S2E2: Getting the Folic Acid Out of Your Diet.

I know it’s poor planning on my part to start this season off with the hardest part of this whole process, but sadly this is the only good way to start. If you skip this step, you can create mountains of problems for future you. Keeping folic acid in sounds good to so many people, but folic acid actually blocks the other, more useful forms of folate from being utilized. I talked a lot about the technical details in this post. This basically makes all the work you’re thinking about doing to add in natural food sources of folate or to take expensive 5-LMTHF supplements, worthless. All the money you spend on those things becomes wasted as well.

Let’s start with a bang.

Folic acid also hangs out in your bloodstream as unmetabolized folic acid, or UMFA which contributes to many health problems for MTHFR folks and non-MTHFR folks alike, including increased risk of many forms of cancer.

This is step one, and ignoring it is far, far easier than actually doing it, but you’ll regret it in the long run. Honestly, it won’t even serve you in the short term because eliminating folic acid from your diet can show you a lot about how you react to folates in general. It’s a huge part of this journey and skipping it isn’t a great option. I know it’s hard but stay with me.

Folate is vital to our functioning as humans and especially to the healthy making of babies, which is a pretty big deal. Folate deficiency during pregnancy leads to major preventable complications like cleft palate, spina bifida, anencephaly, heart defects, low birth weight, and stillbirth. Because it’s so important, many governments around the world have adopted programs to fortify commonly eaten foods with the synthetic form of folate, which is our nemesis, folic acid.

This public health measure has had a tremendous impact on the rate of these birth defects, which is wonderful. It just doesn’t take into account people with the MTHFR mutation, or a culture that generally over-eats and over-supplements the way we are prone to in North America.

As a caveat to public health in general, even for MTHFR folks some folate in the worst form, folic acid, is better than none at all. This measure makes sense for society. The problems start to happen when either there is too much folic acid, which is now very common, or when there are too many compromised copies of the MTHFR gene.

So this week, if you want to follow along with this MTHFR adventure, you are ditching all of the folate fortified foods and starting with a folic-acid-free diet. Nothing else should change. Just get the folic acid out of there. This includes supplements as well so if your multivitamin, B-complex, energy-booster, or meal-replacement has folic acid in it or says “folate” on the label, then it’s out. If you’re dropping supplements, try not to add anything back in right now unless it’s absolutely necessary – we’ll look for particular things in the weeks to come and there’s no sense rushing out to buy something you might be changing shortly.

In the US, there are two foods that are fortified with folic acid. Those are wheat and corn, which are pretty much the backbone of every American meal out there. This means your bread, pasta, tortillas, corn chips, baked goods, even the doughnuts have to go. Here’s a bit more about what to eat and what not to eat for MTHFR folks.

This is the moment when people’s eyes bulge menacingly and a tic starts in one of their eyelids. Typically, spittle flies out of their mouths when they say, “But, but, then what do I eat?”

Have no fear. There is actual food left, but you might have to look around a bit. First off, you can still have wheat products as long as they are certified organic. In order to earn organic certification, they have to be unadulterated. In terms of bread, finding an organic option, or a sprouted whole-grain option is probably the best one.

For pasta, there are not so many organic options, but lots of gluten-free options that are not fortified – look for any pasta that claims to be gluten-free, or rice pasta that is made of rice and therefore not fortified.

For the baked goods, you’re going to be in a bit of trouble. There are some gluten-free options but they’re pretty limited if you’re used to the smorgasbord of wheat-based options. Sorry about that. Even baking at home has to be different because wheat flour is mostly enriched. Some whole wheat flour is safe, but some still has added folate so read your labels.

I can see that tic under your eye intensifying, so let me just reassure you that there is also every meat, veggie, fruit, and nut option under the sun. It is really just your major sources of carbs that are taking a hit. I know, that reassurance is entirely too thin for anybody’s liking.

This is the hardest part of the whole thing, so stick with me – it’s all so much simpler from here. Just keep using the symptom tracker that you started last week to see if you notice anything from the folate elimination. People are often surprised to find that something as mundane as bread can be causing them so much mental and physical pain.

It’s a bit last-minute, but I’m just offering a course starting September 15th called Methylfolate masterclass to answer the #1 question I get, which is, “How do I know when I’m taking the right dose of 5-LMTHF?” If you’re interested you can find out more at tohealthwiththat.com but register now because the cart closes at 11:59 pm Monday the 13th.

Thanks so much for listening today and if any of you are brave enough to come back next week, we’ll lighten it all up with talk about some amazing high-folate foods that you can add in to your diet to give your body good sources of natural folate. It will be great! To everyone who didn’t throw their device out the window when I started talking about not eating wheat, thanks for hanging in there!

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S2E1: Preparing To Get Healthy With MTHFR

I know everyone wants me to say “Buy the first 5-LMTHF product you see and gobble it down,” but I just can’t do that to you because after you tried it, you would hate me forever. And with good reason – jumping into 5-LMTHF before you’re ready to do so can create a kind of nightmare scenario for your body in which you’ve suddenly got a resource that has been in short supply, but none of the supportive structures around that resource. So toxins are dumping left and right but can’t actually be eliminated, neurotransmitters are bobbing up and down like pole vaulters, and mood, energy, and sleep are desperately trying to keep up.  In short, starting that way isn’t pretty. 

The only real correlation I can make with the MTHFR journey is the process of pregnancy. You can try to rush it, but it’s going to work out badly 9 times out of 10. You’ve just got to go at the pace of the project and not get ahead of yourself.

This requires laying a good foundation even though that seems like the boring part. Believe me, in this case, we WANT to prevent fireworks. So this week, let’s talk about doing the prep-work at the very baby beginning of the MTHFR journey. This will require 3 things.

  1. A symptom tracker
  2. One heck of a pantry overhaul and some carbo-loading
  3. A talk with the family, significant others, and maybe your pet hamster.

A symptom tracker is key here, even if you aren’t a total data geek like I am.  The goal is to establish your baseline symptoms this week before you’ve made any big changes and while you’re finishing all of the folic-acid enriched food in your pantry.

Knowing which symptoms to track is half the battle.

For many of us MTHFR folks, folic acid enriched food and supplements contribute to the symptom picture and even just the act of taking those out of your diet (which will be next week’s project) will have a noticeable impact on your symptoms. At this point you want to get a feel for what symptoms might be caused by folic acid because that will make things so much easier down the road. Your future self will thank you.

So let’s do a quick rundown of how to use a symptom tracker. That is something you can start today.  First off, there is a free symptom tracker available for download at tohealthwiththat.com – just sign up for the email list and it’s yours along with a couple of other MTHFR-related freebies.  There are also loads of symptom tracking apps if you prefer the technological method. 

Make a list of all of the symptoms you notice on a daily basis, things like brain fog or fatigue, or whatever it is that is your normal. Also, the ones that show up every now and then, like maybe headaches or menstrual cramps. It doesn’t matter if you think they’re related to MTHFR or not, just add them to the list. Every day, rate each symptom on a scale from 0 – 10. If you’re not experiencing that symptom, it’s a zero. If it’s the worst it could possibly be, it’s a 10. What you’re trying to figure out is your “normal” state.

The goal is to be able to tell when you’re progressing or when a change has been worth it, and when it really hasn’t. Also, when adding something might be causing problems because that is really common for us. Responses to different supplements are incredibly varied with MTHFR and so it is important to keep track of what works for you because there isn’t any one-size-fits all.

What we want this week is to get a clear picture of where you are right now. This is because next week we’re going to make a BIG change. Next week, we’ll take all of the synthetic folic acid out of your diet and supplements. 

Taking synthetic folic acid out of your life has to happen with MTHFR.  There is really only one study done in this area, but it’s hugely compelling and essentially indicates that taking folic acid for people with the MTHFR mutation (or taking too much folic acid for everyone else) actually hinders the pathway it is supposed to help. So instead of converting into the active form of folate, which is 5-LMTHF, folic acid blocks up the conversion process and gets in the way of an already compromised enzyme pathway. The bottom line is that with an MTHFR polymorphism, taking folic acid will make your symptoms, and your functional folate deficiency, worse. 

This Vitamin Could Be Hurting YouAt high doses, folic acid is toxic.

This week, to prepare for that pretty major step, I want you to enjoy your bread and pasta. Wheat products are the most commonly fortified foods globally, and they’ve been fortified with folic acid as a public health measure to prevent birth defects. In that regard, it’s a highly successful program, it just isn’t the best program for MTHFR folks.  I do want to say, however, that if it is a choice between no folate at all and synthetic folic acid, then the synthetic folic acid wins. Some folate is better than none in a starvation situation even if it’s the worst possible form. Assuming that nobody listening to this podcast or reaading the blog post is in a starvation situation, it’s best to avoid folic acid as completely as possible.

If you want to learn more about this, go back to S1E9, This Vitamin Could Be Hurting You podcast episode, or the show notes including research, here.

When you’re shopping for next week, if you want bread it’s going to have to be either gluten-free, which doesn’t have wheat and is therefore generally not fortified, or organic whole wheat, which is also typically not fortified, but check your labels. If it says folic acid or folate anywhere on the label, then it has aded folic acid and you should exclude it.

In good news, the gluten free and organic options have come a long way and there are many more of them. In bad news, the US recently extended their fortification program to include corn products as well, so check all of your labels including those on things like corn chips and tortillas. Also, double check the regulations in your own country. In most places, wheat is the most commonly fortified food, but there could be others as well. 

It is truly important to get the folic acid out of your diet as completely as possible because for many people, it’s actually causing symptoms. This could include depression, anxiety, inflammatory conditions like pain or overarching issues like fatigue or insomnia.

Also, check your vitamins, supplements, energy bars, meal replacement powders, energy drinks, birth control pills, and prescriptions.  If your doctor has given you a prescription that includes folic acid it is important to talk with them before making any changes and find an alternative that will work better for you.  Especially if you are on an antifolate agent such as methotrexate.

Remember, you’re not actually starting the folic acid elimination this week – you’re just doing the prep work. Clear out the pantry, finish your bread and pasta so it isn’t wasted, check your vitamins, supplements, and prescriptions and talk with any practitioners or doctors to make sure everything is smooth and ready for the transition. I don’t know if anybody remembers the movie Office Space, but what we’re doing here is Planning to Plan.

If you’re looking for a free resource about foods commonly fortified with folic acid, there is one in the MTHFR Library in Genetic Rockstars, our MTHFR community. It also has some ideas for MTHFR-safe substitutions.

The third thing that is probably a good idea this week, is talking to the people close to you. This is a process and you may need some support through it. You may also need to tell people why your favorite brunch place is off the menu for a while, because avoiding wheat products is super strange at first and culturally it’s a big committment. We make everything out of wheat, so this is the hardest change you’ll have to make on this entire journey.

I’m glad I warmed this season up with the hardest thing I’ll be asking you to do. That is great marketing on my part. If any of you stay with me, next week we’ll actually start taking the folic acid out of your life. After that, I should have eliminated my audience completely. Thank you so much for listening and I really hope you stick around for all of this.

I have a plan to get healthy with MTHFR, I promise.
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Homocysteine, MTHFR, and Covid-19. What We Know Now.

Of course in a pandemic we all want to know how it might affect us specifically, with all of our genetic differences. That research takes time and money and usually comes after the big stuff (like how does this spread and why does it kill people.)

In good-ish news, Covid-19 has now officially been around long enough for some of the smaller, more specific areas of research to be done. This includes the very first steps on research into the interplay between homocysteine, MTHFR and covid 19.

This particular study came about because there have been big differences in COVID disease severity, in particular in the death rate, between different geographic areas as well as between the genders. The study I am talking about was published in November 2020 in a journal called Medical Hypotheses, which is not peer-reviewed research, but rather includes important theoretical papers, so I do want to emphasize that this information is theoretical and has not been formally researched yet.

Here is a Summary from The Article Entitled: Life-threatening course in coronavirus disease 2019 (COVID-19): Is there a link to methylenetetrahydrofolate reductase (MTHFR) polymorphism and hyperhomocysteinemia?

At the date of publication of this research, Covid-19 was associated with an 8.8% mortality rate in those above 60 years of age, and 0.46% for patients aged below 60 years old. Countries with the highest mortality rates are Italy, Spain, France, Iran, and the USA. A recent report from Italy showed that the vast majority of those infected who were critically ill were older men, 68% of whom had at least one comorbidity. The worldwide mortality rate is higher among men almost by a factor of two.

Mortality rate Male:Female = 1.7:1

In Italy, high rates of ICU admission, ICU mortality, and overall mortality have been seen and the deaths from COVID-19 are often associated with high neutrophils, high levels of pro-inflammatory cytokines, abnormal coagulation tests, and disseminated inter vascular coagulation.

The most common comorbidities among the most critically ill were:

  1. Hypertension
  2. Cardiovascular disease
  3. Hypercholesterolemia
  4. Diabetes

The article goes on to summarize the high points of MTHFR:

  • The MTHFR enzyme is the most important in the methionine pathway.
  • It regulates fundamental processes such as DNA repair, neurotransmitter function, and membrane transport.
  • The C677T mutation has been suggested to be protective against certain cancers including colon and acute lymphatic leukemia.
  • The mutation leads to a thermolabile variant of the MTHFR enzyme in which the dissociation rate of the cofactor Flavin Adenine Dinucleotide (FAD) (this is from B2) is increased, thus reducing the activity of the MTHFR enzyme by 50% or more.
  • In people with a medium skin tone, the function of the MTHFR enzyme is largely preserved as long as they have sufficient dietary folate intake.
  • With insufficient folate intake, the production of 5-LMTHF is reduced, which leads to the accumulation of the key metabolite, homocysteine, to toxic levels.
  • MTHFR is the most common genetic cause of hyperhomocysteinemia.
  • Low folate status resulted in significantly higher levels of homocysteine in men.
  • Research suggests that the C677T mutation is associated with a significantly increased risk of coronary artery disease only in homozygous men.

Other risk factors for the development of high homocysteine are:

  • chronic kidney failure
  • hypothyroidism
  • cancers of the breast, ovary, and pancreas
  • smoking
  • alcohol consumption
  • physical inactivity
  • advanced age
  • male gender

Acute High Homocysteine

In addition to the risks of high homocysteine that we have talked about before, an acute high homocysteine situation can be triggered, independent of folate status, when a systemic inflammatory process is triggered (like, for instance, by a virus). This process boosts inflammation and releases a tremendous amount of reactive oxygen species (free radicals), which can overwhelm your antioxidant defense systems. This is potentially an even greater issue in MTHFR folks because we have the potential for lower glutathione than average. This whole ugly cascade activates something called nuclear transcription factor (or NF-kB), which accelerates viral replication in SARS Co-V. The study also cites a case report in which glutathione supplementation led to a rapid symptom improvement in two cases of Covid-19.

Interestingly, COVID-19 patients’ plasma homocysteine levels show predictive value for the progression of pathological findings on chest CT. This means the higher the patient’s homocysteine is, the more likely they are to show damaging changes in their lung tissue on a chest CT scan. Also, these changes began to show at a lower homocysteine level than the one that is usually used as a medical reference. Negative changes began to show at 10.58 umol/L rather than the 15 umol/L that is normally recognized as a “high” value.

In Covid-19 patients, the higher the patient’s homocysteine is, the more likely they are to show damaging changes in their lung tissue on a chest CT scan.

– Karst M, Hollenhorst J, Achenbach J. Life-threatening course in coronavirus disease 2019 (COVID-19): Is there a link to methylenetetrahydrofolic acid reductase (MTHFR) polymorphism and hyperhomocysteinemia?. Med Hypotheses. 2020;144:110234. doi:10.1016/j.mehy.2020.110234
-(Paraphrased by Amy Neuzil at tohealthwiththat.com)

What Do We Do About High Homocysteine, MTHFR and Covid-19?

This study makes some suggestions.

  • Patients at high risk with Covid-19, such as the elderly with comorbidities, should also be screened for high homocysteine.
  • Those with 8 umol/L Homocysteine or above should implement a folate-rich whole foods diet (fruit, vegetables, whole grains, good protein sources.)
  • These individuals should also add 5-MTHF supplementation.
  • Folic acid should be avoided by these individuals as supplementation can have the opposite of the desired effect, especially in individuals with the MTHFR polymorphism. This is thought to be because unmetabolized folic acid accumulates, which inhibits MTHFR and also folic acid competes at binding sites with 5-MTHF.
  • B6, B12, and B2 should be added as well as they are cofactors for the MTHFR enzyme, or in the methionine pathway.
  • Supplements with demonstrated anti-viral properties can be added, including vitamins A, C, D, E, selenium, zinc, iron, and omega-3 fatty acids.
  • Strong antioxidants including vitamin C and glutathione have shown positive results for Covid-19 outcomes.

At the end of the day, it looks like taking care of yourself appropriately for MTHFR and following the positive steps to balance your methylation that we have been talking about, is actually the best defense for those of us with MTHFR against the worst of the outcomes with Covid-19. Taking positive steps to manage your MTHFR doesn’t mean that you won’t get Covid-19, but hopefully, it will help to reduce your risk of dying from Covid-19. Keep in mind that this study represents a well-researched theory, and it has yet to be proven in clinical trials.

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MTHFR and Depression

Depression is a common thread among all humans – this isn’t limited to MTHFR folks in any way, but as folks with an MTHFR variant, balancing methylation can be an effective way of tackling depression that is often overlooked by doctors and practitioners.

We always hear about neurotransmitters and depression, so much so, that I feel we overlook the fact that there are any other possible contributors. The assumption becomes that if you’re depressed, your neurotransmitters must be off somehow and if we can fix those neurotransmitters, we can fix the depression.

The problem is, this theory doesn’t actually pan out for a lot of people – especially MTHFR people. A drug that boosts the activity of serotonin in the brain should work, but often doesn’t. It has a lot of merit to explore other cuases of depression as well – especially when so many of them are fixable.

MTHFR does, of course, affect neurotransmitters via the BH4 pathway, but my experience clinically has been that balancing all of the other things goes farther than pills for neurotransmitters in most people (there are some highly notable exceptions, of course.)

Many factors play into depression and some of these are related to MTHFR, and some aren’t.

  • Low Folate and Vitamin B12 Status – This link holds true whether the person in question has an MTHFR issue or not. Lower nutritional status regarding folate and B12 means a higher risk of depression. Also, higher serum B12 and folate are shown to predict better treatment outcomes.
  • MTHFR? – It is clear that lower folate levels can increase the risk of depression, and that MTHFR can increase the risk of lower folate levels, but it isn’t absolutely clear if MTHFR increases the risk of depression independently from folate status.  There are several ways that it could – MTHFR polymorphisms have an impact on neurotransmitter formation, and also on DNA methylation, which can boost depression by itself.
  • C677T Status? – Again, this is questionable. This meta-analysis shows a link between C677T status and depression, but the fascinating thing is that another study shows that the strength of the link changes in different geographical areas. This could be due to local changes in diet, but it could also represent a big wild-card factor that tells us we have a lot to learn in this area.
  • High homocysteine – Of course high homocysteine could be a result of low folate status, but there is a clear link between homocysteine and depression (and, don’t forget, a link between MTHFR and homocysteine.)
  • Inflammation – In a classic chicken-or-egg scenario, inflammation and depression are terminally linked. If inflammation rises, so too does depression and likewise, if depression worsens, so too does inflammation. With MTHFR we do have a greater tendency toward both, so it matters to keep your inflammatory processes in check.
  • Oxidative stress – Oxidative stress is your body’s total level of reactive oxygen species (free radicals). Studies show that people with higher levels of markers for oxidative stress also have higher levels of depression and poorer responses to treatment. With MTHFR, we have the potential to have lower glutathione, which is the master antioxidant, meaning we may have higher levels of oxidative stress.
  • Insulin Resistance and Blood Sugar Issues – Research is mixed in this area. There is a clear link between depression and diabetes, but insulin resistance, which is one of the stepping stones on the path to type 2 diabetes, is less clear. The immediate and obvious link between blood sugar fluctuations and mood, is much less difficult. As anyone with a hungry toddler can tell you, the jump between hungry and “hangry” is a short one. Again, with MTHFR we do have a slightly increased tendency towards blood sugar issues, insulin resistance, and ultimately diabetes.
  • Hormones – Again, the links here aren’t clear. Low estrogen in women is linked to perimenopausal depression. Low Testosterone in men is likewise linked to depression. High estrogen presents mood and behavior shifts, and high progesterone brings on the waterworks (between naps). What is clear is that balanced hormones certainly lead to better and steadier moods, where fluctuations or abnormalities might put us into the roughs. MTHFR is, of course, involved in hormone regulation and processing, so righting the balance can be a highly productive step.
  • Sleep – A giant link exists between sleep quality and depression, and most of us have firsthand experience of that (is anybody else’s household entirely grumpy if their sleep is interrupted?)
  • Sedentary Lifestyle – There isn’t particularly a link between MTHFR and sedentary lifestyles, which is great news. There is, however, a big link between sedentary behavior and depression and also between exercise and improved quality of life mentally, emotionally, and physically. This isn’t an MTHFR issue in any way, but I would feel remiss if I left it out of the causes of depression list.

Each of the factors above is measurable and trackable and highly treatable, with or without an MTHFR mutation. Each of those factors can be worked on independently, but also any step toward a healthier lifestyle is going to help in many of those areas.

For example, balancing your methylation (which for us MTHFR folks usually means either taking a good form of folate or if we don’t tolerate folate, then finding a good work-around) will help to raise folate levels, lower homocysteine, and reduce both inflammation and oxidative stress. So one change is influencing four big contributing factors to depression. Does that mean balancing your methylation is going to fix your depression completely? Not necessarily, but it does get us closer to the goal and also improve your chances of responding better to other therapeutic interventions as well.

So from this list, we have a number of natural treatments for depression:

  • Folate, high folate diet, and anything that will help you to balance your methylation
  • B12
  • Exercise
  • Any kind of sleep therapy
  • Lower glycemic index diet for blood sugars
  • Reducing inflammatory foods
  • Antioxidants – especially the ones that cross the blood-brain barrier
  • Anything that will help you balance your hormones
  • Any anti-inflammatory

Every one of those is a book in and of itself, but seriously that is a lot of options to try, and all of them will lead to greater health regardless.

There are also two special factors that we haven’t talked about yet. One pertains more strongly to MTHFR folks, and the other is just a human-nature problem.

  • Childhood Trauma – A significant portion of depression in adults stems from childhood trauma, and unfortunately, people with the MTHFR mutations may be more susceptible to life-long depressive tendencies from childhood traumas than average. This is fixable, but it will take some work. This could be self-guided help through spiritual seeking, prayer, meditation, and self-healing techniques. It could also be professional help in the form of therapy, hypnosis, EMDR, or a myriad of other options.
  • Habit – This conversation is really neglected and so next week’s topic is going to be about expanding the habit idea and giving you some life hacks that you can start to practice at home, but any mental state, no matter what else contributes to it, has the potential for a habit component. This could be depression, anxiety, obsessive thoughts, intrusive thoughts, whatever. And sometimes you have to train yourself to break the habit in the same way that you would with any other bad habit.

I feel like all of this could appear daunting, but if you look at it another way, it also opens up so many opportunities for healing that are often overlooked. It can be incredibly discouraging when your doctor runs out of options for depression, but chances are they haven’t even scratched the surface of this list. Typically doctors look at sleep, blood sugar, and neurotransmitters in terms of depression. You now have the opportunity to dive deeper.

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Happy Holidays from Amy at To Health With That!

This is a holiday year like no other, and it’s pretty easy to get stuck in a mental loop about all of the things we don’t have or can’t do this holiday season. I get it – 2020 has been a b**ch of epic proportions. So instead of thinking of all of those things,

Here’s a list of great things you probably have right this very second:

  • The internet – I swear this is saving humanity right now because we pretty much all have a fail-safe activity if there’s nothing else going on.
  • Skype, Zoom, or some other way to connect with loved ones even if you can’t actually connect with loved ones. I have thought so many times of wagon trains crossing the prairies and families crossing oceans on steam liners. A letter once a month would be very fortunate indeed and here we are grumbling because we can only see our families around the globe in live video chats. It’s just like the future. Plus, we can still mail a good old-fashioned letter if we choose.
  • The brilliance of science – plagues and epidemics in the past had to sweep through entire areas, devastating the population and letting fate choose who lived and died. This one, we have the tools to stop.
  • Knowledge – sometimes, it feels like too much of it. But this year we are flooded with the opportunity to learn more about what is happening in the world around us, how other people are experiencing this situation, and also the inspiring ways some people are working for their communities. When used well, this type of knowledge can be empowering. Of course, it can also be destructive – know your own limits and don’t get into a searching-for-more-bad-news spiral.
  • PPE – in no other epidemic in history has there been such universal access to personal protective equipment. And yes, there was a scramble, in the beginning, to get protective equipment to the places it was most needed, but people globally have access to it now. I mean, have you seen the most notable alternative, a plague mask?
If this getup wouldn’t terrify a patient into getting better, it might at least finish them off quickly. Photo of a German plague doctor circa the 17th century by Juan Antonio Ruiz Rivas, CC BY-SA 3.0 via Wikimedia Commons.
  • Toilet Paper – I only learned to appreciate the value of this commodity after seeing the stress 2020 wrought on the whole supply and demand thing.
My favorite cartoon from 2020. Here’s the original (in Spanish).

Four Horsemen, by Theo Moudakis, published in the Toronto Star is a close second.

Be Joyful This Holiday – No Matter What Else Is Happening

ALWAYS Choose Joy.

Even if your life has some common 2020 stressors – job loss, health issues, isolation, separation from loved ones – there are still things that can bring joy. It might be just the beautiful moment when a cardinal sat and sang on your bird feeder or the way the sunset lit up the rooftops the other day. Joy doesn’t have to be caused by a giant thing (I won the lottery! Yay!) It can be caused by tiny things, well appreciated.

I wish you the best and brightest in 2021 – may we all be nourished, body and soul. May we all know the joys of close friends and warm hearts. May we appreciate the miracles we are surrounded by every day, may we be present in the little moments.

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Energy, MTHFR, and Fatigue.

MTHFR has its sticky little fingers in everything important and energy production is no exception. In fact, fatigue is one of the most common symptoms that I see in my MTHFR clients. Truth be told, it’s one of the most common symptoms I see in *all* of my clients and perhaps fatigue is in fact the modern epidemic we should be most concerned with.

Nevertheless, there is a link between fatigue and MTHFR issues and like everything else about this mutation, it is complex and multi-factorial. More like ten links than one.

Fatigue is one of the most common symptoms that I see in my MTHFR clients. Truth be told, it’s one of the most common symptoms that I see in ALL of my clients.

– amy neuzil tohealthwiththat.com

Factors that can play into fatigue for MTHFR folks

  • Low neurotransmitters – if your norepinephrine, epinephrine, serotonin or dopamine are compromised (or some combination of all of those things, which is highly likely with MTHFR issues), then your subjective experience of having energy is going to be different from average. Mostly, it’s lower than average, but occasionally it can be higher, trending toward states like mania or hypomania, ADHD, agitation, and restlessness. Neurotransmitters are no joke and they color our experience of ourselves strongly.
  • Low melatonin – melatonin is your main sleep hormone, and it’s a direct offshoot of serotonin and needs the same pathway (the BH4 pathway, which is linked directly into the methylation cycle) to be formed. Poorly managed MTHFR issues can slow that pathway and compromise your melatonin. That means poor sleep, inadequate nighttime repair functions, and daytime sleepiness.
  • High inflammation – MTHFR is highly linked to inflammation, through the obvious pathway of increasing homocysteine (an inflammatory marker), to far less obvious factors like slowing detox, increasing free radicals, and decreasing glutathione. Inflammation is far and away one of the greatest causes of pathological fatigue. Here is a great article about it, that also dissects different types of fatigue and fatigue measurement.
  • Oxidative stress (low glutathione) – MTHFR, when unmanaged, can increase resting levels of oxidative stress (meaning it leads to more free radicals and fewer effective antioxidants). This is partly because of the metabolic byproducts of a dysfunctional methylation cycle, partly because of impaired detoxification, and partly because of decreased glutathione production. Oxidative stress can be used as a marker of fatigue in healthy people as well as those diagnosed with chronic fatigue syndrome.
  • Toxin buildup – you may recall that MTHFR is actively necessary for many detoxification reactions and if those aren’t happening, then the trash builds up. Toxin accumulation certainly makes you feel tired because your body has a mountain of work waiting to be done and no resources with which to do it (that would make anybody feel tired.)
  • Cellular energy deficit – the Krebs cycle cogs in with the folate cycle and so if things slow down or get stuck at the MTHFR enzyme, then the production of your cellular energy, called “ATP,” is affected. It might be a slight difference, but over time that can add up to a massive change in your body’s capacity.

Ok, So MTHFR And Fatigue Are Linked. Now What?

Obviously, MTHFR is right in the middle of the fatigue problem, but digging your way out of fatigue, especially when it’s turned into a deeper issue like chronic fatigue or adrenal fatigue, can be a real challenge. Where do you start?

With fatigue, as with all MTHFR issues, start at the beginning. Diet is always your foundation, followed by sleep.

– Amy Neuzil, Tohealthwiththat.com

We have talked about diet quite a bit and I won’t belabor the point, but if you need a refresher here is an article about folic acid toxicity and another about starting on an MTHFR diet. Diet is and always will be the first step – for any chronic health issue, but especially for MTHFR. Skipping this step will likely make your issues worse, no matter what fancy drugs or supplements you throw at it. Here is a full Start Here Guide to MTHFR.

You’re not getting your energy back if you don’t take care of sleep first!

Step Two Is Sleep

Let’s really talk about sleep, because the sleep and fatigue link seems obvious, but sleep can be a thorny problem and isn’t always easy to fix. Also, in a weird demonstration of human behavior, sleep is often overlooked in the treatment of fatigue.

  1. Practice good sleep hygiene. I know if you’re a parent with young kiddos or a shift-worker this entire idea makes you cringe, but try. This means:
    1. No screens one hour before bed (not even phone screens).
    2. No lights in your bedroom – cover all the little indicator lights on electronic devices, the screen on your alarm clock if you still have such a beast, and cover windows and doors completely. The best sleep happens in the true dark.
    3. Set a regular bedtime every night – preferably by 10:00 pm.
    4. Schedule at least 9 hours for sleep. I know this is a sticky one in modern society but try. Your body needs it.
    5. Set a regular wake time. It can seem counterintuitive to wake yourself up when you so desperately need sleep, but our bodies thrive on rhythms and patterns and sleep-wake cycles are no exception.
    6. Keep your sleep environment quiet, or use white noise. We are designed to wake up if there is an unusual noise.
    7. Get some good light exposure in the morning – preferably to actual sunlight, which helps your body establish a good circadian rhythm.
    8. Don’t forget about caffeine! Try stopping your caffeine intake by noon to see if it makes a difference to your sleep quality. If you can’t fathom noon, try 2:00 pm.
  2. Try Magnesium. Magnesium is a mineral that we all need in large quantities. It is responsible for physical relaxation, countering the action of calcium (which is responsible for physical contraction.) It is also well researched for sleep, both alone and in combination with melatonin and zinc. 225 mg is a good starting dose, but you might need more. Especially if you suffer from restless legs.
  3. Melatonin. This is your actual sleep hormone and also acts as an antioxidant for your brain, so lots of benefits here! We talked about it at length when we talked about MTHFR and neurotransmitters because, as we discussed earlier, MTHFR can slow down your own production of this much-needed hormone. 3-5 mg is a great place to start and it can be safely increased (up to 20 mg) or decreased as needed. If you don’t see sleep benefit with a lower dose, try increasing. If you find you’re waking up too early feeling like it’s time to get up, then try decreasing your dose.
  4. Zinc. The MMZ combo makes for some good Zzzzs. See what I did there? Studies used a reasonably low, 11.25 mg dose at bedtime. Just take a look at the graphic for starting doses.
A winning combo to help you sleep like a baby.

Step Three Is To Make Sure Nothing Bigger Is Going On

  1. Talk to your doctor. Always talk to your doctor before making changes, and in this case it’s important to make sure there isn’t something else affecting your sleep or your energy. Fatigue is a common symptom, but it is also one of your body’s best ways of communicating that something isn’t right when there is actually deeper pathology. Testing for thyroid disorders, anemia, deeper sleep issues, and chronic illness is important and shouldn’t be overlooked.
  2. Consider deeper fatigue issues like chronic fatigue and adrenal fatigue. If you have low energy for a long time without clear pathology, there could be something bigger going on. MTHFR folks are prone to both chronic fatigue (see the methylation hypothesis) and adrenal fatigue. Both of these are complex problems that will respond well, if slowly, to appropriate care, But to get appropriate care you have to know what you’re working with. Again, talk to your doctor, naturopathic doctor, DABCI Chiropractor or Traditional Chinese medicine practitioner about it.
See your doctor when you need to!

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These Vitamins Are Absolutely Essential for MTHFR.

The Methylation pathway seems relatively minor. Your body moves a 1-carbon group around. Big deal. And yet, it ties into the major processes of cellular energy formation, waste excretion, neurotransmitter formation, antioxidant recycling, and utilization of key nutrients. This can lead one to believe that folate is the most important nutrient in the universe, but the truth is – there is another vitamin that is necessary for MTHFR. A whole group of them! In fact, we need all the B vitamins for methylation to happen. So let’s take an in-depth look at not only the pathway but also the other nutrients (outside of the main player, folate) which are necessary.

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

The Methylation And Folate Cycles In Gory Detail

The image below shows the methylation pathway and the folate cycle in all their glory, with the cofactors necessary showing in color (click on the image to see a bigger version because it’s eye-crossingly small). You will notice that although folate, which we’ve spent eons talking about, shows up twice, riboflavin, which we haven’t even mentioned yet, is in there four times. With MTHFR issues, it’s easy to start to think it’s all about folate. The truth is, B vitamins function together. MTHFR folks need other B vitamins. Folate doesn’t ever function in isolation and before someone with an MTHFR issue even begins to supplement folate, they should supplement the B vitamins that aren’t directly involved in methylation. This is B1, B2, B3, B5, B6, and B7.

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

With MTHFR issues, it’s easy to start to think it’s all about folate. The truth is, B vitamins work together. MTHFR folks need all of the B vitamins, and they should start the other Bs before they even begin to supplement with folate (B9) or cobalamin (B12).

Amy Neuzil, tohealthwiththat.com

What About The Kreb’s Cycle?

I’m pretty sure that is a question that no-one has actually ever asked, but still. The Krebs Cycle is how your cells generate energy and so we kind of have to discuss it because without the kreb’s cycle, your cells have no energy and if your cells have no energy, you don’t either. Turns out, the feeling of no energy is a common issue for MTFR folks, so this really matters. Take a look at the full cycle below.

As you can see, the various B vitamins in this cycle don’t even include folate – although the folate cycle does join up, so MTHFR folks aren’t out of the woods yet. This figure was taken from: Kennedy, David. (2016). B Vitamins and the Brain: Mechanisms, Dose and Efficacy—A Review. Nutrients. 8. 68. 10.3390/nu8020068. and adapted with color.

If Folate is MTHFR’s Wife, Riboflavin is the Other Vitamin For MTHFR. Riboflavin Is The Mistress.

In fact, Riboflavin, or vitamin B2, is actually a cofactor in the MTHFR reaction itself. Meaning that if you are low on riboflavin it doesn’t matter if your MTHFR is working perfectly, it still isn’t going to happen. For this reason, MTHFR folks need riboflavin just as much as we need folate. Maybe even more so.

Start The Other B Vitamins First.


It may sound counterintuitive, but when you’re starting on your MTHFR journey, it really matters to do things in the right order.

  • Step one (as we’ve discussed) is eliminating the toxic folic acid from your diet and supplements. It’s a good idea to start up an MTHFR lifestyle here too – get a little cleaner, take out as many chemicals as you can, and generally start to avoid toxins.
  • Step two is to incorporate food sources of natural folate.
  • Step three is to add a B vitamin supplement that has all of the other B vitamins, but not any form of folate or cobalamin because MTHFR folks might have different reactions to those and so it’s nice to add them separately. At this time, I believe the only one on the market is B Minus from Seeking Health
  • .After this we can try to optimize your dose of the different types of folate, as well as the different types of cobalamin to make your health perfect.

If You’d Like To Order:

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Please note this is an affiliate link which pays me (Amy) for the referral. Thanks!

It’s easy to forget that nutrition is best when it isn’t just bits and pieces, but rather a complete and balanced diet and supplement routine. Preferably, diet. In an ideal world, we would get all of this from our food, but of course, it’s the real world and sometimes we need to supplement. Regardless, don’t get so hyper-focused on folate that you miss the rest of the B vitamins. B vitamins for MTHFR are all necessary – these are your basic building blocks..

If Folate is MTHFR’s Wife, Riboflavin is MTHFR’s Mistress.

– Amy Neuzil, tohealthwiththat.com

Thanks for listening and join us next week for a deep dive into MTHFR and glutathione, the master antioxidant.

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I Feel Bad With Methylfolate or High Folate Foods

Step one in a healthy MTHFR lifestyle is getting rid of foods with folic acid. This is hard, but pretty much everybody feels good in this scenario. Step two is adding in food sources of natural folate. This is easy, but it doesn’t always go so well. Some people feel bad with methylfolate or food sources of natural folate, which seems insane when it is so vital for everything. . Let’s look at three different scenarios.

High Folate Foods Make Me Depressed.

Congratulations – if high folate foods make you depressed, then chances are, you are in a particular category of MTHFR folks, the depressed undermethylators. For most people with MTHFR, boosting natural folate intake in food sources helps to boost neurotransmitters and increase your serotonin, dopamine, melatonin, and generally make you feel happier. Depressed undermethylators are a whole special category because, for the most part, you won’t be able to tolerate folate. Like, ever. There is a whole long explanation for this involving folate and serotonin and we’re doing a whole post on it in early October. I promise. For now, just understand that people with low serotonin and an MTHFR issue often find that their serotonin gets lower when they begin to take natural folate.

For depressed under-methylators, it is essential to take the artificial folic acid out of your diet. Folic acid is probably increasing your depression without you noticing because you’ve never been away from it

– Amy Neuzil

Foods fortified with folic acid are probably contributing to your depression and you’ve never known because you’ve never tried avoiding them. Mind blown.

There are specific workarounds for this issue, and we’ll talk about them in more detail in October, but if you just can’t wait, then there is a great post about it here.

High Folate Foods Make Me Feel Like I Bathed In Caffeine

Yeah. I’ve been there. The horrible, jittery, can’t-stop-moving feeling is no fun. Especially, when this is how you’re spending the time that is normally allocated to sleep. There are a few reasons for this.

  • Too fast! Your body is freaking out because it hasn’t had methylated folate for a long time (or possibly ever) and now it has a bunch and it doesn’t know what to do. SLOW DOWN. This usually happens when people go from no natural folate to 400 mcg all in one jump. Stop, cut it down to 100 mcg (or less if you are super sensitive), and give your body a chance to adjust. You will probably get to this level, but give your body some time.
  • Too much! If you aren’t used to paying attention to your body’s signals it can be really easy to overshoot the mark. 400 mcg is a general benchmark, but it isn’t written on a stone tablet. Some people methylate optimally at 100 mcg, or 150, or 300. Overmethylators often need very little methylfolate or natural folate to be at their best. This is all very individual so slow down, pay attention to your body’s signals, and don’t worry about what is optimal for someone else. Getting too much is just as hard on your system as not getting enough.
  • Too many things at once. If something else is going on in your life that is stressful for your body or your mind, it is really important not to push too hard with methylation because boosting your natural folate helps your body, but also asks your body to do a bit of work. You probably have a backlog of toxins that can finally be eliminated, a whole lot of repair that has been backlogged, and a variety of internal chores that need to happen. If you’re in the middle of a divorce, or you have the flu, or it’s the middle of allergy season, then your body could be overtaxed. This is okay, and it’s normal. Just be gentle with yourself. Times like this your body needs extra care and lots of the time extra care means doing less, even when the things you’re doing are great for you.
Too much methylfolate makes me feel like… THIS. Photo by Andrea Piacquadio from Pexels

Sometimes you just have to get simpler, take care of the basics, and give yourself some buffers. Sleep more, relax more, keep artificial folic acid out of your diet, and bring more natural folate in when your life settles down.

MTHFR tip from Amy Neuzil

I Feel Worse Than Bad With Methylfolate or A Folate-Rich Diet. Utterly Disgusting – Almost Hungover.

If this looks like you, then you are doing some serious detoxing. Too much, in fact.

  • Brain fog
  • Headache
  • Grouchy
  • Mildly nauseous
  • “Acidic” stomach
  • Can’t focus/low attention
  • Sluggish or heavy feeling
  • Concentration is difficult

This usually happens if you’ve had recent exposure to something that your body didn’t like (like paint fumes or solvents or the perfume counter), if you’re losing weight and liberating some toxins stored in your fat, or if suddenly your body has extra resources (like natural folate) and decides to clean house. When it happens to me I’m generally irritable, headachy, have brain fog and I get generally unpleasant to be around.

Do you feel bad with methylfolate or with a diet high in natural folate? Maybe you’re detoxing.

In this situation, it’s a good idea to step back, back off of your dose of natural folate a little bit, and support your detoxifying. This could be with extra water, fiber (the unsexiest of helpful tools), castor oil packs, more rest, or by sweating it out.

This doesn’t mean that you’re eating too much natural folate in the long-term, but it does mean that for the moment you should ease up and take some extra care of your body, and wait until all the symptoms clear before you increase your natural folate intake again.

Just because you feel bad with methylfolate or this dose of natural folate from foods today, doesn’t mean you will feel bad with this dose every day. Methylation is an ongoing process that mixes in with bunches of other processes in your body and that can get messy. Just take it one day at a time – especially when you’re just starting out. It` does get easier and more stable, so hang in there.

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