on this? Thank you so much for sharing your knowledge on that matter.

    • There doesn’t seem to be consensus on what’s an appropriate dose for either an adult or a child. For my daughter, we based dosage on how she felt mood-wise, as this was the way her symptoms presented. I’ve learned the hard way that more of something isn’t necessarily better. But if you don’t “feel” different on different doses, one option would be to have your homocysteine, folate and B12 levels checked by your doctor. If any of these were off, it might help guide you. Just an fyi, high folate or high B12 can indicate a folate/B12 trap, meaning your body isn’t able to use/convert what it has, rather than meaning you should take less. If you go to http://www.mthfrsupport.com, you may be able to find a clinician who will do a phone consult and offer suggestions. Best of luck!

  34. A million thank yous for this amazing article! My 5 year old son with autism was just diagnosed with the MTHFR mutation A1298C. Our ped suggested a methylfolate and methyl B12…are there any brands that you suggest? We are looking into getting the B12 injections (he got them when he was younger) but a suggestion for the methylfolate would be great. The L form seems to be the best option…thank you again!! I have shared this with so many!

    • I think if you read thru the comments, you’ll find various products discussed. Best of luck!

  35. Hello!

    Thank you for your site! I am heterozygous a1298c. I discovered this last year when terrible depression with no real contributing reason almost took over my life. I take 15mg of deplin a day and 90mg of cymbalta. I will probably always take te cymbalta since my brain doesn’t seem to make enough of the chemicals, and obviously the deplin, for the mutation.

    Now that I know about mthfr, there is a very obvious family history. My older daughter just turned 6 and I am very certain has ADHD but it isn’t affecting her learning yet so we are just trying to work with it. She has always been a challenging, mercurial girl. She comes by it honestly as I was too. Her behaviors are very familiar of me as a young child. I am 99% sure she has the mutation. I plan to get her tested.

    I started her out on 5 mg of methyl folate thinking that if I take 15 mg daily that 1/3 of my dose seemed appropriate or a child. She does better on it than se does off of it, but I am starting to wonder if I have her on too much. If I start decreasing it 1 mg at a time, does that seem slow enough so that she won’t experience any sort of withdrawal trying to fin the right dosage? And what signs signal too much?

    Also, at what point should I consider methyl b12 shots? I have tried 5000mcg of jarrow brand sublingual tablets and don’t notice any benefit. How long does it take?

    Thanks so much!

    • 5mg for a child seems quite high, but there’s no real guide as yet – it seems highly individual. When I went to high with my daughter, I stopped cold turkey for a week to let things calm down. You could taper, but you’ll still be “overfilling the glass” even once you get to the right dose, since there’ll be an excess her body will need to deplete. So if it were me, I’d stop entirely for a few days/week until you saw her behaviors calm down. Then re-start at a lower dose – maybe 500mg and stay there for a week. Then if necessary, move up to 1mg for another week. But…I’m not a doctor and if you have a pediatrician to work with, I’d follow his/her advice. Children aren’t mini-adults. Their bodies work differently. As for the B12 – they work together, so starting them together seems reasonable.

  36. I have been doing a lot of research on nutrigenomics in the last month after receiving my daughter’s test results from 23 and me and processing them through genetic genie. As you said earlier, it is very important to understand the whole cycle and SNPs before supplementing. As I understand it, people with COMT, MAO, or CBS mutations should excerise caution with methyl donors such as methylfolate. “With a COMT + status, it has been clinically observed by physicians that people may have trouble with methyl donors. This can lead to irratability, hyperactivity, or abnormal behavior” (Genetic Genie). There is so much information out there and it is so complex! Each person’s make-up is unique and not everyone will be helped by methylfolate. Some may actually react badly to it. So, I would recommend that anyone considering supplemetation do the testing first followed by a lot of research. MTHFR is just one part of a very large, complicated picture.

    • I totally agree. Some members of my family are COMT +/- and do well on hydroxyB12 while others are COMT +/- and seem to feel better on methylB12. It is highly individual and testing has really helped guide our supplement plans. And even then, we’ve had to tweak based on how we actually feel vs. how the research predicts we “should” or “might” feel on a particular form of a nutrient. Best of luck to you and your family!

  37. Can you clarify for me, your daughter has 1 mutation of the MTHFR gene and your dr recommended/prescribed supplements?
    My 8 yr old daughter recently had a panel of tests done by our pediatrician and I just recieved the results. She has the 1 mutation of the MTHFR gene as well as PANDAS. My pediatrician consulted with the geneticist on the MTHFR and because she only has 1 mutation they didnt recommend any treatment. However we are going to treat her for the PANDAS with 3 weeks of an antibiotic.
    I have just scratched the surface with my research, so this article is extremely informative. Because of the PANDAS it made me wonder if that could make having the mutation be more pronounced. We were surprised by the positive PANDAS (dr said her numbers were in the 500′s?) because she doesnt have tics, etc. But we do have the behavoir challenges with defiance, hyperactivity, inability to relax, etc.)
    My daughter has been diagnosed with ADHD, however I have always questioned the diagnosis and felt her behavoirs are more a result of anxiety. In general, I feel that there are misfirings in her frontal lobe. My daughter does currently take Vayarin which i think has helped take the edge off.

    • Yes, my daughter has one mutation (heterozygous). Her doctor didn’t prescribe anything. He just served as my sounding board and supported my decision to treat methylation defects with the use of supplements to see what sort of results we got. We use an OTC supplement of liquid methylfolate. She takes 67mcg (one drop) every other day. I’m sure to any geneticist this would seem like such an insignificant dose as to be meaningless. But after many years of raising kids with Lyme disease, PANDAS, pyroluria and methylation issues, I’m now a member of what my friend calls “The Church of Whatever Works.” For years, we struggled with bipolar symptoms and all I can say is that our protocol has been working for 2 years now. She’s not on any medications and only takes a daily regimen of vitamins and minerals in doses meant to address methylation hurdles (e.g. she takes only a small dose of niacin but higher than typical doses of molybdenum).

      I can’t say if or how PANDAS may accentuate methylation defects. I know that in my family, our daily methylation protocol does not prevent PANDAS flares (my son has PANDAS). But when we’ve run out of specific supplements, we can see a marked difference in behaviors after a few days. So it definitely helps both during flares and during times of remissions.

  38. I keep saying i could write a book with the series of steps we have taken to support my daughter from all the drs, research, information i have gathered over the past 5 years. And i continue to discover new things that i believe can help us better support her.
    You state bipolar symptons which really resonates with me. That is a term i would use often in describing my daughter’s behaviors.
    Thank you for the feedback. You have given me some great information to begin a new path!

  39. Very interesting article! I discovered 6 months ago i have c677t heterozygously. This article is making me rethink some things. One question….benjamin lynchs website…www.mthfr.net says that regular folic acid needs to be avoided more strictly by homozygous individuals. Since im heterozygous…does that mean i can deal with some regular folic acid? My doctor has me on a b comolex vitamin with regular b12 cobalamin and a folic acid mixture that has regular fokic acid and l5 methylfolate in it. I seem to do better on that…but am not sure. Any comments woukd be appreciated. Also…do you know of any other ways beside 23andme to test for the snps that accompany mthfr? My doctor seems reluctant to try 23andme. Thanks for the great article!

    • Ben Lynch is considered to be a leader in the area of MTHFR issues and I certainly don’t have the training to make me more knowledgeable than him. I can only share my own experiences and understanding. There are some doctors who feel that if you’re heterozygous, you shouldn’t have any problem with folate, since you still have one normally coded MTHFR enzyme. That hasn’t been my own experience. But on the flip side, I haven’t seen the need to entirely restrict my daughter’s folate intake (tho I do limit fortified cereals and don’t give her any supplements containing regular folate just to be on the safe side).

      As for your B Complex, I’d suggest you have your doctor test your homocysteine, B12 and folate blood levels. If they’re high, that would suggest your body isn’t converting/processing the folate into methylfolate well enough and the excess folate or B12 is “puddling up”, unused – showing up as high levels. It’s called a folate trap. If you see this in your blood work, then you could try avoiding/reducing regular folate and taking only l-methylfolate, then retesting after a month to see where you’re at. Most things I’ve read say that the regular cyanocobalamin found in most vitamins is garbage. It’s the cheapest, least bioavailable form of B12. Hydroxycobalamin seems preferred, or adenocobalamin. My daughter uses a sub-lingual methylcobalamin and this seems to be the form she feels best on. Others in my family feel better on hydroxycobalamin. It was a trial and error thing in our house. We tried both hydroxy and methylcobalamin and different family members preferred different forms. To get the rest of the B’s, we use a company called Vitaganics that allows us to custom formulate a B-complex that contains no B12 or B9 (folate) and then we supplement the methylB12 and methylfolate separately.

      But again, how your own body feels and the results of your blood tests are better guides than anything you read on the internet. Regarding 23andMe, there are other companies that do this sort of testing but I’m not familiar with them, so can’t comment one way or the other. Dr Amy Yasko still does similar testing, but for more money. I’d ask your doctor about his/her reluctance about 23andMe. If it’s because of the company’s issues with the FDA, bear in mind that the FDA isn’t questioning the validity of the lab’s results. 23andMe uses a CLIA certified lab. The FDA’s beef is with the interpretive “health reports” 23andMe used to provide, saying things like “you have xyz snp, which means you have a 1.8x greater risk for heart disease.” The FDA challenged 23andMe on where it came up with the 1.8x risk number, arguing that company didn’t have enough research to back up that risk number. So 23andme has stopped providing those reports. No one has ever challenged the validity of the actual raw data on snps that the lab provides. So I guess I’d try to understand your doctor’s concerns. But bear in mind you don’t need a doctor’s signature to order the 23andMe test. You could always do the test and then work with your doctor to thoroughly vett the results and what to do about them. In the end, how you feel and what your labs say is going on in your body is your best guide. Best of luck!

  40. Can someone please explain where you are going to get all of this testing? Do I need to see a geneticist for my child? 23 and me’s site says they do not do health related testing. Does this mutation show up with the basic 23 and me test? How do I get started to find out if my child has this mutation?

    • You can have MTHFR tested by most commercial labs (Quest, Labcorp, et al). To get the full methylation picture, you need to use Yasko’s testing, 23andMe or a similar company. 23andMe gives you the status of most of the genes involved in the methylation cycles along with many other genes. Although 23andMe no longer provides its “Health reports” per its agreement with the FDA, these reports weren’t particularly helpful anyway. The real value in 23andMe is the raw data, which is provided by a CLIA certified lab and isn’t the focus of the FDA’s objections. The problem many people face is in finding someone who can adequately decipher the results and translate this into a usable treatment plan. Even many geneticists don’t seem to be particularly helpful.

      There are a few support groups – MTHFRSupport.com (and its FB page) in particular – that can help laymen and sometimes connect them with clinicians who can offer guidance. Just be aware that not all clinicians are MDs just because they have Dr. in front of their names. I opted to educate myself and then use my kids’ doctor (who’s an osteopath) as a sounding board. I also relied on the links I’ve listed at the end of the article as good resources. But DIY isn’t for everyone. If you’d prefer relying on a clinician, I’d start with mthfrsupport.com and also search Facebook for methylation pages where you can ask for doctor referrals.

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