S2E9: MTHFR Questions

I love it when listeners leave me questions so here is this month’s roundup!

I don’t have a doctor that advises me about MTHFR. A mental health provider suspected the mutation because of years of resistant depression. She did a swab to test genetics for specific medication absorption which included MTHFR testing.we found that I have compound heterozygous mutations. I’ve been on high dose methyl folate and B12 for a few years and wonder if I should be getting regular tests for levels etc. where should I go? I have researched the topic myself online but it’s very confusing and there seems to be no general consensus. Can you help me? Thank you,

– Jamie L

This is a great question, Jamie because so many MTHFR folks are out there doing it on their own. Unfortunately, online and between practitioners, there is absolutely no consensus on the best way to do this, so really it comes down to finding the right way for you.

I notice you mention methylfolate and B12 and that is great, but make sure you’re taking the other B vitamins as well because they are all necessary for this to work – especially riboflavin. Also, if you’ve been taking high doses of methylfolate without other Bs, then cut your dose down before you start them because the dose might be too high once you get the other pieces of the puzzle in there.

In terms of testing, the things we want to look at specifically for MTHFR are folate, B12, and homocysteine. Testing every couple of years is fine. Testing folate is complicated because unmetabolized folic acid can be mixed into your total so the test isn’t so valuable except to show us trends (like it’s getting higher or it’s getting lower). B12 testing is straightforward as is homocysteine testing and if you aren’t familiar with homocysteine, check out Season 1, Episode 40: Homocysteine by The Numbers.

Outside of testing, the biggest determinant of whether or not you’re on track is your symptoms. How are you actually doing? If you’re not where you want to be, then maybe it’s time to work with a practitioner who has knowledge about MTHFR and can help you on your path.

Hi! I have an 8 year old boy. He was diagnosed ADHD at the age of 6. We started him on methylphenidates at age 7. We have tried nearly all of them and none of them agreed with him. We had gene testing done earlier this year and MTHFR came back as “Low to Intermediate activity”. Majority of the ADHD medications came back with lower odds of response. What do I do with this information? We have family history of bipolar and anxiety disorders. The adhd medications really brought out a lot of anxiety in my child. He is very competitive. He is obsessive. My son has a terrible issue with skin rashes that started when he was 4. We had skin patch testing done. He’s allergic to hydrocortisone, formaldehyde, fragrance. Once we took gluten out of his diet as well his rashes were more under control. Every time I listen to your podcasts I think some of my son’s issues point back to his MTHFR. Do I take this to his pediatrician? Do I work with his psychiatrist? Do I see a functional medical doctor? What do we do next?

– Mindy J.

ADHD on top of MTHFR is very common and it’s a difficult situation because the medications that help so many other kiddos just don’t work here. I DO think that addressing the MTHFR is the next best step. I would talk with both his psychiatrist and his pediatrician and see if either of them is comfortable fielding this issue in a way other than prescribing massive doses of folic acid, because that won’t be helpful.

If they aren’t familiar enough with MTHFR, then find a practitioner who is. It’s always best to work with someone local, but if you can’t find someone then I do still work with people one-on-one. Check the Amy + Health Coaching link at the top of the page on tohealthwiththat.com

This is why MTHFR folks need other Bs. It isn’t just about folate.

Hi! I am compound heterozygous so I of course have the C/T and A/C copies. I am hoping to start trying to get pregnant soon and I want to know what vitamins I should be taking that will work with the copies that I have. I am on 5mg of l-methylfolafe right now but no B vitamins. I tried a b complex and it made me very mean and hateful so I have been scared to try anything else. I want to have the best chance at a healthy pregnancy, thank you!

– Breonna H.

Congratulations on future baby-making, Breonna. That is such an exciting time. I’m so glad you brought this up because it’s really common for people to start 5-LMTHF before other B vitamins or B12 and then have weird reactions to other Bs when they start.

It is absolutely crucial that you do start other B vitamins. I think the reason why the B complex made you mean and hateful before was that with the other B vitamins there, suddenly your dose of 5-LMTHF was way too high so it was actually that causing the mood and attitude changes and not the Bs.

Basically what is happening in this situation is that your MTHFR enzyme is still really limited because it needs other B vitamins to work – riboflavin is a direct cofactor and without riboflavin, it just won’t go. So your dietary intake of riboflavin was maxing out the amount of 5-LMTHF that you can use.

So you do need to add a B complex back in there, but before you do, drop your 5-LMTHF down to 1mg for a couple of weeks and then add the B-complex. Also, check the B12 in the B complex because some people have a weird reaction to methyl-B12 too. Here’s a post on all the different forms of B12.

When you do give this a try, let me know how it all goes!

How do my folate levels drop after starting Metanx and multivitamin with active folate?

– Human

This is another great question, and I’m actually guessing a bit because I don’t know where your folate levels were before you started. I can say that what I see often in clients is that they come in with super high folate on lab tests, but functional folate deficiencies. Once we eliminate the folic acid and get them started on active folate then blood levels are technically getting lower because we’re clearing out the unmetabolized folic acid that hangs around in there cluttering up the works. Or at least that’s what we hope to do. Even as folate levels look like they’re dropping, the person is symptomatically improving.

I see that happen a lot, but if that doesn’t sound like what is going on for you, reach out again and give me a bit more detail so I can answer more thoroughly. Just remember that serum folate measures everything in the serum – usually that includes natural folate, 5-LMTHF that has been made by your body, whatever folate you’re taking, PLUS any unmetabolized folic acid that is still kicking around. It isn’t a great test on in terms of value on its own, but what we can do is exactly what you’re doing, which is compare numbers over time. But typically we want this to drop a bit as the unmetabolized folic acid (or UMFA) is leaving your system.

I *love* listener questions and I’d love to answer yours. If you happen to have a question, let me know. There is a video-ask for questions on the home page of tohealthwiththat.com. I’ll try to do an answer podcast every month or two just depending on how many questions come in. I also love meeting you guys in Genetic Rockstars, it’s an MTHFR community away from the craziness of social media with lots of inside information, polls, tips, and generally other MTHFR folks who are talking about their experiences. Please join us at community.tohealthwiththat.com.

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What Else to Take for MTHFR

It’s so easy to jump to the idea that it’s all about folate with MTHFR issues, because let’s face it. The enzyme deals with activating folate. Of course, folate is the point. I will concede to the logic of that argument, but clinically, so many factors go into a healthy methylation cycle that starting with folate is kind of like building the roof of the house before you dig the foundation.

You’ll remember from this post how vital the other B vitamins are to the whole process, appearing many more times in the chemical chain of events than folate or B12 do.

This is why MTHFR folks need other Bs. It isn’t just about folate.

Clearly, all the B family of vitamins need to be supplemented, before you even think about adding a supplemental form of folate (but hopefully, after you have eliminated the toxic folic acid from your diet and tried enhancing natural food sources of folate if you’re following our Start Here Guide to MTHFR.) If you aren’t sure about getting started with B vitamins, there’s a whole post about them here.

Is It All About The B’s Then?

The Bs are crucial, but other things matter too because this pathway is complex and connected to some of our most vital bodily functions, therefore, it needs diverse nutrition. So if you’re wondering what else to take for MTHFR besides folate, it’s a mixed bag.


Choline is an essential nutrient – we can make some, but not enough to meet our daily needs (estimated to be about 550 mg per day). It is also intimately tied to folate status and MTHFR. Choline in our bodies is used to make a variety of substances like acetylcholine, phosphatidylcholine, betaine, and sphingomyelin. These are important for:

  • Muscle function
  • Brain function
  • Membrane integrity
  • Cellular signaling
  • Methyl donor (just like SAMe)
  • Fat transport and metabolism

Here’s a great summary article on the health properties of choline. Choline isn’t necessary for all people to supplement, but it’s a good idea to take a look at your diet and symptoms to see if you might need more. The foods highest in choline, like liver and eggs, are animal products, so vegetarians might be at higher risk for deficiency. Deficiency symptoms are rare, but the most notable is non-alcoholic fatty liver disease, which is also common for MTHFR folks.

Choline function is linked to folate status, especially in MTHFR folks so if you’re having fatty liver issues or if you’ve hit a road block and haven’t tried choline, it could be a good step.


Magnesium is one of the most important nutrients in terms of body functioning and is involved in about 80% of all metabolic processes. Every enzyme that uses or makes ATP (your cells energy source) is magnesium-dependent, and ATP itself is usually bonded to magnesium in something called a chelate. So basically, without magnesium, the wheels come off the cart, fast. Plus, most adults are magnesium deficient – an estimated 60%.

Boosting your magnesium is not as much about being healthy with MTHFR as it is about being healthy.

Boosting magnesium is less about being healthy with MTHFR, and more about just being healthy. Magnesium status is linked to diseases like:

Magnesium is also great for physical and mental relaxation and sleep, and in my humble opinion should be taken by pretty much every human, ever.


Zinc is another nutrient that is tied up with MTHFR. Zinc isn’t a cofactor of the MTHFR enzyme, but zinc deficiency interferes with dietary folate absorption. This means, if you’re stuck somewhere in your MTHFR journey and can’t find a way to move forward, zinc might be your answer. Zinc is especially important if you’re working on fertility because it is highly involved in the formation of healthy sperm and ovum, hormone regulation, and the growth and development of healthy babies.

In vivo and in vitro studies have shown that zinc deficiency decreases the absorption and metabolism of dietary folate.”

I.M.W. Ebisch, C.M.G. Thomas, W.H.M. Peters, D.D.M. Braat, R.P.M. Steegers-Theunissen, The importance of folate, zinc and antioxidants in the pathogenesis and prevention of subfertility, Human Reproduction Update, Volume 13, Issue 2, March/April 2007, Pages 163–174, https://doi.org/10.1093/humupd/dml054 tohealthwiththat.com

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