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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S2E7: B12 and MTHFR

If you’re following along with what we’re doing, last week you added in B vitamins as a group. Typically this goes well for MTHFR folks because other B vitamins help the methylation pathway to turn, but don’t push it too quickly with methyl groups. There is one exception to this, and that is vitamin B 12 – specifically the methylcobalamin form of B12. We’ll talk about that in a minute.

First – let’s check in with where we are in the process. If you haven’t added any B12 yet, then this week we’re going to add it. If you have added B12 then let’s learn a little more about the form that you’re taking and continue to symptom track so we know how your body is responding. Let’s dive into the forms of B12 that are available and what the differences are between them.

If you started with the Seeking health B complex or vitamins then you don’t have to worry about this – they’re designed for MTHFR folks and so don’t have anything methylated in them. If you weren’t able to get those specific products then I want you to go right now to wherever you keep your vitamins and check the label.

The B12 will be called *something*-cobalamin. Cobalamin is the actual vitamin and the *something* is whatever it is bonded to. Just like folate has to be methylated to become its active form, B12 does as well so methylcobalamin is the most biologically active form of B12. It’s also the hardest one for MTHFR folks to tolerate.

This is where your symptom tracking comes in. Now, you wouldn’t be the first person to give me a withering look when I mention symptom tracking for the 800th time. I get it. Everyone is tired of hearing about it. But the problem is, that humans are used to living with symptoms that change on a daily basis and unless you’re paying attention, a lot of these symptoms get dismissed as “normal.” So, it can be “normal” to have intrusive thoughts one day and not other days for no reason you can put your finger on. It can also be normal for one day to be more down or more up than others. Symptoms, especially when they’re minor, changeable, or transient, just get ignored or shuffled off to the side.

This is a great strategy to help you function as a human, but it isn’t so helpful if we’re actually trying to evaluate health changes that you’re making. So if you’ve just added a multivitamin with methylB12 and suddenly you’re having heart palpitations 50% more than you usually do, that is something we need to know. Hence, the symptom tracking. I will step down from my soap box now, and carry on with the discussion on B12.

Vitamin B12 comes in a number of different forms. The most common and widely available is cyanocobalamin. It’s the least expensive form and generally does a fine job for most people. The cyano-prefix is actually short for cyanide, which tends to make people jumpy, but the dose of actual cyanide you get from cyanocobalamin is so negligible as to be a non-issue. Lots of people get nervous about it, but personally I’m not so concerned. It isn’t necessarily the best B12 on the market, but it will do the job. The cyano- group does have to be detoxified, so it does add a small burden that way. This is also the form most commonly found in injectable B12, which is a great option if your absorption is poor or if you have a profound deficiency.

Strangely, different people respond very differently to the forms of B12 and we don’t really have enough research to understand why, so B12 is one of those vitamins that I suggest doing a bit of your own human guinea pigging with (if guinea pigging is an actual thing). As your health journey progresses, it can be helpful to try the different forms separately and see how your body responds. Personally, I don’t do well with the methyl form at all, but respond wonderfully to the hydroxy form of B12. I notice a positive difference with it, where the methyl form just makes me jittery and irritable.

If you do notice any strange symptoms coming up this week and you did start a B12 last week, then check your form. The methyl form is known for giving people anxious, restless, wound-up energy that doesn’t feel good, intrusive thoughts, anxious thoughts, heart palpitations, and it can even be bad enough to push panic attacks or interfere with sleep.

I don’t want to villainize methylcobalamin. It is already methylated, which is a big help for those of us who methylate poorly and can take a burden off of our systems. It doesn’t need to be detoxified and it’s already biologically active. It is the most effective form of B12 for things like nerve health and if you tolerate it, then it’s probably the best form for you.

The hydroxo- form of vitamin B12 still has to be methylated to become biologically active, but it has the advantage of being almost like a sustained release vitamin B12, and so can be extremely helpful if your energy tends to suffer high peaks and low valleys – this one can help to even things out a bit. It’s not as easy to find as some of the other forms, but it can make getting your B12 far easier to bear.

The adenosyl-form of vitamin B12 is actually unique in that this is the form your body puts into storage, which makes it quite different from the other forms. Typically, excess B12 that you take as a supplement just washes out, but the adenosyl- form might actually go into storage. There is some very compelling informtion showing that this form might actually be the best for chronic fatigue , which is now being called myalgic enciphalomyelitis, or ME/CFS.

Research hasn’t kept pace with what people are doing clinically, and so the research on chronic fatigue shows great improvement for some people with B12 and folate supplementation, but doesn’t yet get into the nitty gritty between different forms of B12 or different forms of folate. In fact, all of the research I have seen is done using the cyanocobalamin form of B12, and plain old folic acid. Many chronic fatigue specialists, patients, and community forums indicate that the adenosylcobalamin form of B12 has the most profound effect for them.

If you have noticed an issue with your B12, switching to a hydroxy or adenosyl form might be easier to bear. They metabolize more slowly and so you aren’t faced with the overwhelming rush of energy. We also talked about the different forms of B12 in Season 1, episode 44 so if this episode isn’t enough, check out that one as well.

Again, this is a personal response situation, so if you’ve been taking one form and either don’t notice improvement or have side effects then try switching to a different form and see how you do. We humans are unpredictable creatures and if I’ve learned anything from MTHFR, it’s that the sum total of a human is so much more than their genes, lab tests, and stressors. We are unpredictable creatures and there are no two of us alike.

I am happy to say that the Patreon page is up and running, even if it is in its baby beginnings. If you feel like you’re learning something here and want more of the podcasts – please become a patron of the show on Patreon. It will help get great information to you and to other MTHFR folks as well. Plus, there are some patron perks. Visit Patreon.com/thwt Thanks for listening!

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S2E6: B Vitamins with MTHFR

If you’re following along with our step-by-step process, then you’re well ahead of most people who start their MTHFR journey with Dr. Google. Congratulations. This week we’re going to talk about avoiding one of the biggest mistakes that people make in their MTHFR quest for health, and that is, forgetting that methylfolate isn’t everything.

This is truly the mistake most likely to be made, followed closely by trying to change everything all at once and getting into a tangle.

It’s really easy to think of MTHFR as a “folate thing,” forgetting that the twenty other steps in the pathway that have to happen for MTHFR to have any impact, need other nutrients. Even the one step we’re obsessed with needs other nutrients.

While our mutation does have “folate” in its name and that seems like a compelling reason to focus on folate, if folate is all you focus on, it isn’t going to work out.

I’m not sure if anybody remembers S1E1 when we talked about how MTHFR was like a magic chair, but lets revisit that idea.

MTHFR is a gene. A tiny genetic code that help your body to build an enzyme of the same name. Enzymes are a special type of protein that I like to talk about in terms of being a magic chair. The magic that happens in this chair is like alchemy – it’s a lead to gold type of transition. Essentially, the magic chair turns something reasonably worthless into something incredibly valuable. Like I said, alchemy.

The MTHFR magic chair turns folate, folic acid, and folinic acid into the active form of the nutrient that actually does something in your body. This folate-gold, is called methylfolate or 5-L methyl tetrahydrofolate, if we want to be specific. Without the magic chair, the methylfolate never happens. If methylfolate doesn’t happen then things start breaking down.

MTHFR in the simplest terms possible – it’s a magic chair.

We see errors in cellular reproduction, problems with turning on or off particular genetic signals, trouble building neurotransmitters, inability to kill off damaged cells, toxins piling up, and big issues with conceiving babies, carrying babies, and building the central nervous systems on which healthy babies rely. The methylfolate gold is vital in helping us prevent cancer, prevent heart disease, reproduce, and maintain our mental, physical, and emotional wellbeing. It really is gold.

So for genetically “wild type” humans, which is what researchers call people with the typical MTHFR genes, this enzyme functions as well as it can given their nutritional status. It can still be compromised by lack of quality folate and lack of cofactors, but those are the only things slowing it down.

For MTHFR folks, the different mutations, most commonly C677T or A1298C, cause the chair to change shape a bit. Essentially, they give the chair a lump somewhere really important, like the seat or the headrest. Something that makes it hard for the folate to effectively sit in the chair so it can undergo the magic that turns it into methylfolate gold.

MTHFR mutations that matter are A1298C and C677T

So as the very basic point, I’m hoping you understand that you need the chair and the folate to click together. What we haven’t talked about, is what is needed for the magic to happen. Remember back to our alchemical change here – we’re making lead into gold and that’s a big deal. So obviously some magic happens, and in this particular case that magic needs another nutrient in order to spark. That nutrient is riboflavin. Riboflavin isn’t in the name of our mutation and Dr. Google doesn’t talk about it as much as he or she should.

So circling back to the initial statement, the biggest mistake that I see in people who have been treating their own MTHFR stuff by themselves, is that they forget about other B vitamins.

I have to point out an obvious fact that is easy to overlook. There are no “C vitamins” or “D vitamins.” There is a vitamin C, singular, and a vitamin D, also singular. So why, then, are there so darn many Bs? The bottom line is that the Bs are all Bs because they function largely as a group. No one B vitamin is involved in any big process that doesn’t also involve some or all of the rest of the B vitamins.

Vitamin C is off doing its own thing as an antioxidant, but the Bs are a team. They are all working together all of the time. Folate is a B. Riboflavin is also a B. Guess how many B vitamins you need for all of the functions related to healthy methylation? Well, the trick answer there, is all of them. Especially when you get off into making things like cellular energy or neurotransmitters and detoxifying things. The Bs always work as a team and if you’re missing Bs, then the process is stalled. Riboflavin is nowhere in the name of our mutation, but it is as necessary as folate because riboflavin makes the magic happen.

Is Riboflavin the only other B vitamin you should be taking? Nope. They’re a team, remember? So as you’re following along with the program, now is the time to start the other B vitamins – preferably in a multivitamin. It’s a great way to get everything in one swift stroke, rather than taking an individual pill for each thing.

The issue is that we don’t want folic acid, because it’s essentially toxic for us MTHFR folks, and we aren’t ready to start 5-LMTHF as a supplement yet either. So what can we do? Well, Ben Lynch, another MTHFR mutant who had the foresight to start a supplement company, called Seeking Health, that caters to genetic issues, made some great multivitamins without anything methylated just for this purpose. They can be a great way to start the journey by giving your body the rest of the “B team” without getting into weird territory with the folate.

If you can’t get those particular products, look for a multivitamin that has 5-LMTHF as the form of folate in the lowest dose possible. One a day multis are not the best choice because they usually have 400 micrograms or more just to meet the daily requirement. Many good multis will be in a two per day or even 4 per day format and a lot of times if you start one of those at the lowest possible dose (like taking 1 out of the 4 pills per day that you’re supposed to take) then you can get a reasonable background of B vitamins with a very low dose of methylfolate. Again, make sure the only folate in the product is methylfolate or folinic acid which is also safe for us.

The goal here is to get ready to start a methylfolate supplement by having a great background of other B vitamins.

By this time you have a couple of weeks of symptom tracking since stopping folic acid and since adding in food sources of natural folate. You may have noticed some changes. From those changes we might be able to predict how your methylfolate start will go.

Stopping folic acid made me feel:Adding natural folate makes me feel:5-LMTHF will probably…
BetterWorsebe difficult for me to tolerate so start with none or the very lowest dose possible.
BetterBetterbe a bit easier for me to tolerate. Still start low, but finding a good dose should be smoother.
Worse – – – I’ve never actually seen this so I don’t know.

Interestingly, we can also predict a bit based on your basic state. Last week we talked a bit about basic state so we don’t need to do so again, but overmethylators generally tolerate higher doses of methylfolate than undermethylators do. It’s a guideline and not a general rule so it’s important for everyone to start slowly and carefully.

Make sure you’ve got all the other B vitamins in there first and avoid the most common pitfall people experience when they are relying solely on Dr. Google.

I’m really excited to say that I’m in the process of building a Patreon page, which is a great way for you to show support for this show if you feel like you’re getting something out of it. I love doing the show and I want to keep putting great information out there for free so that it’s reasonably accessible to people of all financial means. But also, at the end of the day, I have to be able to support myself and contribute to my family’s wellbeing. So if you’re able to become a patron on Patreon, I would really appreciate it and I have lots of special content planned. Now, my site isn’t live just yet – I”m in the process of building it out – but when it is it will be found at Patreon.com/thwt. I’ll see what I can do to get it live before next week’s episode.

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S2E4: Adding Food Sources of Folate

Food sources of folate (natural folate, not foods enriched with folic acid) are some of the best foods out there, so with MTHFR we truly are blessed that our healthy foods are also some of the foods that taste the best. Also, high folate foods are heavily represented in Tex-Mex, so there’s another reason to be grateful.

The average person should shoot for about 400 mcg of natural folate daily. For the full nutritional requirements and more information about it, read this post.

Almost all natural food sources – beans, pulses, some meats, fruits, and vegetables, have natural folate in them. It’s easy to come by in a healthy, well-rounded diet. That doesn’t mean that everyone gets good amounts, but if you’ve made any healthy changes to your diet, you’re probably in better shape folate-wise than you think you are. Let’s talk about major food sources.

Beans, Pulses, and Legumes.

These miracle foods are high on the best-foods-for-health list anyway, but if you’re an MTHFR mutant, then so much the better. A few bean-related tips:

  • Cooked from dried beans always have more folate in them than canned.
  • Soaking dried beans before cooking helps to reduce cooking time.
  • Cooking from dried generally takes a while.
  • Mashed beans can be added to almost any recipe in place of oil to add moisture (as you might add applesauce)
  • Bean flour can be used as well – checkpea flour is reasonably easy to find.
  • Beans are high in fiber so if you suddenly start eating them you’ll notice more gas, but as your body gets used to a higher fiber diet the gas will settle down.
  • Beans and other high fiber foods are great for your digestive health and help provide a happy environment for all those good bacteria everyone keeps going on about.
Food typeFolate (mcg) per 100gFolate (mcg) per cup
Lentils (cooked from dried)280358
Black beans (cooked from dried)200256
Black beans (canned)119152
Chickpeas (cooked from dried)220282
Chickpeas (canned)126161
Edamame (frozen)311 398
Red kidney beans (canned)102131
Black eyed peas (cooked from dried)280358
Black eyed peas (canned)95122
Peanut butter (all natural, 100% peanuts)92118
Peanuts237.5304

You’ll notice that a cup of beans will typically provide 50-90% of your daily recommended folate in one fell swoop. Easy peasy.

Fruits and Vegetables

There are a number of great fruit and veggie sources of natural folate as well, and fruits and veggies with two meals will go a long way to racking up those natural folate micrograms.

Food typeFolate (mcg) per 100gFolate (mcg) per cup
Asparagus7 spears – 15412 spears – 264
Avocado81 152
Broccoli6178
Okra5874
Papaya4153
Spinach (cooked)205263
Green peas6685
Orange3646

Condiments

This entire category is pretty much for one line item, which is marmite. Marmite is a yeast extract that is very popular in Great Britain and was the original source from which folate was discovered. 100 g of marmite has a whopping 1250 mcg of folate (unhelpfully labeled folic acid because the terms are interchangeable) but there is no earthly human who could possibly choke down 100g of marmite in one day under threat of mortal peril. A “serving size” on the marmite website contains 100 mcg but it is unclear what the serving size actually is. I’m guessing, it’s enough marmite to spread a thin layer on a piece of toast.

If marmite isn’t a thing you have grown up with, it is something of an acquired taste. I love it and eat it daily – typically on rice cakes because I’m gluten free and typically with a bit of butter and avocado. It’s divine. Two rice cakes like this, you will notice, is also my 400 mcg of folate because it’s marmite and avocado combined. Food genius. Plus, it’s heavenly.

On the marmite website, there is an additional product, which I have not ever seen, called marmite and peanut butter. If you’ve never tried marmite you are probably not as appalled by this thought as I am. I am also very curious. Marmite is salty-tangy and peanut butter is, well, peanut-buttery. The two don’t go together in my mind, but obviously, people like the combo enough to make a mixed product. So what do I know? I do have to point out that peanuts are also high in natural folate.

So the goal here is 400 mcg daily, which is easiest to do if you just plan to accommodate some beans, some fruit and veg, and maybe some marmite to spice things up. Also, if you’ve never tried marmite before I highly recommend you film your reaction the first time you eat it and join the thousands of other marmite reactions on youtube because it’s a pretty vivid flavor. If you do this thing, please loop me in and send me the video – I would love to see it.

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S2E3: Food Cravings And What They Tell You

Alright, so you have done the big scary thing and taken folic acid out of your diet. That. Is. Huge.

Now, you’re in the scattered and strange landscape of the food that is left over. I can’t speak for everyone, of course, but for me, this was a martian landscape. When I eliminated wheat it wasn’t because of the folic acid. It was, in actual fact because I was testing it out to see if I had a food sensitivity. About three years later I discovered my own MTHFR mutation and the whole thing clicked in a big “aha” moment. But I digress.

I took out all the wheat-based foods, which, upon reflection, was about 80% of my food. Let’s face it, I had a little wheat problem. I lived for a good crusty bread dipped in olive oil with a little bit of salt, pepper, and lemon zest. My god. It still makes my mouth water. When I wasn’t eating that, I loved my pasta, tabouleh, barley soup, and I used to make a sprouted grain and nut mixture for breakfasts that was a base of wheat and oats.

Losing most of my food wasn’t pretty. The first three days all I could think about was bread – not the absurd, cardboard based product they passed off as gluten-free bread at that time, but real, crusty, fragrant, lovely bread. At this time I had a bick and mortar practice and was running a wellness center and I’m pretty sure that all of my patients in those three days heard me wax poetic about bread. My office manager, who was on a diet at that time, had to politely ask me to shut up about the bread for a minute because I was making her hungry.

On day three, I remember I sat in the parking lot of a Whole Foods and had to give myself a stern talking-to to prevent the purchase of a Seeduction loaf, which was one of my favorites at the time.

It was a bit sad.

Mysteriously, on day four I woke up entirely indifferent to bread. Like all of a sudden, I just didn’t care so much. It was literally like a switch flipped. If you’re listening to this and nodding sagely, then you know about this switch. Perhaps this switch flipped for you too.

It turns out, this switch is a really great signal from your body, and if you experienced this switch, then you have just learned something incredibly valuable. So let’s talk about the craving switch for a minute.

The Craving Switch

Food cravings are a thing that many people are familiar with. Cravings, especially cravings that are frequent or repeating, can tell you a bit about yourself. They could indicate one of several things:

  • A nutritional deficiency.
  • An emotional hole to be filled.
  • A food sensitivty.

Let’s take a look.

Nutritional Deficiency Cravings

Some cravings arise because your body is looking for a nutrient that is found in a particular type of food. This could be a beneficial fat, a mineral, or a vitamin.

Bear in mind, macronutrient cravings if you’ve been hungry, calorie-deprived, on an intense workout program, or if you’re growing, pregnant, or nursing are a different thing. I’m not talking about a marathoner craving a plate of pasta after a race or a pregnant mama’s pickles and ice cream. Those are somewhat exceptional situations. I’m talking about normal-situation cravings. The hallmarks of this type of craving are:

  • The food you’re craving actually has some nutrition in it. (Hint – it isn’t a snack cake, any kind of candy, or found at the top, middle, or bottom of a bag of chips.)
  • It usually seems a bit random. Like, why-do-I-suddenly-need-oysters? Type random. It can also be why-do-I-always-need-oysters?
  • It may be several different foods that seem unrelated – like if you can’t have oysters, then it’s going to have to be pumpkin seeds.

These types of cravings are surprisingly common and strangely, overlooked. It’s a lot easier to ignore the craving for oysters or pumpkin seeds than it is to ignore the craving for chips. Unfortunately, this one is actually pointing to a nutritional deficiency. Sometimes it takes a bit of work to find it – like why oysters? But with a bit of help from your nutritionist friend on instagram or from the expert internet gremlins at Google, you can figure out what might be provided from that food or group of foods that you’re craving. This could point you to a useful supplement, or possibly to a dietary modification. In the case of oysters, it’s cheaper but far less satisfying to supplement, so choose you own path there.

Emotional Cravings

I think we all know about these. For me, I know it’s an emotional craving if I want creamy carb foods or salty crunchy foods. Those are my emotions talking through that fetuchinni alfredo, lasagne, queso, cheese-smothered nachoes, or pre-menstrual bag of Doritoes. It isn’t nutritional value I’m craving, it’s the filling of an emotional need for comfort, for food-love, for the warm hug that can only be provided by melted cheese.

Sometimes, it’s easy to see the source of the problem. A bad day at work, a crappy relationship bump, or a little pandemic can be enough to trigger these cravings. Sometimes, however, knowing your trigger foods can be a good window into your emotional world – especially if you’re “fine.”

I know lots of people who are “fine” and I myself have been “fine” from time to time. In this context, by “fine” I mean willfully ignoring and or denying any emotional problems exist. Sometimes you’re consciously “fine” and just soldiering on through a stressful situation, but many times you’re unconsciously “fine” and just not letting yourself see how bad things really are internally. If that’s the case, then watching when you reach for your own personal emotional foods can be a great way to pay attention to how your heart is really doing.

This also gives you a good opportunity to either indulge in your emotional craving knowing that you’re doing it as a gift to your soul-self, or to choose a different way to explore and liberate some of those emotions that need a bit of extra care.

Sensitivity Cravings

Finally, we circle back to my wheat cravings and talk about the cravings generated by food sensitivities. Interestingly, three of the “big four” food sensitivity foods have something called an “exorphin” in them. This is basically a food-derived substance that acts on opioid recepors in the gut and brain. You heard me right – opioid receiptors. Like the ones that react to morphine or, say, heroine. The same opioids of the much-talked about “opioid epideminc.”

These exorphins have been shown in research to exert influence over such major neurological functions as pain perception, emotion, and memory. Also gut-related fuctions like motility, hormone release, appetite, and local immunity.

The major players in this game are wheat and grains, which contain gluten exorphones, milk and diary products, which contain casomorphones, and soymorphins from soybeans. Interestingly, spinach also contains an exomorphone called rubiscolins, but for whatever reason spinach sensitivities and also spinach cravings are thin on the ground. As you can imagine, the bulk of these food-sourced opioids set up an addictive response in your neurological cascade that is similar to the one set up by, you guessed it, opioids themselves.

Interestingly for MTHFR folks, there is also some remarkable research showing that these exorphones, specifically the casomorphones decrease glutathione, which is an end product of the methylation cycle, and also SAM, which is our universal methyl donor. This was studied specifically in the context of autism, but applies to everyone with the MTHFR mutation because solid science is showing that gluten and dairy actually slow down the methylation cycle – something that we are forever working to boost.

So if you, like me, experienced the wild cravings after taking the folic acid (and subsequently the wheat and/or corn) out of your diet, then you might want to consider that there is more than just folic acid going on. That you, like me, might have an underlying sensitivity. If you do have a sensitivity, then actually getting the gluten 100% out of your diet – out even from things like soy sauce, licorice, salad dressings and other such micro-sources, could be incredibly worth it.

Now that I am feeling solidly like a fountain of good news, I”ll sign off. I promise, next week we’ll talk about adding in some wonderful foods that are rich in natural folates.

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Gene Expression, Fish Oil, and MTHFR.

Fish oil, which we talked about last week as well, continues to be a big deal for people with the MTHFR mutation. Today, I want to discuss a couple of studies about gene expression, fish oil, and MTHFR, but first I want to make sure everybody understands the basics of gene expression.

When your body makes something out of your genes, it doesn’t just read the DNA and make a protein. There is more to it than that. The process, however, can be broken down into two big chunks – bear in mind that there is far more to it than this as well, but this will help you to understand the research we’re going to talk about..

  1. Transcription -Transcription is the process in which the DNA is opened like a zipper and mRNA is made from one side of the zip, and the resulting mRNA molecule is processed by the body.
  2. Translation – Translation occurs when the mRNA molecule we made above, is used to direct protein synthesis. This is how the MTHFR gene makes the MTHFR enzyme, which is the protein this gene codes for.

mRNA is genetic material just like DNA, but the difference is that while DNA might be the ultimate blueprint, it is also giant, double-stranded, and not easy to work with. RNA of all types, including messenger RNA, is single-stranded and generally transcribed from the master DNA. It is created in small segments and is the signal needed for your body to actually build proteins.

What this means is that mRNA is a good marker, in research, specifically this research about fish oil and MTHFR, for the action of the MTHFR gene and one of the only ways we can measure when the gene is acting.

Gene expression in the homocysteine cycle with Fish Oil and MTHFR

Last week we mentioned that levels of fish oil and homocysteine were linked – the higher the fish oil intake for the person studied, the lower homocysteine levels became. Let’s expand on that.

This study, published in Nutrition Journal, looks at the gene expression, meaning the mRNA levels for different enzymes along the homocysteine pathway. This includes MTHFR, but also other enzymes including MAT, CSE, SAHH, CBS, and MTR. See the diagram to place each enzyme within the pathways for recycling and converting homocysteine.

Human liver cells were treated with either decosahexaenoic acid, DHA, eicosapentaenoic acid, EPA, or alpha-linolenic acid, ALA for 48 hours. A control group with no treatment was also kept for 48 hours and then studied. After that time, mRNA levels were measured from each enzyme in question. It was found that:

  • MTHFR was upregulated by both DHA and ALA.
  • MAT was down regulated by all three treatment groups, but most in the DHA group.
  • CSE expression was increased in the DHA and EPA groups.
  • No significant changes were shown in SAHH, CBS, or MTR.
Omega-3 fatty acids like EPA, DHA, and ALA have an effect on the action of certain gene SNPS and the enzymes they code for.

This study is remarkable because it shows that the action of MTHFR can be influenced with something as simple as fish oil. The next study is even more remarkable.

Pregnancy, Fish Oil, and MTHFR

Methylation is one of the primary drivers of a person’s epigenetic state, and some of the most important methylation happens during gestation, so research involving this period is especially important. This particular study, published in Biomedical Research International, was conducted on rats.

Because previous research has shown that nutritional changes in the mother affect both poly-unsaturated fatty acid metabolism and global methylation in the placenta. This study theorized that the changes are due to some regulation of the maternal enzymes in the methylation cycle by dietary nutrients.

This study divided pregnant rats into six groups.

  • Normal folic acid and B12 (this is the control group)
  • Normal folic acid, B12 deficient
  • Normal folic acid, B12 deficient with omega-3 fatty acids
  • High folic acid, normal B12
  • High folic acid, B12 deficient
  • High folic acid, B12 deficient with omega-3 fatty acids

Placental mRNA levels were tested for MTHFR, MTR, MAT2a, CBS, PEMT, and GAPDH. Placental glutathione and phospholipid analysis were also performed.

In an effort to not bore your pants off, I’ll get to the relevant details about MTHFR.

As expected the mRNA expression of MTHFR was decreased in both B12 deficient groups relative to the normal B12 groups. Interestingly, omega-3 fatty acids were able to return the mRNA to a normal level in the normal folic acid, B12 deficient group but not the high folic acid, B12 deficient group.

This tracks with what we know about folic acid’s double-edged effect on the MTHFR enzyme. A small to normal amount is good (and far better than no folate intake) but too much inhibits the MTHFR enzyme

Placental glutathione levels followed much the same pattern. In the normal folic acid, B12 deficient group the glutathione levels were lower than normal (although not statistically significant). With excess folic acid however, glutathione levels with higher in those rats with normal B12 and significantly lower in the rats with B12 deficiency. Omega-3 fatty acids were able to correct the glutathione level in the normal folic acid, B12 deficient group but not in the excess folic acid group.

My theory about this is that glutathione manufacture is more difficult in the presence of imbalanced folate or B12, but that it increases in the most imbalanced group, which is excess folic acid and deficient B12, in an effort by the body to protect itself with glutathione buffers against increased oxidative stress.

Phospholipid levels tested higher in both B12 deficient groups compared to the control group. In both of those groups omega-3 supplementation reduced them.

This study is so remarkable because we’re looking at the time period when epigenetic is at it’s most potent and when the protective effects of omega-3 fatty acids could potentially alter the course of these pregnancies. While placental levels are being measured, these changes may have an impact for the developing fetus as well. This means that even in the presence of a somewhat unbalanced diet leading to unbalanced methylation, omega-3 fatty acids offer a regulating effect and may mitigate some of the worst of the consequences of the unbalanced diet.

Thus, the metabolisms of folic acid, vitamin B12, and DHA are interdependent on each other possibly through the one-carbon methyl cycle.

Khot V, Kale A, Joshi A, Chavan-Gautam P, Joshi S. Expression of genes encoding enzymes involved in the one carbon cycle in rat placenta is determined by maternal micronutrients (folic acid, vitamin B12) and omega-3 fatty acids. Biomed Res Int. 2014;2014:613078. doi:10.1155/2014/613078

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Lowering Homocysteine with MTHFR

As with everything to do with MTHFR, balancing your methylation and boosting your B vitamins, especially B2, folate or 5-LMTHF, and B12, is the first step. Balance your methylation! There are some other things you can look into as well.

MTHFR Isn’t The Only Cause of High Homocysteine

Of course, our focus is MTHFR, but high homocysteine has other causes as well and the sad truth is, you can have fleas and ticks on the same dog. That is one of my favorite Texas expressions. What I mean by that is that just because you have MTHFR, doesn’t mean you don’t have to also watch out for other causes of high homocysteine. It’s important to manage those too. Other Causes of high homocystein (or hyperhomocysteinemia) include:

  • Poor diet
  • Poor lifestyle
  • Smoking
  • Diabetes
  • Rheumatoid Arthritis
  • Thyroid imbalance
  • Chronic inflammatory diseases
  • Celiac disease
  • Crohn’s disease
  • Long-term use of corticosteroids
  • Prescription medications
    • methotrexate (because it lowers folate)
    • metformin (long term use because it interferes with B12 absorption)
    • hydrochlorothyazide
    • Fibrate type cholesterol-lowering medications
    • Levodopa
    • Anti-epileptic drugs (long-term use)
    • Possibly nicotinic acid or niacin, but research is very conflicted.

If you have one of these underlying conditions or are taking a medication known to elevate homocysteine, then working on that condition or talking with your physician about the medication can be a great place to start. Outside of that, let’s talk about useful steps.

The MTHFR Plan to Lower Homocysteine To Optimal

  1. Balance your methylation – I’ve said it already, but the first step is always boosting your methylation cycle because this is where we tend to stall out with MTHFR. This means following the To Health With That! Plan. Eliminate folic acid, add a methylation-friendly B complex, then add 5-LMTHF, or folinic acid, or whatever workaround you are using if you don’t tolerate folate. If you aren’t familiar with the plan you can start to walk through it here.
  2. Limit your protein intake – The more protein (and consequently methionine) you take in, the more homocysteine your body makes. There’s a full article about the methionine and homocysteine link here.
  3. Quit smoking – As though you needed one more reason why smoking is bad for your health. But yes, smoking raises your homocysteine levels.
  4. Take a look at your alcohol intake – alcohol blocks folate absorption, and so increased drinking can raise your homocysteine levels. This is probably mitigated by extra folate intake, but possibly not.
  5. Balance your coffee intake – As much as it pains me, too much coffee has consequences and high homocysteine is one of them.
  6. Zinc – zinc is a cofactor in some of the enzymes involved in the recycling of homocysteine to methionine, and so zinc deficiency can increase homocysteine levels while zinc supplementation can help to improve beneficial conversion.
  7. NAC – NAC, or N-acetyl cysteine, has been shown to lower homocysteine levels as well as folate supplementation in studies.
  8. Fish oils – in a magical synergy, fish oils + B vitamins work better together than they do apart.
  9. Make sure there aren’t other underlying causes – If you’re doing everything right and your homocysteine still isn’t where you want it to be, it matters to talk to your doctor about other underlying causes. If you’re living the perfect lifestyle, but you still have a low thyroid, then fixing your thyroid is probably the only thing to bring your levels back to balance.

Don’t forget that every little step you take towards getting healthy, counts. They all add together to contribute to your state of health, today. So every little step you take in the right direction, matters. Don’t get discouraged if things don’t move right away, just keep trying.

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Methionine, MTHFR, and Homocysteine.

The link between MTHFR and homocysteine is clear – if you aren’t familiar with that part of the picture, you can brush up with last week’s topic. The link between methionine and homocysteine is clear as well since they loop together in the methionine cycle with dietary methionine converting into homocysteine as a by-product, then being recycled back to methionine using MTHFR.

It’s easy to get into a situation where you assume methionine is “good” and homocysteine is “bad,” but actually for MTHFR, methionine itself is a double-edged sword.

Recommended Intake of Methionine

When it comes to suggested protein intakes per day, it’s pretty hotly debated and the criteria are updated every few years. Generally, requirements for infants are much higher (according to intake in mg/kg body weight) than those of children, and children are in turn higher than those of adults. Again, this is based on an mg/kg measure and not an absolute number.

  • Infants (3-4 months) – 58 mg/kg body weight/day
  • Children 2 years old – 27 mg/kg body weight/day
  • Children 10-12 years old – 22 mg/kg body weight/day
  • Adults – 13 mg/kg body weight/day.

This means for the average 150 pound (or 68 kg) adult, the daily requirement for methionine is 884 mg. That is found in 100 g (or 3.5 oz) or less of a lot of meats. This means that while vegetarians are probably getting the right amount, most meat eaters are significantly overdoing it.

Recommended Daily Protein Intake

This data is also debated, but the best researched reference data from the World Health Organization is below.

AgeProtein intake in grams/kg body weight/day
Infant1.2-1.4 g/kg body weight/day
Children0.8 – 0.97 g/kg body weight/day
Adolescents0.67 – 0.79 g/kg body weight/day
Young Adult0.75 g/kg body weight/day
Adult0.6 g/kg body weight/day
Elderly0.75 g/kg body weight/day
Pregnant0.92 g/kg body weight/day
LactatingBasic rate plus 15 g per day for the first 6 months, 12 g per day thereafter.

This works out to about 46 grams per day for the average woman and 56 grams per day for the average man. In the west, we tend to overdo protein. Most American adults eat about 100 g of protein per day, which is twice the recommended amount. Not only that, the latest trends in nutrition mean that 60% of Americans report that they are trying to increase their protein intake according to the Hartman Group.

Food Sources of Methionine

Methionine is an amino acid, which is the building block of protein, so naturally, it is high in protein-rich foods. The top ten categories of foods according to my food data are:

FoodMethionine
per 100g
Methionine per 6 ozSimilar Foods
Ground Turkey931 mg1583 mgChicken breast, thigh, drumstick.
Beef (skirt steak)905 mg1539 mgOther cuts of beef, lamb, veal, buffalo
Tuna885 mg1505 mgGrouper, salmon, snapper, tilapia, mahi mahi
Lean Pork Chops850 mg1445 mgPork ribs, lean ham, pork bratwurst,
Firm Tofu211 mg532 mgEdamame, soybean sprouts, soy milk
Milk88 mg431 mgYogurt, buttermilk
Low fat ricotta284 mg528 mgParmesan, gruyere, Swiss (other cheeses)
Brazil nuts1124 mg1914 mgHemp, squash, pumpkin, chia, sesame seeds.
Large white beans146 mg196 mgNavy, kidney, black beans.
Quinoa96 mg133.5 mgTeff, wild rice, kamut.

So… Too Much Protein?

In the West, we love our protein. We’re all working on building muscle and improving our lean bodyweight… Except that in reality, most of us aren’t. Most of us are actually working on holding down our office chair and staring at a screen. Still, we’re obsessed with the idea of being fit and lean so we overconsume in different ways than we used to. Most of us eat more than we need in general, and those of us who are “working on our health” are especially prone to working to get too much protein This, of course, leads to the modern issues of obesity and heart disease,

For people with an MTHFR issue, this takes on an added dimension because eating more protein means adding more burden to the methionine (or methylation) cycle and hence the MTHFR enzyme which ties methylation into the folate cycle. Remember how those two cog together like gears?

the MTHFR lifestyle matters because of the way these cycles all interconnect.

Extra protein means your folate cycle has to work harder, your body needs more active folate and more methyl donors, and homocysteine is going to build up. We already talked about how bad homocysteine is when it builds up.

Plus, Lower Methionine Intake Might Mean You Live Longer

Research has long shown that calorie-restricted diets are effective in promoting lifespan. Meaning, the people who eat less usually live the longest, even to the fact that some of the humans with the longest life spans on record have gone through periods of food shortage. Further research has found that limiting methionine intake specifically extends lifespan. That is with or without actual calorie restriction. Also, intermittent fasting, which is one of my favorite health hacks, is a great way to actually have minor calorie restrictions without too much fuss.

Also, methionine restriction is showing promise as a therapeutic approach to limiting the growth of certain types of cancer. This isn’t because methionine is bad – it’s essential for human growth, development, and healthy functioning. We do get more than we need, but also cancer cells have fewer ways to adapt to methionine limitation, while healthy cells can protect themselves better.

In a fascinating study, researchers are also limiting methionine with the use of an oral medication that breaks down methionine (called an oral methionase) to treat Covid-19. The RNA of the coronavirus needs to be methylated, using SAMe, in order to initiate viral replication. Limiting methionine (which limits SAMe) interferes with that step and so slows the viral replication and can potentially reduce viral load. This generally makes me wonder about all of us MTHFR folks and Covid-19. Do we have a survival advantage because it’s harder for us to produce SAMe? Also, should people supplementing with SAMe consider taking a break if they’re in a high-risk situation for COVID?

Even though we are obsessed with getting more protein – I mean, who doesn’t have jerky in their purse right now? We are clearly overdoing it. Reducing protein intake, specifically methionine, would help us all live longer, healthier lives. But it is especially important for MTHFR folks.

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MTHFR and Homocysteine – The Basics

High homocysteine is often the first indication of an MTHFR issue, and it’s certainly the one that doctors take the most seriously. There is a good reason for this. Homocysteine is implicated in heart disease including heart attack and stroke, so it shouldn’t be taken lightly. 

What is Homocysteine?

Homocysteine is an amino acid that is made within your body as a part of methionine metabolism. Amino acids are the basic building blocks of protein, and we take in amino acids every time we eat protein-containing foods.

We need homocysteine in order to make ATP, our cellular energy, and also to make cysteine and ultimately glutathione, which is our master antioxidant. The problem comes when levels get too high, and this happens when your body is unable to recycle homocysteine back into methionine.

The primary recycling pathway relies on the MTHFR enzyme, as well as active folate and B12. There is a secondary pathway called the BHMT pathway that ramps up when homocysteine levels start to rise and this relies on other methylators like betaine, trimethylglycine (TMG), and choline. 

Why does Homocysteine Get High?

As usual, there are a number of reasons and many of them are related to MTHFR.

  • MTHFR compromise – your body recycles homocysteine into methionine in an MTHFR-dependent process. It requires the active form of folate for the process so if your MTHFR is running slowly or inefficiently then homocysteine levels can build up causing inflammation and damage.
  • Folate deficiency – Whether or not you have an MTHFR issue, if you don’t have folate then the recycling doesn’t happen either.
  • B2 or B12 deficiency – Like folate, these vitamins are necessary for methionine recycling, and not having enough of them can raise your homocysteine to an unhealthy level.
  • Too Much Protein intake – This is certainly a first-world problem and a bigger one recently with everyone doing fad diets from Keto to Atkins to Paleo. If you’re taking in higher levels of methionine than your body can easily process, then homocysteine is going to build up. Also, meats and dairy have some naturally occurring homocysteine in them. We’ll talk more about the methionine situation next week.
  • Other medical conditions – thyroid disease, rheumatoid arthritis, and diabetes are linked to higher homocysteine levels.
  • Medications that decrease folate absorption – proton pump inhibitors, birth control pills, antifolate agents, and some anticonvulsant medications interfere with folate absorption or metabolism.
  • High coffee intake – I am sorry to say, high coffee intake is also linked to elevated homocysteine.

What Does Homocysteine Do That’s So Bad?

So many things. Homocysteine is vital, of course, but in this situation, too much of a good thing becomes toxic.

  1. Inflammation – Inflammation is the most well-documented issue to do with homocysteine. It is specifically damaging to cell membranes and the lining of your blood vessels, which is part of why it is so linked to heart disease.
  2. Clotting – Clotting in the blood vessels can lead to heart attack, stroke, pulmonary embolism, and deep vein thrombosis, none of which are good. This is thought to be due to a combination of factors. One is that nitric oxide metabolism is compromised and so blood vessels aren’t able to dilate properly. The other is that thromboxane A2 (TXA2) activity is increased in both blood vessels and platelets, possibly because of a higher free radical burden. This promotes clotting.
  3. Neurological issues – High homocysteine levels are implicated in a number of neurological disorders including stroke and Alzheimer’s disease, but extending to disorders like epilepsy, Parkinson’s, multiple sclerosis, and ALS. The research is unclear in terms of whether homocysteine is actually a causative factor in its own right or just a marker of low B-vitamin status.
  4. Fractures –  Research shows that homocysteine significantly increases fracture risk and it appears to be independent of other risk factors, but it is unclear whether or not B vitamin supplementation decreases that risk.
  5. Microalbuminuria – Microalbuminuria is an abnormal protein in the urine and it indicates a high future risk of cardiovascular disease as well as kidney dysfunction. Every 5 umol/L increase in homocysteine levels is associated with an increased risk of developing microalbuminuria.
  6. Atherosclerosis – As a consequence of the increased inflammation in your arteries, your body is more likely to lay down arterial plaque to protect itself. This isn’t the direction you want to go. High blood pressure – possibly because of the issues with blood vessel dilation, blood pressure and homocysteine go hand in hand. High homocysteine increases the thickness of arterial walls, reduces the elasticity of arteries, and increases the production of stiffer collagen fibers in the vascular system. 
  7. Pregnancy complications – High homocysteine levels have been implicated in spontaneous abortion, placental abruption, and preeclampsia. 

Is There Anything Good About Homocysteine at All?

Homocysteine is certainly an issue for MTHFR folks, but it’s also incredibly helpful for us as a biomarker. Testing your homocysteine gives you an easy way to see if your methylation is becoming unbalanced at the moment. While it’s a small silver lining, it’s still a good one.

We’ll talk more about the role of methionine in this conversation as well as testing homocysteine and optimal levels in the next couple of weeks.

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5-LMTHF vs. Folinic Acid. Which is Best For MTHFR?

I am sure everyone would like a simple answer so they can just buy a product and move on with their lives, but like everything else about MTHFR, this is an individual question.

The very short answer, is both forms will get you there in the end. Don’t worry, I’ve got the much longer answer all ready for you too.

One caveat before we get going – we are entering into unresearched territory here. The effects of 5-LMTHF vs. folinic acid in MTHFR mutants have never actually been studied as a comparison, so the only useful data I can use here in my own clinical experience with myself and my clients. MTHFR is a reasonably new area for scientific research and the research has focused primarily on health risks and disease correlations, as well as basic information about how disease risk changes with folate status, but we are nowhere near the point where we are actually looking at how MTHFR folks feel well.

Fast vs. Slow

In a very real sense, what we are dealing with here, is incredibly fast action, vs. slower steadier action. 5-LMTHF is the active form of folate. As soon as it absorbs, it is useable in a very rapid way. For some MTHFR folks, this is a miracle, but it’s all too much for others. Folinic acid, on the other hand, still has to be converted to the active form, and so has a much slower action because you can only use it as fast as you convert it. For some people, this isn’t enough. For others, it gives the benefits of methylfolate without the scary burst of energy (which can feel like anxiety, heart palpitations, or restlessness if it’s too high.)

If you look at the diagram above, the enzymes are highlighted in grey. You can see that 5-LMTHF is the end-product of all of this. It doesn’t need to be changed into anything else, because it’s already what we’re after. Folinic acid, on the other hand, still needs the MTHFR enzyme, but bypasses “DHFR Slow,” which only folic acid uses (and you know what I think of folic acid) and the “DHFR Fast” which is used by other forms of natural folate. It’s an efficient way to get good active folate even if your MTHFR is slow, just as long as you don’t have folic acid in your diet slowing everything down.

Doesn’t Every MTHFR mutant Need The Active Form?

No. Every MTHFR mutant needs good sources of natural folate, but this could be food sources of natural folate (NOT FOODS FORTIFIED WITH FOLIC ACID), folinic acid, or 5-LMTHF. Ultimately, they are all working on solving the same problem they just do so with different levels of efficiency. Here are some quick facts for you.

  • Natural folate, folinic acid, and 5-LMTHF are all useable by MTHFR mutants as long as they don’t have folic acid in their diet.
  • Folic acid makes natural folate and folinic acid less useful because it blocks receptor sites and slows down the methylation pathway.
  • 5-LMTHF is the only form of folate that bypasses the MTHFR enzyme entirely,
  • Natural folate, folinic acid, and 5-LMTHF are all-natural forms of folate.
  • Folinic acid is easier for many MTHFR mutants to tolerate because it is metabolized more slowly.
  • Often, taking folinic acid for several months will help a person who couldn’t tolerate 5-LMTHF to tolerate a low dose.
  • Some MTHFR folks will never be able to tolerate any forms of folate.
  • Because folinic acid metabolizes more slowly, it typically generates fewer side-effects than 5-LMTHF.

Do MTHFR Mutants Need Both Folinic Acid and 5-LMTHF?

The short answer is that we think so, but maybe not.

Here’s why. Folinic acid converts to 5-LMTHF reasonably easily (using the MTHFR enzyme) but 5-LMTHF has to go through a much more complex backward process to convert back to folinic acid. WE think it is important because these two substances feed into different pathways most easily.

5-LMTHF

  • Bypasses the MTHFR enzyme
  • Supports methylation and production of SAMe
  • Can cross the blood-brain barrier easily
  • Methylates substances like serotonin (to make melatonin), norepinephrine (to make epinephrine)

Folinic Acid

We are nowhere near the point where research is actually asking the question, “How do MTHFR mutants feel well.”

Amy Neuzil, tohealthwiththat.com

Next week we’re going to talk about what to expect when you’re starting to supplement with folate, what symptoms you might see, what is going on in your body an what to do about it.

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